Fontan Patients with a Systemic Left Ventricle Have Greater Exercise Capacity than those with a Systemic Right Ventricle: A Systematic Review and Meta-Analysis.

Cardiopulmonary exercise testing (CPET) is a useful metric to track the functional capacity and prognosis in patients with Fontan circulation. Systemic ventricular morphology may influence CPET interpretation. This systematic review and meta-analysis assessed the impact of systemic ventricular morphology on CPET outcomes. PubMed, Embase, and Cochrane were searched from inception through December 2024. Inclusion criteria were (1) Fontan circulation, (2) CPET via treadmill or cycle ergometer, and (3) outcomes stratified by systemic ventricle. Extracted outcomes included peak VO2, O2-pulse, VE/VCO2 slope, and VO2 at anaerobic threshold (VAT). A random-effects model was used with pooled estimates reported as a mean difference (MD) or standardized mean difference (SMD). Risk of Bias (RoB) was assessed using the Newcastle-Ottawa Scale. Of 1372 screened studies, 27 met inclusion criteria (59% retrospective cohort, 30% cross-sectional, 7% randomized control trials, and 4% quasi-experimental design) encompassing 2972 participants. All studies but one had low RoB with the remainder having some RoB. Patients with a systemic left ventricle (SLV) outperformed those with a systemic right ventricle (SRV) in all metrics including a higher peak VO2 (MD 6.73% predicted; p < 0.01, 95% CI 4.52, 8.95), greater O2-pulse (0.19 SMD; p = 0.04, 95% CI 0.01, 0.38), greater VAT (0.16 SMD; p = 0.01, 95% CI 0.03, 0.28), and lower VE/VCO2 slope (MD - 2.44; p = 0.01, 95% CI - 4.41, - 0.48). These findings suggest superior exercise performance in Fontan patients with a SLV and should inform CPET interpretation. Further prospective studies are warranted to assess their impact on outcomes such as transplant timing or mortality.