Abstract 14660: The Effect of Sacubitril/Valsartan Therapy on Hospitalization and Mortality in Patients Non-Respondent to Cardiac Resynchronization Therapy

Background: Non-responders to Cardiac Resynchronization Therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcomes of heart failure patients with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials; however, limited data are available on the specific cohort of CRT-NRs.

Aim of the study: We have compared heart failure hospitalization (HFH) and mortality rates in three patient cohorts: CRT-NR patients on S/V versus on ACEi/ARB and general HFrEF patients on S/V.

Methods: 275 HF patients, including 70 CRT-NRs receiving S/V at least for 6 months (Group I); 70 CRT-NRs on ACEi/ARB treatment (Group II); and 135 HFrEF patients without CRT indication on S/V therapy at least for 6 months (Group III) were included. CRT-NR was defined as a less than 10% improvement in left ventricular ejection fraction (LVEF) 6 months after device implantation. Rates of HFH and the composite of all-cause mortality/heart transplantation/LVAD therapy were compared with a mean follow-up of 21.5 months. A subgroup analysis was also performed in patients on S/V (Groups I and III) who demonstrated a more versus less than 10% increase in LVEF after 6 months of S/V treatment (S/V super-responders versus S/V moderate responders, respectively).

Results: HFH rates were similar in Groups I and III (28.5% vs. 28.1%, respectively; p>0.05), while significantly higher (54.2%) in Group II (p=0.02). No significant difference in the composite mortality endpoint was demonstrated between the three groups (22.8% vs. 24.2% vs. 22.2%, p=0.08). On S/V treatment, 13 out of the 70 (18.5%) CRT-NR patients (Group I) and 24 out of the 135 (17.8%) HFrEF patients (Group III) were found to be SV super-responders. Comparing these 37 patients with the 168 S/V moderate responders, neither the HFH (24.3% vs 30.9%, p=0.07), nor the composite mortality rates (24.3% vs 23.2%, p=0.53) demonstrated significant differences.

Conclusion: S/V treatment in CRT-NRs improved hospitalization rates similarly to what was observed in a general HFrEF population. No benefit in mortality rates was demonstrated in this cohort. The extent of change in LVEF on S/V was not predictive of a better response on HFH or mortality.