Abstract
Background: There are no proven pharmacologic strategies for HFpEF; therefore, lifestyle interventions must be developed to prevent disease progression in those at high risk for developing HFpEF (Stage A). We performed a randomized, double blind, placebo controlled trial evaluating the effect of 1-year of high intensity interval training (HIIT) and polyunsaturated fatty acid supplementation (PUFA) on key risk factors in Stage A HFpEF. Hypothesis: Long duration (1-year) HIIT and PUFA (1.6g/daily Omega-3-Acid Ethyl Esters) will reduce visceral adiposity, improve aerobic fitness, and reverse vascular stiffness in middle-aged subjects with cardio-metabolic risk factors. Methods: Individuals with stage A HFpEF (n= 73; 40-55 years; BMI>30 kg/m 2 ; visceral fat > 2 kg; NT-proBNP>40pg/ml or hscTnT>3.0 pg/ml) were randomized to HIIT + PUFA (n=22)/placebo (n=24) or yoga + PUFA (n=15)/placebo (n=19). We assessed visceral fat (DEXA), aerobic fitness (VO 2 max), cardiac output (Q C , acetylene rebreathe), peripheral oxygen extraction (a-vO 2 -difference), and arterial stiffness (pulse wave velocity and augmentation index; tonometry). Data are presented as mean change and 95% CI. Results: 1-year of HIIT decreased body fat (-1.26%, CI: -2.43 to -0.58; p=0.036) and had a similar but less consistent effect on visceral fat (-0.28 kg, CI: -0.62 to 0.04; p=0.083). Aerobic capacity increased by ~24% (ΔVO 2 : 4.41 mL/kg/min, CI: 3.22 to 5.61; p<0.0001), due to improved peak Q C (1.84 L/min, CI: 0.34 to 2.24; p=0.017) and a-vO 2 -difference (1.31 mL/100mL, CI: 0.13 to 2.49; p=0.031). While large elastic arterial stiffness was unchanged (PWV: -21 cm/s, CI: -61 to 19; p=0.299), augmentation index was reduced (-5.23%, CI: -9.18 to -1.35; p=0.009) indicative of improved ventricular-arterial coupling. There was no independent effect of PUFA, or interaction between HIIT and PUFA for any outcomes. Conclusions: 1-year HIIT improved leanness, aerobic fitness, peak Q C and a-vO 2 -difference, and ventricular-arterial coupling in middle-aged Stage A HFpEF. There was no independent or additive effect of PUFA administration. This is the first randomized trial to demonstrate that regular HIIT can reverse cardiometabolic impairments in Stage A HFpEF.
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