Phenomapping to detect non-invasively patients with combined-postcapillary pulmonary hypertension

Background The combination of pre- and postcapillary forms of pulmonary hypertension (PH) is called ‘combined-postcapillary PH’. Nowadays, detection of this phenotype requires right heart catheterization. Purpose Using dense phenotypic data (phenomapping), we aimed to detect noninvasively combined-postcapillary PH. Methods We included 82 patients (mean age 67.8 ± 11.6 y, males 47%) from a referral center with mean pulmonary artery pressure (PAP) ≥ 25 mmHg and wedge pressure (WP) > 15 mmHg. Combined-postcapillary PH was defined by diastolic pressure gradient ≥ 7 mmHg and/or pulmonary vascular resistance (PVR) > 3 WU. Phenotypic domains (including clinical, laboratory, imaging and hemodynamic variables) were imputed for missing values, filtered when correlated (coefficient > 0.6), grouped using agglomerative hierarchical clustering and participants were separated using penalized model-based clustering. Phenogroups were compared for phenotypic domains and 2-years all-causes mortality was analyzed by Cox regression. Results Mean PAP, WP, cardiac index and PVR were 39.6 ± 9.8, 23.2 ± 5.2, 2.96 ± 0.77 and 3.21 ± 1.77 respectively. Among 65 phenotypic domains, 31 entered the model from which heatmap was drawn (Fig 1) and 3 phenogroups were identified. Combined-postcapillary PH was found in 90% of phenogroup 3 remarkable by older age females ( P P  = 0.73) but in phenogroup 2, characterized by younger males with altered ejection fraction and only 27% combined-PH forms (HR 3.74 [1.2–11.3], P  = 0.02). Conclusion From heterogeneous clinical presentation, phenomapping using statistical learning algorithms allowed to identify non-invasively a population at high risk of combined-postcapillary PH.