Europace Advance Access published online on July 18, 2007
Europace, doi:10.1093/europace/eum143
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Efficacy of cardiac resynchronization therapy in very old patients: the Insync/Insync ICD Italian Registry
1 Belcolle Hospital, Via Monfalcone 20/A, 01100 Viterbo, Italy; 2 IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy; 3 Niguarda Hospital, Milan, Italy; 4 S. Filippo Neri Hospital, Rome, Italy; 5 Policlinico S. Matteo IRCCS, Pavia, Italy; 6 Careggi Hospital, Firenze, Italy; 7 Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy; 8 Civile Hospital, Asti, Italy; 9 S. Camillo Hospital, Rieti, Italy; 10 Istituto Auxologico S. Luca Hospital, Milano, Italy; 11 Medtronic Italia, Rome, Italy
Manuscript submitted 1 March 2007. Accepted after revision 21 June 2007.
* Corresponding author. Tel: +39 0761 339451; fax: +39 0761 339278. E-mail address: a_achilli{at}virgilio.it
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Aims To assess the effects of cardiac resynchronization therapy (CRT) in
80-year-old patients vs. patients <80 years, in terms of clinical, functional, and echocardiographic parameters after 12 month of CRT, survival, and incidence of arrhythmic events.
Methods and results The study population consisted of 1181 CRT patients (85 were 80 years old). They were enrolled in a national observational registry and underwent baseline evaluation and periodical follow-up visits. In the overall population, New York Heart Association class and ejection fraction (EF) improved and ventricular diameters decreased. Similar changes were observed in the two groups. In the study population, 157 patients died, 144 (13%) in the <80 years group and 13 (15%) in the 80 years group. There was a higher all-cause mortality (log-rank test, P = 0.015) among 80 years patients, with a trend towards higher sudden cardiac death (SCD) (P = 0.057), but similar non-SCD (P = 0.293). Using the combined endpoint of SCD or appropriate shock from a defibrillator for ventricular fibrillation, no significant differences resulted between groups (P = 0.455). In both groups, lower EF was associated with higher mortality.
Conclusion Cardiac resynchronization therapy demonstrated similar efficacy in patients aged 80 years and in those under 80, in terms of clinical and functional parameters and reverse remodelling. Similarly, CRT resulted in comparable effects on death for heart failure and on SCD.
Key Words: Cardiac resynchronization therapy, Heart failure, Elderly
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
As we age, the incidence and prevalence of heart failure (HF) increases. Probable reasons are the age-related changes in ventricular function (particularly diastolic function), the cumulative effects of hypertension, and other chronic risk factors, in addition to the improved survival rate after acute myocardial infarction in middle age and the enhanced therapy for acute HF.1
Advanced age represents a predictor of limited tolerance to cardiovascular drugs and can prevent therapy optimization. In addition, very old individuals are poorly represented in large-scale clinical trials designed to evaluate the efficacy and safety of new treatments for HF.2 Nonetheless, the prognosis of HF patients remains poor, regardless of the adoption of recommended pharmacological treatment.
Cardiac resynchronization therapy (CRT) has become an accepted adjunct therapy for patients with drug-refractory HF and ventricular conduction delay. Cardiac resynchronization therapy optimizes ventricular contractility by decreasing areas of focal dyssynchrony through atrial synchronized biventricular pacing, coordinating right ventricular and left ventricular (LV) contraction.
Several studies have demonstrated that CRT improves quality of life, New York Heart Association (NYHA) class, and exercise performance, and reduces HF hospitalizations and mortality in patients with moderately and severely symptomatic HF and intraventricular conduction delay.3–6 Recently, CRT was introduced in the guidelines for the management of chronic HF,7,8 with the highest level of evidence.
Generally, resynchronization trials have excluded very old patients (>80 years old), and little data exist on the outcomes after CRT in the elderly. This represents an important limitation, since almost half of the patients evaluated in community studies are >80 years old.9
Our retrospective analysis aimed to assess the effects of CRT in systolic HF patients at least 80 years old vs. patients <80, in terms of clinical, functional, and echocardiographic parameters, survival, and incidence of arrhythmic events.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Patient selection
Between 1999 and 2005, patients successfully implanted with biventricular pacing devices for CRT delivery (CRT-D), with or without defibrillator capability (CRT models 8040, 8042; CRT-D models 7272, 7277, 7279, Medtronic Inc., Minneapolis, MN, USA), have been enrolled in the InSync/InSync ICD Italian Registry.
All patients had been enrolled according to the following criteria:
- symptomatic chronic HF (NYHA class III–IV),
- left ventricle ejection fraction (EF)
35% on echocardiography,
- QRS duration >130 ms,
- at least one hospitalization for HF within the 12 months prior to device implantation.
Informed consent approved by Local Ethic Committees was obtained from all patients.
Study procedures
The devices and the pacing leads were implanted by means of standard techniques via cephalic and/or subclavian vein access. The target site for LV lead implantation was a lateral or postero-lateral coronary vein. Patients underwent baseline evaluation and periodic follow-up visits.
Baseline study procedures included demographics and medical history data collection, electrocardiogram (ECG) recording, NYHA classification, and echocardiographic examination. At each follow-up visit, ECG, NYHA classification, and echocardiographic examination were repeated.
The EF was assessed using the modified biplane Simpson’s rule.10 Left ventricular end-systolic (LVESD) and end-diastolic (LVEDD) diameters were determined using M-mode echocardiography under two-dimensional guidance in the parasternal long-axis view, according to the guidelines of the American Society of Echocardiography.11
For the evaluation of the effects of CRT on patient clinical and functional status, we compared the clinical and echocardiographic parameters recorded at baseline and at the 12 month follow-up visit for surviving patients; otherwise, the last observation was carried forward. Mortality data were obtained by hospital file review or direct telephone contact.
Events were classified as cardiac death (defined as SCDs or non-SCDs) and non-cardiac death. According to the Hinkle–Thaler classification,12 SCD was defined as an abrupt, unexpected death occurring within 1 h from the insurgence of symptoms. Non-SCD was mainly represented by progressive HF defined as unstable, clinical progression of deteriorating pump function in the setting of active therapy, most often in an intensive care setting. All deaths not complying with the aforementioned criteria were classified as non-cardiac death.
In addition, in patients implanted with a CRT-D system, we evaluated a combined endpoint of death or first appropriate episode of ventricular fibrillation detected and terminated by the device.
Statistical analysis
Continuous data were expressed as means ± SD. Categorical data were expressed by percentages. Differences between mean data were compared by a t-test for Gaussian variables and by Mann–Whitney or Wilcoxon non-parametric test for non-Gaussian variables, respectively, for independent or paired samples. Differences in proportions were compared by a 
2 analysis or Fisher’s exact test, as appropriate.
Univariable Cox regression analysis was used for the analysis of predictors of death. All variables associated to a P-value <0.1 at univariable analysis were entered into the multivariable Cox regression analysis.
Mortality rate was summarized by the construction of Kaplan–Meier curves, and the distributions of the groups were compared by a log-rank test.
A P-value <0.05 was considered significant for all tests. All statistical analyses were performed using SPSS software (SPSS for Windows, version 12.0, SPSS Inc., Chicago, IL, USA).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Patient population
The study population consisted of 1181 patients; of which, 85 were 80 years old or more. The median (25–75 percentile) follow-up was 14 (8–23) months and was comparable in the two groups. The demographics, baseline clinical parameters, and pharmacological therapy are listed for the whole study population, for the patients aged <80 years, and for those aged
80 years are shown in Table 1.
|
At the time of implant, a higher prevalence of females and patients in NYHA class IV was observed in the
80 years group (P = 0.006), whereas a smaller QRS duration (P = 0.032) as well as LVEDD (P = 0.009) and LVESD (P = 0.029) were measured. Renal dysfunction, pulmonary disease, and diabetes were all common concomitant conditions and were equally prevalent in both groups.
A significantly larger use of diuretics was reported in 80 years patients (P = 0.044), whereas the use of angiotensin-converting enzymes (ACE)-inhibitors or angiotensin-receptor blockers (ARBs) was more common in younger patients (P = 0.024). Moreover, 415 patients (38%) in the <80 years group received a CRT-D, with respect to 10 (12%) in the 80 years group.
At the time of the implant, no major complication occurred; in particular, the administration of contrast medium was not followed by acute renal failure or exacerbation of renal insufficiency in any patient. During the follow-up, LV leads dislodged in 48 (4.4%) patients aged <80 years and in 2 (2.4%) patients aged 80 years (P = NS). Moreover, 20 (1.8%) pocket erosions were reported in the <80 years group.
Clinical outcomes
The comparison of clinical and echocardiographic parameters recorded at baseline and at the 12 month follow-up visit is reported in Table 2 for the two groups of patients. A significant improvement in NYHA functional class was observed in both groups. In all patients, the mean QRS duration significantly decreased; an increase in EF occurred in both groups with significant reductions of LVEDD and LVESD. Comparing the relative differences of the observed variables, similar changes from baseline to follow-up were observed in the two groups (Table 2).
|
Mortality
In the overall study population, 157 of 1181 patients died (rate 12.4 per 100 patient-years of follow-up). There were 144 deaths in the under-80 group (rate 12.1) and 13 deaths in the
80 years group (rate 17.3, P = 0.180). Of these, 57 deaths were classified as non-SCD (rate 4.5); 27 among under-80 patients (rate 4.4) and 5 in the older group (rate 6.7, P = 0.352). Forty-six events were classified as SCD (rate 3.6); 41 in the under-80 group (rate 3.4) and 5 in the older group (rate 6.7, P = 0.148). The survival curves for all-cause mortality (log-rank test, P = 0.015), non-SCD (log-rank test, P = 0.293), and SCD (log-rank test, P = 0.057), obtained by Kaplan–Meier analysis, are shown in Figure 1A–C.
|
The analysis was repeated for the combined endpoint of SCD or, for CRT-D holders, first episode of ventricular fibrillation detected and terminated by the device. A total of 16 patients (all under 80) experienced at least one episode of treated ventricular fibrillation. The survival curves for the combined endpoint (log-rank test, P = 0.455) are reported in Figure 1D.
Predictors of death
As summarized in Table 3, univariable analysis indicated that male gender and NYHA class IV were significantly related to death for any cause among subjects of the <80 years group; these variables together with ischaemic aetiology, EF, and chronic atrial fibrillation were included in the multivariable model (all P < 0.100). This analysis indicated that depressed EF, considered as continuous variable, and the presence of chronic atrial fibrillation represent independent predictors of death for any cause among patients of the <80 years group. In the 80 years group, low EF emerged as a predictor at univariable analysis, whereas no other variables showed P < 0.100 and were not included in multivariable model (Table 4).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Heart failure is associated with high mortality, especially in the elderly. Data from In-CHF Registry2
and the Diamond Study13 showed an all-cause mortality ranging from 27 to 37% at 1 year in the subset of very aged patients with severe HF. In addition, HF is a condition that dramatically impairs the quality of life, particularly in older patients and mostly when it is associated with typical age-associated comorbidities.
In the last decade, important differences have emerged between patients recruited in controlled drug trials and real-world patients with HF.14 Indeed, registries allow us to follow patients with a profile similar to that seen in the community, in terms of age, gender, comorbidities, adherence, and compliance to the treatment reported in international guidelines.
In clinical practice, also patients referred for CRT device implant may present several conditions that distinguish them from the perfect candidate represented by the international guidelines. However, few studies have investigated the effects of CRT in populations with atrial fibrillation, pacemaker dependence, non-optimal medical therapy, and specifically, advanced age.
Patient population
Several baseline characteristics of our study population were consistent with those of patients enrolled in previous trials on CRT3–6: a predominance of male gender and NYHA functional class III, the ischaemic aetiology in about one-half of patients, a marked systolic dysfunction as revealed by reduced EF and severe LV dilatation, and a prolonged QRS duration.
Nonetheless, 16% of patients were in chronic atrial fibrillation, a percentage similar to the reported prevalence of atrial fibrillation in patients with clinically overt HF15; in 20% of patients, CRT was initiated by upgrading a pre-existing device. Moreover, in our population, we recorded a marked underprescription of HF medications with respect to international recommendations. This observation is in line with the results of previous studies16,17 describing common clinical practice.
In the group of 80 years patients, we observed a higher proportion of females and a higher NYHA class that reveals, as previously reported,2 a worse functional status in the elderly. However, mean LV diameters appeared lower in this group, probably due to the higher proportion of females.
The fact that the prevalence of comorbidities in the 80 years group was similar to that observed in younger patients, probably indicates that elderly patients were selected on the basis of a relatively good clinical status.
The baseline drug regimen was characterized by an extensive administration of diuretics and by a suboptimal use of ß-blockers and ACE-inhibitors in both groups. In particular, the use of inhibitors of the rennin–angiotensin–aldosterone system was lower in 80 years patients, in agreement with previous works.2,18
No major complication occurred during the implant procedure, and device-related complications observed during the follow-up were relatively rare in both study groups. The complication rates were in line with those reported in CARE-HF trial,6 with a follow-up of comparable duration: lead displacements in 6% and pocket erosions in 2% of the patients.
Clinical outcome
At the 12 month follow-up visit, CRT resulted in significant and comparable benefits in both study groups, as evidenced by the improvement in clinical, functional, and echocardiographic parameters. Specifically, the results we observed in the 80 years group are in line with those reported by Bleeker et al.19 in a population of patients who were 70 years old.
In our study, 68% of the 80 years patient had improvement in symptoms, as documented by an increase in the number of patients determined to be in NYHA class I or II after 12 months. Concurrently, CRT resulted in enhanced EF and reduced LV diameters, thus supporting the hypothesis of a favourable reverse remodelling produced also in very old patients.
Mortality
Our long-term observation of patients treated with CRT revealed mortality rates comparable with the results of previous controlled trials.5,6 Most deaths were due to cardiac causes, as expected in a population with advanced HF.2
The analysis of the survival curves for all-cause mortality evidenced a worse outcome among 80 years patients. This observation is not surprising, in view of the advanced age and the poor baseline clinical status of the group, as shown by the higher proportion of NYHA class IV patients; on the other hand, the mortality rate was considerably lower than that reported for population studies carried out in the elderly.2,13
The CARE-HF study suggested that most of the reduction in mortality with CRT was due to a decrease in the rate of deaths caused by worsening HF.6 Similarly, a recent meta-analysis of randomized controlled trials20 confirmed that CRT predominantly reduces worsening HF mortality, not affecting SCD.
In our population, we did not show any difference between groups for non-SCDs. On the contrary, SCD occurred more frequently in patients aged 80 years. However, when the combined endpoint of SCD or treated ventricular fibrillation was considered, no significant differences resulted between groups. In fact, during the study, episodes of ventricular fibrillation detected and terminated by the CRT-D device occurred only in younger patients, with consequent prevention of SCD in this group. This analysis was performed to take into account the reduction in sudden deaths due to the defibrillator therapy, in order to minimize the potential bias introduced by the uneven proportion of patients implanted with CRT-D in the two groups. In fact, our data confirm that in current clinical practice, CRT devices with defibrillator therapy are considered mainly for younger patients with longer life expectancy.
In conclusion, our results support the hypothesis that CRT presents the same effects on deaths due to cardiac causes in patients aged <80 years and those aged 80 years.
Predictors of death
In the <80 years group, we identified a low EF at baseline and the presence of chronic atrial fibrillation as predictors of all-cause mortality among the variables considered in our analysis, in line with previous observations and epidemiological studies.21,22 This finding seems to challenge previous results obtained with CRT in patients with chronic atrial fibrillation.23 One plausible explanation is that our patients presenting with atrial fibrillation did not systematically undergo atrioventricular junction ablation that guarantees permanent therapy delivery, precluding the fusion of paced and residual, spontaneously conducted beats, and was demonstrated to be associated to positive outcome.24
In our group of very old patients with severe cardiac dysfunction and advanced NYHA class, only the low EF demonstrated to be associated to higher mortality.
In both groups, QRS duration, which in previous studies was shown to be a weak predictor of CRT response in terms of mid-term clinical outcome,25,26 failed to predict the endpoint of death for any cause.
Limitations
This work presents typical limitations of similar non-randomized studies, i.e. potential bias in patient selection as well as lack of control group and possible placebo response.
However, registries similar to the Insync/Insync ICD Italian Registry help by providing results that are fully representative of clinical practice and to collect data for cohorts usually underrepresented in prospective trials. This is the case of very old patients who have typically been excluded from CRT trials.
Moreover, the absence of an endpoint adjudication committee may have affected the accuracy of the mode of death determination. In particular, in our analysis, abrupt, unexpected death of an ambulatory patient was assumed to be due to a malignant cardiac arrhythmia. Obviously, in the absence of ECG recordings or post-mortem device interrogation, inaccurate classification of death is plausible. However, according to Hinkle and Thaler,12 a terminal acute illness of short duration (<1 h) is a good indicator of the occurrence of an arrhythmic death.
|
Conclusions |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Our results demonstrate similar efficacy of CRT in patients aged
80 years and in those <80 years old, in terms of clinical and functional parameters and in terms of reverse remodelling. Similarly, CRT resulted in comparable effects on death for worsening HF and on SCD regardless of age. Therefore, CRT can be indicated in patients with HF refractory to medical therapy even if very old. In fact, in these patients, it provides several advantages with respect to conventional pharmacological therapy: it is a real selective therapy not involving systemic processes or side effects, frequently unpredictable; moreover, the improvements in cardiac function can be rapidly and objectively quantified and occur at reduced metabolic demand. |
Appendix |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
Centres and investigators participating in the InSync/InSync ICD Italian Registry:
M. Gasparini, P. Galimberti, F. Regoli, E. Gronda, Istituto Clinico Humanitas IRCCS, Rozzano-Milano; M. Lunati, G. Cattafi, G. Magenta, M. Paolucci, R. Vecchi, Niguarda Cà Granda Hospital, Milano; M. Santini, R. Ricci, San Filippo Neri Hospital, Roma; F. Gaita, M. Bocchiardo, P. DiDonna, D. Caponi, Civile Hospital, Asti; L. Tavazzi, M. Landolina, F. Frattini, R. Rordorf, F. Pentimalli, A. Vicentini, Policlinico S. Matteo IRCCS, Pavia; L. Padeletti, P. Pieragnoli, Careggi Hospital, Firenze; A. Vincenti, S. DeCeglia, A. Cirò, S. Gerardo Dei Tintori Hospital, Monza (MI); A. Curnis, G. Mascioli, Spedali Civili Hospital, Brescia; A. Puglisi, S. Bianchi, Fatebenefratelli Hospital, Roma; M. Sassara, A. Achilli, F. Turreni, P. Rossi, Belcolle Hospital, Viterbo; G.B. Perego, S. Luca Auxologico Hospital, Milano; P.A. Ravazzi, P. Diotallevi, S.S. Antonio e Biagio e Cesare Arrigo Hospital, Alessandria; M. Tritto, Mater Domini Hospital, Castellanza (VA); A. Carboni, D. Ardissino, G. Gonzi, V. Serra, Civile Hospital, Parma; G. Vergara, S. Maria Del Carmine Hospital, Rovereto (TN); G. Boriani, M. Biffi, C. Martignani, L. Frabetti, S. Orsola M. Malpighi Hospital, Bologna; G. Luzzi, Policlinico Consorziale Hospital, Bari; F. Laurenzi, S. Camillo Hospital, Roma; G. Pistis, Mauriziano Hospital, Torino; A. Cesario, G.B. Grassi Hospital, Ostia (RM); G. Zanotto, Civile Hospital, Verona; S. Orazi, S. Camillo Hospital, Rieti; R. Ometto, C. Bonanno, S. Bortolo Hospital, Vicenza; G. Molon, E. Barbieri, S. Cuore Don Calabria Hospital, Negrar (VR); A. Raviele, G. Gasparini, Umberto I Hospital, Mestre (VE); G. Botto, M. Luzi, A. Sagone, S. Anna Hospital, Como; A. Vado, S. Croce e Carle Hospital, Cuneo; A. Montenero, Multimedica Hospital, Sesto S. Giovanni (MI); G. Inama, Maggiore Hospital, Crema; B. Sassone, Civile Hospital, Bentivoglio (BO); M. Briedda, F. Zardo, S. Maria degli Angeli Hospital, Pordenone; E. Bertaglia, ULSS13 Hospital, Mirano (VE); A. Proclemer, S. Maria della Misericordia Hospital, Udine; F. Zanon, Civile Hospital Rovigo; M. Disertori, L. Gramegna, M. DelGreco, D. Dallafior, S. Chiara Hospital, Trento; C. Tomasi, A. Maresta, M. Piancastelli, S. Maria delle Croci Hospital, Ravenna; A. Bridda, S. Martino Hospital, Belluno; R. Mantovan, Cà Foncello Hospital, Treviso; A. Fusco, A. Vicentini, Polispecialistica Pederzoli Hospital, Peschiera del Garda (VR); P. Baraldi, S. Agostino Hospital, Modena; G. Lonardi, Civile Hospital, Legnago (VR); W. Rahue, S. Maurizio Hospital, Bolzano; P. Delise, Civile Hospital Conegliano (TV); C. Menozzi, S. Maria Nuova, Reggio Emilia; P. Babudri, Borgo Roma Hospital, Verona; R. Marconi, C. eG. Mazzoni Hospital, Ascoli Piceno; G. De Fabrizio, F. Alfano, G. Moscati, Avellino; G. Barbato, Maggiore Hospital, Bologna; P. Gelmini, Civile Hospital Desenzano del Garda (BS); DiSabato, S. Leopoldo Mandic Hospital, Merate (LC); S. Ricci, Ramazzini Hospital, Carpi (MO); M.D. Aulerio, S. Biagio Hospital, Domodossola (VB); G.L. Morgagni, R. Latini, Civile Hospital Macerata; G. Bardelli, Fornaroli Hospital, Magenta (MI); R. Paulichl, F. Tappeiner Hospital, Merano (BZ); M. Bernasconi, M. Marzegalli, S. Carlo Borromeo, Milano; G. Neri, Montebelluna Hospital, Treviso; E. Occhetta, Hospital Maggiore della Carità, Novara; P. Bocconcelli, S. Salvatore Hospital, Pesaro; A. Capucci, Civile Hospital, Piacenza; A. Campana, S. Giovanni di Dio e Ruggi d’Aragona Hospital, Salerno; N. Dibelardino, Civile Hospital, Velletri (RM); A. Vaglio, Giovanni e Paolo Hospital, Venezia.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
The authors would like to thank Tiziana De Santo and Paola Di Stefano (Clinical Service Team, Medtronic Italy) for the careful statistical analysis of the data, and Jane Moore, for her assistance in editing this manuscript.
Conflict of interest: S.V. and A.D. are employees of Medtronic, Inc.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsAppendixAcknowledgementsReferences |
|---|
[1] American Heart Association. Heart Disease and Stroke Statistics: 2005 Update (2005) Dallas, TX: American Heart Association.
[2] Pulignano G, Del Sindaco D, Tavazzi L, Lucci D, Gorini M, Leggio F, et al. Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J (2002) 143:45–55.[CrossRef][Web of Science][Medline]
[3] Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med (2001) 344:873–80.
[4] Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med (2002) 346:1845–53.
[5] Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med (2004) 350:2140–50.
[6] Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med (2005) 352:1539–49.
[7] Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J (2005) 26:1115–40.
[8] Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). Circulation (2005) 112:1116–43.
[9] Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, et al. Congestive heart failure in the community. A study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation (1998) 98:2282–9.
[10] Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantification of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr (1989) 2:358–67.[Medline]
[11] Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation (1978) 58:1072–83.
[12] Hinkle LE, Thaler HT. Clinical classification of cardiac deaths. Circulation (1982) 65:457–64.
[13] Gustafsson F, Torp-Pedersen C, Seibaek M, Burchardt H, Kober L, DIAMOND Study Group. Effect of age on short and long-term mortality in patients admitted to hospital with congestive heart failure. Eur Heart J (2004) 25:1711–7.
[14] Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, et al. Most hospitalized older persons do no met the enrollment criteria for clinical trials in heart failure. Am Heart J (2003) 146:250–7.[CrossRef][Web of Science][Medline]
[15] Ehrlich JR, Nattel S, Hohnloser SH. Atrial fibrillation and congestive heart failure: specific considerations at the intersection of two common and important cardiac disease sets. J Cardiovasc Electrophysiol (2002) 13:399–405.[CrossRef][Web of Science][Medline]
[16] Di Lenarda A, Scherillo M, Maggioni AP, Acquarone N, Ambrosio GB, Annicchiarico M, et al. Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds—the TEMISTOCLE study. Am Heart J (2003) 146:E12.[CrossRef][Medline]
[17] Maggioni AP, Sinagra G, Opasich C, Geraci E, Gorini M, Gronda E, et al. Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Heart (2003) 89:299–305.
[18] Gambassi G, Forman DE, Lapane KL, Mor V, Sgadari A, Lipsitz LA, et al. Management of heart failure among very old persons living in long-term care: has the voice of trials spread? The SAGE Study Group. Am Heart J (2000) 139:85–93.[Web of Science][Medline]
[19] Bleeker GB, Schalij MJ, Molhoek SG, Boersma E, Steendijk P, van der Wall EE, et al. Comparison of effectiveness of cardiac resynchronization therapy in patients <70 versus 70 years of age. Am J Cardiol (2005) 96:420–2.[CrossRef][Web of Science][Medline]
[20] Rivero-Ayerza M, Theuns DA, Garcia-Garcia HM, Boersma E, Simoons M, Jordaens LJ. Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials. Eur Heart J (2006) 27:2682–8.
[21] Likoff MJ, Chandler SL, Kay HR. Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol (1997) 59:634–8.
[22] Baldasseroni S, De Biase L, Fresco C, Marchionni N, Marini M, Masotti G, et al. Cumulative effect of complete left bundle-branch block and chronic atrial fibrillation on 1-year mortality and hospitalization in patients with congestive heart failure. A report from the Italian network on congestive heart failure (in-CHF database). Eur Heart J (2002) 23:1692–8.
[23] Molhoek SG, Bax JJ, Bleeker GB, Boersma E, van Erven L, Steendijk P, et al. Comparison of response to cardiac resynchronization therapy in patients with sinus rhythm versus chronic atrial fibrillation. Am J Cardiol (2004) 94:1506–9.[CrossRef][Web of Science][Medline]
[24] Gasparini M, Auricchio A, Regoli F, Fantoni C, Kawabata M, Galimberti P, et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol (2006) 48:734–43.
[25] Molhoek SG, Van Erven L, Bootsma M, Steendijk P, Van Der Wall EE, Schalij MJ. QRS duration and shortening to predict clinical response to cardiac resynchronzation therapy in patients with end-stage heart failure. Pacing Clin Electrophysiol (2004) 27:308–13.[CrossRef][Medline]
[26] Gasparini M, Mantica M, Galimberti, Marconi M, Genovese L, Faletra F, et al. Beneficial effects of biventricular pacing in patients with a narrow QRS. Pacing Clin Electrophysiol (2003) 26:169–74.[CrossRef][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. W.X. Foley, S. Chalil, K. Khadjooi, R. E.A. Smith, M. P. Frenneaux, and F. Leyva Long-term effects of cardiac resynchronization therapy in octogenarians: a comparative study with a younger population Europace, November 1, 2008; 10(11): 1302 - 1307. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||