Pathophysiological Principles Underlying the Effect of Sacubitril-Valsartan on Hypertension-Induced Cardiovascular Remodeling

Myocardial remodeling is a process executed by cardiomyocytes, other cells within the myocardium (i.e, endothelial cells, fibroblasts, pericytes, and immune cells), and cells recruited from the circulation (e.g, immune and inflammatory cells) in response to mechanical and non-mechanical stimuli. As a result, the composition, volume, and physiology of cardiomyocytes, the interstitial matrix, and the coronary vessels undergo interrelated changes. These changes detrimentally affect the clinical outcomes of patients with hypertensive heart disease (HHD), due to the risk of fibrillation and increased ventricular stiffness leading to systolic or diastolic dysfunction. Therefore, to reduce cardiovascular remodeling is the main aim for the overall clinical care of these patients.Several drugs, such as angiotensin-converting enzyme inhibitors, beta blockers, and aldosterone antagonists, have been consistently shown to decrease remodeling in animal models and in clinical trials, and are currently widely used to decrease myocardial remodeling. A combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin receptor antagonist, which has positive clinical outcomes in patients with heart failure with reduced ejection fraction, has recently gained public and scientific attention for patients with heart failure with preserved ejection fraction. By promoting the accumulation of natriuretic peptides, which have natriuretic and vascular smooth muscle relaxant properties and by reducing the effects of the renin-angiotensin-aldosterone system, the combination of these two drugs has cardioprotective and antihypertensive effects and reduces cardiovascular fibrosis. It is noteworthy, that sacubitril/valsartan showed a better effect on cardiac remodeling and reversal fraction compared with ACE inhibitor perindopril in rats. However, these are only preliminary data and more extensive studies should be conducted in both experimental and clinical settings in order to fully reveal the mechanisms of action of the drug in the management of various types of arterial hypertension.