Interventricular septal thickness for cardiomyopathic phenotype enrichment in patients with established left ventricular hypertrophy

We evaluated whether interventricular septal thickness in diastole (IVSd) ≥ 15 mm enriches cardiomyopathic phenotypes among adults with established left ventricular hypertrophy (LVH) and whether broader clinical-echocardiographic features improve triage. We studied 1,127 adults undergoing echocardiography from 2017 to 2019 who met established LVH criteria (sex-specific left ventricular mass index elevation and both IVSd and posterior wall thickness ≥ 13 mm). The primary phenotype was hypertrophic cardiomyopathy, Fabry disease, or amyloidosis. The composite phenotype occurred in 108 patients (9.6%) and was more frequent with IVSd ≥ 15 mm than 13.0–14.9 mm (16.2% vs. 3.6%, p < 0.001). After adjustment, IVSd ≥ 15 mm remained associated with the composite phenotype (odds ratio 2.38, 95% CI 1.35–4.20), with a graded association per 1-mm increase (odds ratio 1.50, 95% CI 1.33–1.70). At 15 mm, sensitivity, specificity, positive predictive value, and negative predictive value were 80.6%, 55.7%, 16.2%, and 96.4%; at 18 mm, case-finding yield increased to 41.7% but 58 of 108 cases were missed. A five-variable model improved discrimination over IVSd alone (area under the curve [AUC] 0.839 vs. 0.787; ΔAUC 0.052; p = 0.007; derivation AUC 0.857, temporal validation AUC 0.788), whereas adding binary IVSd ≥ 15 mm to conventional clinical-echocardiographic variables yielded minimal incremental discrimination (ΔAUC 0.003) and minimal additional net benefit. In established LVH, IVSd ≥ 15 mm identifies cardiomyopathic enrichment, with the composite association driven predominantly by hypertrophic cardiomyopathy, but is best used as a prompt for etiologic review rather than a diagnostic rule. A compact five-variable model may support triage.