P775Effect of sacubitril-valsartan in reducing physical frailty in patients with advanced heart failure in waiting list for heart transplantation
Authors: Cacciatore F , Golino P , Amarelli C , Maiello C , Mattucci I , Salerno G , Di Maio M , Curcio F , Benincasa G , Bonaduce D , Abete P , Napoli C 
Published: October 2019

Abstract

Background
Treatment with valsartan/sacubitril was found to be associated both with reduction in mortality risk for HF.

Purpose
To investigate the effect of sacubitril/valsartan on physical frailty (PF) in advanced HF patients in waiting list for heart transplantion (HT) in a two years follow-up study.

Methods
We enrolled 45 consecutive patients (status 2B UNOs). Patients tolerant to ACE-inhibitor and/or ARBs were treated with valsartan/sacubitril. Patients were required to have left ventricular ejection fraction (LVEF) of ≤35% and to be taking a stable dose of a β-blocker and an ACE inhibitor or an ARB for at least 4 weeks before enrollment. The dosage of sacubitril/valsartan was increased if tolerance was good. Frailty was assessed using an adapted version of Fried's Frailty Phenotype used in advanced HF patients in waiting list for transplantation. Patients were followed up until HT, device (TAH/LVAD) implant, or last follow-up visit.

Results
Mean NYHA class was 3.1±0.4, with 5.7% NYHA 2, 62.9% NYHA 3 and 31.4% NYHA 3B. LVEF was 25.1±6.4, VO2 max (ml/kg/min) was 10.3±2.3, cardiac index (L/min/m2) was 2.3±0.6, and NT-proBNP (pg/ml) was 4054.8±3977. At 3 months, 31.5% of patients received the target dose of 97/103 mg/BID, 31.6% the half dose (49/51mg BID) and 26.3% the low dose (24/26 mg BID) and 10.5% the half low dose (24/26 mg daily). The baseline mean value of physical frailty was 3.86±0.8, specifically 94.3% showed exhaustion, 91.4% physical inactivity, 88.6% weakness, 85.7% slowness and 28.6% loss of appetite. All patients had a frailty score ≥3. During follow-up there were no deaths. After treatment, NYHA class improved significantly (2.4±0.6 vs 3.1±0.4; p=0.002), with 5.7% NYHA 1, 48.6% NYHA 2, 42.9% NYHA 3 and 2.9% NYHA 3B (p<0.001). VO2 max consumption, Six Minute Walking Test increased while pulmonary systolic blood pressure, VE/VCO2 slope, and NT-proBNP, decreased. Both Diastolic and Systolic BP decrease, but only DBP was statistically significant. No differences were observed during follow-up for LVEF, E/E', TAPSE, IVC. A significant reduction in furosemide dosage was observed (103.57±71.3 mg to 81.4±54.6 mg; p=0.040) while no differences were observed in mineral corticoids antagonist and metolazone. These improvements occurred from the first month of treatment and were still significantly present at the end of follow up. PF decreased (3.86±0.8 vs 1.44±1.26; p<0.000) with a significant reduction in all domain of PF. 28.5% had a frailty score ≥3.

Conclusions
Our study shows an improvement in PH in patients with advanced HF in waiting list for HT after therapy with sacubitril/valsartan. These changes seem to appear very early after introduction of the treatment and to be maintained over time. The improvement in all physical domain was paralleled by VO2 max and 6-minute walking test increase. The pro-BNP-NT reduction was significant in the first month of treatment and remain quite stable in the follow-up.