PMID 36894992

Research
All papers

Hypermethylation of ACADVL is involved in the high-intensity interval training-associated reduction of cardiac fibrosis in heart failure patients

Hsu CC, Wang JS, Shyu YC, Fu TC, Juan YH, Yuan SS, Wang CH, Yeh CH, Liao PC, Wu HY, Hsu PH

Question

Is HIIT-associated DNA methylation, especially ACADVL hypermethylation, involved in reduced cardiac fibrosis in heart-failure patients?

Summary

Twelve heart-failure patients completed 36 supervised hospital-based cycling HIIT sessions over 3-4 months. VO2peak, LV function, and CMR-LGE fibrosis measures improved, and mechanistic cell experiments suggested ACADVL methylation may be involved. Because the study had no control group and a very small sample, the findings are promising but not definitive.

Methodology

  • Stable heart-failure patients diagnosed by Framingham criteria.
  • 12 participants.
  • Bicycle ergometer.
  • Work intervals: 3 min at 80% VO2peak.
  • Recovery: 3 min at 40% VO2peak.
  • Intensity: 80% and 40% of VO2peak.
  • 30 min.
  • 2-3 sessions/week.
  • 3-4 months.
  • Single-arm pre-post translational clinical study with cell-model experiments
  • VO2peak, Cardiac fibrosis, and ACADVL methylation were tracked.

Outcomes

VO2peak

VO2peak increased after HIIT.

19.0 +/- 1.1 to 21.8 +/- 1.1 mL/kg/min; p=0.009.

Improved

LV fibrosis

Middle and apical LV myocardial fibrosis decreased.

Middle 30.9 +/- 1.2% to 27.2 +/- 0.8%, p=0.013; apical 33.4 +/- 1.6% to 30.1 +/- 1.6%, p=0.021.

Improved

LV function

LV volume decreased and LVEF increased after HIIT.

LV volume decreased 15-40%, p<0.05; LVEF increased about 30%, p=0.010.

Improved

ACADVL

Post-HIIT serum reduced HCF migration and ACADVL was hypermethylated.

HCF migration p=0.044; ACADVL methylation 4.474-fold increase, p=0.044.

Mixed

Insights

  • For heart-failure populations, HIIT evidence belongs in a medically supervised cardiac-rehabilitation context.
  • The 3-minute 80%/40% VO2peak cycling structure is reproducible, but not appropriate for unscreened app users.
  • Fibrosis and methylation findings should be treated as promising mechanistic signals.

Limitations

  • Very small sample of 12 heart-failure patients.
  • No non-HIIT control group.
  • Pandemic limited patient inclusion.
  • Cell, proteomic, and methylation analyses used smaller subsets.
  • Limited serum samples prevented further mechanistic investigation.

Safety

  • No adverse events were reported in the article.
  • Participants were stable heart-failure patients screened against ACSM absolute exercise contraindications and other high-risk conditions.
  • The protocol was hospital-based and should not be generalized to unsupervised cardiac HIIT.