Aldosterone Accelerates Systolic Decline in Volume-Overload Heart Failure

High-output heart failure (HF) occurs with sustained volume overload. Hence, clarifying how compensated high-output states transition to maladaptive HF is essential for developing interventions that preserve cardiac function. Therefore, this study investigated the mechanism by which volume overload induced by aortocaval shunt (AVS) and aldosterone (Ald) affects the progression of myocardial function and structural remodeling. AVS was surgically induced in rats, and osmotic mini-pumps delivering Ald (1.0 μg·h^-1) for 4 weeks were intraperitoneally implanted. Cardiac function and structure were serially assessed using echocardiography before surgery and at 4, 12, and 24 weeks under isoflurane. At 23 weeks, atrial natriuretic peptide was analyzed, and at 24 weeks, comprehensive electrophysiological, hemodynamic, morphometric, and histological examinations were performed to characterize cardiopathy. Early diastolic mitral annular velocity (E') remained relatively unchanged after 24 weeks, whereas early diastolic filling wave (E) velocity, atrial contraction wave velocity, and E/E' ratio increased. However, AVS did not markedly reduce systolic function; it was associated with progressive elevation of cardiac output, left ventricular hypertrophy, and dilation. Histological and morphometric analyses confirmed concentric hypertrophy, eccentric remodeling, and focal fibrosis. Ald induced similar diastolic changes and structural remodeling but caused an earlier decline in systolic function at 8 weeks. These findings demonstrate a 2-phase trajectory of high-output stress: an early compensated stage with elevated filling pressure, followed by a decompensated stage with progressive systolic decline. Moreover, Ald accelerates this systolic decline. Therefore, targeting Ald receptors in the early compensation phase may protect against systolic impairment caused by volume overload.