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

PMID: 36894992
Journal: Journal of Translational Medicine
Published: 2023-03-10
Authors: 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.

## Population

- Stable heart-failure patients diagnosed by Framingham criteria.
- Sample size: 12
- Age: 20-80 years eligible
- Fitness level: Reduced aerobic capacity; baseline VO2peak 19.0 +/- 1.1 mL/kg/min
- Health status: Stable heart failure under optimized guideline-based management

## Methodology

- Single-arm pre-post translational clinical study with cell-model experiments
- 36 sessions over 3-4 months
- Hospital-based cycling HIIT and laboratory cardiac-fibroblast experiments

## Protocol

- Heart-failure cycling HIIT.
- Modality: Bicycle ergometer.
- Work intervals: 3 min at 80% VO2peak.
- Recovery: 3 min at 40% VO2peak.
- Sets or repetitions: Alternating intervals for 30 min.
- Intensity: 80% and 40% of VO2peak.
- Session duration: 30 min.
- Frequency: 2-3 sessions/week.
- Program length: 3-4 months.

## Outcomes

### VO2peak
Status: improved
VO2peak increased after HIIT.

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

### LV fibrosis
Status: improved
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.

### LV function
Status: improved
LV volume decreased and LVEF increased after HIIT.

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

### ACADVL
Status: mixed
Post-HIIT serum reduced HCF migration and ACADVL was hypermethylated.

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

## Practical 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 And Adherence

- 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.

## Original Sources

- [PubMed](https://pubmed.ncbi.nlm.nih.gov/36894992/) (pubmed)
- [DOI](https://doi.org/10.1186/s12967-023-04032-7) (doi)
- [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999524/) (full text)

## Agent Guidance

Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.