Cardiac Resynchronization Therapy
Martin G. St. John Sutton, Jeroen Bax, Mariell Jessup, Josep Brugada, Martin Schalij, eds.
324 pages. London, UK: Informa UK Ltd, 2007. $235. ISBN 1–84184–637–8.
Over the past several years, cardiac resynchronization therapy (CRT) clearly has established itself as a central therapy in the management of moderate to severe congestive heart failure in the setting of dilated cardiomyopathy with intraventricular conduction delay. In 2007, >70 000 of these devices were implanted in the United States, and ≈35% of all implantable cardioverter-defibrillators that were newly implanted or replaced last year have CRT capability. Randomized prospective clinical trials have demonstrated enhanced survival, improved exercise capacity and functional class, and durable reverse left ventricular remodeling with CRT in a majority of patients studied. In some patients, the response to therapy can be dramatic.
Despite the growing enthusiasm of heart failure specialists and electrophysiologists in applying this therapy, several limitations are apparent and numerous questions remain unanswered. Approximately one third of patients fail to demonstrate subjective improvement or to remodel their ventricles in a positive fashion over time. This lack of response may be closely tied to patient selection. Clinical trials to date have relied on QRS duration to identify patients with mechanical dyssynchrony, but the correlation of electrical and mechanical events is far from perfect. Various methods of quantifying mechanical dyssynchrony with greater accuracy than the surface ECG, including strain rate, tissue Doppler and 3-dimensional echocardiography, and magnetic resonance imaging are competing for superiority in recent published studies. Once implanted, the optimal method of programming atrioventricular and interventricular delay is abstruse to most cardiologists and implanting physicians. Employing CRT in patients with right ventricular conduction delay on surface ECG and in those with persistent atrial fibrillation remains somewhat controversial, and the role of CRT in patients who require ventricular pacing in the setting of poor ventricular performance without heart failure frequently needs clarification. For the implanting physician, few compiled educational resources are available related to coronary venous anatomy, technique of implantation, and management of complications.
It is against this background that Cardiac Resynchronization Therapy, a multiauthored text edited by a distinguished group of heart failure, imaging, and arrhythmia experts, has recently been published. The text aims to address several of these questions with a comprehensive review of the field from the varied perspectives of epidemiologists, physiologists, and clinical heart failure, imaging, arrhythmia, and pacemaker specialists.
The overall strength of this text lies in this comprehensive and wide-ranging scope. It is organized into 26 relatively short chapters, the majority of which are excellent and several of which are outstanding. The initial chapters provide background with an examination of the epidemiology of congestive heart failure in order to put the prevalence of dyssynchrony and application of CRT into broader context. The results of all completed clinical trials through 2006 are exhaustively presented in graphic detail, with the appropriate contrasts of inclusion criteria and emphasis on the hard clinical end points that have emerged as the field has matured. Retrospective analysis of the published data is used in consideration of appropriate patient selection, focusing on patients most and least likely to benefit.
Of special note in the early portion of the text is an outstanding section on the pathophysiology of left ventricular dyssynchrony, with an examination of the mechanical and energetic consequences of late mechanical activation. The relationship of strain imposed by dyssynchrony to the current understanding of altered gap junction protein and intracellular kinase expression in animal models is presented in well-illustrated detail. Included here is a concise discussion of altered stress-strain loops with regard to myocardial regional work, and the favorable response to CRT in dyssynchrony models. An insightful analysis of the limitations of longitudinal strain rate analysis is presented, with a discussion on the potential for regional variation in contractility to give the false impression of mechanical dyssynchrony even during synchronous electrical activation. Early sections of the text also include an overview of mechanisms of remodeling, including an examination of the progression of altered LV geometry during progressive dilatation, and an excellent analysis of the mechanism of mitral regurgitation with LV enlargement. The mechanisms by which CRT reduces mitral regurgitation and improves diastolic function are discussed at length.
The middle third of the text has its greatest appeal for electrophysiologists and those wishing to improve their understanding of CRT implantation and the nuts and bolts of device programming. The chapter devoted to coronary venous system anatomy is superb and provides a concise up-to-date review of the standard anatomy and commonly encountered patterns of anatomic variation. This section is remarkably well illustrated with correlation of gross anatomic specimens, computed tomography scans, cardiac magnetic resonance imagery scans, fluoroscopic images, and coronary sinus venograms. Both antiquated and contemporary anatomic terminologies are reconciled and overall venous anatomy is illustrated with respect to more familiar cardiac landmarks. A discussion of implantation techniques is comprehensive, but probably a little too rich with anecdotal experience, some aspects of which may prove more helpful to the implanting physician than others. CRT devices are frequently implanted as upgrades to preexisting systems. Implantation challenges in these scenarios are common but not substantively dealt with here.
The issue of optimal device programming is a difficult one for most clinicians for several reasons. No consensus has emerged relative to the importance of optimizing therapy and its contribution in clinical benefit or, importantly, whether optimized programming can convert a nonresponder to a responder at all. Optimization methods are not intuitive and require a niche of expertise that spans both electrophysiology and echocardiography. Some electrophysiologists are not sufficiently versed in interpretation of echocardiographic indices of diastolic filling, contractility, and stroke volume; and echocardiographers may not appreciate the subtleties of atrioventricular delay programming, dynamic adjustments, refractory periods, latency, and proprietary pacing algorithms. The chapters devoted to optimization of atrioventricular delay and interventricular delay review all these considerations in a concise and easy to read fashion, and in this respect go a long way toward bridging these gaps. Included is a summary of the most commonly employed methods with a critical review of each and correlation to methods used in clinical trials. These chapters are an extremely valuable resource for the commonly encountered clinical question of how best to optimize programming.
The remainder of the text is somewhat more loosely organized and focuses on the question of appropriate patient selection and the use of various techniques to distinguish populations likely to respond to CRT from those in which CRT implantation is not likely to lead to clinical benefit. Tissue Doppler evaluation of mechanical dyssynchrony, the technique for which the largest body of peer reviewed evidence is available, is fully considered. Emerging techniques are included but not presented in substantial detail, a choice that reflects their more investigational nature. The question of preimplantation selection in order to improve the overall rate of successful therapy is a central one and certainly worthy of discussion. At this stage, however, there may not be enough out there to serve as a foundation for extensive review in a resource text. This paucity of data is reflected in this multiauthored text by some redundancy in the question without much substance in the answer.
The exception to this rule is a wonderfully written chapter focused on the contribution of acute and chronic ischemia to the pattern of asynchrony, a discussion that sheds light on the reported trend of more robust and durable response in nonischemic versus ischemic populations. The text closes with review of the published data with regard to CRT benefit in special populations of patients, namely those with right bundle-branch block and those with chronic atrial fibrillation. The structure of ongoing multicenter trials aimed at gauging the benefit of CRT in treating mildly symptomatic patients and in preventing the progression of congestive heart failure is adequately discussed.
Overall, this is an excellent text. It is well edited and hits the intended mark of providing a useful and practical handbook for electrophysiologists, heart failure specialists, echocardiographers, general cardiologists, and trainees. To the extent that it was intended to provide a wide perspective on the field, it succeeds, and does so without sacrificing the detail required for those who are interested in more focused clinical questions within the field of resynchronization therapy.