Valvular involvement, phenotypic heterogeneity and outcomes in adults with left-to-right shunt congenital heart disease.

Abstract

Background: In adults with significant left-to-right shunt congenital heart disease (CHD), valvular involvement may represent an additional source of haemodynamic and remodelling burden beyond shunt loading alone, but its distribution, pulmonary haemodynamic correlates, prognostic relevance and multidimensional phenotypic patterns remain insufficiently defined.

Methods: Consecutive adults with non-complex, unrepaired left-to-right shunt CHD, pulmonary-to-systemic flow ratio >1.5 on right heart catheterisation and available echocardiographic data were retrospectively studied between 2015 and 2019. Patients were stratified by pre-tricuspid or post-tricuspid shunt location. Left-sided, right-sided and bilateral valvular involvement was evaluated in relation to invasive haemodynamics, cardiac remodelling and survival. Factor analysis of mixed data followed by hierarchical clustering was performed within each subgroup.

Results: Among 452 adults, 351 had pre-tricuspid shunts and 101 had post-tricuspid shunts. Left-sided, right-sided and bilateral valvular involvement occurred in 30.2%, 81.8% and 29.1% of pre-tricuspid cases and 28.7%, 42.6% and 16.8% of post-tricuspid cases, respectively. In pre-tricuspid shunts, right-sided involvement was associated with greater pulmonary vascular load and right-heart enlargement, whereas left-sided and bilateral involvement were associated with higher filling pressures, lower estimated mixed venous oxygen saturation and multichamber remodelling. Associations in post-tricuspid shunts were less consistent and mainly involved mixed venous oxygen saturation and chamber enlargement. Left-sided and bilateral involvement was associated with lower survival in pre-tricuspid shunts, whereas no significant survival differences were observed in post-tricuspid shunts. Clustering identified two pre-tricuspid and three post-tricuspid phenotypes. Mortality was higher in the high-burden pre-tricuspid cluster (17.5% vs 4.3%; false discovery rate-adjusted log-rank p<0.001), but did not differ significantly across post-tricuspid clusters (p=0.260).

Conclusions: Valvular involvement was common and showed shunt location-specific associations with haemodynamics and cardiac remodelling. Integrated assessment of valve status, chamber remodelling and haemodynamics may enhance phenotypic characterisation beyond shunt magnitude alone, although its prognostic and clinical relevance requires further validation.