Abstract
IMPORTANCE: Heart rate variability biofeedback (HRVB) is a self-regulation intervention that targets autonomic nervous system activity through guided breathing and visualization. Investigating its effects on cardiovascular responses to psychological stress may clarify its therapeutic potential for patients with coronary artery disease (CAD). OBJECTIVE: To examine the effects of HRVB on myocardial blood flow (MBF) changes during a mental stress challenge in individuals with CAD. DESIGN, SETTING, AND PARTICIPANTS: This single-center pilot randomized clinical trial included participants aged 30 to 79 years with CAD recruited in a university hospital setting and enrolled from March 30 to November 9, 2016 (data were analyzed from January to August 2025 for final reporting). Participants were followed up for 2 months. INTERVENTION: Six weeks of HRVB training and prescribed daily practice vs usual care (standard medical care with the intervention received after study completion). MAIN OUTCOMES AND MEASURES: Myocardial blood flow changes after an arithmetic mental stress challenge, as measured by rubidium-82 positron emission tomography at baseline and again after 8 weeks. Linear mixed models examined the effects of HRVB on mental stress myocardial flow reserve (MFR), which is the ratio of MBF with mental stress to MBF at rest, while adjusting for baseline flow levels. RESULTS: Data were analyzed from 21 participants (12 HRVB, 9 usual care) with mean (SD) age of 65 (6) years; 13 (61.9%) were male. In the HRVB group, the mean MFR with mental stress at baseline was 1.07 (95% CI, 0.94-1.22) and after the intervention was 1.16 (95% CI, 1.06-1.26). In the usual care group, the mean MFR with mental stress at baseline was 1.20 (95% CI, 1.05-1.38) and at the follow-up visit was 1.15 (95% CI, 0.94-1.40). While the within-group changes were not statistically significant, between-group difference in change from baseline to follow-up was significant. Specifically, the change in MFR in the HRVB group was 0.10 (95% CI, 0.01-0.19) units greater than the change in the usual care group (P = .03). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of participants with CAD, HRVB resulted in an increased MFR with mental stress compared with usual care. These results suggest potential benefits of HRVB during periods of mental stress and support the need for larger clinical trials to further investigate the efficacy of HRVB in cardiovascular disease prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02657382.