Diagnostic Accuracy of a Precision Medicine Blood Test for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients with Newly-Diagnosed Heart Failure with Reduced Ejection Fraction - A Pilot Study

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with pulmonary vascular dysfunction, particularly during exercise. Pulmonary vasodilators may favorably reduce pulmonary artery (PA) tone in HFpEF, but this could theoretically worsen left atrial hypertension and pulmonary congestion. Objective: To evaluate whether the inhaled b-adrenergic agonist albuterol would improve PA vascular function during exercise in HFpEF. Methods: We performed a randomized double blind placebo controlled trial testing the effects of inhaled albuterol on resting and exercise hemodynamics in HFpEF using high fidelity micromanometer catheters and expired gas analysis. The primary end point was pulmonary vascular resistance (PVR) during exercise. Results: Subjects with HFpEF (n=30) underwent resting and exercise hemodynamic assessment and were then randomized 1:1 to inhaled, nebulized albuterol or placebo, followed by repeat assessment of rest and exercise hemodynamics. Albuterol improved the primary endpoint of exercise PVR as compared to placebo (¡0.6 §0.5 vs +0.1 §0.7 Wood units, p=0.003). As compared to placebo, albuterol enhanced PA compliance with exercise, improved cardiac output reserve and RV-PA coupling, reduced right atrial and pulmonary artery pressures, and enhanced left ventricular transmural distending pressure during exercise (all p<0.01), with no untoward increase in pulmonary capillary hydrostatic pressures. Conclusions: Albuterol improves pulmonary vascular function and cardiac hemodynamics with exercise in patients with HFpEF. Further study is warranted to evaluate the chronic efficacy of b-agonists and other pulmonary vasoactive medicines in this population. Clinical Trial Registration: Inhaled Beta-adrenergic agonists to Treat Pulmonary Vascular Disease in Heart Failure with Preserved Ejection Fraction (BEAT HFpEF) -NCT02885636.