Echocardiographic Wall Thickness Heterogeneity as Marker of Hypertrophic Cardiomyopathy: A Proof-of-Concept Analysis From the Prospective Multicenter IMAGE-HCM Study

Background Hypertrophic cardiomyopathy (HCM) is characterized by marked phenotypic heterogeneity that may not be fully captured by conventional maximal wall thickness measurements. Wall thickness standard deviation (WTSD), a quantitative measure of regional myocardial thickness variability, may provide additional insight into disease-specific remodeling and improve phenotypic characterization. Aims and Methods We aimed to evaluate, for the first time, the feasibility and diagnostic performance of WTSD measured by transthoracic echocardiography (TTE) in patients with hypertrophic phenotypes, using CMR-derived WTSD as a reference. Specifically, we assessed the feasibility, reproducibility, and diagnostic agreement of TTE-derived WTSD with CMR, its diagnostic performance for identifying HCM, its ability to detect subtle or early hypertrophic remodeling in women. Results We retrospectively analyzed 51 patients with hypertrophic phenotype who fulfilled study inclusion criteria. Thirty-seven patients had overt HCM, while 14 had non-HCM hypertrophic phenotypes. Patients with overt HCM exhibited significantly greater myocardial wall-thickness heterogeneity than those with non-HCM hypertrophic phenotypes. WTSD was higher in HCM patients by both CMR (3.4 ± 1.3 vs. 2.6 ± 0.9, p = 0.020) and TTE (3.9 ± 1.3 vs. 2.3 ± 0.9, p = 0.001). Importantly, TTE-derived WTSD showed good agreement with CMR-derived WTSD (r = 0.86, 95% CI 0.72-0.93, p<0.001), providing evidence for the reproducibility of WTSD assessment across imaging modalities. TTE-derived WTSD demonstrated comparable diagnostic performance to CMR-derived WTSD for identifying overt HCM. CMR-derived WTSD identified overt HCM with an optimal cut-off value ≥2.3 (AUC 0.70, 95% CI 0.54–0.85; p = 0.028), while echocardiographic WTSD showed comparable performance (AUC 0.69, 95% CI 0.52–0.84; p = 0.030). Conclusions WTSD represents a quantitative marker of myocardial wall-thickness heterogeneity that, to our knowledge, has not previously been systematically measured and validated using TTE. Echocardiographic WTSD demonstrated excellent agreement with CMR-derived WTSD and showed comparable ability to distinguish overt HCM from non-HCM hypertrophic phenotypes. Prospective multicenter studies are warranted to externally validate these findings and establish the clinical and prognostic implications of WTSD.