Treatment with Sacubitril‐Valsartan Reduces Muscle Sympathetic Nerve Activity and Improves Functional Capacity in Heart Failure Patients with Reduced Ejection Fraction

Background Chronic sympathetic overactivity and reduced functional capacity, characteristics of heart failure with reduced ejection fraction (HFrEF), are associated with poor prognosis and an increased risk of mortality in this patient group. Sacubitril‐valsartan, a recently approved angiotensin receptor neprilysin inhibitor (ARNI), reduces the risk of death from cardiovascular causes or hospitalization for heart failure in patients with HFrEF, but the mechanisms underlying its benefits are not fully understood. This study tested the hypothesis that treatment with sacubitril‐valsartan reduces muscle sympathetic nerve system activity and improves functional capacity in patients with HFrEF. Methods In nine Class II and III patients with HFrEF (69±3 yrs; 28.6±1.2 kg/m 2 ), measurements of muscle sympathetic nerve activity (MSNA), functional capacity (six‐minute walk test (6MWT) distance), and blood pressure (BP) were performed at baseline prior to being transitioned to sacubitril‐valsartan. The measurements were repeated after two months of treatment with sacubitril‐valsartan. Results Sacubitril‐valsartan treatment reduced MSNA burst frequency (baseline: 43±3 bursts/min; 2‐month: 36±3 bursts/min, p =0.05) and burst incidence (baseline: 68±5 bursts/min; 2‐month: 55±5 bursts/min, p =0.02), as well as improved 6MWT distance (baseline: 446±26 m; 2‐month: 500±30 m, p <0.001). The changes in MSNA burst frequency and burst incidence were not correlated with the change in 6MWT distance ( r =0.13 and r =0.11, respectively; both p >0.05). No changes in BP were observed with the treatment ( p >0.05). Conclusion Sacubitril‐valsartan reduced sympathetic nervous system activity and improved functional capacity in patients with HFrEF, providing new evidence for the potential favorable effect of this new drug class on autonomic and functional outcomes in this patient group. Support or Funding Information This project is funded in part by the National Institutes of Health (HL118313; D.W.W., R56AG057584; R.S.R., T32HL139451; R.S.R. (recipient) and K.B. (trainee)), the U.S. Department of Veterans Affairs (I01RX001311; D.W.W., I01RX001697; R.S.R., I01RX002323; R.S.R., I21RX001433; R.S.R., I01RX000182; R.S.R.), and the American Heart Association (18POST33960192; K.B.).