Author + information
- Mitchell N. Faddis, MD, PhD∗ ()
- Department of Internal Medicine, Cardiovascular Division, Washington University in St. Louis, St. Louis, Missouri
- ↵∗Address for correspondence:
Dr. Mitchell Faddis, Department of Internal Medicine, Cardiovascular Division, Washington University in Saint Louis, 660 South Euclid Avenue, St. Louis, Missouri 63110.
- biventricular pacing
- cardiac resynchronization therapy
- heart failure
- pacing-induced cardiomyopathy
- right ventricular pacing
The observation that ventricular pacing, compared with ventricular activation through the native conduction system, is associated with acute worsening of myocardial performance was first made in 1925 by Wiggers (1) at the dawn of modern cardiac physiology investigation. Through work in the ensuing 90 years, we know that right ventricular (RV) pacing or left bundle branch block (LBBB) results in a left ventricular (LV) contraction pattern that is dyssynchronous. As a result of the out-of-phase contraction and relaxation of the LV septal and lateral walls, there is a loss of stroke work to internal energy transfer from a contracting wall to the opposite wall that is in relaxation. An additional consequence of the dyssynchronous LV contraction pattern is that the LV lateral wall, which contracts last, is overstretched and performs a disproportionate fraction of the total stroke work. As a result of this understanding from nearly a century of investigations, it may seem surprising that the clinical entity of pacing-induced cardiomyopathy (PICM) has only recently been clearly defined (2). The evolution of our understanding of the clinical role of LV dyssynchrony in the pathogenesis of chronic systolic heart failure has followed a circuitous path. In this issue of JACC: Clinical Electrophysiology, the report by Khurshid et al. (3) provides strong support for cardiac resynchronization therapy (CRT) as the most direct treatment to address the pathogenesis of PICM.
The impact of chronic LV dyssynchronization through LBBB or chronic ventricular pacing on worsened clinical outcomes has come from several lines of evidence. Among patients with a cardiomyopathy associated with chronic systolic heart failure, morbidity and mortality rates are worsened by the presence of LBBB (4) or chronic ventricular pacing (5). Beginning with pioneering work in the 1990s, multiple clinical trials have established that resynchronization of the LV by simultaneous LV and RV stimulation with CRT could change the natural history of chronic systolic heart failure by improving LV structure and performance through the process of LV reverse remodeling, and thereby improve congestive heart failure symptoms, morbidity, and survival (6). Through basic science aimed at understanding the mechanisms underlying dyssynchronous heart failure and LV reverse remodeling, the impact of chronic LV dyssynchrony and its improvement with cardiac resynchronization are now known to reflect a host of complex cellular and molecular mechanisms that are set in motion by chronic LBBB or chronic RV pacing (7). In the realm of pacing to treat symptomatic bradycardia through pacing, multiple trials have demonstrated that chronic RV pacing is associated with worse outcomes compared with atrial-based pacing with its associated ventricular stimulation through the native conduction system (8,9). The link between dyssnychronous LV contraction triggering a cardiomyopathy is convincing.
The surprising observation is not that PICM exists, but rather that it does not happen in all patients subjected to chronic RV apical pacing. In the largest published database that has examined the incidence of PICM, Kiehl et al. (2) analyzed records of 823 consecutive patients with normal LV ejection fraction (LVEF) and complete heart block treated with chronic RV pacing, and 12.3% developed PICM over a mean follow-up of 4.3 years with an average reduction in the LVEF from 58% to 34%. The authors note that inherent selection bias and nonsystematic follow-up likely yielded an underestimate of the true incidence of PICM and the time course of its development. A limited utilization of CRT was observed with only 29 of 101 patients identified with PICM treated with CRT. In the CRT-treated group, an 84% response rate defined by >10% improvement in LVEF or a reduction in LV end-systolic volume of >15% was observed. The report clearly established that PICM is not a rare entity, and PICM did seem to respond to CRT uniquely well, although this treatment modality was substantially underutilized.
Khurshid et al. (3) present a retrospective analysis of a cohort of patients identified with PICM who were treated with CRT. Their analysis presents the largest cohort to date that has been published of PICM patients treated by CRT. In 69 patients with PICM who received CRT, 59 (85.5%) responded with an absolute improvement of ≥5% in the LVEF, a mean change in LVEF from 29.3% to 45.3%, or an absolute increase in LVEF of 16%. Among patients with a standard indication for CRT with severe cardiomyopathy, LV conduction delay, and heart failure symptoms, the nonresponse rate is expected to be about 30%. This 50% reduction in the typical CRT nonresponse rate is likely due to the more direct treatment of the cause of the cardiomyopathy in PICM patients: LV dyssynchrony. This is in contrast to results of CRT from clinical trials with patients who had LV dyssynchrony together with other processes such as coronary artery disease or a primary cardiomyopathy that may limit the CRT response due to the extent of LV fibrotic remodeling.
Several observations from this report are very helpful to further extend our understanding of the treatment of PICM with CRT. In the first, the authors observe that the median time between diagnosis of PICM and treatment with CRT was 1.5 years, and 25% of the group with the biggest response to CRT had the diagnosis of PICM for more than 2 years. This observation seems to suggest that the cardiomyopathy associated with PICM is less prone than other forms of cardiomyopathy to irreversible structural remodeling of the LV that would preclude a response to CRT. In the second, the authors had a large number of sequential echocardiograms available to look carefully at the time course of recovery of the LVEF following CRT implantation. The expected time course of the change in LVEF after CRT in the presence of typical indications for CRT is that most of the change in LVEF occurs acutely with little additional change chronically (10). In contrast, the patients in this cohort had, in many cases, sustained improvement out to 2 years after implantation of CRT.
An important consideration in the care of patients with a significant cardiomyopathy is management of sudden cardiac death risk. Of 59 PICM patients with an LVEF below 35%, a standard criterion for consideration of ICD implantation, 39 (72.2%) had an improvement in the LVEF with CRT to >35% over 7 months. Four (5.8%) patients experienced monomorphic ventricular tachycardia during the median follow-up period of 7 months. In 3 of these patients, the LVEF at the time of CRT implantation was <35% and had responded to CRT with normalization of the LVEF by the time of the ventricular arrhythmia. Although the patient numbers are small and the follow-up period is limited, the occurrence of monomorphic ventricular tachycardia during follow-up suggests the presence of a permanent myocardial substrate for arrhythmia, despite improvements with CRT, and an elevated ventricular arrhythmia risk annualized to around 10% per year. The authors argue, on the basis of these observations, that a reasonable approach to management is to initially implant a CRT pacemaker in PICM patients followed by an upgrade to a CRT defibrillator in those who went on to develop a sustained ventricular arrhythmia. Although the argument is speculative, the competing risks of repeated device implant procedures and lethal ventricular arrhythmias are real and seem to justify a more conservative approach with CRT defibrillator implantation in patients with standard indications for ICD implantation as primary prevention of sudden death.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Faddis has reported that he has no relationships relevant to the contents of this paper to disclose.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institution and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
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