Europace Advance Access originally published online on June 7, 2006
Europace 2006 8(7):502-505; doi:10.1093/europace/eul054
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CRT
Influence of biventricular pacing on myocardial dispersion of repolarization in dilated cardiomyopathy patients
1 Department of Cardiology, Second University of Naples, Via Leonardo Bianchi 1, 80100 Naples, Italy ; 2 Department of Cardiology, Monaldi Hospital, Via Leonardo Bianchi 1, 80100 Naples, Italy
Manuscript submitted 27 October 2005. Accepted after revision 15 March 2006.
* Corresponding author. Department of Cardiology, Second University of Naples, Via Vittorio Veneto, 396 Torre Annunziata, Naples 80058, Italy. Tel: +39 (0) 3382841171; fax: +39 (0) 817064277. E-mail address: ammendolaernesto{at}libero.it
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Abstract |
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Aims The aim of our study was to evaluate the effect of cardiac resyncronization therapy on QT dispersion (QTd), JT dispersion (JTd), and transmural dispersion of repolarization (TDR), markers of heterogeneity of ventricular repolarization in a study population with severe heart failure.
Methods and results Fifty patients (43 male, 7 female, age 60.2±3.1 years) suffering from congestive heart failure (n=39 NYHA class III; n=11 NYHA class IV) as a result of coronary artery disease (n=19) or of dilated cardiomyopathy (n=31), with sinus rhythm (SR), QRS duration >120 ms (mean QRS duration=156±21 ms), an ejection fraction <35%, left ventricular end-diastolic diameter >55 mm, presence of atrioventricular asynchrony, intra- and inter-ventricular asynchrony, underwent permanent biventricular pacemaker implantation. A 12-lead standard electrocardiogram was performed at baseline, during right-, left-, and biventricular pacing (BiVP) and QTd, JTd, and TDR were assessed. BiVP significantly reduced QTd (73.93±19.4 ms during BiVP vs. 91±6.7 ms in SR, P=0.004), JTd (73.18±17.16 ms during BiVP vs. 100.72±39.04 at baseline, P=0.003), TDR (93.16±15.60 vs. 101.55±19.08 at baseline, P<0.004), compared with SR. Right ventricular endocardial pacing and left ventricular epicardial pacing both increased QTd (RVendoP 94±51 ms, P<0.03; LVepiP 116±71 ms, P<0.02), and TDR (RVendoP 108.13±19.94 ms, P<0.002; LVepiP 114.71±26.1, P<0.05). There was no effect on JTd during right and left ventricular stimulation.
Conclusions BiVP causes a statistically significant reduction of ventricular heterogeneity of repolarization and has an electrophysiological anti-arrhythmic influence on the arrhythmogenic substrate of dilated cardiomyopathy.
Key Words: Biventricular pacing, QT dispersion, JT dispersion, Heart failure, Transmural dispersion of repolarization
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Introduction |
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Congestive heart failure (CHF) remains a major health problem worldwide, despite considerable progress in its management. The incidence and prevalence of this disease continues to increase because of an ageing population, which, in part, is related to the use of new pharmacological and non-pharmacological therapies.1
–6 The patients with advanced heart failure frequently have conduction disturbances that play an important role in worsening cardiac systolic function and in increasing risk of death.7,8 In recent years, a new therapeutic approach, biventricular pacing (BiVP), has been introduced as an adjunctive therapy to pharmacological treatments in patients with severe CHF and intra-ventricular conduction delay. BiVP stimulates or senses the right atrium and then, stimulates both ventricles in order to resynchronize their action. Many studies have demonstrated that BiVP in patients with advanced CHF significantly improves ventricular haemodynamics, quality-of-life, exercise capacity, and reduces mortality and hospitalization rates.9–11 Little is known yet about the influence of cardiac resynchronization therapy (CRT) on the heterogeneity of ventricular repolarization,11,12 which represents the arrhythmogenic substrate of dilated cardiomyopathy and is identified on the electrocardiogram by QT dispersion (QTd), JT dispersion (JTd), and transmural dispersion of repolarization (TDR). The aim of our study was to evaluate the effect of BiVP on electrocardiographic parameters of heterogeneity of ventricular repolarization, both spatial (QTd, JTd) and transmural (TDR). |
Methods |
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Selection of patients
The study population consisted of 50 patients (43 male, 7 female, age 60.2±3.1 years) suffering from CHF (n=39 NYHA class III; n=11 NYHA class IV) as a result of coronary artery disease (n=19) or of dilated cardiomyopathy (n=31). All patients were in sinus rhythm (SR) and demonstrated a QRS duration >120 ms on the standard 12-lead electrocardiogram. All patients included showed an ejection fraction <35%, left ventricular end-diastolic diameter >55 mm, presence of atrioventricular asynchrony, intra- and inter-ventricular asynchrony. All patients were taking heart failure medications (ACE-inhibitors, beta-blockers, diuretics, spironolactone), which remained unchanged during 6 weeks before the permanent biventricular pacemaker implantation. None of the patients was on class I or III anti-arrhythmic drug therapy.
Implantation of pacemaker
All patients underwent their first permanent biventricular pacemaker implantation. All leads were transvenously implanted. The atrial lead was placed high in the right atrium, the right ventricular lead was placed in the right ventricular apical endocardium, and the left ventricular lead was placed in an epicardial posterolateral vein, via coronary sinus access similar to the methods described by others.13 A venogram helped to optimize the position of the lead. The pacemakers were triple-output devices that made use of standard dual-chamber technology, with built-in adapters to synchronize the pacing of the two ventricles. Results of the implantations were assessed from the positions of the leads on chest X-ray films and from changes in the width of the QRS interval on 12-lead surface electrocardiogram.
Study protocol
Each patient had a 12-lead surface electrocardiogram, recorded at a speed of 50 mm/s performed before pacemaker implantation and at the end of the follow-up period, 12 months after the procedure. The ECG recording was performed during SR, right ventricular endocardial pacing (RVendoP), left ventricular epicardial pacing (LVepiP), and BiVP. Each stimulation continued for 3 min. Special attention was paid to eliminate all correctable causes of noise, such as muscle tremor, and to minimize electromagnetic frequency interference generated by electrical sources close to the lead array. The pacing sequences were randomly switched between the patients and no effects on the results were observed. The study was approved by the local Ethics Committee and written informed consent was obtained from all patients prior to enrolment.
Data acquisition and electrocardiogram measurements
Twelve-lead body surface electrocardiograms were recorded at a speed of 50 mm/s. The analysis was performed by one investigator only. QRS duration, QT interval, JT interval, and Tpeak-end interval measurement was performed with the use of computer software (Configurable Measurement System) using digitizer 34180 (Calcomp, Anaheim, CA, USA). The variability of the measurements was 0.36±5 ms, not statistically significant. The standard correlation was 95% (95% CI –6.73 to 6.01). In each electrocardiogram lead, the analysis included three consecutive heart cycles, whenever possible. Leads were excluded from analysis when the end of the T-wave was not clearly distinguishable or the signal quality was too poor for analysis. The QRS interval was measured from the start of the Q wave or, in the absence of the Q wave, from the start of R wave to the end of S, that is to its return to the isoelectric line. The QT interval was measured from the initial deflection of the QRS complex to the end of the T wave, that is to the point where the T wave returned to the isoelectric line. In case there was a U wave, the QT interval was measured to the lowest part of the curve between the T and U waves. The JT interval was derived by subtracting the QRS duration from the QT interval. The Tpeak-end interval was defined as the interval from the maximum T-wave amplitude to the end of the T-wave.14 QTd was the difference between the maximal and the minimal QT value in all leads.15 The difference between the maximal and the minimal JT value in all leads was defined as JTd. TDR was defined as the interval between the peak to the end of the T wave,16,17 for our analysis we have considered the mean value. Measurements were corrected for heart rate using Bazett's formula.
Statistical analysis
Statistical analysis was performed using Student's t-test for paired data and one-way analysis of variance (ANOVA) coupled with Fisher's LSD test among three or more groups. Data are presented as mean±SD. Differences were considered to be significant at a P-value <0.05. Analyses were performed using the statistical package SPSS 9.0 software for Windows.
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Results |
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Patients demonstrated a significant baseline ventricular activation delay with an average QRS duration at 156±21 ms, attributable to left bundle-branch block, intra-ventricular conduction delay or right bundle-branch block. BiVP resulted in a statistically significant reduction in QRS duration (132±16 ms during BiVP vs. 156±21 ms at baseline, n=50, P=0.02). RVendoP and LVepiP, on the other hand, led to a marked prolongation in ventricular activation time (Figure 1).
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The effects of pacing site on QTd values are shown in Figure 2. BiVP significantly reduced QTd, compared with SR (73.93±19.4 ms during BiVP vs. 91±36.7 in SR, n=50, P=0.004). RVendoP and LVepiP both caused a significant increase in QTd value (RVendoP 94±51 ms, P<0.03; LVepiP 116±71 ms, P<0.02).
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There was no statistically significant effect on JTd during RVendoP and LVepiP compared with SR, whereas BiVP significantly decreased the JTd (73.18±17.16 ms during BiVP vs. 100.72±39.04 at baseline n=50, P=0.003; Figure 3).
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The transmural dispersion of repolarization (TDR) was significantly increased during RVendoP (108.13± 19.94 ms; P<0.002) and LVepiP (114.71± 26.1 ms; P<0.05), whereas BiVP significantly decreased the TDR (93.16±15.60 ms; P<0.004), compared with SR (101.55±19.08 ms; Figure 4).
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Discussion |
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In our study, we evaluated the pacing site-dependent change in markers of ventricular repolarization heterogeneity in a population of 50 patients with CHF. The ventricular repolarization heterogeneity is an expression of regional (QTd, JTd) and TDR differences in cellular action potential duration and in ventricular recovery time. In heart failure patients, the preferential prolongation of the M cell action potential results in the development of TDR, which can be estimated from the electrocardiogram as the interval between the peak and the end of the T wave.18
Previous studies
Previous electrophysiological studies,19–21 have highlighted the role of ventricular repolarization heterogeneity on the genesis of ventricular malignant arrhythmias in heart failure patients. In the failing myocardium, increase in QTd, JTd, and TDR values increases the risk of development of malignant ventricular arrhythmias, probably via two mechanisms. First, it facilitates transmural early after-depolarization propagation; second, it could cause intramural functional conduction blocks that predispose to re-entrant polymorphic ventricular tachyarrhythmia.22 Several studies have suggested that TDR and JTd are clinically useful in assessing arrhythmia risk,23,24 because they are parameters less-dependent on ventricular depolarization and reflect the ventricular repolarization heterogeneities better than QTd in patients with intra-ventricular conduction abnormalities.25,26 Medina-Ravell et al.12 in a recent experimental study suggested a potentially harmful influence of CRT on ventricular repolarization. The authors found that BiVP or LVepiP prolong QT interval, increase TDR, and may be a potential risk for the development of torsade de pointes in a subset of patients. A subsequent electrophysiological study by Fish et al.27 confirmed this hypothesis. Nevertheless, Abraham et al.11 and Bristow et al.28 in two distinct prospective, randomized studies did not find any excess mortality due to sudden death in a population with chronic heart failure and BiVP. However, in the study of Medina-Ravell et al.12 QTd, JTd and Tpeak-end was not estimated at baseline and during BiVP. From our point of view these data are very important.
Main findings
In our study, differences in various parameters of ventricular repolarization heterogeneity (QTd, JTd, TDR) during RVendoP, LVepiP, and BiVP in heart failure patients have been obtained using a standard 12-lead ECG. Our data, in contrast to the findings of Medina-Ravell et al.,12 showed that BiVP reduced the QTd, JTd, and TDR and, with them, the relative risk of malignant ventricular arrhythmias. Nevertheless, in accordance with Medina-Ravell et al.12 and those of Fish et al.,27 epicardial pacing of left ventricle has been shown to increase ventricular heterogeneity of repolarization, probably because of reversal of the physiological ventricular activation. Normally, ventricular activation starts with endocardium via subendocardial Purkinje network and spreads through the ventricular wall, although the epicardium is activated last, it repolarizes first, producing a repolarization sequence, which is opposite to that of activation.14 Furthermore, our data showed that lone RVendoP increased QTd and TDR less than left epicardial ventricular stimulation.
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Limitations |
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QT interval and Tpeak-end measurements were made on 12-lead ECGs, with the use of computer software and digitizer by an experienced observer. However, there remains an absence of indisputable, generally accepted criteria for the definition of the end of T interval implying some degree of possible error in the measurements. The 12-lead surface ECG, compared with body surface mapping or vector cardiography, gives an incomplete picture of cardiac electric activity, so QTd could not be a true manifestation of local heterogeneity of repolarization.
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Conclusions |
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BiVP causes a statistically significant reduction of all parameters proposed to estimate the heterogeneity of ventricular repolarization (QTd, JTd, TDR), compared with SR, whereas both RVendoP and LVepiP cause an increment in heterogeneity of ventricular repolarization. In conclusion, our data show that CRT could have an electrophysiological anti-arrhythmic influence on the arrhythmogenic substrate of dilated cardiomyopathy, reducing the risk of development of malignant ventricular arrhythmias.
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Acknowledgements |
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We gratefully acknowledge the expert technical assistance of engineer Dr C. Ciardiello (Guidant Corporation).
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References |
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