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Advances in perioperative pacing
Advances in Perioperative Pacing Phat P. Pham and Seshadri Balaji Cardiac resynchronization therapy with biventricular pacing has become a significant management tool in adults with heart failure. In children, right rather than just left ventricular failure, is a key problem in the postoperative period. Also, congenital heart defects vary widely in their nature and prognosis. There are now preliminary reports in the literature of the use of multiple temporary pacing sites after congenital heart surgery and acute comparison of the effects of unsynchronized versus synchronized pacing in the postoperative period. These studies support the use of cardiac resynchronization pacing at least as a temporary measure in cases of acute heart failure after surgery in patients with congenital heart disease. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 8:28-33 © 2005 Elsevier Inc. All rights reserved. KEYWORDS: Cardiac resynchronization therapy, congenital heart disease, perioperative pacing, tissue Doppler imaging, right bundle-branch block, biventricular pacing
H
eart failure is defined as the inability of the heart to maintain adequate cardiac output to supply the body’s oxygen consumption demand. As a result of decreased oxygen supply to the tissues, the body reverts to anaerobic metabolism, which increases lactic acid production. Decreased cardiac output also decreases the mixed venous saturation due to the increased oxygen extraction by the tissues. As a result of the decreased perfusion pressure and supply of nutrients to the tissues, the complex feedback loop mechanism from various organs increases sympathetic tone, causing elevated heart rate, vasoconstriction, and contractility to improve perfusion. The management strategies of acute and chronic heart failure differ slightly in light of the recent understanding of the chronic exposure to sympathomimetic neurohormones. Current practices for treatment of acute heart failure include further augmenting the sympathetic tone (especially on the heart), decreasing vasoconstriction, and limiting the excess of total body fluid. In chronic heart failure, the prolonged exposure to increased sympathetic tone has detrimental effects on the heart and the vascular organs. Thus, the strategy differs by including blockade of sympathetic tone and maintaining euvolemia.1 Investigators have recently demonstrated an additional effective pacing tool for the management of acute and chronic heart failure in adult patients. Cardiac resynchronization is Oregan Health and Science University, Portland, OR. Address reprint requests to Seshadri Balaji, MD, Department of Pediatrics (Cardiology), 707 SW Gaines Rd, Mailcode CDRC-P, Portland, OR 97239.
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1092-9126/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.pcsu.2005.01.010
the use of cardiac pacing to improve cardiac output and associated symptoms in patients with congestive heart failure (CHF). It has been shown that in patients with left ventricular (LV) dysfunction and CHF, the electrical and mechanical coupling of the ventricular contraction is disorganized. The dyssynchronous contraction of the various LV wall segments in heart failure has been demonstrated using MRI, 3-D echocardiography, and tissue Doppler echocardiography.2,3 Dyssynchrony results in wasting the overall mechanical energy of the cardiac systolic cycle, leading to decreased cardiac output. By using artificial cardiac pacing with the specific placement of the leads in areas of late contraction, systolic contraction can be “resynchronized.” More importantly, the investigators showed that inappropriate placement of the pacing leads can lead to increased dyssynchrony, decreased cardiac output, and worsening heart failure symptoms.4 There are also reports of patients with conventional pacing systems who develop dilated cardiomyopathy that improves when the pacing system is changed to one that results in resynchronization. This leads some experts to think that dyssynchronous contraction is not only a result of a stretched, dilated, sick myocardium seen in chronic CHF but can occur in healthy myocardium with inappropriate myocardial activation.
Postoperative Low Cardiac Output Syndrome In the postoperative care of patients with congenital heart disease (CHD), low cardiac output syndrome (acute heart
Advances in perioperative pacing failure) is often seen in the first 24 to 48 hours. This results from multiple factors, such as residual or unrecognized structural defects, continuation of preoperative ventricular dysfunction, myocardial dysfunction related to intraoperative support techniques, type of surgical repair, complications of surgery, pulmonary hypertension, infection, dysrhythmia, or loss of normal conduction. The current strategy to manage low cardiac output is to identify the causes and stratify them as a surgical or medical. If the cause is thought to be inadequate surgery or something structural such as a residual shunt, reoperation to improve cardiac output is considered. However, when all anatomic surgical repairs are appropriate for the patient, medical management is implemented. Standard postoperative care to improve cardiac output includes optimizing preload with appropriate fluid resuscitation, improving contractility with intropes, and/or afterload reduction. Poor cardiac output associated with arrhythmias can be managed with temporary standard epicardial pacing or antiarrhythmic medications.5 In terms of risk and benefit, each strategy has inherent disadvantages or a physiologic expense. For example, using inotropic support can improve perfusion pressure and cardiac output but increases O2 consumption, which can have a counter effect on cardiac output. The mechanical support strategies, such as VAD or ECMO, have high risk of morbidity and mortality. These strategies cannot be applied for a prolonged period of time. The ideal support for postsurgical cardiac care is a strategy that would increase cardiac output with minimal risk and expense to the organs. Cardiac resynchronization therapy (CRT) is one such strategy that has been recently demonstrated in adult patients with LV dysfunction and CHF to improve cardiac output.6 Is there a role for CRT in the postoperative CHD population?
Historical Perspective on Cardiac Resynchronization Therapy The first CRT study was reported in 1983, with four patients using a LV pacing site in comparison with no pacing.7 The study’s primary endpoint was the measurement of left ventricular ejection fraction (LVEF) with radionuclide imaging. The initial results showed improvement in LVEF of ⬎25%. However, no systematic investigation was reported until 13 years later. Initial clinical studies of CRT focused on the effects of atrioventricular delay (AVD). By optimizing the AVD time between atrial and ventricular systole, investigators maximized the ventricular filling time and prevented diastolic mitral regurgitation.8 By the mid 1990s, investigators focused on the intraventicular timing and targeted ventricular dyssynchrony.9 During synchronous contraction of the LV, the timing difference between the first and the last electrical and mechanical events of the LV is not greater than 40 milliseconds in adult patients. Dyssynchronous contraction results in alteration of this timing whereby parts of the ventricle activate sooner than others, as seen with intrinsic bundle branch
29 blocks or from single site pacing. When translated to mechanical efficiency, areas of early contraction do not result in ejection, and areas of late contraction occur when the rest of the ventricle is at peak contraction or at beginning of relaxation. Thus, early or late activation and contraction result in wasted work. The end result is decreased systolic contraction and decreased cardiac output. To counteract the area of late activation, investigators directly stimulated (by pacing) the LV alone or RV and LV (also known as biventricular pacing). Multiple acute CRT studies in adults reported improved cardiac output, increased systolic pressure, lower pulmonary wedge pressure, and enhanced ventricular systolic function by increasing dP/dT and pressure volume loops.10,11 These short-term studies showed increased systolic function with decreased myocardial energy consumption and decreased sympathetic activity. The obvious evolution of successful acute studies is the application of this strategy in long-term clinical trials. There have been six large, multicenter randomized trials of CRT in adults with severe CHF.12-17 These investigators discovered similar results found in the acute studies, such as improved dP/dT, decreased QRS duration, and improved symptoms such as increased 6-minute walk distance and improved quality of life by standard questionnaires. One of the multicenter studies (COMPANION)17 was prematurely halted by the Data and Safety Monitoring Board because it had reached its primary endpoint of reduction in hospitalization and overall mortality compared with the placebo group. The FDA has approved CRT for the treatment of patients with moderate to severe CHF who are refractory to medical treatment and who have cardiac dyssynchrony as demonstrated by QRS prolongation on the ECG.
Right Ventricular Failure and Congenital Heart Disease Unlike adults with LV failure from ischemic heart disease or idiopathic dilated cardiomyopathy, in children, CHD is the main cardiac problem. In the acute postoperative period, RV dysfunction (and not just LV failure) can be a significant problem. There are few evidence-based therapeutic approaches to the failing RV. With overwhelming evidence for beneficial effects of CRT in adults with LV dysfunction and CHF, there is great interest in applying this therapy in children with LV and RV failure associated with repair of CHD.
CRT in Children Immediately After Repair of Congenital Heart Disease There are case reports of adults and children using CRT immediately after cardiac repair to help wean from extracorporeal circulation.18,19 There is some evidence for the use of CRT in children in the postoperative period after CHD repair. There have been two small studies evaluating CRT in the immediate postoperative period in children with CHD as an adjunctive treatment for acute heart failure.
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P.P. Pham and S. Balaji
Figure 1 Janousek et al20 used two standard RA leads (one active [⫺] and one indifferent [⫹]), three RV leads (RVOT [⫺], RVOT [⫹], and RV free wall [⫺]), and one LV free wall lead (⫺).
Janousek et al20 evaluated the role of atrioventricular and interventricular synchrony in 20 children with CHD repair. The study included CHD patients with biventricular cardiac repair who had atrioventricular or interventricular conduction delay and the need for inotropic support. The patients had extra temporary epicardial pacing leads in the operating room. These leads included right atrial (RA) leads, three RV leads (two RVOT, one free-wall), and one LV free-wall lead (Fig 1). The pacing maneuver was done in the pediatric ICU soon after the surgical repair. The endpoints were measurements of systolic BP, atrial pressures, and length of QRS duration. The investigators showed significant increase in systolic BP and pulse pressure and decreased atrial pressure with AV synchronization by adjustment of AV delay in dualchamber pacing. In individuals who exhibited interventricular dyssynchrony measured by prolonged QRS duration with LBBB or RBBB pattern, they were able to improve systemic BP and decrease QRS duration through multisite pacing in the RV or biventricular pacing. In individuals with RBBB, it was hypothesized that the QRS duration was narrowed by bypassing the block by simultaneously pacing the two or three RV leads. In patients with LBBB, both ventricles were paced (ie, biventricular pacing). This study also shows a correlation of decreased QRS duration with increased systemic BP. In a similar study evaluating CRT in postoperative CHD
patients, Zimmerman et al21 evaluated resynchronization in three different groups. There were two groups of two-ventricle repair patients (a group with and a group without “ventricular surgery”) and a single-ventricle repair group. RV pacing was used in the two-ventricle groups, whereas multisite pacing was used in the single-ventricle patients. Patients included in the study had preexisting RBBB or intraventricular conduction delay as a result of surgery. Lead placement included two standard RA leads and three RV leads (RVOT, RV free-wall, and lateral RV). In the single-ventricle patients, the two active ventricular leads were placed as far as possible from each other on the free wall, and the third indifferent lead was placed near the apex (Fig 2). The pacing protocol included dual-chamber pacing using DDD mode with optimization of the AVD time to attain the shortest QRS duration. All 29 patients included in the study were paced with the same protocol in the pediatric ICU except for two patients who received pacing in the operating room to assist with weaning from cardiopulmonary bypass. This study showed significant improvement in the primary end-point measurements (cardiac index [CI] using Fick method and systolic blood pressure in association with decreased QRS duration) in all three groups. However, there was no improvement on lactate level. Unlike Janousek et al’s study,20 these investigators did not see a correlation between QRS duration and CI or
Advances in perioperative pacing
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Figure 2 Zimmerman et al21 used two standard RA leads (one active [⫺] and one indifferent [⫹]) and three RV leads (RVOT [⫺], mid-anterior RV [⫹], and lateral RV [⫺]).
systolic BP. This was the first study evaluating CRT in the single-ventricle patients. The mechanism for improvement seen with multisite pacing in a univentricular heart is not well understood. The investigators hypothesized that by activating the single ventricle from the multiple sites, the different segments had more synchronous contraction. In both of these studies, patients with ventricular dyssynchrony were selected by evaluating the electrical abnormality of the conduction system. It was assumed that prolongation of the QRS duration is associated with asynchronous mechanical contraction. There have been reports in the adult population showing that a third of the CHF patients with prolonged QRS duration did not improve with CRT. Furthermore, a group of patients with short QRS duration improved significantly after initiation of CRT.22,23 This caused many experts to speculate that QRS duration might not be the best marker for dyssynchrony. Tissue Doppler imaging (TDI) has been shown to be a better modality in evaluating the ventricular mechanical properties and has been used for the evaluation of LV dyssynchrony in adults with heart failure.24 In recently presented preliminary data using TDI in children with CHD who underwent CRT immediately after surgery,25 we characterized the mechanical contraction timing of the ventricles. This study included patients with CHD under-
going a two-ventricle repair and preexisting or de novo intraventricular conduction delay with RBBB pattern on ECG. Temporary pacing leads were placed in the operating room (two standard leads in the RA, two in the RV [RV apex, RV base], and one LV lead [LV free-wall]) (Fig 3). Pacing was performed in the pediatric ICU. Atrial-only pacing from the RA leads was taken as the baseline. Standard RV pacing was done with RA and RV leads. Biventricular pacing was performed using the RA, RV, and LV leads. The AV delay for RV and biventricular pacing was set at 80% of the PR interval noted during atrial (baseline) pacing to ensure ventricular capture. Cardiac output (by Fick method), QRS duration, and TDI data were evaluated between the RA (baseline) pacing, standard atrioventricular RV pacing, and RV and LV (biventricular) pacing. The QRS duration was significantly prolonged with standard RV pacing but shortened with biventricular pacing. We found no specific blood pressure trend during the 10 minutes of pacing for each mode. CI, calculated by Fick method, was unchanged from baseline to standard RV pacing. There was a significant increase of CI with biventricular pacing. TDI data corroborated the hemodynamic data by showing ventricular dyssynchrony during standard RV pacing but resynchronization with biventricular pacing.
P.P. Pham and S. Balaji
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Figure 3 Pham et al25 used two standard RA leads (one active [⫺] and one indifferent [⫹]), two RV leads (RV base [⫺] and RV apex [⫹]), and one LV free wall lead (⫺).
RV pacing in this study did not resynchronize the RV delay, as was seen in the two previously described studies. TDI showed that standard RV pacing caused dyssynchrony with no improvement in CI. Biventricular pacing was a better mode for CRT in this group of patients. The reason for the finding that RV pacing alone did not lead to restoration of synchrony in patients with RV conduction delay in our study is unclear. There are many possible explanations. One hypothesis is that the RBBB associated with CHD surgical repair might be a peripheral block and thus contributes no significant RV delay. Another explanation is that the placement of RV pacing leads was not optimal for bypassing the RBBB. In either scenario, RV pacing in these individuals caused eccentric depolarization and dyssynchrony. The data also showed CI improvement with biventricular pacing compared with baseline pacing. TDI showed that baseline and biventricular pacing had synchronous contractions; however, although pacing was done at the same heart rate, hemodynamic data favored biventricular pacing with higher cardiac output. One potential reason for the difference could be the AV delay. The AV delay for the biventricular mode had to be shortened to 80% of the baseline atrial pacing to assure appropriate capture of ventricular sites, which may explain this significant difference in cardiac output. These three previous studies addressed the resynchroniza-
tion issues for patients with RV conduction delay and dysynchrony. In their study, Vanagt et al26 described an optimal site for perioperative pacing in CHD children with two-ventricle repair and normal atrioventricular conduction. The investigators paced eight children at three different sites (standard RV, LV free wall, and the novel LV apex) and compared it with sinus rhythm. They showed that LV apex pacing has the least detrimental effects on LV dP/dT and pulse pressure compared with sinus rhythm. In some patients LV dP/dT improved compared with baseline. The investigators hypothesized that the LV apex lead is near the distal Purkinje system. By pacing at this point, the electrical activation wave can easily propagate from the epicardium through a thin LV apex wall to the endocardium then proceeds in a basal direction where it simulates an activation pattern similiar to normal sinus rhythm. The investigators suggest that LV apex is a site of choice for short-term ventricular pacing after CHD surgery.
Implications There is evidence that biventricular pacing can be a useful tool to augment cardiac efficiency in patients after repair of congenital heart defects. This argues for the placement of additional temporary pacing leads in patients thought to be
Advances in perioperative pacing likely to have a difficult postoperative period. Usually this implies placing an extra lead on the LV surface. The technical difficulty of placing this lead has to be balanced in each case against the benefit expected from pacing. Whether the shortterm benefit demonstrated by acute studies will be maintained on the long term remains to be shown. There are a number of unanswered questions about this new approach to pacing. The question of whether RV pacing alone is sufficient in patients with RBBB remains to be answered. Also, the optimal site for RV pacing is unknown. Many adult studies have shown nonresponders. Why some patients do not respond to this approach remains to be elucidated. The role of intraoperative tissue Doppler echo to identify the best site for pacing leads needs evaluation. Despite many caveats, CRT has shown potential to be an adjunctive tool for managing patients with postoperative acute cardiac failure and should be considered in all such patients.
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References 1. Packer M, Coats AJ, Fowler MB, et al: Effect of carvedilol on survival in severe chronic heart failure. New Engl J Med 344:1651-1658, 2001 2. Szili-Torok T, Jordaens LJ, Bruining N, et al: Dynamic three-dimensional echocardiography offers advantages for specific site pacing. Circulation 107:e30, 2003 3. Sogaard P, Egeblad H, Pedersen AK, et al: Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation 106:2078-2084, 2002 4. Dekker AL, Phelps B, Dijkman B, et al: Epicardial left ventricular lead placement for cardiac resynchronization therapy: Optimal pace site selection with pressure-volume loops. J Thorac Cardiovasc Surg 127: 1641-1647, 2004 5. Roth S: Postoperative care, in Chang A, Hanley FL, Wernovsky G, Wessel D (eds): Pediatric Cardiac Intensive Care. Baltimore, MD, Williams & Wilkins, 1998, pp 163-188 6. Abraham WT, Fisher WG, Smith AL, et al: Evaluation MSGMIRC: Cardiac resynchronization in chronic heart failure. New Engl J Med 346:1845-1853, 2002 7. De Teresa PCJ: An even more physiological pacing: Changing the sequence of ventricular activation. Presented at the VIIth World Symposium of Cardiac Pacing 8. Gold M, Feliciano Z, Gottlieb S, et al: Dual-chamber pacing with a short atrioventricular delay in congestive heart failure: A randomized study. J Am Coll Cardiol 26:967-973, 1995 9. 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 96:3273-3277, 1997 10. Kass DA, Chen CH, Curry C, et al: Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 99:15671573, 1999 11. Leclercq C, Cazeau S, Le Breton H, et al: Acute hemodynamic effects of
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19.
20.
21.
22.
23.
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biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol 32:1825-1831, 1988 Auricchio A, Stellbrink C, Sack S, et al: The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: Rationale, design, and endpoints of a prospective randomized multicenter study. Am J Cardiol 83:130D-135D, 1999 Abraham WT: Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: The Multicenter InSync Randomized Clinical Evaluation (MIRACLE). J Card Fail 6:369-380, 2000 Linde C, Leclercq C, Rex S, et al: Long-term benefits of biventricular pacing in congestive heart failure: Results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol 40:111118, 2002 Gras D, Mabo P, Tang T, et al: Multisite pacing as a supplemental treatment of congestive heart failure: Preliminary results of the Medtronic Inc. InSync Study. Pacing Clin Electrophysiol 21:22492255, 1998 Saxon LA, Boehmer JP, Hummel J, et al: Biventricular pacing in patients with congestive heart failure: two prospective randomized trials. The VIGOR CHF and VENTAK CHF Investigators. Am J Cardiol 83:120D123D, 1999 Bristow MR, Feldman AM, Saxon LA: Heart failure management using implantable devices for ventricular resynchronization: Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. COMPANION Steering Committee and COMPANION Clinical Investigators. J Card Fail 6:276285, 2000 Abdel-Rahman U, Kleine P, Seitz U, et al: Biventricular pacing for successful weaning from extracorporal circulation in an infant with complex tetralogy of Fallot. Pediatr Cardiol 23:553-554, 2002 Foster A, Gold M, McLaughlin J: Acute hemodynamic effects of atriobiventricular pacing in humans. Ann Thorac Surg 59:294-300, 1995 Janousek J, Vojtovic P, Hucin B, et al: Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects. Am J Cardiol 88:145-152, 2001 Zimmerman FJ, Starr JP, Koenig PR, et al: Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Ann Thorac Surg 75:1775-1780, 2003 Gasparini M, Mantica M, Galimberti P, et al: Beneficial effects of biventricular pacing in patients with a “narrow” QRS. Pacing Clin Electrophysiol 26:169-174, 2003 Achilli A, Sassara M, Ficili S, et al: Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and “narrow” QRS. J Am Coll Cardiol 42:2117-2124, 2003 Sogaard P, Egeblad H, Kim WY, et al: Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 40:723-730, 2002 Pham P, Balaji S, Shen I, et al: Impact of conventional versus biventricular pacing on hemodynamics and tissue Doppler imaging indices of resynchronization in post-operative children with right ventricular conduction delay [abstract]. Circulation 110(suppl III):III-761, 2004 Vanagt WY, Verbeek XA, Delhaas T, et al: Acute hemodynamic benefit of left ventricular apex pacing in children. Ann Thorac Surg 79:932936, 2005
H
eart failure is defined as the inability of the heart to maintain adequate cardiac output to supply the body’s oxygen consumption demand. As a result of decreased oxygen supply to the tissues, the body reverts to anaerobic metabolism, which increases lactic acid production. Decreased cardiac output also decreases the mixed venous saturation due to the increased oxygen extraction by the tissues. As a result of the decreased perfusion pressure and supply of nutrients to the tissues, the complex feedback loop mechanism from various organs increases sympathetic tone, causing elevated heart rate, vasoconstriction, and contractility to improve perfusion. The management strategies of acute and chronic heart failure differ slightly in light of the recent understanding of the chronic exposure to sympathomimetic neurohormones. Current practices for treatment of acute heart failure include further augmenting the sympathetic tone (especially on the heart), decreasing vasoconstriction, and limiting the excess of total body fluid. In chronic heart failure, the prolonged exposure to increased sympathetic tone has detrimental effects on the heart and the vascular organs. Thus, the strategy differs by including blockade of sympathetic tone and maintaining euvolemia.1 Investigators have recently demonstrated an additional effective pacing tool for the management of acute and chronic heart failure in adult patients. Cardiac resynchronization is Oregan Health and Science University, Portland, OR. Address reprint requests to Seshadri Balaji, MD, Department of Pediatrics (Cardiology), 707 SW Gaines Rd, Mailcode CDRC-P, Portland, OR 97239.
28
1092-9126/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.pcsu.2005.01.010
the use of cardiac pacing to improve cardiac output and associated symptoms in patients with congestive heart failure (CHF). It has been shown that in patients with left ventricular (LV) dysfunction and CHF, the electrical and mechanical coupling of the ventricular contraction is disorganized. The dyssynchronous contraction of the various LV wall segments in heart failure has been demonstrated using MRI, 3-D echocardiography, and tissue Doppler echocardiography.2,3 Dyssynchrony results in wasting the overall mechanical energy of the cardiac systolic cycle, leading to decreased cardiac output. By using artificial cardiac pacing with the specific placement of the leads in areas of late contraction, systolic contraction can be “resynchronized.” More importantly, the investigators showed that inappropriate placement of the pacing leads can lead to increased dyssynchrony, decreased cardiac output, and worsening heart failure symptoms.4 There are also reports of patients with conventional pacing systems who develop dilated cardiomyopathy that improves when the pacing system is changed to one that results in resynchronization. This leads some experts to think that dyssynchronous contraction is not only a result of a stretched, dilated, sick myocardium seen in chronic CHF but can occur in healthy myocardium with inappropriate myocardial activation.
Postoperative Low Cardiac Output Syndrome In the postoperative care of patients with congenital heart disease (CHD), low cardiac output syndrome (acute heart
Advances in perioperative pacing failure) is often seen in the first 24 to 48 hours. This results from multiple factors, such as residual or unrecognized structural defects, continuation of preoperative ventricular dysfunction, myocardial dysfunction related to intraoperative support techniques, type of surgical repair, complications of surgery, pulmonary hypertension, infection, dysrhythmia, or loss of normal conduction. The current strategy to manage low cardiac output is to identify the causes and stratify them as a surgical or medical. If the cause is thought to be inadequate surgery or something structural such as a residual shunt, reoperation to improve cardiac output is considered. However, when all anatomic surgical repairs are appropriate for the patient, medical management is implemented. Standard postoperative care to improve cardiac output includes optimizing preload with appropriate fluid resuscitation, improving contractility with intropes, and/or afterload reduction. Poor cardiac output associated with arrhythmias can be managed with temporary standard epicardial pacing or antiarrhythmic medications.5 In terms of risk and benefit, each strategy has inherent disadvantages or a physiologic expense. For example, using inotropic support can improve perfusion pressure and cardiac output but increases O2 consumption, which can have a counter effect on cardiac output. The mechanical support strategies, such as VAD or ECMO, have high risk of morbidity and mortality. These strategies cannot be applied for a prolonged period of time. The ideal support for postsurgical cardiac care is a strategy that would increase cardiac output with minimal risk and expense to the organs. Cardiac resynchronization therapy (CRT) is one such strategy that has been recently demonstrated in adult patients with LV dysfunction and CHF to improve cardiac output.6 Is there a role for CRT in the postoperative CHD population?
Historical Perspective on Cardiac Resynchronization Therapy The first CRT study was reported in 1983, with four patients using a LV pacing site in comparison with no pacing.7 The study’s primary endpoint was the measurement of left ventricular ejection fraction (LVEF) with radionuclide imaging. The initial results showed improvement in LVEF of ⬎25%. However, no systematic investigation was reported until 13 years later. Initial clinical studies of CRT focused on the effects of atrioventricular delay (AVD). By optimizing the AVD time between atrial and ventricular systole, investigators maximized the ventricular filling time and prevented diastolic mitral regurgitation.8 By the mid 1990s, investigators focused on the intraventicular timing and targeted ventricular dyssynchrony.9 During synchronous contraction of the LV, the timing difference between the first and the last electrical and mechanical events of the LV is not greater than 40 milliseconds in adult patients. Dyssynchronous contraction results in alteration of this timing whereby parts of the ventricle activate sooner than others, as seen with intrinsic bundle branch
29 blocks or from single site pacing. When translated to mechanical efficiency, areas of early contraction do not result in ejection, and areas of late contraction occur when the rest of the ventricle is at peak contraction or at beginning of relaxation. Thus, early or late activation and contraction result in wasted work. The end result is decreased systolic contraction and decreased cardiac output. To counteract the area of late activation, investigators directly stimulated (by pacing) the LV alone or RV and LV (also known as biventricular pacing). Multiple acute CRT studies in adults reported improved cardiac output, increased systolic pressure, lower pulmonary wedge pressure, and enhanced ventricular systolic function by increasing dP/dT and pressure volume loops.10,11 These short-term studies showed increased systolic function with decreased myocardial energy consumption and decreased sympathetic activity. The obvious evolution of successful acute studies is the application of this strategy in long-term clinical trials. There have been six large, multicenter randomized trials of CRT in adults with severe CHF.12-17 These investigators discovered similar results found in the acute studies, such as improved dP/dT, decreased QRS duration, and improved symptoms such as increased 6-minute walk distance and improved quality of life by standard questionnaires. One of the multicenter studies (COMPANION)17 was prematurely halted by the Data and Safety Monitoring Board because it had reached its primary endpoint of reduction in hospitalization and overall mortality compared with the placebo group. The FDA has approved CRT for the treatment of patients with moderate to severe CHF who are refractory to medical treatment and who have cardiac dyssynchrony as demonstrated by QRS prolongation on the ECG.
Right Ventricular Failure and Congenital Heart Disease Unlike adults with LV failure from ischemic heart disease or idiopathic dilated cardiomyopathy, in children, CHD is the main cardiac problem. In the acute postoperative period, RV dysfunction (and not just LV failure) can be a significant problem. There are few evidence-based therapeutic approaches to the failing RV. With overwhelming evidence for beneficial effects of CRT in adults with LV dysfunction and CHF, there is great interest in applying this therapy in children with LV and RV failure associated with repair of CHD.
CRT in Children Immediately After Repair of Congenital Heart Disease There are case reports of adults and children using CRT immediately after cardiac repair to help wean from extracorporeal circulation.18,19 There is some evidence for the use of CRT in children in the postoperative period after CHD repair. There have been two small studies evaluating CRT in the immediate postoperative period in children with CHD as an adjunctive treatment for acute heart failure.
30
P.P. Pham and S. Balaji
Figure 1 Janousek et al20 used two standard RA leads (one active [⫺] and one indifferent [⫹]), three RV leads (RVOT [⫺], RVOT [⫹], and RV free wall [⫺]), and one LV free wall lead (⫺).
Janousek et al20 evaluated the role of atrioventricular and interventricular synchrony in 20 children with CHD repair. The study included CHD patients with biventricular cardiac repair who had atrioventricular or interventricular conduction delay and the need for inotropic support. The patients had extra temporary epicardial pacing leads in the operating room. These leads included right atrial (RA) leads, three RV leads (two RVOT, one free-wall), and one LV free-wall lead (Fig 1). The pacing maneuver was done in the pediatric ICU soon after the surgical repair. The endpoints were measurements of systolic BP, atrial pressures, and length of QRS duration. The investigators showed significant increase in systolic BP and pulse pressure and decreased atrial pressure with AV synchronization by adjustment of AV delay in dualchamber pacing. In individuals who exhibited interventricular dyssynchrony measured by prolonged QRS duration with LBBB or RBBB pattern, they were able to improve systemic BP and decrease QRS duration through multisite pacing in the RV or biventricular pacing. In individuals with RBBB, it was hypothesized that the QRS duration was narrowed by bypassing the block by simultaneously pacing the two or three RV leads. In patients with LBBB, both ventricles were paced (ie, biventricular pacing). This study also shows a correlation of decreased QRS duration with increased systemic BP. In a similar study evaluating CRT in postoperative CHD
patients, Zimmerman et al21 evaluated resynchronization in three different groups. There were two groups of two-ventricle repair patients (a group with and a group without “ventricular surgery”) and a single-ventricle repair group. RV pacing was used in the two-ventricle groups, whereas multisite pacing was used in the single-ventricle patients. Patients included in the study had preexisting RBBB or intraventricular conduction delay as a result of surgery. Lead placement included two standard RA leads and three RV leads (RVOT, RV free-wall, and lateral RV). In the single-ventricle patients, the two active ventricular leads were placed as far as possible from each other on the free wall, and the third indifferent lead was placed near the apex (Fig 2). The pacing protocol included dual-chamber pacing using DDD mode with optimization of the AVD time to attain the shortest QRS duration. All 29 patients included in the study were paced with the same protocol in the pediatric ICU except for two patients who received pacing in the operating room to assist with weaning from cardiopulmonary bypass. This study showed significant improvement in the primary end-point measurements (cardiac index [CI] using Fick method and systolic blood pressure in association with decreased QRS duration) in all three groups. However, there was no improvement on lactate level. Unlike Janousek et al’s study,20 these investigators did not see a correlation between QRS duration and CI or
Advances in perioperative pacing
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Figure 2 Zimmerman et al21 used two standard RA leads (one active [⫺] and one indifferent [⫹]) and three RV leads (RVOT [⫺], mid-anterior RV [⫹], and lateral RV [⫺]).
systolic BP. This was the first study evaluating CRT in the single-ventricle patients. The mechanism for improvement seen with multisite pacing in a univentricular heart is not well understood. The investigators hypothesized that by activating the single ventricle from the multiple sites, the different segments had more synchronous contraction. In both of these studies, patients with ventricular dyssynchrony were selected by evaluating the electrical abnormality of the conduction system. It was assumed that prolongation of the QRS duration is associated with asynchronous mechanical contraction. There have been reports in the adult population showing that a third of the CHF patients with prolonged QRS duration did not improve with CRT. Furthermore, a group of patients with short QRS duration improved significantly after initiation of CRT.22,23 This caused many experts to speculate that QRS duration might not be the best marker for dyssynchrony. Tissue Doppler imaging (TDI) has been shown to be a better modality in evaluating the ventricular mechanical properties and has been used for the evaluation of LV dyssynchrony in adults with heart failure.24 In recently presented preliminary data using TDI in children with CHD who underwent CRT immediately after surgery,25 we characterized the mechanical contraction timing of the ventricles. This study included patients with CHD under-
going a two-ventricle repair and preexisting or de novo intraventricular conduction delay with RBBB pattern on ECG. Temporary pacing leads were placed in the operating room (two standard leads in the RA, two in the RV [RV apex, RV base], and one LV lead [LV free-wall]) (Fig 3). Pacing was performed in the pediatric ICU. Atrial-only pacing from the RA leads was taken as the baseline. Standard RV pacing was done with RA and RV leads. Biventricular pacing was performed using the RA, RV, and LV leads. The AV delay for RV and biventricular pacing was set at 80% of the PR interval noted during atrial (baseline) pacing to ensure ventricular capture. Cardiac output (by Fick method), QRS duration, and TDI data were evaluated between the RA (baseline) pacing, standard atrioventricular RV pacing, and RV and LV (biventricular) pacing. The QRS duration was significantly prolonged with standard RV pacing but shortened with biventricular pacing. We found no specific blood pressure trend during the 10 minutes of pacing for each mode. CI, calculated by Fick method, was unchanged from baseline to standard RV pacing. There was a significant increase of CI with biventricular pacing. TDI data corroborated the hemodynamic data by showing ventricular dyssynchrony during standard RV pacing but resynchronization with biventricular pacing.
P.P. Pham and S. Balaji
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Figure 3 Pham et al25 used two standard RA leads (one active [⫺] and one indifferent [⫹]), two RV leads (RV base [⫺] and RV apex [⫹]), and one LV free wall lead (⫺).
RV pacing in this study did not resynchronize the RV delay, as was seen in the two previously described studies. TDI showed that standard RV pacing caused dyssynchrony with no improvement in CI. Biventricular pacing was a better mode for CRT in this group of patients. The reason for the finding that RV pacing alone did not lead to restoration of synchrony in patients with RV conduction delay in our study is unclear. There are many possible explanations. One hypothesis is that the RBBB associated with CHD surgical repair might be a peripheral block and thus contributes no significant RV delay. Another explanation is that the placement of RV pacing leads was not optimal for bypassing the RBBB. In either scenario, RV pacing in these individuals caused eccentric depolarization and dyssynchrony. The data also showed CI improvement with biventricular pacing compared with baseline pacing. TDI showed that baseline and biventricular pacing had synchronous contractions; however, although pacing was done at the same heart rate, hemodynamic data favored biventricular pacing with higher cardiac output. One potential reason for the difference could be the AV delay. The AV delay for the biventricular mode had to be shortened to 80% of the baseline atrial pacing to assure appropriate capture of ventricular sites, which may explain this significant difference in cardiac output. These three previous studies addressed the resynchroniza-
tion issues for patients with RV conduction delay and dysynchrony. In their study, Vanagt et al26 described an optimal site for perioperative pacing in CHD children with two-ventricle repair and normal atrioventricular conduction. The investigators paced eight children at three different sites (standard RV, LV free wall, and the novel LV apex) and compared it with sinus rhythm. They showed that LV apex pacing has the least detrimental effects on LV dP/dT and pulse pressure compared with sinus rhythm. In some patients LV dP/dT improved compared with baseline. The investigators hypothesized that the LV apex lead is near the distal Purkinje system. By pacing at this point, the electrical activation wave can easily propagate from the epicardium through a thin LV apex wall to the endocardium then proceeds in a basal direction where it simulates an activation pattern similiar to normal sinus rhythm. The investigators suggest that LV apex is a site of choice for short-term ventricular pacing after CHD surgery.
Implications There is evidence that biventricular pacing can be a useful tool to augment cardiac efficiency in patients after repair of congenital heart defects. This argues for the placement of additional temporary pacing leads in patients thought to be
Advances in perioperative pacing likely to have a difficult postoperative period. Usually this implies placing an extra lead on the LV surface. The technical difficulty of placing this lead has to be balanced in each case against the benefit expected from pacing. Whether the shortterm benefit demonstrated by acute studies will be maintained on the long term remains to be shown. There are a number of unanswered questions about this new approach to pacing. The question of whether RV pacing alone is sufficient in patients with RBBB remains to be answered. Also, the optimal site for RV pacing is unknown. Many adult studies have shown nonresponders. Why some patients do not respond to this approach remains to be elucidated. The role of intraoperative tissue Doppler echo to identify the best site for pacing leads needs evaluation. Despite many caveats, CRT has shown potential to be an adjunctive tool for managing patients with postoperative acute cardiac failure and should be considered in all such patients.
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References 1. Packer M, Coats AJ, Fowler MB, et al: Effect of carvedilol on survival in severe chronic heart failure. New Engl J Med 344:1651-1658, 2001 2. Szili-Torok T, Jordaens LJ, Bruining N, et al: Dynamic three-dimensional echocardiography offers advantages for specific site pacing. Circulation 107:e30, 2003 3. Sogaard P, Egeblad H, Pedersen AK, et al: Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation 106:2078-2084, 2002 4. Dekker AL, Phelps B, Dijkman B, et al: Epicardial left ventricular lead placement for cardiac resynchronization therapy: Optimal pace site selection with pressure-volume loops. J Thorac Cardiovasc Surg 127: 1641-1647, 2004 5. Roth S: Postoperative care, in Chang A, Hanley FL, Wernovsky G, Wessel D (eds): Pediatric Cardiac Intensive Care. Baltimore, MD, Williams & Wilkins, 1998, pp 163-188 6. Abraham WT, Fisher WG, Smith AL, et al: Evaluation MSGMIRC: Cardiac resynchronization in chronic heart failure. New Engl J Med 346:1845-1853, 2002 7. De Teresa PCJ: An even more physiological pacing: Changing the sequence of ventricular activation. Presented at the VIIth World Symposium of Cardiac Pacing 8. Gold M, Feliciano Z, Gottlieb S, et al: Dual-chamber pacing with a short atrioventricular delay in congestive heart failure: A randomized study. J Am Coll Cardiol 26:967-973, 1995 9. 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 96:3273-3277, 1997 10. Kass DA, Chen CH, Curry C, et al: Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 99:15671573, 1999 11. Leclercq C, Cazeau S, Le Breton H, et al: Acute hemodynamic effects of
18.
19.
20.
21.
22.
23.
24.
25.
26.
biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol 32:1825-1831, 1988 Auricchio A, Stellbrink C, Sack S, et al: The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: Rationale, design, and endpoints of a prospective randomized multicenter study. Am J Cardiol 83:130D-135D, 1999 Abraham WT: Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: The Multicenter InSync Randomized Clinical Evaluation (MIRACLE). J Card Fail 6:369-380, 2000 Linde C, Leclercq C, Rex S, et al: Long-term benefits of biventricular pacing in congestive heart failure: Results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol 40:111118, 2002 Gras D, Mabo P, Tang T, et al: Multisite pacing as a supplemental treatment of congestive heart failure: Preliminary results of the Medtronic Inc. InSync Study. Pacing Clin Electrophysiol 21:22492255, 1998 Saxon LA, Boehmer JP, Hummel J, et al: Biventricular pacing in patients with congestive heart failure: two prospective randomized trials. The VIGOR CHF and VENTAK CHF Investigators. Am J Cardiol 83:120D123D, 1999 Bristow MR, Feldman AM, Saxon LA: Heart failure management using implantable devices for ventricular resynchronization: Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. COMPANION Steering Committee and COMPANION Clinical Investigators. J Card Fail 6:276285, 2000 Abdel-Rahman U, Kleine P, Seitz U, et al: Biventricular pacing for successful weaning from extracorporal circulation in an infant with complex tetralogy of Fallot. Pediatr Cardiol 23:553-554, 2002 Foster A, Gold M, McLaughlin J: Acute hemodynamic effects of atriobiventricular pacing in humans. Ann Thorac Surg 59:294-300, 1995 Janousek J, Vojtovic P, Hucin B, et al: Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects. Am J Cardiol 88:145-152, 2001 Zimmerman FJ, Starr JP, Koenig PR, et al: Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Ann Thorac Surg 75:1775-1780, 2003 Gasparini M, Mantica M, Galimberti P, et al: Beneficial effects of biventricular pacing in patients with a “narrow” QRS. Pacing Clin Electrophysiol 26:169-174, 2003 Achilli A, Sassara M, Ficili S, et al: Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and “narrow” QRS. J Am Coll Cardiol 42:2117-2124, 2003 Sogaard P, Egeblad H, Kim WY, et al: Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 40:723-730, 2002 Pham P, Balaji S, Shen I, et al: Impact of conventional versus biventricular pacing on hemodynamics and tissue Doppler imaging indices of resynchronization in post-operative children with right ventricular conduction delay [abstract]. Circulation 110(suppl III):III-761, 2004 Vanagt WY, Verbeek XA, Delhaas T, et al: Acute hemodynamic benefit of left ventricular apex pacing in children. Ann Thorac Surg 79:932936, 2005