Abstract 4343917: Myocardial stiffness properties are improved in heart failure with preserved ejection fraction (HFpEF) in pigs by a regular exercise regime

Abstract

Background: Left ventricular (LV) pressure overload (LVPO) causes LV hypertrophy and resistance to LV filling, notably increased LV chamber stiffness and LV myocardial stiffness (Kc, Km, respectively), and ultimately causes increased pulmonary capillary wedge pressure (PCWP) and the development of heart failure with preserved ejection fraction (HFpEF). Exercise programs in HFpEF patients have been promising, but whether an exercise program superimposed with progressive LVPO would alter LV stiffness properties and thus HFpEF progression remains unclear. Methods/Results: Pigs (25 kg) underwent progressive LVPO for 5 weeks without (n=8) or with daily exercise (n=8, 10 degrees elevation, 2.5 mph, 10 min, 5 days/week). LV function and geometry was determined at baseline and weekly by transthoracic echocardiography whereby Kc and Km were computed by validated algorithms including speckle tracking echocardiography (Figure). In both LVPO groups, LV mass increased by over 55% from baseline, and while Kc and Km increased in a time dependent manner with LVPO, the increase in LV stiffness properties was significantly reduced in the LVPO exercise group, which was particularly evident for Km. At 5 weeks, PCWP was lower in the LVPO exercise group (10.52 ± 0.35 vs 11.88 ± 0.34 mmHg, p<0.05). LV collagen percent area by histomorphometry was reduced in the LVPO exercise group compared to LVPO (5.96 ± 0.50 vs 10.82 ± 0.39 %, p<0.05). Thus, this model of progressive LVPO caused time dependent increases in LV stiffness properties, fibrosis and emergence of a HFpEF phenotype whereby these changes were blunted with a superimposed exercise protocol. Conclusions: The unique and significant findings from this study were that with a continuous and progressive LVPO stimulus, a superimposed regular exercise protocol did not alter the LV hypertrophic response, but reduced time dependent increases in LV stiffness properties, particularly Km, and a structural basis for this effect was the prevention of myocardial fibrosis.