Patient-specific modifiers of survival benefit in cardiac resynchronization therapy - A multicentre interaction analysis

Background: Cardiac resynchronization therapy (CRT) is a key intervention for patients with heart failure. The choice between a CRT with defibrillator therapy (CRT-D) and a CRT with pacemaker (CRT-P) is influenced by individual clinical characteristics. This study explores the interaction between these clinical variables and the benefit of CRT-D versus CRT-P on all-cause mortality. Methods: All patients who underwent CRT implantation in three European centres were included in a multicentre, retrospective registry. The impact of clinical variables on all-cause mortality was analysed using interaction tests within multivariable Cox proportional hazard models. Significant interactions were explored to assess how patient characteristics modify the effect of CRT-D compared with CRT-P. Results: A total of 2271 patients with CRT implantation were included. CRT-D was associated with a 35% reduction in all-cause mortality compared with CRT-P [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.53-0.80]. Significant interactions were observed for left bundle branch block (LBBB) morphology (P = 0.028), left ventricular ejection fraction (LVEF, P = 0.025) and renal function (P = 0.019). The survival benefit of CRT-D was pronounced in patients with LBBB (HR 0.57; 95% CI 0.44-0.73) but was not significant in those without LBBB (HR 0.81; 95% CI 0.59-1.10). For LVEF at implant, CRT-D provided benefit between 17.9% and 37.6%. Similarly, CRT-D improved outcomes in patients with an estimated glomerular filtration rate >31.8 mL/min but not in those with more advanced renal impairment. No interaction was observed with age at implant (P = 0.286). Conclusions: This study provides insights into the benefits of CRT-D over CRT-P, identifying LBBB morphology, LVEF and renal function as key covariates associated with implantable cardioverter-defibrillator (ICD) therapy's benefit.