The role of sacubitril/valsartan in the management of cardiac resynchronization therapy non-responders: a retrospective analysis

Aims: Optimal medical therapy after cardiac resynchronization therapy (CRT) implantation is important in heart failure (HF) with reduced ejection fraction (HFrEF) patients. Although sacubitril/valsartan (SV) is a mainstay in the treatment of HFrEF, its efficacy in the management of CRT non-responders has not been emphasized. We aimed to investigate the efficacy of SV in CRT non-responders. Methods and results: We analysed 175 HFrEF patients who received CRT implantation between January 2010 and January 2019. CRT responder was defined as a decrease in left ventricular (LV) end-systolic volume > 15% on echocardiography 6 months after implantation. Medical records were retrospectively reviewed. Patients underwent follow-up for HF rehospitalization, heart transplantation (HT), implantation of a LV assistant device (LVAD), cardiac death, and all-cause death. Among the study population, 164 patients were evaluated for CRT response; 54 (33%) were CRT non-responders. Four patients (6%) who received SV before CRT implantation were excluded, leaving 50 patients for analysis. Twenty-two non-responders (44%) received SV. There was no significant difference in baseline characteristics between SV users and non-users (n = 28). During follow-up, SV users had significantly lower incidence of all-cause death [1 (5%) vs. 10 (36%), P = 0.022] and tended to have lower HF rehospitalization [6 (27%) vs. 16 (57%), P = 0.068] and cardiac death (including HT and LVAD implant) [2 (9%) vs. 10 (36%), P = 0.064]. Kaplan-Meier survival analysis revealed that SV use was associated with a lower risk of cardiac death (including HT and LVAD implant) (log-rank P = 0.029). Conclusions: SV treatment was related to a lower incidence of cardiac death including HT and LVAD implant in CRT non-responders. The optimization of HF management, including SV, should be considered in CRT non-responders.ope