Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach. Methods: Left ventricular MWT was measured in 3 cohorts: a Reference Cohort of healthy adults (n = 5,067, no comorbidities), a Population Cohort (n = 43,239, with comorbidities), and an HCM Cohort from 6 international centers (n = 2,424). Measurement used cardiovascular magnetic resonance (CMR) and a validated artificial intelligence algorithm. The Reference Cohort was used to developed demographically adjusted LVH thresholds, and individualized z-scores based on age, sex, and body surface area (BSA), which were used to explore the other cohorts. Results: The traditional ≥15-mm threshold classified 4.3% (n = 1,854) of the Population Cohort as hypertrophic, with a significant sex skew (89% male). Demographic-adjusted LVH thresholds (range: 10-17 mm) reduced ascertainment to 2.2% (n = 945), reducing the sex skew (56% male). Similar reductions in bias with height, weight, and age also occurred. The HCM cohort was found to have a 2:1 male-to-female ratio. A significant proportion of patients received diagnoses of HCM despite having MWT below the traditional LVH threshold (<15 mm): 27% of female individuals and 18% of male individuals. Using demographic-adjusted LVH thresholds reduced these proportions to 7% of female individuals and 15% of male individuals (P < 0.0001). Female patients had lower absolute MWT (18 mm vs 19 mm; P < 0.001) but higher MWT z-scores (5.1 vs 4.5; P = 0.05). Conclusions: Age, sex, and body size influence the normal heart MWT. Using a fixed LVH threshold ≥15 mm biases LVH ascertainment in both population and HCM cohorts. A demographic-adjusted approach for LVH improves ascertainment and diagnostic accuracy.