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ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death
A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias…

Douglas P. Zipes, A. John Camm, Martin Borggrefe, Alfred E. Buxton, Bernard Chaitman, Martin Fromer, Gabriel Gregoratos, George Klein, Arthur J. Moss, Robert J. Myerburg, Silvia G. Priori, Miguel A. Quinones, Dan M. Roden, Michael J. Silka, Cynthia Tracy, Silvia G. Priori, Jean-Jacques Blanc, Andrzej Budaj, A. John Camm, Veronica Dean, Jaap W. Deckers, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith McGregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Luis Tamargo, José Luis Zamorano, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Elliott M. Antman, Jeffrey L. Anderson, Sharon A. Hunt, Jonathan L. Halperin, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel
DOI: http://dx.doi.org/10.1093/europace/eul108 746-837 First published online: 25 August 2006

Preamble

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will constitute the primary basis for preparing recommendations in these guidelines.

The ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines make every effort to avoid any actual, potential, or perceived conflict of interest that might arise as a result of an industry relationship or personal interest of the writing committee. Specifically, all members of the Writing Committee, as well as peer reviewers of the document, were asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. Writing Committee members are also strongly encouraged to declare a previous relationship with industry that might be perceived as relevant to guideline development. If a Writing Committee member develops a new relationship with industry during his or her tenure, he or she is required to notify guideline staff in writing. The continued participation of the Writing Committee member will be reviewed. These statements are reviewed by the parent Task Force, reported orally to all members of the Writing Committee at each meeting, and updated and reviewed by the Writing Committee as changes occur. Please refer to the methodology manuals for further description of the policies used in guideline development, including relationships with industry, which are available on the ACC, AHA and ESC World Wide Web sites (http://www.acc.org/clinical/manual/manual_introltr.htm, http://circ.ahajournals.org/manual, and http://www.escardio.org/knowledge/guidelines/Rules, respectively). Please see Appendix 1 for author relationships with industry and Appendix 2 for peer reviewer relationships with industry that are pertinent to these guidelines.

These practice guidelines are intended to assist health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis and management of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available, current scientific evidence and are intended to improve patient care. If these guidelines are used as the basis for regulatory/payer decisions, the ultimate goal is quality of care and serving the patient's best interests. The ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all of the circumstances presented by that patient. There are circumstances in which deviations from these guidelines are appropriate.

The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines and will be considered current unless they are updated, revised, or sunsetted and withdrawn from distribution. The executive summary and recommendations are published in the September 5, 2006 issue of the Journal of the American College of Cardiology, September 5, 2006 issue of Circulation, and September 17, 2006 issue of the European Heart Journal. The full-text guideline is e-published in the same issues of the Journal of the American College of Cardiology and Circulation and published in the September 2006 issue of Europace, as well as posted on the ACC (www.acc.org), AHA (www.americanheart.org), and ESC (www.escardio.org) World Wide Web sites. Copies of the full text and the executive summary are available from all 3 organizations.

Sidney C. Smith, Jr., MD, FACC, FAHA, FESC, Chair, ACC/AHA Task Force on Practice Guidelines.

Silvia G. Priori, MD, PhD, FESC, Chair, ESC Committee for Practice Guidelines.

1. Introduction

Several excellent guidelines already exist on treating patients who have ventricular arrhythmias (Table 1). The purpose of this document is to update and combine the previously published recommendations into one source approved by the major cardiology organizations in the United States and Europe. We have consciously attempted to create a streamlined document, not a textbook, that would be useful specifically to locate recommendations on the evaluation and treatment of patients who have or may be at risk for ventricular arrhythmias. Thus, sections on epidemiology, mechanisms and substrates, and clinical presentations are brief, because there are no recommendations for those sections. For the other sections, the wording has been kept to a minimum, and clinical presentations have been confined to those aspects relevant to forming recommendations.

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Table 1

Clinical practice guidelines and policy statements that overlap with ACC/AHA/ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of SCD

DocumentSponsorCitation
Guidelines
 SCDESCEur Heart J 2001;22:1374–450
 SyncopeESCEur Heart J 2004;25:2054–72
 Exercise testingACC/AHACirculation 2002;106:1883–92
 Cardiac pacemakers and antiarrhythmia devicesACC/AHA/NASPECirculation 2002;106:2145–61
 EchocardiographyACC/AHAJ Am Coll Cardiol 2003;42:954–70
 Supraventricular arrhythmiasACC/AHA/ESCEur Heart J 2003;24:1857–97
J Am Coll Cardiol 2003;42:1493–531
 SCD UpdateESCEur Heart J 2003;24:3–5
 Congenital heart diseaseESCEur Heart J 2003;24:1035–84
 European guidelines on CVD preventionESCEur J Cardiovasc Prev Rehab 2003;10(Suppl 1):S1–78
 Infective endocarditisESCEur Heart J 2004;25:267–76
 Pericardial diseaseESCEur Heart J 2004;25:587–610
 Pulmonary arterial hypertensionESCEur Heart J 2004;25:2243–78
 AED use in EuropeESC/ERCEur Heart J 2004;25:437–45
 ST-elevation myocardial infarctionACC/AHAJ Am Coll Cardiol 2004;44:e1–211
 Chronic heart failureACC/AHAJ Am Coll Cardiol 2005;46:e1–82
 Chronic heart failureESCEur Heart J 2005;26:1115–40
 CPR and ECCAHA/ILCORCirculation 2005;112:IV-1–203
 ResuscitationERCResuscitation 2005;67(Suppl):539–86
 Valvular heart diseaseACC/AHAJ Am Coll Cardiol 2006;48:e1–e148
Statements
 Invasive electrophysiology studies, catheter ablation, and cardioversionACC/AHAJ Am Coll Cardiol 2000;36:1725–36
 Hypertrophic cardiomyopathyACC/ESCEur Heart J 2003;24:1965–91
J Am Coll Cardiol 2003;42:1687–713
 Cardiovascular disease during pregnancyESCEur Heart J 2003;24:761–81
 Physical activity and recreational sports AHA for young patients with genetic CVDCirculation 2004;109:2807–16
 36th Bethesda Conference: Eligibility recommendations for competitive athletes with cardiovascular abnormalitiesACCJ Am Coll Cardiol 2005;45:1318–75
  • The guidelines from the ACC, AHA, and ESC are available at www.acc.org, www.americanheart.org, and www.escardio.org, respectively. ACC, American College of Cardiology; AHA, American Heart Association; CVD, cardiovascular disease; CPR, cardiopulmonary resuscitation; ECC, emergency cardiovascular care; ERC, European Resuscitation Council; ESC, European Society of Cardiology; ILCOR, International Liaison Committee on Resuscitation; NASPE, Heart Rhythm Society (formerly North American Society for Pacing and Electrophysiology); SCD, sudden cardiac death.

1.1. Organization of committee and evidence review

Writing Committee members were selected with attention to cardiovascular subspecialties, broad geographical representation, and involvement in academic medicine and clinical practice. The Writing Committee on the Management of Patients With Ventricular Arrhythmias and Prevention of Sudden Cardiac Death also included members of the ACC/AHA Task Force on Practice Guidelines, ESC Committee on Practice Guidelines, ACC Board of Trustees, ACC Board of Governors, ESC Board, the European Heart Rhythm Association (EHRA), and the Heart Rhythm Society (HRS).

The committee was co-chaired by A. John Camm, MD, FACC, FAHA, FESC, and Douglas P. Zipes, MD, MACC, FAHA, FESC. This document was reviewed by 2 official reviewers nominated by the ACC, 2 official reviewers nominated by the AHA, 2 official reviewers nominated by the ESC, 1 official reviewer from the ACC/AHA Task Force on Practice Guidelines, reviewers from the EHRA and HRS, and 18 content reviewers, including members from ACCF Clinical Electrophysiology Committee, AHA Council on Clinical Cardiology, Electrocardiography, and Arrhythmias, and AHA Advanced Cardiac Life Support Subcommittee.

The committee conducted comprehensive searching of the scientific and medical literature on ventricular arrhythmias and sudden cardiac death (SCD). Literature searching was limited to publications on humans and in English from 1990 to 2006. The search parameters were extended for selected topics when a historical reference was needed or if limited studies existed in English. In addition to broad-based searching on ventricular arrhythmias and SCD, specific targeted searches were performed on ventricular arrhythmias and SCD and the following subtopics: mechanisms, substrates, clinical presentations, ECG, exercise testing, echocardiography, imaging, electrophysiological (EP) testing, drug therapy (antiarrhythmic and nonantiarrhythmic), implantable and external cardioverter devices, ablation, surgery, acute specific arrhythmias (e.g., acute coronary syndrome [ACS], heart failure [HF], stable sustained monomorphic ventricular tachycardia [VT], torsades de pointes), specific pathology (e.g., congenital heart disease, myocarditis, endocrine disorders, renal failure), cardiomyopathies, genetic arrhythmias, structurally normal hearts, athletes, elderly, gender, pediatric, and drug-induced arrhythmias. The complete list of keywords is beyond the scope of this section. The committee reviewed all compiled reports from computerized searches and conducted additional manual searching. Literature citations were generally restricted to published manuscripts appearing in journals in the Index Medicus. Because of the scope and importance of certain ongoing clinical trials and other emerging information, published abstracts were cited in the text when they were the only published information available.

The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention for management of patients with ventricular arrhythmias and prevention of SCD summarize both clinical evidence and expert opinion. Once recommendations were written, a Classification of Recommendation and Level of Evidence grade was assigned to each recommendation.

Classification of Recommendations and Level of Evidence are expressed in the ACC/AHA/ESC format as follows:

Classification of Recommendations

  • Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective.

  • Class II: Conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a procedure or treatment.

    • Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.

    • Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

  • Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.

Level of Evidence

  • Level of Evidence A: Data derived from multiple randomized clinical trials or meta-analyses.

  • Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies.

  • Level of Evidence C: Only consensus opinion of experts, case studies, or standard-of-care.

The schema for classification of recommendations and level of evidence is summarized in Table 2, which also illustrates how the grading system provides an estimate of the size of treatment effect and an estimate of the certainty of the treatment effect.

Table
Table 2

Applying classification of recommendations and level of evidence†

Recommendations with respect to therapy have considered the following:

  1. The therapy to be offered (implantable cardioverter-defibrillator [ICD], antiarrhythmic drugs, surgery, and miscellaneous other treatments).

  2. The point at which therapy is offered (primary prevention for those who are at risk but have not yet had a life-threatening ventricular arrhythmia or sudden cardiac ‘death’ episode, or secondary for those patients who have already experienced such arrhythmias or events).

  3. The purpose of therapy (life preservation or symptom reduction/improved quality of life).

  4. The etiology of the arrhythmia substrate (coronary heart disease [CHD], cardiomyopathy, or other conditions).

  5. The functional status of the patient (New York Heart Association [NYHA] functional class).

  6. The state of left ventricular (LV) function (LV ejection fraction [LVEF]).

  7. The specific arrhythmia concerned (e.g., sustained monomorphic VT, polymorphic VT, and ventricular fibrillation [VF]).

Not all therapeutic combinations are clinically relevant, and many have no evidence base and probably will not have one in the future because of the lack of clinical relevance or the relative rarity of the particular grouping. In many instances, the probable value of therapy may be reasonably inferred by the response of similar patients to specific therapies.

1.2. Prophylactic implantable cardioverter-defibrillator recommendations across published guidelines

The ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices,1 the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction,2 the ESC 2001 and 2003 Guidelines on Prevention of Sudden Cardiac Death,3,4 the ESC 2005 Guidelines for the Diagnosis and Treatment of Chronic Heart Failure,5a and the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult6 include a large number of recommendations on ICD therapy that merit attention.

Recommendations for prophylactic ICD implantation based on ejection fractions (EFs) have been inconsistent because clinical investigators have chosen different EFs for enrollment in trials of therapy, average values of the EF in such trials have been substantially lower than the cutoff value for enrollment, and subgroup analyses of clinical trial populations based on EF have not been consistent in their implications. Substantial differences between guidelines have resulted. However, no trial has randomized patients with an intermediate range of EFs. For instance, there is no trial that has specifically studied patients with an LVEF between 31% and 35%, yet recommendations have been set for such patients on the basis of data derived from trials that studied groups with EFs less than or equal to 30%, others that enrolled patients with an EF less than or equal to 35%, and one trial that enrolled patients with an EF less than or equal to 40%. Recognizing these inconsistencies, this Guideline Writing Committee decided to construct recommendations to apply to patients with an EF less than or equal to a range of values. The highest appropriate class of recommendation was then based on all trials that recruited patients with EFs within this range. In this way, potential conflicts between guidelines were reduced and errors due to drawing false conclusions relating to unstudied patient groups were minimized (Table 3).

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Table 3

Inconsistencies between ACC/AHA/ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of SCD and other published ACC/AHA and ESC guidelines with respect to ICD therapy for primary prevention to reduce total mortality by a reduction in SCD

Group addressed in recommendationGuideline and class of recommendation with level of evidencea for each group
2005 ACC/AHA HF2005 ESC HF2004 ACC/AHA STEMI2002 ACC/AHA/NASPE PM and ICDComment from the ACC/AHA/ESC VA and SCD guidelines
LVD d/t MI, LVEF 30% or less, NYHA II, IIIClass I; LOE: BClass I; LOE: AClass IIa; LOE: BClass IIa; LOE: BVA and SCD has combined all trials that enrolled patients with LVD d/t MI into one recommendation, Class I; LOE: A
LVD d/t MI, LVEF 30% to 35%, NYHA II, IIIClass IIa; LOE: BClass I; LOE: AN/AN/A
LVD d/t MI, LVEF 30% to 40%, NSVT, positive EP studyN/AN/AClass I; LOE: BClass IIb; LOE: B
LVD d/t MI, LVEF 30% or less, NYHA IClass IIa; LOE: BN/AN/AN/AVA and SCD has expanded the range of LVEF to 30% to 35% or less for patients with LVD d/t MI and NYHA functional class I into one recommendation, Class IIa; LOE: B
LVD d/t MI, LVEF 31% to 35% or less, NYHA IN/AN/AN/AN/A
NICM, LVEF 30% or less, NYHA II, IIIClass I; LOE: BClass I; LOE: AN/AN/AVA and SCD has combined all trials of NICM, NYHA II, III into one recommendation, Class I; LOE: B
NICM, LVEF 30% to 35%, NYHA II, IIIClass IIa; LOE: BClass I; LOE: AN/AN/A
NICM, LVEF 30% or less, NYHA IClass IIb; LOE: CN/AN/AN/AVA and SCD has expanded the range of LVEF to 30% to 35% or less for patients with NICM and NYHA functional class I into one recommendation, Class IIb; LOE: B.
NICM, LVEF 31% to 35% or less, NYHA IN/AN/AN/AN/A
  • ACC/AHA HF, ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult;6 ACC/AHA/NASPE PM and ICD, ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices;1 ACC/AHA STEMI, ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction;2 EP, electrophysiological; ESC HF, ESC 2005 Guidelines for the Diagnosis and Treatment of Chronic Heart Failure;5 LOE, level of evidence; LVD d/t MI, left ventricular dysfunction due to prior myocardial infarction; LVEF, left ventricular ejection fraction; N/A, populations not addressed; NICM, nonischemic cardiomyopathy; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association functional class; SCD, sudden cardiac death; VA, ventricular arrhythmias.aFor an explanation of Class Recommendation and Level of Evidence, see Table 2. For further discussion, please see the Introduction.

It is important to note that experts can review the same data and arrive at different interpretations. Attempting to homogenize heterogeneous trials invariably leads to varying interpretations of the trial data. Furthermore, differences between the United States and Europe may modulate how recommendations are implemented. Guidelines are composed of recommendations on the basis of the best available medical science; however, implementation of these recommendations will be affected by the financial, cultural, and societal differences between individual countries.

1.3. Classification of ventricular arrhythmias and sudden cardiac death

This classification table is provided for direction and introduction to the guidelines (Table 4).

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Table 4

Classification of ventricular arrhythmias

Classification by clinical presentationReference
Hemodynamically stableAsymptomaticThe absence of symptoms that could result from an arrhythmia7
Minimal symptoms, e.g., palpitationsPatient reports palpitations felt in either the chest, throat, or neck as described by the following:

 • Heartbeat sensations that feel like pounding or racing

 • An unpleasant awareness of heartbeat

 • Feeling skipped beats or a pause
7
Hemodynamically unstablePresyncopePatient reports presyncope as described by the following:

 • Dizziness

 • Lightheadedness

 • Feeling faint

 • ‘Graying out’
7
SyncopeSudden loss of consciousness with loss of postural tone, not related to anesthesia, with spontaneous recovery as reported by the patient or observer. Patient may experience syncope when supine7
Sudden cardiac deathDeath from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms7a
Sudden cardiac arrestDeath from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms, in whom medical intervention (e.g., defibrillation) reverses the event7
Classification by electrocardiography
Nonsustained VTThree or more beats in duration, terminating spontaneously in less than 30 s.7
VT is a cardiac arrhythmia of three or more consecutive complexes in duration emanating from the ventricles at a rate of greater than 100 bpm (cycle length less than 600 ms)
MonomorphicNonsustained VT with a single QRS morphology7
PolymorphicNonsustained VT with a changing QRS morphology at cycle length between 600 and 180 ms7
Sustained VTVT greater than 30 s in duration and/or requiring termination due to hemodynamic compromise in less than 30 s7
MonomorphicSustained VT with a stable single QRS morphology7
PolymorphicSustained VT with a changing or multiform QRS morphology at cycle length between 600 and 180 ms7
Bundle-branch re-entrant tachycardiaVT due to re-entry involving the His-Purkinje system, usually with LBBB morphology; this usually occurs in the setting of cardiomyopathy7
Bidirectional VTVT with a beat-to-beat alternans in the QRS frontal plane axis, often associated with digitalis toxicity7
Torsades de pointesCharacterized by VT associated with a long QT or QTc, and electrocardiographically characterized by twisting of the peaks of the QRS complexes around the isoelectric line during the arrhythmia:

 • ‘Typical,’ initiated following ‘short-long-short’ coupling intervals

 • Short coupled variant initiated by normal-short coupling
7
Ventricular flutterA regular (cycle length variability 30 ms or less) ventricular arrhythmia approximately 300 bpm (cycle length—200 ms) with a monomorphic appearance; no isoelectric interval between successive QRS complexes7
Ventricular fibrillationRapid, usually more than 300 bpm/200 ms (cycle length 180 ms or less), grossly irregular ventricular rhythm with marked variability in QRS cycle length, morphology, and amplitude7
Classification by disease entity
Chronic coronary heart disease
Heart failure
Congenital heart disease
Neurological disorders
Structurally normal hearts
Sudden infant death syndrome
Cardiomyopathies
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
  • LBBB, left bundle-branch block; VT, ventricular tachycardia.

2. Epidemiology

The epidemiology of ventricular arrhythmias spans a range of risk descriptors and clinical applications, ranging from premature ventricular complexes (PVCs) and nonsustained ventricular tachycardia (NSVT) in normal subjects to SCD due to ventricular tachyarrhythmias in patients with and without structural heart disease.9 Epidemiological patterns have implications that help improve profiling risk based on individual subject characteristics and for efficient designs of clinical trials.10 Techniques include identification of clinical and lifestyle risk factors for disease development, measurement of risk among subgroups of patients with established disease, and the newly emerging field of genetic epidemiology.9,11

2.1. Ventricular arrhythmias

2.1.1. Premature ventricular complexes and nonsustained ventricular tachycardia

Single and repetitive forms of PVCs have been studied for their role in risk prediction in several contrasting clinical circumstances, including implications in apparently normal subjects compared with those with identified disease states, in steady-state pathophysiology versus transient events, and in inactive subjects versus those under physical stress. The epidemiological implications vary for each of these contingencies.

2.1.1.1. Premature ventricular complexes in the absence of heart disease

Among presumably normal individuals, estimates of the prevalence of PVCs and NSVT vary according to the sampling technique used and the source of data. PVCs were recorded on standard 12-lead electrocardiograms (ECGs) in 0.8% of subjects in a healthy military population, with a range of 0.5% among those under the age of 20 y to 2.2% of those over 50 y of age.12 In a study of middle-aged men, both with and without known heart disease, a 6-h monitor sampling technique identified a 62% incidence of asymptomatic ventricular arrhythmias, more than one half of which were infrequent single PVCs.13 The incidence, frequency, and complexity of ventricular arrhythmias were greater in the presence of known or suspected heart disease, and mortality risk implications were absent in those without heart disease.13,14 In contrast to PVCs and monomorphic patterns of NSVT, polymorphic ventricular tachyarrhythmias in the absence of structural heart disease are indicators of risk.15 Many nonsustained polymorphic VT events occurring in individuals free of grossly evident structural abnormalities of the heart are due to abnormalities at a molecular level or a consequence of electrolyte disturbances or adverse drug effects.

In the Tecumseh, Michigan, communitywide cardiovascular epidemiology study, PVCs in subjects with structurally normal hearts carried no adverse prognostic significance under the age of 30 y, but in those older than 30 y, PVCs and short runs of NSVT began to influence risk.16 More recent studies provide conflicting implications regarding risk in asymptomatic subjects. In one study,17 asymptomatic ventricular arrhythmias in the absence of identifiable heart disease predicted a small increase in risk, while another study18 suggested no increased risk.

In contrast to the apparently non-life-threatening implication of PVCs at rest, PVCs elicited during exercise testing, even in apparently normal individuals, appear to imply risk over time. In one study,19 PVCs and NSVT induced during exercise correlated with increased risk of total mortality, while in another study,20 both exercise- and recovery-phase PVCs correlated with risk, with the greater burden associated with recovery-phase arrhythmias. A selection bias, based on indications for stress testing, may have influenced these observations.21

2.1.1.2. Premature ventricular complexes in the presence of established heart disease

PVCs and runs of NSVT in subjects with structural heart disease contribute to an increased mortality risk, the magnitude of which varies with the nature and extent of the underlying disease. Among survivors of myocardial infarction (MI), frequent and repetitive forms of ventricular ectopic activity, accompanied by a reduced EF, predict an increased risk of SCD during long-term follow-up.2123 Most studies cite a frequency cutoff of 10 PVCs per hour and the occurrence of repetitive forms of ventricular ectopy as thresholds for increased risk. Several investigators have emphasized that the most powerful predictors among the various forms of PVCs are runs of NSVT.21,22 Although the specificity of this relationship is now questioned. The power of risk prediction conferred by the presence of PVCs and NSVT appears to be directly related to the extent of structural disease as estimated by EF and to cardiovascular limitations as estimated by functional capacity.24

Ventricular arrhythmias during ambulatory recording in patients with HF do not specifically predict risk for SCD.25 Risk is already high because of the underlying disease. Suppression of ambient ventricular arrhythmias is no longer considered a therapeutic target for prevention of death in the post-MI or nonischemic cardiomyopathy subgroups.

2.1.2. Ventricular tachycardia and ventricular fibrillation during acute coronary syndromes

Observations of both post-MI patients26 and survivors of cardiac arrest that occurred during the acute phase of transmural MI27 suggest that life-threatening ventricular tachyarrhythmias occurring during the first 24 to 48 h of MI do not imply continuing risk over time. A study done on follow-up after in-hospital VF does suggest an adverse prognosis over the ensuing 6 mo,28 but the patients were not selected for acute-phase arrhythmias. Later in-hospital VF has previously been reported to confer long-term risk.29 In contrast, patients presenting with non-ST-elevation myocardial infarction (NSTEMI) are at increased long-term risk of SCD,30 possibly related in part to a persistent propensity for ventricular tachyarrhythmias.31 Such patients have generally been excluded from clinical trials for interventions targeting long-term arrhythmic death risk because of low absolute risk, but it remains unclear whether the magnitude of risk is modulated by the extent of myocardial damage that occurs during the acute event. The long-term risk implications of sustained VT and VF during the acute phase of MI may also be applied to frequent PVCs and runs of NSVT.32 It is important to stress that the clinician's ability to recognize individuals with reversible or transient causes of ventricular tachyarrhythmias is limited.33

2.2. Sudden cardiac death

2.2.1. Incidence of sudden cardiac death

The geographical incidence of SCD varies as a function of CHD prevalence in different regions.3 Estimates for the United States3438 range from less than 200,000 to more than 450,000 SCDs annually, with the most widely used estimates in the range of 300,000 to 350,000 SCDs annually.39 The variation is based, in part, on the inclusion criteria used in individual studies. Overall, event rates in Europe are similar to those in the United States,3 with significant geographic variations reported.

The temporal definition of SCD strongly influences epidemiological data.40 The proportion of all natural deaths due to SCD is 13% when a definition of 1 h from onset of symptoms is used. In contrast, the communitywide study in Maastricht, the Netherlands, reported that 18.5% of all deaths were SCD, using a 24-h definition.41 The application of a 24-h definition of SCD increases the fraction of all natural deaths falling into the ‘sudden’ category but reduces the proportion of all sudden natural deaths that are due to cardiac causes.40

Approximately 50% of all CHD deaths are sudden and unexpected, occurring shortly (instantaneous to 1 h) after the onset of a change in clinical status, with some geographical variation in the fraction of coronary deaths that are sudden.42 The decreasing age-adjusted CHD mortality does not imply a decrease in absolute numbers of cardiac or sudden deaths43,44 because of the growth and aging of the U.S. and European populations and the increasing prevalence of chronic heart disease.45

2.2.2. Population subgroups and risk prediction

Three factors affect the ability to identify subjects and population subgroups at risk and consideration of strategies for prevention of SCD:

  • Absolute numbers and event rates (incidence) among population subgroups (Figure 1)

  • Clinical subgroups in which SCDs occur

  • Time dependence of risk.39

Figure 1

Absolute numbers of events and event rates of SCD in the general population and in specific subpopulations over 1 y. General population refers to unselected population age greater than or equal to 35 y, and high-risk subgroups to those with multiple risk factors for a first coronary event. Clinical trials that include specific subpopulations of patients are shown in the right side of the figure. AVID, Antiarrhythmics Versus Implantable Defibrillators; CASH, Cardiac Arrest Study Hamburg; CIDS, Canadian Implantable Defibrillator Study; EF, ejection fraction; HF, heart failure; MADIT, Multicenter Automatic Defibrillator Implantation Trial; MI, myocardial infarction; MUSTT, Multicenter UnSustained Tachycardia Trial; SCD-HeFT, Sudden Cardiac Death in Heart Failure Trial. Modified with permission from Myerburg RJ, Kessler KM, Castellanos A. SCD. Structure, function, and time-dependence of risk. Circulation 1992;85:I2–10.

The overall incidence of SCD in the United States is 1 to 2 per 1000 population (0.1% to 0.2%) annually, with some variations in estimates based on differences in various sources of data. This large population base includes those in whom SCD occurs as a first cardiac event, as well as those for whom SCDs can be predicted with greater accuracy because they are included in higher risk subgroups (Figure 1). Higher levels of risk resolution can be achieved by identification of more specific subgroups. However, the corresponding absolute number of deaths becomes progressively smaller as the subgroups become more focused, limiting the potential impact of interventions to a much smaller fraction of the total population.10 At least 50% of all SCDs due to CHD occur as a first clinical event or among subgroups of patients thought to be at relatively low risk for SCD.43

2.2.3. Time-dependent risk

The risk of SCD after a clinical event is not linear as a function of time.39,46 Survival curves after major cardiovascular events, which identify risk for both sudden and total cardiac death, demonstrate that the most rapid rate of attrition usually occurs during the first 6 to 18 mo after the index event. Curves with these characteristics have been generated from data on survivors of out-of-hospital cardiac arrest, new onset of HF, and unstable angina and on high-risk subgroups of patients with recent MI. In contrast to inherent (baseline) risk patterns over time, however, benefit patterns from controlled trials may show divergence of curves early (e.g., post-MI beta-blocker therapy, clopidogrel in ACSs) or later (e.g., angiotensin-converting enzyme [ACE] inhibitors and statins). Mortality is highest in the first month after acute MI (AMI) in patients with EF of less than 30%.47

2.2.4. Age, heredity, gender, and race

The incidence of SCD increases as a function of advancing age,48 in parallel with the age-related increase in the incidence of total CHD deaths, but may undergo a relative decrease in the eighth decade and beyond because of competing causes of death. The incidence is 100-fold less in adolescents and adults younger than 30 y (1 in 100 000 per year) than it is in adults older than 35 y.4951 The proportion of coronary deaths and of all cardiac causes of death that are sudden is highest in the younger age groups.

Hereditary factors that contribute to CHD risk have been thought to operate nonspecifically for the SCD syndrome. However, several studies have identified mutations and relevant polymorphisms along multiple steps of the cascade from atherogenesis to plaque destabilization, thrombosis, and arrhythmogenesis, each of which is associated with a risk of a coronary event.5255 Integration of these individual markers may provide more powerful individual risk prediction in the future.56 In addition, 2 population studies suggest that SCD, as an expression of CHD, clusters in specific families.57,58 There is a large preponderance of SCD in males compared with females during the young adult and early middle-age years because of the protection females enjoy from coronary atherosclerosis before menopause.5961 As coronary event risk increases in postmenopausal women, SCD risk increases proportionately. Even though the overall risk is much lower in younger women, the established coronary risk factors are still predictive of events.59,6163

Studies comparing racial differences in risk of SCD among whites and African Americans with CHD in the United States have yielded conflicting and inconclusive data. However, some studies have demonstrated excess risk of cardiac arrest and SCD among African Americans compared with whites.61,64 SCD rates among Hispanic populations were lower.61

2.2.5. Risk profiles and sudden cardiac death

Biological and behavioral risk profiling for coronary artery disease, using the conventional risk factors for coronary atherogenesis,65 is useful for identifying levels of population risk but has limited value for distinguishing individual patients at risk for SCD. Multivariate analyses of selected risk factors for atherogenesis have determined that approximately one half of all SCDs occur among the 10% of the population in the highest risk decile. Thus, the cumulative risk associated with conventional risk factors for coronary atherosclerosis exceeds the simple arithmetic sum of the individual risks.65 The comparison of risk factors in the victims of SCD with those in people who developed any manifestations of coronary artery disease does not provide useful patterns. In addition, certain angiographic and hemodynamic patterns discriminate SCD risk from non-SCD risk only under limited conditions.66

Markers of risk that move beyond the direct lipid deposition concept of atherogenesis into more complex pathobiology are now being identified, largely focusing on mechanisms responsible for destabilization of lipid-laden plaques. Inflammatory markers, such as C-reactive protein and other indicators of inflammation and destabilization,67 have entered into risk formulations, offering potentially useful additions to conventional risk markers.68,69 In addition, familial clustering of SCD as a specific manifestation of the disease57,58 may lead to identification of specific genetic abnormalities that predispose to SCD.5254,70

Hypertension is an established risk factor for CHD and also emerges as a risk factor for SCD.71 Both the ECG pattern of left ventricular hypertrophy (LVH) and echocardiographic evidence or LVH are associated with a higher proportion of sudden and unexpected cardiac death. Intraventricular conduction abnormalities such as left bundle-branch block (LBBB) are also suggestive of a disproportionate number of SCD.72,73

There are also meaningful associations between cigarette smoking, obesity, diabetes, and lifestyle and SCD. The Framingham Study demonstrates that cigarette smokers have a 2- to 3-fold increase in SCD risk; this is one of the few risk factors in which the proportion of CHD deaths that are sudden increases in association with the risk factor.72 In addition, in a study of 310 survivors of out-of-hospital cardiac arrest, the recurrent cardiac arrest rate was 27% at 3 y of follow-up among those who continued to smoke after their index event, compared with 19% in those who stopped.74 Obesity is a second factor that appears to influence the proportion of coronary deaths that occur suddenly.72

Associations between levels of physical activity and SCD have been studied, with varying results.75 A high resting heart rate with little change during exercise and recovery is a risk factor for SCD. Epidemiological observations have suggested a relationship between sedentary activity and increased CHD death risk. The Framingham Study, however, showed an insignificant relationship between low levels of physical activity and incidence of SCD but a high proportion of sudden to total cardiac deaths at higher levels of physical activity.72 An association between acute physical exertion and SCD demonstrated a 17-fold relative increase for the risk of SCD during vigorous exercise for the entire populations (active and inactive). For the habitually inactive, the relative risk was 74.76 Habitual vigorous exercise attenuates risk.76,77 Therefore, these data indicate that, while the risk of cardiac arrest is higher during vigorous exercise (especially among individuals who are usually sedentary), habitual exercise attenuates the risk of cardiac arrest, both during exercise and at rest.78

The magnitude of recent life changes in the realms of health, work, home, and family and personal and social factors have been related to MI and SCD.7982 There is an association between significant elevations of life-change scores during the 6 mo before a coronary event, and the association is particularly striking in victims of SCD. After controlling for other major prognostic factors, the risk of SCD and total mortality is increased by social and economic stresses,83 and alteration of modifiable lifestyle factors has been proposed as a strategy for reducing risk of SCD in patients with CHD.84 Acute psychosocial stressors have been associated with risk of cardiovascular events, including SCD.85,86 The risk appears to cluster around the time of the stress and appear to occur among victims at preexisting risk, with the stressor simply advancing the time of an impending event.85 The possibility of physical stress-induced coronary plaque disruption has also been suggested.87

3. Mechanisms and substrates

3.1. Substrate for ventricular arrhythmias

The substrate for SCD varies depending on the underlying structural heart disease, if any, and ranges from no obvious evidence of structural damage to advanced cardiomyopathic states. Most studies suggest that three quarters of the patients dying of SCD have CHD. Extensive coronary atherosclerosis is generally found, with a high proportion of hearts having 3- or 4-vessel coronary disease involvement. Anatomical findings at autopsy include acute changes in coronary plaque morphology, such as thrombus, plaque disruption, or both, in more than 50% of cases of sudden coronary death. Hearts that have myocardial scars and no acute infarction show active coronary lesions in approximately 50% of cases.88 Erosion of proteoglycan- and smooth muscle cell-rich plaques lacking a superficial lipid core, or plaque rupture, is a frequent pathological finding.89 Plaque rupture appears to be more common in older women.90 However, these anatomical abnormalities are not represented by specific clinical risk factors different from those that identify patients with CHD in general. Naturally, the substrate will be different depending on the nature of the heart disease. As noted in Section 2, other diseases predisposing to SCD include both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), right ventricular (RV) cardiomyopathy, congenital abnormalities (especially coronary artery anomalies), coronary artery spasm, and other less common problems.44,46,91 Obesity, hypertension, lipid abnormalities, and diabetes are important risk factors.9295 The heritable abnormalities of RV cardiomyopathy and HCM are the major substrates found in the sudden deaths of pre-coronary artery age groups.9698 The cumulative risk of SCD has been estimated at 15% to 20% of adults with aortic stenosis, with the risk being higher in symptomatic patients and equal to or less than 5% in asymptomatic patients.99 Mitral valve prolapse is usually non-life threatening, and its link with SCD has never been conclusively demonstrated.3 Reported SCD rates in patients with Wolff-Parkinson-White (WPW) syndrome have been 0.15%, due in most to the development of atrial fibrillation (AF) with a rapid ventricular response that degenerates to VF.100,101

Genetic influences modulate the risk of SCD in the setting of coronary (and likely other) heart disease.3,55,102 The Paris Prospective Study I, analyzing more than 7000 men followed for an average of 23 y, found that a parental history of SCD increased the relative risk of SCD for offspring to 1.8, without elevating the risk for MI. When both parents had SCD, the relative risk for SCD in offspring was 9.4.58 A retrospective study performed on cardiac arrest survivors in King County, Washington, also reported family history to be a significant, independent risk for SCD, with an odds ratio of 1.57.57 Genetic influences may act through multiple, though not necessarily exclusive, mechanisms: by modulating the fixed substrate, atherothrombosis, electrogenesis impulse propagation, neural control and regulation.

In 5% to 10% of cases, SCD occurs in the absence of CHD or cardiomyopathy. There exists a group of inherited abnormalities such as the long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome, and catecholaminergic VT, which can precipitate SCD without overt structural changes in the heart.103105 Abnormalities in potassium and sodium channels, in ankyrin B, and in the ryanodine receptor of the sarcoplasmic reticulum which is responsible for release of the calcium required for cardiac muscle contraction, can disrupt the normal electrical processes of the heart to cause life-threatening ventricular arrhythmias. It is important to stress that some individuals can have inherited abnormalities that are not manifest until triggered by an external event. For example, autonomic modulation associated with certain types of activity, as well as drugs that affect cardiac repolarization, can convert a subclinical genetic abnormality to SCD. It is highly likely that additional genetic causes of SCD will be found in the future.56

Among the genetic factors, the most common are DNA variants called ‘polymorphisms’ that may be present in a large proportion of the population and create susceptibility for SCD. Single nucleotide polymorphisms (SNPs) are DNA variants that can be associated with a functional consequence. For example, a polymorphism identified in the alpha 2b adrenergic receptor is associated with an increased risk of MI and SCD.106 Studies such as these require validation before they enter clinical practice. Nevertheless, because millions of SNPs are present in the DNA of each individual, a specific combination of polymorphisms in different genes, interacting with a specific trigger or substrate, may be required to create a risk for SCD.56

3.2. Mechanisms of sudden cardiac death

The rhythm most often recorded at the time of sudden cardiac arrest is VF. Previous studies suggest that 75% to 80% occur via this mechanism and 15% to 20% are attributed to bradyarrhythmias, including advanced atrioventricular (AV) block and asystole.107 Bayes de Luna et al.108 noted that in 157 ambulatory patients who had SCD while undergoing Holter recording, 62.4% had VF, 16.5% had bradyarrhythmias, 12.7% had torsades de pointes, and 8.3% had primary VT. The true incidence of bradyarrhythmias is not clear because a rhythm beginning as VF may appear to be asystole when the first ECG is recorded. However, a study reported by Cobb et al.37 suggests that VF accounts for a smaller proportion of events than previously thought. Advanced AV block or significant bradycardia can cause VF. It is difficult to identify accurately the EP mechanism(s) responsible for SCD. The reason for this is that the mechanisms may be multifactoral and are quite likely to be different depending on the specific cardiac abnormality and a rhythm can start via one mechanism and be perpetuated via another. It is also important to remember that while many studies have investigated EP mechanisms responsible for the onset of VT and VF and their continuation, no class I or III antiarrhythmic agent109 has clearly been demonstrated to reduce total and SCD mortality in patients at risk for SCD. (7a,109) In fact, it is the drugs without direct EP actions on cardiac muscle or specialized conducting tissue that have been shown effective for prevention of SCD. These drugs include beta blockers, ACE inhibitors, angiotensin receptor-blocking agents, lipid-lowering agents, spironolactone, and fibrinolytic and antithrombotic agents; some data also suggest a protective effect of n-3 fatty acids,110 although this remains to be confirmed111 (see Section 6.4).

Because SCD is for the most part the result of a ventricular tachyarrhythmia, these drugs must be acting on the fundamental biochemical, ischemic, fibrotic, or other processes that underlie the onset or maintenance of the life-threatening ventricular arrhythmias. Thought of in this fashion, VF can be considered a final common pathway for the expression of an electrically unstable heart. The fundamental mechanisms of cardiac arrest include electromechanical dissociation, asystole and heart block, and VF, with VF being the most common. It is the ‘upstream’ events triggering the electrical instability upon which these drugs probably act. While we unquestionably need to pursue investigations into the electrophysiology of these ventricular tachyarrhythmias, more study needs to be applied to the drugs affecting upstream events, because these events appear to yield the greatest dividends, at least for the present, and must be the reason why the asymptomatic, apparently stable, individual suddenly develops SCD at a particular time on a particular day. It must be that a dynamic factor or factors, possibly transient, interact with a fixed substrate to precipitate the arrhythmia. The possibilities fill a long list and include such things as physical activity, transient ischemia, pH and electrolyte changes, inflammation, hypoxia, stretch, ion channel abnormalities, neuroendocrine actions, drugs, and so forth, all of which are capable of modulating conduction in ways we mostly do not understand. More permanent changes could also occur, such as plaque rupture, as mentioned earlier.112

4. Clinical presentations of patients with ventricular arrhythmias and sudden cardiac death

Ventricular arrhythmias can occur in individuals with or without a cardiac disorder. There is a great deal of overlap between clinical presentations (Table 5) and the severity and type of heart disease. For example, stable and well-tolerated VT can occur in the individual with previous MI and impaired ventricular function. The prognosis and management are individualized according to symptom burden and severity of underlying heart disease, in addition to the clinical presentation.

View this table:
Table 5

Clinical presentations of patients with ventricular arrhythmias and sudden cardiac death

• Asymptomatic individuals with or without electrocardiographic abnormalities
• Persons with symptoms potentially attributable to ventricular arrhythmias
 ○ Palpitations
 ○ Dyspnea
 ○ Chest pain
 ○ Syncope and presyncope
• Ventricular tachycardia that is hemodynamically stable
• Ventricular tachycardia that is not hemodynamically stable
• Cardiac arrest
 ○ Asystolic (sinus arrest, atrioventricular block)
 ○ Ventricular tachycardia
 ○ Ventricular fibrillation
 ○ Pulseless electrical activity

4.1. Asymptomatic

Ventricular arrhythmias may be detected as an incidental finding during ECG monitoring or physical examination. They may also be uncovered during an attempt to further define prognosis in an individual with known heart disease. In general, treatment is indicated to prevent potential morbidity (e.g., ‘tachycardia-induced cardiomyopathy’), reduce symptom burden, or reduce the risk of SCD. There is no reason to treat asymptomatic ventricular arrhythmias in the absence of such potential benefit. The major determinants of risk of SCD are related more to the type and severity of associated cardiac disease and less to the frequency or classification of ventricular arrhythmia.44,113 Certain arrhythmias such as rapid polymorphic VT may be compelling to treat even in the asymptomatic individual without evident heart disease. Nonetheless, such arrhythmias are rarely asymptomatic and are probably related to ionic channel abnormalities yet to be elucidated.114,115 NSVT in the patient with previous MI and impaired LV function indicates increased risk of SCD and the need for further evaluation or treatment.116 The contribution of asymptomatic ventricular arrhythmias to the patient's management is not well established for other cardiac diseases such as DCM117 or HCM.118

4.2. Symptoms potentially related to ventricular arrhythmias

Palpitations or a perception of cardiac rhythm irregularity may be caused by the whole spectrum of arrhythmias and are also frequently reported in patients in the absence of any arrhythmia.119 Less frequently, patients with VT may present with symptoms of paroxysmal dyspnea or chest pain in the absence of a sensation of rapid heart beating. In such instances, the dyspnea or chest pain may be related to the hemodynamic consequences of tachycardia. ‘Presyncope’ is a vague term that is poorly defined but probably is interpreted by most as a feeling of impending syncope.120 It is not specific as a symptom. VT may be a cause of undiagnosed syncope, especially in patients with structural heart disease.121 Patients with poor ventricular function and inducible VT or VF have a high incidence of subsequent appropriate therapies when implanted with an ICD.122128 Similar patients with poor ventricular function may be at risk of SCD.129 Patients with sudden onset of very rapid VT such as torsades de pointes with the repolarization syndromes will typically present with syncope or seizure rather than an awareness of rapid heart beating or palpitations.130

4.2.1. Hemodynamically stable ventricular tachycardia

Patients with slower, stable VT may be asymptomatic but more frequently present with a sensation of rapid heart beating possibly accompanied by dyspnea or chest discomfort. The stability or tolerance of VT is related to the rate of tachycardia, presence of retrograde conduction, ventricular function, and the integrity of peripheral compensatory mechanisms. A presentation with stable, relatively well-tolerated VT does not suggest the absence of heart disease and can be observed in patients with very poor LV function. Even patients with poor ventricular function may not be aware of palpitations during VT. Presentation with stable VT does not in itself indicate a benign prognosis in patients with significant heart disease.131 Incessant VT, although hemodynamically stable, can be a cause of hemodynamic deterioration leading to HF.132 In patients with an ICD, the VT rate can fall below the lower rate of VT detection, causing underdetection of VT that can prevent arrhythmia termination. Immediate reinitiation of the VT following proper ICD therapy can also result in hemodynamic deterioration and an early battery depletion.132,133

4.2.2. Hemodynamically unstable ventricular tachycardia

The term ‘hemodynamically unstable’ has not been rigidly defined but is widely used. It connotes a tachycardia associated with hypotension and poor tissue perfusion that is considered to have the imminent potential to lead to cardiac arrest or shock if left untreated. Hemodynamically unstable VT is usually, but not exclusively, observed in patients with poor ventricular function. Patients with normal ventricular function can have unstable VT or VF if the tachycardia is rapid enough, as in the LQTS and other abnormal repolarization syndromes.103 Some patients with a normal heart and idiopathic monomorphic VT or even supraventricular tachycardia (SVT) can become hypotensive during the arrhythmia because of a vasovagal reaction.

4.3. Sudden cardiac arrest

Rapid sustained VT or VF results in presentation with markedly impaired tissue perfusion and loss of consciousness as a result of inadequate cardiac output, leading to SCD if not expediently reversed. Sudden cardiac arrest may be the presenting symptom with any cardiac disease or even in individuals with no apparent heart disease.44 The initiating mechanism of sudden cardiac arrest may or may not be related to arrhythmia.

5. General evaluation of patients with documented or suspected ventricular arrhythmias

5.1. History and physical examination

Palpitations, presyncope, and syncope are the 3 most important symptoms requiring further characterization in patients suspected of having ventricular arrhythmias. Palpitations are usually of a sudden onset/offset pattern and may be associated with presyncope and/or syncope. Sudden episodes of collapse with loss of consciousness without any premonition that usually last for a few seconds must raise the suspicion of conduction defects or ventricular arrhythmias. Other symptoms related to underlying structural heart disease may also be present, especially chest discomfort, dyspnea, and fatigue. A thorough drug history including dosages used must be included in the evaluation of patients suspected of having ventricular arrhythmias. Two important studies57,58 have confirmed that a positive family history of SCD is a strong independent predictor of susceptibility to ventricular arrhythmias and SCD, as noted earlier. Physical examination is often unrevealing in patients suspected of having ventricular arrhythmias unless the arrhythmia occurs while the patient is being examined or has other findings indicative of structural heart disease.

5.2. Noninvasive evaluation

5.2.1. Resting electrocardiogram

Recommendations

Class I

  • Resting 12-lead ECG is indicated in all patients who are evaluated for ventricular arrhythmias. (Level of Evidence: A)

A standard resting 12-lead ECG allows not only identification of various congenital abnormalities associated with ventricular arrhythmias and SCD (e.g., LQTS, SQTS, Brugada syndrome, ARVC) but also identification of various other ECG parameters, such as those due to electrolyte disturbances, or evidence suggesting underlying structural disease, such as bundle-branch block, AV block, ventricular hypertrophy, and Q waves indicative of ischemic heart disease or infiltrative cardiomyopathy. QRS duration and repolarization abnormalities are both independent predictors of SCD. A prolonged QRS duration greater than 120 to 130 ms has been shown in a number of studies to be associated with increased mortality in patients with a reduced LVEF (equal to or less than 30%). Prospective studies have also reported an association between ST-segment depression or T-wave abnormalities and increased risk of cardiovascular death and SCD in particular. These studies have demonstrated a risk ratio for cardiovascular death of 2.16 (95% confidence interval [CI] 1.30 to 3.58) to 2.4 (95% CI 1.70 to 3.53) in the presence of an ‘ischemic’ ECG134 and 4.4 (95% CI 2.6 to 7.4) for SCD in the presence of an abnormal T-wave axis.135,136 A prolonged QTc interval is also an independent predictor of SCD. QTc greater than 420 ms has been shown to have a higher risk of cardiovascular death relative to a shorter QTc. And a QTc greater than 440 ms significantly predicted cardiovascular death with adjusted relative risk of 2.1.137 Although a prolonged QTc interval predicts SCD, it is worth noting that some data suggest that the correlation between QTc and survival may be ‘J-shaped.’ In other words, relatively short QTc intervals have also been associated with increased risk. For instance, it has been reported that patients with a mean QTc shorter than 400 ms during 24-h ECG have a more than 2-fold risk of dying suddenly than do patients with a mean QTc between 400 and 440 ms after a 2-y follow-up.138 A QTc less than 300 ms is often used to define the SQTS, which is an independent predictor of SCD.139,140

5.2.2. Exercise testing

Recommendations

Class I

  1. Exercise testing is recommended in adult patients with ventricular arrhythmias who have an intermediate or greater probability of having CHD by age, gender, and symptoms* to provoke ischemic changes or ventricular arrhythmias. (Level of Evidence: B) *See Table 4 in the ACC/AHA 2002 Guideline Update for Exercise Testing141 for further explanation of CHD probability.

  2. Exercise testing, regardless of age, is useful in patients with known or suspected exercise-induced ventricular arrhythmias, including catecholaminergic VT, to provoke the arrhythmia, achieve a diagnosis, and determine the patient's response to tachycardia. (Level of Evidence: B)

Class IIa

  • Exercise testing can be useful in evaluating response to medical or ablation therapy in patients with known exercise-induced ventricular arrhythmias. (Level of Evidence: B)

Class IIb

  1. Exercise testing may be useful in patients with ventricular arrhythmias and a low probability of CHD by age, gender, and symptoms.* (Level of Evidence: C) *See Table 4 in the ACC/AHA 2002 Guideline Update for Exercise Testing 141 for further explanation of CHD probability.

  2. Exercise testing may be useful in the investigation of isolated premature ventricular complexes (PVCs) in middle-aged or older patients without other evidence of CHD. (Level of Evidence: C)

Class III

  • See Table 1 in the ACC/AHA 2002 Guideline Update for Exercise Testing141 for contraindications. (Level of Evidence: B)

Exercise-ECG is commonly used in the evaluation of patients with ventricular arrhythmias. Its most common application is for detection of silent ischemia in patients suspected of having underlying CHD.141 In patients with known or silent CHD or cardiomyopathies, the presence of frequent PVCs during or after exercise has been associated with greater risk for serious cardiovascular events but not specifically SCD.19,20,24 Exercise-induced PVCs in apparently normal individuals should not be used to dictate therapy unless associated with documented ischemia or sustained VT. With the exception of beta blockers, at the present time the use of antiarrhythmic drugs to abolish exercise-induced PVCs has not been proved to be effective in reducing SCD.

Exercise testing in adrenergic-dependent rhythm disturbances, including monomorphic VT and polymorphic VT, may be useful in evaluating symptomatic subjects and evaluating response to therapy. Ambulatory ECG or event monitoring may fail to capture the arrhythmia, particularly if the patient is relatively sedentary. Moreover, exercise testing may provide prognostic information in these patients, given that the presence of exercise-induced ventricular ectopy increases mortality at 12 mo by 3-fold relative to patients with ectopy at rest only.142 Patients with exercise-induced paired ventricular complexes or VT have a lower survival rate than those with exercise-induced simple ventricular ectopy.143

Although the safety of supervised exercise testing is well established, less data are available in patients at risk for serious ventricular arrhythmias. In one series, exercise testing in patients with life-threatening ventricular arrhythmias was associated with a 2.3% incidence of arrhythmias requiring cardioversion, intravenous drugs, or resuscitation.144 Such an exercise study may still be warranted because it is better to expose arrhythmias and risk under controlled circumstances. Exercise testing should be performed where resuscitation equipment and trained personnel are immediately available.

5.2.3. Ambulatory electrocardiography

Recommendations

Class I

  1. Ambulatory ECG is indicated when there is a need to clarify the diagnosis by detecting arrhythmias, QT-interval changes, T-wave alternans (TWA), or ST changes, to evaluate risk, or to judge therapy. (Level of Evidence: A)

  2. Event monitors are indicated when symptoms are sporadic to establish whether or not they are caused by transient arrhythmias. (Level of Evidence: B)

  3. Implantable recorders are useful in patients with sporadic symptoms suspected to be related to arrhythmias such as syncope when a symptom-rhythm correlation cannot be established by conventional diagnostic techniques. (Level of Evidence: B)

The use of continuous or intermittent ambulatory recording techniques can be very helpful in diagnosing a suspected arrhythmia, establishing its frequency, and relating symptoms to the presence of the arrhythmia. Silent myocardial ischemic episodes may also be detected. A 24- to 48-h continuous Holter recording is appropriate whenever the arrhythmia is known or suspected to occur at least once a day. For sporadic episodes producing palpitations, dizziness, or syncope, conventional event monitors are more appropriate because they can record over extended periods of time.145

New implantable recorders are capable of monitoring the rhythm and can record on patient activation or automatically for prespecified criteria. Although these devices require surgical implantation, they have been shown to be extremely useful in diagnosing serious tachyarrhythmias and bradyarrhythmias in patients with life-threatening symptoms such as syncope.120,146

5.2.4. Electrocardiographic techniques and measurements

Recommendations

Class IIa

  • It is reasonable to use TWA to improve the diagnosis and risk stratification of patients with ventricular arrhythmias or who are at risk for developing life-threatening ventricular arrhythmias. (Level of Evidence: A)

Class IIb

  • ECG techniques such as signal-averaged ECG (SAECG), heart rate variability (HRV), baroflex sensitivity, and heart rate turbulence may be useful to improve the diagnosis and risk stratification of patients with ventricular arrhythmias or who are at risk of developing life-threatening ventricular arrhythmias. (Level of Evidence: B)

ICD trials, especially Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, have highlighted the need to develop novel tools in order to identify patients at highest risk of ventricular arrhythmias and SCD. Numerous modalities exist at present for assessing this risk but only 2 are currently approved by the U.S. Food and Drug Administration (FDA): SAECG and TWA. However, HRV and baroflex sensitivity also show considerable promise. SAECG improves the signal-to-noise ratio of a surface ECG, permitting the identification of low-amplitude (microvolt level) signals at the end of the QRS complex referred to as ‘late potentials.’ Late potentials indicate regions of abnormal myocardium demonstrating slow conduction, a substrate abnormality that may allow for reentrant ventricular arrhythmias, and they are believed to serve as a marker for the presence of an EP substrate for reentrant ventricular tachyarrhythmias. The presence of an abnormal SAECG was shown to increase the risk of arrhythmic events by 6- to 8-fold in a post-MI setting.147 However, the restoration of patency to the infarct-related coronary artery with fibrinolysis or angioplasty and the widespread use of surgical revascularization have modified the arrhythmogenic substrate, leading to a noticeable reduction in the predictive power of this tool. SAECG in isolation, therefore, is no longer useful for the identification of post-MI patients at risk of ventricular arrhythmias. However, a high negative predictive value of 89% to 99% rendered the SAECG a useful tool with which to exclude a wide-complex tachycardia as a cause of unexplained syncope.148,149

TWA, which is a fluctuation in the amplitude or morphology of the T wave that alternates every other beat assessed during exercise testing or atrial pacing, has been shown to be an effective tool for identifying high-risk patients post-MI150 and in the presence of ischemic or nonischemic cardiomyopathy. This association appears to be independent of EF and equally strong in patients with ischemic and nonischemic cardiomyopathy. TWA appears to have a very high negative predictive accuracy.151153 TWA may also be used to identify risk of arrhythmic mortality in patients with LV dysfunction due to prior MI.154 In a small study of patients with MADIT II characteristics (post-MI with EF less than or equal to 30%), a microvolt TWA test was found to be better than QRS duration at identifying a high-risk group and also a low-risk group unlikely to benefit from ICD therapy.155

HRV, which is a beat-to-beat variation in cardiac cycle length resulting from autonomic influence on the sinus node of patients in sinus rhythm, has been shown to independently predict the risk of SCD and total mortality in patients post-MI156 both with and without impaired LV function.157159 Observational studies also suggest its usefulness in the presence of nonischemic cardiomyopathy, but this has to be confirmed with large clinical trials. There are many different forms of heart rate analysis, some of which, such as heart rate turbulence, may be more productive than others. Reduced baroflex sensitivity, a quantitative assessment of the ability of the autonomic nervous system to react to acute stimulation involving primarily vagal reflexes, compared with a continuous assessment of basal sympathovagal information provided by HRV, has also proved successful in assessing the risk of SCD both alone (increased inducibility of arrhythmic events including VT during EP testing)160,161 and when used in combination with HRV (increased risk of cardiac mortality post-MI)157 and TWA (increased risk of arrhythmic events if both parameters are abnormal in a cohort of patients with ICDs).162 Additional prospective studies are needed to further clarify the role of these ECG parameters in assessing risk in differing clinical settings.

5.2.5. Left ventricular function and imaging

Recommendations

Class I

  1. Echocardiography is recommended in patients with ventricular arrhythmias who are suspected of having structural heart disease. (Level of Evidence: B)

  2. Echocardiography is recommended for the subset of patients at high risk for the development of serious ventricular arrhythmias or SCD, such as those with dilated, hypertrophic, or RV cardiomyopathies, AMI survivors, or relatives of patients with inherited disorders associated with SCD. (Level of Evidence: B)

  3. Exercise testing with an imaging modality (echocardiography or nuclear perfusion [single-photon emission computed tomography (SPECT)]) is recommended to detect silent ischemia in patients with ventricular arrhythmias who have an intermediate probability of having CHD by age, symptoms, and gender and in whom ECG assessment is less reliable because of digoxin use, LVH, greater than 1-mm ST-segment depression at rest, WPW syndrome, or LBBB. (Level of Evidence: B)

  4. Pharmacological stress testing with an imaging modality (echocardiography or myocardial perfusion SPECT) is recommended to detect silent ischemia in patients with ventricular arrhythmias who have an intermediate probability of having CHD by age, symptoms, and gender and are physically unable to perform a symptom-limited exercise test. (Level of Evidence: B)

Class IIa

  1. MRI, cardiac computed tomography (CT), or radionuclide angiography can be useful in patients with ventricular arrhythmias when echocardiography does not provide accurate assessment of LV and RV function and/or evaluation of structural changes. (Level of Evidence: B)

  2. Coronary angiography can be useful in establishing or excluding the presence of significant obstructive CHD in patients with life-threatening ventricular arrhythmias or in survivors of SCD, who have an intermediate or greater probability of having CHD by age, symptoms, and gender. (Level of Evidence: C)

  3. LF imaging can be useful in patients undergoing biventricular pacing. (Level of Evidence: C)

5.2.5.1. Echocardiograph

Echocardiography is the imaging technique that is most commonly used because it is inexpensive in comparison with other techniques such as MRI and cardiac CT, it is readily available, and it provides accurate diagnosis of myocardial, valvular, and congenital heart disorders associated with ventricular arrhythmias and SCD163,164 (Table 6). In addition, LV systolic function and regional wall motion can be evaluated and, in a majority of patients, EF can be determined.165 Echocardiography is therefore indicated in patients with ventricular arrhythmias suspected of having structural heart disease and in the subset of patients at high risk for the development of serious ventricular arrhythmias or SCD, such as those with dilated, hypertrophic or RV cardiomyopathies, AMI survivors, or relatives of patients with inherited disorders associated with SCD. The combination of echocardiography with exercise or pharmacological stress (commonly known as ‘stress echo’) is applicable to a selected group of patients who are suspected of having ventricular arrhythmias triggered by ischemia and who are unable to exercise or have resting ECG abnormalities that limit the accuracy of ECG for ischemia detection.164 Anomalous origin of coronary arteries can be detected by echocardiography or other imaging techniques.

View this table:
Table 6

Conditions associated with ventricular arrhythmias that can be diagnosed with echocardiography

Disease entityDiagnostic accuracy
Dilated cardiomyopathyHigh
Ischemic cardiomyopathyHigh
Hypertension with moderate to severe LVHHigh
Hypertrophic cardiomyopathyHigh
Valvular heart diseaseHigh
ARVCModerate
Brugada syndromePoor
  • ARVC, arrhythmogenic right ventricular cardiomyopathy; LVH, left ventricular hypertrophy.

5.2.5.2. Cardiac magnetic resonance imaging

Advances in cardiac MRI have made possible the use of this imaging technique to evaluate both the structure and function of the beating heart. The excellent image resolution obtained with current techniques allows for the accurate quantification of chamber volumes, LV mass, and ventricular function.166168 This is of particular value to patients with suspected arrhythmogenic RV cardiomyopathy (ARVC), in whom MRI provides excellent assessment of RV size, function, and regional wall motion and, importantly, may allow the detection of fatty infiltration within the RV myocardium.169,170 RV angiography may also be useful. Cardiac MRI increasingly is being applied and validated for the detection of ischemia (adenosine stress perfusion and dobutamine stress wall motion studies) and the detection and quantification of infarction/fibrosis, a substrate for VT. The cost and availability of cardiac MRI are becoming more competitive. Cardiac MRI can provide a comprehensive cardiac evaluation in a single study. It is important to stress that, as with all imaging modalities, accurate interpretation affects its usefulness.171

5.2.5.3. Cardiac computed tomography

As with MRI, the field of CT has advanced greatly with the development of fast scanners with better resolution that allow tomographic imaging of the heart and coronary arteries. These systems allow precise quantification of LV volumes, EF, and LV mass with results comparable to MRI but in addition provide segmental images of the coronary arteries from which the extent of calcification can be quantified.172176 The majority of cardiac disorders associated with serious ventricular arrhythmias or SCD are assessed well with echocardiography. Cardiac CT can be used in selected patients in whom evaluation of cardiac structures is not feasible with echocardiography and MRI is not available. There is currently no incremental clinical benefit derived from imaging the coronary arteries by cardiac CT in patients with ventricular arrhythmias.

5.2.5.4. Radionuclide techniques

Myocardial perfusion SPECT using exercise or pharmacological agents is applicable for a selected group of patients who are suspected of having ventricular arrhythmias triggered by ischemia and who are unable to exercise or have resting ECG abnormalities that limit the accuracy of ECG for ischemia detection. Myocardial perfusion SPECT can also be used to assess viability in patients with LV dysfunction due to prior MI.177 Accurate quantification of LVEF is possible with gated radionuclide angiography (multiple gated acquisition scan) and thus this technique may be helpful in patients for whom this measurement is not available with echocardiography.

5.2.5.5. Coronary angiography

In patients with life-threatening ventricular arrhythmias or in survivors of SCD, coronary angiography plays an important diagnostic role in establishing or excluding the presence of significant obstructive coronary artery disease. It is common for these patients to undergo this procedure as part of their diagnostic evaluation, particularly if they have an intermediate or greater probability for CHD. Detailed recommendations regarding imaging and exercise testing can be found in the respective guidelines.141,164,177

5.3. Electrophysiological testing

EP testing with intracardiac recording and electrical stimulation at baseline and with drugs has been used for arrhythmia assessment and risk stratification for SCD. EP testing for the evaluation of VT was introduced in 1972 by Wellens et al.178 The sensitivity, specificity, and predictive values of EP testing have been extensively assessed by various authors, usually in small patient groups. EP testing is used to document the inducibility of VT, guide ablation, evaluate drug effects, assess the risks of recurrent VT or SCD, evaluate loss of consciousness in selected patients with arrhythmias suspected as a cause, and assess the indications for ICD therapy.121,179183 The yield of EP testing varies fundamentally with the kind and severity of the underlying heart disease, the presence or absence of spontaneous VT, concomitant drug therapy, the stimulation protocol, and the site of stimulation. Highest induction rates and reproducibility are observed in patients after MI.184186

To evaluate patients with ventricular arrhythmias, most centers use 8 ventricular stimuli at drive cycle lengths between 600 and 400 ms at the RV apex, at twice diastolic threshold and the pulse duration of 0.5 to 2 ms, delivering 1 to 3 ventricular extrastimuli at baseline. This test may be repeated during isoproterenol infusion.187189 The prematurity of extrastimuli is increased until refractoriness or induction of sustained ventricular tachyarrhythmia is achieved. Long-short cycle sequences may be tested. Because premature ventricular stimulation with a very short coupling interval is more likely to induce VF as opposed to monomorphic VT, it may be reasonable to limit the prematurity of the extrastimuli to a minimum of 180 ms when studying patients for whom only inducible sustained monomorphic VT would be considered a positive endpoint.190 EP testing may be repeated at the RV outflow tract (RVOT) or LV.189 In some patients with rate-dependent induction of VT, rapid atrial or ventricular stimulation may induce VT.191

5.3.1. Electrophysiological testing in patients with coronary heart diseases

Recommendations

Class I

  1. EP testing is recommended for diagnostic evaluation of patients with remote MI with symptoms suggestive of ventricular tachyarrhythmias, including palpitations, presyncope, and syncope. (Level of Evidence: B)

  2. EP testing is recommended in patients with CHD to guide and assess the efficacy of VT ablation. (Level of Evidence: B)

  3. EP testing is useful in patients with CHD for the diagnostic evaluation of wide-QRS-complex tachycardias of unclear mechanism. (Level of Evidence: C)

Class IIa

  • EP testing is reasonable for risk stratification in patients with remote MI, NSVT, and LVEF equal to or less than 40%. (Level of Evidence: B)

Drug testing for assessing antiarrhythmic drug efficacy has largely been abandoned. EP testing was required in the MADIT, Multicenter UnSustained Tachycardia Trial (MUSTT), and Beta-Blocker Strategy plus Implantable Cardioverter Defibrillator (BEST-ICD) trials and others, but not in the MADIT II, Sudden Cardiac Death in Heart Failure (SCD-HeFT), or Antiarrhythmics Versus Implantable Defibrillators (AVID) trials. Inducibility of VT in patients with NSVT on Holter monitoring identified a population at high risk for VT/VF and ICD use in the MADIT trial.192

In a MUSTT trial substudy, the ECG characteristics of NSVT (rate, duration, frequency, occurrence in-hospital vs. out-of-hospital) did not correlate with inducibility.193195 Survival was worse for in-hospital compared with out-of-hospital NSVT,193 suggesting that different risk stratification criteria may be necessary in asymptomatic ambulatory patients. In a MADIT II substudy, inducibility was 36%. Lower heart rate, lower EF, and a longer interval between MI and an EP study correlates with higher inducibility.196

In patients with CHD, asymptomatic NSVT, and an EF less than 40%, inducibility of sustained VT ranges between 20% and 40%.116 Inducibility conferred a worse prognosis. Inducibility identifies patients at high risk of subsequent VT and that the absence of inducibility indicated a low risk with MADIT-like patients.197 However, these patients had a high rate of percutaneous revascularization. In CHD patients with a low EF (less than 30%), noninducibility does not portend a good prognosis.198 Persistent inducibility while receiving antiarrhythmic drugs predicts a worse prognosis.199 Patients in whom amiodarone suppressed VT inducibility or slowed VT to a mean cycle length of greater than 400 ms had 30% higher mortality compared with patients who did not respond to amiodarone and had an ICD placed instead.200 EP-guided antiarrhythmic drug effectiveness in patients with NSVT who had induced sustained VT conferred no benefit.195

The prognostic value of inducible ventricular flutter and VF is still controversial. Limited data on the prognostic value of inducible ventricular flutter suggest that it may be an important endpoint.201,202

5.3.2. Electrophysiological testing in patients with dilated cardiomyopathy

In DCM, EP testing plays a minor role in the evaluation and management of VT. This is related to low inducibility, reproducibility of EP study, and the predictive value of induced VT203,204 (see Section 9.1).

5.3.3. Electrophysiological testing in repolarization anomalies due to genetic arrhythmia syndromes

5.3.3.1. Long QT syndrome

EP testing has not proved useful in LQTS103,205 (see Section 11.1.1 for further discussion).

5.3.3.2. Brugada syndrome

The role of EP testing for risk stratification in Brugada syndrome is debated,104,206208 and it will probably remain undefined until prospective data are obtained in patients studied with a uniform protocol in a large population with adequate follow-up (see Section 11.1.3 for further discussion).

5.3.3.3. Hypertrophic cardiomyopathy

The value of EP testing in HCM has been controversial (see Section 9.2 for further discussion).

5.3.3.4. Arrhythmogenic right ventricular cardiomyopathy

The arrhythmic manifestations of ARVC are variable.96 The prognostic role of EP testing in patients presenting with isolated PVCs or NSVT is not known. The response to EP testing may be influenced by the severity of the disease. Progression of disease has to be considered (see Section 9.3 for further discussion).

5.3.4. Electrophysiological testing in patients with outflow tract ventricular tachycardia

EP testing for the evaluation of outflow tract VT is basically similar to that for other VT entities. It is motivated by the need to establish precise diagnosis to guide curative catheter ablation209,210 (see Section 12.1 for further discussion).

5.3.5. Electrophysiological testing in patients with syncope

Recommendations

Class I

  • EP testing is recommended in patients with syncope of unknown cause with impaired LV function or structural heart disease. (Level of Evidence: B)

Class IIa

  • EP testing can be useful in patients with syncope when bradyarrhythmias or tachyarrhythmias are suspected and in whom noninvasive diagnostic studies are not conclusive. (Level of Evidence: B)

Syncope is a transient symptom that may be caused by an underlying rhythm disorder with or without an associated cardiac disease. EP testing is used to document or exclude the arrhythmic cause of syncope.120,211 It is most useful in patients with CHD and LV dysfunction. EP testing is usually not the first evaluation step but rather is complementary to a full syncope work-up. Lack of correlation between symptoms and a documented arrhythmia elicited during EP testing may lead to overinterpretation or underinterpretation of the predictive value of the results. Transient drug effects that can provoke syncope may remain undetected. Other causes such as a neurological etiology need to be considered in some patients.

5.3.5.1. Electrophysiological testing when bradyarrhythmia is suspected

Syncope can be due to bradyarrhythmias from sinus node dysfunction or AV block. Antiarrhythmic drugs, beta-blocking agents, cardiac glycosides, and calcium channel blockers can induce symptomatic bradycardia. EP testing can be used to document or provoke bradyarrhythmias or AV block when other investigations have failed to provide conclusive information. The diagnostic yield varies greatly with the selected patient populations.212 EP testing is more useful in the presence of structural heart disease.213 The diagnostic yield in the absence of structural heart disease or abnormal ECG is low. False-positive results of EP testing can be present in up to 24% of the patients. In syncopal patients with chronic BBB and reduced EF (less than 45%), EP-induced VT is present in up to 42%.184,214,215 In patients with syncope and BBB, false-negative EP studies are common.216,217 EP testing in patients with sporadic bradycardia and syncope has limited sensitivity, even when adding electropharmacological stress such as intravenous procainamide or atropine.218 EP testing can provoke nonspecific tachyarrhythmic responses in patients with preserved LV function who do not have structural heart disease.219

5.3.5.2. Electrophysiological testing when supraventricular tachyarrhythmia is suspected

The role of EP testing is to document the type of tachyarrhythmia and to guide management of patients. In a mixed population, the diagnostic yield of EP testing was 5%.220 In supraventricular tachyarrhythmias, syncope is rarely the only symptom and palpitations are usually present as well. Vasodepressive reaction in a few patients with induced SVT, mainly AV node reentry,221 may be the cause of syncope. Syncope did not correlate with the rate or cycle length of preexcited R-R intervals in WPW syndrome during AF.221

5.3.5.3. Electrophysiological testing when ventricular tachycardia is suspected

Syncope in patients with structural heart disease and, in particular, significant LV dysfunction is ominous. NSVT on Holter monitoring, syncope, and structural heart disease are highly sensitive for predicting the presence of inducible VT.184 Syncope associated with heart disease and reduced EF has high recurrence and death rates,222,223 even when EP testing results are negative. EP testing is useful in patients with LV dysfunction due to prior MI (EF less than 40%) but not sensitive in patients with nonischemic cardiomyopathy.184 Induction of polymorphic VT or VF, especially with aggressive stimulation techniques, is not specific. In CHD, the diagnostic yield may reach 50%.222 In HCM, EP testing is not diagnostic in the majority of patients.224 Induction of nonspecific VTs in 23% of patients with slightly reduced EF has been observed.225

6. Therapies for ventricular arrhythmias

6.1. General management

The selection of appropriate therapy for the management of ventricular arrhythmias (PVCs, NSVT, sustained monomorphic and polymorphic VT, and ventricular flutter/VF) necessitates an understanding of the etiology and mechanism of the arrhythmia, an appreciation of the associated medical conditions that may contribute to and/or exacerbate the arrhythmia, the risk posed by the arrhythmia, and risk-to-benefit aspects of the selected therapy.31,99,226235 Management of the manifest arrhythmia may involve discontinuation of offending proarrhythmic drugs, specific antiarrhythmic therapy with drugs, implantable devices, ablation, and surgery.

6.2. Drug therapy

With the exception of beta blockers, the currently available antiarrhythmic drugs have not been shown in randomized clinical trials to be effective in the primary management of patients with life-threatening ventricular arrhythmias or in the prevention of SCD. As a general rule, antiarrhythmic agents may be effective as adjunctive therapy in the management of arrhythmia-prone patients under special circumstances. Because of potential adverse side effects of the available antiarrhythmic drugs, these agents must be used with caution. This section provides general comments about drug and interventional therapy for life-threatening arrhythmias. The recommendations and level of evidence for specific therapy of ventricular arrhythmias that occur in various cardiac disease states are provided in other sections of these guidelines, with the exception of recommendations on ablation, which are located in Section 6.6.

Many marketed cardiac and noncardiac drugs prolong ventricular repolarization and have the potential to precipitate life-threatening ventricular tachyarrhythmias202,236239 (see Section 13.6). Some patients are more susceptible than others to the QT-prolonging effects of these drugs even at an ordinary dosage, possibly due to a genetic propensity or female gender. More commonly, the proarrhythmic effect of the agent is related to elevated drug blood levels as a result of excessive dosage, renal disease, or drug interactions. Once it is appreciated that a patient's ventricular arrhythmia may be due to QT prolongation from one or more prescribed medications, the possible offending therapies should be discontinued and appropriate follow-up monitoring of ventricular repolarization and cardiac rhythm should be carried out.

6.3. Antiarrhythmic drugs

6.3.1. Value of antiarrhythmic drugs

Uses of antiarrhythmic drugs in the acute setting are described in Section 7.

The available antiarrhythmic drugs can be classified by the Vaughan Williams 4-level schema (type I: fast sodium channel blockers, type II: beta blockers, type III: repolarization potassium current blockers, type IV: calcium channel antagonists)240 or by the more mechanistic and clinically relevant Sicilian Gambit.241 The Vaughan Williams schema is somewhat outdated because antiarrhythmic drugs have complex actions that do not easily fit into 1 of the 4 specified classes of drug effects. This classification is of limited usefulness when choosing an antiarrhythmic drug to manage a specific arrhythmia. The Sicilian Gambit, introduced in 1991, was an attempt to provide a classification of antiarrhythmic drugs based on their mechanism of action and on arrhythmogenic mechanisms.

6.3.1.1. Beta blockers

These drugs are effective in suppressing ventricular ectopic beats and arrhythmias as well as in reducing SCD in a spectrum of cardiac disorders in patients with and without HF. Beta blockers are safe and effective antiarrhythmic agents that can be considered the mainstay of antiarrhythmic drug therapy.242,243 The mechanism of antiarrhythmic efficacy of this class of drugs involves competitive adrenergic-receptor blockade of sympathetically mediated triggering mechanisms, slowing of the sinus rate, and possibly inhibition of excess calcium release by the ryanodine receptor.244

6.3.1.2. Amiodarone and sotalol

Amiodarone has a spectrum of actions that includes block of potassium repolarization currents that can inhibit or terminate ventricular arrhythmias by increasing the wavelength for reentry. The overall long-term survival benefit from amiodarone is controversial, with most studies showing no clear advantage over placebo. A few studies and one meta-analysis of several large studies have shown reduction in SCD using amiodarone for LV dysfunction due to prior MI and nonischemic DCM,245247 but the SCD-HeFT trial showed no survival benefit from amiodarone compared with placebo. 7a,248. Chronic administration of amiodarone is associated with complex drug interactions and a host of adverse side effects involving the lung, liver, thyroid, and skin. As a general rule, the longer the therapy and the higher dose of amiodarone, the greater is the likelihood that adverse side effects will require discontinuance of the drug. Sotalol, like amiodarone, is effective in suppressing ventricular arrhythmias, but it has greater proarrhythmic effects and has not been shown to provide a clear increase in survival; worsening ventricular arrhythmias occur in 2% to 4% of treated patients.249

6.3.1.3. Efficacy of antiarrhythmic drugs

Overall, the available antiarrhythmic drugs other than beta blockers should not be used as primary therapy in the management of ventricular arrhythmias and the prevention of SCD. The efficacy of non-beta-blocker antiarrhythmic drugs is equivocal at best, and each drug has significant potential for adverse events including proarrhythmia.

6.3.2. Special considerations where antiarrhythmic drugs may be indicated

Amiodarone therapy may be considered in special situations;109 secondary subset analyses indicate possible survival benefit when amiodarone is combined with beta blockers.250,251 However, the SCD-HeFT study showed no benefit in patients with NYHA functional class II HF and potential harm in patients with NYHA functional class III HF and EF equal to or less than 35%.8 Azimilide was shown to decrease the risk of appropriate and inappropriate shocks in patients with ICDs.252 Both sotalol and amiodarone have also been shown to reduce the frequency of ICD shock therapy.253,254

6.3.2.1. Patients with ventricular tachyarrhythmias who do not meet criteria for an implantable cardioverter-defibrillator

Beta blockers are the first-line therapy, but if this therapy at full therapeutic dose is not effective, then amiodarone or sotalol can be tried with monitoring for adverse effects during administration.

6.3.2.2. Patients with implantable cardioverter-defibrillators who have recurrent ventricular tachycardia/ventricular fibrillation with frequent appropriate implantable cardioverter-defibrillator firing

This scenario, in its extreme, has been called defibrillator (tachycardia) storm, and it requires the addition of antiarrhythmic drugs and/or catheter ablation for control of the recurrent VT and associated ICD shocks. Sotalol is effective in suppressing atrial and ventricular arrhythmias;253 the combination of beta blockers and amiodarone is an alternative approach. Because many such patients have low EF and poor renal function, amiodarone and beta blockers rather than sotalol can be the first-line therapy for defibrillator storm. Sotalol should be avoided in patients with severely depressed LV function or significant HF. Animal studies255,256 and a case report showed the benefits of neural modulation via spinal cord approaches.257 Intravenous amiodarone has been useful.

6.3.2.3. Patients with implantable cardioverter-defibrillators who have paroxysmal or chronic atrial fibrillation with rapid rates and inappropriate implantable cardioverter-defibrillator firing

Control of the rapid ventricular response to atrial tachyarrhythmias is essential, and combination therapy with a beta blocker and/or a calcium channel blocker is useful. Amiodarone has been used off-label for rate control if other therapies are contraindicated, not tolerated, or ineffective. Ablation of the AV node may be required when pharmacological therapy is not effective.

6.4. Nonantiarrhythmic drugs

Use of nonantiarrhythmic drugs in the acute setting is further discussed in Section 7.

6.4.1. Electrolytes

Administration of potassium and magnesium, either as intravenously in the acute setting or orally for chronic augmentation in the blood levels of these electrolytes, can favorably influence the EP substrate involved in ventricular arrhythmias. These drugs are especially useful in the presence of hypokalemia and hypomagnesemia and should be considered as adjunctive therapies in the absence of low-level electrolytes. Adverse remodeling occurs in the ventricle following MI or in association with nonischemic cardiomyopathy; these structural changes with secondary ion channel alterations can exacerbate the potential for ventricular arrhythmias. Several drugs, such as ACE inhibitors, angiotensin II receptor antagonists, and aldosterone blockade with spironolactone or eplerenone, improve the myocardial substrate through reverse remodeling, and these therapies have been associated with a reduction in SCD as well as non-SCD.110,258 It is important to remember that electrolyte disturbances are common in patients with HF, particularly those using high doses of loop diuretics.

6.4.2. Antithrombins/antiplatelets

In a retrospective analysis of more than 6700 patients participating in the Studies Of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, antithrombin therapy was associated with reduction in SCD.259 Antiplatelet therapy that included aspirin and anticoagulant therapy contributed to this reduction in SCD, possibly as a result of reducing the frequency of coronary thrombotic occlusions in this high-risk group of patients.

6.4.3. n-3 Fatty acids and lipids

Increasing experimental and clinical evidence suggests that n-3 fatty acids are antiarrhythmic260 and may prevent SCD in humans.261 However, data are conflicting. In a randomized trial in patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation did not reduce the risk of VT/VF and perhaps was proarrhythmic in some patients.262 However, a second similar study found a trend toward prolongation of the first VT/VF event or death from any cause (p=0.057) and significant risk reduction when all probable VT/VF events were included.262,263

Findings indicate that statins reduce the occurrence of life-threatening ventricular arrhythmias in high-risk cardiac patients with electrical instability.264 Both of these therapies suggest that the mechanism of the antiarrhythmic effects may be related to EP stabilization of the bilipid myocyte membrane involved in maintaining electrolyte gradients.

6.5. Implantable and external cardioverter devices

6.5.1. Implantable cardioverter-defibrillator

Several prospective multicenter clinical trials have documented improved survival with ICD therapy in high-risk patients with LV dysfunction due to prior MI and nonischemic cardiomyopathy8,192,265270 (Figure 2). ICD therapy, compared with conventional or traditional antiarrhythmic drug therapy, has been associated with mortality reductions from 23% to 55% depending on the risk group participating in the trial, with the improvement in survival due almost exclusively to a reduction in SCD. The trials may be subcategorized into 2 types: primary prevention (prophylactic) trials in which the subjects have not experienced a life-threatening ventricular arrhythmia or a symptomatic equivalent and secondary prevention trials involving subjects who have had an abortive cardiac arrest, a life-threatening VT, or unexplained syncope with work-up suggesting a high probability that a ventricular tachyarrhythmia was the cause of the syncope.

Figure 2

Major implantable cardioverter-defibrillator (ICD) trials. Hazard ratios (vertical line) and 95% confidence intervals (horizontal lines) for death from any cause in the ICD group compared with the non-ICD group. CABG, coronary artery bypass graft surgery; EP, electrophysiological study; LVD, left ventricular dysfunction; LVEF, left ventricular ejection fraction; MI, myocardial infarction; N, number of patients; NICM, nonischemic cardiomyopathy; NSVT, nonsustained ventricular tachycardia; PVCs, premature ventricular complexes; SAECG, signal-averaged electrocardiogram. *Includes only ICD and amiodarone patients from CASH. For expansion of trial names, see Appendix 3.

Important ICD advancements continue to occur in the transvenous implantation procedure, generator size reduction, system longevity, arrhythmia detection, and multiprogrammable features. However, it is important to remember that device failure, although rare, can occur. Current ICDs include options for single-chamber, dual-chamber, and biventricular cardiac resynchronization pacing for nonshock termination of ventricular arrhythmia in addition to multilevel shock discharge for VT or VF. Problems associated with ICD therapy include inappropriate shock discharge mostly for AF with rapid ventricular response, defibrillator storm with appropriate recurrent ICD discharge for recurrent ventricular tachyarrhythmias or inappropriate discharge for a multiplicity of reasons, infections related to device implantation, and exacerbation of HF when a high percentage of the heartbeats are paced from the RV apex, especially when ventricular function is already compromised. It is probably advisable to limit RV pacing to a minimum for any given patient. Possible solutions include the selection of an appropriately low minimum rate and an appropriately long AV interval. Avoidance of overly aggressive rate acceleration in rate-modulated modes and, in some recent pacemaker models, the use of an automatic pacing mode selecting algorithms that strongly favor atrial over ventricular pacing.271 The HF is likely to occur in the setting of advanced LV dysfunction with the ICD unit programmed to dual-chamber (DDD) pacing at heart rates that dominate the rhythm, thus contributing to paced ventricular desynchronization.

The ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices, the ACC/AHA 2004 Guidelines for Management of Patients With ST-Elevation Myocardial Infarction, the ESC 2001 and 2003 Guidelines on Prevention of SCD, the ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure, and the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult include a large number of recommendations on ICD therapy which merit attention.16 Details and background references are provided in the full-text guidelines, which are on the ACC, AHA, HRS (formerly known as NASPE), and ESC Websites. The findings from the SCD-HeFT trial provide additional evidence that the ICD is effective in high-risk cardiac patients with ischemic and nonischemic cardiomyopathy.8 Differences in the recommendations in these guidelines from those previously published reflect primarily data from new studies. Detailed discussion on the considerations for therapy recommendations is found in the Introduction. However, there are inconsistencies among guidelines regarding the EF cutoff used in the recommendations.

6.5.2. Automated external defibrillator

The automated external defibrillator (AED) saves lives when external defibrillation can be rendered within minutes of onset of VF. The AED represents an efficient method of delivering defibrillation to persons experiencing out-of-hospital cardiac arrest, and its use by both traditional and nontraditional first responders appears to be safe and effective.272,273 Appropriate device location to reduce time delay after onset of cardiac arrest is critical. Federal, state, and community efforts have been effective in placing AEDs in schools, sporting events, high-density residential sites, and airports as well as on airplanes and in police and fire department vehicles.274277 Approximately 80% of cardiac arrests occur in the home, and placement of AEDs in the home appears to be reasonable and appropriate for patients at high risk for life-threatening arrhythmias. Federal regulatory authorities in the United States have approved the AED for home use in families with high-risk inherited arrhythmias such as the LQTS and HCM. The FDA has now approved over-the-counter sales of AEDs.

6.5.3. Wearable automatic defibrillator

The wearable automatic defibrillator is a vestlike device worn under the clothing that continuously monitors heart rhythm and automatically delivers an electric shock when VF is detected. This device is worn continuously on a 24-h-a-day basis, except when the wearer is bathing or showering. The wearable automatic defibrillator has been approved in the United States by the FDA for cardiac patients with a transient high risk for VF such as those awaiting cardiac transplantation, those at very high risk after a recent MI or an invasive cardiac procedure, or those requiring temporary removal of an infected implanted defibrillator for antibiotic therapy.

6.6. Ablation

Recommendations

Class I

  1. Ablation is indicated in patients who are otherwise at low risk for SCD and have sustained predominantly monomorphic VT that is drug resistant, who are drug intolerant, or who do not wish long-term drug therapy. (Level of Evidence: C)

  2. Ablation is indicated in patients with bundle-branch reentrant VT. (Level of Evidence: C)

  3. Ablation is indicated as adjunctive therapy in patients with an ICD who are receiving multiple shocks as a result of sustained VT that is not manageable by reprogramming or changing drug therapy or who do not wish long-term drug therapy (206,278). (Level of Evidence: C)

  4. Ablation is indicated in patients with WPW syndrome resuscitated from sudden cardiac arrest due to AF and rapid conduction over the accessory pathway causing VF (279). (Level of Evidence: B)

Class IIa

  1. Ablation can be useful therapy in patients who are otherwise at low risk for SCD and have symptomatic nonsustained monomorphic VT that is drug resistant, who are drug intolerant or who do not wish long-term drug therapy. (Level of Evidence: C)

  2. Ablation can be useful therapy in patients who are otherwise at low risk for SCD and have frequent symptomatic predominantly monomorphic PVCs that are drug resistant or who are drug intolerant or who do not wish long-term drug therapy. (Level of Evidence: C)

  3. Ablation can be useful in symptomatic patients with WPW syndrome who have accessory pathways with refractory periods less than 240 ms in duration (279). (Level of Evidence: B)

Class IIb

  1. Ablation of Purkinje fiber potentials may be considered in patients with ventricular arrhythmia storm consistently provoked by PVCs of similar morphology (280). (Level of Evidence: C)

  2. Ablation of asymptomatic PVCs may be considered when the PVCs are very frequent to avoid or treat tachycardia-induced cardiomyopathy (281). (Level of Evidence: C)

Class III

  • Ablation of asymptomatic relatively infrequent PVCs is not indicated. (Level of Evidence: C)

6.6.1. Catheter ablation—background

The specific application of radiofrequency (RF) ablation to VT has evolved as the technology has developed. RF ablation can be applied in the treatment of VT in patients with LV dysfunction due to prior MI, cardiomyopathy, bundle-branch reentry, and various forms of idiopathic VT.282294

6.6.2. No apparent structural heart disease

Specific mapping and ablation techniques that are used differ depending on the type of VT. While patients with no overt structural heart disease account for a small percentage of patients with VT, they are of particular interest for ablation therapy as this technique may be curative.295,296 These typically present as a single VT arising from the RV with an LBBB inferior axis morphology or from the LV with a right bundle-branch block (RBBB) morphology and, in general, are associated with a good prognosis.289,297300

6.6.3. Bundle-branch reentrant VT

Bundle-branch reentrant VT is often associated with cardiomyopathy.279 RF catheter ablation of the bundle branches is curative of the arrhythmia but not of the underlying structural abnormality.301 Because of the severity of underlying heart disease and the high prevalence of conduction abnormalities, adjunct device therapy should be strongly considered in these patients.301

6.6.4. Structural heart disease

VT is a common complication of structural heart disease and carries significant risk for mortality in CHD patients with low EF. In those with extensive structural abnormalities, especially those with prior MI, multiple morphologies of VT are often present. As a result, ablation of a single VT morphology can provide palliation but not eliminate the need for device or antiarrhythmic therapy. In these patients, VT can originate in, or involve, extensive areas of the myocardium and standard RF delivery carries a relatively low success rate.302304 Given the inhomogeneous scarring present in ischemic VT, mapping techniques have evolved that take into account the complex nature of the circuits, including bystander regions of abnormal conduction. The newer 3-dimensional mapping systems permit anatomical reconstructions and correlation of EP characteristics with anatomy.190,305308 These systems have led to an approach whereby circuits can be mapped during sinus rhythm and can facilitate ablation in the ischemic patient who often does not tolerate VT well.303,309312 Use of these techniques may result in better long-term success rates.313

6.6.5. Additional ablation tools

Depending on the arrhythmic substrate, VT circuits can be close to the endocardium or exist deeper within the myocardium. The focal lesion of traditional RF delivery systems may not create lesions deep enough to penetrate intramyocardial circuits. As a result, saline-irrigated cooled-tip catheters have been developed and used in VT ablation. Cooling the tip of the catheter permits deeper tissue heating. Preliminary results are promising, but further data are needed.314 Another novel technique involves transthoracic pericardial access for mapping and ablation. This technique was developed to address VTs that are extremely deep within the myocardium or actually epicardial. It involves inserting a sheath into the pericardial space and performing mapping from the epicardium.206,315,316 Few centers have taken on this approach. This technique must be performed with surgical support available if needed, and caution must be taken to avoid the epicardial coronary arteries.317,318 Another novel technique, not used recently, is transcoronary chemical ablation of incessant VT and VF.319,320 A more recent technique involves spinal cord modulation to suppress ventricular arrhythmias.255257 Additional studies have suggested that catheter ablation of VF in structurally normal hearts may be feasible by targeting dominant triggers from the distal Purkinje system. These techniques are still considered highly experimental.280,317,318,321

6.7. Surgery and revascularization procedures

Surgical therapy for the management of ventricular arrhythmias may involve ablation or surgical resection of an arrhythmogenic focus, cardiac sympathectomy, or aneurysm resection. Surgical or percutaneous coronary revascularization with improved coronary blood flow and reduction in myocardial ischemia has favorable antiarrhythmic effects. (See the ACC/AHA 2004 Guideline Update for Coronary Artery Bypass Graft Surgery.322)

6.7.1. Antiarrhythmic surgery

In patients with recurrent VT refractory to drugs, implanted defibrillators, and RF catheter ablation, direct surgical ablation or resection of the arrhythmogenic focus is an approach that continues to be used in experienced centers. Surgery requires accurate preoperative and intraoperative mapping to determine the site or sites of the tachycardia. Some centers use a scar-based approach to resecting arrhythmogenic sites. The short- and long-term success rates of map-guided surgical therapy for recurrent-refractory VT are based mostly on the older literature, and few reports are available to evaluate risk-to-benefit considerations in the current era in patients refractory to catheter ablation and implanted defibrillators.323

Left cervicothoracic sympathetic ganglionectomy was introduced in 1971 for the treatment of adrenergically triggered life-threatening ventricular arrhythmias associated with the LQTS.324 This procedure, performed through a limited supraclavicular approach, involves resection of the lower half of the left stellate ganglion and removal of at least the second and third thoracic sympathetic ganglia on the left side.325 This surgical therapy is associated with reduction in the frequency of arrhythmogenic syncope in this syndrome and may be useful as adjunctive therapy in high-risk LQTS patients who have recurrent syncope and/or aborted cardiac arrest despite combined ICD and beta-blocker therapy or in LQTS patients who cannot tolerate beta blockers.326

Large myocardial aneurysms secondary to MI are associated with hemodynamic compromise and are frequently accompanied by major ventricular arrhythmias. In selected patients, aneurysm resection can improve cardiac function and, along with map-guided EP mapping and resection of arrhythmogenic ventricular myocardium, may reduce or eliminate the accompanying ventricular arrhythmias.327

6.7.2. Revascularization for arrhythmia management

In patients with ventricular arrhythmias, assessment for the presence of obstructive coronary disease and active ischemia is essential. Coronary revascularization involving either percutaneous balloon/stent angioplasty or bypass surgery is effective anti-ischemic therapy. A review of coronary revascularization studies reveals improved survival and reduction in SCD during long-term follow-up.328,329 If obstructive CHD is complicated by ventricular arrhythmias, especially in patients with left main and proximal left anterior descending coronary artery disease, there is a reasonable likelihood that revascularization will reduce the frequency and complexity of the arrhythmias and, in some patients, will eliminate such arrhythmias. No controlled trials have evaluated the effects of myocardial revascularization on VT or VF. However, observational studies suggest that:

  • Sustained monomorphic VT in patients with prior MI is unlikely to be affected by revascularization.330

  • Myocardial revascularization is unlikely to prevent recurrent cardiac arrest in patients with markedly abnormal LV function, even if the original arrhythmia appeared to result from transient ischemia.331

Further discussion can be found in Section 8.7.

Because ventricular arrhythmias are not always reduced by revascularization332,333 and may in fact be exacerbated by unrecognized procedure-related MI, careful postprocedure monitoring for arrhythmia suppression is indicated. Suppression of ischemia-mediated ventricular arrhythmias and improvement in survival associated with coronary revascularization may have contributed to the lack of ICD efficacy in the Coronary Artery Bypass Graft (CABG) Patch Trial.265 In patients undergoing revascularization surgery following aborted cardiac arrest unrelated to an AMI, it is reasonable to implant a defibrillator after revascularization surgery in view of the assumed high-risk state. However, it is reasonable not to implant an ICD if there was direct, clear evidence of myocardial ischemia immediately preceding the onset of VF and there was no evidence for prior MI (see also Sections 8.1 and 8.3).

7. Acute management of specific arrhythmias

7.1. Management of cardiac arrest

Cardiac arrest is characterized by an abrupt loss of effective blood flow, sufficient to cause immediate loss of consciousness, leading immediately to death if untreated. The most common electrical mechanisms for cardiac arrest are VF and pulseless VT (see Section 3), but substantial numbers of cardiac arrests begin as severe bradyarrhythmias, asystole, or pulseless electrical activity. Survival probabilities are better for victims presenting with VT/VF than for those with bradyarrhythmic or asystolic mechanisms. A rapid response time is the major determinant of survival.

Recommendations

Class I

  1. After establishing the presence of definite, suspected, or impending cardiac arrest, the first priority should be activation of a response team capable of identifying the specific mechanism and carrying out prompt intervention. (Level of Evidence: B)

  2. Cardiopulmonary resuscitation (CPR) should be implemented immediately after contacting a response team. (Level of Evidence: A)

  3. In an out-of-hospital setting, if an AED is available, it should be applied immediately and shock therapy administered according to the algorithms contained in the documents on CPR 334,335 developed by the AHA in association with the International Liaison Committee on Resuscitation (ILCOR) and/or the European Resuscitation Council (ERC). (Level of Evidence: C)

  4. For victims with ventricular tachyarrhythmic mechanisms of cardiac arrest, when recurrences occur after a maximally defibrillating shock (generally 360 J for monophasic defibrillators), intravenous amiodarone should be the preferred antiarrhythmic drug for attempting a stable rhythm after further defibrillations. (Level of Evidence: B)

  5. For recurrent ventricular tachyarrhythmias or nontachyarrhythmic mechanisms of cardiac arrest, it is recommended to follow the algorithms contained in the documents on CPR334,335 developed by the AHA in association with ILCOR and/or the ERC. (Level of Evidence: C)

  6. Reversible causes and factors contributing to cardiac arrest should be managed during advanced life support, including management of hypoxia, electrolyte disturbances, mechanical factors, and volume depletion. (Level of Evidence: C)

Class IIa

  • For response times greater than or equal to 5 min, a brief (less than 90 to 180 s) period of CPR is reasonable prior to attempting defibrillation. (Level of Evidence: B)

Class IIb

  • A single precordial thump may be considered by health care professional providers when responding to a witnessed cardiac arrest. (Level of Evidence: C)

A number of strategies for responding to unexpected cardiac arrest have resulted in improved survival probabilities for cardiac arrest victims.336 Nonetheless, the absolute number and proportion of survivors remain low,337 except in unique circumstances where there is an extraordinarily rapid response time to victims in VF or VT. A decrease in cardiac arrest survival occurs at about 7% to 10% per minute if no CPR is initiated and at 3% to 4% per minute with bystander CPR. In contrast, when immediate defibrillation in highly protected environments is available, such as in monitored intensive care units and EP laboratories, where response times of less than 30 s are usually achievable, survival from VF is greater than 90%, the exception being patients with pathophysiological conditions that favor the persistence of this potentially fatal arrhythmia. Survivability falls off rapidly after the initial 2 min from the onset of cardiac arrest, so that by 4 to 5 min survivability may be 25% or less, and by 10 min it is less than 10%. Studies have suggested that while immediate defibrillation is the preferred method within 1 to 2 min after the onset of cardiac arrest, a brief period of CPR to provide oxygenation of the victim improves survivability when time to defibrillation is longer.338340

Advanced life support activities, other than those directly related to electrical methods for control of tachyarrhythmias, led to the generation of complex protocols to guide responders. These documents, published by the AHA334 and the ERC,335 cover the broad expanse of clinical circumstances and considerations of mechanisms. They provide management information, stratified for special circumstances such as age of the victim (from infancy to the elderly), pathophysiological status, and survival probabilities. The response algorithms to these various circumstances are complex and the reader is referred to the source documents for details.334,335 As management guidelines, these documents are classified as Level of Evidence: C, but they are derived from a combination of varied studies and opinion that range from Level of Evidence: A, B, or C. Abbreviated versions for tachyarrhythmias and nontachyarrhythmic mechanisms are shown in Figure 3.

Figure 3

Advanced cardiac life support pulseless arrest algorithm. Reprinted with permission from Circulation 2005;112:IV57–66. AED, automated external defibrillator; BLS, basic life support; CPR, cardiopulmonary resuscitation; IV/IO, intravenous/intraosseous; PEA, pulseless electrical activity; VF, ventricular fibrillation; VT, ventricular tachycardia.

Consistent with the AHA/ERC 2005 guidelines, the amount of energy and timing of shocks for treatment of VT in patients with pulses are determined by the patient's condition and the morphological characteristics of the VT. Unstable monomorphic VT is treated with synchronized cardioversion, while unstable polymorphic VT is treated as VF using high-energy unsynchronized shocks at defibrillation doses. Monomorphic VT in patients with pulses generally responds well to monophasic waveform cardioversion synchronized shocks at initial energies of 100 J or higher. More data are needed before specific comparative recommendations can be made for energy doses of biphasic devices. Synchronized cardioversion is generally not recommended to treat unstable polymorphic VT because of unreliable synchronization to a QRS complex and high-energy unsynchronized shock at defibrillation doses is recommended. If there is any doubt whether monomorphic or polymorphic VT is present in the unstable patient, shock delivery should not be delayed for detailed rhythm analysis. The initial recommended shock energy with a biphasic defibrillator is 150 to 200 J (use recommended device-specific dose; in absence of a recommended dose, 200 J should be used) and an equal or higher dose is recommended for second and subsequent shocks. If a monophasic defibrillator is used, 360 J is used for all shocks. Lower energy levels should not be used for unsynchronized shocks because they can provoke VF when given in an unsynchronized mode. After shock delivery, the health care provider should be prepared to provide immediate CPR and follow the advanced cardiac life support (ACLS) pulseless arrest algorithm if pulseless arrest develops (Figure 3).

The general goals of advanced life support are to establish hemodynamically effective cardiac rhythm, to optimize ventilation, and to maintain and support the restored circulation. While 3 successive (‘stacked’) shocks were recommended in the previous version of the ECC guidelines,341 a 1-shock strategy is now recommended to minimize time between chest compressions and shock delivery and resumption of chest compressions6,334,335 (see Figure 3). Epinephrine, 1 mg intravenously, is administered and followed by repeated defibrillation attempts at 360 J. Epinephrine may be repeated at 3- to 5-min intervals with defibrillator shocks in-between doses,334 but high-dose epinephrine does not appear to provide added benefit.342

Intravenous amiodarone has replaced intravenous lidocaine and other antiarrhythmic medications for the management of resistant ventricular tachyarrhythmias causing repeated episodes of ventricular tachyarrhythmias.343 Amiodarone need not be given routinely to the individual who responds to initial defibrillation with a stable rhythm. If there is sufficient clinical evidence that a cardiac arrest was heralded by the onset of an ACS, intravenous lidocaine may still be used for resistant arrhythmias. Beta blockers may be preferred for ACSs if not already being taken. For pharmacological hemodynamic support during cardiac arrest management, vasopressin has been suggested as an alternative to epinephrine,344 but the evidence for superiority is not clearly established. Responses to nontachyarrhythmic cardiac arrest largely focus on control of metabolic and transient factors that may precipitate bradyarrhythmic events or pulseless electrical activity (Figure 3).

Simultaneously, the rescuer should focus on ventilation to correct the chemistry of the blood, efforts that render the heart more likely to reestablish a stable rhythm (i.e., improved oxygenation, reversal of acidosis, and improvement of the underlying EP condition). Although adequate oxygenation of the blood is crucial in the immediate management of the metabolic acidosis of cardiac arrest, additional correction can be achieved if necessary by intravenous administration of sodium bicarbonate. This is recommended for circumstances of known or suspected preexisting bicarbonate-responsive causes of acidosis, certain drug overdoses, and prolonged resuscitation runs.334 The more general role for bicarbonate during cardiac arrest has been questioned; but in any circumstance, much less sodium bicarbonate than was previously recommended is adequate for treatment of acidosis in this setting. Excessive quantities can be deleterious.

In patients in whom acute hyperkalemia is the triggering event for resistant VF, or who have hypocalcemia or are toxic from Ca2+ entry-blocking drugs, 10% calcium gluconate, 5 mL to 20 mL infused at a rate of 2 to 4 mL/min, may be helpful.334 Calcium should not be used routinely during resuscitation, even though ionized Ca2+ levels may be low during resuscitation from cardiac arrest. Some resistant forms of polymorphic VT or torsades de pointes, rapid monomorphic VT or ventricular flutter (rate greater than or equal to 260/min), or resistant VF may respond to intravenous beta-blocker therapy (propranolol, 1-mg intravenous boluses to a total dose of up to 15 to 20 mg; metoprolol, 5 mg intravenously, up to 20 mg) or intravenous MgSO4 (1 to 2 g intravenously given over 1 to 2 min).

The approach to the patient with bradyarrhythmic or asystolic arrest or pulseless electrical activity differs from the approach to patients with tachyarrhythmic events of VT/VF.334 Once this form of cardiac arrest is recognized, efforts should focus first on establishing control of the cardiorespiratory status (i.e., continue CPR, intubate, and establish intravenous access), then on reconfirming the rhythm (in 2 leads if possible), and finally on taking actions that favor the emergence of a stable spontaneous rhythm or attempt to pace the heart. Possible reversible causes, particularly for bradyarrhythmia and asystole, should be considered and excluded (or treated) promptly. These include pulmonary embolus, AMI, hypovolemia, hypoxia, cardiac tamponade, tension pneumothorax, preexisting acidosis, drug overdose, hypothermia, and hyperkalemia. Cardiac pacing for bradyarrhythmic or asystolic arrests is usually ineffective,345 but reversal of hypoxemia, acidosis, or electrolyte imbalances may help in some instances. Epinephrine (1.0 mg intravenously every 3 to 5 min) is commonly used in an attempt to elicit spontaneous electrical activity or increase the rate of a bradycardia. For asystole and pulseless electrical activity, atropine as 1.0 mg intravenously/intraosseously, repeated every 3 to 5 min up to a total of 3 doses or 0.03 to 0.04 mg/kg is recommended. For bradycardia, atropine 0.5 mg intravenously/intraosseously, repeated every 3 to 5 min up to a total dose of 0.04 mg/kg, is recommended. Sodium bicarbonate, 1 mEq/kg, may be tried for known or suspected preexisting hyperkalemia or bicarbonate-responsive acidosis.

7.1.1. Arrhythmias associated with acute coronary syndromes

For recommendations, see Section 7.1 in these guidelines and refer to the current guidelines on ACLS.334,335

ACS can give rise to a life-threatening arrhythmia that may be the first manifestation of ischemia. The mechanisms of these arrhythmias may be different from those seen in chronic stable ischemic heart disease. Arrhythmias during acute ischemia may be related to re-entry, abnormal automaticity, or triggered activity and are affected by a variety of endogenous factors such as potassium levels and autonomic states. These arrhythmias may cause many of the reported sudden deaths in patients with ischemic syndromes. VF or sustained VT has been reported in up to 20% of AMIs.346,347

The incidence of VF (occurring within 48 h of the onset of the ACS) may be decreasing owing to aggressive revascularization limiting infarct size and to increased beta-blocker use.348 VF occurring early in the ACS has been associated with an increase in hospital mortality but not with increased long-term mortality.346 Prophylaxis with lidocaine may reduce the incidence of VF in the ACS but appears to be associated with increased mortality likely owing to bradycardia and this treatment has largely been abandoned.349 Use of prophylactic beta blockers in the setting of AMI reduces the incidence of VF, and this practice is encouraged when appropriate. Similarly, correction of hypomagnesemia and hypokalemia is encouraged because of the potential contribution of electrolyte disturbances to VF.350

More recent data showed the benefit of the eplerenone, an aldosterone antagonist, in reducing the risk of SCD mortality by 37% (p=0.051) 30 d after randomization in patients after AMI (when initiated at a mean of 7.3 d after AMI) in addition to conventional therapy in patients with an LVEF less than or equal to 40% and signs of HF.351

7.1.1.1. Pulseless ventricular tachycardia/ventricular fibrillation

In the event of pulseless VT or VF in ACS, the standard ACLS protocol is initiated including unsynchronized electric shock following basic assessment of airway and initiation of CPR. Energy delivery consists of 1 or more monophasic shocks at 360 J or biphasic shocks at a dose range demonstrated by manufacturer to be effective. If not available, a dose of 200 J is recommended for the first shock and an equal or higher dose for subsequent shocks. The optimal dose for biphasic shocks has not been determined, and no waveform or escalating energy levels recommendations can be made for biphasic defibrillators at this time. If return to normal rhythm is not accomplished by defibrillation, the ACLS protocol for pulseless VT or VF is followed. This includes epinephrine (1 mg intravenously every 3 to 5 min) or vasopressin (40 U intravenously once only; 1 dose of vasopressin intravenously/intraosseously may replace either the first or second dose of epinephrine), and amiodarone (300-mg or 5-mg/kg intravenous push, with a possible repeat 150-mg intravenous push once only), or as a second tier, lidocaine (1.0 to 1.5 mg/kg with repeat dose of 0.5 to 0.75 mg intravenously/intraosseously up to a total dose of 3 mg/kg). Additional second-tier therapy includes intravenous magnesium (1 to 2 g) or procainamide (30 mg/min up to 17 mg/kg). The latter is considered acceptable but is no longer recommended.334

Following resuscitated VF, prophylactic drug infusion, typically with amiodarone plus a beta blocker, may be continued. The antiarrhythmic should be withdrawn as appropriate to assess the presence of ongoing arrhythmias.

7.1.1.2. Idioventricular rhythm and nonsustained ventricular tachycardia

Neither idioventricular rhythm nor NSVT (lasting less than 30 s) occurring in the setting of ACS serves as a reliably predictive marker for early VF. In fact, accelerated idioventricular rhythm has been associated with reperfusion.352 As such, these arrhythmias do not warrant prophylactic antiarrhythmic therapy. However, sustained and/or hemodynamically compromising VT in ACS requires suppressive therapy.2 Management of pulseless VT follows the ACLS guidelines for pulseless VT/VF.

7.1.1.3. Unstable sustained ventricular tachycardia

For recurrent VT, if VT is monomorphic and the EF is normal, either procainamide, sotalol, amiodarone, or lidocaine can be used. Alternately, if the EF is low, amiodarone or lidocaine is recommended (amiodarone 150 mg intravenously over 10 min or lidocaine 0.5 to 0.75 mg/kg intravenous push). If the VT is polymorphic and the baseline QT is normal, correction of underlying ischemia and electrolyte abnormalities is emphasized. This may be followed by, or performed concurrently with, administration of a beta blocker or lidocaine or amiodarone or procainamide or sotalol. If the VT is polymorphic and the EF is low, treatment with amiodarone 150 mg intravenously over 10 min or lidocaine 0.5 to 0.75 mg/kg intravenous push is recommended. In polymorphic VT, if the baseline QT is prolonged, correction of electrolytes is emphasized and other treatments may include magnesium, overdrive pacing, isoproterenol, phenytoin, or lidocaine.

7.1.1.4. Bradycardia and heart block

Bradycardia and heart block can occur as a result of MI. The likelihood of developing complete heart block complicating MI increases in the presence of underlying conduction system disease. Occurrence of heart block as a result of MI has been associated with an increase in hospital mortality but does not predict long-term mortality in those surviving to discharge.353 The increase in hospital mortality is related to the extensive amount of myocardial damage required to develop heart block rather than to the heart block itself. While pacing has not been shown to increase long-term survival post-MI, it is still indicated in symptomatic bradyarrhythmias associated with AMI, and pacing guidelines are as stated in the 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction2 and the ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices.1

7.1.2. Ventricular tachycardia associated with low troponin myocardial infarction

Recommendations

Class I

  • Patients presenting with sustained VT in whom low-level elevations in cardiac biomarkers of myocyte injury/necrosis are documented should be treated similarly to patients who have sustained VT and in whom no biomarker rise is documented. (Level of Evidence: C)

Prolonged episodes of sustained monomorphic VT may be associated with rise in cardiac biomarkers due to myocardial metabolic demands exceeding supply, especially in patients with CHD. Such patients usually have a history of MI. It is reasonable to evaluate for myocardial ischemia in patients exhibiting these findings. When sustained VT is accompanied by a modest elevation in cardiac enzymes, it should not be assumed that a new MI occurred to cause the tachycardia. In the absence of other data, it should be assumed that patients experiencing sustained monomorphic VT are at risk for recurrent VT and should be treated for this arrhythmia in the same manner as are patients without biomarker release accompanying VT.

7.2. Sustained monomorphic ventricular tachycardia

Recommendations

Class I

  1. Wide-QRS tachycardia should be presumed to be VT if the diagnosis is unclear. (Level of Evidence: C)

  2. Direct current cardioversion with appropriate sedation is recommended at any point in the treatment cascade in patients with suspected sustained monomorphic VT with hemodynamic compromise. (Level of Evidence: C)

Class IIa

  1. Intravenous procainamide (or ajmaline in some European countries) is reasonable for initial treatment of patients with stable sustained monomorphic VT. (Level of Evidence: B)

  2. Intravenous amiodarone is reasonable in patients with sustained monomorphic VT that is hemodynamically unstable, refractory to conversion with countershock, or recurrent despite procainamide or other agents. (Level of Evidence: C)

  3. Transvenous catheter pace termination can be useful to treat patients with sustained monomorphic VT that is refractory to cardioversion or is frequently recurrent despite antiarrhythmic medication. (Level of Evidence: C)

Class IIb

  • Intravenous lidocaine might be reasonable for the initial treatment of patients with stable sustained monomorphic VT specifically associated with acute myocardial ischemia or infarction. (Level of Evidence: C)

Class III

  • Calcium channel blockers such as verapamil and diltiazem should not be used in patients to terminate wide-QRS-complex tachycardia of unknown origin, especially in patients with a history of myocardial dysfunction. (Level of Evidence: C)

Electrical cardioversion is always indicated for hemodynamically unstable tachycardia. Managing the patient presenting with well-tolerated, wide-QRS tachycardia is facilitated by differentiating between VT, SVT with aberrant conduction, and preexcited tachycardia.354 This can usually be accomplished by consideration of the history and examination of the 12-lead ECG during tachycardia. The hemodynamic status of the patient is not helpful in distinguishing these mechanisms. A working diagnosis of VT is appropriate when the diagnosis is unclear because VT is more prevalent, especially in the patient with structural heart disease, and therapy directed inappropriately at SVT may have adverse consequences.355,356 Monomorphic VT is usually related to a structural abnormality such as MI scarring but is mechanistically heterogeneous. Some ‘idiopathic’ VTs respond well and terminate with intravenous verapamil or adenosine, and those expert in arrhythmia management may choose to treat the acute episode with these agents.357,358 If these unique VT entities cannot be recognized with confidence, it is prudent to assume that one is dealing with VT related to structural heart disease.

Correction of potentially causative or aggravating conditions such as hypokalemia and ischemia is an early priority. Timely termination is usually desirable even if VT is well tolerated. This can be achieved with cardioversion, antiarrhythmic medications, or pacing techniques. DC cardioversion even at early stage or as ‘first line’ is reasonable.359,360 Advantages include the absence of proarrhythmia and high efficacy in a timely fashion. Cardioversion does not prevent recurrence, and a major disadvantage is the need for deep sedation or anesthesia. Caution needs to be exercised if the patient also has concurrent AF (e.g., double tachycardia). If such is the case, the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation need to be followed when feasible.361

Initial treatment often includes the administration of intravenous antiarrhythmic medication. The advantages include the lack of necessity for anesthesia and ready availability. Disadvantages include delay in termination, failure to terminate in some patients, and adverse effects including hypotension and proarrhythmia. Although drugs such as flecainide, propafenone, and sotalol are available in intravenous preparations in some countries, only intravenous procainamide, lidocaine, and amiodarone are widely available. Intravenous ajmaline is used frequently in some European countries. Intravenous amiodarone loading has proved useful in unstable and recurrent VT, especially when VT is recurrent after countershock and other antiarrhythmic measures.362366 It is also reasonable in patients in whom oral amiodarone is required after the intravenous phase. It has proved superior to lidocaine in improving survival to hospital in patients with cardiac arrest and shock-resistant VF.343 Although intravenous amiodarone has an early effect on AV nodal conduction and early antiadrenergic effects, the effects on myocardial conduction and refractoriness are gradual in onset and maximum effect may not be seen for weeks or months.367369 Intravenous amiodarone is not ideal for early conversion of stable monomorphic VT. Intravenous procainamide is more appropriate when early slowing of the VT rate and termination of monomorphic VT are desired.370,371 Close monitoring of blood pressure and cardiovascular status is recommended in the presence of congestive HF or severe LV dysfunction as intravenous procainamide can cause transient hypotension.372 Lidocaine is effective when VT is thought to be related to myocardial ischemia.373,374

7.3. Repetitive monomorphic ventricular tachycardia

Recommendations

Class IIa

  • Intravenous amiodarone, beta blockers, and intravenous procainamide (or sotalol or ajmaline in Europe) can be useful for treating repetitive monomorphic VT in the context of coronary disease375 and idiopathic VT. (Level of Evidence: C)

Repetitive monomorphic VT is characterized electrocardiographically by frequent ventricular ectopy and salvos of NSVT with intervening sinus rhythm. It typically occurs at rest and is self-terminating although the arrhythmia can be present for much of the time.376 Although this terminology can refer to mechanistically diverse arrhythmias, it generally refers to idiopathic VT, most frequently the RV outflow type.377379 This tachycardia can cause palpitations or, rarely, tachycardia-related cardiomyopathy.380 Many patients have no symptoms related to the arrhythmia. In some patients, tachycardia is provoked by exercise.297 An electrocardiographically similar presentation is less frequent in patients with structural heart disease and, specifically, previous MI.375

Treatment is rarely required on an urgent basis, and chronic management should be based on symptoms and frequency of tachycardia. Tachycardia-induced cardiomyopathy is unusual in this entity, and there is usually no need to treat asymptomatic patients with preserved LV function. For patients with mild symptoms, reassurance may be the only treatment necessary. Repetitive monomorphic VT is usually an issue of chronic management (pharmacologically or by ablation), and the strategy will vary considerably dependent on the clinical situation and etiology of the VT. Beta-blocking agents or calcium channel blockers are often effective. Ablation is generally successful in problematic RV outflow tachycardia.381 When acute therapy is required, antiarrhythmic drug selection will depend on etiology and underlying ventricular function, with drug selection considerations similar to that described for sustained monomorphic VT (see Section 7.2 for further discussion).

7.4. Polymorphic VT

Recommendations

Class I

  1. Direct current cardioversion with appropriate sedation as necessary is recommended for patients with sustained polymorphic VT with hemodynamic compromise and is reasonable at any point in the treatment cascade. (Level of Evidence: B)

  2. Intravenous beta blockers are useful for patients with recurrent polymorphic VT, especially if ischemia is suspected or cannot be excluded. (Level of Evidence: B)

  3. Intravenous loading with amiodarone is useful for patients with recurrent polymorphic VT in the absence of abnormal repolarization related to congenital or acquired LQTS. (Level of Evidence: C)

  4. Urgent angiography with a view to revascularization should be considered for patients with polymorphic VT when myocardial ischemia cannot be excluded. (Level of Evidence: C)

Class IIb

  • Intravenous lidocaine may be reasonable for treatment of polymorphic VT specifically associated with acute myocardial ischemia or infarction. (Level of Evidence: C)

Polymorphic VT may be sustained, generally requiring urgent electrical cardioversion, or self-terminating with interludes of sinus rhythm. It is useful to distinguish polymorphic tachycardia associated with normal repolarization from that associated with abnormal repolarization (e.g., prolonged QT interval). Both VTs may be similar with gross irregularity of rate and QRS morphology with phasic increase and decrease of QRS amplitude often described as ‘torsades de pointes’ (see Section 7.5. for further discussion).

Polymorphic VT with a normal QT interval during intervening sinus rhythm is most frequently seen in the context of acute ischemia or MI, but the QRS pattern during VT is not specific and may be seen with other cardiac disease states such as cardiomyopathy or HF or in the absence of overt cardiac disease (e.g., idiopathic polymorphic VT, catecholaminergic VT).15,382,383 Intravenous beta blockers are useful in this context and improve mortality in the setting of recurrent polymorphic VT with AMI.384 Intravenous loading with amiodarone is also useful.341,385,386 Urgent coronary angiography should be considered in the setting or recurrent polymorphic VT when ischemia is suspected or cannot be excluded.387 In all instances, treatment of HF and associated correctable conditions and repletion of potassium and magnesium should be done concurrently with the above.

7.5. Torsades de pointes

Recommendations

Class I

  1. Withdrawal of any offending drugs and correction of electrolyte abnormalities are recommended in patients presenting with torsades de pointes. (Level of Evidence: A)

  2. Acute and long-term pacing is recommended for patients presenting with torsades de pointes due to heart block and symptomatic bradycardia. (Level of Evidence: A)

Class IIa

  1. Management with intravenous magnesium sulfate is reasonable for patients who present with LQTS and few episodes of torsades de pointes. Magnesium is not likely to be effective in patients with a normal QT interval. (Level of Evidence: B)

  2. Acute and long-term pacing is reasonable for patients who present with recurrent pause-dependent torsades de pointes. (Level of Evidence: B)

  3. Beta blockade combined with pacing is reasonable acute therapy for patients who present with torsades de pointes and sinus bradycardia. (Level of Evidence: C)

  4. Isoproterenol is reasonable as temporary treatment in acute patients who present with recurrent pause-dependent torsades de pointes who do not have congenital LQTS. (Level of Evidence: B)

Class IIb

  1. Potassium repletion to 4.5 to 5 mmol/L may be considered for patients who present with torsades de pointes. (Level of Evidence: B)

  2. Intravenous lidocaine or oral mexiletine may be considered in patients who present with LQT3 and torsades de pointes. (Level of Evidence: C)

Marked QT interval prolongation and the morphologically distinctive polymorphic VT torsades de pointes occur in 3 common settings: in congenital LQTS, in a drug-associated form, and in patients with advanced conduction system disease that has progressed to heart block (see Section 11.1.1 for further discussion). Torsades de pointes complicating heart block is managed with temporary pacing followed by permanent pacing. Other causes, such as severe electrolyte abnormalities alone or central nervous system injury, are less common. Presentation with frequently recurring torsades de pointes in the congenital syndrome is unusual. In this setting, catecholamines should be avoided. However, other maneuvers useful in the drug-associated form (magnesium, potassium, pacing) can be used, and pacing along with beta blockade or lidocaine may be considered.388

7.6. Incessant ventricular tachycardia

Recommendations

Class I

  • Revascularization and beta blockade followed by intravenous antiarrythmic drugs such as procainamide or amiodarone are recommended for patients with recurrent or incessant polymorphic VT due to acute myocardial ischemia. (Level of Evidence: C)

Class IIa

  • Intravenous amiodarone or procainamide followed by VT ablation can be effective in the management of patients with frequently recurring or incessant monomorphic VT. (Level of Evidence: B)

Class IIb

  1. Intravenous amiodarone and intravenous beta blockers separately or together may be reasonable in patients with VT storm. (Level of Evidence: C)

  2. Overdrive pacing or general anesthesia may be considered for patients with frequently recurring or incessant VT. (Level of Evidence: C)

  3. Spinal cord modulation may be considered for some patients with frequently recurring or incessant VT. (Level of Evidence: C)

7.6.1. Clinical features

The syndrome of very frequent episodes of VT requiring cardioversion has been termed ‘VT storm’ (see Section 13.5 for further discussion). Frequent appropriate ICD shocks represent another variant. While a definition of greater than 2 episodes in 24 h has been used,389,390 much more frequent episodes can also occur. Hemodynamically stable VT lasting hours has been termed ‘incessant’. Management guidelines for these syndromes rely on anecdotal evidence because they are rare, there are multiple potential underlying mechanisms, and no randomized trials have been conducted.

Severe underlying heart disease is frequently present. More rarely, VT storm can occur (e.g., in Brugada syndrome, LQTS, catecholaminergic VT, or in drug overdose) in patients who have a structurally normal heart. ‘VT storm’ can be monomorphic or polymorphic. Polymorphic VT storm in a patient with coronary disease is strongly suggestive of acute myocardial ischemia; pauses may occur prior to polymorphic VT even in the absence of QT prolongation. Pause-dependent VT with marked QT prolongation should be managed as torsades de pointes (see Section 7.5), although acute ischemia can also present in this fashion.391 Frequent appropriate ICD shocks may represent part of the natural history of advanced heart disease and may or may not portend a serious deterioration in underlying prognosis.392

7.6.2. Management

The first step in VT storm is to identify and correct inciting factors, commonly including drugs, electrolyte disturbances, and acute myocardial ischemia (see Sections 13.5 and 13.6 for further discussion). With frequent ICD shocks, electrograms and programming should be reviewed to determine if device reprogramming is desirable.393,394

Intravenous beta blockade should be considered for a polymorphic VT storm as it is the single most effective therapy. Revascularization procedures may be urgently needed. It is of utmost importance to try and understand the substrate of incessant arrhythmias, because if a diagnosis is established, a targeted treatment may be possible. For example, in Brugada syndrome, quinidine or isoproterenol may terminate incessant arrhythmias.139,395 In acute ischemia, intravenous amiodarone seems more effective than other antiarrhythmic drugs.396 Intra-aortic balloon counterpulsation can be tried. Pacing may be useful especially if the tachycardia onset is pause dependent. Other potential therapies include ablation397 or general anesthesia.398 Autonomic alternative via spinal cord modulation may be tried.

Monomorphic VT storm can be managed by intravenous antiarrhythmics (e.g., amiodarone, procainamide) to slow the rate but may aggravate the tachycardia by promoting frequent or incessant episodes. Ablation can also be effective. ICD therapy may eventually be needed.

8. Ventricular arrhythmia and sudden cardiac death related to specific pathology

8.1. Left ventricular dysfunction due to prior myocardial infarction

Recommendations

Class I

  1. Aggressive attempts should be made to treat HF that may be present in some patients with LV dysfunction due to prior MI and ventricular tachyarrhythmias. (Level of Evidence: C)

  2. Aggressive attempts should be made to treat myocardial ischemia that may be present in some patients with ventricular tachyarrhythmias. (Level of Evidence: C)

  3. Coronary revascularization is indicated to reduce the risk of SCD in patients with VF when direct, clear evidence of acute myocardial ischemia is documented to immediately precede the onset of VF. (Level of Evidence: B)

  4. If coronary revascularization cannot be carried out and there is evidence of prior MI and significant LV dysfunction, the primary therapy of patients resuscitated from VF should be the ICD in patients who are receiving chronic optimal medical therapy and those who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A)

  5. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with LV dysfunction due to prior MI who are at least 40 d post-MI, have an LVEF less than or equal to 30% to 40%, are NYHA functional class II or III, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A) (See Section 1.2.)

  6. The ICD is effective therapy to reduce mortality by a reduction in SCD in patients with LV dysfunction due to prior MI who present with hemodynamically unstable sustained VT, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A)

Class IIa

  1. Implantation of an ICD is reasonable in patients with LV dysfunction due to prior MI who are at least 40 d post-MI, have an LVEF of less than or equal to 30% to 35%, are NYHA functional class I on chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B) (See Section 1.2.)

  2. Amiodarone, often in combination with beta blockers, can be useful for patients with LV dysfunction due to prior MI and symptoms due to VT unresponsive to beta-adrenergic‐blocking agents. (Level of Evidence: B)

  3. Sotalol is reasonable therapy to reduce symptoms resulting from VT for patients with LV dysfunction due to prior MI unresponsive to beta-blocking agents. (Level of Evidence: C)

  4. Adjunctive therapies to the ICD, including catheter ablation or surgical resection, and pharmacological therapy with agents such as amiodarone or sotalol are reasonable to improve symptoms due to frequent episodes of sustained VT or VF in patients with LV dysfunction due to prior MI. (Level of Evidence: C)

  5. Amiodarone is reasonable therapy to reduce symptoms due to recurrent hemodynamically stable VT for patients with LV dysfunction due to prior MI who cannot or refuse to have an ICD implanted. (Level of Evidence: C)

  6. Implantation is reasonable for treatment of recurrent ventricular tachycardia in patients post-MI with normal or near normal ventricular function who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIb

  1. Curative catheter ablation or amiodarone may be considered in lieu of ICD therapy to improve symptoms in patients with LV dysfunction due to prior MI and recurrent hemodynamically stable VT whose LVEF is greater than 40%. (Level of Evidence: B)

  2. Amiodarone may be reasonable therapy for patients with LV dysfunction due to prior MI with an ICD indication, as defined above, in patients who cannot or refuse to have an ICD implanted. (Level of Evidence: C)

Class III

  1. Prophylactic antiarrhythmic drug therapy is not indicated to reduce mortality in patients with asymptomatic nonsustained ventricular arrhythmias. (Level of Evidence: B)

  2. Class IC antiarrhythmic drugs in patients with a past history of MI should not be used. (Level of Evidence: A)

Considerations taken by the Writing Committee in formulating recommendations for this section are discussed in detail in the Introduction.

Patients with chronic CHD manifest 3 general types of ventricular tachyarrhythmias: NSVT (defined as 3 or more repetitive ventricular beats in a row lasting up to 30 s in duration at a rate greater than 100 beats per minute), sustained VT, and cardiac arrest resulting from VT or VF. The cardiac mortality of patients with all types of ventricular tachyarrhythmias is high. The high mortality results from nonsudden, as well as sudden, cardiac death. These arrhythmias may result from myocardial ischemia, or effects of HF, in addition to primary electrical abnormalities. Aggressive attempts should be made to treat HF and to search for and correct myocardial ischemia in patients with ventricular tachyarrhythmias. In some cases, appropriate treatment of ischemia and HF will abolish the arrhythmia (primarily polymorphic VT, VF, and NSVT). Even if specific antiarrhythmic therapy is necessary, the frequency and tolerance of arrhythmias may be improved with appropriate therapy for ischemia and HF.

8.1.1. Nonsustained ventricular tachycardia

Most NSVT in patients with chronic CHD is brief and does not cause symptoms. There is no evidence that suppression of asymptomatic NSVT prolongs life. Thus, there is no indication to treat NSVT, except in the relatively uncommon circumstances where frequent (incessant) or very rapid episodes compromise hemodynamic stability. In such cases, NSVT may be treated with pharmacological antiarrhythmic therapy, catheter ablation, or surgical resection. When NSVT causes symptoms that require therapy, attempts should be made to characterize the NSVT electrocardiographically, in order to determine whether the NSVT is related to prior MI or arises by a distinct mechanism that may be especially amenable to RF catheter ablation, such as tachycardia arising from the ventricular outflow tract. Initial pharmacological therapy of symptomatic NSVT should consist of beta adrenergic‐blocking agents, if they are not already being used at an adequate dosage. Pharmacological therapy in patients with symptomatic NSVT unresponsive to beta adrenergic–blocking agents would most appropriately be amiodarone or sotalol.

8.1.2. Sustained ventricular tachycardia

The treatment of sustained VT in patients with chronic CHD should be tempered by the clinical manifestations produced by the tachycardia, as well as the frequency of episodes. Patients who present with sustained monomorphic VT that does not precipitate cardiac arrest or cause severe hemodynamic instability are usually, but not always, at relatively low risk for SCD (2% yearly).399,400 Twelve-lead ECGs should be obtained during episodes of sustained VT, and the morphology assessed to be certain that it is consistent with location of prior MI(s). The possibility should be considered that patients with prior MI may develop sustained VT unrelated to the infarction, due to other mechanisms such as bundle-branch reentry or idiopathic VT. If episodes are relatively infrequent, the ICD alone may be the most appropriate initial therapy, because antitachycardia pacing therapies or high-energy shock therapy may reduce the need for hospitalization and pharmacological antiarrhythmic therapy. Suitable adjunctive therapies include catheter ablation, surgical resection, and pharmacological therapy with agents such as sotalol or amiodarone.

Curative therapy of sustained VT using either surgical resection or catheter ablation should be considered in patients with frequent recurrences of VT unresponsive to antiarrhythmic drugs. Patients in whom the tachycardia is hemodynamically stable may be considered for curative catheter ablation. The major limitation to catheter ablation is the fact that most patients with sustained VT resulting from prior MI have multiple tachycardias, and it is often difficult to ablate all tachycardias completely, using currently available RF ablation technology. Some patients have only 1 or 2 tachycardia circuits and may be cured of their arrhythmia by catheter ablation. However, they may develop new VT in the future using a different circuit. Although all morphologically distinct tachycardias may not be cured by catheter ablation, the tachycardia substrate may be modified sufficiently to decrease the frequency of arrhythmia episodes. Ablation of the tachycardia using surgery to resect or modify the arrhythmia substrate is an alternative therapy that may be suitable for patients in whom catheter ablation is unsuccessful.

Following correction of ischemia, patients who present with sustained VT that causes severe hemodynamic compromise may benefit from EP testing. Such testing will occasionally reveal curable arrhythmias such as bundle-branch reentry. In addition, the results of testing often help in appropriate programming of implantable defibrillators. The ICD is the primary therapy for such patients.

8.1.3. Treatment of ventricular fibrillation and cardiac arrest survivors

Patients experiencing cardiac arrest due to VF that does not occur within the first 24 to 48 h of AMI may be at risk for recurrent cardiac arrest. As is the case for patients presenting with sustained VT, such patients should be evaluated and treated for myocardial ischemia. If there is direct, clear evidence of acute myocardial ischemia immediately preceding the onset of VF and there is no evidence of prior MI, the primary therapy should be complete coronary revascularization. If coronary revascularization cannot be carried out and there is evidence of prior MI and significant LV dysfunction, the primary therapy of patients resuscitated from VF should be the ICD.

8.1.4. Primary prevention of sudden cardiac death

All patients with CHD are at risk for SCD, and most SCD occurs in patients without severe LV dysfunction. However, in the absence of symptomatic arrhythmias, patients without prior MI and even those with prior MI whose LVEF is greater than 40% are at such low risk that prophylactic therapy is not indicated. Nevertheless, the risk for SCD in patients who do not have symptomatic arrhythmias, without prior MI, and those with prior MI whose LVEF is greater than 40% is sufficiently low that prophylactic therapy is not indicated at the present time. In addition, when EF is greater than 40%, the risk of SCD is low enough that prophylactic antiarrhythmic therapy is not indicated for patients with asymptomatic arrhythmias, such as NSVT.

Subpopulations of patients remain at risk for SCD for years after the AMI. Multiple factors in addition to reduced EF have been demonstrated to contribute to the risk for SCD after MI; these include the presence of NSVT, symptomatic HF, and sustained monomorphic VT inducible by EP testing. The only specific antiarrhythmic treatment proved consistently effective to reduce risk of both SCD and total mortality is the ICD. ICD therapy is indicated to reduce the risk of SCD in 2 patient groups: patients whose LVEF is less than or equal to 40% as a result of prior MI and who have spontaneous NSVT and sustained monomorphic VT inducible by EP testing,267 and patients whose LVEF is less than 30% as a result of an MI that occurred greater than or equal to 40 d earlier when HF (NYHA functional class II or III symptoms) is present.248,268 The rationale for recommending that an ICD be used in patients with symptomatic HF, in addition to reduced EF, is that the evidence for ICD benefit is strongest in such patients; most patients enrolled in primary prevention trials had symptomatic HF.8 Evaluation of the need for an ICD and implantation should be deferred until at least 3 mo after revascularization procedures (i.e., surgical bypass grafting or percutaneous angioplasty) to allow adequate time for recovery of ventricular function following revascularization. In general, ICD implantation should be deferred until at least 40 d after AMI in patients meeting the above criteria in order to allow time for recovery of ventricular function and because ICD therapy has not been demonstrated to improve survival when implanted within 40 d after MI.152,248,401403 In cases of doubt, an EP study could be considered.

Amiodarone therapy has been thought to be relatively safe in patients with prior MI who had symptomatic arrhythmias that required suppression. Although randomized trials have not demonstrated a survival benefit when empiric amiodarone is initiated early after MI, mortality was not increased, and arrhythmic deaths showed a consistent trend toward reduction with amiodarone treatment.404,405 However, in patients with advanced HF (NYHA functional class III), amiodarone may not be beneficial.8,248 Thus, amiodarone should not be used routinely after MI but is probably the safest agent to use to suppress symptomatic arrhythmias.

8.1.5. Use of implantable cardioverter-defibrillator for ventricular tachycardia in patients with normal or near normal left ventricular ejection fraction

Recurrent sustained VT is usually treated by management of the underlying condition, prevention of predisposing and trigger factors, and the use of antiarrhythmic therapies such as class I and class III antiarrhythmic drugs. The use of antiarrhythmic agents may predispose the patient to proarrhythmic complications that might pose significant threats to life. Increasingly, the ICD is being used effectively to treat these arrhythmias, which in themselves may not be life-threatening, in order to avoid the relative ineffectiveness and adverse complications of pharmaceutical therapy. In the case of monomorphic VT, antitachycardia pacing is often applied successfully without provocation of untoward symptoms. On the other hand, polymorphic VT or VF, whether or not related to antiarrhythmic drug treatment, may require shock therapy. In any event, the strategy of using devices to manage such arrhythmias appears to be clinically successful, although expensive.

8.2. Valvular heart disease

Recommendations

Class I

  • Patients with valvular heart disease and ventricular arrhythmias should be evaluated and treated following current recommendations for each disorder. (Level of Evidence: C)

Class IIb

  • The effectiveness of mitral valve repair or replacement to reduce the risk of SCD in patients with mitral valve prolapse, severe mitral regurgitation, and serious ventricular arrhythmias is not well established. (Level of Evidence: C)

Ventricular arrhythmias occurring in patients with valvular heart disease can be caused by any of the mechanisms responsible for ventricular arrhythmias in other cardiac diseases. These patients can have associated CHD, myocardial dysfunction, severe LVH, adrenergic-dependent rhythm disturbances, or an inherited molecular abnormality. Valve abnormalities are not likely to cause ventricular arrhythmias but may contribute by virtue of their effect on the myocardium. Although SCD in patients with significant valvular lesions is frequently caused by a serious ventricular arrhythmia, it is uncertain whether the event is triggered by preexisting ventricular arrhythmias. In general, there is more knowledge on the risk for SCD in patients with aortic valve disease compared with other valvular lesions. Although the overall risk is small, sudden arrhythmic death appears to be more frequent in aortic stenosis than in other lesions: approximately 0.4% per year for aortic stenosis, less than 0.2% per year for regurgitation, and less than 0.2% per year for mitral valve disease.406,407

Most patients who die suddenly have been symptomatic from their valvular disease.406 Although recurrent NSVT may place a patient with severe aortic stenosis at risk for syncope, the management of such a patient is usually guided by the severity of the valvular lesion. To date, there are insufficient data demonstrating reduction in ventricular arrhythmias as a result of valve repair or replacement in most patients with valvular disease. For these reasons, patients with valvular heart disease and ventricular arrhythmias should be evaluated and treated following current recommendations for each disorder.406 The presence of a ventricular arrhythmia alone does not constitute an indication for valve repair or replacement. An exception to this general guideline has been suggested for patients with myxomatous mitral valve prolapse (MVP) and serious ventricular arrhythmias, in whom there may be an increased risk for SCD, particularly in the subgroup that also has a flail leaflet.408,409 For this reason, the frequent occurrence of ventricular arrhythmias in patients with severe myxomatous mitral regurgitation has been considered a class IIb indication for surgery,406 although its effectiveness in reducing SCD has not been established. The role of QT prolongation in subgroups of patients with MVP remains unclear.3,410

Patients with mild valvular lesions who have no LV enlargement, LVH or depressed function should be managed as if they had no structural heart disease.

8.3. Congenital heart disease

Recommendations

Class I

  1. ICD implantation is indicated in patients with congenital heart disease who are survivors of cardiac arrest after evaluation to define the cause of the event and exclude any reversible causes. ICD implantation is indicated in patients who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

  2. Patients with congenital heart disease and spontaneous sustained VT should undergo invasive hemodynamic and EP evaluation. Recommended therapy includes catheter ablation or surgical resection to eliminate VT. If that is not successful, ICD implantation is recommended. (Level of Evidence: C)

Class IIa

  • Invasive hemodynamic and EP evaluation is reasonable in patients with congenital heart disease and unexplained syncope and impaired ventricular function. In the absence of a defined and reversible cause, ICD implantation is reasonable in patients who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

Class IIb

  • EP testing may be considered for patients with congenital heart disease and ventricular couplets or NSVT to determine the risk of a sustained ventricular arrhythmia. (Level of Evidence: C)

Class III

  • Prophylactic antiarrhythmic therapy is not indicated for asymptomatic patients with congenital heart disease and isolated PVCs. (Level of Evidence: C)

Congenital heart disease represents a diverse spectrum of anatomical and physiological defects with significant differences in respect to natural history, preoperative and postoperative physiology, and the risk of arrhythmias and late SCD. Overall, congenital heart defects are the leading cause of infant mortality (less than 1 y of age) in the industrialized world. However, with advances in cardiovascular medicine, this mortality rate has been reduced from 105 to 59 deaths per 100 000 live births between 1980 and 1995.411 Nearly all defects can now be repaired or palliated, with estimates of greater than 1 million worldwide long-term survivors of surgery for congenital heart disease.412 Although the short- and long-term survival of these patients is a matter of ongoing study, it is apparent that patients with certain defects have an increased risk of late sudden and total cardiac mortality.413 Given the overall low incidence of late SCD in postoperative congenital heart disease patients, no prospective randomized clinical trials have been performed to define either risk factors for SCD or the role of primary prevention therapies. Therefore, the level of evidence for most recommendations is class C.

During infancy and childhood, greater than 75% of deaths in patients with congenital heart disease are in-hospital events, most occurring during the perioperative period.414 The remaining deaths occur as out-of-hospital or emergency department events, often in patients with other congenital anomalies or sepsis. Therefore, the number of very young patients with congenital heart disease who are victims of arrhythmic SCD is quite small.

Beyond 20 y of age, there is a progressive increase in the incidence of sudden and total cardiac mortality in postoperative congenital heart disease patients.413 Hence, most studies of sudden death in congenital heart disease have evaluated adolescents and young adults.415 Five congenital heart defects have been associated with the greatest risks of late SCD: tetralogy of Fallot, d- and l-transposition of the great arteries, aortic stenosis, and functional single ventricle.413,416,417

The largest number of late SCD studies in postoperative patients with congenital heart disease have been for tetralogy of Fallot. A meta-analysis of 39 studies including 4627 patients showed that the combination of ventricular dysfunction and complex ventricular ectopy was the primary correlate of late SCD.418 Although more than 20 risk factors for SCD have been proposed,419 volume overload due to pulmonary insufficiency and QRS duration greater than 160 ms appear to be the additional factors most likely to be associated with an increased risk of SCD due to ventricular arrhythmias.420,421 The results of EP testing for risk stratification in these patients have been inconsistent, in part due to variable study protocols and definitions of response to such testing.422424

Postoperative patients with d-transposition of the great arteries appear to have a differing risks for late SCD, based on whether they have undergone an atrial (Mustard or Senning) or arterial switch procedure. A very high incidence of late atrial arrhythmias has been noted in patients following atrial switch procedures, complicated by profound sinus bradycardia.425,426 The mechanism of SCD appears to be atrial flutter with 1:1 AV conduction, followed by myocardial ischemia resulting in polymorphic VT or VF.427 In both d- and l-transposition, progressive ventricular dysfunction may also result in ventricular arrhythmias as the cause of SCD.416,428

In general, postoperative patients with unexplained syncope should undergo both hemodynamic and EP evaluation. A high incidence of inducible sustained ventricular arrhythmias has been reported in syncopal postoperative patients who have complex ventricular ectopy.429,430 Furthermore, a positive response to EP testing, independent of the clinical indication, may identify patients with a high-risk of late SCD.423 Conversely, isolated ventricular ectopy is common in older postoperative congenital heart disease patients. In the absence of ventricular dysfunction or symptoms, isolated ventricular ectopy has minimal prognostic significance, and the risks of antiarrhythmic drug treatment can exceed any potential benefit.431 There remain many patients with simple or complex ventricular ectopy, with vague symptoms, or modest impairment of ventricular function who require individual judgment regarding the need for evaluation and treatment.432 Also, there are nonarrhythmic causes of late sudden death in postoperative patients, including cerebral or pulmonary embolism, endocarditis, and aneurysm rupture.413,416

Another class of congenital anomalies that may result in SCD is coronary artery abnormalities. The most common congenital coronary artery anomaly causing SCD in the young is anomalous origin of the left coronary artery from the right sinus of Valsalva. The proposed mechanism of SCD is that either acute angulation of the coronary ostium or compression of the left coronary artery as it traverses the region between the aortic wall and RVOT results in acute myocardial ischemia and the development of VT or VF. The risk of SCD appears greatest during the first 3 decades of life. Diagnosis may be difficult as only one third of patients have a prior history or exertional syncope or angina. Definitive diagnosis by coronary angiography is an indication for surgical revascularization. Similar risks for SCD have also been reported for anomalous origin of the right coronary artery from the left sinus of Valsalva.433

Anomalous origin of the left coronary artery from the pulmonary artery generally presents during the first month of life. With the normal decline in pulmonary vascular resistance, myocardial ischemia and dysfunction develop as coronary perfusion is shunted to the pulmonary circulation. When the diagnosis is established by echocardiography during infancy, surgical reimplantation of the left coronary ostium is generally associated with recovery of ventricular function. However, a small percentage of these patients may survive an early MI and subsequently develop extensive right to left coronary artery collateral circulation. These patients may present years or decades later with angina, HF, or ventricular arrhythmias.434

8.4. Metabolic and inflammatory conditions

Although disorders in this category are important causes of life-threatening ventricular arrhythmias, the occurrence of VT/SCD is relatively rare and hence, in most cases, there are few trial data as to how the arrhythmias should best be managed. Data relating to the prevention of life-threatening ventricular arrhythmias are even more sparse. All recommendations in this section therefore have Level of Evidence B or C.

Acute emergencies, as a consequence of any underlying ailment in this section, should be managed conventionally.

8.4.1. Myocarditis, rheumatic disease, and endocarditis

Recommendations

Class I

  1. Temporary pacemaker insertion is indicated in patients with symptomatic bradycardia and/or heart block during the acute phase of myocarditis. (Level of Evidence: C)

  2. Acute aortic regurgitation associated with VT should be treated surgically unless otherwise contraindicated. (Level of Evidence: C)

  3. Acute endocarditis complicated by aortic or annular abscess and AV block should be treated surgically unless otherwise contraindicated. (Level of Evidence: C)

Class IIa

  1. ICD implantation can be beneficial in patients with life-threatening ventricular arrhythmias who are not in the acute phase of myocarditis, as indicated in the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices,1 who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. Antiarrhythmic therapy can be useful in patients with symptomatic NSVT or sustained VT during the acute phase of myocarditis. (Level of Evidence: C)

Class III

  • ICD implantation is not indicated during the acute phase of myocarditis. (Level of Evidence: C)

8.4.1.1. Myocarditis

Myocarditis is an inflammatory process affecting the cardiac myocardium and is most often related to infection. However, other toxic exposures, such as exposure to radiation, chemicals, and other physical agents, can lead to cardiac inflammation. The most common infectious agents leading to myocarditis are viruses.435,436 Other infective agents causing myocarditis include bacteria, fungi, protozoa, metazoa, spirochete, and rickettsia.435,437453 Immunosuppression does not appear to reliably influence prognosis significantly and is not recommended at this time.453

The acute course of myocarditis varies, as does its presentation.454 Presentation ranges from an asymptomatic finding detected because of transient ST-T changes noted on an ECG to a fulminant and life-threatening condition with symptoms that mimic ischemia. Acute management is largely supportive but may be quite aggressive depending on the presentation.455 Cardiac arrhythmias associated with acute myocarditis can range from conduction abnormalities to difficult to suppress life-threatening ventricular arrhythmias. Death can occur related to HF and arrhythmias including heart block.444,445,455460 Patients with arrhythmias or syncope may require antiarrhythmic drugs and/or device therapy.461 Temporary pacemaker insertion is indicated in patients with acute myocarditis who present with symptomatic heart block as it would be in other causes of acute symptomatic heart block. Pacing is indicated in patients with symptomatic sinus node dysfunction or AV block as a sequela of myocarditis as it would be in other causes of sinus or AV node dysfunction.

Acute myocarditis can lead to chronic cardiomyopathy through a variety of mechanisms.455 In patients with residual severe cardiomyopathy and ventricular arrhythmias, defibrillators and/or biventricular devices are implanted for the same indications as recommended in the sections on HF and cardiomyopathy.

Idiopathic giant cell myocarditis is fairly uncommon but is of particular note as it typically affects young individuals and is usually fatal if untreated.462467 The diagnosis is confirmed by endomyocardial biopsy. Patients may develop heart block, requiring temporary or permanent pacemakers. An ICD and antiarrhythmic drugs such as amiodarone may be needed for VT.462

Lyme carditis is a complication of Lyme disease affecting between 0.3% and 8% of those infected with Borrelia burgdorferi.468471 Patients can develop varying degrees of AV conduction abnormalities. Junctional rhythm and asystolic pauses can occur. LV dysfunction is generally mild, and the process is usually self-limiting when treated with antibiotics.468 Persistent heart block is rare, but in such cases permanent pacing may be needed.469,472 VT, usually nonsustained, has been reported infrequently.473475

Cardiac involvement has been frequently reported in patients with acquired immunodeficiency syndrome (AIDS) and is also seen in patients with human immunodeficiency virus (HIV) infection without AIDS.476479 SCD has been reported with primary myocardial HIV involvement.480,481 QT prolongation and arrhythmias have been attributed to drug therapy.482484

Chagas disease is caused by the protozoan Trypanosoma cruzi; it is transmitted by an insect vector and is common in Central and South America. Acute myocarditis is rare but over one third develop late myocardial damage with progressive HF and have poor survival. Conduction defects with progression to complete heart block are common. Life-threatening ventricular arrhythmias are common. Amiodarone appears to be effective in treating ventricular tachyarrhythmias, and death occurs as a result of either refractory HF or arrhythmias.485 Device therapy including the ICD is frequently used in the late phase.486 In those with good functional status (e.g., NYHA functional class I and II), SCD is a rare event when patients are treated with amiodarone. However, VT recurrence rate is high at 30% per year. RF ablation from the epicardial surface has been reported to be useful therapy in this indication. In those with advanced HF, drug therapy is of little benefit and arrhythmia recurrence rates approach 100%. Mortality is high in these patients, on average 40% mortality in 1 y.487

8.4.1.2. Rheumatic disease

Acute rheumatic fever causes a pancarditis involving the pericardium, myocardium, and endocardium. Sinus tachycardia and PR prolongation are common. Bundle-branch block, nonspecific ST-T wave changes, and atrial and ventricular premature complexes may occur. Complete heart block and ventricular arrhythmias are rare.488490 It has been associated with prolonged QT interval and torsades de pointes.489

8.4.1.3. Endocarditis

Infective endocarditis can occur as subacute bacterial endocarditis or acute bacterial endocarditis. Subacute bacterial endocarditis is most often related to infections with streptococcal species and less commonly with Staphylococcus aureus, S. epidermidis, and fastidious Haemophilus sp. Typically, it will develop on abnormal valves after asymptomatic bacteremias from infected gums or the genitourinary or gastrointestinal tract. Acute endocarditis more often is related to infections with S. aureus, group A hemolytic streptococci, pneumococci, or gonococci and with less virulent microorganisms. It can develop on normal valves.491 Untreated endocarditis is almost always fatal. Prosthetic valve endocarditis comprises a substantial proportion of all cases of infective endocarditis. Although the overall incidence of infective endocarditis has not changed over the past 3 decades, the age of presentation has increased. Where right-sided endocarditis occurs, it is often related to intravenous drug abuse.

Endocarditis of the aortic and mitral valves has been associated with rapid death owing to acute valvular disruption, emboli to the coronary arteries, or abscesses in the valvular rings or the septum.492,493 While these deaths are often rapid, they typically are not classified as sudden deaths. Uncommonly, endocarditis has been associated with SCD related to tamponade secondary to rupture.494,495 The development of cardiac rhythm disturbances portends poorly in infective endocarditis.496 Abscess formation in the valve annulus can result in first- or second-degree heart block. This occurs more often in aortic than mitral valve endocarditis.497 More advanced heart block can occur if the abscess erodes into the septum and disrupts the conduction system. New-onset heart block in a patient with endocarditis is highly specific for abscess.498 Patients with perivalvular abscess are at higher risk for other complications such as embolization and death.499

Antimicrobial therapy will be given as appropriate to the specific causative organism.500 Surgery is recommended in those with recurrent emboli or refractory HF or those who do not respond to antimicrobial therapy. Most physicians believe that abscess formation or fungal endocarditis is an indication for surgery.501,502 The acute hemodynamic compromise related to acute aortic regurgitation secondary to endocarditis can result in VT and is an indication for early surgery.498,499,503 Drug treatment of arrhythmias does not differ from generally accepted clinical principles. Surgery may be indicated in the presence of documented myocardial involvement or abscess formation.504

8.4.2. Infiltrative cardiomyopathies

Recommendations

Class I

  • In addition to managing the underlying infiltrative cardiomyopathy, life-threatening arrhythmias should be treated in the same manner that such arrhythmias are treated in patients with other cardiomyopathies, including the use of ICD and pacemakers in patients who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

The association between the infiltrative cardiomyopathies and VT/SCD is well documented. In all cases, where appropriate, treatment of the underlying condition must accompany management of cardiac manifestations.

8.4.2.1. Sarcoidosis

One quarter of patients with sarcoidosis have cardiac lesions, but there is a poor correlation between symptoms and myocardial involvement even in the most advanced cases, and hence SCD may be the first manifestation.505 In proven cases of cardiac sarcoidosis, supraventricular and ventricular arrhythmias occur frequently (73%) and bundle-branch block is present in about two thirds of patients.

Approximately one quarter of these patients develop complete heart block; a similar proportion has congestive cardiac failure. The ECG and Holter monitor are not sensitive or specific enough for detecting myocardial involvement but can be useful for the identification of rhythm disturbances once the diagnosis has been confirmed by other means (e.g., thallium-201 and gallium-67 SPECT or MRI). Myocardial biopsy, although insensitive, has a high specificity for the diagnosis of myocardial sarcoidosis. Corticosteroid therapy may reduce the number of premature ventricular complexes and episodes of tachycardia, rendering the arrhythmia easier to treat;506 the danger of SCD may also be diminished and an improvement may also be seen in conduction defects. The use of immunosuppression by no means eliminates the risk of further occurrence of arrhythmias. The resolution of granulomas may leave a substrate for arrhythmogenesis. Prospective trial data do not exist, but spontaneous VT, severe LV dysfunction, and severe intraventricular conduction disturbance warrant ICD and/or pacemaker therapy as appropriate.507

8.4.2.2. Amyloidosis

Cardiac involvement in amyloidosis, irrespective of the subtype or chemotherapeutic intervention, carries a very poor prognosis. In the AL subtype, the median survival is 6 mo with a 6% 3-y survival rate.508,509 Progressive HF is usually the mode of death, but bradyarrhythmia and especially VT may be the terminal event. Complex ventricular arrhythmias are common, affecting 57% of patients; 29% have couplets and 18% have NSVT.510 Cardiac troponins, especially troponin T;511 the presence of couplets on Holter recordings;510 LV wall thickness, especially greater than 12 to 15 mm on 2-dimensional echocardiography;512 the presence of late potentials on SAECG;513 and prolonged infra-His (HV) conduction time on EP studies514 may all be independent predictors of mortality. Elevated cardiac troponins may influence the final decision as median survival in patients with detectable values is 6 to 8 mo compared with 21 to 22 mo in those with undetectable levels.511 QTc is prolonged in patients with cardiac amyloid, but this does not seem to correlate with life-threatening arrhythmias.515 The use of permanent pacemakers and ICD devices may not influence long-term outcome but in familial cases may be used as a bridge to transplantation.516

8.4.2.3. Fabry disease

Fabry disease is an X-linked recessive lysosomal storage disorder caused by deficiency of lysosomal alpha-galactosidase. Fabry cardiomyopathy has a prevalence of 3% to 6% in male patients with unexplained LVH.517,518 Female carriers with low alpha-1 galactosidase activity may also exhibit cardiac manifestations.519 Although cardiac involvement causes a range of ECG abnormalities and conduction disturbances with AV block, ventricular arrhythmias and SCD appear to be very rare.520525 Improvements of cardiac hypertrophy and conduction abnormalities have been obtained with enzyme replacement therapy.526

8.4.2.4. Hemochromatosis

Up to one third of homozygotes with hemochromatosis have cardiac involvement. Although the natural course of untreated cardiac involvement is progressive HF, ventricular arrhythmias have been reported;527,528 their incidence and that of SCD are however, unknown. Early detection and appropriate management of hemochromatosis are essential for a favorable outcome as cardiac and liver involvement may be reversible in the early stages of the disease.529 Arrhythmias are managed conventionally.

8.4.3. Endocrine disorders and diabetes

Recommendations

Class I

  1. The management of ventricular arrhythmias secondary to endocrine disorders should address the electrolyte (potassium, magnesium, and calcium) imbalance and the treatment of the underlying endocrinopathy. (Level of Evidence: C)

  2. Persistent life-threatening ventricular arrhythmias that develop in patients with endocrine disorders should be treated in the same manner that such arrhythmias are treated in patients with other diseases, including use of ICD and pacemaker implantation as required in those who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  3. Patients with diabetes with ventricular arrhythmias should generally be treated in the same manner as patients without diabetes. (Level of Evidence: A)

8.4.3.1. Introduction

Endocrine disorders can induce VT/SCD by excess or insufficient hormone activity on myocardial receptors (e.g., pheochromocytoma, hypothyroidism). The endocrinopathy can also cause myocardial changes (e.g., acromegaly) or electrolyte disturbances produced by hormone excess (e.g., hyperkalemia in Addison disease and hypokalemia in Conn syndrome), and certain endocrine disorders can accelerate the progression of conditions such as underlying structural heart disease secondary to dyslipidemia or hypertension, increasing the risk of serious arrhythmias.

8.4.3.2. Thyroid disorders

Thyrotoxicosis commonly causes atrial arrhythmias; cases of VT/SCD are extremely uncommon but may occur with concomitant electrolyte disturbances.530 VT/SCD are more common in hypothyroidism, the basic underlying mechanism being possibly related to prolongation of the QT interval.531,532 Thyroxin replacement therapy usually corrects this abnormality and prevents any further arrhythmias, but antiarrhythmic drugs, such as procainamide, have been used successfully in an emergency.531

8.4.3.3. Pheochromocytoma

Pheochromocytoma may present with VT/SCD, but there are no data to quantify its incidence, best mode of management, or response to treatment. The incidence is likely to be low and possibly exacerbated by reversible catecholamine-induced HCM/DCM.533 Not only will conventional antagonism of catecholamine excess with alpha receptor blockers followed by beta blockade help control hypertension and reverse or prevent any further structural deterioration,534 but there is anecdotal evidence that it prevents recurrence of ventricular arrhythmia.535 Early definite surgical treatment of the pheochromocytoma should be a priority, especially in cases with documented life-threatening arrhythmias. In some patients with VT associated with pheochromocytoma, a long QT interval has been identified.536,537

8.4.3.4. Acromegaly

SCD is an established manifestation of acromegaly, and life-threatening arrhythmias are likely to be an important cause.538 Up to one half of all acromegalic patients have complex ventricular arrhythmias on 24-h Holter recordings, and of these, approximately two thirds are repetitive.539 There is a strong correlation between these ventricular arrhythmias and LV mass and duration of the disease but not hormone levels.539 Appropriate surgical management of the pituitary tumor is paramount for improved long-term outcome, as cardiac changes are reversible, especially in the young.540,541 Somatostatin analogues such as octreotide and lanreotide have both been shown to reduce LVH and improve the ventricular arrhythmia profile.542544

8.4.3.5. Primary aldosteronism, addison disease, hyperparathyroidism, and hypoparathyroidism

Severe electrolyte disturbances form the basis of arrhythmogenesis and VT/SCD associated with the previously mentioned endocrinopathies. ECG changes including prolongation of QRS and QTc intervals can accompany the electrolyte disturbance. Electrolyte imbalance requires immediate attention before definitive treatment of the underlying cause.545549

8.4.3.6. Diabetes

Diabetes is a major risk factor for premature and accelerated atherosclerosis, resulting in an increased incidence of MI, stroke, and death compared with a similar age- and gender-matched population without diabetes.95 The management of atherosclerotic complications that predispose to ventricular arrhythmias and SCD in patients with diabetes is similar to that in patients with diabetes.550

In addition to atherosclerosis and hyperglycemia that predispose the patient with diabetes to ventricular arrhythmias and SCD, autonomic neuropathy, transient hypoglycemic episodes that may occur with drug therapy, and target end-organ damage, such as renal failure, that results in hyperkalemia and occasionally hypokalemic episodes as a result of treatment, augment the risk of SCD.551557 Restrictive cardiomyopathy may be a late complication in some patients with diabetes.

Hypoglycemic episodes increase sympathetic tone. The likelihood of ventricular arrhythmias is enhanced, particularly when they occur in a patient with autonomic neuropathy. Severe hypoglycemia is associated with ventricular repolarization abnormalities, prolongation of the QT interval, and ventricular arrhythmias.551,552 Beta blockers have been shown to reduce the magnitude of these abnormalities during experimental hypoglycemia.558 Although they may mask symptoms of hypoglycemia, beta blockers significantly improve survival rates in patients with diabetes, and indications for their use are similar to those for patients with diabetes.559 In a prespecified diabetic subgroup of patients with diabetes and LVH enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial, losartan appeared to afford better protection against SCD than atenolol.560 ACE inhibitors or angiotensin-2 blockers are recommended in all patients with vascular complications of diabetes if no contraindications exist.

8.4.4. End-stage renal failure

Recommendations

Class I

  1. The acute management of ventricular arrhythmias in end-stage renal failure should immediately address hemodynamic status and electrolyte (potassium, magnesium, and calcium) imbalance. (Level of Evidence: C)

  2. Life-threatening ventricular arrhythmias, especially in patients awaiting renal transplantation, should be treated conventionally, including the use of ICD and pacemaker as required, in patients who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Cardiovascular causes account for at least 40% of deaths in patients with end-stage renal failure and 20% of these are sudden. Arrhythmias often occur during hemodialysis sessions and for at least 4 to 5 h afterward. During this period, hemodynamic status and fluctuations in electrolytes, especially potassium, magnesium, and calcium, are likely to play a crucial role in triggering events and should be monitored carefully. LQTS has been reported occasionally, sometimes related to therapy with sotalol.561 Risk factors predisposing to ventricular arrhythmias include LVH, hypertension, anemia, cardiac dysfunction, and underlying CHD.562 Of these, systolic blood pressure and myocardial dysfunction have been suggested to be the more important determinants of complex arrhythmia.563 Unfortunately, there are few data on how individuals at highest risk might be identified and treated. Restricted vascular access may influence the choice of therapy.

8.4.5. Obesity, dieting, and anorexia

Recommendations

Class I

  • Life-threatening ventricular arrhythmias in patients with obesity, anorexia, or when dieting should be treated in the same manner that such arrhythmias are treated in patients with other diseases, including ICD and pacemaker implantation as required. Patients receiving ICD implantation should be receiving chronic optimal medical therapy and have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIa

  • Programmed weight reduction in obesity and carefully controlled re-feeding in anorexia can effectively reduce the risk of ventricular arrhythmias and SCD. (Level of Evidence: C)

Class III

  • Prolonged, unbalanced, very low calorie, semistarvation diets are not recommended; they may be harmful and provoke life-threatening ventricular arrhythmias. (Level of Evidence: C)

Extreme disorders of eating, and overzealous methods of rectifying them quickly, are all associated with SCD. In overweight individuals, this risk is particularly evident in the severely obese with a 40 to 60 times higher incidence compared with that in the aged-matched general population.564,565 This is most likely to be related to life-threatening ventricular arrhythmias, but changes in the conduction system of young obese victims of SCD have also been reported.566 Some obese individuals have prolonged QTc intervals567,568 and studies have also documented an increased QT dispersion in these individuals.569 Cardiomyopathy of obesity (e.g., cardiomegaly, LV dilatation, and myocyte hypertrophy in the absence of interstitial fibrosis) is the most common association with SCD,92 and this can occur in normotensive individuals.570 Ventricular premature complexes are 30 times more common in obese patients with LVH compared with lean subjects. The complexity of the ventricular ectopy correlates with ventricular diastolic diameter and LV mass.571 Obstructive sleep apnea may play a role in the genesis of arrhythmias and HF in obese individuals.572

The risk of SCD in obesity can be significantly reduced by weight loss. Cardiomyopathy of obesity is reversible, at least in the early stages of the disease,573,574 as are most ECG changes including prolonged QTc intervals.568,569,575 Weight reduction strategies must therefore be advocated in all obese patients at risk, but these must involve well-balanced low-calorie diets. Prolonged, unbalanced, very low calorie, semistarvation diets (especially liquid protein diets) have been reported to cause cardiac arrhythmias and SCD by a variety of mechanisms. Such diets must be avoided especially in those with underlying cardiac abnormalities.576580

Reported mortality rates in anorexia nervosa fluctuate from 5% to 20%, but the actual rate is likely to be around 6%.581 Up to one third of these deaths, including those occurring during re-feeding, are said to be due to cardiac causes but no precise data exist on SCD. Prolonged periods of starvation result in not only anatomical abnormalities such as cardiac muscle atrophy and pericardial effusions,582 but also ECG abnormalities, including sinus bradycardia and prolongation of the QTc interval, an effect that is likely to be compounded by the presence of concurrent electrolyte disturbances.582584 SCD is therefore a frequent cause of mortality in this cohort. Low weight, low body mass index, and rapid weight loss immediately preceding assessment are the most important independent predictors of QTc interval prolongation.582 Most of the cardiac manifestations of anorexia nervosa are completely reversible by appropriate re-feeding.582 The ‘re-feeding syndrome’ is characterized by cardiac, neurological, and hematological complications triggered by fluid and electrolyte disturbances during the re-feeding of chronically starved individuals.585 Cardiac complications of this syndrome usually occur within the first week of re-feeding and are typically associated with severe degrees of malnutrition (less than 70% ideal body weight),586 hypophosphatemia,587 and total parenteral nutrition.588

8.5. Pericardial diseases

Recommendations

Class I

  • Ventricular arrhythmias that develop in patients with pericardial disease should be treated in the same manner that such arrhythmias are treated in patients with other diseases including ICD and pacemaker implantation as required. Patients receiving ICD implantation should be receiving chronic optimal medical therapy and have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

SCD can occur in the course of pericardial disease resulting from a variety of pathological processes; these include both constrictive and restrictive processes, resulting from trauma, inflammation, neoplastic, and infectious etiologies. There is no evidence linking specific ventricular arrhythmias with these diseases. Reports of SCD in patients with pericardial diseases suggest that primary hemodynamic processes (i.e., acute tamponade, herniation of myocardium through pericardium) are responsible for the vast majority of SCD in such patients.589592

8.6. Pulmonary arterial hypertension

Recommendations

Class III

  • Prophylactic antiarrhythmic therapy generally is not indicated for primary prevention of SCD in patients with pulmonary arterial hypertension (PAH) or other pulmonary conditions. (Level of Evidence: C)

SCD is responsible for 30% to 40% of mortality in patients with PAH. It appears more commonly in patients with primary PAH than in those with thromboembolic PAH.593 Patients experiencing SCD have lower partial pressure of oxygen than do those free of sudden death.594 SCD in patients with severe PAH appears to occur not only as a result of (presumed) ventricular arrhythmias but also as a result of pulmonary artery rupture or dissection.595,596 Cardiac arrhythmias may also result from ischemia. Marked dilatation of the main pulmonary artery has been reported to cause myocardial ischemia as a result of compression of the left main coronary artery.597 Cardiac catheterization is associated with increased risk of death, including documented VF in this population.598 In addition to patients with PAH, ventricular arrhythmias occur in persons with sleep disordered breathing and may be responsible for SCD in patients with sleep apnea.599

No trials of prophylactic antiarrhythmic therapy have been conducted in patients with PAH or other pulmonary conditions. Antiarrhythmic therapy is not indicated for prevention of SCD in patients with PAH or other pulmonary conditions.600,601 Good clinical judgment should be used in the management of asymptomatic arrhythmias in such patients, as they may be prone to proarrhythmic effects of antiarrhythmic agents. Furthermore, such patients may be at high risk during surgical procedures, such as ICD implantation.

8.7. Transient arrhythmias of reversible cause

Recommendations

Class I

  1. Myocardial revascularization should be performed, when appropriate, to reduce the risk of SCD in patients experiencing cardiac arrest due to VF or polymorphic VT in the setting of acute ischemia or MI. (Level of Evidence: C)

  2. Unless electrolyte abnormalities are proved to be the cause, survivors of cardiac arrest due to VF or polymorphic VT in whom electrolyte abnormalities are discovered in general should be evaluated and treated in a manner similar to that of cardiac arrest without electrolyte abnormalities. (Level of Evidence: C)

  3. Patients who experience sustained monomorphic VT in the presence of antiarrhythmic drugs or electrolyte abnormalities should be evaluated and treated in a manner similar to that of patients with VT without electrolyte abnormalities or antiarrhythmic drugs present. Antiarrhythmic drugs or electrolyte abnormalities should not be assumed to be the sole cause of sustained monomorphic VT. (Level of Evidence: B)

  4. Patients who experience polymorphic VT in association with prolonged QT interval due to antiarrhythmic medications or other drugs should be advised to avoid exposure to all agents associated with QT prolongation. A list of such drugs can be found on the Web sites www.qtdrugs.org and www.torsades.org. (Level of Evidence: B)

The mortality of cardiac arrest survivors is high, even when the cause of the initial arrest appears to be a transient or correctable abnormality, and much of the mortality appears due to recurrent cardiac arrest.33,602 The most common putative reversible causes of arrest are acute ischemia and electrolyte imbalance. Other common potential causes to which cardiac arrest is attributed include proarrhythmic effects of antiarrhythmic drugs.603 No controlled trials have evaluated the effects of myocardial revascularization on VT or VF. However, observational studies suggest that:

  • Sustained monomorphic VT in patients with prior MI is unlikely to be affected by revascularization.330

  • Myocardial revascularization is sufficient therapy only in patients surviving VF in association with myocardial ischemia when ventricular function is normal and there is no history of MI.604

The short-term (hospital) mortality of patients in whom primary VF complicates the acute phase of MI is high. However, patients who survive the initial hospitalization after Q-wave MI have survival virtually identical to patients without VF in the acute phase of infarction.605 The low risk for late cardiac arrest appears to apply only to patients experiencing Q-wave infarction; patients with an infarction defined by biomarker elevations without development of new Q waves have a significantly higher risk of late cardiac arrest.606,607 Transient ischemia resulting from coronary artery spasm may cause polymorphic VT or VF.608 In such cases, treatment of coronary spasm is may be sufficient to prevent recurrent arrhythmia.609,610 Coronary artery spasm may increase the risk of ventricular arrhythmias and SCD.

Electrolyte abnormalities, including hypokalemia and hypomagnesemia, facilitate development of VT in predisposed patients receiving antiarrhythmic agents and other drugs associated with the LQTS. However, hypokalemia can also result from cardiac arrest and should not otherwise be assumed to be the cause of cardiac arrest, except under unusual circumstances.611 Correction of hypokalemia does not affect inducibility of monomorphic VT occurring after MI. Electrolyte abnormalities should not be assumed to be the cause of cardiac arrest, except in the presence of drug-induced LQTS.

In patients who develop polymorphic VT in association with drug-induced QT prolongation, withdrawal of the offending antiarrhythmic or other agent is usually sufficient to prevent arrhythmia recurrence. If ventricular function is normal, no therapy beyond drug withdrawal, avoidance of future drug exposure, and correction of electrolyte abnormalities is necessary. However, if ventricular function is abnormal, cardiac arrest or syncope should not be attributed solely to antiarrhythmic drugs, and evaluation and treatment should be similar to patients experiencing such events in the absence of antiarrhythmic drugs.

Occasionally, patients develop monomorphic sustained VT only in the presence of antiarrhythmic drugs without QT prolongation. In such cases, it may appear that the development of spontaneous VT is dependent on drug administration. In most patients exhibiting this behavior, the monomorphic VT is inducible by EP testing in the absence of antiarrhythmic drugs.612,613

9. Ventricular arrhythmias associated with cardiomyopathies

9.1. Dilated cardiomyopathy (nonischemic)

Recommendations

Class I

  1. EP testing is useful to diagnose bundle-branch reentrant tachycardia and to guide ablation in patients with nonischemic DCM. (Level of Evidence: C)

  2. EP testing is useful for diagnostic evaluation in patients with nonischemic DCM with sustained palpitations, wide-QRS-complex tachycardia, presyncope, or syncope. (Level of Evidence: C)

  3. An ICD should be implanted in patients with nonischemic DCM and significant LV dysfunction who have sustained VT or VF, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A)

  4. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with nonischemic DCM who have an LVEF less than or equal to 30% to 35%, are NYHA functional class II or III, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B) (See Section 1.2.)

Class IIa

  1. ICD implantation can be beneficial for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. ICD implantation can be effective for termination of sustained VT in patients with normal or near normal ventricular function and nonischemic DCM who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIb

  1. Amiodarone may be considered for sustained VT or VF in patients with nonischemic DCM. (Level of Evidence: C)

  2. Placement of an ICD might be considered in patients who have nonischemic DCM, LVEF of less than or equal to 30% to 35%, who are NYHA functional class I receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C) (See Section 1.2.)

Considerations taken by the Writing Committee in formulating recommendations for this section are discussed in detail in the Introduction.

9.1.1. Risk stratification

The 5-y mortality for DCM has been recently estimated at 20% with SCD accounting for approximately 30% (8% to 51%) of deaths.614,615 Ventricular arrhythmias, both symptomatic and asymptomatic, are common, but syncope and SCD are infrequent initial manifestations of the disease.616,617 The incidence of SCD is highest in patients with indicators of more advanced cardiac disease who are also at highest risk of all cause mortality. Although VT and/or VF is considered the most common mechanism of SCD, bradycardia, pulmonary embolus, electromechanical dissociation and other causes account for up to 50% of SCDs in patients with advanced HF.107,618,619 Risk stratification is difficult in DCM. SCD occurs less frequently in patients with less advanced cardiac disease but the proportion of SCD to all-cause death is higher in this group.617,618,620 Predictors of overall outcome also predict SCD and generally reflect severity of disease (EF, end-diastolic volume, older age, hyponatremia, pulmonary capillary wedge pressure, systemic hypotension, AF).614 Unfortunately, they do not specifically predict arrhythmic death and are not useful in the patient with less severe disease.3,621 Even a low EF (less than 20%) may not have high positive predictive value for SCD.622624 Syncope has been associated with a higher risk of SCD regardless of the proven etiology of the syncope223,625 and patients with ICD implantation receive appropriate shocks comparable to a secondary prevention cohort.223,625,626 Premature ventricular complexes and NSVT correlate with the severity of cardiac disease and occur in the majority of patients with severe LV dysfunction.619,627,628 This limits the utility of ventricular arrhythmias as risk stratifiers as they would be expected to be sensitive but not specific. It has been suggested that the presence of NSVT may be more specific in the individual with better LV function.3 Induction of VT by EP testing has been shown to predict SCD625 but unfortunately failure to induce VT misses most individuals destined to die suddenly.129,627,629,630 Microvolt TWA has been suggested to predict SCD in a cohort study of 137 patients with DCM.151 The study included 37 patients with an indication for ICD and most endpoints occurred in this group. Nonetheless, the positive predictive value was relatively modest (0.22), as was EF less than 35% (0.15). Idiopathic DCM has heterogeneous etiologies but is familial in at least 40% of cases, being usually autosomal dominant with variable penetrance but also X-linked.631634 Unfortunately, genetic information is not currently useful for risk stratification.

9.1.2. Electrophysiological testing

In DCM, EP testing plays a minor role in the evaluation and management of VT. This is related to low inducibility, low reproducibility of EP testing, and low predictive value of induced VT.203,204 The multicenter CAT trial included 104 patients with DCM and LVEF less than 30% without sustained VT/VF.635 NSVT during Holter monitoring was recorded in 52%. With use of a complete EP testing protocol, only 2.9% of patients had sustained VT and 9.6% had VF induced. However, symptomatic patients may have various supraventricular tachyarrhythmias, typical and atypical atrial flutter or AF, requiring EP testing for diagnostic purposes or to guide ablation. Bundle-branch reentry may be suspected in patients with DCM, intraventricular conduction defects during sinus rhythm, and LBBB pattern tachycardia.636

9.1.3. Management

The treatment of DCM is often based on individual patient presentation and local physician experience. Pharmaceuticals that have improved overall mortality in patients with HF, such as beta blockers and ACE inhibitors, have also reduced SCD.622,637640 Amiodarone is generally preferred to treat patients with symptomatic arrhythmias because of the absence of significant negative hemodynamic effects and low proarrhythmic potential, although controlled comparative trials of drugs are not available. Amiodarone has been suggested to improve mortality in uncontrolled trials.641 In controlled trials, amiodarone reduced the incidence of SCD in a population of patients with predominately nonischemic DCM637 but not in a study of HF patients where the majority had CHD.638 The ICD has been shown to be superior to amiodarone for secondary prevention of VT and VF in studies where the majority of patients had CHD.266,642,643 The subgroup with nonischemic DCM in these studies benefited from the ICD more than did those with CHD.644

The role of the ICD in primary prophylaxis has been controversial. The Cardiomyopathy Trial (CAT) enrolled patients with recently diagnosed DCM and was discontinued early due to futility largely because of a lower-than-expected incidence of all-cause mortality.635 This was a relatively small study (50 patients in the ICD arm and 54 in the control group), although the 5-y follow-up showed fewer deaths in the ICD group versus control (13 vs. 17, respectively). In the AMIOVERT study,645 103 patients with DCM, EF less than 35%, and NSVT were randomized to amiodarone or ICD. The primary endpoint was total mortality, and the study was stopped prematurely due to futility. The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE)646648 randomized 458 patients with nonischemic cardiomyopathy, EF less than 35%, and frequent PVCs or NSVT to receive best medical therapy with or without ICD. There was a trend toward reduction of mortality with ICD therapy, but this was not significant.

The DEFINITE patients were randomized to receive best medical therapy with or without an ICD, and the primary endpoint was all-cause mortality. After 2 y, mortality was 13.8% in the standard therapy group versus 8.1% among those receiving an ICD, amounting to a 5.7% absolute reduction and a 35% relative risk reduction with ICD implantation. This failed to reach statistical significance (p=0.06), but the findings are comparable to those of other similar trials.647,648 The SCD-HeFT compared amiodarone, ICD, and best medical therapy in 2521 patients with CHD or nonischemic cardiomyopathy who were in NYHA functional class II or III HF with EF less than 35%. The drug arm (amiodarone) was double blinded and placebo controlled. The median follow-up was 45.5 mo. The total mortality in the medical group was 7.2% per year over 5 y with a risk reduction of 23% in the ICD group versus placebo (CI 0.62 to 0.96, p=0.007). Relative risk reduction was comparable for LV dysfunction due to prior MI and nonischemic groups, but absolute mortality was lower in the nonischemic group, resulting in a greater number to treat per life saved. There was no mortality difference between the amiodarone and placebo groups.8 Further risk stratification may decrease the number of individuals needed to treat to save a life in this population.649 With the exception of DEFINITE (25% in the ICD arm), trials assessing ICD in primary prophylaxis of DCM did not generally include asymptomatic patients with NYHA functional class I and therefore the efficacy of ICD in this population is not fully known.650 Because mortality is low in this subgroup, the benefit of ICD therapy is at best moderate.

9.1.4. Genetic analysis

The clinical applicability of genetic analysis to DCM is still limited as knowledge in this area does not allow genotyping of most individuals clinically affected by the disease. Patients with DCM and AV block and patients with DCM and skeletal muscle diseases have a higher probability of being successfully genotyped. When a pathogenetic mutation is identified, it becomes possible to establish a presymptomatic diagnosis of the disease among family members and to provide them with genetic counseling to monitor progression of the disease and to assess the risk of transmitting the disease to offspring. Based on current knowledge, genetic analysis does not contribute to further risk stratification in DCM.

9.2. Hypertrophic cardiomyopathy

Recommendations

Class I

  • ICD therapy should be used for treatment in patients with HCM who have sustained VT and/or VF and who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

Class IIa

  1. ICD implantation can be effective for primary prophylaxis against SCD in patients with HCM who have 1 or more major risk factor (see Table 7) for SCD and who are receiving chronic optimal medical therapy and in patients who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. Amiodarone therapy can be effective for treatment in patients with HCM with a history of sustained VT and/or VF when an ICD is not feasible. (Level of Evidence: C)

View this table:
Table 7

 Risk factors for sudden cardiac death in hypertrophic cardiomyopathy

Major risk factorPossible in individual patients
Cardiac arrest (VF)AF
Spontaneous sustained VTMyocardial ischemia
Family history of premature sudden deathLV outflow obstruction
Unexplained syncopeHigh-risk mutation
LV thickness greater than or equal to 30 mmIntense (competitive) physical exertion
Abnormal exercise BP
Nonsustained spontaneous VT
  • AF, atrial fibrillation; BP, blood pressure; LV, left ventricular; VF, ventricular fibrillation; VT, ventricular tachycardia.

  • Modified with permission from Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687–713.

Class IIb

  1. EP testing may be considered for risk assessment for SCD in patients with HCM. (Level of Evidence: C)

  2. Amiodarone may be considered for primary prophylaxis against SCD in patients with HCM who have 1 or more major risk factor for SCD (see Table 7) if ICD implantation is not feasible. (Level of Evidence: C)

9.2.1. Risk Stratification

Most individuals with HCM are asymptomatic and the first manifestation may be SCD.651657 SCD is usually related to ventricular arrhythmia with varying contribution of triggers such as ischemia, outflow obstruction, or AF.653656,658 SCD is less frequently due to bradycardia.659 The annual mortality from HCM has been estimated as high as 6% from tertiary centers,653,660,661 but community-based studies suggest a more benign disease in the majority of individuals, with an annual mortality in the range of 1% or less.662667 This relatively low incidence creates a challenge for risk stratification because the false-positive values for any stratifier may overwhelm the true-positive values.668 Features suggesting higher risk of SCD have been derived from observational studies.98,662,669677 In one study, 23 of 480 patients died suddenly over a mean follow-up of 6.5 y.678 The risk of SCD was directly related to LV wall thickness with essentially no mortality over 20 y with wall thickness less than 20 mm and mortality of almost 40% for wall thickness greater than or equal to 30 mm. Patients with such extreme wall thickness were the youngest and frequently asymptomatic. Five of 12 patients in this category under the age of 18 died suddenly. Others have suggested that patients with extreme septal hypertrophy also have other risk factors, and the independent value of extreme septal hypertrophy is less clear.98,679 The degree of outflow obstruction has been shown to predict cardiovascular death674,678 but not SCD.678 Athletes with HCM should not participate in most competitive sports with the possible exception of sports of low dynamic and low static intensity.680682 Participation in low-to-moderate athletic activities may be allowed in selected low-risk patients.683

Cardiac MRI684 and CT685 have been suggested to be helpful in assessing extent of disease and predicting SCD. A history of SCD in one or more family members has been considered to signify higher risk.653,660,686 This is intuitively logical and related closely to the suggestion that certain specific genetic abnormalities have been associated with increased risk of SCD;687691 the role of genetic testing as a predictor of SCD is likely to increase.687 Syncope has been associated with increased risk of SCD.657,692695 The severity of other symptoms such as dyspnea, chest pain, and effort intolerance has not been correlated with increased risk of SCD.695,696 A flat or hypotensive response to upright or supine exercise testing in patients younger than 40 y has been shown to be a risk factor for SCD, although the positive predictive value of this finding is low.658 A normal blood pressure response identifies a low-risk group.658,697699 The presence of VT on Holter monitoring665,696,700702 has been associated with a higher risk of SCD, although the positive predictive accuracy is relatively low. The absence of VT appears to have good negative predictive value. VT induced in the EP laboratory97 has also been associated with a higher risk of SCD, although others have suggested that VT induced in this setting with aggressive stimulation techniques is not specific.703,704

A consensus document on HCM from the American College of Cardiology and European Society of Cardiology categorized known risk factors for SCD as ‘major’ and ‘possible in individual patients’705 (see Table 7).

It is clear that many of the risk factors listed in Table 7 are interdependent, and the major independent risk factors may prove to be the extent of disease and the genetic abnormality. The absence of risk factors identifies a low-risk group, but the positive predictive value of any single risk factor is limited. Risk stratification based on incorporation of multiple risk factors would likely improve positive predictive accuracy.693

9.2.2. Electrophysiological testing

The value of EP testing in HCM has been controversial.706 In 1989, Fananapazir et al.707 showed by using 2 premature stimuli that only 16% of patients with cardiac arrest or syncope in the setting of HCM had inducible sustained VT. In a later study, the same group published data on 230 patients, including 155 patients reported earlier.97,707 Patients with inducible VT had a poorer prognosis than those without inducible VT. Induced VT was often polymorphic. The response to EP testing was considered to be an important predictive factor for outcome, together with a history of syncope or cardiac arrest. In a prospective study of 29 patients with HCM, 8 of them presenting with syncope, EP testing with up to 3 extrastimuli at 3 cycle lengths including LV stimulation failed to distinguish patients with from those without syncope.224 In patients who received an ICD for primary prevention, the estimated appropriate discharge rate was 5% per year.708

9.2.3. Management

The mainstay of pharmacological management for the symptomatic patient has been beta blockers or verapamil, which probably exert their effect by reducing heart rate and decreasing contractility.653,660 Disopyramide has been similarly used presumably for its negative inotropic effect.709 AF can be especially problematic,710,711 with sudden clinical deterioration as a result of high ventricular rates and loss of atrial filling. In addition, it is associated with increased risk of embolism, HF, and death. The high rate of embolism warrants anticoagulation with warfarin even though this has not been validated in this group of patients by a large randomized trial. Amiodarone is widely used and considered the most effective antiarrhythmic agent, although large controlled comparative trials are not available.710,712 Medical therapy has not been proved to be beneficial in the prevention of disease progression in the asymptomatic individual and is generally not indicated. Nonetheless, treatment with beta blockers and/or calcium antagonists is tempting even in asymptomatic individuals if they are younger and have severe hypertrophy or significant gradients.660 It is intuitively reasonable that optimal medical therapy and control of comorbidities will also reduce the risk of SCD, although this has not been rigidly demonstrated.

Although no randomized studies are available, the ICD has been used in patients with cardiac arrest, sustained VT, or VF, with a high percentage of patients receiving appropriate discharge during follow-up at a rate of 11% per year.708 The ICD implanted in a subgroup of patients for primary prophylaxis on the basis of perceived high risk for SCD (syncope, family history of SCD, NSVT, inducible VT, septal thickness greater than or equal to 30 mm) resulted in a lower rate of appropriate discharge of 5% per year.708 Amiodarone has been shown useful in prevention of SCD in nonrandomized studies,712,713 while other studies have suggested symptomatic improvement but have not shown complete prevention of SCD.714,715 Placebo-controlled studies or studies that compared ICD with amiodarone are not available, and the role of amiodarone in prevention of SCD is unclear. Amiodarone is unlikely to be superior to the ICD for this purpose, and a comparative study may never be done.716 The ICD is not indicated in the majority of asymptomatic patients with HCM, who will have a relatively benign course. Its role is individualized in the patient considered to be at high risk for SCD.3,717,718 Although precise risk stratification has not been validated, patients with multiple risk factors (especially severe septal hypertrophy, greater than or equal to 30 mm) and those with SCD (especially multiple SCDs) in close relatives appear to be at sufficiently high risk to merit consideration of ICD therapy.

9.2.4. Genetic analysis

Genetic analysis is useful in families with HCM because whenever a pathogenetic mutation is identified, it becomes possible to establish a presymptomatic diagnosis of the disease among family members and to provide them with genetic counseling to assess the risk of disease development and transmission of the disease to offspring. Genetic analysis may contribute to risk stratification in selected circumstances.

9.3. Arrhythmogenic right ventricular cardiomyopathy

Recommendations

Class I

  • ICD implantation is recommended for the prevention of SCD in patients with ARVC with documented sustained VT or VF who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

Class IIa

  1. ICD implantation can be effective for the prevention of SCD in patients with ARVC with extensive disease, including those with LV involvement, 1 or more affected family member with SCD, or undiagnosed syncope when VT or VF has not been excluded as the cause of syncope, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. Amiodarone or sotalol can be effective for treatment of sustained VT or VF in patients with ARVC when ICD implantation is not feasible. (Level of Evidence: C)

  3. Ablation can be useful as adjunctive therapy in management of patients with ARVC with recurrent VT, despite optimal antiarrhythmic drug therapy. (Level of Evidence: C)

Class IIb

EP testing might be useful for risk assessment of SCD in patients with ARVC. (Level of Evidence: C)

9.3.1. Risk stratification

ARVC (‘dysplasia’) is suspected in patients, typically a young man, with RV arrhythmias or in relatives of individuals with known ARVC. Syncope, presyncope, and, less frequently, biventricular failure are also observed.719,720 The ventricular arrhythmias have LBBB morphology that spans the spectrum of simple ventricular ectopy, sustained and NSVT, or VF. ARVC needs to be considered along with idiopathic RV outflow VT in the individual with ventricular ectopy and VT coming from the RV outflow region. In contrast to ARVC, idiopathic RV outflow VT is usually not associated with the ECG abnormalities seen with ARVC, is more common in women, and is initiated by isoproterenol infusion instead of by EP testing.721,722 The ECG in ARVC frequently shows precordial T-wave inversion, usually over V1 to V3, and QRS duration greater than 110 ms.721 Low voltage potentials following the QRS (epsilon waves) are characteristic but seen relatively infrequently, and late potentials are observed on the SAECG in greater than 50% of individuals.721,723,724

Unfortunately, SCD is frequently the first manifestation of the disease.96,725,726 A standardized diagnostic scheme has been formulated to establish a clinical diagnosis on a point score basis.727 The annual incidence of SCD has varied, ranging from 0.08% to 9%.720,728730 In an autopsy series, 24 of 27 patients were determined to have died suddenly and 3 to have died of congestive HF.731 SCD occurs relatively frequently during exercise or during stress, but SCD with no apparent provocation is not uncommon.732 In one Italian series, up to 25% of SCD in athletes was related to ARVC.733 Although SCD usually occurs in individuals with grossly visible RV abnormalities, it can occur in those with only microscopic abnormalities and no obvious RV enlargement.734 RV dilation, precordial repolarization abnormalities, and LV involvement have been associated with risk of sudden death.730,735,736 Certain genetic types may be associated with higher risk of SCD.737 SCD in 1 or more family members intuitively suggests a higher risk of SCD in an affected individual, but this has not been well quantified.170

9.3.2. Electrophysiological testing

The arrhythmic manifestations of the disease are variable.96 The prognostic role of EP testing in patients presenting with isolated PVCs or NSVT is not known. The response to EP testing may be influenced by the severity of the disease. Progression of disease has to be considered. EP testing has been evaluated in a limited number of patients for risk stratification. Di Biase et al.738 used EP testing in 17 patients with ‘mild’ dysplasia and induced VT only in patients with spontaneous sustained VT. VT was induced in 90% of 12 patients with spontaneous sustained VT.739 The positive predictive value for recurrent VT was only 55%. Sustained VT could not be induced in 20 patients presenting with NSVT.736 In this study, inducibility was 88% in 24 of 27 patients presenting with sustained VT. EP testing, in general, is used to reproduce clinical VT and to guide ablation.740,741

9.3.3. Management

The treatment of ARVC is often based on individual patient presentation and local physician experience. The ICD has been used in patients with unexplained syncope, sustained VT, or VF with a high incidence of appropriate shocks.742 Although there are no specific large randomized trials in ARVC to support this, the situation is sufficiently ‘similar’ to those disease states such as previous MI where these indications are well established.266,718,741,743 ICD treatment in individuals with a known family history of SCD or unexplained syncope is intuitively compelling but not rigidly proved. The impact of medical therapy on mortality is not established. RF ablation has been used in selected patients for VT in medically refractory patients.744 Elimination of 1 or more clinical tachycardias by RF ablation is useful for management of symptoms but may not be sufficient to prevent SCD. Operative therapy in the form of total electrical RV disconnection has proved successful in medically refractory patients with normal LV function but does carry a risk of postoperative right HF.745 Heart transplantation and ventricular assist devices are an option in patients with biventricular failure.

9.3.4. Genetic analysis

Genetic analysis is useful in families with RV cardiomyopathy, because whenever a pathogenetic mutation is identified, it becomes possible to establish a presymptomatic diagnosis of the disease among family members and to provide them with genetic counseling to monitor the development of the disease and to assess the risk of transmitting the disease to offspring. Based on current knowledge, genetic analysis does not contribute to risk stratification in RV cardiomyopathy.

9.4. Neuromuscular disorders

Recommendations

Class I

  • Patients with neuromuscular disorders who have ventricular arrhythmias should generally be treated in the same manner as patients without neuromuscular disorders. (Level of Evidence: A)

Class IIb

  • Permanent pacemaker insertion may be considered for neuromuscular diseases such as myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb dystrophy, and peroneal muscular atrophy with any degree of AV block (including first-degree AV block) with or without symptoms, because there may be unpredictable progression of AV conduction disease. (Level of Evidence: B)

The inherited neuromuscular disorders may predispose to atrial arrhythmias, conduction defects, advanced AV block, monomorphic VT, polymorphic VT, and SCD.746755 An exhaustive list of the inherited neuromuscular disorders is beyond the scope of this guideline. Table 8 lists some of the more common disorders associated with cardiovascular manifestations, produced in some cases by degeneration of the specialized conduction tissue and in others by degenerative changes in atrial and myocardial tissue predisposing to cardiomyopathy and ventricular arrhythmias. In many cases, the resting ECG is abnormal, with first-degree AV block, bundle-branch block, Q waves, ST-T abnormalities, or PVCs.753,754

View this table:
Table 8

Frequency of events in neuromuscular disorders associated with heart disease

InheritanceHBVACM
Muscular dystrophies
 DuchenneX-linked+++++
 BeckerX-linked+++++
 X-lined dilated CMX-linked++++
 Limb-girdle 1BAD++++++++
 Limb-girdle 2C–2FAR+++++
 Myotonic MDAD+++++++
 Emery-Dreifuss MD and associated disordersX-linked, AD, AR++++++++
Other conditions
 Friedreich's ataxiaAR++++
 Kearns-Sayre syndrome++++++
  • + To +++ represents a comparison between the various medical conditions and the relative frequency of an event. AD, autosomal dominant; AR, autosomal recessive; CM, cardiomyopathy; HB, heart block; MD, muscular dystrophy; VA, ventricular arrhythmias; +, low-frequency event; ++, intermediate-frequency event; +++, high-frequency event.

The clinical presentation, indicating the potential substrate for SCD, is quite variable, ranging from asymptomatic to the symptoms of syncope, lightheadedness, and palpitations. There are no large series of asymptomatic patients treated with devices and the timing of pacemaker/ICD implantation is not clear based on the available literature. In general, the more advanced the cardiac involvement is (conduction or structural), the more likely it is that a serious arrhythmia will occur. SCD is a well-recognized complication of some of the neuromuscular diseases and progression of the conduction abnormalities may be unpredictable.756762 Once cardiac involvement occurs, particularly with the muscular dystrophies, the clinician should maintain a low threshold for investigating symptoms or ECG findings to determine the need for pacemaker insertion, invasive EP studies, or ICD implantation. Screening for underlying cardiovascular manifestations with a resting 12-lead ECG or echocardiogram to determine cardiac involvement should be part of the routine clinical assessment, independent of symptom status. The relative likelihood of a patient with an inherited neuromuscular disorder developing a conduction disturbance, ventricular arrhythmia, or cardiomyopathy is listed in Table 8. In general, the indications for device therapy in patients with Duchenne, Becker, X-linked cardiomyopathies, limb-girdle 2C to 2F, and Friedreich ataxia should follow standard pacing/ICD guidelines as for patients with dilated cardiomyopathies. The reader is referred to the ACC/AHA/NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmic Devices for a comprehensive listing of indications.1 In an asymptomatic subject with normal ECG and no cardiovascular manifestations, pacemaker or ICD implantation is generally not indicated.

Indications for pharmacological or device therapy in patients with myasthenia gravis, Guillain-Barre syndrome, or an acute cerebrovascular event are quite different than those for the above-mentioned inherited neuromuscular disorders. Treatment is often temporary to manage the acute event and not usually required on a long-term basis.

10. Heart failure

Recommendations

Class I

  1. ICD therapy is recommended for secondary prevention of SCD in patients who survived VF or hemodynamically unstable VT, or VT with syncope and who have an LVEF less than or equal to 40%, who are receiving chronic optimal medical therapy, and who have a reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A)

  2. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with LV dysfunction due to prior MI who are at least 40 d post-MI, have an LVEF less than or equal to 30% to 40%, are NYHA functional class II or III receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A) (See Section 1.2.)

  3. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with nonischemic heart disease who have an LVEF less than or equal to 30% to 35%, are NYHA functional class II or III, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B) (See Section 1.2.)

  4. Amiodarone, sotalol, and/or other beta blockers are recommended pharmacological adjuncts to ICD therapy to suppress symptomatic ventricular tachyarrhythmias (both sustained and nonsustained) in otherwise optimally treated patients with HF. (Level of Evidence: C)

  5. Amiodarone is indicated for the suppression of acute hemodynamically compromising ventricular or supraventricular tachyarrhythmias when cardioversion and/or correction of reversible causes have failed to terminate the arrhythmia or prevent its early recurrence. (Level of Evidence: B)

Class IIa

  1. ICD therapy combined with biventricular pacing can be effective for primary prevention to reduce total mortality by a reduction in SCD in patients with NYHA functional class III or IV, are receiving optimal medical therapy, in sinus rhythm with a QRS complex of at least 120 ms, and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

  2. ICD therapy is reasonable for primary prevention to reduce total mortality by a reduction in SCD in patients with LV dysfunction due to prior MI who are at least 40 d post-MI, have an LVEF of less than or equal to 30% to 35%, are NYHA functional class I, are receiving chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B) (See Section 1.2.)

  3. ICD therapy is reasonable in patients who have recurrent stable VT, a normal or near normal LVEF, and optimally treated HF and who have a reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  4. Biventricular pacing in the absence of ICD therapy is reasonable for the prevention of SCD in patients with NYHA functional class III or IV HF, an LVEF less than or equal to 35%, and a QRS complex equal to or wider than 160 ms (or at least 120 ms in the presence of other evidence of ventricular dyssynchrony) who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

Class IIb

  1. Amiodarone, sotalol, and/or beta blockers may be considered as pharmacological alternatives to ICD therapy to suppress symptomatic ventricular tachyarrhythmias (both sustained and nonsustained) in optimally treated patients with HF for whom ICD therapy is not feasible. (Level of Evidence: C)

  2. ICD therapy may be considered for primary prevention to reduce total mortality by a reduction in SCD in patients with nonischemic heart disease who have an LVEF of less than or equal to 30% to 35%, are NYHA functional class I receiving chronic optimal medical therapy, and who have a reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B) (See Section 1.2.)

Considerations taken by the Writing Committee in formulating recommendations for this section are discussed in detail in the Introduction.

Ventricular arrhythmias and SCD are common in patients with symptomatic acute and chronic HF and LV systolic dysfunction. The cause of HF likely influences the mechanisms and types of ventricular arrhythmias. The guidelines and comments in this section refer to patients with the symptomatic HF; not just abnormal LVEF (refer to the ACC/AHA Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult for definitions.6

Arrhythmia management in the setting of acute HF takes place concurrently with attempts at hemodynamic stabilization. Evaluation of arrhythmias in the setting of acute HF necessitates a search for correctable mechanical problems such as catheters placed for hemodynamic monitoring that are causing ventricular or supraventricular arrhythmias. In addition, meticulous attention needs to be given to such factors as pharmacological agents used in the management of acute heart failure and electrolyte and oxygen status. Given its relatively rapid onset of action and its superior safety profile in patients with HF, the use of intravenous amiodarone for the management of life-threatening arrhythmias during acute HF has gained widespread acceptance.

In the acutely ill patient with HF, SVT and AF or atrial flutter may impose hemodynamic decompensation, and aggressive therapy may be needed. Vagotonic measures rarely work in the setting of acute HF. Poorly tolerated SVT may be better treated acutely by synchronous cardioversion, which may be accomplished at relatively low energies (e.g., 50 to 100 J biphasic). Verapamil may be effective at suppressing reentrant SVTs that are dependent on the AV node. Care should be taken to avoid excessive myocardial suppression related to the negative inotropic effects of verapamil. Intravenous amiodarone may be more effective at rate control of AF or atrial flutter and may restore sinus rhythm. In HF patients, amiodarone either alone or with electrical cardioversion is effective at slowing the heart rate and achieving cardioversion.763,764

In the setting of acute HF, ventricular arrhythmias may be especially poorly tolerated and early cardioversion should be performed, rather than attempting pharmacological termination of arrhythmia. Patients with advanced myocardial disease often have intraventricular conduction delays, making the distinction of ventricular from supraventricular arrhythmias challenging. Regardless of the origin of an unstable arrhythmia, cardioversion is appropriate. Amiodarone is preferred for longer-term administration and is generally well tolerated hemodynamically.765 Catheter ablation may be an appropriate adjunctive therapy in selected patients.

NSVT can be documented on 24-h ambulatory ECG monitoring in 30% to 80% of chronic HF patients without arrhythmia symptoms.25,766,767 Although NSVT is associated with increased mortality risk in this population, the weight of evidence does not show a specific link between NSVT and SCD,25,766,768 although one trial has suggested a link.767 There is no evidence that suppression of NSVT has a favorable effect on prognosis in patients with HF.638 Thus, asymptomatic NSVT should not be treated by antiarrhythmic medication. If NSVT causes symptoms that require therapy, amiodarone is probably the safest agent to use for treatment, although amiodarone treatment in NYHA functional class III patients in the SCD-HeFT trial was associated with possibly increased mortality.8,248

Polymorphic VT in association with or not in association with QT prolongation may occur during exacerbation of HF. These arrhythmias may resolve with the treatment of HF.

SCD accounts for approximately 50% of deaths in patients with HF. However, there is little evidence that empiric antiarrhythmic therapy can reduce the risk of SCD. Earlier trials of empiric therapy with amiodarone have yielded conflicting results, with some demonstrating reduced mortality and others showing no improvement in survival.637,638 The SCD-HeFT trial showed no survival benefit to patients with HF (NYHA functional class II and III) and LVEF less than or equal to 35% treated with amiodarone empirically.8

ICD therapy did not improve the survival of patients with HF due to nonischemic DCM in 2 small trials.635,645 However, the SCD-HeFT trial demonstrated a 23% reduction in total mortality with ICD treatment in comparison to placebo.8 These results are consistent with the results of DEFINITE and earlier trials of patients with CHD and LV dysfunction, some of whom had symptomatic HF.192,267,268 ICD in combination with biventricular pacing may improve survival and improve symptoms of patients with advanced HF (NYHA functional class III and IV) over short-term follow-up (1 to 2 y).

Biventricular pacing may be used to synchronize the contraction of the LV in patients with abnormal ventricular activation. Cardiac resynchronization therapy has been shown to improve hemodynamics, increase LVEF, extend exercise tolerance, and improve quality of life.769,770 In patients with a poor functional status (NYHA functional class III or IV), reduced ventricular function (LVEF less than or equal to 35%), and a wide-QRS complex (at least 120 ms), biventricular pacing without ICD therapy has consistently led to a reduction of mortality and hospital admissions for the treatment of HF.771,772 It has therefore been strongly recommended (class I) elsewhere6 that biventricular pacing should be considered for the treatment of such patients. This guideline considers therapies for the management of ventricular arrhythmias and SCD. In 1 recent study772 that recruited patients with NYHA class III through IV HF, an EF equal to or less than 35%, and a QRS complex equal to or greater than 160 ms (or at least 120 ms in the presence of other evidence of ventricular dyssynchrony), sudden death was also significantly reduced when biventricular pacing was applied. However, in another study771 that recruited similar patients, except that the QRS complex had simply to equal or exceed 120 ms, sudden death was not prevented by resynchronization therapy alone. The value of biventricular pacing without additional ICD support for the reduction of sudden death remains controversial.773,774

11. Genetic arrhythmia syndromes

11.1. General concepts for risk stratification

LQTS, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT) (Online Mendelian Inheritance in Man [OMIM] Nos. 192500, 152427, 603830, 600919, 176261, 603796, 601144, and 604772)775 are inherited arrhythmogenic diseases. They share genetically determined susceptibility to VT and SCD in the absence of recognizable structural abnormalities of the heart. These syndromes are by definition rare diseases, because they have an estimated prevalence below 5 in 10 000 (Definition 1295/1999/EC of the European Parliament 770).

Given the limited number of individuals affected by these diseases, certain aspects should be considered before developing recommendations for risk stratification and management of patients with these diseases.

  • Most of the data available for these conditions derive from large registries that have followed patients over time, recording outcome information. No randomized studies are available, and most likely they will never be conducted in these uncommon conditions. Therefore, the level of evidence for recommendation in these conditions is B or C depending on the size of the available registries and on the duration of the follow-up of enrolled patients. (This Writing Committee has decided to consider Level of Evidence: B for data collected by the registries on LQTS because they are based on large number of patients with a long follow-up and to use a Level of Evidence: C for the Brugada syndrome and CPVT registries, which have a much shorter observation time for enrolled patients.)

  • Data on the natural history of these diseases are potentially biased by the fact that it is more likely that a highly symptomatic case is referred to a registry. This potential bias is likely to be more pronounced in the more recent registries (ARVC, Brugada syndrome, and CPVT) than in those that have been collecting patient information for decades (LQTS).

  • Some concepts applied for risk stratification are common to the different inherited arrhythmogenic diseases. For example, the severity of the ECG phenotype is generally a marker of increased risk of SCD in most of these diseases. In LQTS, the ‘severe’ phenotype is represented by the presence of a QTc exceeding 500 ms,103,776 in the Brugada syndrome by the spontaneous presence of ST-segment elevation in the right precordial leads,104,777 and in CPVT by VT induced by exercise stress testing.105,778

  • Because these diseases are characterized by electrical abnormalities occurring in the structurally intact heart, the use of the ICD is always indicated with a class I indication in the secondary prevention of cardiac arrest. Its use in primary prevention is more debated, considering the young age of patients at diagnosis. In LQTS and in CPVT, pharmacological therapy with beta blockers is effective in reducing the risk of cardiac events. In these diseases, therefore, beta blockers are recommended as first-line treatment in all affected individuals, class I indication, and the use of the ICD is recommended for higher-risk subgroups.104,105,777,779 In the Brugada syndrome, no effective pharmacological treatment is known and therefore the use of prophylactic ICD should be targeted to high-risk patients.104,777

  • Genetic information is progressively entering clinical practice and is being integrated in the risk stratification schemes.103,780

  • In general, a family history of SCD has not proved useful in stratifying risk in affected patients.

  • Avoidance of competitive sports is recommended by some, but not others, for all patients affected by inherited arrhythmogenic disorders even when physical activity is not considered to be the trigger for arrhythmic episodes, such as in patients with Brugada syndrome and LQT3 (see Section 13.1).

A concise overview of clinical manifestations and the recommendations for risk stratification and management of the individual diseases is outlined in the following subsections.

11.1.1. Long QT syndrome

Recommendations

Class I

  1. Lifestyle modification is recommended for patients with an LQTS diagnosis (clinical and/or molecular). (Level of Evidence: B)

  2. Beta blockers are recommended for patients with an LQTS clinical diagnosis (i.e., in the presence of prolonged QT interval). (Level of Evidence: B)

  3. Implantation of an ICD along with use of beta blockers is recommended for LQTS patients with previous cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: A)

Class IIa

  1. Beta blockers can be effective to reduce SCD in patients with a molecular LQTS analysis and normal QT interval. (Level of Evidence: B)

  2. Implantation of an ICD with continued use of beta blockers can be effective to reduce SCD in LQTS patients experiencing syncope and/or VT while receiving beta blockers and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

Class IIb

  1. Left cardiac sympathetic neural denervation may be considered for LQTS patients with syncope, torsades de pointes, or cardiac arrest while receiving beta blockers. (Level of Evidence: B)

  2. Implantation of an ICD with the use of beta blockers may be considered for prophylaxis of SCD for patients in categories possibly associated with higher risk of cardiac arrest such as LQT2 and LQT3 and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

11.1.1.1. Causes and risk factors

The LQTS is an inherited disease characterized by prolonged ventricular repolarization (QT interval) and by ventricular tachyarrhythmias that may manifest as syncopal events. Cardiac arrhythmias are often elicited by stress and emotion, although in some cases they may also occur at rest or during sleep.781 Two patterns of inheritance have been identified: the more common autosomal dominant Romano-Ward and Timothy syndromes782,783 and the much rarer autosomal recessive cases. The latter are usually more severe, often but not always involving consanguineous marriages, and are often associated with congenital deafness (the Jervell Lange-Nielsen syndrome784). Mutations in 8 genes have been identified: 7 of them encode cardiac ion channel subunits785790 and 1 encodes an anchoring protein that has been implicated in controlling ion channel targeting specific membrane sites.791 The distinguishing features of some of the genetic variants of the disease have been identified and incorporated in risk stratification algorithms.

11.1.1.2. Risk stratification

Even before the identification of the genetic subtypes, QT interval duration was identified as the strongest predictor of risk for cardiac events (syncope, SCD) in LQTS,776 and it remains so. A normal QT interval in an ungenotyped family member portends a good prognosis.792 A QTc exceeding 500 ms (corresponding to the upper QTc quartile among affected genotyped individuals) identifies patients with the highest risk of becoming symptomatic by age 40.103 Patients with the Jervell Lange-Nielsen and other homozygous syndromes and patients with LQTS associated with syndactyly790,793 are at higher risk. A family history of SCD has not proved to be a risk factor for SCD.779,794

Genetic testing is often useful in probands with a clinical diagnosis of LQTS to provide more accurate risk stratification and to guide therapeutic strategies.

Symptoms in LQTS range from SCD to syncope and near syncope. Patients resuscitated from SCD have an especially ominous prognosis, with a relative risk of 12.9 of experiencing another cardiac arrest.779 In addition, affected patients may be identified because of QT prolongation detected incidentally or because they are relatives of affected individuals and are found to be mutation carriers in genetic screening; prognosis in such family members tends to be better than that for the proband. Risk is increased during the immediate postpartum period.795

It has been shown that the interplay between genetic defect, QT duration, and gender may provide an algorithm for risk stratification.103 Patients with the highest risk of becoming symptomatic are LQT1 and LQT2 patients with a QTc greater than 500 ms and males with LQT3 irrespective of QT interval duration.103 LQT3 patients may represent a group at higher risk.780 Among LQT2 patients, those with a mutation resulting in a change in the pore region of the protein796 appear to be at higher risk of cardiac events than are those with mutations in other regions of the gene. Beta blockers are highly effective in LQT1, whereas they offer incomplete protection in LQT2 and LQT3.797

11.1.1.3. Ventricular arrhythmias

Syncope in LQTS patients is usually attributed to severe ventricular arrhythmias (although other causes can occur). Syncopal events are usually associated with stress, emotion, or exercise; however, gene-specific triggers for cardiac events have been identified in the 3 most common genetic variants of the disease. Individuals affected by the LQT1 form of the disease (mutations in the KCNQ1 or KvLQT1 gene encoding the ion channel that conducts the potassium current IKs) are more susceptible to cardiac events occurring during exercise798 and particularly during swimming.799,800 LQT2 patients harbor mutations in the KCNH2 (or HERG) gene encoding the channel conducting the potassium current IKr are susceptible to cardiac events occurring during rest or emotion, and characteristically with acoustic stimuli.800,801 Finally, LQT3 patients carrying mutations in the SCN5A gene encoding the cardiac sodium channel are susceptible to cardiac events occurring at rest and during sleep.798 A description of the long QT subtypes is given in Table 9.

View this table:
Table 9

Long QT syndrome subtypes

VariantGeneChromosomeFunction
LQT1KCNQ111p15.5IKs alpha subunit
LQT2KCNH27q35–35IKr alpha subunit
LQT3SCN5A3p21–23INa alpha subunit
LQT4ANK24q25-2targeting protein
LQT5KCNE121p22.1–22.2IKs beta subunit
LQT6KCNE221p22.1–22.2IKr beta subunit
LQT7KCNJ217p23.1–24.2IK1
LQT8CACNA1C12p13.3ICa alpha subunit
JLN1KCNQ111p15.5IKs alpha subunit
JLN2KCNE121p22.1–22.2IKr beta subunit

The mean age for first manifestation of the disease is 12 y, but there is a wide range from the first year of life to as late as the fifth through sixth decades. Documentation of the arrhythmia during cardiac events is relatively uncommon in LQTS: when arrhythmias are recorded, the characteristic polymorphic VT, ‘torsades de pointes’, is identified;781,802 SCD may be the first manifestation of the disease.

11.1.1.4. Lifestyle changes

It is recommended that all patients affected by LQTS avoid competitive sports activity.682 For LQT1 patients, swimming should be specifically limited or performed under supervision. LQT2 patients should avoid exposure to acoustic stimuli especially during sleep (avoidance of telephone and alarm clock on the night stand). All patients with LQTS should avoid drugs known to prolong the QT interval and those that deplete potassium and magnesium.

11.1.1.5. Andersen syndrome

In 1971, Andersen et al.803 reported the case of an 8-y-old with short stature, hypertelorism, broad nasal root, and defect of the soft and hard palate. The definition of Andersen syndrome was used for the first time in 1994 by Tawil et al.804 to describe a clinical disorder consisting of 3 major features: potassium-sensitive periodic paralysis, ventricular arrhythmias, and dysmorphic features (similar to those described by Andersen in 1971). The presence of a varying degree of QT interval prolongation was pointed out in the first systematic description of the disease.804 Subsequently, Sansone et al.805 strengthened its crucial diagnostic significance. Besides showing QT interval prolongation, Andersen syndrome patients may also present with repolarization abnormalities consisting in a late repolarization component resembling an enlarged U wave. Bidirectional VT has been also reported as a distinguishing pattern of arrhythmias in Andersen syndrome. Andersen syndrome is also referred to as LQT7 even if it has been debated whether it should be considered part of the spectrum of the LQTSs.806 Despite SCD being reported,807 arrhythmias do not appear to be a major cause of death in Andersen syndrome and the disease often has a benign outcome.805,808

The genetic background of Andersen syndrome was recently elucidated through genomewide linkage analysis by Plaster et al.,804 who successfully linked this disorder to the locus 17q23 in a large family. A candidate gene screening was carried out in the critical region and a missense mutation was identified in the KCNJ2 gene. Additional mutations were subsequently identified in 8 unrelated individuals, thus providing the proof that KCNJ2 is the cause of at least some of the Andersen syndrome cases. KCNJ2 encodes an inwardly rectifier potassium channel, Kir2.1, that is highly expressed in the heart, where it appears to act as a determinant factor of phase 4 repolarization and of resting membrane potential. Mutations in KCNJ2 are found in approximately 40% of patients with Andersen syndrome.

Little is known about risk stratification and management of patients with Andersen syndrome. Patients seem to have ventricular arrhythmias but not a high incidence of cardiac arrest. The benefit of prophylactic treatment with beta blockers has not been defined even if most patients with prolonged QT are usually treated with these agents on empiric grounds. The beneficial role of calcium channel blockers has also been proposed based on the arrhythmia suppression observed in a single patient.809

11.1.1.6. Genetic analysis

Genetic analysis is very important for identifying all mutation carriers within an LQTS family. Once identified, silent carriers of LQTS genetic defects may be treated with beta blockers for prophylaxis of life-threatening arrhythmias. Furthermore, silent mutation carriers should receive genetic counseling to learn about the risk of transmitting LQTS to offspring.

In patients affected by LQTS, genetic analysis is useful for risk stratification103 and for making therapeutic decisions.810 Although genetic analysis is not yet widely available, it is advisable to try to make it accessible to LQTS patients.

11.1.2. Short QT syndrome

The first report of a clinical condition characterized by abnormally short repolarization was made by Gussak et al. in 2000.140 These authors described 2 siblings and their mother, all with a persistently short QT interval (260 to 275 ms) with peaked and narrow T waves in the absence of structural heart disease. These authors proposed that a QT interval shorter than 300 ms is diagnostic for SQTS. In 2003, Gaita et al.811 reported 2 families with SQTS and showed that all affected patients had a QTc less than 300 ms with a QT interval less than 280 ms. Shortly thereafter, a novel form of SQTS in patients with a QTc up to 320 ms was identified.812 At present, it is still undefined whether the diagnosis of SQTS should be based on QT or QTc and which is the sensitivity and specificity of different QT/QTc interval cutoff values.

Morphological T-wave abnormalities accompany the abbreviated repolarization in SQTS. Several patients have tall and peaked T waves or asymmetrical T waves with a normal ascending phase and a very rapid descending limb. Clinical parameters for diagnosis are not yet known, so genetic analysis seems useful to confirm diagnosis in suspected cases.

Up to now, only 23 cases of SQTS from 6 different families have been reported813 and the present experience suggests that the disease may be highly lethal. It should be considered, however, that when only a very limited cohort of patients is available, the severity of a disease tends to be overestimated, because symptomatic patients are identified because of their life-threatening arrhythmias while asymptomatic patients remain underdiagnosed. No information is available on whether specific triggers may precipitate cardiac events, as cardiac arrest has occurred both at rest and under stress. Mutations in at least 3 genes encoding for cardiac ion channel proteins highly expressed in the cardiac muscle may cause SQTS.

The first identified SQTS gene is KCNH2,814 which was found to harbor mutation leading to a remarkable increase in the IKr current. Bellocq et al.815 reported another gain-of-function mutation affecting the KCNQ1 gene in a 70-y-old man presenting with idiopathic VF and short QT interval at the ECG. The third gene is KCNJ2, identified as the cause of abnormally short ventricular repolarization with a peculiar T-wave morphology (extremely fast terminal limb and a quasi-normal ST segment and ascending T-wave phase) by Priori et al.816

It is interesting to note that all 3 SQTS genes (KCNH2, KCNQ1, and KCNJ2) also cause LQTS. The ECG phenotypes depend on the opposite biophysical consequences of the underlying mutations, with loss-of-function mutations being associated with LQTS and gain-of-function mutation being the cause of SQTS.

EP investigations have shown that both atrial and ventricular effective refractory periods are shortened in SQTS and programmed electrical stimulation usually induces ventricular tachyarrhythmias. Whether inducibility of ventricular arrhythmias is predictive of adverse clinical outcome remains unclear (Table 10).

View this table:
Table 10

Genetic variants of short QT syndrome

Locus nameChromosomal locusInheritanceGene symbolProteinReference
SQTS17q3p2135–q36Autosomal dominantKCNH2IKr potassium channel alpha subunit (HERG)Brugada et al. 813
SQTS211p15.5Autosomal dominantKCNQ1IKs potassium channel alpha subunit (KvLQT1)Bellocq et al. 814
SQTS317q23.1–q24.2Autosomal dominantKCNJ2IK1 potassium channel (Kir2.1)Priori et al. 815

The management of patients with SQTS is still poorly defined.817 In patients with mutation on the KCNH2 gene, it has been suggested that quidinidine may be effective in suppressing inducibility at programmed electrical stimulation, but whether this also confers long-term prevention of cardiac arrest is unknown. For the other genetic forms of SQTS, the efficacy of quinidine is less clear and the use of the ICD may be considered, even if it may be associated with an increased risk of inappropriate shocks due to T-wave oversensing.817

11.1.2.1. Genetic analysis

Genetic analysis may help identify silent carriers of SQTS-related mutations; however, the risk of cardiac events in genetically affected individuals with a normal ECG is currently not known. Similarly, given the limited number of patients with SQTS so far identified, at present, genetic analysis does not contribute to risk stratification.

11.1.3. Brugada syndrome

Recommendations

Class I

  • An ICD is indicated for Brugada syndrome patients with previous cardiac arrest receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIa

  1. An ICD is reasonable for Brugada syndrome patients with spontaneous ST-segment elevation in V1, V2, or V3 who have had syncope with or without mutations demonstrated in the SCN5A gene and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. Clinical monitoring for the development of a spontaneous ST-segment elevation pattern is reasonable for the management of patients with ST-segment elevation induced only with provocative pharmacological challenge with or without symptoms. (Level of Evidence: C)

  3. An ICD is reasonable for Brugada syndrome patients with documented VT that has not resulted in cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  4. Isoproterenol can be useful to treat an electrical storm in the Brugada syndrome. (Level of Evidence: C)

Class IIb

  1. EP testing may be considered for risk stratification in asymptomatic Brugada syndrome patients with spontaneous ST elevation with or without a mutation in the SCN5A gene. (Level of Evidence: C)

  2. Quinidine might be reasonable for the treatment of electrical storm in patients with Brugada syndrome. (Level of Evidence: C)

11.1.3.1. Causes and risk factors

The Brugada syndrome is associated with a characteristically abnormal ECG and a high risk of SCD in individuals with a structurally normal heart.818 The Brugada pattern ECG shows J-point segment elevation in leads V1 to V3 and RBBB in some patients; the ECG pattern can be present always or intermittently. Occasionally, J-point elevation has been reported in other (e.g., inferior) leads. The disease is transmitted with an autosomal dominant pattern of inheritance. The clinical expression of the phenotype is modified by gender as 90% of the affected individuals with a diagnostic ECG are male. Only 1 Brugada syndrome disease gene has been identified so far, the cardiac sodium channel gene (SCN5A);819 non-SCN5A loci have also been reported but the disease gene(s) at these loci remain to be identified. Cardiac events (syncope or cardiac arrest) occur predominantly in males in the third and fourth decades of life, although presentation with cardiac arrest in neonates or children have been reported.104,777,820 Fever is a predisposing factor for cardiac arrest in the Brugada syndrome.800,818,821824

11.1.3.2. Risk stratification

Because implantation of an ICD is the only prophylactic measure able to prevent SCD, risk stratification is of major importance in these patients.

11.1.3.3. Family history

As with LQTS, there are no data showing that family history predicts cardiac events among family members. Therefore, it should not be assumed that asymptomatic individuals with the characteristic ECG but without family history are at low risk or that family members of an individual with SCD are at increased risk.104

11.1.3.4. Electrocardiography

ST-segment elevation can occur spontaneously or be exposed by administration of sodium channel blockers such as flecainide, procainamide, or ajmaline.825 There is agreement that patients with a spontaneous pattern have a worse prognosis than individuals in whom the typical ECG is observed only after pharmacological drug challenge.104,777

11.1.3.5. Clinical symptoms

Patients with history of syncope and the ECG pattern of spontaneous ST-segment elevation have a 6-fold higher risk of cardiac arrest than patients without syncope and the spontaneous ECG pattern.104

11.1.3.6. Electrophysiological testing

The role of EP testing for risk stratification is debated. Brugada et al.206,207 suggested that EP testing has a pivotal role in risk stratification: in their large study, EP testing had a low positive predictive value (23%), but over a 3-y follow-up, it had a very high negative predictive value (93%). By contrast, Priori et al.104,826 reported that EP testing has a low accuracy in predicting individuals who will experience cardiac arrest. Priori et al.104,208 proposed that noninvasive risk stratification based on the ECG and symptoms provides an accurate alternative for risk stratification.

11.1.3.7. Genetic defect

Because only a single gene has been linked to the Brugada syndrome, there is still insufficient information about the contribution of genetic defects in predicting clinical outcome. Mutations in the SCN5A gene do not identify a subset of patients at higher risk of cardiac events.104

11.1.3.8. Ventricular arrhythmias

SCD is caused by rapid polymorphic VT or VF frequently occurring at rest or during sleep. Patients with Brugada syndrome usually do not have ventricular extrasystoles or nonsustained runs of VT at Holter recording. Therefore, the therapeutic approach for these patients is centered on the prevention of cardiac arrest. Basic science studies and clinical studies suggest a role for block of the transient outward potassium current by quinidine in reducing arrhythmia frequency.827,828 Quinidine and isoproterenol may be useful in patients with arrhythmia storm even in the presence of an ICD.139,395,829

11.1.3.9. Genetic analysis

Genetic analysis may help identify silent carriers of Brugada syndrome-related mutations so that they can remain under clinical monitoring to detect early manifestations of the syndrome. Furthermore, once identified, silent mutation carriers should receive genetic counseling and discussion of the risk of transmitting the disease to offspring. Based on current knowledge, genetic analysis does not contribute to risk stratification.

11.1.4. Catecholaminergic polymorphic ventricular tachycardia

Recommendations

Class I

  1. Beta blockers are indicated for patients who are clinically diagnosed with CPVT on the basis of the presence of spontaneous or documented stress-induced ventricular arrhythmias. (Level of Evidence: C)

  2. Implantation of an ICD with use of beta blockers is indicated for patients with CPVT who are survivors of cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIa

  1. Beta blockers can be effective in patients without clinical manifestations when the diagnosis of CPVT is established during childhood based on genetic analysis. (Level of Evidence: C)

  2. Implantation of an ICD with the use of beta blockers can be effective for affected patients with CPVT with syncope and/or documented sustained VT while receiving beta blockers and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIb

  • Beta blockers may be considered for patients with CPVT who were genetically diagnosed in adulthood and never manifested clinical symptoms of tachyarrhythmias. (Level of Evidence: C)

11.1.4.1. Causes and risk factors

CPVT is characterized by ventricular tachyarrhythmias that develop during physical activity or acute emotion in the presence of an unremarkable resting ECG.778 The first episodes often manifest during childhood, although late-onset cases have been described.830

The disease can be transmitted as an autosomal dominant as well as an autosomal recessive trait. Half of the autosomal dominant cases are caused by mutations in the gene encoding the cardiac ryanodine receptor (RyR2), responsible for calcium release from the stores of the sarcoplasmic reticulum.831,832 The recessive form is caused by mutations in the gene encoding calsequestrin (CASQ2), a calcium-buffering protein in the sarcoplasmic reticulum.833

11.1.4.2. Risk stratification

Too few patients with CPVT have been reported to allow the definition of a risk stratification scheme. Beta blockers appear to be effective. Patients who have had an episode of VF are considered at higher risk and are usually implanted with an ICD along with beta-blocker therapy. The recurrence of sustained VT or of hemodynamically nontolerated VT while receiving beta blockers is usually considered a marker of higher risk and an ICD is often recommended in these patients. EP testing is not useful for management and risk stratification because CPVT patients are usually not inducible.105,778

11.1.4.3. Ventricular arrhythmias

Supraventricular and ventricular arrhythmias are usually reproducibly induced by exercise stress when the heart rate reaches a threshold of 120 to 130 beats per minute. Isolated PVCs usually develop first and are followed shortly after by short runs of NSVT. If the patient continues to exercise, the duration of VT runs progressively increase and VT may become sustained. A beat-to-beat alternating QRS axis that rotates by 180°, ‘bidirectional VT,’ is the typical pattern of CPVT-related arrhythmias. CPVT patients can also present with irregular polymorphic VT or VF.105,778

Beta blockers prevent recurrences of syncope in the majority of patients,105,778 even if VT and SVT usually can still be elicited during exercise stress test. If syncope occurs in a patient taking a beta blocker, the implantation of an ICD is recommended.105 However, ICD therapy requires careful programming of the device to prevent needless therapy for nonsustained episodes of ventricular tachyarrhythmia.

11.1.4.4. Genetic analysis

Genetic analysis may help identify silent carriers of catecholaminergic VT-related mutations; once identified silent carriers may be treated with beta blockers to reduce the risk of cardiac events and may receive appropriate genetic counseling to assess the risk of transmitting the disease to offspring. Based on current knowledge, genetic analysis does not contribute to risk stratification.

12. Arrhythmias in structurally normal hearts

12.1. Idiopathic ventricular tachycardia

Recommendations

Class I

  • Catheter ablation is useful in patients with structurally normal hearts with symptomatic, drug-refractory VT arising from the RV or LV or in those who are drug intolerant or who do not desire long-term drug therapy. (Level of Evidence: C)

Class IIa

  1. EP testing is reasonable for diagnostic evaluation in patients with structurally normal hearts with palpitations or suspected outflow tract VT. (Level of Evidence: B)

  2. Drug therapy with beta blockers and/or calcium channel blockers (and/or IC agents in RVOT VT) can be useful in patients with structurally normal hearts with symptomatic VT arising from the RV. (Level of Evidence: C)

  3. ICD implantation can be effective therapy for the termination of sustained VT in patients with normal or near normal ventricular function and no structural heart disease who are receiving chronic optimal medical therapy and who have reasonable expectation of survival for more than 1 y. (Level of Evidence: C)

12.1.1. Demographics and presentation of outflow tract ventricular tachycardia

VT arising from the RV is the most common form of VT in apparently healthy people and is associated with a good prognosis in those without overt structural heart disease.291,294,297,377,834844 This VT usually has a left bundle-branch, inferior-axis morphology. It often presents as nonischemic exercise-induced and/or repetitive monomorphic VT. Symptoms tend to be mild and syncope is rare.722 Left ventricular outflow tract (LVOT) VT can arise in the absence of overt structural abnormalities and accounts for a small percentage of the overall cases of VT. The ECG recorded during sinus rhythm in patients with RVOT tachycardia helps distinguish it from the more serious condition of RV dysplasia where the ECG is more often abnormal.722 RVOT has long been thought to be idiopathic in nature, but this characterization has relied on conventional imaging and diagnostic techniques such as stress testing, echocardiography, and coronary angiography.297,834,835,843,845847 More recently, MRI has been applied to the evaluation of patients with VT arising from the RV in the absence of defined abnormalities on conventional testing particularly to exclude ARVC.210,262 LVOT VT can be classified by site of origin to either an endocardial origin; coronary cusp origin; or epicardial origin.232 VT arising from the LVOT and from the LV septum typically presents in the third to fifth decades of life.694 LVOT VT is more common in men than in women. This VT may be incessant and may be provoked by exercise.

12.1.2. Mechanisms

Several EP mechanisms have been associated with RVOT VT, including abnormal automaticity and triggered activity. The most common form of RVOT VT is related to triggered activity arising from delayed afterdepolarizations and is thought to be dependent on intracellular calcium overload and cyclic adenosine monophosphate.377,840,841 RVOT VT is frequently adenosine sensitive, may terminate with vagal maneuvers, and is facilitated by catecholamines. As such, it is often not easily inducible at baseline EP testing and may require rapid burst pacing or stimulation by isoproterenol.210,722 LV VT arising from the outflow tract may be reentrant but can also result from enhanced automaticity. Incessant LV VT has been related to a triggered mechanism associated with delayed afterdepolarizations.4,694 Idiopathic LV tachycardia can be verapamil sensitive, adenosine sensitive, and propranolol sensitive.697702

12.1.3. Electrophysiological testing

EP is motivated by the need to establish precise diagnosis to guide curative catheter ablation.209,210 Outflow tract VT in the absence of concomitant cardiac disease does not carry an adverse prognosis, although syncope can occur.848 The prognostic value of inducibility of ventricular arrhythmias has not been systematically evaluated. Inducibility of 80% has been reported in 35 patients with RVOT when EP testing was performed with up to 3 extrastimuli and isoproterenol infusion if required.300 In another study, a rate of induction of only 3% was observed, but this increased to by 80% with isoproterenol infusion alone.210 Induction with burst pacing has also been useful.297

VTs arising from the LVOT or aortic cusps have been described. These appear to be mechanistically and prognostically similar to RVOT VT. Induction of LVOT VT by EP testing is not consistent, although the arrhythmia may be provoked. It can be provoked during isoproterenol infusion.378

12.1.4. Management

Clinical treatment of RVOT or LVOT VT often involves beta and calcium channel blockers. Type IC antiarrhythmic drugs have been found to be useful in RVOT VT.297,837,849852 In patients who remain symptomatic or for whom drug therapy fails, catheter ablation of the arrhythmia focus in the RVOT should be considered. Acute success rates for RVOT ablation have been reported in excess of 90%.210,722 However, long-term success varies and may depend on the degree or presence of other abnormalities.

12.1.5. Demographics and presentation of other idiopathic left ventricular tachycardias

So-called idiopathic LV VT can arise from the LVOT or from the fascicles of the specialized conduction system. Fascicular VT can be classified into 3 types according to origin and QRS morphology during VT. Left posterior fascicular VT typically has an RBBB and superior axis morphology and is the more common form of fascicular VT. VT arising from the left anterior fascicle has an RBBB and right-axis deviation configuration and is less common. Rarely, fascicular VT will arise from fascicular location high in the septum and has a narrow QRS and normal axis configuration. This VT presents in the third to fifth decades of life695 and is equally distributed between the sexes.

12.1.6. Mechanisms and treatment

Left fascicular VT typically is reentrant and may respond to beta or calcium channel blockers. However, in patients who do not tolerate medical treatment or for whom medical treatment has failed, ablation can be considered. Ablation of posterior fascicular VT is guided by recording made either during sinus rhythm or in VT demonstrating a discrete potential preceding the earliest ventricular electrogram.703,704,709,853 Newer 3-dimensional mapping devices that do not require the presence of sustained VT can facilitate ablation in these patients.710

12.2. Electrolyte disturbances

Recommendations

Class I

  • Potassium (and magnesium) salts are useful in treating ventricular arrhythmias secondary to hypokalemia (or hypomagnesmia) resulting from diuretic use in patients with structurally normal hearts. (Level of Evidence: B)

Class IIa

  1. It is reasonable to maintain serum potassium levels above 4.0 mM/L in any patient with documented life-threatening ventricular arrhythmias and a structurally normal heart. (Level of Evidence: C)

  2. It is reasonable to maintain serum potassium levels above 4.0 mM/L in patients with acute MI. (Level of Evidence: B)

  3. Magnesium salts can be beneficial in the management of VT secondary to digoxin toxicity in patients with structurally normal hearts. (Level of Evidence: B)

Although changes in extracellular potassium, extracellular and intracellular magnesium (especially with associated hypokalemia), and intracellular calcium are all associated with EP changes that are arrhythmogenic, life-threatening ventricular arrhythmias in patients with structural heart disease should not be attributed solely to changes in these ionic concentrations. Changes in potassium concentration may occur after cardiac arrest or may accompany certain disease states such as periodic paralysis.

A rapid rise in extracellular potassium, hypokalemia (less than 3.5 mM), and hypomagnesemia are all associated with ventricular arrhythmias and SCD in patients with structurally normal hearts (some of whom may have underlying channelopathies) and in an AMI setting.591,854867 Hypomagnesemia is classically associated with polymorphic VT or torsades de pointes, which together with ventricular arrhythmias in an AMI setting may respond to intravenous magnesium.868871 Hypokalemia with or without hypomagnesemia may be responsible for ventricular arrhythmias in subjects with hypertension and congestive cardiac failure (precipitated by the use of thiazide and loop diuretics),855,856,872 acute starvation,873 acute alcohol toxicity/withdrawal, and those with ventricular arrhythmias associated with digoxin and other Vaughan Williams class 1 antiarrhythmic drugs.865,874,875 Significant hypocalcemia can prolong the QT interval.

Changes in the extracellular ionic concentrations of calcium required to produce EP changes that may contribute to ventricular arrhythmias are not encountered in clinical practice. Occasionally, hyperparathyroidism can cause important elevations in serum calcium concentrations. Intracellular fluctuations in calcium concentration influenced by drugs (e.g., digitalis glycosides), exercise (e.g., catecholamines), and reperfusion following myocardial ischemia, however, can trigger EP changes that may lead to life-threatening arrhythmias. The protective effects of beta blockade in the latter settings may in part be due to the inhibition of calcium influx into myocytes.

12.3. Physical and toxic agents

12.3.1. Alcohol

Recommendations

Class I

  1. Complete abstinence from alcohol is recommended in cases where there is a suspected correlation between alcohol intake and ventricular arrhythmias. (Level of Evidence: C)

  2. Persistent life-threatening ventricular arrhythmias despite abstinence from alcohol should be treated in the same manner that such arrhythmias are treated in patients with other diseases, including an ICD, as required, in patients receiving chronic optimal medical therapy and who have reasonable expectation of survival for more than 1 y. (Level of Evidence: C)

The relationship between alcohol ingestion and VT/SCD is indisputable; what is controversial however, is its exact nature.876 A number of studies claim a J-shaped relationship with risk lowest in individuals with low alcohol intake (i.e., 2 to 6 drinks per week) compared with those who rarely or never consume alcohol877 and those with a high alcohol intake (i.e., more than 3 to 5 drinks per day)878,879 and binge drinking habits, the ‘holiday heart syndrome’.880883 The reason for this relationship is probably the protective effects of low to moderate alcohol consumption on the risk of CHD.884 This is contested by a meta-analysis where lower protective and harmful effects were found in women, in men living in countries outside the Mediterranean area, and in studies where fatal events were used as the outcome. Furthermore, unlike low-risk patients without CHD, in middle-aged men with established CHD, low to moderate alcohol intake (1 to 14 units per week) was not associated with any significant benefit.885 Alcohol ingestion may therefore reduce the incidence of VT/SCD due to coronary events, but its effect on life-threatening arrhythmias correlates directly with the amount and duration of alcohol intake and even small quantities may be significant in susceptible individuals.

The mechanisms associated with alcohol-induced VT/SCD are complex and not entirely related to the presence of alcohol-induced cardiomyopathy. Alcohol has a negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by the indirect actions from enhanced release of catecholamines.886 EP studies have shown alcohol to induce various arrhythmias including VT in patients with and without cardiomyopathy.887,888 LVH and remodeling is an early response to heavy drinking;889 one third of alcoholics demonstrate diastolic dysfunction correlating with consumption890 and 20% to 26% develop DCM within 5 y.891 In these patients, myocyte and nuclear hypertrophy, interstitial fibrosis, and myocyte necrosis provide the substrate for arrhythmogenesis.892 QTc is prolonged in patients with proved alcoholic liver disease in the absence of electrolyte disturbances and may act as the trigger to life-threatening arrhythmias.893

12.3.2. Smoking

Recommendations

Class I

  • Smoking should be strongly discouraged in all patients with suspected or documented ventricular arrhythmias and/or aborted SCD. (Level of Evidence: B)

Cigarette smoking is an independent risk factor for SCD regardless of underlying CHD.58,894897 The vast majority of these deaths are arrhythmic. In females who smoke 25 or more cigarettes per day, the risk of ventricular arrhythmia and SCD is increased 4-fold, similar to that conferred by a history of MI.62 It is a long-term risk factor898 and continues to be so in survivors of out-of-hospital cardiac arrest who fail to give up smoking.74 Cessation of smoking significantly reduces risk of SCD. There are no data available to allow identification of individuals at greatest risk.

12.3.3. Lipids

Recommendations

Class I

  • Statin therapy is beneficial in patients with CHD to reduce the risk of vascular events, possibly ventricular arrhythmias, and SCD. (Level of Evidence: A)

Class IIb

  • n-3 polyunsaturated fatty acid supplementation may be considered for patients with ventricular arrhythmias and underlying CHD. (Level of Evidence: B)

The association of high total, very low-density lipoprotein (VLDL), or low-density lipoprotein (LDL) cholesterol levels, a low HDL cholesterol level together with high triglyceride and apolipoprotein B levels with increased risk of VT/SCD is almost entirely due to concurrent CHD. Appropriate lipid management strategies, especially the use of statins, reduces the risk of SCD by preventing recurrent fatal MI and ventricular arrhythmia.899901 The effect of lipid lowering on SCD in primary prevention has not been addressed, but a relative risk reduction of 30% to 40% would be expected in parallel with the reduction in the risk of CHD death.902,903

Free fatty acid or nonesterified fatty acid levels are also an independent risk factors for SCD but not fatal MI.94 However, the widely held belief from clinical studies that dietary n-3 PUFA may confer protection from arrhythmic death in subjects with and without documented underlying CHD,904,905 in patients who have manifest previously,904911 has been challenged by a small multicenter, double-blinded, randomized, placebo-controlled trial of n-3 PUFA in 200 patients with ICD and a recent episode of ventricular arrhythmia.262 This study showed a trend toward a higher incidence of VT/VF in patients randomized to fish oil, a trend that correlated with n-3 PUFA levels. An actuarial analysis of time to recurrent events showed significantly more events in patients randomized to fish oil.

13. Ventricular arrhythmias and sudden cardiac death related to specific populations

13.1. Athletes

Recommendations

Class I

  1. Preparticipation history and physical examination, including family history of premature or SCD and specific evidence of cardiovascular diseases such as cardiomyopathies and ion channel abnormalities, is recommended in athletes. (Level of Evidence: C)

  2. Athletes presenting with rhythm disorders, structural heart disease, or other signs or symptoms suspicious for cardiovascular disorders should be evaluated as any other patient but with recognition of the potential uniqueness of their activity. (Level of Evidence: C)

  3. Athletes presenting with syncope should be carefully evaluated to uncover underlying cardiovascular disease or rhythm disorder. (Level of Evidence: B)

  4. Athletes with serious symptoms should cease competition while cardiovascular abnormalities are being fully evaluated. (Level of Evidence: C)

Class IIb

  • Twelve-lead ECG and possibly echocardiography may be considered as preparticipation screening for heart disorders in athletes. (Level of Evidence: B)

It is generally accepted that preparticipation screening for medical conditions should be a requirement for clearance to participate in competitive athletics, but there are no uniformly accepted standards for screening. Because the risk of SCD among athletes appears to exceed the risk in comparably aged populations,912 attention to cardiovascular screening is of special importance.

Competitive athletics has been defined as ‘participation in an organized team or individual sport that requires regular competition against others as a central component, that places a high premium on excellence and achievement and requires some form of systematic training’.913,914 Preparticipation screening of athletes has been discussed in various conferences, and policy statements, although802,915,916 the screening programs vary greatly in different countries. The major causes of SCD in athletes are HCM (36%), coronary artery anomalies (19%), ARVC, and myocarditis. In Italy, the incidence of the former as a cause of SCD has been reduced considerably due to an ECG and echocardiographic screening program.917

13.1.1. Screening and management

13.1.1.1. Screening

Preparticipation cardiovascular screening focuses in general on a young population group (aged less than 30 y), among whom most anomalies will be congenital, although some might be acquired disorders.680,915,918 The multiple mechanisms and diseases involved in sudden death in young athletes have been reviewed.919 Drug intake may have an important effect on the cardiovascular system and may lead to coronary artery spasm (cocaine), modification of repolarization by drugs in susceptible individuals (i.e., antibiotics, antiarrhythmics, antidepressant agents), and blunted heart rate response during exercise (beta blockers).920 Special consideration is required in athletes who are middle-aged and older.914

Screening of athletes is a difficult task. The low incidence of anomalies makes screening not very cost effective, although one study has suggested that ECG screening is more cost effective than echocardiographic screening.921,922 Routine physical examination might not reveal clinically significant anomalies, and personal or family histories have limited value. The resting ECG can disclose rhythm disturbances, abnormal repolarization syndromes such as the LQTS, the Brugada syndrome, the WPW syndrome, and the depolarization and repolarization abnormalities associated with HCM. However, nonspecific variations commonly observed on ECGs recorded from adolescents and young athletes may be confounding. Echocardiography may show structural anomalies but will not disclose anomalies of the coronary arteries.

Nonetheless, it is recommended that all candidates undergo screening tests, such as ECG and, when appropriate, echocardiography (e.g., abnormal ECG, family history), beyond the history and physical examination. The impact of additional screening requires further clarification; the financial burden for subsequent investigation in case of suspected anomalies might be considerable.

13.1.1.2. Management of arrhythmias, cardiac arrest, and syncope in athletes

In athletes, risk factors might be aggravated or attenuated but not abolished by regular physical activity. For legal and ethical reasons, athletes receiving cardiovascular drugs and devices such as pacemakers and ICDs are generally not allowed to participate in high-grade competition. Exceptions, such as beta adrenergic‐blocking agents, depend on legal and regulatory guidelines. According to the World Anti-Doping Code established by the World Anti-Doping Agency (WADA), one of the bodies of the International Olympic Committee and accepted by all international sports federations, beta blockers and diuretics are prohibited in some particular sports. The list of particular sports can be found on the WADA World Wide Web site at www.wada-ama.org and is available as a downloadable file.923

Athletes presenting with syncope or presyncope should not participate in competitive sports until the cause is determined to be both benign and treatable. Increase of PVCs during exercise requires careful evaluation. They might be caused by structural anomalies, including coronary artery anomalies, abnormal origin of coronary artery, mitral valve prolapse, ARVC, and HCM or DCM. Endurance training is commonly accompanied by sinus bradycardia, junctional rhythm, and Wenckebach AV conduction on ECG. These are generally adaptive responses in apparently normal individuals. The distinction between adaptive LV chamber enlargement and a mild form of cardiomyopathy might be difficult. Athletes with nonsustained and asymptomatic exercise-induced ventricular arrhythmias may participate in low-intensity competitive sports provided that no structural heart disease has been demonstrated.924 Recommendations for disqualification from high-intensity sports have been stated in an advisory paper914 and a Bethesda Conference.682,802

Athletes presenting with rhythm disorders, cardiac anomalies, or syncope should be treated as any other patients. One must keep in mind that high-grade physical activity may aggravate the anomaly.

13.2. Gender and pregnancy

Recommendations

Class I

  1. Pregnant women developing hemodynamically unstable VT or VF should be electrically cardioverted or defibrillated. (Level of Evidence: B) (See Section 7.)

  2. In pregnant women with the LQTS who have had symptoms, it is beneficial to continue beta-blocker medications throughout pregnancy and afterward, unless there are definite contraindications. (Level of Evidence: C)

13.2.1. QT Interval

Typically, women have longer QT intervals than do men, and this difference is more pronounced at slower heart rates. The corrected QT interval in males decreases at puberty and then gradually increases as androgen levels fall. By age 50, gender differences in QT intervals have largely equalized.925 A similar shortening of the QT interval at puberty has been noted in males genotypically characterized with LQTSs.926 These observations strongly support a hormonal effect on QT and hence arrhythmia susceptibility. In women with the congenital LQTS, the risk of cardiac arrest is greater during the postpartum period compared with before or during pregnancy.795 The relative tachycardia seen during pregnancy may serve to shorten the QT interval and be protective. Beta blockers have a major benefit during the postpartum period when the heart rate naturally falls. Beta blockers can generally be used safely during pregnancy. Most are excreted in breast milk. Use during pregnancy is generally well tolerated by both the mother and the fetus, although a decrease in fetal heart rate can be seen. Several studies have demonstrated an increased susceptibility in women to torsades de pointes, likely related to the longer baseline QT interval and perhaps to differences in drug pharmacodynamics.927 The incidence of both congenital and acquired forms of long QT intervals and resultant torsades de pointes is higher in women than in men.776,928 In the Long QT Registry, 70% of the subjects and 58% of affected family members are women.929 Until puberty, males in the registry were found to be more likely than females to have cardiac arrests or syncope, but subsequently, the incidence of these potentially fatal events predominated in females.926 Several studies have shown that drug-induced torsades de pointes is more common in women than in men.930933 ICD therapy should be strongly considered in patients with long-term QT syndromes who are drug resistant and those with marked potential for life-threatening arrhythmias.1

13.2.2. Pregnancy and postpartum

Recommendations on management of cardiovascular diseases during pregnancy, including ventricular arrhythmias, have been summarized elsewhere.934 Palpitations are extremely common during pregnancy, and several studies have shown an increase in the symptoms of SVT during pregnancy.935937 While most palpitations are benign during pregnancy, new-onset VT is of concern.938,939 Although the presence of structural heart disease should be sought in these women, often VT occurs in the absence of overt structural heart disease and may be related to elevated catecholamines.938 As such, these arrhythmias may be beta blocker sensitive. In women presenting with new-onset VT during the last 6 wk of pregnancy or in the early postpartum period, the possibility of postpartum cardiomyopathy should be ruled out.940 In women with non-long QT-related sustained VT during pregnancy, antiarrhythmic therapy may be indicated with intravenous lidocaine acutely or procainamide long term. Amiodarone can have deleterious effects on the fetus, including hypothyroidism, growth retardation, and premature birth. Prophylactic therapy with a cardioselective beta blocker may be effective. Sotalol can be considered if beta-blocker therapy is ineffective.941 For women with known structural heart disease, pregnancy may present significant risk. Pulmonary edema, stroke, or cardiac death can occur in up to 13% of such pregnancies.942 Independent predictors of risk in women with heart disease include prior history of arrhythmias, cyanosis, poor functional class, LV systolic dysfunction, and LV outflow obstruction.942 Potentially life-threatening ventricular tachyarrhythmias should be terminated by electrical cardioversion. Beta 1-selective beta blockers alone, amiodarone alone (noting cautions about birth defects above), or in combination may be used, and ICD may be needed as its presence does not contraindicate future pregnancies.

13.2.3. Special concerns regarding specific arrhythmias

WPW syndrome and orthodromic AV reciprocating tachycardia are more common in men than in women.943,944 In addition, in patients with WPW syndrome manifest pathways are more common in men. Conversely, antidromic AV ventricular reciprocating tachycardia is more common in women than in men. However, AF degenerating to VF is more common in men than in women.100 For symptomatic WPW syndrome, the treatment of choice is RF ablation. The outcomes are similar in both sexes.945947 Management of symptomatic WPW during pregnancy may require initiation of antiarrhythmic drugs to block the accessory pathway and, in some, long-term monitoring.

The incidence of SCD at any age is greater in men than in women.948 In part, this may be related to the more common occurrence of coronary disease in men. However, even matched cohorts without CHD show a male preponderance. Classic predictors such as obesity, LVH, hyperlipidemia, and tobacco use are associated with CHD and VT more in men than in women.898 For women, hyperglycemia, elevated hematocrit, and decreased vital capacity are more important predictors for CHD and VT.898 The impact of diabetes is seen in both sexes but is much more pronounced in women. While NSVT and PVCs have been associated with increased risk of sudden death in men with or without CHD, no such association has been seen in women.898 Similarly, while PVCs post-MI in men have been associated with increased mortality, this does not hold true for women.949

13.3. Elderly patients

Recommendations

Class I

  1. Elderly patients with ventricular arrhythmias should generally be treated in the same manner as younger individuals. (Level of Evidence: A)

  2. The dosing and titration schedule of antiarrhythmic drugs prescribed to elderly patients should be adjusted to the altered pharmacokinetics of such patients. (Level of Evidence: C)

Class III

  • Elderly patients with projected life expectancy less than 1 y due to major comorbidities should not receive ICD therapy. (Level of Evidence: C)

13.3.1. Epidemiology

Ventricular arrhythmias are common in elderly populations, and the incidence increases in the presence of structural heart disease.404,950952 It must be noted that the elderly are a heterogeneous group. In different studies, elderly patients are defined anywhere from greater than 60 y to greater than 85 y of age. This lack of uniformity raises concerns regarding the applicability of study results to the entire elderly population.

Ventricular arrhythmias can be found in 70% to 80% of persons over the age of 60 y and complex ventricular ectopy is common in this age group, although many such persons are often asymptomatic.953956 Complex ventricular arrhythmias often presage new major coronary events and SCD in patients with CHD and other types of structural heart disease.957,958 The incidence of SCD increases with advancing age.959,960 In elderly patients with CHD, the proportion of cardiac deaths that are sudden decreases,36,961 whereas the proportion of ‘out of hospital’ SCD increases progressively with advancing age.36,414

Although greater than 80% of patients who die suddenly from cardiac causes have CHD, elderly patients with DCM and valvular heart disease are also at risk.957,961 SCD has also been documented in elderly patients with HCM,662 ARVC,962 and surgically repaired tetralogy of Fallot,963 particularly in patients with LV dysfunction. Brugada syndrome and congenital LQTS are uncommon causes of SCD in elderly patients.929,964

In the peri-infarction period, cardiac arrest (used as SCD surrogate) is more common in elderly patients. Data from the Second National Registry of Myocardial Infarction (NRMI-2) indicate that age greater than 75 y was associated with a higher likelihood of in-hospital cardiac arrest with an odds ratio of 1.6 (CI 1.5 to 1.7).965

13.3.2. Pharmacological therapy

The management of ventricular arrhythmias and the prevention of SCD in elderly patients do not differ appreciably from those recommended for the general population. However, when prescribing antiarrhythmic drugs to elderly patients, one must take into account the physiological changes that occur with advancing age and adjust drug regimens accordingly. Such changes include decreased renal and hepatic clearance and altered volume of distribution of pharmacological agents. Additionally, changes in body composition and the presence of comorbidities must be considered. Therefore, drug therapy should be initiated at lower than the usual dose and titration of the drug should take place at longer intervals and smaller doses.

The empiric use of most antiarrhythmic drugs to treat NSVT and other complex ventricular ectopy has been shown to be ineffective in preventing SCD and is even deleterious under certain circumstances.966970 Advanced age has been found to increase the susceptibility to adverse cardiac events from class IC antiarrhythmic drugs.969 Amiodarone is the only antiarrhythmic drug shown to improve prognosis in survivors of cardiac arrest, based on a meta-analysis of 15 randomized trials971 (see Section 6.3.1 for further discussion).

Amiodarone, however, is a drug associated with numerous side effects particularly in elderly patients who are prone to develop side effects and who are commonly on multiple drugs increasing the risk of drug interactions.404,972 Therefore, when considering amiodarone therapy for the prevention of SCD in an elderly patient who is receiving multiple drugs for comorbid conditions, the treating physician must weigh the potential benefit of such therapy against its potential side effects and decide whether amiodarone, device therapy, or no therapy is most appropriate for this particular patient.

Beta blockers, along with several agents that do not possess classic antiarrhythmic properties (e.g., ACE inhibitors, angiotensin receptor blockers, statins), have been shown in many studies to reduce all-cause mortality and SCD after AMI in all age groups, including the elderly.110,973976 In the Beta Blocker Heart Attack trial, subgroup analysis demonstrated that the greatest benefit of beta blockers occurred in the group aged 60 to 69 y.973 The combination of beta blockers and amiodarone may reduce all-cause mortality and SCD to a greater extent than amiodarone alone,404,405 and in a post-hoc analysis of the CAST data, patients treated with an antiarrhythmic drug who were also receiving beta blockers had a lower SCD rate than those treated only with an antiarrhythmic drug.977 Beta blockers have also been shown to reduce all-cause mortality and SCD in patients with severe HF.978,979 In these studies, subgroup analysis showed equivalent benefit from beta blocker therapy in younger and older patients.

Despite the demonstrated efficacy in reducing all-cause mortality and SCD, beta blockers are underused in the elderly. A retrospective analysis of the use of beta blockers after MI in patients greater than age 65 y found that only 21% of 3737 patients without contraindications were so treated. Patients who received these agents had a 43% lower 2-y mortality than patients not so treated.980 Similarly, a study of clinical practices and sources of therapeutic variation found a strong, independent negative association between age and odds of treatment with beta blockers after MI.981 These findings are a matter of great public health concern.

13.3.3. Device therapy

Several randomized, prospective trials have demonstrated the efficacy of ICDs in reducing SCD in patients with CHD at high risk for SCD (primary prevention) and in patients resuscitated from SCD (secondary prevention) compared with antiarrhythmic drug therapy.192,266268,642,643

All of the above-referenced studies included substantial numbers of patients over the age of 65 y. Subgroup analysis in AVID and MADIT II trials demonstrated equivalent benefits from ICD implantation in older and younger patients.266,268 In the Cardiac Arrest Study Hamburg (CASH) study, patients older than 65 y derived a greater benefit from ICD implantation than younger patients.643 It is therefore appropriate to infer that the results of these trials are applicable to elderly patients across the board.

Data comparing the efficacy and complications of ICD therapy in older and younger patients are sparse. In a retrospective study comparing the efficacy of ICD therapy in patients over age 65 with that of patients under 65,982 no significant difference in surgical morbidity or length of hospital stay following ICD implantation was noted between the 2 groups. Furthermore, similar survival rates were calculated for the 2 groups at 1, 2, and 3 y post-ICD implantation.

Similarly in an observational study983 of 450 patients who received either epicardial (46%) or transvenous (54%) ICDs, the 3-, 5-, and 7-y survival for arrhythmic mortality was similar for younger and older patients. Perioperative morbidity was also similar in all patient groups.

Despite these documented benefits of ICD implantation, many physicians have been hesitant to subject elderly patients to such interventions and the role of device therapy in this age group has been controversial. However, several observational studies have shown that the invasive approach in managing patients with life-threatening ventricular arrhythmias is equally beneficial in the elderly and in younger patients.984986 From 1985 to 1995, the use of ICDs in older patients grew from 1% to 13%; this was associated with improved medium-term survival.987

Very elderly patients with multiple comorbidities and limited life expectancy may not be appropriate candidates for ICD therapy even if they meet standard criteria. In such circumstances, the clinical judgment of the primary treating physician and the desires of the patient and/or his or her family take precedence over general guideline recommendations. Nevertheless, there is evidence from a study988 that octogenarians who die suddenly can be highly functional even in the month before their death. This information supports the concept that SCD often strikes fully functional elderly patients who could benefit from an ICD implantation if they meet appropriate criteria.

13.4. Pediatric patients

Recommendations

Class I

  1. An ICD should be implanted in pediatric survivors of a cardiac arrest when a thorough search for a correctable cause is negative and the patients are receiving optimal medical therapy and have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

  2. Hemodynamic and EP evaluation should be performed in the young patient with symptomatic, sustained VT. (Level of Evidence: C)

  3. ICD therapy in conjunction with pharmacological therapy is indicated for high-risk pediatric patients with a genetic basis (ion channel defects or cardiomyopathy) for either SCD or sustained ventricular arrhythmias. The decision to implant an ICD in a child must consider the risk of SCD associated with the disease, the potential equivalent benefit of medical therapy, as well as risk of device malfunction, infection, or lead failure and that there is reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)

Class IIa

  1. ICD therapy is reasonable for pediatric patients with spontaneous sustained ventricular arrhythmias associated with impaired (LVEF of 35% or less) ventricular function who are receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: B)

  2. Ablation can be useful in pediatric patients with symptomatic outflow tract or septal VT that is drug resistant, when the patient is drug intolerant or wishes not to take drugs. (Level of Evidence: C)

Class III

  1. Pharmacological treatment of isolated PVCs in pediatric patients is not recommended. (Level of Evidence: C)

  2. Digoxin or verapamil should not be used for treatment of sustained tachycardia in infants when VT has not been excluded as a potential diagnosis. (Level of Evidence: C)

  3. Ablation is not indicated in young patients with asymptomatic NSVT and normal ventricular function. (Level of Evidence: C)

The incidence of SCD due to cardiovascular disease is significantly less in pediatric than in adult patients. Current estimates are that deaths due to cardiovascular disease in individuals younger than 25 y of age account for less than 1% of all cardiac mortality.36 Due to this low event rate, population-based epidemiological studies have been required to define the incidence of unexpected, sudden death in pediatric patients. These studies have been relatively consistent, with an event rate between 1.3 and 4 deaths per 100 000 patient years.49,989991 A definite or probable cardiac cause has been estimated in 70% of young, unexpected sudden death victims.433 This compares with the estimated SCD rate of 100 per 100 000 patient years in adult patients.992 Given the low incidence of events, no randomized clinical trials have been performed to define either risk stratification for SCD in the young or the role of primary prevention therapies. Therefore, the level of evidence for most recommendations in young patients is class C.

Despite these limitations, several groups of young patients have been identified who are at an increased risk of SCD compared with the general population. These include patients with congenital heart disease, coronary artery anomalies, cardiomyopathies, and primary arrhythmic diagnoses such as the LQTSs.993 The risk of SCD and significance of ventricular arrhythmias in these patients are discussed in the individual sections in this report regarding these topics. This section discusses ventricular arrhythmias in the general pediatric population and its significance as a risk factor for SCD.

SCD in pediatric patients with WPW syndrome is uncommon and occurs primarily in patients with prior syncope, multiple accessory pathways, or short refractory periods. Therefore, in selected patients, an EP study may be indicated and ablation performed if the patient is symptomatic or the refractory period of the accessory pathway is equal to or less than 240 ms.279

Isolated PVCs are common in infants, with 15% of all newborns reported as having some ventricular ectopy during 24-h ambulatory ECG monitoring. The prevalence of ventricular ectopy decreases to less than 5% in children but then increases to 10% by 10 y of age and 25% during late adolescence and early adulthood.994996 For the vast majority of young patients with ventricular ectopy, the primary objective is to exclude any associated functional or structural heart disease, in which case PVCs may have prognostic significance.434,997 Simple ventricular ectopy in the absence of heart disease has not been demonstrated to have adverse prognostic significance.

Sustained ventricular arrhythmias may also occur in infants, most commonly, it is an accelerated idioventricular rhythm. By definition, this is a ventricular rhythm no more than 20% faster than the sinus rate and occurring in the absence of other heart disease.998 This arrhythmia typically resolves spontaneously during the first months of life. This is in contrast to the rare infant with incessant VT, which may be due to discrete myocardial tumors or cardiomyopathy.999,1000 VF and SCD have been reported in these infants, most often following the administration of intravenous digoxin or verapamil for a presumptive diagnosis of SVT.1001,1002 These ventricular arrhythmias may respond to antiarrhythmic treatment or be amenable to surgical resection. Sustained VT in infants may also be caused by hyperkalemia or associated with one of the LQTSs, particularly those forms with AV block or digital syndactyly.790,1003,1004

There is considerable debate regarding the sudden infant death syndrome (SIDS) and potential role of the LQTS in causing some of these deaths.1005,1006 However, population-based studies have demonstrated a 40% decline in the incidence of SIDS associated with avoidance of sleeping in the prone position, supporting apnea, or impaired respiratory regulation as the primary cause of SIDS in most cases.1007 Definition of the cause(s) of SIDS remains an area of ongoing investigation and includes autonomic dysfunction and ventricular arrhythmias due to genetic causes.

Beyond the first year of life, most children with complex ectopy or hemodynamically tolerated VT appear to have a good prognosis.233,1008 The cause of these arrhythmias remains unknown, and they often spontaneously resolve. Pharmacological suppression of these ventricular arrhythmias is generally ineffective and may increase the risk of an adverse outcome.

RVOT and LVOT tachycardia and LV septal tachycardia may be diagnosed during childhood or adolescence. The criteria for diagnoses of these specific arrhythmias are discussed in Section 12. The general prognosis for these arrhythmias is mostly benign, with treatment for symptomatic patients with catheter ablation offering a high rate of cure. As with other pediatric arrhythmias, a primary objective is to exclude any associated cardiovascular disease. Catecholaminergic or exercise-induced polymorphic VT is one exception to the benign prognosis for hemodynamically tolerated VT in patients with an otherwise normal heart. Although patients with this form of VT may not be overtly symptomatic, they are at risk for SCD.105 Also, symptomatic ventricular arrhythmias may be the initial presentation of cardiomyopathy in young patients.834,1009

The role and benefit of ICD implantation for the prevention of SCD in young children with advanced ventricular dysfunction have not been defined. In older children and adolescents, prophylactic ICD implantation may be considered,