Sacubitril/Valsartan Therapy for 14 Months Induces a Marked Improvement of Global Longitudinal Strain in Patients With Chronic Heart Failure: A Retrospective Cohort Study

BACKGROUND: Clinical efficacy of sacubitril/valsartan administered for the recommended indication of chronic heart failure (CHF) patients with New York Heart Association (NYHA) classes II-III appears to be higher than 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 could 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 angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). For the rest, the therapies practiced in the two groups, patients under sacubitril/valsartan and controls, were almost identical, including similar doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs) in the two cohorts, plus loop diuretics, with the latter administered at variable doses. The endpoints were the variations of LVEF and global left ventricular longitudinal strain (GLS) over a study period not shorter than 1 year. RESULTS: One hundred thirty-two patients were collected within our retrospective cohort study, of whom 44 were treated with sacubitril/valsartan and 88 were 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 controls, LVEF was improved after a year of therapy from 38.071 ± 5.445% (mean ± standard deviation) to 41.595 ± 5.282%. On the contrary, no significant improvement in the controls could be identified for the GLS, from -12.059 ± 4.016% to -12.250 ± 4.287%. In analogy with controls, patients assigned to sacubitril/valsartan showed a significant increase in LVEF after 1 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 demonstrated 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) axis. For the GLS in particular, a clear superiority emerges in comparison with conventional therapy including ACE inhibitor or ARBs. From these data, the hypothesis could be derived of a possible useful role of sacubitril/valsartan also for the therapy of HFpEF. In this regard, more exhaustive clarifications ensuing from the ongoing randomized controlled trials (RCTs) are eagerly awaited.