Effect of Sacubitril-Valsartan on Estimated Pulmonary Artery Systolic Pressure in Patients With Heart Failure With Reduced Ejection Fraction Heart Failure

Worldwide, the burden of heart failure has increased to an estimated 23 million people, and approximately 50% of cases are heart failure with reduced ejection fraction (HFrEF). Heart failure is a clinical syndrome characterized by dyspnea or exertional limitation due to impairment of ventricular filling or ejection of blood or both.

Heart failure with reduced ejection fraction HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. Assessment for heart failure begins with obtaining a medical history and physical examination. Also central to diagnosis are elevated natriuretic peptides above age- and context-specific thresholds and identification of left ventricular systolic dysfunction with LVEF of 40% or less as measured by echocardiography. Treatment strategies include the use of diuretics to relieve symptoms and application of an expanding armamentarium of disease-modifying drug and device therapies.

The Pulmonary hypertension definition has been changed recently to include mean Pulmonary artery pressure, 20 mm Hg, and Pulmonary vascular resistance, 2.0 WU, for distinguishing each of the hemodynamic Pulmonary hypertension subgroups: isolated precapillary, combined precapillary/postcapillary, and isolated postcapillary Pulmonary hypertension.

The goals of therapy of heart failure with reduced ejection fraction are to reduce morbidity (ie, reduce symptoms, improve health-related quality of life and functional status, and decrease the rate of hospitalization), and to reduce mortality.

Attempts to treat PH in HFpEF-PH have resulted in a succession of failures, despite approaching this problem from different pathobiological angles. The endothelin receptor antagonist bosentan, which is effective in pulmonary arterial hypertension, has failed in HFpEF-PH.3 The potent phosphodiesterase type 5 inhibitor sildenafil increases cyclic guanosine monophosphate (cGMP) levels, causing endogenous nitric oxide-mediated vasodilatation in both systemic and pulmonary vasculature. Despite the initial positive trial in the field reported by Guazzi et al., other attempts have failed to show a reduction in pulmonary artery pressure (PAP) or improvement in other haemodynamic parameters in HFpEF-PH. Increased cGMP levels by oral soluble guanylate cyclase stimulators also increase cGMP levels but do not affect PAP, pulmonary vascular resistance, or transpulmonary pressure gradient. Lastly, direct NO donors were examined in the INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction) trial but resulted in no benefit in terms of exercise capacity, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, New York Heart Association (NYHA) functional class, diastolic function, or N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

Management of heart failure with reduced ejection fraction HFrEF includes management of the cause of heart failure and associated conditions, monitoring, preventative care, care coordination, education and support for heart failure self-management (including lifestyle modification and daily monitoring), pharmacologic therapy, cardiac rehabilitation, palliative care, device therapy (including cardiac resynchronization therapy, implantable cardioverter defibrillator, and mechanical circulatory support [eg, LV assist device]) and cardiac transplantation .

The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) is a particulate guanylyl cyclase activator that increases natriuretic peptides, which signal through cGMP and exert potent antimitogenic and vasodilatory effects.

Sacubitril/valsartan is the latest "disease-modifying drug" approved for the management of patients with heart failure with reduced ejection fraction (HFrEF) In addition to a reduction in the rate of mortality and hospitalization, both randomized clinical trials and real-life studies have shown that sacubitril/valsartan induced the "reverse remodeling" of the left ventricle (LV), with a reduction in the ventricular volumes, an increase in the ejection fraction (EF) [4,5], an improvement in the diastolic function and a reduction in the degree of functional mitral regurgitation.

In 2022 paper was published on the effect of Sacubitril/valsartan on pulmonary artery pressure in patients with heart failure with preserved function and shows these results Sacubitril/valsartan significantly reduced mean pulmonary artery pressure in patients with heart failure with preserved ejection fraction "HFpEF", independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and quality of life. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH .

In this study will be conducted to estimate the effect of (valsartan-sacubitril) on pulmonary artery systolic pressure in patient with HFrEF We will assume a research question which will be to what extent the use of (valsartan-sacubitril) does started from (50 mg bid to 200 mg bid) will cause reducing in pulmonary artery systolic pressure.