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. 2010 Jan 20;15(1):36–42. doi: 10.1111/j.1542-474X.2009.00337.x

Optimization of Repolarization during Biventricular Pacing: A New Target in Patients with Biventricular Devices?

Cengizhan Türkoğlu 1, Farid Aliyev 1, Cengiz Çeliker 1, Gökhan Çetin 1, Gökhan Alici 1, Işil Uzunhasan 1, Inci Firatli 1
PMCID: PMC6932386  PMID: 20146780

Abstract

Background: Evaluation of repolarization during sequentional biventricular pacing.

Methods: Patients with biventricular devices, and left ventricular leads placed to the basal part of lateral left ventricular wall were enrolled. QRS, QTc, JTc, and corrected Tpeak‐Tend intervals were compared during sequentional biventricular, left ventricular, and right ventricular pacing.

Results: Five patients with nonischemic and five with ischemic cardiomyopathy due to anterior myocardial infarction were enrolled. No correlation was observed between values of repolarization among patients. The optimal values of repolarization were significantly different from values of echocardiographically guided hemodynamic optimization. Two patients with biventricular pacing‐induced ventricular fibrillation were successfully treated by reprogramming of V‐V delay according to interventricular delay resulting in shorter Tpeak‐Tend interval, although delayed effect of amiodarone in one of these patients cannot be ruled out.

Conclusions: Patients with biventricular devices may be prone to development of ventricular arrhythmias depending on programmed V‐V interval. We suggest that optimization of repolarization may be performed in patients with biventricular pacemakers in the absence of backup ICD and those with frequent episodes of ventricular tachyarrhythmias, although this finding deserves further study.

Ann Noninvasive Electrocardiol 2010;15(1):36–42

Keywords: biventricular pacing, cardiac resynchronization therapy, optimization, repolarization, ventricular tachyarrhythmias

Cardiac resynchronization therapy (CRT) has been established as adjunctive therapeutic tool for patients with drug refractory heart failure. Symptomatic improvement and decrease in frequency of hospitalizations has been reported in patients with biventricular pacemakers. But it is still not well established, whether CRT reduces or increases susceptibility to potentially life‐threatening arrhythmias. Both decrease and increase in frequency of ventricular arrhythmias were reported following initiation of biventricular pacing. 1 , 2 , 3 , 4 , 5 In this study, we measured different repolarization indices during sequentional biventricular, right ventricular endocardial, left ventricular epicardial pacing, and sinus rhythm in patients with implanted biventricular pacemakers and ICDs.

METHODS

Both patients with ischemic and nonischemic cardiomyopathy were screened. To rule out possible effects of left ventricular pacing sites, only patients with epicardial leads implanted at the basal segments of lateral left ventricular wall were enrolled into the study. Location of the tip of LV lead was evaluated with conventional flouroscopic examination. Localization of previous myocardial infarction could affect indices of repolarization. For this reason, only patients with previous anterior myocardial infarction were enrolled into the study.

Hemodynamic echo‐guided optimization was performed according to best aortic tissue velocity integral (TVI) value, and optimal programmed V‐V delays were noted for each patient.

Twelve‐lead electrocardiograms were recorded in the cardiac electrophysiology (EP) laboratory setting with PC‐controlled EP system (EP‐Tracer/70, Cardioteck, Maastricht, the Netherlands).

QRS duration, QT, QTc, JT, JTc, Tpeak‐Tend, and corrected Tpeak‐Tend intervals were measured and calculated during sinus rhythm, right ventricular endocardial, left ventricular epicardial, simultaneous, and sequentional biventricular pacing. Each pacing was maintained at a constant rate, above sinus rhythm for 5 minutes. QRS, QT, JT, and Tpeak‐Tend intervals were measured during the last 10 seconds of each 5‐minute pacing.

RESULTS

Ten eligible patients were enrolled. Five of them had nonischemic (patients 1–5) and another five had ischemic cardiomyopathy (patients 6–10). All of the study patients were CRT‐responders. Left ventricular ejection fraction was not different between patients with ischemic and nonischemic cardiomyopathy (15 ± 5.6 vs 17 ± 8.3). Indexes of repolarization were measured for each study patient and these are presented in 1, 2, 3, 4. There was no correlation among patients in respect to QRS width, shortest QTc, JTc, and corrected Tpeak‐Tend intervals. Values varied significantly in the same patients at different programmed values of V‐V delays. The shortest and longest values obtained for each patient are presented for comparison in Table 5. Comparison of programmed V‐V delays in respect to optimal aortic TVI, narrowest QRS, shortest QTc, JTc, and corrected Tpeak‐Tend intervals are presented in Table 6.

Table 1.

QRS Duration Measured during Sinus Rhythm, Right Ventricular Endocardial, Left Ventricular Epicardial, and Different Modes of Sequentional Biventricular Pacing

Pt. No. QRS (msec)
SR RV endo LV epi LV80RV LV60RV LV40RV LV20RV LV0RV RV20LV RV40LV RV60LV RV80LV
 1 186 192 207 198 216 b 195 171 165 a 177 177 186 192
 2  99 159 186 b 183 165 147 147 129 a 135 150 153 168
 3 123 207 174 180 162 174 165 156 153 a 177 183 186 b
 4 153 213 189 180 180 171 153 147 a 156 165 183 195
 5 147 228 228 234 b 228 207 189 177 171 a 180 195 216
 6 183 198 159 147 156 153 153 141 a 141 a 162 186 b 180
 7 228 294 312 b 237 210 207 204 a 204 a 207 227 228 240
 8 198 288 216 a 252 282 246 246 240 246 246 258 282 b
 9 147 150 150 162 156 156 144 a 168 162 144 a 162 186 b
10 NA 216 210 b 210 192 180 161 156 126 a 126 a 162 192
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Shortest and longest QRS for each of the patients are presented as bold numerical values (ashortest and blongest). Values obtained during sinus rhythm and right ventricular pacing are presented only for comparison.

NA = not applicable.

Table 2.

QTc Intervals Measured during Sinus Rhythm, Right Ventricular Endocardial, Left Ventricular Epicardial, and Different Modes of Sequentional Biventricular Pacing

Pt. No. QTc Interval (msec)
SR RV endo LV epi LV80RV LV60RV LV40RV LV20RV LV0RV RV20LV RV40LV RV60LV RV80LV
 1 530 520 570 b 540 535 520 480 a 490 485 489 489 530
 2 420 490 530 b 495 460 460 490 450 a 460 470 495 530 b
 3 430 500 510 b 500 465 470 430 a 440 440 470 470 485
 4 475 500 475 465 450 460 450 a 460 470 475 480 495 b
 5 530 550 655 b 595 535 510 500 490 a 520 520 520 570
 6 520 535 530 b 450 515 525 480 445 a 490 490 515 520
 7 515 620 875 b 660 620 560 515 480 a 570 610 665 650
 8 650 625 580 580 625 625 b 590 580 560 a 580 600 610
 9 517 514 535 550 564 571 550 492 a 578 b 542 578 b 571
10 NA 564 585 b 564 557 535 478 485 457 a 457 a 492 535
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Shortest and longest QTc interval for each of the patients is presented as bold numerical value (ashortest and blongest). Values obtained during sinus rhythm and right ventricular pacing are presented only for comparison.

NA = not applicable.

Table 3.

JTc Intervals Measured during Sinus Rhythm, Right Ventricular Endocardial, Left Ventricular Epicardial, and Different Modes of Sequentional Biventricular Pacing

Pt. No. JTc interval (msec)
SR RV endo LV epi LV80RV LV60RV LV40RV LV20RV LV0RV RV20LV RV40LV RV60LV RV80LV
 1 310 300 320 b 320 280 a 280 a 280 a 310 280 305 295 300
 2 290 280 275 265 a 270 285 290 285 275 275 280 320 b
 3 300 295 335 b 320 305 300 260 a 285 285 300 295 300
 4 280 270 260 245 240 a 265 285 285 300 b 295 280 290
 5 380 320 425 b 360 300 a 300 a 305 305 335 330 330 330
 6 310 315 325 315 335 340 b 315 300 315 250 a 305 315
 7 280 330 552 b 435 400 345 320 300 a 370 390 420 395
 8 435 320 340 b 300 a 320 340 b 310 310 300 a 305 310 310
 9 332 321 342 a 357 364 378 385 350 400 b 378 385 350
10 NA 326 278 a 307 321 b 321 285 314 285 314 300 321 b
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Shortest and longest JTc interval for each of the patients is presented as bold numerical value (ashortest and blongest). Values obtained during sinus rhythm and right ventricular pacing are presented only for comparison.

NA = not applicable.

Table 4.

Corrected Tpeak‐Tend Intervals Measured during Sinus Rhythm, Right Ventricular Endocardial, Left Ventricular Epicardial, and Different Modes of Sequentional Biventricular Pacing

Pt. No. Corrected Tpeak‐Tend Interval (msec)
SR RV endo LV epi LV80RV LV60RV LV40RV LV20RV LV0RV RV20LV RV40LV RV60LV RV80LV
 1 162 137 181 b 151 144 129 107 a 137 114 129 125 133
 2  90 167 144 110 116 125 120 101 a 112 120 148 175 b
 3 108 153 114  99  84 a  84 a  99 120 114 129 132 147 b
 4 198 212 188 171 158 a 171 171 178 185 182 209 b 205
 5 186 159 192 b 159 123 a 123 a 129 132 141 135 132 153
 6 185 169 140 120 133 146 b 114  94 a 130 124 130 140
 7 144 150 354 b 168 160 144 120 a 120 a 150 174 198 192
 8 143 300 208 a 260 267 280 254 254 254 287 300 306 b
 9 164 171 114 a 128 164 157 121 142 200 b 178 192 164
10 NA 178 164 171 b 164 128 121 121 107 a 135 121 164
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Shortest and longest Tpeak‐Tend interval for each of the patients is presented as bold numerical value (ashortest and blongest). Values obtained during sinus rhythm and right ventricular pacing are presented only for comparison.

NA = not applicable.

Table 5.

Shortest and Longest Values of Repolarization Measured at Different Programmed V‐V Delays are Presented for Comparison

Pt. No. Shortest QTc (msec/V‐V delay) Longest QTc (msec/V‐V delay) Shortest JTc (msec/V‐V delay) Longest JTc (msec/V‐V delay) Shortest Tp‐Te (msec/V‐V delay) Longest Tp‐Te (msec/V‐V delay)
 1 480/LV20RV 570/LVepi 280/LV20RV and LV40RV and LV60RV 320/LVepi 107/LV20RV 181/LVepi
 2 450/LV0RV 530/LVepi and RV80LV 265/LV80RV 320/RV80LV 101/LV0RV 175/RV80LV
 3 430/LV20RV 510/LVepi 260/LV20RV 335/LVepi 84/LV40RV and LV60RV 147/RV80LV
 4 450/LV20RV 495/RV80LV 240/LV60RV 300/RV20LV 158/LV60RV 209/RV60LV
 5 490/LV0RV 655/LVepi 300/LV40RV and LV60RV 425/LVepi 123/LV40RV and LV60RV 192/LVepi
 6 445/LV0RV 530/LVepi 250/RV40LV 340/LV40RV 94/LV0RV 146/LV40RV
 7 480/LV0RV 875/LVepi 300/LV0RV 552/LVepi 120/LV0RV and LV20RV 208/LVepi
 8 560/RV20LV 625/LV40RV 300/LV80RV and RV20LV 340/LVepi and LV40RV 208/LVepi 306/RV80LV
 9 492/LV0RV 578/RV20LV and RV60LV 342/LVepi 400/RV20LV 114/LV epi 200/RV20LV
10 457/RV20LV and RV40LV 585/LVepi 278/LVepi 321/LV60RV 107/RV20LV 171/LV80RV
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Table 6.

Optimal Values of Echo‐Guided V‐V Delay are Compared to Interventricular Delays, which Result in Narrowest QRS, and Shortest QTc, JTc, and Tpeak‐Tend Intervals

Patient No. Optimal Echo‐Guided V‐V Delay Optimal V‐V Delay for QRS Width Optimal QTc Interval Optimal JTc Interval Optimal Corrected Tpeak‐Tend
 1 LV0RV LV0RV LV20RV LV20RV LV20RV LV40RV LV60RV RV20LV
 2 LV0RV LV0RV LV40RV LV60RV LV80RV LV60RV LV0RV
 3 LV0RV RV20LV LV20RV LV20RV LV40RV LV60RV
 4 LV0RV LV20RV LV20RV LV60RV LV60RV
 5 LV0RV RV20LV LV0RV LV40RV LV60RV LV40RV LV60RV
 6 LV0RV LV0RV RV20LV LV0RV RV40LV LV0RV
 7 LV60RV LV0RV LV0RV LV0RV LV0RV LV20RV
 8 LVP only LVP only LVP only LV0RV LV80RV LV80RV RV20LV LVP only
 9 LV0RV LV20RV RV40LV LV0RV LVP only LVP only
10 LV0RV RV20LV RV40LV RV20LV RV40LV LVP only RV20LV
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Two of the patients (patients 1 and 7), had frequent episodes of ventricular fibrillation following implantation of biventricular ICD. None of them had any episode of ventricular tachycardia or fibrillation prior to initiation of biventricular pacing. Note that for patient 7, best aortic TVI value was achieved during programmed left ventricular activation, which preceded right ventricular activation by 60 msecs (LV60RV), while his narrowest QRS duration, and shortest QTc, JTc, and corrected Tpeak‐Tend intervals were measured during simultaneous biventricular pacing (LV0RV) or when right ventricular activation preceded left ventricular activation by 20 msecs (RV20LV). The same discrepancy was observed in patient 1. Patient 7 continued to develop frequent episodes of arrhythmia, despite intravenous loading dose of amiodarone. Abolishment of episodes of ventricular fibrillation was achieved by programming V‐V delay according to optimal (shortest) Tpeak‐Tend interval, although we cannot rule out possible delayed effect of amiodarone.

DISCUSSION

Some data suggest that CRT may reduce the risk of arrhythmias. However, proarrhythmia from CRT has also been reported. First, CRT has been associated with an increase in or new onset of monomorphic VT possibly related to site of stimulation with respect to site of infarction. 1 , 2 , 3 , 4 , 5 , 6 Second, CRT has appeared causative for polymorphic VT/VF as well, perhaps related to altered repolarization, including transmural dispersion of repolarization. 1 , 7 However, some studies have shown no difference in dispersion of repolarization and microvolt T‐wave alternans 8 , 9 and even decrease in ECG markers of ventricular dispersion of repolarization was reported 10 in CRT recipients. Also several studies reported decrease in the frequency of VT/VF after initiation of biventricular pacing. 11 Theoretically, decrease in the frequency of ventricular arrhythmia in patients with CRT may be related to decrease in sympathetic tone secondary to improve in cardiac output, reduced wall stress, and electromechanical dyssynchrony, but findings of our study suggest that, repolarization‐guided optimization of V‐V delay may also decrease frequency of ventricular arrhythmias in patients with heart failure. 12 , 13 , 14 , 15

Biventricular pacing was reported to have minimal effects on parameters of ventricular repolarization, when compared to left ventricular epicardial pacing. 16 But we have observed that individual patient may have shortest Tpeak‐Tend interval during left ventricular pacing.

Previously, effect of biventricular and left ventricular pacing on QT interval was investigated as an index of ventricular repolarization. But in our opinion QT and QTc interval should not be considered as a marker of repolarization in patients with implantable pacemakers. This point of view was supported by observation of other investigators and is related to fact that pacing‐induced prolongation of ventricular depolarization frequently results in prolongation of QT interval, making it inaccurate parameter of ventricular repolarization. 1 , 7 , 17 , 18 Absence of correlation between pacing‐induced prolongation of QT interval and torsades de pointes, in addition, supports the above‐mentioned effect. 19 We suggest, that measurement of corrected JT and preferably Tpeak‐Tend interval may be more appropriate in this setting.

Previous studies, which aimed investigation of repolarization abnormalities in patients with biventricular pacemakers, performed comparison of various indices of repolarization obtained during sinus rhythm, right ventricular endocardial, left ventricular epicardial, and simultaneous biventricular pacing modes. But there was lack of data obtained during sequentional biventricular pacing.

In this study, we proposed that different programmed V‐V intervals in the same patient may result in deterioration or improvement of repolarization abnormalities. For this reason, we enrolled patients with both ischemic and nonischemic cardiomyopathy, with left ventricular leads implanted to the basal part of lateral left ventricular wall (nine of them were implanted percutaneously via branches of coronary sinus and one was implanted with minithoracotomy in patient 10). Patients with ischemic cardiomyopathy, all had previous anterior myocardial infarction. This strict selection method was performed to avoid potential effect of pacing site and localization of infarction on indices of ventricular repolarization. At the end of study, we have observed no correlation between optimal echo‐guided V‐V delays, optimal QTc, JTc, and Tpeak‐Tend intervals. This surprising finding suggests that individual patient may require optimization of repolarization indices to avoid occurrence of PMVT or VF, as it was observed in patients 1 and 7. However, possible delayed effect of amiodarone could contribute to the abolishment of VF episodes in patient 7.

Echocardiographic optimization of both A‐V and V‐V delays in patients with biventricular pacemakers was frequently performed to achieve best hemodynamic response and clinical improvement. Results of our study suggest that, not only echocardiographic optimization, but also optimization of repolarization may be performed in selected group of patients. Taking into account the fact that optimization of repolarization is a time‐consuming method, it may be difficult to apply this technique to all patients following implantation of biventricular devices. Another important aspect is presence of discrepancy between echo‐guided and repolarization‐guided optimal V‐V delays. Thus, routine optimization of repolarization will result in increased number of nonresponders. In our opinion, patients with biventricular pacemakers (not ICDs) and those with frequent episodes of ventricular tachyarrhythmias should undergo optimization of repolarization indices and simultaneous echocardiographic assessment. In patients with frequent ventricular tachyarrhythmias, V‐V values should be programmed according to optimal Tpeak‐Tend interval. Otherwise in patients without back‐up ICD therapy, V‐V delays should be programmed to values, which result in shortest Tpeak‐Tend intervals and TVI values, which are better than those obtained during sinus rhythm. However, all of these above‐presented suggestions deserve further investigation. Additionally, we would like to remind that optimal A‐V and V‐V delays are not stable and tend to change over time. So, results of this study do not provide us with information about stability of repolarization values over long periods of time.

STUDY LIMITATION

The main limitation of this study is small number of patients. However, we tried to exclude possible effect of lead position and infarct location on values of ventricular repolarization. Another important limitation is absence of proof that just reprogramming of V‐V delay alone will always result in termination of CRT‐related ventricular arrhythmias.

Financial support: None.

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