Identification of Distinct Subgroups in Moderately Severe Rheumatic Mitral Stenosis Using Data-Driven Phenotyping of Longitudinal Hemodynamic Progression

BACKGROUND: Rheumatic mitral stenosis is a significant cause of valvular heart disease. Pulmonary arterial systolic pressure (PASP)reflects the hemodynamic consequences of mitral stenosis and is used to determine treatment strategies. However, PASP progressionand expected outcomes based on PASP changes in patients with moderately severe mitral stenosis remain unclear.METHODS AND RESULTS: A total of 436 patients with moderately severe rheumatic mitral stenosis (valve area 1.0–1.5cm2) wereenrolled. Composite outcomes included all-causemortality and hospitalization for heart failure. Data-drivenphenotyping identified2 distinct trajectory groups based on PASP progression: rapid (8.7%) and slow (91.3%). Patients in the rapid progressiongroup were older and had more diabetes and atrial fibrillation than those in the slow progression group (all P<0.05). The initialmean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group(6.2±2.4 mm Hg versus 5.1±2.0 mm Hg [P=0.001] and 42.3±13.3 mm Hg versus 33.0±9.2 mm Hg [P<0.001], respectively). Therapid progression group had a poorer event-freesurvival rate than the slow progression group (log-rankP<0.001). Rapid PASPprogression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio, 3.08[95% CI, 1.68–5.64];P<0.001). Multivariate regression analysis revealed that PASP >40 mm Hg was independently associatedwith allocation to the rapid progression group (odds ratio, 4.95 [95% CI, 2.08–11.99];P<0.001).CONCLUSIONS: Rapid PASP progression was associated with a higher risk of the composite outcomes. The main independentpredictor for rapid progression group allocation was initial PASP >40 mm Hg.