High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction

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.

Methodology

Stable, optimally medically treated patients with symptomatic chronic heart failure with reduced ejection fraction, NYHA class II-III and LVEF <=35%.
261 participants.
Treadmill or bicycle.
Work intervals: 4 minutes.
Recovery: 3 minutes active recovery at moderate intensity.
Intensity: 90%-95% maximal heart rate.
38 minutes including warm-up and cool-down.
3 supervised sessions per week.
12 weeks.
Investigator-initiated randomized controlled multicenter clinical trial with three groups.
Left ventricular end-diastolic diameter, Peak oxygen uptake, Left ventricular ejection fraction, and Serious adverse events were tracked.

Outcomes

Left ventricular end-diastolic diameter

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.

Mixed

Peak oxygen uptake

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.

Mixed

52-week maintenance

At 1-year follow-up, there were no differences in primary or secondary endpoints between groups.

No clear change

Training intensity fidelity

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.

Mixed

Serious adverse events

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.

Mixed

Quality of life

There were no within-group or between-group differences in reported quality-of-life measures.

No clear change

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

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.