Bi-ventricular pacing in congestive cardiac failure

Transcription

1 European Heart Journal (2000) 21, doi: /euhj , available online at on Review Article Bi-ventricular pacing in congestive cardiac failure Current experience and future directions S. Walker, T. M. Levy, A. J. S. Coats, N. S. Peters and V. E. Paul on behalf of the Imperial College Cardiac Electrophysiology Group, Imperial College, London, U.K. Introduction Despite many recent advances in the medical management of congestive cardiac failure, specifically with angiotensin-converting enzyme inhibition and betablockade, the prognosis and quality of life of patients with heart failure remains poor. Recent reports have suggested that intervention with biventricular pacing may help a subgroup of patients with heart failure. The intention of this review article was to summarize and comment upon the current evidence supporting the use of biventricular pacing for medically refractory congestive cardiac failure. We have also outlined future clinical and research directions for this new, but as yet unproven, therapeutic approach. Background The incidence and prevalence of congestive cardiac failure is increasing due to improved survival from both myocardial infarction and hypertension. In Europe a prevalence of cardiac failure of around 3 9% [1] has been reported with an annual incidence of around 1 3 cases per 1000 population aged over 25 years per year, rising to 11 6 cases per year in those over 85 years [2]. Drug therapies including angiotensin-converting enzyme inhibitors [3], beta-blockers [4] and digoxin [5] have improved the survival and functional class of patients with ventricular failure, but nevertheless many patients remain markedly symptomatic despite maximal medical therapy [6,7]. Furthermore patients with left ventricular failure are at high risk of death, mediated by progressive failure or sudden death, despite optimal medical management [3,8 10]. Key Words: Heart failure, biventricular pacing. Revision submitted 8 August 1999, and accepted 18 August Correspondence: Dr S. Walker, Department of Cardiology, Harefield Hospital, Royal Brompton and Harefield NHS Trust, Uxbridge, Middlesex UB9 6JH, U.K X/00/ $35.00/0 A significant minority of patients with congestive failure have marked prolongation of the QRS complex of the ECG [11,12]. This prolongation of the QRS complex, acting as a marker of inter-ventricular conduction abnormality, is a specific indicator of decreased left ventricular systolic function [13]. In addition the development of new QRS prolongation is associated with deterioration in patients with known left ventricular disease [14 16]. It has been demonstrated that QRS duration broadens as the severity of left ventricular failure worsens [17], whilst a number of authors have also demonstrated that a broad QRS complex is an independent marker for increased risk of death in heart failure patients [18 20]. It has been proposed that resynchronization of abnormal atrioventricular and inter-ventricular asynchrony with biventricular pacing may symptomatically improve patients with medically refractory ventricular failure. The potential mechanisms for improvement include restoration of left ventricular septal mechanical synchrony, reduction in pre-systolic mitral regurgitation and optimization of diastolic function, with the maximization of diastolic filling time [21,22]. In this report we discuss the current experience with biventricular pacing in the management of medically refractory left ventricular failure and summarize the ongoing studies investigating this novel therapeutic modality. Initial experience with biventricular pacing Cazeau and Bakker published the first case reports, introducing left ventricular pacing, in 1994 [22,23]. They described the beneficial use of biventricular pacing systems for NYHA functional class III/IV congestive cardiac failure in association with QRS prolongation. In the patients described left ventricular pacing was achieved with thoracoscopic epicardial lead placement. In 1995 the results of acute haemodynamic studies, undertaken in 18 surgical patients comparing atrial, 2000 The European Society of Cardiology

2 Review 885 right ventricular, left ventricular and biventricular temporary pacing h after elective coronary artery bypass grafting (CABG), were reported [24]. The authors discovered that atriobiventricular pacing, with a fixed atrioventricular delay of 150 msec, improved cardiac output and decreased systemic vascular resistance compared with atrial, atrio-right ventricular or atrio-left ventricular dual chamber pacing. Further clinical and acute haemodynamic evidence for the potential benefits of left ventricular stimulation came with the publication of the early experience of multisite pacing for end-stage heart failure in eight patients [25]. Biventricular pacing increased the mean cardiac index, decreased the mean V wave and decreased pulmonary capillary wedge pressure when compared with right sided pacing (apex, septum and outflow tract). This report, however, describes a high early mortality with this technique. This can be explained by the severity of the patients left ventricular impairment at inclusion into the study and by the associated risk of thoracoscopic left ventricular lead placement. In an attempt to elucidate the underlying haemodynamic changes resulting in these observed benefits two acute studies of the effects of biventricular pacing were subsequently reported. Blanc et al. [26] report the results of an evaluation of the haemodynamic effects of pacing at different ventricular sites in patients with systolic left ventricular impairment, whereas Saxon et al. [21] investigated the echocardiographic response to right ventricular apical, right ventricular outflow tract, left ventricular apical and biventricular temporary pacing in 11 patients with depressed left ventricular function undergoing cardiac surgery. The authors of the first study report that with both biventricular pacing and left ventricular pacing alone there were significant improvements in systemic blood pressure, pulmonary capillary wedge pressure and V wave amplitude as measured by invasive right heart catheterization compared with baseline measurements and right ventricular pacing alone. Similar results have subsequently been confirmed by a separate group, although these authors investigated biventricular pacing but not left ventricular pacing alone [27]. Saxon s group reported that echocardiographic ejection fraction improved with biventricular pacing but not with other pacing modes. In addition, biventricular pacing restored normal segmental left ventricular contraction sequence when compared to baseline ventricular activation. Experience with transvenous biventricular pacing The feasibility of biventricular pacing was increased when in 1998 Daubert et al. published the results of an assessment of a fully transvenous permanent biventricular pacing system [28]. This was an important advance in view of the surgical morbidity and mortality associated with thoracoscopic lead placement. The transvenous system initially employed a number of slim bodied non-specific unipolar pacing leads for left ventricular capture, but subsequently used a specifically designed left ventricular pacing lead the Medtronic 2188 (Medtronic Inc, MN, U.S.A.), inserted into a left ventricular vein via the coronary sinus. The use of this system also avoids the known problems of long-term epicardial pacing of increasing pacing thresholds and high risk of exit block [29]. The authors conclude that permanent left ventricular transvenous pacing is possible (Figs 1 and 2) in most patients, with good safety and long-term results. Following on from these results, a large multicentre study investigating the safety and efficacy of biventricular pacing in left ventricular failure has reported its initial results. The InSync study is a Canadian and European trial investigating the effects of biventricular pacing in patients with NYHA functional class III/IV heart failure. It is a non-randomized un-blinded study. Although full results are awaited the preliminary results have been published [30]. Over a 10-month period, 68 of the 81 patients enrolled underwent satisfactory biventricular pacing. No system related implant complication occurred. Thirteen of the patients have died during follow-up. In the survivors there was a clinical benefit from pacing, corroborated by a significant improvement of a mean of 1 NYHA functional class, and significant improvements in Minnesota living with heart failure questionnaire results and distance covered in a 6-min walk test. Future directions in biventricular pacing There are a number of biventricular pacing issues that remain to be addressed. The beneficial functional effects of biventricular pacing need to be confirmed in randomized, controlled studies. Furthermore the optimal configuration for biventricular pacing also needs to be considered. Considerations include the optimal site for left ventricular pacing, whether left ventricular pacing alone can be as beneficial as biventricular pacing and whether certain patient groups can be pre-selected as likely to benefit from biventricular pacing. The combined use of biventricular pacemakers and implantable cardioverter defibrillators also needs to be addressed. Lastly, and most importantly, the safety of biventricular pacing must be confirmed in large randomized mortality studies. Ongoing studies of bi-ventricular pacing in heart failure Randomized, blinded investigations into the efficacy of biventricular pacing are underway. The Multi-Site Stimulation in Cardiomyopathy MUSTIC [31] and Multi-center InSync Randomized Clinical Evaluation MIRACLE studies are both prospective randomized,

3 886 S. Walker et al. Figure 1 Coronary sinus angiogram, taken with a balloon occlusive catheter, demonstrating typical coronary sinus anatomy. From inferiorly, the tributaries of the coronary sinus identified are the mid-cardiac vein, postero-lateral cardiac vein, lateral cardiac vein and great cardiac vein. Previously inserted right ventricular pacing lead is visible. blinded controlled studies comparing no pacing with biventricular pacing in patients with severe congestive cardiac failure and sinus rhythm. In addition, the MUSTIC study is investigating the effects of biventricular pacing compared to right ventricular pacing in patients with congestive cardiac failure and previous His ablation for medically refractory atrial fibrillation. Both studies utilize transvenous endocardial left ventricular pacing via the tributaries of the coronary sinus. The results of both are due in the year The Pacing Therapies for Congestive Heart Failure (PATH CHF) study has a more complicated design, with a blinded randomized crossover comparison of biventricular pacing with the best univentricular pacing mode, as determined by acute haemodynamic testing at implant. To enable this protocol to be followed, the patients in this study have two DDD pacemakers implanted, one with a right ventricular lead and one with an epicardial left ventricular lead positioned thorascopically. The VIGOR Congestive Heart Failure (VIGOR CHF) study prospectively randomizes patients between biventricular pacing and no pacing followed by longer-term follow-up with pacing in both groups. Again this study utilizes epicardial left ventricular pacing leads placed thorascopically [32]. The PATH-CHF study has reported its initial results [33], which demonstrate a non-significant trend towards benefit from biventricular pacing when compared to no pacing. Furthermore there was no difference between biventricular and best univentricular pacing. Future directions in bi-ventricular pacing research The optimal site for left ventricular lead placement for biventricular pacing is still to be determined. However, inter-patient retrospective analysis of the acute implantation data of the first 25 patients implanted as part of the PATH CHF study have shown that optimal acute haemodynamic change is produced with mid-lateral epicardial left ventricular pacing [33]. Preliminary results of implantation analysis of the haemodynamic effects of pacing each of five further patients at different sites have confirmed the mid-lateral wall as the optimal pacing site. In addition, better haemodynamic results were obtained with apical or mid-anterior sites when compared to basal stimulation [34]. Whilst these early results emphasize the need for careful left ventricular lead placement, these optimal sites are not accessible in many patients due to the constraints of current lead technology. In an attempt to overcome this difficulty, leads positioned using coronary angioplasty technology are under investigation. These leads may offer access to, and stability within, veins otherwise inaccessible to the

4 Review 887 Figure 2 Final left and right ventricular lead positions in the same patient as in Fig 1. The left ventricular lead is positioned in the great cardiac vein. pacing specialist. The Guidant Easy-Track system (Guidant, St Paul, MN, U.S.A.) has been tested in animals and humans with satisfactory early results [35]. This over-the-wire lead is disadvantaged, however, as it has a hollow lumen, open to the blood stream throughout its length, which is likely to become thrombozed during chronic use. This has potential long-term problems associated with infective risk and lead removal. The Medtronic lead (Medtronic Inc, MN, U.S.A.) utilizes a side-wire design with the guidewire passing through a specifically modified lead tip only, and not throughout the whole length of the lead [36]. This may make the lead more difficult to position but avoids the potential complications of an open lead lumen. More studies are required with both types of design to fully elucidate the potential benefits and pitfalls of these leads. However, the increased choice of final left ventricular lead position that these leads may offer will have important implications as regards the final left ventricular pacing site chosen for optimal haemodynamic benefit. Whilst a number of authors have demonstrated the acute haemodynamic superiority of biventricular over right ventricular pacing [21,25,37] it is still unclear whether lone left ventricular pacing can offer the same benefits as biventricular stimulation. Acute haemodynamic comparison of left and biventricular pacing has shown equivalent or even superior improvement with left ventricular pacing [26]. Furthermore in longer-term use the PATH CHF preliminary results indicate that best univentricular pacing may be equivalent to biventricular pacing [33]. Publication of the full results of this study is awaited. There are no other longer-term data to support lone left ventricular pacing and further studies are required in this area. The final area of consideration regards patient identification for biventricular pacing. Proposed indicators of subsequent beneficial effects include baseline QRS width [38], degree of QRS shortening with biventricular pacing [3940] and baseline NYHA III/IV symptoms [41]. Indices that fail to predict responders to biventricular pacing include baseline ECG PRinterval [42] and aetiology of heart failure (ischaemic vs dilated cardiomyopathy) [42]. Future directions in the identification of patients for biventricular pacing include further attempts to identify responders before implantation is undertaken, to avoid unnecessary operation in those who will not benefit from pacing. Combined use of bi-ventricular pacemakers and implantable cardioverter defibrillators Implantable cardioverter defibrillators (ICD) have been shown to improve prognosis in patients at high risk of sudden death [43]. However in patients with heart failure there is concern that ICDs may not prolong life but simply convert the mode of death from sudden death to progressive ventricular failure [44,45]. The simultaneous use of biventricular pacemakers and ICDs could potentially have mortality and morbidity benefits in patients

5 888 S. Walker et al. with medically refractory congestive cardiac failure that ICDs alone cannot produce. Combined fully transvenous biventricular pacemaker/ ICD implantation has been reported in case series [46,47]. Combined device use, however, does carry the potential for complications associated with device interaction [48]. Single devices that can pace biventricularly and function as antitachycardia devices are currently under investigation in the PATH CHF II and VENTAK Congestive Heart Failure (VENTAK CHF) studies [32]. There are, however, a number of potential problems associated with the use of single devices for biventricular pacing/ ICD function. If the device uses both left and right ventricular leads for sensing function there is a theoretical possibility of double counting both inputs, resulting in a falsely high sensed ventricular rate. This would have disastrous consequences for device antitachycardia function. Although less likely with epicardial leads, there is also an increased risk of far-field atrial sensing with endocardial left ventricular leads positioned transvenously. This could again result in a falsely raised sensed ventricular rate. Devices that pace both ventricles but utilize bipolar right ventricular sensing only are under development and offer the best configuration for both appropriate biventricular pacing and ICD function. Summary Bi-ventricular pacing strategies for heart failure are currently limited or investigational. The aim of biventricular pacing in ventricular failure is to optimize any atrio-ventricular, inter-ventricular or intraventricular electrical asynchrony that accompanies and contributes to the mechanical dysfunction of ventricular disease. Preliminary clinical reports and acute haemodynamic studies have confirmed the potential benefits of biventricular pacing. However, these were confounded by the need for thoracoscopic placement of the left ventricular pacing lead. With the subsequent development of a fully transvenous left ventricular pacing system, the accessibility and safety of biventricular pacing increased markedly allowing the InSync safety and efficacy study to be undertaken. The results of blinded randomized studies investigating this treatment modality are awaited. Furthermore the results with lone left ventricular pacing or more highly selected left ventricular lead positions are required. If these studies confirm functional improvement with biventricular pacing the results of long-term mortality and economic benefit studies will be required before the technique can achieve widespread acceptance. The contribution of combined biventricular ICDs and enhanced lead technology is also awaited. References [1] Mosterd A, Hoes A, de Bruyne M et al. Prevalence of heart failure and left ventricular dysfunction in the general population. 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Clinical interactions between pacemakers and automatic implantable cardioverter-defibrillators. J Am Coll Cardiol 1990; 16(3): Appendix The Imperial College Electrophysiology Group Nucleus Nicholas S. Peters, Vince Paul, Richard Sutton, David Lefroy, Andrew Coats, D. Wyn Davies, Stuart Webb, Max Lab, Jonathan Clague. Members Stuart Walker, Richard J Schilling, Tony Chow, Prapa Kanagaratnam, Vias Markides, Dominic Lamb, Terry Levy, Huw Griffiths, Steven Rex, Arvinder Kurbaan, Ameet Bakhai, David Heaven, Gita Mathur, Sujani Itty.