Reversing the Cardiac Effects of Sedentary Aging in Middle Age—A Randomized Controlled Trial

Abstract

Background: Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness. Methods: Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo 2 max) was measured to quantify changes in fitness. Results: Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo 2 max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P <0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P =0.0018), whereas there was no change in controls (group×time P <0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P =0.83). Exercise increased LV end-diastolic volume (group×time P <0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P =0.007). Conclusions: In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02039154.