Abstract 15822: Cardiac Effects of EDG-7500, a Novel Cardiac Sarcomere Regulator: In vitro and in vivo Evidence for Slowing Isovolumic Contraction and Improved Ventricular Compliance

• Published in: Circulation (New York, N.Y.) N.Y.), 2023-11, Vol.148 (Suppl_1)
• Main Authors: Del Rio, Carlos L, Ma, Weikang, Irving, Thomas, Roof, Steve, Tolley, Jessica, Duvall, Mike, Hawryluk, Natalie, RUSSELL, ALAN, Semigran, marc, Evanchik, Marc
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.148.suppl_1.15822

Abstract only Background: Hypertrophic Cardiomyopathy (HCM) is a disease where excess acto-myosin crossbridge formation results in hyperdynamic contraction, LV hypertrophy, and diastolic dysfunction due to increased myocardial stiffness. Conventional negative inotropes alleviate, to some degree, the systolic alteration in HCM, but do not improve LV filling. EDG-7500 is a small molecule that preferentially decreases diastolic tension and slows the velocity of myocardial force generation by regulating, but not inhibiting, cardiac myosin. This study assessed pharmacodynamic responses to EDG-7500. Methods: Myofilament biomechanics and sarcomere structure were evaluated on LV permeabilized pig fibers. In vivo, dogs were instrumented for arterial pressure and LV pressure-volume recordings. Data were obtained with vehicle, EDG-7500 (n = 5; 0.3 mg/kg IV), or metoprolol (2-4 mg/kg IV, n = 3); systemic and LV hemodynamics and load-independent function were examined. *:P