Left Ventricle Hemodynamic Force Analysis to Assess Cardiac Functional Changes in Obstructive Hypertrophic Cardiomyopathy
摘要
Hypertrophic cardiomyopathy (HCM) impacts 1 in 500 adults globally, and without proper treatment can cause cardiac failure. HCM is characterized by hypercontractility of the heart and thickening of the left ventricle walls. In about two-thirds of HCM cases, the cardiac wall thickening is predominantly localized to the ventricular septum in such a way that obstructs blood flow to the aorta (obstructive HCM). Obstructive HCM leads to elevated pressure gradients across the left ventricle outflow tract during heart contraction (systole) and abnormal trans-mitral blood flow velocities during heart wall relaxation (diastole). All of these characteristics (structural changes, pressure gradients, and trans-mitral blood flow) are used to diagnose HCM and determine a treatment plan. Mavacamten is a first-in-class cardiac myosin inhibitor recently approved to treat obstructive HCM. Treatment with mavacamten reduces pressure gradients and improves symptoms by diminishing cardiac hypercontractility. While clinical trials with mavacamten show promising results, we still do not fully understand short- and long-term effects of mavacamten on cardiac function. To assess the effects of mavacamten, we evaluated left ventricular hemodynamic force in patients with symptomatic obstructive HCM compared to healthy patients (no evidence of cardiomyopathy). Hemodynamic force provides a sensitive measurement of the interaction of the blood flow through the left ventricle and the cardiac walls, providing critical information about heart function. We found that patients with obstructive HCM appear to have a somewhat near-normal hemodynamic force profile prior to treatment with mavacamten, but with diastolic dysfunction that greatly differs from patient to patient. We found that after 24 weeks of treatment, peak hemodynamic force consistently decreased during systole in patients who clinically responded well to the treatment, showing improved systolic function. Diastolic changes in hemodynamic force profiles were highly variable across patients, warranting further exploration.