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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 FractionA Randomized Clinical Trial

Educational Objective
To learn the effect of differing modes of exercise on peak oxygen consumption (V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF).
1 Credit CME
Key Points

Question  Is there a difference in change in peak oxygen consumption (V̇o2) among patients with heart failure with preserved ejection fraction (HFpEF) treated with differing modes of exercise?

Findings  This randomized clinical trial included 180 patients with HFpEF assigned to high-intensity interval training, moderate continuous training, or a control of guideline-based physical activity advice. At 3 months, the changes in peak V̇o2 were 1.1, 1.6, and −0.6 mL/kg/min, respectively. There was no statistically significant difference between high-intensity interval and moderate continuous training, and neither group met the a priori–defined minimal clinically important difference of 2.5 mL/kg/min compared with the guideline control.

Meaning  These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF.

Abstract

Importance  Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects.

Objective  To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF.

Design, Setting, and Participants  Randomized clinical trial at 5 sites (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway) from July 2014 to September 2018. From 532 screened patients, 180 sedentary patients with chronic, stable HFpEF were enrolled. Outcomes were analyzed by core laboratories blinded to treatment groups; however, the patients and staff conducting the evaluations were not blinded.

Interventions  Patients were randomly assigned (1:1:1; n = 60 per group) to high-intensity interval training (3 × 38 minutes/week), moderate continuous training (5 × 40 minutes/week), or guideline control (1-time advice on physical activity according to guidelines) for 12 months (3 months in clinic followed by 9 months telemedically supervised home-based exercise).

Main Outcomes and Measures  Primary end point was change in peak V̇o2 after 3 months, with the minimal clinically important difference set at 2.5 mL/kg/min. Secondary end points included changes in metrics of cardiorespiratory fitness, diastolic function, and natriuretic peptides after 3 and 12 months.

Results  Among 180 patients who were randomized (mean age, 70 years; 120 women [67%]), 166 (92%) and 154 (86%) completed evaluation at 3 and 12 months, respectively. Change in peak V̇o2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs −0.6 mL/kg/min (difference, 1.5 [95% CI, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs −0.6 mL/kg/min (difference, 2.0 [95% CI, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, −0.4 [95% CI, −1.4 to 0.6]). No comparisons were statistically significant after 12 months. There were no significant changes in diastolic function or natriuretic peptides. Acute coronary syndrome was recorded in 4 high-intensity interval training patients (7%), 3 moderate continuous training patients (5%), and 5 guideline control patients (8%).

Conclusions and Relevance  Among patients with HFpEF, there was no statistically significant difference in change in peak V̇o2 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. These findings do not support either high-intensity interval training or moderate continuous training compared with guideline-based physical activity for patients with HFpEF.

Trial Registration  ClinicalTrials.gov Identifier: NCT02078947

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Article Information

Corresponding Author: Martin Halle, MD, Department of Prevention and Sports Medicine, Accredited Centre for Sports Cardiology/EAPC, School of Medicine, University Hospital Klinikum rechts der Isar, Technical University of Munich, Georg-Brauchle-Ring 56, D-80992 Munich, Germany (martin.halle@mri.tum.de).

Accepted for Publication: December 28, 2020.

Author Contributions: Mr Mueller and Dr Haller had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Mueller and Drs Winzer, van Craenenbroeck, and Halle contributed equally.

Concept and design: Edelmann, Haller, Beckers, Christle, Linke, Wisløff, Adams, Pieske, Halle.

Acquisition, analysis, or interpretation of data: Mueller, Winzer, Duvinage, Gevaert, Edelmann, Haller, Pieske-Kraigher, Beckers, Bobenko, Hommel, Van de Heyning, Esefeld, von Korn, Christle, Haykowsky, Linke, Van Craenenbroeck, Halle.

Drafting of the manuscript: Mueller, Duvinage, Haller, Haykowsky, Halle.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Duvinage, Haller, Halle.

Obtained funding: Wisløff, Adams, Pieske, Halle.

Administrative, technical, or material support: Mueller, Gevaert, Edelmann, Beckers, Bobenko, Van de Heyning, von Korn, Christle, Linke, Wisløff, Adams, Halle.

Supervision: Mueller, Winzer, Edelmann, Pieske-Kraigher, Beckers, Van de Heyning, von Korn, Christle, Linke, Wisløff, Adams, Pieske, Van Craenenbroeck, Halle.

Conflict of Interest Disclosures: Dr Mueller reported receiving grants from Deutsche Forschungsgemeinschaft (DFG) through the TUM International Graduate School of Science and Engineering during the conduct of the study. Dr Winzer reported receiving personal fees from Novartis (honoraria for lectures and advisory board activities), Boehringer Ingelheim (honoraria for advisory board activities), and CVRX (honoraria for lectures) outside the submitted work. Dr Duvinage reported receiving grants from Novartis outside the submitted work. Dr Van de Heyning reported receiving speaker fees from Abbott, Daiichi Sankyo, and Edwards Lifesciences outside the submitted work. Dr Linke reported receiving speaker fees from Abbott, Medtronic, Edwards Lifesciences, AstraZeneca, Boston Scientific, and Novartis; grants from Edwards Lifesciences and Novartis; advisory board fees from Transverse Medical, Picardia, Edwards Lifesciences, and Heart Leaflet Technology; and stock options from Claret Medical and Transverse Medical, and being a co-owner of Dresden Cardiovascular Research Institute and Core Laboratories outside the submitted work. Dr Pieske reported receiving personal fees from Bayer Healthcare (steering committee, lectures), Merck (steering committee, lectures), Novartis (steering committee, lectures), Servier, AstraZeneca (lectures), Bristol-Myers Squibb (lectures), and Medscape (lectures) outside the submitted work. Dr Van Craenenbroeck reported receiving grants from the Flemish Research Funds (FWO) during the conduct of the study. Dr Halle reported receiving grants from the TUM International Graduate School of Science and Engineering during the conduct of the study and grants from Novartis (principal investigator of the Activity Study in HFrEF) and personal fees from Bristol-Myers Squibb, Berlin Chemie-Menarini, Novartis, Daiichi-Sankyo, AstraZeneca, Roche, Abbott (advisory board on exercise and diabetes), Sanofi, Pfizer, Boehringer Ingelheim, and Bayer outside the submitted work. No other disclosures were reported.

Funding/Support: This trial was funded by the European Commission, Framework Program 7, grant No. EU-602405-2; the Deutsche Forschungsgemeinschaft (DFG) through the TUM International Graduate School of Science and Engineering (IGSSE); and the Flemish Research Funds (FWO) through a Senior Clinical Investigator grant to Dr van Craenenbroeck.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The OptimEx-Clin Study Group members are listed in Supplement 2.

Data Sharing Statement: See Supplement 3.

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