Predictors of Reverse Left Ventricular Remodeling with Sacubitril\Valsartan Therapy in Heart Failure and Reduced Ejection Fraction

Introduction: The use of combined angiotensin receptor blockers (ARB) /neprilysine inhibitors (ARNI) in patients with heart failure and reduced ejection fraction (HFrEF), is associated with reduced morbidity and mortality. Several attempts were made to identify patients who would benefit most from ANRI therapy, yet the questions whether ARNI may possess a more pronounced effect in specific HFrEF patient-subgroups, and whether responsiveness to ARNI may be predicted by different patient characteristics, largely remain unanswered.

Purpose: To assess the effect of sacubitril/valsartan on left ventricular ejection fraction (LVEF) and LV dimensions in a real-life cohort of HFrEF patients, while analyzing patient characteristics that may predict positive remodeling response to ARNI.

Methods: ARNI-treated HFrEF patients followed at the Sheba Medical Center HF-outpatient clinic included in the study. Clinical and echocardiographic parameters were evaluated retrospectively prior to ARNI initiation, and during therapy, while assessing reverse LV remodeling parameters.

Results: The cohort included 99 patients (mean age 60 years, 90% male) with 47 patients (47%) demonstrating reverse LV remodeling response to ARNI (regarded as LVEF increase). Overall, LVEF increased by 17% post ARNI (23.8 to 27.9%, p<0.001). Subgroup analysis revealed several characteristics associated with significant LVEF improvement, including; baseline LVEF <30%, non-ischemic HF etiology, lack of cardiac resynchronization therapy (CRT), hypertension, and better initial functional class (p value=0.001 for all). Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and non-ischemic HF gained most benefit from ARNI with an average 52% improvement in LVEF (20 to 30%, p<0.001). Significant LVEF improvment and reduction in LV dimension was also noted in subgroups combining lower LVEF, non-ischemic HF and no CRT.

Conclusion: ARNI treatment is associated with reverse LV remodeling in selected patient populations, and especially those with LVEF<30%, non-ischemic HF and no CRT.