Varying Physical Activity for Patients With HFpEF Fails to Increase VO2 Levels

Published on: 

A comparison of patients with heart failure with preserved ejection fraction (HFpEF) randomized to 1 of 2 physical activities did not show a significant increase in peak oxygen consumption (VO2) vs guideline-based physical activity.

A comparison of patients with heart failure with preserved ejection fraction (HFpEF) randomized to high-intensity interval training (HIIT) or moderate continuous training (MCT) did not show a significant increase in their peak oxygen consumption (VO2) vs guideline-based physical activity (GBPA). The results appeared recently in JAMA.

The mean patient age was 70 years, 67% were women, mean peak VO2 was 18.8 mL/kg/min, and mean body mass index was 30.0. Evaluations were carried out at 3 months (in clinic) and 12 months (via telemedicine for home-based exercise).

Although endurance exercise has proven results for VO2 improvement in patients with HFpEF, the method examined in this study did not, the authors noted. “To date, only 1 trial in 11 patients with HFpEF examined the effect of a 1-year exercise intervention,” they said.

Their primary outcome was change in peak VO2 at 3 months, and secondary outcomes were changes in cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months.

Overall, no statistically significant mean (SD) differences in VO2 were evident by the 12-month mark:

  • HIIT: 0.9 (3.0) mL/kg/min
  • MCT: 0 (3.1) mL/kg/min
  • GBPA: −0.6 (3.4) mL/kg/min (P = .11)

However, quality of life improvements as measured by the Kansas City Cardiomyopathy Questionnaire were noticeable when comparing MCT and GBPA (11; 95% CI, 2-19) vs HIIT and GBPA (4; 95% CI, –3 to 12) or MCT (–6; 95% CI, –15 to 2).

Results were more apparent at 3 months, where analyses for change in peak VO2 produced the following:

  • HIIT vs GBPA: 1.1 vs −0.6 mL/kg/min (difference, 1.5; 95% CI, 0.4-2.7; P = .01)
  • MCT GBPA: 1.6 vs −0.6 mL/kg/min (difference, 2.0; 95% CI, 0.9-3.1; P = .001)
  • HIIT vs MCT: 1.1 vs 1.6 mL/kg/min (difference, −0.4; 95% CI, −1.4 to 0.6 P = .41)

A maximal cardiopulmonary exercise test was performed at baseline to individualize exercise intensity and adapted for repeat evaluation at 6 weeks and 3 and 6 months. The benchmark for minimal clinical improvement had been set at 2.5 mL/kg/min. No significant changes were seen in diastolic function or natriuretic peptides.

Acute coronary syndrome was the most common adverse event (AE), occurring in 4 (7%) patients in the HIIT group, 3 (5%) in the MCT group, and 5 (8%) in the control group. AEs occurred most in the MCT group (67%), followed by the HIIT (62%) and GBPA (48%) groups.

The international study took place from July 2014 to September 2018 in 5 locations in 3 countries: Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway. Three groups of sedentary patients with chronic, stable HFpEF (New York Heart Association class II-III disease/exertional dyspnea), were divided evenly for 1 year among the following:

  • HIIT for 3 weekly sessions of 38 minutes each (n = 60; 10-minute warm-up at 35%-50% heart rate reserve [HRR], 4 x 4-minute intervals at 80%-90% HRR, interspaced by 3 minutes of active recovery)
  • MCT for 5 weekly sessions of 40 minutes each (n = 60; 35%-50% HRR)
  • GBPA, comprising 1-time advice (n = 60; the control group)

“Among patients with HFpEF, there was no statistically significant difference in change in peak VO2 at 3 months between those assigned to high-intensity interval vs moderate continuous training, and neither group met the prespecified minimal clinically important difference compared with the guideline control,” the authors stated. “Furthermore, neither group met the a priori–defined minimal clinically important difference of 2.5 mL/kg/min compared with the guideline control at any time point.”

They do not recommend prescribing HIIT or MCT over GBPA for patients with HFpEF.

Possible limitations on their findings include the low adherence rates to the study’s exercise regimens (50% of patients performed just 70% of the training sessions) and staff being unblinded to treatment group assignment, which may have biased the maximal exhaustion measure during the cardiopulmonary exercise test.

Last week, the FDA approved Entresto (sacubitril/valsartan) for HFpEF, making it the first medication with this indication.


Mueller S, Winzer EB, Duvinage A, et al; OptimEx-Clin Study Group. Effect of high-intensity interval training, moderate continuous training, or guideline-based physical activity advice on peak oxygen consumption in patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2021;325(6):542-551. doi:10.1001/jama.2020.26812