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

Area of Science:

• Cardiology
• Medical Diagnostics
• Biomedical Engineering

Background:

• Hypertrophic cardiomyopathy (HCM) is a primary cause of sudden cardiac death.
• Current diagnosis relies on a fixed threshold (≥15-mm maximum wall thickness) for left ventricular hypertrophy (LVH).
• This fixed threshold may lead to diagnostic biases in certain populations.

Purpose of the Study:

• To propose and validate a novel method for diagnosing LVH in HCM.
• The method adjusts LVH thresholds based on individual demographic factors (age, sex, body surface area).
• To offer an alternative to the current one-size-fits-all diagnostic approach.

Main Methods:

• Left ventricular maximum wall thickness (MWT) was measured using cardiovascular magnetic resonance (CMR) and AI in three cohorts: healthy adults (n=5,067), general population (n=43,239), and HCM patients (n=2,424).
• A reference cohort was used to develop demographically adjusted LVH thresholds and individualized z-scores.
• These adjusted thresholds and z-scores were applied to the population and HCM cohorts to assess diagnostic accuracy and bias.

Main Results:

• The traditional ≥15-mm LVH threshold overestimated hypertrophy in the general population (4.3%, 89% male) and showed significant sex bias.
• Demographic-adjusted thresholds (10-17 mm range) reduced overall ascertainment (2.2%) and sex bias (56% male).
• Adjusted thresholds improved HCM diagnosis, reducing misclassification of female patients (from 27% to 7%) and male patients (from 18% to 15%) with MWT below 15 mm.

Conclusions:

• Normal heart MWT is influenced by individual demographics like age, sex, and body size.
• A fixed LVH threshold of ≥15 mm introduces significant ascertainment bias in both general and HCM populations.
• Demographic-adjusted LVH thresholds enhance diagnostic accuracy and reduce bias in HCM identification.