# High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction PMID: 28082387 Journal: Circulation Published: 2017-02-28 Authors: Ellingsen Ø, Halle M, Conraads V, Støylen A, Dalen H, Delagardelle C, Larsen AI, Hole T, Mezzani A, Van Craenenbroeck EM, Videm V, Beckers P, Christle JW, Winzer E, Mangner N, Woitek F, Höllriegel R, Pressler A, Monk-Hansen T, Snoer M, Feiereisen P, Valborgland T, Kjekshus J, Hambrecht R, Gielen S, Karlsen T, Prescott E, Linke A, SMARTEX Heart Failure Study (Study of Myocardial Recovery After Exercise Training in Heart Failure) Group ## Question To test whether supervised HIIT is superior to moderate continuous training for improving left ventricular dimensions and exercise capacity in patients with heart failure with reduced ejection fraction. ## Summary This multicenter randomized trial tested 12 weeks of supervised HIIT, moderate continuous training, or a recommendation of regular exercise in patients with stable heart failure with reduced ejection fraction. HIIT was not superior to moderate continuous training for left ventricular remodeling or peak oxygen uptake. Both supervised exercise programs improved aerobic capacity more than regular exercise advice at 12 weeks, but the improvements were not maintained at 52 weeks. Training-intensity fidelity was a major issue: many HIIT participants trained below target, and many MCT participants trained above target. ## Population - Stable, optimally medically treated patients with symptomatic chronic heart failure with reduced ejection fraction, NYHA class II-III and LVEF <=35%. - Sample size: 261 - Age: Median 60 years; IQR 53-70. - Sex: 19% women. - Fitness level: Median baseline VO2peak 17.1 mL/kg/min, IQR 14.2-20.3. - Health status: Stable chronic heart failure with reduced ejection fraction; median LVEF 29%, IQR 24%-34%. ## Methodology - Investigator-initiated randomized controlled multicenter clinical trial with three groups. - 12-week supervised intervention with 52-week follow-up from training start. - Nine European centers with supervised cardiac rehabilitation-style exercise sessions. - Randomized and controlled study design. ## Protocol - HIIT. - Modality: Treadmill or bicycle. - Work intervals: 4 minutes. - Recovery: 3 minutes active recovery at moderate intensity. - Sets or repetitions: Four intervals. - Intensity: 90%-95% maximal heart rate. - Session duration: 38 minutes including warm-up and cool-down. - Frequency: 3 supervised sessions per week. - Program length: 12 weeks. - MCT and RRE. - Modality: MCT: treadmill or bicycle; RRE: home exercise advice plus periodic supervised moderate training. - Work intervals: MCT continuous exercise; RRE current-recommendation home exercise. - Sets or repetitions: MCT one continuous bout; RRE one moderate-intensity session every three weeks plus home exercise advice. - Intensity: MCT 60%-70% maximal heart rate; RRE supervised sessions 50%-70% maximal heart rate. - Session duration: MCT 47 minutes; RRE supervised session duration not specified. - Frequency: MCT 3 supervised sessions per week; RRE supervised session every 3 weeks. - Program length: 12 weeks supervised intervention, then unsupervised continuation encouraged to 52 weeks. ## Outcomes ### Left ventricular end-diastolic diameter Status: mixed HIIT was not significantly different from MCT at 12 weeks, but HIIT improved LVEDD more than RRE; MCT was not significantly different from RRE. HIIT vs MCT -1.2 mm (95% CI -3.6 to 1.2), P=0.45; HIIT vs RRE -2.8 mm (95% CI -5.2 to -0.4), P=0.02; MCT vs RRE -1.6 mm (95% CI -4.2 to 1.1), P=0.34. ### Peak oxygen uptake Status: mixed HIIT was not significantly different from MCT, but both HIIT and MCT improved VO2peak more than RRE at 12 weeks. HIIT vs MCT -0.4 mL/kg/min (95% CI -1.7 to 0.8), P=0.70; HIIT vs RRE +1.4 mL/kg/min (95% CI 0.2 to 2.6), P=0.02; MCT vs RRE +1.8 mL/kg/min (95% CI 0.5 to 3.0), P=0.003. ### 52-week maintenance Status: no clear change At 1-year follow-up, there were no differences in primary or secondary endpoints between groups. ### Training intensity fidelity Status: mixed Median relative training intensity was 90% maximal heart rate in HIIT and 77% in MCT; the achieved difference was smaller than prescribed, with substantial off-target training. HIIT 90% (IQR 88%-92%); MCT 77% (IQR 74%-82%); adjusted difference 10% (95% CI 8%-13%), P<0.001; 51% of HIIT below target and 80% of MCT above target. ### Serious adverse events Status: mixed SAEs were not statistically different, but were numerically higher in HIIT than MCT at 52 weeks; three events occurred during or within three hours of supervised HIIT. 52-week total SAEs: HIIT 32 (39%), MCT 18 (25%), RRE 26 (34%), P=0.16. ### Quality of life Status: no clear change There were no within-group or between-group differences in reported quality-of-life measures. ## Practical Insights - In clinical cardiac populations, prescribed HIIT intensity can be difficult to achieve even with supervision and heart-rate monitoring. - A 4x4-minute HIIT format should not be assumed superior to moderate continuous training for stable HFrEF. - Actual intensity monitoring and maintenance after supervised programming are critical because 12-week improvements were not maintained at 52 weeks. ## Limitations - Intensity separation between HIIT and MCT was less than intended and partly overlapped. - HIIT target of 90%-95% maximal heart rate may have been too high and MCT target of 60%-70% too low for some patients. - Questionnaires were limited for assessing physical activity outside supervised sessions. - Women were underrepresented at 19%. - The study was not powered to assess safety or clinical events. ## Safety And Adherence - Serious adverse events were not statistically different during supervised intervention or at 52 weeks, but the study was not powered to assess safety. - At 52 weeks, total patients with SAEs were HIIT 32 (39%), MCT 18 (25%), and RRE 26 (34%). - Three events occurred during or within three hours of supervised exercise in the HIIT group: ventricular arrhythmia with cardiac arrest, inappropriate ICD discharge unrelated to arrhythmia, and dizziness without detectable cardiovascular cause. ## Original Sources - [PubMed](https://pubmed.ncbi.nlm.nih.gov/28082387/) (pubmed) - [DOI](https://doi.org/10.1161/CIRCULATIONAHA.116.022924) (doi) - [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325251/) (full text) ## Agent Guidance Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.