Comparable Benefits in Heart Failure Hospitalization and Survival with Sacubitril/Valsartan Therapy in CRT Nonresponders and HFrEF Patients Without CRT Indication

<b>Background:</b> Sacubitril/valsartan (S/V) improves left ventricular (LV) function and clinical outcome in heart failure (HF) with reduced ejection fraction (HFrEF). Data on its clinical value in the specific cohort of HFrEF patients demonstrating no adequate response to cardiac resynchronization therapy (CRT nonresponders; CRT-NRs) are limited. Herein, we investigated the impact of S/V initiated as a replacement for ACEi/ARB therapy in CRT nonresponder (CRT-NR) patients. <b>Methods:</b> Our HF database was searched to identify CRT-NRs who received S/V treatment for at least 6 months as a replacement for ACEi/ARB (Group I; 70 patients) and CRT-NRs who remained on ACEi/ARB (Group II, 70). In addition, HFrEF patients without CRT indication who received S/V therapy for at least 6 months (Group III; 135) were also included in this analysis. The primary endpoint was the composite of all-cause mortality including heart transplantation (HTx) or left ventricular assist device implantation (LVAD) and HF hospitalization (HFH). Secondary endpoints were (i) all-cause mortality+HTx+LVAD and (ii) HFH analyzed separately. <b>Results:</b> Over a median follow-up of 22 months, the primary composite endpoint occurred in 27 out of 70 patients (38.57%) in Group I, 43 out of 70 patients (61.42%) in Group II, and 60 out of 135 patients (44.42%) in Group III. The differences were significant between Groups I and II (<i>p</i>: 0.005), as well as between Group II and III (<i>p</i>: 0.012), while the two groups on S/V (Group I and III) demonstrated similar outcomes (<i>p</i> = 0.465). HFH analyzed separately as a secondary endpoint occurred in 19 out of 70 patients (27.14%) in Group I, 38 out of 70 patients (54.28%) in Group II, and 36 out of 135 patients (26.66%) in Group III (Group I vs. II <i>p</i>: 0.001; Groups II vs. III <i>p</i>: 0.001, Group I vs. III, <i>p</i>: 0.896). All-cause mortality+HTx+LVAD analyzed separately as the other secondary endpoint demonstrated no significant differences among the three groups. <b>Conclusions:</b> S/V therapy improved HFH but not mortality in CRT-NR patients. Comparable improvement was demonstrated after SV in the CRT-NR and in the general HFrEF cohort with no CRT indication.