CRT-D improves survival in non-ischemic CMP, JACC study advocates CRT-D over CRT-P.

The addition of defibrillation support (ICD) in patients undergoing device based cardiac resynchronization therapy (CRT) is well established in ischemic cardiomyopathy (ICMP). But the superiority of CRT-D (CRT PLUS ICD) over CRT-P (pacing alone CRT) in patients with non-ischemic cardiomyopathy (NICM) has always been a grey area in cardiology. Doran et al in their latest published post-hoc analysis of COMPANION trial have shown benefit for the use of CRT-D in patients with advanced NICM who are CRT eligible and illuminate the need for more investigation in this area to provide more precision for ICD recommendations.

Among patients with ICMP, ICDs have been shown to reduce mortality and improve outcomes but there is a question as to whether ICDs are effective in patients with NICM. The DANISH trial did not demonstrate statistically significant improvement in all-cause mortality (ACM) in patients with NICM undergoing ICD implantation; although recent meta-analyses have challenged these results.

COMPANION trial was the first study to demonstrate superiority for major clinical event reduction of CRT over OPT (optimal pharmacological therapy) in patients with HFrEF and intraventricular conduction delays. Doran et al conducted a post-hoc analyses of the COMPANION trial using Cox proportional hazards modeling stratified by HFrEF etiology of nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM). The primary outcome was all-cause mortality (ACM), and secondary outcomes were the combination of cardiovascular mortality or heart failure hospitalization and sudden cardiac death.

A total of 1,520 patients were included in the trial, of whom 838 (55%) had ICM and 682 (45%) NICM as HFrEF etiologies (13). The numbers of patients randomized to OPT alone, OPT with CRT-P, and OPT with CRT-D were, respectively, 181, 332, and 325 among those with ICM and 127, 285, and 270 among those with NICM.

The chief results from this analysis were:

1. Among patients with NICM therapy with CRT-D versus CRT-P was associated with a significant reduction in ACM.

2. This mortality benefit was not apparent in patients with ICM.

3. In contrast to ACM, for sudden cardiac death the CRT-D versus CRT-P analysis was associated with a reduction in event rate associated with CRT-D in both patients with NICM and those with ICM.

4. There was no difference between for CRT-P and CRT-D for secondary endpoints.

Lack of difference between the two types of CRT therapy on cardiovascular mortality or HF hospitalization reflects the dominant impact of mechanical resynchronization on this HF hospitalization–driven endpoint.

The most likely explanation for the differences between DANISH and COMPANION regarding the benefit of an ICD in CRT-eligible patients with NICM is differences in the severity of HFrEF (NYHA Class II patients were majority in DANISH vs. NYHA III and IV patients in COMPANION), creating a patient population with much higher SCD risk among COMPANION patients with NICM.

The findings of this study further support the need for personalization of approach to selection of HF therapies, including CRT-D, by HF etiology. The results of this study should at a minimum strengthen guideline recommendations for ICD therapy for NICM among CRT-eligible patients.

SOURCE; JACC heart failure: J Am Coll Cardiol HF. 2021 Jun, 9 (6) 439–449