Improving Risk Stratification in Hypertrophic Cardiomyopathy: A Novel Score Combining Echocardiography, Clinical, and Medication Data

TL;DR

This study presents a new explainable machine learning risk score for hypertrophic cardiomyopathy that significantly outperforms existing models in predicting 5-year cardiovascular outcomes using routinely collected data.

Contribution

The paper introduces a robust, interpretable ML risk score that combines echocardiography, clinical, and medication data, validated across multiple cohorts, for improved risk stratification in HCM.

Findings

ML model achieved an AUC of 0.85, outperforming the ESC score (0.56).

External validation showed superior risk separation with a significant log-rank p-value.

The risk score remains stable over time in patients without events.

Abstract

Hypertrophic cardiomyopathy (HCM) requires accurate risk stratification to inform decisions regarding ICD therapy and follow-up management. Current established models, such as the European Society of Cardiology (ESC) score, exhibit moderate discriminative performance. This study develops a robust, explainable machine learning (ML) risk score leveraging routinely collected echocardiographic, clinical, and medication data, typically contained within Electronic Health Records (EHRs), to predict a 5-year composite cardiovascular outcome in HCM patients. The model was trained and internally validated using a large cohort (N=1,201) from the SHARE registry (Florence Hospital) and externally validated on an independent cohort (N=382) from Rennes Hospital. The final Random Forest ensemble model achieved a high internal Area Under the Curve (AUC) of 0.85 +- 0.02, significantly outperforming the ESC score (0.56 +- 0.03). Critically, survival curve analysis on the external validation set showed superior risk separation for the ML score (Log-rank p = 8.62 x 10^(-4) compared to the ESC score (p = 0.0559). Furthermore, longitudinal analyses demonstrate that the proposed risk score remains stable over time in event-free patients. The model high interpretability and its capacity for longitudinal risk monitoring represent promising tools for the personalized clinical management of HCM.