Sacubitril/valsartan improves left ventricular longitudinal deformation in heart failure patients with reduced ejection fraction.

Background: Clinical efficacy of sacubitril/valsartan administered for the recommended indication of patients with reduced (<40%) left ventricular ejection fraction (HFrEF) belonging to NYHA classes II-III appears to be higher than that one would expect based on the drug-induced variations of the left ventricular ejection fraction (LVEF). More thorough investigations with the use of indicators of longitudinal systolic function have been therefore recommended, to verify whether a part of the clinical improvement achieved with the use of sacubitril/valsartan might be supported by a reverse remodeling ensuing from changes other than a simple LVEF increase.

Methods: In the present retrospective cohort study, which collected the pertinent data from two centers devoted to clinical management of outpatients with CHF and dating back to the years 2017 and 2018, we separated patients treated with sacubitril/valsartan from those treated with conventional medical therapy, including ACE inhibitors (ACEi) or angiotensin receptor blockers (ARBs). For the rest, the therapies practiced in the two cohorts - patients under sacubitril/valsartan and controls - were almost identical, including similar doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs), plus loop diuretics, the latter administered at variable doses depending on the signs and symptoms of congestion. The endpoints were the variations of LVEF and global left ventricular longitudinal strain (GLS) over a study period not shorter than one year.

Results: Patients collected within our retrospective cohort study were 132, of whom 44 treated with sacubitril/valsartan and 88 subjected to conventional therapy. All patients were marked by heart failure with reduced (LVEF<40%) left ventricular ejection fraction (HFREF). The mean duration of the retrospective observation period was 14±3 months. In the controls, LVEF was improved after one year of therapy - from 38.071±5.445% (mean±SD) to 41.595±5.282%; P=0.003. On the contrary, no significant improvement in the controls was identified for the GLS - from -12.059±4.016% to -12.250±4.287%; P=0.406. In analogy with controls, patients assigned to sacubitril/valsartan showed a significant increase in LVEF after one year of treatment - from 39.714±4.789% to 42.119±5.683%- (P<0.001). However, differently from the controls, sacubitril/valsartan group exhibited a significant improvement in GLS - from -10.142±3.080% to -18.238±7.284%; P<0.001).

Conclusions: The present retrospective cohort study demonstrates that the use of sacubitril/valsartan for HFREF patients, extended for a mean duration of 14 months, yields a significant improvement in the echocardiographic parameters of systolic function along the transverse (LVEF)and longitudinal (GLS) axes. For the GLS in particular a clear superiority emerges in comparison with conventional therapy including ACE-i or ARBs. From this data the hypothesis of a possible useful role of sacubitril/valsartan also for the therapy of HFpEF could be derived. In this regard, more exhaustive clarifications ensuing from the ongoing randomized controlled trials are eagerly awaited.