Clinical phenotyping of acute heart failure patients with concomitant pulmonary hypertension using a finite mixture model: a multicenter retrospective cohort study

Heart failure (HF) with pulmonary hypertension (PH) is clinically heterogeneous, and conventional classifications based on left ventricular ejection fraction may inadequately capture this heterogeneity. We applied finite mixture model (FMM) clustering to phenotype this population. From the Chang Gung Research Database (2007–2018), we identified 944 patients hospitalized for acute HF with PH (mean pulmonary artery pressure > 20 mmHg on right heart catheterization). FMM clustering was applied to mixed clinical, echocardiographic, laboratory, and hemodynamic variables, and HF hospitalization and cardiovascular (CV) death were compared across phenogroups. Six phenogroups emerged: 2 HF with preserved ejection fraction (HFpEF) phenotypes (phenogroup 1, PH-dominant; phenogroup 2, atrial fibrillation–dominant), a coronary-predominant mixed-ejection-fraction phenotype (phenogroup 3), and 3 HF with reduced ejection fraction (HFrEF) phenotypes (phenogroups 4–6). The HFrEF phenogroups showed survival comparable to HFpEF but higher HF hospitalization, and phenogroup 3 had the highest CV mortality and HF hospitalization (all-cause mortality, 65.4%). Within the HFpEF spectrum, phenogroup 1 was distinguished by severe pulmonary vascular disease and right ventricular pressure overload (pulmonary vascular resistance, median 6.4 [interquartile range 3.4–10.6] Wood units) versus phenogroup 2 (1.9 [1.2–2.9] Wood units); despite comparable HF hospitalization (log-rank P = 0.392), phenogroup 1 had significantly higher CV mortality (log-rank P = 0.022). FMM-based phenotyping resolved clinically distinct subgroups whose outcomes diverged beyond ejection fraction. Notably, within the HFpEF spectrum, the phenogroup characterized by high pulmonary vascular resistance had higher CV mortality, which argues for including pulmonary vascular hemodynamics, alongside LVEF and comorbidity, in the risk stratification of HF with RHC-confirmed PH.