Sex differences in cardiac function and clinical outcome in patients with a Fontan circulation

Background This study aims to assess sex differences with regards to outcome, cardiovascular dimensions, and functional capacity in patients with a Fontan circulation. Methods In this single-center prospective, standardised cohort study of 60 Fontan patients (30 females, 50%) aged ≥10 years, the association between sex and the combined outcome variable of all-cause mortality, heart/heart-lung transplantation (including listing) and Fontan-related hospitalisation was investigated. Secondary outcome measures included functional capacity and ventricular dimensions, measured by cardiac magnetic resonance imaging (CMR), cardiopulmonary exercise testing (CPET) and concomitant clinical assessment. Results Baseline characteristics including age, diagnosis and surgical history did not differ between female and male patients. During a median follow-up time of 5.75 (5.4–6.0) years, the combined outcome variable occurred in 17 (28%) patients. Female Fontan patients had 13 (43%) adverse events and males 4 (13%). Event-free survival differed significantly (p ​= ​0.040). At baseline, the majority of males was in NYHA class I (n ​= ​19, 63%), whereas the majority of females was in NYHA class II or III (n ​= ​20, 67%) (p ​= ​0.036). Male Fontan patients had about 25% higher end-diastolic volume (p ​= ​0.001) indexed for body surface area (BSA), 28% higher indexed end-systolic volume (p ​= ​0.004) and 25% more indexed ventricular mass (p ​< ​0.001). Conclusions In Fontan patients, event-free survival is significantly higher in males compared to females. Relevant sex differences in ventricular dimensions as well as functional capacity exist, which exceed the differences seen in the healthy population. These differences should be considered when analysing and interpreting cut-off values to improve risk stratification.