Cardiac Rehabilitation for Fontan Circulation Patients: A Systematic Review, and Meta-Analysis

Abstract

Background and Objectives: Despite advances in the surgical management of patients with Fontan circulation, their exercise capacity and quality of life remain significantly impaired. Exercise-based cardiac rehabilitation (CR) offers promising improvements in these areas, but the implementation and adherence to these programmes are often inconsistent. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Materials and Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted on 24 August 2023. Studies were screened and assessed for quality using the Cochrane RoB Tool 2 and STROBE checklist. Meta-analysis was performed using a continuous random-effects model to determine the effectiveness of various CR interventions, including aerobic exercise training (AET), resistance training, and inspiratory muscle training (IMT). Results: A total of 26 studies (7 RCTs, 19 cohorts) comprising 22 distinct cohorts were included, with a total sample size of 428 Fontan patients. The interventions ranged from 4 weeks to 24 months and included AET (18 studies), resistance training (11 studies), and IMT (6 studies). The meta-analysis revealed significant improvements in exercise capacity, with a pooled mean difference in peak VO₂ of 1.947 (95% CI: 1.491 to 2.402, p < 0.001). Subgroup analyses showed that combined AET and resistance training had the most robust effect, with a mean difference of 2.11 (95% CI: 1.57 to 2.65, p < 0.001). Home-based interventions showed significant benefits, while supervised and hybrid interventions did not show statistically significant differences. Publication bias was identified, particularly in home-based interventions, where smaller studies demonstrated larger effect sizes, as confirmed by Egger's test (Intercept = 2.417, 95% CI: 1.498 to 3.337, p = 0.001). However, no significant bias was detected in supervised or hybrid interventions, which displayed symmetrical distributions in funnel plots and non-significant Egger's test results. Conclusions: CR appears to be an effective intervention for improving exercise capacity in Fontan patients, particularly when combining AET with resistance training. Home-based programmes offer promising results, though the potential for publication bias, especially in smaller studies, warrants cautious interpretation of these findings. Further research is needed to refine protocols, explore long-term outcomes, and determine the underlying mechanisms, particularly for patients with more severe clinical presentations. The low incidence of adverse events across the studies reinforces the safety of these interventions.

Keywords: Fontan circulation; aerobic exercise; cardiac rehabilitation; exercise training; meta-analysis; systematic review; univentricular heart.

Figure 1

Prisma flow diagram of the study selection. In total, 1999 articles were identified by the online databases and 6 articles were manually included. After removing the duplicates, 1146 articles were screened. After screening by title/abstract, a full-text screening was done for 44 of the 1146 articles. Of these articles, 26 adhered to all inclusion criteria and were subsequently included in the systematic review and meta-analysis.

Figure 2

Forest plot demonstrating the effect of cardiac rehabilitation interventions by evaluating the parameter peak VO2, regarding intervention type, using a continuous random-effects model. The overall pooled effect showed a significant improvement in peak VO2 after participating in a cardiac rehabilitation intervention (p < 0.001). Subgroup analysis investigated the effect of different types of cardiac rehabilitation interventions. AET: Aerobic exercise training. IMT: Inspiratory muscle training.

Figure 3

Forest plot demonstrating the effect of cardiac rehabilitation interventions by evaluating the parameter peak VO2, regarding rehabilitation setting, using a continuous random-effects model. The overall pooled effect showed a significant improvement in peak VO₂ after participating in a cardiac rehabilitation intervention (p < 0.001). Subgroup analysis investigated if the setting of the cardiac rehabilitation intervention influenced the effect.

Figure 4

Forest plot demonstrating the effect of cardiac rehabilitation interventions by evaluating the parameter peak work, regarding intervention type, using a continuous random-effects model. The overall pooled effect did not show a significant improvement in peak work after participating in a cardiac rehabilitation intervention (p = 0.0128). Subgroup analysis investigated the effect of different types of cardiac rehabilitation interventions.

Figure 5

Funnel plot showing potential publication bias for peak VO₂ across various intervention types. The plot includes aerobic exercise training (AET), resistance training, inspiratory muscle training (IMT), AET combined with resistance, and AET combined with IMT. The dashed lines represent the 95% pseudo-confidence intervals, and the solid line indicates the estimated overall effect size (mean difference) across all studies.

Figure 6

Funnel plot depicting potential publication bias in studies assessing peak VO₂, stratified by rehabilitation setting: home-based, supervised, and hybrid interventions. The dashed lines represent the 95% pseudo-confidence intervals, while the solid line indicates the estimated overall effect size across all studies.

Figure 7

Funnel plot illustrating potential publication bias for peak work across all intervention types, including aerobic exercise training (AET), resistance training, inspiratory muscle training (IMT), and a combination of AET and resistance. The dashed lines represent the 95% pseudo-confidence intervals, while the solid line shows the estimated overall effect size (Cohen’s d).