Abstract 16660: Precision Diagnosis of Hypertrophic Cardiomyopathy: A New Definition of Inappropriate Hypertrophy

Abstract

Introduction: The definition of hypertrophic cardiomyopathy (HCM), unaltered for 50 years, requires unexplained left ventricular hypertrophy with a maximum wall thickness (MWT) ≥15mm in probands. However, this doesn’t consider age, sex and body-size which is inadequate for a precision therapy era. Aim: To develop a personalised definition of inappropriate hypertrophy using cardiac MRI and evaluate potential care implications. Methods: Healthy reference cardiac MRIs from the Framingham Heart Study, UK Biobank, and multiple healthy volunteer studies were analysed by a validated AI algorithm. Generalized additive mixed models accounting for age, sex, and body surface area (BSA) established a personalized hypertrophy threshold for MWT (>95% prediction interval) and conditional Z-scores. We assessed the discordance in HCM diagnosis between a “≥15mm” and “personalized hypertrophy” threshold applied to the UK Biobank and clinical HCM cohorts. Results: In healthy subjects (n=5,255), 36% of MWT variation was explained by age, sex and BSA. In the UK Biobank (n=44,690), using ≥15mm, there is a substantial sex skew; 8% of males and 1% of females are classified as hypertrophic. With a personalized threshold, this reduces to 3% of males and 2% of females classified as hypertrophic. 17% of subjects have a predicted hypertrophy threshold of 15mm (with 46% predicted ≤ 14mm, 37% predicted ≥16mm). In clinical HCM cohorts (n=1,854) across 5 centres in 4 countries (UK, USA, Italy, Portugal), females had thinner hearts (17.7 vs 19.1mm; p<0.001) but more relative hypertrophy evidenced by greater deviation (Z-scores) from their predicted MWT (5.4 vs 5.1; p=0.05). Conclusion: We propose a new, personalised definition for hypertrophy that mitigates for significant age, sex and BSA confounding inherent in a 15mm cut point. We have identified potential for under/over diagnosis in a population cohort and suboptimal risk stratification in smaller, younger and/or female HCM patients.