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.