Short‐term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction: A randomized controlled study

• Published in: European journal of heart failure Vol. 26; no. 1; pp. 117 - 126
• Main Authors: Nesterov, Sergey V., Räty, Johanna, Nammas, Wail, Maaniitty, Teemu, Galloo, Xavier, Stassen, Jan, Laurila, Sanna, Vasankari, Tuija, Huusko, Jenni, Bax, Jeroen J., Saraste, Antti, Knuuti, Juhani
• Format: Journal Article
• Language: English
• Published: Oxford, UK John Wiley & Sons, Ltd 01.01.2024
• Subjects: Aged; Aminobutyrates; Angiotensin Receptor Antagonists - adverse effects; Biphenyl Compounds - therapeutic use; Double-Blind Method; Drug Combinations; Echocardiography; Heart Failure; Humans; Middle Aged; Oxygen Consumption; Perfusion; Positron emission tomography; Prospective Studies; Stroke Volume; Tetrazoles; Valsartan - therapeutic use; Ventricular function; Ventricular Function, Left; Heart failure; Oxygen consumption; Ventricular function; Echocardiography; Perfusion; Positron emission tomography
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1002/ejhf.3072

Aims We sought to evaluate the mechanism of angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan‐only control group in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results The study was a phase IV, prospective, randomized, double‐blind, parallel‐group study in patients with New York Heart Association class II–III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6‐week run‐in period, all patients received valsartan therapy, which was up‐titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11C‐acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan‐only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (−4.5 mmHg; p = 0.026) and systolic blood pressure (−9.8 mmHg; p = 0.0007), myocardial perfusion (−0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (−296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (−5.4%) compared with the run‐in period and remained unchanged in the control group (+0.5%), the between‐treatment group difference was not significant (p = 0.088). Conclusions We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan‐only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients. This randomized, prospective, double‐blind, parallel group study investigated short‐term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in patients with heart failure and reduced ejection fraction (HFrEF). Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11C‐acetate positron emission tomography (PET) imaging before and after 6 weeks of therapy. Energetic efficiency of cardiac work remained unchanged in both treatment arms. However, there were reduction in blood pressure (BP), myocardial perfusion and left ventricular (LV) mechanical work as compared with the control group. ARNI, angiotensin receptor‐neprilysn inhibitor; EF, ejection fraction; hs‐cTnT, high‐sensitivity cardiac troponinT; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide. [Correction added on 12 February 2024, after first online publication: The caption and list of abbreviations have been updated in this version.]