Effect of right ventricular pacing in patients with complete left bundle branch block

TABLE II Cox Regression Analysis for Development of New Coronary Events Variable Age Prior CAD Men Aortic sclerosis

Parameter Estimate

Standard Error

p Value

RR

95% CL

0.006 1.029 0.228 0.564

0.004 0.072 0.075 0.074

0.170 0.0001 0.002 0.0001

1.006 2.798 1.256 1.758

(0.997, 1.015) (2.428, 3.225) (1.084, 1.454) (1.521, 2.031)

CL 5 confidence limits; RR 5 relative risk.

study (p 5 0.031, p ,0.00001 and p ,0.00001, respectively). Because older subjects with valvular aortic sclerosis are at increased risk of new coronary events, they should be evaluated for CAD and have risk factor modification, including cessation of smoking, treatment of hypercholesterolemia, and treatment of hypertension. Older subjects with prior CAD had a 2.8 times higher chance of developing a new coronary event than those without prior CAD, after controlling the confounding effects of other prognostic variables. Men had a 1.3 times higher probability of developing new coronary events than women, after controlling the confounding effects of other prognostic variables. Older subjects with valvular aortic sclerosis had a 1.8 times higher chance of developing a new coronary event than those without valvular

aortic sclerosis, after controlling the confounding effects of other prognostic variables. 1. Aronow WS, Schwartz KS, Koenigsberg M. Corre-

lation of serum lipids, calcium, and phosphorus, diabetes mellitus and history of systemic hypertension with presence or absence of calcified or thickened aortic cusps or root in elderly patients. Am J Cardiol 1987; 59:998 –999. 2. Mohler ER, Sheridan MJ, Nichols R, Harvey WP, Waller BF. Development and progression of aortic valve stenosis: atherosclerotic risk factors–a causal relationship? A clinical morphologic study. Clin Cardiol 1991;14:995–999. 3. Mautner GC, Mautner SL, Cannon RO III, Hunsberger SA, Roberts WC. Clinical factors useful in predicting aortic valve structure in patients .40 years of age with isolated aortic stenosis. Am J Cardiol 1993;72:194 –198. 4. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM, for the Cardiovascular Health Study. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol 1997;29:630 – 634. 5. Mautner GC, Roberts WC. Reported frequency of coronary arterial narrowing by angiogram in patients with valvular aortic stenosis. Am J Cardiol 1992;69: 539 –540. 6. Aronow WS, Ahn C, Shirani J, Kronzon I. Comparison of frequency of new coronary events in older persons with mild, moderate, and severe valvular aortic stenosis with those without aortic stenosis. Am J Cardiol 1998;81:647– 649. 7. Shirani J, Yousefi J, Roberts WC. Major cardiac findings at necropsy in 366 American octogenarians. Am J Cardiol 1995;75:151–156. 8. Livanainen AM, Lindroos M, Tilvis R, Heikkila J, Kupari M. Natural history of aortic valve stenosis of varying severity in the elderly. Am J Cardiol 1996; 78:97–101. 9. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O’Brien KD. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 1994;90:844 – 853. 10. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol 1987;60:1182. 11. Roberts WC. Sudden cardiac death: definitions and causes. Am J Cardiol 1986;57:1410 –1413.

Effect of Right Ventricular Pacing in Patients With Complete Left Bundle Branch Block Ste´phane Garrigue, MD, S. Serge Barold, MD, Nathalie Valli, MD, Laurent Gencel, Pierre Jais, MD, Michel Haissaguerre, MD, and Jacques Cle´menty, MD

MD,

linical and experimental studies comparing singlechamber atrial with atrioventricular (AV) synC chronous pacing have shown that ventricular stimula-

RV pacing with spontaneous ventricular activation in heart failure patients with and without LBBB.

tion causes deterioration in systolic and diastolic left ventricular (LV) performance secondary to aberrant ventricular activation.1–3 However, the mechanical and hemodynamic consequences of right ventricular (RV) pacing in patients with complete left bundle branch block (LBBB) have not been well characterized, especially in the presence of congestive heart failure when the incidence of LBBB is relatively high.4 Therefore, we compared the functional effect of

The study consisted of an acute randomized crossover study of 10 highly selected patients with dual pacemakers implanted for electrophysiologic criteria, sinus rhythm, and spontaneous AV conduction (Table I).5 All RV leads were implanted at the apex and atrial leads in the right atrial appendage. Group I consisted of 5 heart failure patients with LBBB defined as QRS duration .120 ms, and notching of the QRS with an initial R wave in leads I and aVL and the left precordial leads.6 Group II consisted of 5 heart failure patients without LBBB or other intraventricular conduction disorders. The groups were closely matched in terms of age (65 years), gender, symptoms of chronic heart failure (according to New York Heart Association classification), presence of chronic ischemic heart disease, pacemaker indication, and PR interval (615 ms). Patients with severe mitral regurgitation were

From the Departments of Clinical Cardiac Pacing & Electrophysiology and Nuclear Medicine, Hoˆpital Cardiologique du Haut-Le´veˆque, University of Bordeaux, Pessac, France; and the University of Rochester, School Medicine and Dentistry, Rochester, New York. Dr. Garrigue’s address is: Centre Hospitalier et Universitaire de Bordeaux II, Hoˆpital Cardiologique du Haut-Le´veˆque, service du Professeur Jacques Cle´menty, 19 avenue de Magellan, 33604 Pessac Cedex, France. Manuscript received August 19, 1998; revised manuscript received and accepted September 29, 1998.

600

©1999 by Excerpta Medica, Inc. All rights reserved.

•••

0002-9149/99/$–see front matter PII S0002-9149(98)00923-0

excluded from the study.7 All 10 patients exhibited grade I to II functional systolic mitral regurgitation revealed by Doppler echocardiography. Each patient in group I was given a number and matched with one in group II to facilitate comparison (Figure 1). Patients 2, 4, and 5 in both groups exhibited end-diastolic mitral regurgitation during spontaneous AV conduction (Table I). The protocol consisted of 2 phases. For each patient, pacemakers initially were programmed randomly to AAI or DDD mode, at a rate exceeding the intrinsic heart rate by 5 ppm to match the rate in both pacing modes. In the second phase, the alternative pacing mode was programmed at the same rate. During DDD pacing, the AV delay was programmed to the longest duration that permitted complete ventricular capture without fusion. We verified the absence of fusion by observing paced complexes with the same duration (in ms) and morphology in all 12 surface electrocardiographic leads as those recorded during VVI pacing. Spontaneous AV conduction was manually determined on the surface electrocardiogram (50 mm/s) by 2 observers using leads I, II, and V5 recorded simultaneously. Patients underwent sequential radionuclide ventriculographic studies in each pacing mode after reaching a steady state of 30 minutes. The radionuclide procedure used red blood cells labeled in vivo with 30 mCi of technetium-99m. Imaging was performed using a digital camera equipped with a high-sensitivity, parallel-hole collimator oriented in a strict anterior, but also the best septal, left anterior oblique projection to isolate the left and right ventricles. In all cases, during DDD pacing, the ventricular pacing spike served as the gating trigger. In addition to global LV ejection fraction, regional ejection fraction was determined for LV septal and LV free wall segments. The time delay from the ventricular spike during RV pacing or the onset of the spontaneous QRS (earliest activation in lead I, II, or V5) to the onset of contraction of the last activated LV segment was calculated; this parameter was defined as the modified LV electromechanical delay. For that purpose, phase and amplitude images of the first harmonic of the Fourier transform were obtained for each pixel. A histogram of phase values restricted to the LV area was analyzed, and the synchronism of the contraction was expressed as the SD of the distribution of the LV phases.8 The modified LV electromechanical delay was provided by calculation of the area under the LV phase histograms obtained by Fourier analysis.8,9 This method was used to convert the phase values into time and provides accurate measurements for intraventricular delays.8,10 A third harmonic fit of the resultant time versus the radioactivity curve, generated from 24 automatically fit LV regions of interest, was used to generate peak filling rate and time to peak filling.10,11 Data are presented as mean 6 SD for quantitative variables. Because of the small sample size, the nonparametric paired Wilcoxon test was used to compare variables between the 2 pacing modes in the same patient. Variables compared between different groups

were analyzed by the nonparametric Kruskal-Wallis test. To evaluate the intraindividual variations, 2 patients (1 with and the other without LBBB) underwent the same radionuclide procedure 5 times in AAI and DDD modes. SD reached 61.6% for LV ejection fraction and 69 ms for the modified LV electromechanical delay. Patient data were statistically similar, because patients in groups I and II were matched clinically and electrophysiologically except for the presence of LBBB (Table I). Spontaneous heart rate was comparable in the 2 groups (65 6 5.7 beats/min in group I vs 66 6 4.8 beats/min in group II, p 5 NS). The QRS width was significantly longer in group I than in group II (131 6 4 vs 91 6 2 ms, p 5 0.02) (Table I). In each group, there was no significant difference in systolic blood pressure between AAI and DDD modes, respectively (124 6 23 vs 131 6 26 mm Hg in group I; 129 6 19 vs 135 6 16 mm Hg in group II ; p 5 NS). There was no significant difference in the AV values between the 2 groups during DDD pacing (162 6 19 ms in group I vs 160 6 28 ms in group II, p 5 NS) (Table II) as well as during AAI pacing (207 6 26 ms in group I vs 206 6 35 ms in group II, p 5 NS) (Table II). The mean modified LV electromechanical delay was significantly longer with AAI compared with DDD mode in group I (131 6 19 vs 98 6 7 ms, p ,0.01) (Table II and Figure 1A). In contrast, the mean modified LV electromechanical delay was longer during DDD than AAI pacing in group II (58 6 20 ms in AAI mode vs 110 6 41 ms in DDD, p ,0.01) (Figure 1A). During AAI pacing, patients in group I showed a significantly longer modified LV electromechanical delay than patients in group II, whereas in the DDD mode, the modified LV electromechanical delay demonstrated no statistical difference (Table II). The mean pacing rate was 69 6 5 ppm in group I vs 71 6 4 ppm in group II (p 5 NS). In group I (with LBBB), LV ejection fraction in the AAI mode was significantly lower than in the DDD mode (29.4 6 13.5% vs 35.2 6 15%, p 5 0.03) (Table II and Figure 1B). In contrast, patients in group II had a significantly higher LV ejection fraction in the AAI than in the DDD mode (38 6 9.5% vs 34.6 6 10%, p 5 0.03) (Table II). LV septal regional ejection fraction was significantly improved in group I with DDD mode compared with AAI mode (17.2 6 13% vs 23.8 6 11%, p 5 0.01) (Figure 2A). Likewise, patients in group I had an LV free wall regional ejection fraction significantly higher in the DDD than in the AAI mode (50.6 6 25% vs 60 6 26%, p 5 0.05) (Figure 2B). Conversely, patients in group II revealed a nonsignificant effect of DDD compared with AAI pacing for LV septal regional ejection fraction (28.6 6 11% vs 23.2 6 14%, p 5 NS) as well as for LV free wall regional ejection fraction (56.2 6 12% vs 51.2 6 17%, p 5 NS) (Figure 2). Peak filling rate was similar in AAI and DDD pacing modes in both patient groups (1.39 6 0.45 EDV/s in group I vs 1.6 6 0.26 in group II during AAI pacing, p 5 NS; 1.26 6 0.76 end-diastolic volume/s BRIEF REPORTS

601

TABLE I Characteristics of Patients in Groups I and II Patient

Age (yr) & Sex

Indication for PM

CHF (NYHA)

IHD

HR (beats/min)

QRS Width (ms)

PR Interval (ms)

With LBBB 1 2 3 4 5

Group I 74 M 72 F 82 M 72 F 59 M

SND AVB1, CI SND AVB1, CI AVB1, CI

2 2 2 3 3

1 1 1 2 1

58 65 62 70 72

126 131 132 136 131

185 230 165 220 225

131 6 4*

205 6 28

Mean 6 SD (%) Without LBBB 1 2 3 4 5

72 6 8 (40% F) Group II 74 M 68 F 78 M 69 F 64 M

40% SND

2.4 6 0.55

60%1

65 6 5.7

SND AVB1, CI SND AVB1, CI AVB1, CI

2 2 2 3 3

1 1 1 2 1

60 69 63 72 68

Mean 6 SD (%)

71 6 5 (40% F)

40% SND

2.4 6 0.55

60%1

66 6 4.8

89 89 92 91 93 91 6 2*

175 220 155 235 235 204 6 37

*p ,0.05 between patients in groups I and II (Kruskal-Wallis test). ABV1 5 first-degree atrioventricular block; CHF 5 chronic heart failure; CI 5 chronotropic incompetence5; HR 5 spontaneous heart rate; IHD 5 ischemic heart disease; LBBB 5 complete left bundle branch block; NYHA 5 symptoms of heart failure at the time of the study, according to the criteria of the New York Heart Association classification; PM 5 pacemaker; SND 5 sinus node disease.

FIGURE 1. A, radar graphs of modified LV electromechanical delay (ms) in each patient group (with and without LBBB). Matched patients have the same attributed number (i.e., no. 1 in group I matched with no. 1 in group II). Patients without LBBB (group II) exhibit a shorter modified LV electromechanical delay in AAI than in DDD pacing, but the converse is seen in all patients with LBBB (group I). B, radar graphs representing LV ejection fraction (%) in each patient group (with and without LBBB). All patients without LBBB had a higher LV ejection fraction in the AAI than in the DDD mode, whereas the converse is seen in all patients with LBBB.

in group I vs 1.49 6 0.17 end-diastolic volume/s in group II during DDD pacing, p 5 NS). The time to peak filling was longer in group I during DDD than AAI pacing, but this was not statistically significant (497 6 48 vs 538 6 53 ms, p 5 0.12). In group II, the time to peak filling was similar for both pacing modes (572 6 90 vs 561 6 51 ms, p 5 NS). •••

This acute study demonstrated that, in heart failure patients with LBBB, RV apical pacing in the DDD mode improves LV hemodynamic performance when compared with AAI pacing at the same rate and comparable AV interval. Hemodynamic improvement during RV pacing was associated with significant shortening of the modified LV electromechanical delay. Conversely, in heart failure patients without LBBB, 602 THE AMERICAN JOURNAL OF CARDIOLOGYT

VOL. 83

RV pacing decreased LV ejection fraction and substantially prolonged the modified LV electromechanical delay. Although our population is small, there was a significant correlation between the magnitude of modified LV electromechanical delay shortening and LV ejection fraction improvement (r 5 0.71, p 5 0.01). This suggests a gradual effect so that the shorter the modified LV electromechanical delay, the more homogeneous the LV contraction. However, the reason for a shorter LV activation time during RV pacing compared with spontaneous LV activation in LBBB patients is unclear, but may be related to earlier LV activation by pacing compared with conduction via the right bundle branch. Xiao et al7 performed a similar study, but their methodology using echocardiography differed substantially from ours. They studied FEBRUARY 15, 1999

TABLE II Left Ventricular Systolic Parameters Calculated by Radionuclide Ventriculography LV Ejection Fraction (%)

Modified LV Electromechanical Delay (ms)

AV Delay (ms)

Patient No.

AAI

DDD

AAI

DDD

AAI

DDD

With LBBB 1 2 3 4 5

Group I 46 32 38 14 17

49 33 52 19 23

105 123 156 140 132

89 95 97 108 101

190 230 170 220 225

165 170 130 165 180

Mean 6 SD

29.4 6 13.5

35.2 6 15*

131 6 19†

98 6 7*

207 6 26

162 6 19*

Without LBBB 1 2 3 4 5 Mean 6 SD

Group II 48 43 43 25 31 38 6 9.5

47 41 36 21 28 34.6 6 10*

38 48 72 86 45 58 6 20†

86 66 98 172 130 110 6 41*

185 220 155 235 235 206 6 35

135 175 125 180 185 160 6 28*

*p ,0.05 between AAI and DDD pacing modes for the same patient group (paired Wilcoxon test); †p ,0.05 between patients with and without LBBB for the same pacing mode (Kruskal-Wallis test).

FIGURE 2. Regional LV function. A, LV septal wall regional ejection fraction during AAI and DDD modes. DDD pacing shows a significant increase in both regional LV ejection fraction compared with AAI only in patients with LBBB. No difference was observed in patients without LBBB. B, LV free wall regional ejection fraction during AAI and DDD modes. Results were similar to those of the LV septal wall regional ejection fraction for patients in groups I and II.

patients with VVI pacemakers, and measurements were obtained from cardiac cycles with a PR interval .200 ms without mention of the longest allowable PR interval. Pacing rates were not identical in their patients with LBBB during RV pacing and spontaneous rhythm, and the PR intervals during AV conduction were not specified. They defined LV electromechanical delay as the interval from the Q wave to the onset of mitral regurgitation.7 Accordingly, these investigators found a longer LV electromechanical delay in patients with LBBB during RV pacing than during spontaneous AV conduction,7 the opposite of our data. This discrepancy is probably related to the occurrence of mitral regurgitation before the onset of contraction of all LV segments. This is the reason we defined a “modified” LV electromechanical delay in our study,

because this parameter reflects more closely the delay from the onset of the QRS complex to the time when all LV segments have begun to contract. Therefore, this modified LV electromechanical delay seems a better parameter of ventricular synchrony or asynchrony. Our acute study showing that RV pacing can reduce the degree of LV asynchrony in LBBB and improve LV function may explain the observations that conventional DDD pacing12,13 and preliminary experience with biventricular pacing with short AV delay14,15 suggest hemodynamic benefit, both acutely and on a limited long-term basis, in patients with significant LV intraventricular conduction disorders more often than those without these BRIEF REPORTS

603

abnormalities. Our findings underscore the need for long-term studies to determine whether the benefit of RV pacing can be sustained. Furthermore, the general recommendations to program the AV delay of a dual-chamber pacemaker to permit spontaneous conduction for better LV function may be inappropriate in patients with LBBB.3,16,17 1. Askenazi J, Alexander JH, Koenigsberg DI, Belic N, Lesch M. Alteration of left ventricular performance by left bundle branch block simulated with atrioventricular sequential pacing. Am J Cardiol 1984;53:99 –104. 2. Burkhoff D, Oikawa RY, Sagawa K. Influence of pacing site on canine left ventricular contraction. Am J Physiol 1986;251:H428 –H435. 3. Rosenqvist M, Isaaz K, Botvinick E, Dae MW, Cockrell J, Abbott JA, Schiller NB, Griffin JC. Relative importance of activation sequence compared to AV synchrony in left ventricular function. Am J Cardiol 1991;67:148 –156. 4. Schneider JF, Thomas HE Jr, McNamara PM, Kannel WB. Clinical-electrocardiographic correlates of newly acquired left bundle branch block: the Framingham Study. Am J Cardiol 1985;55:1332–1338. 5. Katritis D, Camm AJ. Chronotropic incompetence: a proposal for definition and diagnosis. Br Heart J 1993;70:400 – 402. 6. Grines CD, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF. Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony. Circulation 1989;79:845– 853. 7. Xiao HB, Brecker SJD, Gibson DG. Differing effects of right ventricular pacing and left bundle branch block on left ventricular function. Br Heart J 1993;69:166 –173.

8. Ormerod OJM, Barber RW, Wraight EP. The reliability of first harmonic

Fourier analysis fitting to simulated time activity curve. Nucl Med Commun 1986;7:157–163. 9. Santomauro M, Fazio S, Ferraro S, Maddalena G, Papaccioli G, Pappone C, Betocchi S, Chiarello M. Fourier analysis in patients with different pacing modes. PACE 1991;14:1351–1358. 10. Ormerod OJM, Barber RW, Wraight EP. The accuracy of functional parameters extracted from left ventricular time activity curves by multiple Fourier harmonic fitting: a simulation study. Nucl Med Commun 1986;7:91–103. 11. Links JM, Raichlen JS, Wagner HN Jr, Reid PR. Assessment of the site of ventricular activation by Fourier analysis of gated blood-pool studies. J Nucl Med 1985;26:27–32. 12. Brecker SJ, Gibson DG. What is the role of pacing in dilated cardiomyopathy? Eur Heart J 1996;17:819 – 824. 13. Glickson M, Hayes DL, Nishimura RA. Newer clinical applications of pacing. J Cardiovasc Electrophysiol 1997;8:1190 –1203. 14. Cazeau S, Ritter P, Lazarus A, Gras D, Backdach H, Mundler O, Mugica J. Multisite pacing for end-stage heart failure: early experience. PACE 1996;19(part II):1748 –1757. 15. Blanc JJ, Etienne Y, Gilard M, Mansourati J, Munier S, Boschat J, Benditt DG, Lurie KG. Evaluation of different ventricular pacing sites in patients with severe heart failure. Results of an acute hemodynamic study. Circulation 1997; 96:3273–3277. 16. Leclercq C, Gras D, Le Holloco A, Nicol L, Daubert C. Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing. Am Heart J 1995;129:1133–1141. 17. Vardas PE, Simantirakis EN, Parthenakis FI, Chrysostomakis SI, Skalidis EI, Zuridakis EG. AAIR versus DDDR pacing in patients with impaired sinus node chronotropy: an echocardiographic and cardiopulmonary study. PACE 1997;20: 1762–1768.

Resumption of Motor Vehicle Operation in Vasovagal Fainters Keith G. Lurie,

MD,

Demosthenes Iskos, MD, Scott Sakaguchi, and David G. Benditt, MD

asovagal syncope is the most common cause of fainting. Consequently, physicians often are V faced with making a decision regarding resumption of motor vehicle operation in this subset of fainters. Although a relatively recent set of published recommendations may guide physicians in their decision process,1 the actual status of clinical practice is unknown. This study evaluates current medical practice with regard to the method by which physicians specializing in the treatment of cardiac rhythm disturbances arrived at recommendations regarding resumption of driving for patients with vasovagal syncope. To this end, we conducted an international survey on the topic of driving and vasovagal syncope. •••

Physicians in 9 countries who specialize in the care of patients with cardiac arrhythmias were queried regarding their approach to the evaluation and treatment of vasovagal syncope. By way of example, the following are representative of the 12 questions posed to each physician: From the Cardiac Arrhythmia Center and the Syncope Center, Department of Medicine, Cardiovascular Division, University of Minnesota School of Medicine, Minneapolis, Minnesota. Dr. Benditt’s address is: Cardiovascular Division, University of Minnesota School of Medicine, Box 508 UMHC, Minneapolis, Minnesota 55455. Manuscript received June 16, 1998; revised manuscript received and accepted September 1, 1998.

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©1999 by Excerpta Medica, Inc. All rights reserved.

MD,

Gerard J. Fahy,

MB,

1. How many patients with vasovagal syncope have you treated? 2. Do you use tilt table testing to (1) diagnose patients with vasovagal syncope, and (2) guide drug therapy during follow-up? 3. How long before you let the patient drive again if (1) he/she was initially tilt positive but became tilt negative with treatment, or (2) he/she continued to be tilt positive despite treatment? 4. Does the fact that the patient develops syncope only when standing, but not while sitting, influence your decision to permit driving? 5. Do you differentiate between driving a commercial vehicle and driving a private car when restricting driving in patients with vasovagal syncope? In addition, physicians were asked to report any motor vehicle accident that may have occurred as a result of a vasovagal syncopal event, both before and after treatment was initiated. Data are expressed as mean 6 SEM. Sixty-six physicians responded to the survey (65% response rate). Fifty-one respondents practiced in 22 states in the United States, and 15 practiced in 8 other countries (Spain, United Kingdom, France, Italy, Germany, Canada, Taiwan, and Hong Kong). They reported having treated .11,500 patients with vasovagal syncope. Routine use of upright tilt-table testing to substantiate a diagnosis of vasovagal syncope was 0002-9149/99/$–see front matter PII S0002-9149(98)00924-2