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Electrogram-Based Optimal Atrioventricular and Interventricular Delays of Cardiac Resynchronization Change Individually During Exercise
Canadian Journal of Cardiology 27 (2011) 351–357
Clinical Research
Electrogram-Based Optimal Atrioventricular and Interventricular Delays of Cardiac Resynchronization Change Individually During Exercise Gregory Golovchiner, MD,a Paul Dorian, MD, MSc,a Iqwal Mangat, MD,a Victoria Korley, MD,a Kamran Ahmad, MD,a Khairi Sharef, MD,a Emoke Posan, MD, PhD,a Eugene Crystal, MD,b Suzan O’Donnell, MSc,a and Arnold Pinter, MDa a
St. Michael’s Hospital, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada
b
Sunnybrook Hospital, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada
ABSTRACT
RÉSUMÉ
Background: Limited data suggest that optimal atrioventricular (AV) and interventricular (VV) delays are different at rest than during exercise in patients with heart failure. We assessed the feasibility and reproducibility of an electrogram-based method of optimization called QuickOpt at rest and during exercise. Methods: Patients with a St Jude Medical cardiac resynchronization therapy implantable cardioverter-defibrillator were subjected to a graded treadmill test, and QuickOpt was repeatedly measured prior to, during, and after the exercise. Results: Twenty-four patients (16 males, aged 67.4 ⫾ 7.7 years) participated. At rest, delays (in ms) were 110.4 ⫾ 20.1 for sensed AV delay and –70 (LV pacing first) to ⫹20 (RV pacing first) for VV delay. The changes in QuickOpt-derived delays at rest were not significant despite change in body position. During exercise, QuickOpt-derived AV delays did not change in 11 patients, were shorter during peak exercise in 8 patients, and were longer in 3 patients (average value during peak exercise was 126.5 ⫾ 15.8 ms, P ⫽ 0.04 compared to baseline). The QuickOpt-derived VV delay gradually shifted toward earlier right ventricular pacing during exercise in 19 patients, while no changes
Introduction : Des données limitées suggèrent que les délais atrioventriculaires (AV) et interventriculaires (IV) optimaux sont différents au repos par rapport aux délais obtenus durant l’exercice chez les patients ayant une insuffisance cardiaque. Nous avons évalué la faisabilité et la reproductibilité d’une méthode d’optimisation à l’aide de l’électrogramme appelée QuickOpt au repos et durant l’exercice. Méthodes : Les patients portant un défibrillateur cardioverteur implantable St Jude Medical pour une thérapie de resynchronisation cardiaque ont été soumis à une épreuve d’effort gradué sur tapis roulant, et le QuickOpt a été mesuré de manière répétitive avant, pendant et après l’exercice. Résultats : Vingt-quatre patients (16 hommes âgés de 67,4 ⫾ 7,7 ans) ont participé. Au repos, les délais (en ms) ont été de 110,4 ⫾ 20,1 pour le délai AV défini et –70 (VG stimulé en premier) à ⫹20 (VD stimulé en premier) pour le délai IV. Les changements dans les délais avec le QuickOpt au repos n’ont pas été significatifs, en dépit du changement de position du corps. Durant l’exercice, les délais AV avec le QuickOpt n’ont pas changé chez 11 patients, ont été plus courts durant le pic de l’exercice chez 8 patients et ont été plus longs chez 3 patients (la valeur moyenne durant le pic de l’exercice a été de
Cardiac resynchronization therapy (CRT) has been shown to improve heart failure symptoms, exercise capacity and mortality in patients with New York Heart Association (NYHA) Class III-IV heart failure symptoms, an ejection fraction ⱕ 35%, and QRS duration ⬎120 ms.1,2 However, up to 30% of patients receiving CRT do not respond to this therapy.3-6 Optimization of atrioventricular (AV) delay7-13 and interventricular (VV) delay14-16 has been shown to improve acute hemodynamic re-
sponse and translate into limited short-term clinical benefit in some studies.17-21 There is no consensus on how to measure optimization. Resting echocardiography is the most commonly used modality for CRT optimization, but it is time consuming and there is no “gold standard” method.13,22 Since most patients receiving CRT have NYHA Class III heart failure symptoms, improvement in exercise capacity is one of the major goals. On the other hand, these patients spend most of their time resting and reverse remodelling would presumably occur with optimal resting delays. Limited and controversial data exist regarding changes in optimal AV and VV delays during exercise.7,13,23-25 If such changes exist, patients may possibly benefit from automatically adjusted AV and VV delays depending on their level of activity.
Received for publication November 5, 2010. Accepted December 16, 2010. Corresponding author: Dr Arnold Pinter, St Michael’s Hospital, 30 Bond St, Toronto, Ontario M5B 1W8, Canada. Tel.: ⫹1-416-864-5104; fax: ⫹1416-864-5104. E-mail: [email protected] See page 356 for disclosure information.
0828-282X/$ – see front matter © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.cjca.2010.12.047
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were seen in 3 patients, and a shift occurred toward earlier left ventricular pacing in 2 patients (average value during peak exercise was –30.7 ⫾ 22.2; P ⫽ 0.001 compared to baseline). There was no correlation between changes in the QuickOpt-derived AV and VV delays and heart rate. Conclusions: The application of electrogram-based algorithm is feasible both at rest and during exercise. The results are reproducible. QuickOpt-derived AV and VV delays individually change during exercise.
126,5 ⫾ 15,8 ms, P ⫽ 0,04 comparativement à la ligne de base). Le délai IV avec le QuickOpt a changé graduellement vers le début de la stimulation du ventricule droit durant l’exercice chez 19 patients, tandis qu’aucun changement n’a été observé chez 3 patients, et un changement est apparu vers le début de la stimulation du ventricule gauche chez 2 patients (la valeur moyenne durant le pic de l’exercice a été –30,7 ⫾ 22,2; P ⫽ 0,001 comparativement à la ligne de base). Il n’y a eu aucune corrélation entre les changements dans les délais AV et IV avec le QuickOpt, et la fréquence cardiaque. Conclusions : L’application d’un algorithme à l’aide de l’électrogramme est réalisable tant au repos que durant l’exercice. Les résultats sont reproductibles. Les délais IV et AV du QuickOpt changent individuellement durant l’exercice.
One form of electrogram-based method of optimization called QuickOpt is used in St Jude Medical CRT devices and allows a simple and quick optimization of the AV and VV delays, providing an opportunity to test it during exercise. A yet unpublished study presented at the 31st Annual Scientific Sessions of the Heart Rhythm Society showed no difference in the response rate to CRT between patients randomly assigned to resting QuickOpt optimization versus patients assigned to echocardiographic optimization.26,27 This finding, however, does not preclude a potential benefit in exercise tolerance and/or exercise-related symptoms from optimized CRT during exertion if the optimal exercise AV and VV delay is different from the resting values. To date, no data are available about the reproducibility of the QuickOpt method and the optimal AV and VV delays during different levels of graded exercise. The aims of the present prospective study were to assess whether (1) it is feasible to carry out QuickOpt measurements during graded exercise; (2) QuickOpt measurements are reproducible, and (3) the QuickOpt AV and VV delays are different during exercise and at rest.
after the completion of atrial electrical activation and contraction. Since the paced AV delay was calculated by adding 50 ms to the sensed AV delay, we will only describe the sensed AV delay measurements. The algorithm optimizes the VV delay by calculating optimal VV ⫽ 0.5 ⫻ (⌬ ⫹ ), where the conduction delay ⌬ is the difference between the time of peak intrinsic activation at the LV versus the RV lead and the correction term is the difference in VV conduction delay between pacing from the right ventricle and from the left ventricle. A VV delay ⬍ 0 indicates LV pacing first. During the test, each chamber is paced with a short AV delay to prevent fusion of the activation fronts. The optimization of the AV and VV delays is independent from the lead positions.34,35 Patients were subjected to a graded treadmill stress test using the modified Naughton protocol.36 Criteria for study termination were symptoms of fatigue, dyspnea, dizziness, chest pain, or reaching maximal predicted heart rate. During the evaluation, including the stress test, the programmed AV and VV delays were unchanged from baseline. Blood pressure, heart rate, and QuickOpt were measured prior to exercise in standing position, during the 3rd minute of every stage, immediately after stopping exercise and then every 3 minutes during recovery until the heart rate returned to baseline. Repeated QuickOpt measurements were performed 3 times with 1-minute interval between measurements in sitting position prior to exercise and 3 times in standing position on the treadmill prior to exercise to assess the reproducibility of the measurements.
Methods Consecutive patients with St Jude Medical CRT devices (all with a CRT implantable defibrillator) were included in the study that was conducted between May 2007 and December 2009. The indication for CRT device implantation was NYHA functional class III- IV heart failure symptoms despite optimal medical therapy, left ventricular end-diastolic dimension ⬎ 60 mm, left ventricular ejection fraction (LVEF) of ⱕ 35%, and QRS duration of ⱖ 120 ms.28 Patients were included in the study at least 1 month after the device implantation. Patients with NYHA functional class IV heart failure at the time of recruitment; not in sinus rhythm or with conditions that precluded QuickOpt measurements such as complete AV block were excluded. The study was approved by the St Michael’s Hospital Research Ethics Board. The optimal AV and VV delays were measured using the electrogram-based method called QuickOpt, which is available in St Jude Medical CRT devices such as Atlas ⫹HF V-34, Atlas II ⫹HF V-367, and Promote RF 3213-36. The method details have been described previously.29-35 In brief, for optimization of the sensed AV delay, the algorithm measured the width of the atrial intrinsic depolarization and added an offset factor of 30 ms if the intrinsic depolarization was ⱖ 100 ms or 60 ms if it was ⬍ 100 ms, such that ventricular pacing was delivered
Statistical analysis The results are presented as mean ⫾ SD or median, as appropriate. Repeated sitting and standing measurements were analyzed for variance in each patient. The difference between sitting and standing position, as well as between exercise measurements during every stage and standing position, was analyzed using Wilcoxon signed rank test. Correlation of changes in AV or VV delays and the heart rate was calculated using the nonparametric Spearman rho. Results Twenty-four patients participated in the study. The patients’ characteristics are presented in Table 1. The QuickOptderived AV and VV delay measurements were feasible in every patient during exercise, and it took approximately 50-80 seconds (faster with higher heart rates during exercise).
Golovchiner et al. Optimal Atrioventricular and Interventricular Delays Table 1. Patient characteristics (N ⫽ 24) Age, y Range Average ⫾ SD Gender, male Cardiac disease Coronary artery disease Nonischemic cardiomyopathy Indications for ICD Primary Secondary NYHA class at implant II III IV Medications ACEI/ARB -Blockers Amiodarone ECG LBBB Nonspecific intraventricular conduction delay QRS duration Range, ms Average ⫾ SD, ms Programmed delays* Sensed AV delay, ms, range Sensed AV delay, ms, average ⫾ SD VV delay, ms, range
54-78 67.4 ⫾ 7.7 16 (66.7%) 13 (54%) 11 (46%) 21(88%) 3 (12%) At implant At recruitment 0 21 22 3 2 0 24 (100%) 24 (100%) 5 (21%) 22 (92%) 2 (8%) 122-246 161.7 ⫾ 20.0 90-150 110.4 ⫾ 20.1 –70 to ⫹10
AV, atrioventricular; NYHA, New York Heart Association; LBBB, left bundle branch block; SD, standard deviation; VV, interventricular. * Programmed delays at admission for the stress-test.
Baseline measurements Baseline resting QuickOpt-derived AV delays and VV delay measurements showed consistent results with minimal differences in individual patients. The QuickOpt measurement of AV delays was impossible in 2 patients with sinus bradycardia and no sensed atrial events. For those patients, only VV delays were analyzed and presented in Results. Sitting position. The range of the QuickOpt-derived optimal resting sensed AV delays in the whole patient group was 100150 ms, with a mean of 125.0 ⫾ 15.9 ms. The QuickOptderived optimal AV delay during the 3 repeat measurements showed no difference in 16 patients, and a maximum of 10-ms difference in the other 6 patients (median difference 0 ms, range 0-10 ms). The QuickOpt-derived optimal VV delay ranged from – 65 ms (LV pacing first) to ⫹20 ms (RV pacing first), with a mean of –31.7 ⫾ 24.0 ms. No variation was observed in 12 patients during the repeated measurements, and only 1 patient had a variation of ⬎ 5 ms (median difference 0 ms, range 0-10 ms). Standing position. The average heart rate was 70.0 ⫾ 9.0 beats/ min, and blood pressure was 115.7 ⫾15.5/64.5 ⫾ 8.0 mm Hg in the standing position. The range of the QuickOpt-derived optimal resting sensed AV delays was 110-150 ms, with a mean of 126.3 ⫾ 16.1 ms. Repeated measurements showed no variation in 14 patients and up to 10-ms difference in the other 8 patients (median difference 0 ms, range 0-10 ms). The range of the QuickOpt-derived optimal VV delay was –70 ms to ⫹ 20 ms,
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with a mean of -30.9 ⫾ 22.0 ms. During repeated measurements, no variation was observed in 11 patients, and only 1 patient had a variation of ⬎ 5 ms (median difference 5 ms, range 0-10 ms). There was no difference in the QuickOpt-derived optimal AV delay (P ⫽ 0.094) and VV delay (P ⫽ 0.201) between sitting and standing positions. Changes with exercise The summary of exercise test duration, heart rate, blood pressure, and QuickOpt-derived optimal AV and VV delay changes is presented in Table 2. The changes in the QuickOpt-derived optimal AV and VV delays during exercise and recovery are presented in Figure 1 (mean changes) and Figure 2 (individual changes). AV delay During exercise, the QuickOpt-derived optimal AV delay did not change in 11 patients (1 of those patients performed only 1 stage of exercise). In 4 patients, the QuickOpt-derived AV delay shortened progressively during the exercise. In 4 patients, the QuickOpt-derived AV delay shortened during the first stage, but there were no additional changes at later stages. The QuickOpt-derived AV delay prolonged in 3 patients (1 of whom performed only 1 stage of exercise). VV delay In 18 patients, there was a change in the QuickOpt-derived optimal VV delay toward earlier RV pacing by 5-50 ms. The change was gradual throughout the exercise stages in 9 patients, whereas it changed at the first stage with no additional changes during the other stages of exercise in 5 patients. Two of the latter patients performed only 1 stage of exercise. In 1 patient, the QuickOpt-derived VV delay changed initially toward earlier LV pacing, but at the later stages it progressively changed toward earlier RV pacing. In 2 patients, there was a shift toward earlier LV pacing by 10 ms. The QuickOpt-derived VV delay did not change in 3 patients who exercised for 12-15 minutes and had an increase in heart rate by 33-45 beats/min. Table 2. Exercise parameters No. of stages performed
No. of patients
1 2 3 4 5
2 8 5 3 6
Parameters (mean ⫾ SD) METs Exercise duration, min Heart rate, bpm Percent of maximal predicted HR Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Recovery duration, min Changes in delays, ms (mean ⫾ SD) AV delay VV delay
3.9 ⫾ 1.0 10.1 ⫾ 4.1
Rest (standing)
Peak exercise
70.0 ⫾ 9.0
99.5 ⫾ 14.8
67.9 ⫾ 11.0 115.4 ⫾ 15.7 137.7 ⫾ 17.4 6.0 ⫾ 1.7
63.8 ⫾ 7.5
73.0 ⫾ 9.9
126.5 ⫾ 15.8 120.9 ⫾ 15.7* ⫺30.7 ⫾ 22.2 ⫺20.2 ⫾ 26.1†
* P ⫽ 0.04. P ⫽ 0.001. Negative value means LV pacing preceding RV pacing.
†
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Figure 1. (A) Average changes in the QuickOpt-derived atrioventricular (AV) delays from the resting baseline values during exercise and recovery (mean ⫾ SD). Negative changes indicate shorter delays. (B) Average changes in the QuickOpt-derived interventricular (VV) delays from the resting baseline values during exercise and recovery (mean ⫾ SD). Positive changes indicate shift toward earlier right ventricular (RV) pacing. LV, left ventricular.
Overall, every patient except 1 experienced a change in at least 1 of the QuickOpt-derived AV delay or VV delay parameters during exercise.
lay also returned to baseline in most patients, but it remained ⱖ 5 ms from baseline in 4 patients (Fig. 2).
Changes during recovery
Relationship between the heart rate and the AV and VV delays
The QuickOpt-derived optimal AV delay returned to baseline in most patients, but it remained ⱖ 10 ms different from baseline in 6 patients. The QuickOpt-derived optimal VV de-
There was no correlation between the change in heart rate during exercise and the change in the QuickOpt-derived AV delay or VV delay (r ⫽ – 0.133, P ⫽ 0.227; and r ⫽ 0.171,
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dation of the measurements was not carried out in our study because the patients were subjected to a walk test on treadmill to more closely reflect their day-to-day activity. The reproducibility of QuickOpt measurements has not been reported previously. In this study, repeated measurements at rest showed reproducible results with minimal difference in sitting and standing positions. The maximal variance for any individual patient did not exceed 10 ms despite conducting measurements with the patients in 2 body positions. During the recovery phase after exercise, QuickOpt-derived AV and VV delays returned to the baseline values in most patients, support the reproducibility of the method. The finding that the QuickOpt-derived AV and VV delays did not completely return to the baseline values probably reflects prolonged physiological changes postexercise in this patient population. Increasing the response to CRT therapy
Figure 2. Individual QuickOpt-derived atrioventricular (AV) and interventricular (VV) values at rest, during peak exercise and at the end of recovery. (Top) AV delay. (Bottom) VV delay. (Grey dashed lines with large circles) Average value.
P ⫽ 0.095; respectively). The resting heart rate showed no correlation with the QuickOpt-derived AV delay during maximal exercise (r ⫽ – 0.236, P ⫽ 0.291), whereas a weak correlation was observed with the QuickOpt-derived VV delay at peak exercise (r ⫽ – 0.447, P ⫽ 0.033). Discussion The main new findings of the present study are the validated reproducibility of electrogram-based measurements of AV and VV delays, the feasibility of those measurements during graded exercise test, and the observed individual changes during exercise, with a shift toward earlier RV pacing in the majority of the patients. These AV and VV delay changes could not be predicted from the baseline characteristics or the heart rate change during exercise. The electrogram-based method and its reproducibility Previous studies of the QuickOpt method showed good correlation with optimization using echocardiogram-based methods for the AV and VV delays at rest.29-35,37 In a recently published study, QuickOpt was evaluated at rest and during a single grade exercise test. An agreement was observed between aortic velocity-time integral measurements and the QuickOpt method.38 The results of the current study demonstrate that the method is easy to use, and it is feasible both at rest and during graded treadmill exercise. Echocardiogram-based vali-
Prior to implantation of a CRT device, patient selection has an important role in the outcome of CRT therapy.39 Newer imaging modalities such as three-dimensional echocardiography may predict response to CRT therapy.40 Following the implantation procedure, optimization of the AV and VV delays has the potential to improve response to CRT therapy in selected patients. In unselected CRT patient populations, however, the value of AV delay or AV and VV delay optimization was questioned in recent studies.26,27,41 Importantly, those studies evaluated the effect of optimization at rest only. The results of this study indicate dynamic and individual changes to the optimal AV and VV delays during exercise. Optimization of the AV and VV delay during exercise may improve exercise tolerance and related symptoms, thus increasing the response to CRT therapy. AV delay In our study, there was a significant shortening of the average QuickOpt-derived AV delay during peak exercise compared with rest, but the direction, the magnitude and the pattern of change during the various stages of exercise were highly individual. Previous studies in CRT patients showed that the optimal resting AV delay is individual, and the optimization of the resting AV and VV delay may result in improvement of the acute and mid-term response to CRT.17-21,37,38 While the optimal AV delay shortens during exercise in patients with a dual chamber pacemaker for AV block and no left ventricular dysfunction or heart failure,42 existing data on the effect of exercise on optimal AV delay in CRT patients is limited and controversial.23-25 In one study, the optimal AV delay was found to be longer at increased heart rates,23 while another study found the opposite.24 A more recent study, using echocardiography to optimize AV delay, found a shorter AV delay during exercise than at rest in 27%, unchanged in 23%, and longer in 50% of the patients.13 Two other recent studies also showed individual response in the optimal AV delay during exercise, which is in line with our findings.25,38 One of the studies suggested that the optimal AV delay during exercise could be predicted from the resting measurements.25 In our study, there was no correlation between resting heart rate, change of heart rate, or resting AV delay and the AV delay during exercise. Similarly, no correlation was found between resting parameters and the optimal VV delay during exercise.
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A study by Valzania et al.38 evaluated the QuickOpt method during a single-stage supine bicycle exercise test and found no changes in the average QuickOpt-derived AV delay, and no individual changes were discussed. As seen in our study or the study by Mokrani et al.,13 averaging the changes can mask the magnitude of individual changes due to the different direction of changes in individual patients. Further, we noticed that in some patients, the optimal AV delay did not change during the first stage of exercise but shortened during the later stages of exercise. VV delay Current evidence suggests that sequential pacing is better than simultaneous RV and LV pacing, with LV being paced first in most cases.7,14-17,43,44 In accordance, the QuickOpt measurements in our study indicated an optimal resting VV delay of 0 ms in 1 patient only. Two previous studies evaluated optimal VV delay during exercise. One of those studies used echocardiography during supine bicycle exercise and found a tendency toward earlier RV activation during exercise in half of the patients.7 The study by Valzania et al.38 found changes in the QuickOpt-derived VV delay in 54% of the patients (median 10 ms, range 5-70 ms) but did not report the direction of changes. In our study, the majority of patients (79%) had a shift toward earlier RV pacing during exercise based on the QuickOpt measurements. The direction of change was similar in most but not all patients, and there were individual differences in the magnitude of change and the pattern of change during the various stages of exercise. Some patients required more than 1 stage of exercise to develop the change in the QuickOpt-derived VV delay, which may explain why there were more patients with a change in their QuickOpt-derived VV delay in our study than in the other 2 studies. Based on the calculation that QuickOpt uses, a shift toward earlier RV pacing reflects faster VV conduction during exercise, although we cannot fully explain the reasons and why it is variable in individuals. Study limitations Our study was designed to assess the reproducibility of QuickOpt measurements and describe the changes of QuickOpt-derived AV and VV delays with exercise as a pilot study for a future study design to evaluate potential clinical benefits of optimizing AV and VV delays during exercise. Given the descriptive nature of the observations and the relatively small number of patients involved in the study, explanation of some of the findings such as the shift toward earlier RV pacing or the high individual variation in the AV and VV delay changes cannot be answered from this study. Conclusions In summary, this study demonstrates that QuickOpt is a feasible and reproducible method to measure AV and VV delay at rest as well as during graded exercise. There are individual differences in the changes to the QuickOpt-derived AV and VV delays during exercise: Not only is the direction of changes is variable, but also their pattern during the various stages of exercise. The next step should be to verify that optimization of the AV and VV delays during exercise translate into clinical benefit, such as an increase in 6-minute walk distance.
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Disclosures Dr Dorian received a consulting fee from St Jude Medical. Dr Crystal received an unrestricted educational grant from St Jude Medical. Dr Pinter received grant support from St Jude Medical unrelated to this study. None of the authors have any conflicts of interest to disclose.
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33. Meine M, Min X, Kordmann M, et al. IEGM based method for estimating optimal AV delay in cardiac resynchronization therapy. J Card Fail 2004;10(suppl 4):S74.
18. Sawhney NS, Waggoner AD, Garhwal S, et al. Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy. Heart Rhythm 2004;1:562-7. 19. Hardt SE, Yazdi SHF, Bauer A, et al. Immediate and chronic effects of AV-delay optimization in patients with cardiac resynchronization therapy. Int J Cardiol 2007;115:318-25. 20. Leon AR, Abraham WT, Brozena S, et al. Cardiac resynchronization with sequential biventricular pacing for the treatment of moderate-to-severe heart failure. J Am Coll Cardiol 2005;46:2298-304. 21. Vidal B, Sitges M, Marigliano A, et al. Optimizing the programmation of cardiac resynchronization therapy devices in patients with heart failure and left bundle branch block. Am J Cardiol 2007;100:1002-6. 22. Mullens W, Tang WHW, Grimm RA. Using echocardiography in cardiac resynchronization therapy. Am Heart J 2007;154:1011-20. 23. Scharf C, Li P, Muntwyler J, et al. Rate-dependent AV delay optimization in cardiac resynchronization therapy. PACE 2005;28:279-84. 24. Melzer C, Bondke H, Korber T, et al. Should we use the rate-adaptive AV delay in cardiac resynchronization therapy-pacing? Europace 2008;10:53-8. 25. Whinnett ZI, Briscoe C, Davies JER, et al. The atrioventricular delay of cardiac resynchronization can be optimized hemodynamically during exercise and predicted from resting measurements. Heart Rhythm 2008;5: 378-86. 26. Abraham WT, Gras D, Yu CM, et al. Rationale and design of a randomized clinical trial to assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy: the Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial. Am Heart J 2010;159:944-8.e1. 27. Abraham W. LBCT I. Presented at Heart Rhythm Society 31st Annual Scientific Sessions; May 12-15, 2010; Denver. 28. Tang AS, Ross H, Simpson CS, et al; on behalf of the Canadian Heart Rhythm Society and the Canadian Cardiovascular Society. Canadian Cardiovascular Society/Canadian Heart Rhythm Society position paper on implantable cardioverter defibrillator use in Canada. Can J Cardiol 2005; 21(suppl A):11A-8A.
34. Baker JH, McKenzie J, Beau S, et al. Acute evaluation of programmerguided AP/VP and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dual-chamber ICD implants. J Cardiovasc Electrophysiol 2007;18:185-91. 35. Min X, Meine M, Baker JH, et al. Estimation of the optimal VV delay by an IEGM-based method in cardiac resynchronization therapy. PACE 2007;30:S19-22. 36. Patterson J, Naughton J, Pietras R, et al. Treadmill exercise in assessment of the functional capacity of patients with cardiac disease. Am J Cardiol 1972;30:757-62. 37. Anselmino M, Antolini M, Amellone C, et al. Optimization of cardiac resynchronization therapy: echocardiographic vs semiautomatic device algorithms. Congest Heart Fail 2009;15:14-8. 38. Valzania C, Eriksson MJ, Boriani G, et al. Cardiac resynchronization therapy during rest and exercise: comparison of two optimization methods. Europace 2008;10:1161-9. 39. Auger D, Ducharme A, Harel F, et al. Patient assessment for cardiac resynchronization therapy: past, present and future of imaging techniques. Can J Cardiol 2010;26:27-34. 40. Lau C, Abdel-Qadir HM, Lashevsky I, et al. Utility of three-dimensional echocardiography in assessing and predicting response to cardiac resynchronization therapy. Can J Cardiol 2010;26:475-80. 41. Ellenbogen KA, Gold MR, Meyer TE, et al. Primary results from the SmartDelay Determined AV optimization: a comparison to other AV delay methods used in Cardiac Resynchronization Therapy (SMARTAV) Trial: a randomized trial comparing empirical, echocardiographyguided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. Circulation 2010;122:26660-8. 42. Sheppard RC, Ren JF, Ross J, et al. Doppler echocardiographic assessment of the hemodynamic benefits of rate adaptive AV delay during exercise in paced patients with complete heart block. Pacing Clin Electrophysiol 1993;16:2157-67.
29. Porciani MC, Rao CM, Mochi M, et al. A real-time three-dimensional echocardiographic validation of an intracardiac electrogram-based method for optimizing cardiac resynchronization therapy. Pacing Clin Electrophysiol 2008;31:56-63.
43. Bordachar P, Lafitte S, Reuter S, et al. Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing. J Am Coll Cardiol 2004;44:2157-65.
30. Meine M, Min X, Kordmann M, et al. IEGM based method for estimating optimal VV delay in cardiac resynchronization therapy [abstract]. Europace 2004;6(suppl 1):116.
44. Brignole M, Oddone D, Maggi R, et al. Resynchronization of the left ventricular contraction by tailored programming of right and left ventricular pacing. Europace 2008;10:489-95.
Clinical Research
Electrogram-Based Optimal Atrioventricular and Interventricular Delays of Cardiac Resynchronization Change Individually During Exercise Gregory Golovchiner, MD,a Paul Dorian, MD, MSc,a Iqwal Mangat, MD,a Victoria Korley, MD,a Kamran Ahmad, MD,a Khairi Sharef, MD,a Emoke Posan, MD, PhD,a Eugene Crystal, MD,b Suzan O’Donnell, MSc,a and Arnold Pinter, MDa a
St. Michael’s Hospital, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada
b
Sunnybrook Hospital, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada
ABSTRACT
RÉSUMÉ
Background: Limited data suggest that optimal atrioventricular (AV) and interventricular (VV) delays are different at rest than during exercise in patients with heart failure. We assessed the feasibility and reproducibility of an electrogram-based method of optimization called QuickOpt at rest and during exercise. Methods: Patients with a St Jude Medical cardiac resynchronization therapy implantable cardioverter-defibrillator were subjected to a graded treadmill test, and QuickOpt was repeatedly measured prior to, during, and after the exercise. Results: Twenty-four patients (16 males, aged 67.4 ⫾ 7.7 years) participated. At rest, delays (in ms) were 110.4 ⫾ 20.1 for sensed AV delay and –70 (LV pacing first) to ⫹20 (RV pacing first) for VV delay. The changes in QuickOpt-derived delays at rest were not significant despite change in body position. During exercise, QuickOpt-derived AV delays did not change in 11 patients, were shorter during peak exercise in 8 patients, and were longer in 3 patients (average value during peak exercise was 126.5 ⫾ 15.8 ms, P ⫽ 0.04 compared to baseline). The QuickOpt-derived VV delay gradually shifted toward earlier right ventricular pacing during exercise in 19 patients, while no changes
Introduction : Des données limitées suggèrent que les délais atrioventriculaires (AV) et interventriculaires (IV) optimaux sont différents au repos par rapport aux délais obtenus durant l’exercice chez les patients ayant une insuffisance cardiaque. Nous avons évalué la faisabilité et la reproductibilité d’une méthode d’optimisation à l’aide de l’électrogramme appelée QuickOpt au repos et durant l’exercice. Méthodes : Les patients portant un défibrillateur cardioverteur implantable St Jude Medical pour une thérapie de resynchronisation cardiaque ont été soumis à une épreuve d’effort gradué sur tapis roulant, et le QuickOpt a été mesuré de manière répétitive avant, pendant et après l’exercice. Résultats : Vingt-quatre patients (16 hommes âgés de 67,4 ⫾ 7,7 ans) ont participé. Au repos, les délais (en ms) ont été de 110,4 ⫾ 20,1 pour le délai AV défini et –70 (VG stimulé en premier) à ⫹20 (VD stimulé en premier) pour le délai IV. Les changements dans les délais avec le QuickOpt au repos n’ont pas été significatifs, en dépit du changement de position du corps. Durant l’exercice, les délais AV avec le QuickOpt n’ont pas changé chez 11 patients, ont été plus courts durant le pic de l’exercice chez 8 patients et ont été plus longs chez 3 patients (la valeur moyenne durant le pic de l’exercice a été de
Cardiac resynchronization therapy (CRT) has been shown to improve heart failure symptoms, exercise capacity and mortality in patients with New York Heart Association (NYHA) Class III-IV heart failure symptoms, an ejection fraction ⱕ 35%, and QRS duration ⬎120 ms.1,2 However, up to 30% of patients receiving CRT do not respond to this therapy.3-6 Optimization of atrioventricular (AV) delay7-13 and interventricular (VV) delay14-16 has been shown to improve acute hemodynamic re-
sponse and translate into limited short-term clinical benefit in some studies.17-21 There is no consensus on how to measure optimization. Resting echocardiography is the most commonly used modality for CRT optimization, but it is time consuming and there is no “gold standard” method.13,22 Since most patients receiving CRT have NYHA Class III heart failure symptoms, improvement in exercise capacity is one of the major goals. On the other hand, these patients spend most of their time resting and reverse remodelling would presumably occur with optimal resting delays. Limited and controversial data exist regarding changes in optimal AV and VV delays during exercise.7,13,23-25 If such changes exist, patients may possibly benefit from automatically adjusted AV and VV delays depending on their level of activity.
Received for publication November 5, 2010. Accepted December 16, 2010. Corresponding author: Dr Arnold Pinter, St Michael’s Hospital, 30 Bond St, Toronto, Ontario M5B 1W8, Canada. Tel.: ⫹1-416-864-5104; fax: ⫹1416-864-5104. E-mail: [email protected] See page 356 for disclosure information.
0828-282X/$ – see front matter © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.cjca.2010.12.047
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were seen in 3 patients, and a shift occurred toward earlier left ventricular pacing in 2 patients (average value during peak exercise was –30.7 ⫾ 22.2; P ⫽ 0.001 compared to baseline). There was no correlation between changes in the QuickOpt-derived AV and VV delays and heart rate. Conclusions: The application of electrogram-based algorithm is feasible both at rest and during exercise. The results are reproducible. QuickOpt-derived AV and VV delays individually change during exercise.
126,5 ⫾ 15,8 ms, P ⫽ 0,04 comparativement à la ligne de base). Le délai IV avec le QuickOpt a changé graduellement vers le début de la stimulation du ventricule droit durant l’exercice chez 19 patients, tandis qu’aucun changement n’a été observé chez 3 patients, et un changement est apparu vers le début de la stimulation du ventricule gauche chez 2 patients (la valeur moyenne durant le pic de l’exercice a été –30,7 ⫾ 22,2; P ⫽ 0,001 comparativement à la ligne de base). Il n’y a eu aucune corrélation entre les changements dans les délais AV et IV avec le QuickOpt, et la fréquence cardiaque. Conclusions : L’application d’un algorithme à l’aide de l’électrogramme est réalisable tant au repos que durant l’exercice. Les résultats sont reproductibles. Les délais IV et AV du QuickOpt changent individuellement durant l’exercice.
One form of electrogram-based method of optimization called QuickOpt is used in St Jude Medical CRT devices and allows a simple and quick optimization of the AV and VV delays, providing an opportunity to test it during exercise. A yet unpublished study presented at the 31st Annual Scientific Sessions of the Heart Rhythm Society showed no difference in the response rate to CRT between patients randomly assigned to resting QuickOpt optimization versus patients assigned to echocardiographic optimization.26,27 This finding, however, does not preclude a potential benefit in exercise tolerance and/or exercise-related symptoms from optimized CRT during exertion if the optimal exercise AV and VV delay is different from the resting values. To date, no data are available about the reproducibility of the QuickOpt method and the optimal AV and VV delays during different levels of graded exercise. The aims of the present prospective study were to assess whether (1) it is feasible to carry out QuickOpt measurements during graded exercise; (2) QuickOpt measurements are reproducible, and (3) the QuickOpt AV and VV delays are different during exercise and at rest.
after the completion of atrial electrical activation and contraction. Since the paced AV delay was calculated by adding 50 ms to the sensed AV delay, we will only describe the sensed AV delay measurements. The algorithm optimizes the VV delay by calculating optimal VV ⫽ 0.5 ⫻ (⌬ ⫹ ), where the conduction delay ⌬ is the difference between the time of peak intrinsic activation at the LV versus the RV lead and the correction term is the difference in VV conduction delay between pacing from the right ventricle and from the left ventricle. A VV delay ⬍ 0 indicates LV pacing first. During the test, each chamber is paced with a short AV delay to prevent fusion of the activation fronts. The optimization of the AV and VV delays is independent from the lead positions.34,35 Patients were subjected to a graded treadmill stress test using the modified Naughton protocol.36 Criteria for study termination were symptoms of fatigue, dyspnea, dizziness, chest pain, or reaching maximal predicted heart rate. During the evaluation, including the stress test, the programmed AV and VV delays were unchanged from baseline. Blood pressure, heart rate, and QuickOpt were measured prior to exercise in standing position, during the 3rd minute of every stage, immediately after stopping exercise and then every 3 minutes during recovery until the heart rate returned to baseline. Repeated QuickOpt measurements were performed 3 times with 1-minute interval between measurements in sitting position prior to exercise and 3 times in standing position on the treadmill prior to exercise to assess the reproducibility of the measurements.
Methods Consecutive patients with St Jude Medical CRT devices (all with a CRT implantable defibrillator) were included in the study that was conducted between May 2007 and December 2009. The indication for CRT device implantation was NYHA functional class III- IV heart failure symptoms despite optimal medical therapy, left ventricular end-diastolic dimension ⬎ 60 mm, left ventricular ejection fraction (LVEF) of ⱕ 35%, and QRS duration of ⱖ 120 ms.28 Patients were included in the study at least 1 month after the device implantation. Patients with NYHA functional class IV heart failure at the time of recruitment; not in sinus rhythm or with conditions that precluded QuickOpt measurements such as complete AV block were excluded. The study was approved by the St Michael’s Hospital Research Ethics Board. The optimal AV and VV delays were measured using the electrogram-based method called QuickOpt, which is available in St Jude Medical CRT devices such as Atlas ⫹HF V-34, Atlas II ⫹HF V-367, and Promote RF 3213-36. The method details have been described previously.29-35 In brief, for optimization of the sensed AV delay, the algorithm measured the width of the atrial intrinsic depolarization and added an offset factor of 30 ms if the intrinsic depolarization was ⱖ 100 ms or 60 ms if it was ⬍ 100 ms, such that ventricular pacing was delivered
Statistical analysis The results are presented as mean ⫾ SD or median, as appropriate. Repeated sitting and standing measurements were analyzed for variance in each patient. The difference between sitting and standing position, as well as between exercise measurements during every stage and standing position, was analyzed using Wilcoxon signed rank test. Correlation of changes in AV or VV delays and the heart rate was calculated using the nonparametric Spearman rho. Results Twenty-four patients participated in the study. The patients’ characteristics are presented in Table 1. The QuickOptderived AV and VV delay measurements were feasible in every patient during exercise, and it took approximately 50-80 seconds (faster with higher heart rates during exercise).
Golovchiner et al. Optimal Atrioventricular and Interventricular Delays Table 1. Patient characteristics (N ⫽ 24) Age, y Range Average ⫾ SD Gender, male Cardiac disease Coronary artery disease Nonischemic cardiomyopathy Indications for ICD Primary Secondary NYHA class at implant II III IV Medications ACEI/ARB -Blockers Amiodarone ECG LBBB Nonspecific intraventricular conduction delay QRS duration Range, ms Average ⫾ SD, ms Programmed delays* Sensed AV delay, ms, range Sensed AV delay, ms, average ⫾ SD VV delay, ms, range
54-78 67.4 ⫾ 7.7 16 (66.7%) 13 (54%) 11 (46%) 21(88%) 3 (12%) At implant At recruitment 0 21 22 3 2 0 24 (100%) 24 (100%) 5 (21%) 22 (92%) 2 (8%) 122-246 161.7 ⫾ 20.0 90-150 110.4 ⫾ 20.1 –70 to ⫹10
AV, atrioventricular; NYHA, New York Heart Association; LBBB, left bundle branch block; SD, standard deviation; VV, interventricular. * Programmed delays at admission for the stress-test.
Baseline measurements Baseline resting QuickOpt-derived AV delays and VV delay measurements showed consistent results with minimal differences in individual patients. The QuickOpt measurement of AV delays was impossible in 2 patients with sinus bradycardia and no sensed atrial events. For those patients, only VV delays were analyzed and presented in Results. Sitting position. The range of the QuickOpt-derived optimal resting sensed AV delays in the whole patient group was 100150 ms, with a mean of 125.0 ⫾ 15.9 ms. The QuickOptderived optimal AV delay during the 3 repeat measurements showed no difference in 16 patients, and a maximum of 10-ms difference in the other 6 patients (median difference 0 ms, range 0-10 ms). The QuickOpt-derived optimal VV delay ranged from – 65 ms (LV pacing first) to ⫹20 ms (RV pacing first), with a mean of –31.7 ⫾ 24.0 ms. No variation was observed in 12 patients during the repeated measurements, and only 1 patient had a variation of ⬎ 5 ms (median difference 0 ms, range 0-10 ms). Standing position. The average heart rate was 70.0 ⫾ 9.0 beats/ min, and blood pressure was 115.7 ⫾15.5/64.5 ⫾ 8.0 mm Hg in the standing position. The range of the QuickOpt-derived optimal resting sensed AV delays was 110-150 ms, with a mean of 126.3 ⫾ 16.1 ms. Repeated measurements showed no variation in 14 patients and up to 10-ms difference in the other 8 patients (median difference 0 ms, range 0-10 ms). The range of the QuickOpt-derived optimal VV delay was –70 ms to ⫹ 20 ms,
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with a mean of -30.9 ⫾ 22.0 ms. During repeated measurements, no variation was observed in 11 patients, and only 1 patient had a variation of ⬎ 5 ms (median difference 5 ms, range 0-10 ms). There was no difference in the QuickOpt-derived optimal AV delay (P ⫽ 0.094) and VV delay (P ⫽ 0.201) between sitting and standing positions. Changes with exercise The summary of exercise test duration, heart rate, blood pressure, and QuickOpt-derived optimal AV and VV delay changes is presented in Table 2. The changes in the QuickOpt-derived optimal AV and VV delays during exercise and recovery are presented in Figure 1 (mean changes) and Figure 2 (individual changes). AV delay During exercise, the QuickOpt-derived optimal AV delay did not change in 11 patients (1 of those patients performed only 1 stage of exercise). In 4 patients, the QuickOpt-derived AV delay shortened progressively during the exercise. In 4 patients, the QuickOpt-derived AV delay shortened during the first stage, but there were no additional changes at later stages. The QuickOpt-derived AV delay prolonged in 3 patients (1 of whom performed only 1 stage of exercise). VV delay In 18 patients, there was a change in the QuickOpt-derived optimal VV delay toward earlier RV pacing by 5-50 ms. The change was gradual throughout the exercise stages in 9 patients, whereas it changed at the first stage with no additional changes during the other stages of exercise in 5 patients. Two of the latter patients performed only 1 stage of exercise. In 1 patient, the QuickOpt-derived VV delay changed initially toward earlier LV pacing, but at the later stages it progressively changed toward earlier RV pacing. In 2 patients, there was a shift toward earlier LV pacing by 10 ms. The QuickOpt-derived VV delay did not change in 3 patients who exercised for 12-15 minutes and had an increase in heart rate by 33-45 beats/min. Table 2. Exercise parameters No. of stages performed
No. of patients
1 2 3 4 5
2 8 5 3 6
Parameters (mean ⫾ SD) METs Exercise duration, min Heart rate, bpm Percent of maximal predicted HR Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Recovery duration, min Changes in delays, ms (mean ⫾ SD) AV delay VV delay
3.9 ⫾ 1.0 10.1 ⫾ 4.1
Rest (standing)
Peak exercise
70.0 ⫾ 9.0
99.5 ⫾ 14.8
67.9 ⫾ 11.0 115.4 ⫾ 15.7 137.7 ⫾ 17.4 6.0 ⫾ 1.7
63.8 ⫾ 7.5
73.0 ⫾ 9.9
126.5 ⫾ 15.8 120.9 ⫾ 15.7* ⫺30.7 ⫾ 22.2 ⫺20.2 ⫾ 26.1†
* P ⫽ 0.04. P ⫽ 0.001. Negative value means LV pacing preceding RV pacing.
†
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Figure 1. (A) Average changes in the QuickOpt-derived atrioventricular (AV) delays from the resting baseline values during exercise and recovery (mean ⫾ SD). Negative changes indicate shorter delays. (B) Average changes in the QuickOpt-derived interventricular (VV) delays from the resting baseline values during exercise and recovery (mean ⫾ SD). Positive changes indicate shift toward earlier right ventricular (RV) pacing. LV, left ventricular.
Overall, every patient except 1 experienced a change in at least 1 of the QuickOpt-derived AV delay or VV delay parameters during exercise.
lay also returned to baseline in most patients, but it remained ⱖ 5 ms from baseline in 4 patients (Fig. 2).
Changes during recovery
Relationship between the heart rate and the AV and VV delays
The QuickOpt-derived optimal AV delay returned to baseline in most patients, but it remained ⱖ 10 ms different from baseline in 6 patients. The QuickOpt-derived optimal VV de-
There was no correlation between the change in heart rate during exercise and the change in the QuickOpt-derived AV delay or VV delay (r ⫽ – 0.133, P ⫽ 0.227; and r ⫽ 0.171,
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dation of the measurements was not carried out in our study because the patients were subjected to a walk test on treadmill to more closely reflect their day-to-day activity. The reproducibility of QuickOpt measurements has not been reported previously. In this study, repeated measurements at rest showed reproducible results with minimal difference in sitting and standing positions. The maximal variance for any individual patient did not exceed 10 ms despite conducting measurements with the patients in 2 body positions. During the recovery phase after exercise, QuickOpt-derived AV and VV delays returned to the baseline values in most patients, support the reproducibility of the method. The finding that the QuickOpt-derived AV and VV delays did not completely return to the baseline values probably reflects prolonged physiological changes postexercise in this patient population. Increasing the response to CRT therapy
Figure 2. Individual QuickOpt-derived atrioventricular (AV) and interventricular (VV) values at rest, during peak exercise and at the end of recovery. (Top) AV delay. (Bottom) VV delay. (Grey dashed lines with large circles) Average value.
P ⫽ 0.095; respectively). The resting heart rate showed no correlation with the QuickOpt-derived AV delay during maximal exercise (r ⫽ – 0.236, P ⫽ 0.291), whereas a weak correlation was observed with the QuickOpt-derived VV delay at peak exercise (r ⫽ – 0.447, P ⫽ 0.033). Discussion The main new findings of the present study are the validated reproducibility of electrogram-based measurements of AV and VV delays, the feasibility of those measurements during graded exercise test, and the observed individual changes during exercise, with a shift toward earlier RV pacing in the majority of the patients. These AV and VV delay changes could not be predicted from the baseline characteristics or the heart rate change during exercise. The electrogram-based method and its reproducibility Previous studies of the QuickOpt method showed good correlation with optimization using echocardiogram-based methods for the AV and VV delays at rest.29-35,37 In a recently published study, QuickOpt was evaluated at rest and during a single grade exercise test. An agreement was observed between aortic velocity-time integral measurements and the QuickOpt method.38 The results of the current study demonstrate that the method is easy to use, and it is feasible both at rest and during graded treadmill exercise. Echocardiogram-based vali-
Prior to implantation of a CRT device, patient selection has an important role in the outcome of CRT therapy.39 Newer imaging modalities such as three-dimensional echocardiography may predict response to CRT therapy.40 Following the implantation procedure, optimization of the AV and VV delays has the potential to improve response to CRT therapy in selected patients. In unselected CRT patient populations, however, the value of AV delay or AV and VV delay optimization was questioned in recent studies.26,27,41 Importantly, those studies evaluated the effect of optimization at rest only. The results of this study indicate dynamic and individual changes to the optimal AV and VV delays during exercise. Optimization of the AV and VV delay during exercise may improve exercise tolerance and related symptoms, thus increasing the response to CRT therapy. AV delay In our study, there was a significant shortening of the average QuickOpt-derived AV delay during peak exercise compared with rest, but the direction, the magnitude and the pattern of change during the various stages of exercise were highly individual. Previous studies in CRT patients showed that the optimal resting AV delay is individual, and the optimization of the resting AV and VV delay may result in improvement of the acute and mid-term response to CRT.17-21,37,38 While the optimal AV delay shortens during exercise in patients with a dual chamber pacemaker for AV block and no left ventricular dysfunction or heart failure,42 existing data on the effect of exercise on optimal AV delay in CRT patients is limited and controversial.23-25 In one study, the optimal AV delay was found to be longer at increased heart rates,23 while another study found the opposite.24 A more recent study, using echocardiography to optimize AV delay, found a shorter AV delay during exercise than at rest in 27%, unchanged in 23%, and longer in 50% of the patients.13 Two other recent studies also showed individual response in the optimal AV delay during exercise, which is in line with our findings.25,38 One of the studies suggested that the optimal AV delay during exercise could be predicted from the resting measurements.25 In our study, there was no correlation between resting heart rate, change of heart rate, or resting AV delay and the AV delay during exercise. Similarly, no correlation was found between resting parameters and the optimal VV delay during exercise.
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A study by Valzania et al.38 evaluated the QuickOpt method during a single-stage supine bicycle exercise test and found no changes in the average QuickOpt-derived AV delay, and no individual changes were discussed. As seen in our study or the study by Mokrani et al.,13 averaging the changes can mask the magnitude of individual changes due to the different direction of changes in individual patients. Further, we noticed that in some patients, the optimal AV delay did not change during the first stage of exercise but shortened during the later stages of exercise. VV delay Current evidence suggests that sequential pacing is better than simultaneous RV and LV pacing, with LV being paced first in most cases.7,14-17,43,44 In accordance, the QuickOpt measurements in our study indicated an optimal resting VV delay of 0 ms in 1 patient only. Two previous studies evaluated optimal VV delay during exercise. One of those studies used echocardiography during supine bicycle exercise and found a tendency toward earlier RV activation during exercise in half of the patients.7 The study by Valzania et al.38 found changes in the QuickOpt-derived VV delay in 54% of the patients (median 10 ms, range 5-70 ms) but did not report the direction of changes. In our study, the majority of patients (79%) had a shift toward earlier RV pacing during exercise based on the QuickOpt measurements. The direction of change was similar in most but not all patients, and there were individual differences in the magnitude of change and the pattern of change during the various stages of exercise. Some patients required more than 1 stage of exercise to develop the change in the QuickOpt-derived VV delay, which may explain why there were more patients with a change in their QuickOpt-derived VV delay in our study than in the other 2 studies. Based on the calculation that QuickOpt uses, a shift toward earlier RV pacing reflects faster VV conduction during exercise, although we cannot fully explain the reasons and why it is variable in individuals. Study limitations Our study was designed to assess the reproducibility of QuickOpt measurements and describe the changes of QuickOpt-derived AV and VV delays with exercise as a pilot study for a future study design to evaluate potential clinical benefits of optimizing AV and VV delays during exercise. Given the descriptive nature of the observations and the relatively small number of patients involved in the study, explanation of some of the findings such as the shift toward earlier RV pacing or the high individual variation in the AV and VV delay changes cannot be answered from this study. Conclusions In summary, this study demonstrates that QuickOpt is a feasible and reproducible method to measure AV and VV delay at rest as well as during graded exercise. There are individual differences in the changes to the QuickOpt-derived AV and VV delays during exercise: Not only is the direction of changes is variable, but also their pattern during the various stages of exercise. The next step should be to verify that optimization of the AV and VV delays during exercise translate into clinical benefit, such as an increase in 6-minute walk distance.
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Disclosures Dr Dorian received a consulting fee from St Jude Medical. Dr Crystal received an unrestricted educational grant from St Jude Medical. Dr Pinter received grant support from St Jude Medical unrelated to this study. None of the authors have any conflicts of interest to disclose.
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