Cardiac Resynchronization Therapy Reduces New Onset Ventricular Arrhythmias
May 1, 2017 4 minutes read
By Joshua D. Moss, MD
Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco
Dr. Moss reports no financial relationships relevant to this field of study.
SYNOPSIS: In an analysis of the landmark Resynchronization in Ambulatory Heart Failure Trial, patients without prior ventricular arrhythmias randomized to cardiac resynchronization therapy experienced significantly less new onset ventricular arrhythmias than those randomized to implantable cardioverter defibrillator alone.
SOURCE: Sapp JL, Parkash R, Wells GA, et al. Cardiac resynchronization therapy reduces ventricular arrhythmias in primary but not secondary prophylactic implantable cardioverter defibrillator patients: Insight from the Resynchronization in Ambulatory Heart Failure Trial. Circ Arrhythm Electrophysiol 2017 Mar;10(3). pii: e004875. doi: 10.1161/CIRCEP.116.004875.
The positive effects of cardiac resynchronization therapy (CRT) in patients with significant left ventricular (LV) dysfunction, congestive heart failure (CHF), and widened QRS have been well demonstrated. Amelioration of symptoms, reduction in heart failure admissions, and improved survival are well documented in prospective, randomized, controlled trials, such as COMPANION, CARE-HF, REVERSE, and MADIT-CRT. However, there have been conflicting data on the effects of CRT on the incidence and frequency of ventricular arrhythmias (VA).
In the Resynchronization in Ambulatory Heart Failure Trial (RAFT), 1,787 patients with New York Heart Association (NYHA) class II or III heart failure, LV ejection fraction (EF) ≤ 30% and intrinsic QRS duration ≥ 120 msec or paced QRS duration ≥ 200 msec, were randomized to either implantable cardioverter defibrillator (ICD) alone or ICD plus CRT (CRT-D). After mean follow-up of 40 months, mortality was significantly lower in the CRT-D group (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.91; P = 0.003). Heart failure hospitalizations also were reduced significantly, although adverse events (particularly lead dislodgement) were higher in the first 30 days post-implant.
In this post hoc analysis of RAFT, the authors evaluated data on VAs detected by the implanted devices. Device interrogations were performed one month after implant and every six months thereafter, and device data were available for 1,764 of 1,787 patients implanted. All devices were programmed with ventricular tachycardia (VT) detection at 150 bpm (or slower if clinically indicated), with a threshold of 16 beats for initial detection.
VAs were common, occurring in 49.4% of patients over a mean follow-up of 40.7 ± 19.2 months, and occurred significantly more in patients who had a history of pre-implant VA (“secondary prophylaxis” indication) vs. those who did not (“primary prophylaxis”). In the entire cohort, the time to occurrence of VA was not different significantly in patients with CRT-D vs. ICD alone. However, among the primary prophylaxis patients, CRT-D was associated with significant prolongation in time to VA compared with a simple ICD (HR, 0.86; 95% CI, 0.74-1.00; P = 0.044). There was not the same protective effect among the secondary prophylaxis patients. The mean number of VA or ICD therapies per person per year at risk was 5.91 in secondary prophylaxis patients with CRT-D, significantly more than the 3.36 in patients with an ICD alone. This resulted in a trend toward more anti-tachycardia pacing therapies, though not more ICD shocks. The authors concluded that in heart failure patients without prior VA who met criteria for CRT, significantly fewer new onset VAs were observed in those treated with CRT than those treated with ICD alone.
COMMENTARY
Nearly every electrophysiologist who implants CRT devices has treated patients who seemed to develop new or more frequent VA after initiating biventricular pacing. Discontinuation of LV pacing often is considered in such patients, particularly in the setting of VT storm when multiple treatment strategies often are employed simultaneously.
The Sapp et al study adds valuable information to our knowledge about the pro-arrhythmic and/or antiarrhythmic effects of biventricular pacing, information that, at a minimum, will help facilitate conversations with patients about the potential risks and benefits of CRT. Particularly, in what are more often “borderline” candidates for CRT based on current guidelines — for example, non-left bundle branch block pattern on ECG or QRS durations only slightly longer than 120 msec — the longer implant procedure time, added hardware, and reduced battery life of CRT devices may make some patients and physicians lean toward a simple ICD. Knowing that there may be a benefit with CRT in a primary prophylaxis indication could be an additional incentive to proceed with the more complex device.
The major strengths of the study are the large patient population and the randomized distribution of simple ICDs vs. CRT-D devices. However, important limitations must be considered. Multivariate analysis was not performed to eliminate potential confounding effects. The actual percentage of time patients with a CRT-D device had biventricular capture (not just delivery of a pacing stimulus by the device) probably is not known. The presence or absence of VA was based entirely on device detection, which is limited by device programming — particularly in the secondary prophylaxis group, where amiodarone use was significantly higher and slower arrhythmias may have been missed. Also, the devices were implanted before the era of quadripolar LV leads and multisite pacing, both of which allow for more CRT “customization” and may further affect VA burden.
It will be important to determine if there are more specific predictors for new onset or increased burden of VA after CRT initiation, such as proximity of the pacing electrodes to areas of scar, timing of LV vs. RV pacing, or inducibility of VA with programmed stimulation from either the chosen LV or RV pacing sites. The data presented here should serve to further encourage referral for consideration of CRT in appropriate patients, including those with a secondary prophylaxis indication. Still, helping our patients understand potential risks and benefits associated with implanted device therapy and minimizing the morbidity associated with ICD shocks should remain priorities.
In an analysis of the landmark Resynchronization in Ambulatory Heart Failure Trial, patients without prior ventricular arrhythmias randomized to cardiac resynchronization therapy experienced significantly less new onset ventricular arrhythmias than those randomized to implantable cardioverter defibrillator alone.
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