Exercise-based cardiac rehabilitation and parasympathetic function in patients with coronary artery disease: a systematic review and meta-analysis

Purpose The effects of exercise-based cardiac rehabilitation (CR) on parasympathetic modulation are controversial. This systematic review and meta-analysis aims to (a) determine the effect of exercise-based CR on heart-rate-derived indices associated with cardiac parasympathetic modulation in resting and post-exercise conditions in coronary artery disease (CAD) patients and (b) identify the possible moderator variables of the effect of exercise-based CR on parasympathetic modulation. Methods We searched CENTRAL and Web of Science up to November 2018 for the following terms: adult CAD patients, controlled exercise-based CR interventions and parasympathetic modulation measured in resting (vagal-related heart rate variability [HRV] indices of the root mean square of the differences in successive in RR interval [RMSSD] and high frequency [HF]) and post-exercise (heart rate recovery [HRR]) pre- and post-intervention. We estimated a random-effects model of standardised mean difference (SMD) and mean difference (MD) for vagal-related HRV indices and HRR, respectively. We assessed the influence of categorical and continuous variables. Results The overall effect size showed significant differences in RMSSD (SMD+ = 0.30; 95% confidence interval [CI] = 0.12-0.49) and HRR (MD+ = 5.35; 95% CI = 4.08-6.61 bpm) in favour of the exercise-based CR group. The overall effect size showed no differences in HF between groups (SMD+ = 0.14; 95% CI, -0.12-0.40). Heterogeneity analyses reached statistical significance, with high heterogeneity for HF (p < 0.001; I-2 = 70%) and HRR (p < 0.001; I-2 = 85%). Analysis of the moderator variables showed that the effect on HRR is greater in young patients (p = 0.008) and patients treated with percutaneous intervention (p = 0.020). Conclusions Exercise-based CR improves the post-exercise parasympathetic function, with greater effects in younger CAD patients and in those who were revascularised with percutaneous intervention. The effects on resting parasympathetic function are more controversial due to methodological inconsistencies in measuring HRV, with the use of RMSSD recommended instead of HF because its results show higher consistency. Future studies involving women, focusing on methodological issues, and performing other training methods are needed to increase our knowledge about this topic.