Usefulness of myocardial work assessment for the understanding of mechanisms underlying sacubitril/valsartan efficacy in patients with heart failure and reduced ejection fraction

Abstract

Type of funding sources: None.  Sacubitril/valsartan has shown the ability in reducing the risk of death and of hospitalization in patients with HF (heart failure) and is recommended in patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite conventional therapies. Strain imaging derived myocardial work (MW) is an emerging tool for the evaluation of left ventricular (LV) mechanics by incorporating both systolic deformation and afterload burden in the analysis. To evaluate in a prospective fashion the impact of sacubitril/valsartan therapy in HF patients on MW derived parameters in relation with standard echocardiographic indices. We recruited thirteen HF patients with indication to sacubitril/valsartan therapy according to current guidelines. Sacubitril/valsartan therapy titrated at the maximum tolerated dose. A comprehensive echo-Doppler exam, including speckle tracking derived assessment of global longitudinal strain (GLS) (in absolute value), was performed before and after a three months therapy with sacubitril/valsartan. Parameters of MW such as global work index (GWI), global constructive work (GCW) global wasted work (GWW) and global work efficiency (GWE) were calculated according to standardized procedures. Patients with more than mild aortic and mitral stenosis and/or regurgitation were excluded. Other exclusion criteria included permanent and/or persistent atrial fibrillation and inadequate echo images. The 13 patients (M/F = 11/2, age: 57 ± 8.2 years, aetiology: idiopathic in 3 patients, ischaemic in 7 patients and chemotherapy related cardiotoxicity in 3 patients, NYHA Class: II in 7 and III in 6 patients). All patients tolerated sacubitril/valsartan therapy. After the three months therapy an improvement of  LVEF (from 32.3 ± 2% to 36.2± 6%, p = 0.015), GLS (from 9.8 ± 1% to 11.6 ± 2%, p = 0.019), GWI (from 845.0 ± 175.0 mmHg% to 1091.6 ± 336.8 mmHg%, p = 0.003), GCW (from  993.4± 211.6 mmHg% to 1262.7 ± 404 mmHg%, p = 0.002) and GWE (from 77 ± 11% to 81 ± 10%, p = 0.002) was observed, without significant changes in GWW (from 190 ± 121 mmHg% to 211 ± 145 mmHg%, p = 0.307). We also found a positive correlation between the magnitude of LVEF improvement and the baseline values of GCW (r = 0.66, p = 0.014). This relation remained significant even after adjusting for the extent of systolic blood pressure reduction (r = 0.54, p = 0.033). Three months sacubitril/valsartan therapy significantly improves standard and advanced indices of LV systolic function. This improvement is due to the increase of constructive work more than to the reduction of wasted work and the increase of LVEF can be predicted by the global constructive work levels at baseline. MW assessment may help to understand the mechanisms underlying the sacubitril/valsartan therapy efficacy in HF patients. Abstract Figure.