Cardiac Resynchronization Therapy (CRT) with or without Defibrillation in Patients with Non-Ischemic Cardiomyopathy: A Systematic Review and Meta-analysis

Background - Cardiac resynchronization therapy (CRT) represents a major medical advance in patients with heart failure (HF) with electrical dysschrony to improve symptoms, reduce hospitalization, and increase survival both in the presence and absence of implantable-cardioverter defibrillator (ICD) therapy. However, among CRT-eligible patients with non-ischemic cardiomyopathy (NICM), the benefit of defibrillator therapy in addition to CRT remains unclear. A systematic review and meta-analysis comparing outcomes of patients with NICM and HF who underwent CRT with ICD (CRT-D) vs. CRT only (CRT-P) was therefore performed. Methods - A literature search from inception through February 2020 was conducted in PubMed and Cochrane Review Databases for all studies reporting outcomes of CRT-D versus CRT-P in CRT-eligible patients with NICM. Studies reporting non-stratified outcomes including patients with ischemic cardiomyopathy were excluded. The primary end point of interest was all-cause mortality. A random effects model using hazards ratio (HR) was utilized to calculate a cumulative HR for all-cause mortality. The GRADE approach assessed the certainty of evidence across outcomes. Results - Of a total of 1,478 potential citations, the search yielded eight citations that met inclusion and exclusion criteria. There was one randomized controlled trial which included a sub-group of 645 CRT-eligible NICM patients (322 with CRT-D and 323 with CRT-P). Seven observational studies representing 9,944 CRT-eligible patients with NICM (6,865 CRT-D implantation and 3,079 with CRT-P) were included in a pooled meta-analysis. The cumulative adjusted HR for all-cause mortality for CRT-D versus CRT-P was 0.92 (95% CI; 0.83, 1.03); I 2 = 0 though with low certainty of evidence. There may be little difference in infection and cardiac mortality between CRT-D versus CRT-P devices (HR: 0.82; 95% CI: 0.29, 2.20 moderate certainty of evidence, and HR: 0.68; 95% CI: 0.37, 1.25, low certainty of evidence, respectively). Conclusions - In this meta-analysis, the addition of defibrillator therapy was not significantly associated with a reduction in all-cause mortality in CRT-eligible patients with NICM.