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HIIT for HFpEF? Results Mixed in Exercise Trial

— Boosting intensity not obviously helpful

MedpageToday
A senior woman uses the shoulder press machine at the gym

High-intensity interval training (HIIT) did not beat traditional exercise in raising exercise capacity for sedentary patients with heart failure with preserved ejection fraction (HFpEF), according to the OptimEx-Clin trial.

HIIT and moderate continuous training groups yielded similar improvements in peak oxygen consumption (VO2) from baseline to 3 months (+1.1 vs +1.6 mL/kg/min) -- both too modest to meet a prespecified minimal clinically-important threshold in comparison with controls (-0.6 mL/kg/min).

Neither HIIT nor traditional exercise remained associated with improved exercise capacity at 12 months compared with controls, who got no supervised exercise training, only guideline-directed advice on physical activity, reported Martin Halle, MD, of the Technical University of Munich, Germany, and colleagues .

"These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF," Halle's team concluded.

Yet the data shouldn't be interpreted to say exercise doesn't work for these patients, cautioned an .

The study's prespecified 2.5-mL/kg/min threshold for peak VO2 improvement over controls was "overly ambitious because 1.0 mL/kg/min is traditionally accepted as a clinically meaningful improvement, particularly among patients with HF who have severely reduced baseline peak VO2," argued Ambarish Pandey, MD, of UT Southwestern Medical Center in Dallas, and Dalane Kitzman, MD, of Wake Forest School of Medicine in Winston-Salem, North Carolina.

Also, Halle's group suggested that it is possible that adherence was just too low for exercise training to have induced significant long-term effects in the trial.

"Adherence to exercise protocols is a major concern in long-term exercise intervention studies. In the present trial, despite telemedical support, which proved to have high acceptance even in the group of elderly individuals, only about one half of the patients performed at least 70% of the prescribed training sessions during home-based exercise training," according to the authors.

Exercise training is one of the few interventions proven to improve symptoms in the growing population of patients with HFpEF. No pharmacotherapy has withstood rigorous testing in this population.

The OptimEx-Clin trial was conducted at five sites in Europe in 2014-2018. Investigators screened 532 and enrolled 180 sedentary patients with HFpEF (mean age 70 years, 67% women, mean BMI 30.0).

Study participants were randomized to one of three groups for 12 months: HIIT (three times a week at 38 minutes per session), moderate continuous training (five times per week at 40 minutes per session), or controls receiving one-time guideline-based advice on physical activity. The two exercise arms underwent 3 months of supervised training plus 9 months of home-based exercise with remote heart rate monitoring.

However, actual exercise fell short of targets. The HIIT group attended a median 2.5 training sessions per week (totaling 96 minutes) in the clinic; this fell to 2.0 sessions (or 77 minutes) at home. Similarly, moderate continuous training was performed at a median 4.4 supervised sessions per week (or 176 minutes), and 3.6 sessions at home (144 minutes).

There were no significant changes in diastolic function or natriuretic peptides in the trial.

"In accordance with most of the previous exercise trials in HFpEF, the present study failed to demonstrate that the improvement in exercise capacity at 3 months was related to changes in diastolic function. These findings underscore that apart from diastolic dysfunction, other mechanisms likely contributed to the observed improvement in peak VO2," study authors said.

Halle and colleagues noted that serious adverse event rates were considerably higher in OptimEx-Clin than in previous exercise trials in HFpEF, reflecting a sicker, multimorbid population. For example, an acute coronary syndrome occurred in 7% of HIIT patients, 5% of moderate continuous training patients, and 8% of guideline controls.

HIIT was supposed to be especially attractive to patients because it requires fewer and shorter sessions for physical conditioning. Although it did not surpass moderate continuous training in the trial, the findings highlight the importance of enhancing long-term adherence and reducing extracardiac contributors to exercise intolerance, Pandey and Kitzman wrote in their editorial.

Limitations of the study included non-blinded study staff and the lack of exercise echocardiography assessing changes of diastolic function during exercise.

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    Nicole Lou is a reporter for ľֱ, where she covers cardiology news and other developments in medicine.

Disclosures

The study was supported by grants from the European Commission, Deutsche Forschungsgemeinschaft, and Flemish Research Funds.

Halle reported receiving grants from Novartis and personal fees from Bristol-Myers Squibb, Berlin Chemie-Menarini, Novartis, Daiichi-Sankyo, AstraZeneca, Roche, Abbott, Sanofi, Pfizer, Boehringer Ingelheim, and Bayer.

Pandey reported serving on the advisory board of Roche Diagnostics.

Kitzman disclosed consulting for AbbVie, Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, Novo Nordisk, AstraZeneca, St Luke's Hospital, and Novartis; grant funding from Novartis, Bayer, Novo Nordisk, and AstraZeneca; and stock ownership in Gilead Sciences.

Primary Source

JAMA

Mueller S, et al "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; DOI: 10.1001/jama.2020.26812.

Secondary Source

JAMA

Pandey A, Kitzman DW "Searching for the optimal exercise training regimen in heart failure with preserved ejection fraction" JAMA 2021; 325(6): 537-539. DOI: 10.1001/jama.2020.26347.