Phenotypic diversity in moderate rheumatic mitral stenosis with prognostic implications: insights from a multicenter registry and clustering analysis

Abstract Background Rheumatic mitral stenosis (MS) remains a significant cause of morbidity and mortality. Identifying distinct phenotypes in rheumatic MS may facilitate a deeper understanding of differential prognoses and help individualized management. We aim to investigate whether cluster analysis identifies distinct phenotypes with different prognosis in moderate rheumatic MS. Method From 3,140 patients diagnosed with MS within the Multicenter MitrAl STEnosis with Rheumatic Etiology (MASTER) registry between 2001 and 2021, a subset of 698 individuals of moderate MS with accessible demographic, laboratory, and echocardiographic information was analyzed. Patients were grouped into phenotypically distinct 3 clusters. The primary outcome was all-cause mortality. The secondary outcome was defined as undergoing mitral valve (MV) intervention: surgical replacement or percutaneous valvuloplasty. Results Three distinct clusters were identified: Cluster 1 (n=323) represented a relatively "healthy" phenotype; Cluster 2 (n=139) included older patients with significant comorbidities and aortic valve dysfunction; Cluster 3 (n=236) was characterized by atrial fibrillation (AF) with bi-atrial remodeling, elevated mitral diastolic pressure gradient (MDPG), and right ventricular systolic pressure (RVSP) (Figure 1). Over a median follow-up of 5.97 (interquartile range, 1.6-11.5) years, cluster 1 exhibited the most favorable outcomes, whereas cluster 2 exhibited the poorest prognosis of all-cause death (log-rank p