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| Reversing the cardiac effects of sedentary aging in middle age-a randomized controlled trial: implications for heart failure prevention |
| Howden EJ, Sarma S, Lawley JS, Opondo M, Cornwell W, Stoller D, Urey MA, Adams-Huet B, Levine BD |
| Circulation 2018 Apr 10;137(15):1549-1560 |
| clinical trial |
| 6/10 [Eligibility criteria: Yes; Random allocation: Yes; Concealed allocation: No; Baseline comparability: Yes; Blind subjects: No; Blind therapists: No; Blind assessors: Yes; Adequate follow-up: Yes; Intention-to-treat analysis: No; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed* |
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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 (VO2max) was measured to quantify changes in fitness. RESULTS: Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88 +/- 11%. VO2max 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 x 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 x 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 x time p < 0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading x group x 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.
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