Acute Hemodynamic Benefit of Left Ventricular Apex Pacing in Children

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Acute Hemodynamic Benefit of Left Ventricular Apex Pacing in Children Ward Y. Vanagt, MD, Xander A. Verbeek, PhD, Tammo Delhaas, MD, PhD, Marc Gewillig, MD, PhD, Luc Mertens, MD, PhD, Patrick Wouters, MD, PhD, Bart Meyns, MD, PhD, Willem J. Daenen, MD, and Frits W. Prinzen, PhD Departments of Physiology and Pediatrics, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands, and Departments of Pediatric Cardiology, Anesthesiology, and Cardiothoracic Surgery, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium

Background. Despite the fact that pacing at the right ventricular apex acutely and chronically decreases left ventricular contractile function, this pacing site is still conventionally used in adults and children. Because animal studies showed beneficial effects of left ventricular pacing, we compared the hemodynamic performance of left ventricular apex, left ventricular free wall, and right ventricular apex pacing in children. Methods. Studies were performed in 10 children (median age, 2.5 years; range, 2 months to 17 years) undergoing surgery for congenital heart disease with normal systemic left ventricular anatomy and intraventricular conduction. High-fidelity left ventricular and arterial pressure measurements were performed during epicardial right ventricular apex and left ventricular apex and free wall pacing.

Results. Left ventricular apex pacing increased the maximum rate of rise of left ventricular pressure and pulse pressure significantly relative to right ventricular apex pacing (by 7.7% ⴞ 7.2% and 7.7% ⴞ 7.0%, respectively) without changes in end-diastolic left ventricular pressure. Left ventricular free wall pacing did not significantly improve hemodynamics as compared with right ventricular apex pacing. The QRS duration was not different among pacing at the three sites. Conclusions. In this short-term study left ventricular apex pacing is hemodynamically superior to right ventricular apex and left ventricular free wall pacing in children. Therefore, the left ventricular apex appears a favorable pacing site after pediatric cardiac surgery. (Ann Thorac Surg 2005;79:932– 6) © 2005 by The Society of Thoracic Surgeons

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single-site LV lateral wall pacing is better than RV pacing. Furthermore, in animal studies pacing from the LV apex resulted in better LV function than pacing the RV apex or other LV sites [8 –10]. The objective of this study was to evaluate the hemodynamic effect of epicardial LV apex and LV free wall (LVFW) pacing as compared with epicardial RV apex pacing in children. Epicardial pacing is widely used and even preferred over endocardial pacing in small children. The study was performed during postoperative recovery from cardiopulmonary bypass, and hemodynamic and electrocardiographic measurements were made during pacing from different ventricular sites. This setting was chosen because currently the LV apex can only be reached using surgical intervention.

everal studies have shown that right ventricular (RV) apex pacing results in impaired hemodynamic performance, both in laboratory animals [1] and in adults [2]. Also in children RV apex pacing proved to impair cardiac function on an acute basis [3] as well as after long-term pacing [4]. Chronic RV apex pacing in children is associated with histopathologic changes, including increased myofiber size variation, fat deposition, and fibrosis [5]. The RV apex is still the most commonly used pacing site in children and adults with atrioventricular (AV) block or other indications for ventricular pacing, but other ventricular pacing sites are being explored. The high RV septum has been investigated as an alternative to RV apex pacing in adults, but the results are not consistently in favor of high-septal pacing [2]. There is some evidence that high RV septal pacing maintains left ventricular (LV) function better than RV apex pacing in children [3], but proper stable positioning of the pacing lead in the high septum appears even more difficult in pediatric than in adult hearts. Studies in animals [1] and patients [6, 7] indicate that

Patients and Methods The study was performed at the University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium. The study protocol was conducted in accordance with the guidelines formulated by the Institutional Review Board.

Accepted for publication Aug 23, 2004. Address reprint requests to Dr Prinzen, Dept of Physiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands; e-mail: [email protected].

© 2005 by The Society of Thoracic Surgeons Published by Elsevier Inc

Dr Prinzen discloses that his research is financially supported by Medtronic, Inc, and Guidant Corp.

0003-4975/05/$30.00 doi:10.1016/j.athoracsur.2004.08.053

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Table 1. Patient Characteristics

Patient Number 1 2 3 4 5 6 7 8 9 10 a

Age (y)

Diagnosis

Surgical Procedure

Percent Change in LVdPdtmax (LV apex vs RV apex pacing)

0.2 0.3 0.3 0.6 2.1 2.9 4.4 9.3 13.5 17.7

ASD/VSD TOF ASD/VSD TOF ASD ASD/VSD VSD SubAS AS MVP

Patch Patch ⫹ PA dilation Patch Patch ⫹ PA dilation Patch Patch Patcha Myotomya Ross Annuloplasty ⫹ ring

20.7 9.2 3.0 10.7 ⫺3.2 5.4 6.4 0.6 17.2 6.6

Percent Change in Pulse Pressure (LV apex vs RV apex pacing) 15.4 5.9 1.2 17.0 ⫺2.2 2.5 3.6 14.7 11.2

Surgery complicated by AV block.

AS ⫽ aortic stenosis; ASD ⫽ atrial septal defect; LV ⫽ left ventricular; LVdPdtmax ⫽ maximal rate of rise of LV pressure; MVP ⫽ mitral valve prolapse; PA ⫽ pulmonary artery; RV ⫽ right ventricular; SubAS ⫽ subaortic stenosis; TOF ⫽ tetralogy of Fallot; VSD ⫽ ventricular septal defect.

Study Group The study group consisted of 10 patients, 8 boys and 2 girls, median age 2.5 years (range, 0.2 to 17.7 years). Patient characteristics (age, diagnosis, and surgical procedure) are presented in Table 1. Patients with these congenital heart defects were studied because multiple temporary epicardial pacing leads are implanted routinely for backup pacing after surgical repair. Moreover, arterial, central venous, and left atrial pressure catheters were already in situ for monitoring these patients during recovery from surgery. All patients had biventricular physiology and, hence, separated systemic and pulmonary circulation after repair. None of the patients were in heart failure, had intraventricular conduction disturbances, or were pacemaker-dependent before the surgical procedure.

Instrumentation Instrumentation for pacing and hemodynamic measurements was performed before closure of the chest but after the cardiac surgical procedure. Two epicardial temporary pacing leads (Flexon 3-0; Sherwood-Davis & Geck, St. Louis, MO) were attached to the right atrial appendage. For ventricular pacing, the indifferent electrode was attached subcutaneously and unipolar temporary pacing leads (Flexon 3-0) were placed epicardially at the RV apex, LV apex, and basal part of the LVFW. An LV pressure catheter (Pigtail 3F; Cook Inc, Bloomington, IN) was inserted in the left atrium and passed through the mitral valve into the LV cavity. Furthermore, the tracings from electrocardiographic lead II and from the radial artery pressure catheter were recorded.

Pacing Protocol Ventricular pacing was started when the heart had resumed its pump function after surgery and after disconnection from cardiopulmonary bypass. Pacing was per-

formed with an external pacemaker using atrial sensing and ventricular pacing (VDD mode; models 5346/5388; Medtronic Inc, Minneapolis, MN). The AV interval was programmed at 50% of the preoperative intrinsic PQ time to guarantee complete ventricular activation initiating from the pacing site. Two patients had AV block after surgery (one second-degree [Mobitz II] block and one third-degree block, patients 7 and 8 in Table 1, respectively). They were also paced in the VDD mode with short AV intervals for comparability with the other patients. Pacing sites were varied in random order during the pacing protocol, and all measurements lasted for 1 minute. Only the acute effects of changing the pacing site were assessed, as some fluctuation in baseline values was still present after the recent disconnection from cardiopulmonary bypass. For both LV pacing sites, the change relative to RV apex pacing was calculated. To minimize the effects of ventilation on the results, the last complete ventilatory cycle before and the first complete ventilatory cycle after changing the pacing site were analyzed. During the entire study protocol, no changes in mechanical ventilation or intravenous medication were made and no surgical interventions were performed.

Data Acquisition and Processing All hemodynamic and electrophysiologic data were monitored and recorded during sinus rhythm and pacing from the ventricular sites. Data were recorded using Powerlab software (ADInstruments Inc, Colorado Springs, CO) and analysis was performed off-line using Matlab (The Mathworks Inc, Natick, MA) and Hemo (homemade) software. The paced AV interval and QRS duration were assessed from the electrocardiogram (lead II). From the LV pressure tracing, LV end-diastolic pressure and maximal LV systolic pressure were determined. Also, the maximal

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Table 2. Hemodynamic Resultsa

Variable LVPsys LVdPdtmax LVdPdtmin LVPed (mm Hg) Pulse pressure Heart rate

RV Apex Pacing Absolute Values 79.5 ⫾ 14.3 mm Hg 918 ⫾ 251 mm Hg/sc 724 ⫾ 188 mm Hg/s 13.0 ⫾ 3.8 40.2 ⫾ 11.5 mm Hgc 128 ⫾ 30 bpm

LV Apex Pacing Relative to RV Apex (%)a 2.7 ⫾ 4.1 7.7 ⫾ 7.2b 2.6 ⫾ 7.6 ⫺0.6 ⫾ 6.2 7.7 ⫾ 7.0b ⫺1.8 ⫾ 20.6

LVFW Pacing Relative to RV Apex (%)a 0.3 ⫾ 6.3 0.2 ⫾ 6.6c ⫺1.8 ⫾ 8.1 0.0 ⫾ 6.5 1.8 ⫾ 7.2 0.4 ⫾ 24.2

ANOVA p Value NS 0.002 NS NS 0.016 NS

Baseline value during RV apex pacing, change ⫾ standard deviation relative to RV apex pacing during LV apex and LVFW pacing and analysis of variance p value for overall group comparison. Changes relative to RV apex pacing expressed as percentage of change, except for LVPed, expressed in b c mm Hg. p ⬍ 0.05 versus RV apex pacing; p ⬍ 0.05 versus LV apex pacing.

a

ANOVA ⫽ analysis of variance; LV ⫽ left ventricular; LVdPdtmax ⫽ maximal rate of rise of LV pressure; LVdPdtmin ⫽ maximal rate of fall of LV pressure; LVFW ⫽ LV free wall; LVPed ⫽ end-diastolic LV pressure; LVPsys ⫽ maximal systolic LV pressure; NS ⫽ not significant; RV ⫽ right ventricular.

rate of rise (LVdPdtmax) and fall of the LV pressure curve were assessed and used as indexes of LV contractility and relaxation, respectively [1]. Pulse pressure from the radial artery pressure tracing was calculated as a measure of stroke volume [11]. In 1 patient (patient 7 in Table 1) the arterial pressure tracing could not be analyzed owing to technical problems.

Statistical Analysis Statistical analysis was performed on absolute values, and each patient served as his or her own control. One-way analysis of variance for repeated measures was performed. Only if this analysis showed a significant difference between any of the groups was post hoc analysis with Bonferroni correction used for comparison between specific pairs of pacing sites. A p value of less than 0.05 was considered statistically significant.

Results The hemodynamic data presented in Table 2 are the absolute baseline values during RV apex pacing and the relative changes (other than millimeters of mercury reported for end-diastolic LV pressure) during LV apex and LVFW pacing as compared with RV apex pacing. Changing the pacing site did not significantly influence heart rate, maximal systolic LV pressure, or end-diastolic LV pressure (Table 2). The LVdPdtmax was significantly higher during LV apex pacing than during RV apex and LVFW pacing. Pulse pressure was also significantly higher during LV apex pacing than during RV apex pacing. Figure 1 shows the relative changes in LVdPdtmax and pulse pressure among pacing sites in individual patients. Only 1 patient (patient number 5 in Table 1) showed a minor decrease in cardiac function during LV apex pacing. In all other patients, LVdPdtmax and pulse pressure were higher during LV apex than during RV apex and LVFW pacing, although the extent to which these variables changed differed among patients (Fig 1, Table 1). The maximal rate of fall of LV pressure was not significantly different among pacing sites, indicating little influence of the pacing site on LV relaxation.

The QRS duration was not significantly different among RV apex, LV apex, and LVFW pacing (120 ⫾ 26 ms, 120 ⫾ 29 ms, and 130 ⫾ 18 ms, respectively).

Comment This study indicates that LV apex pacing generally results in better LV pump function in terms of contractility (LVdPdtmax) [1] and stroke volume (pulse pressure) [11] than pacing at the conventional site, the RV apex. This beneficial effect appears specific for the LV apex and not attributable to the difference between LV and RV pacing because pacing at the LVFW did not improve hemodynamics. Similar results have been described with more sophisticated techniques in dogs without heart failure [9, 10]. In the LV the working myocardium is activated first at the LV endocardium in low septal and anterior free wall regions, close to the LV apex endocardium [12, 13]. From these exits of the Purkinje system the LV activation wavefront travels from apex to base with small differences in activation between septum and LVFW [12, 13]. Pacing at the LV apex would thus provide a fairly physiologic sequence of activation. In the absence of changes in preload and afterload, LVdPdtmax is a reliable measure of LV contractility [1]. It

Fig 1. Percentage changes in maximal rate of rise of left ventricular pressure (LVdPdtmax; left panel, n ⫽ 10) and in pulse pressure (right panel, n ⫽ 9) for individual patients with right ventricular (RV) apex pacing as reference value (# ⫽ p ⬍ 0.05 versus left ventricular apex pacing). (RV apex ⫽ RV apex pacing; LV apex ⫽ left ventricular apex pacing; LVFW ⫽ left ventricular free wall pacing.)

should be noted that the values for LVdPdtmax are relatively low in this study, even for pediatric patients. This is probably caused by a combination of the anesthesia and the recovery from cardiopulmonary bypass. The changes in pulse pressure give a good estimation of changes in stroke volume [11]. The observed changes in LVdPdtmax and pulse pressure when changing pacing site cannot be attributed to differences in ventricular filling because LV end-diastolic pressure did not change significantly. The hemodynamic differences among pacing sites occurred despite similar QRS duration. This finding is also in accordance with other studies in which QRS duration was not a useful predictor of LV function during pacing [10, 14]. Pacing was performed with fixed, short AV delays. However, the effects of AV synchrony appear to be of minor importance in children without failing hearts [15]. Furthermore, canine data show that LV apex pacing with short AV delays results in hemodynamic performance at sinus rhythm level [10].

Possible Clinical Implications The pediatric patient population was chosen because during cardiac surgery temporary pacing leads are routinely implanted epicardially. Furthermore, the epicardial approach is frequently used for chronic pacing in small children and in those with contraindications to endocardial pacing. The increased performance of LV apex pacing in our heterogeneous study group indicates that LV apex pacing is widely applicable in children and potentially also adult patients. The results of the present study indicate that the LV apex is the preferred pacing site for short-term pacing in children without heart failure. In the case of poor LV function after surgery, optimal site pacing might facilitate weaning from cardiopulmonary bypass, as has been described with biventricular pacing [14, 16, 17]. Furthermore, LV apex pacing could possibly avoid the need for increasing doses of inotropic agents. Chronic pacing initiated in childhood generally has a more protracted course as compared with adults [3]. Therefore, the identification of pacing sites that prevent the development of functional or structural abnormalities is clinically very relevant.

Limitations of the Study The group of children studied is small and inhomogeneous with respect to age and underlying cardiac disease. Owing to the setup of the study, only the acute effects of pacing at different sites have been assessed. Measurements were performed around the transition from one to the other pacing site, thus before autonomic reflexes could alter vascular properties. In this way the difference in hemodynamic effect of pacing between two sites could be studied more accurately. Although in the long run the amplitude of the hemodynamic effect might change, unfavorable electrical asynchrony remains to have detrimental effects for a period of at least several months [18, 19].


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Although these results are promising, further studies are required to investigate whether LV apex pacing can also prevent the reduction in cardiac pump function [4] and the structural abnormalities [5] associated with chronic RV pacing, as was found with chronic His-bundle pacing in puppies [20]. For chronic application it is important to realize that little is known about lead stability, pacing thresholds, and possible complications associated with long-term LV apex pacing. In all patients in this study, an LV apical electrode could easily be inserted. However, the presence of coronary vessels or fibrous and adipose tissue could possibly hinder electrode placement. Furthermore, stimulation of the diaphragm should be excluded by testing of pacing thresholds, which tend to increase postsurgically.

Conclusion Left ventricular apex pacing acutely improves LV function as compared with pacing at the RV apex, the routinely used ventricular pacing site in children. We advocate the use of the LV apex as the site of choice for short-term ventricular pacing in children. Follow-up studies are indicated to evaluate the potential benefits of chronic LV apex versus RV apex pacing.

References 1. Prinzen FW, Peschar M. Relation between the pacing induced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol 2002;25: 484 –98. 2. de Cock CC, Giudici MC, Twisk JW. Comparison of the haemodynamic effects of right ventricular outflow-tract pacing with right ventricular apex pacing: a quantitative review. Europace 2003;5:275– 8. 3. Karpawich PP, Mital S. Comparative left ventricular function following atrial, septal, and apical single chamber heart pacing in the young. Pacing Clin Electrophysiol 1997;20: 1983– 8. 4. Tantengco MV, Thomas RL, Karpawich PP. Left ventricular dysfunction after long-term right ventricular apical pacing in the young. J Am Coll Cardiol 2001;37:2093–100. 5. Karpawich PP, Rabah R, Haas JE. Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 1999;22:1372–7. 6. Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997;96: 3273–7. 7. Puggioni E, Brignole M, Gammage M, et al. Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation. J Am Coll Cardiol 2004;43: 234 – 8. 8. Tyers GF. Optimal electrode implantation site for asynchronous dipolar cardiac pacing. Ann Surg 1968;167:168 –79. 9. Peschar M, de Swart H, Michels KJ, Reneman RS, Prinzen FW. Left ventricular septal and apex pacing for optimal pump function in canine hearts. J Am Coll Cardiol 2003;41: 1218 –26. 10. Prinzen FW, Van Oosterhout MF, Vanagt WY, Storm C, Reneman RS. Optimization of ventricular function by improving the activation sequence during ventricular pacing. Pacing Clin Electrophysiol 1998;21:2256 – 60.

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11. Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation 2000;102:3053–9. 12. Spach MS, Barr RC. Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog. Circ Res 1975;37:243–57. 13. Durrer D, van Dam RT, Freud GE, Janse MJ, Meijler FL, Arzbaecher RC. Total excitation of the isolated human heart. Circulation 1970;41:899 –912. 14. Zimmerman FJ, Starr JP, Koenig PR, Smith P, Hijazi ZM, Bacha EA. Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Ann Thorac Surg 2003;75:1775– 80. 15. Horenstein MS, Karpawich PP, Tantengco MV. Single versus dual chamber pacing in the young: noninvasive comparative evaluation of cardiac function. Pacing Clin Electrophysiol 2003;26:1208 –11.


16. Abdel-Rahman U, Kleine P, Seitz U, Moritz A. Biventricular pacing for successful weaning from extracorporal circulation in an infant with complex tetralogy of Fallot. Pediatr Cardiol 2002;23:553– 4. 17. Kleine P, Doss M, Aybek T, Wimmer-Greinecker G, Moritz A. Biventricular pacing for weaning from extracorporeal circulation in heart failure. Ann Thorac Surg 2002;73: 960 –2. 18. van Oosterhout MF, Prinzen FW, Arts T, et al. Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall. Circulation 1998;98:588 –95. 19. Yu CM, Chau E, Sanderson JE, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438 – 45. 20. Karpawich PP, Justice CD, Chang CH, Gause CY, Kuhns LR. Septal ventricular pacing in the immature canine heart: a new perspective. Am Heart J 1991;121:827–33.

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