Differentiating HFmr/rEF from HFpEF using standard 12-lead ECG measurements: an interpretable machine learning study

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BACKGROUND: Differentiating heart failure (HF) with mildly reduced/reduced ejection fraction (HFmr/rEF) from HF with preserved ejection fraction (HFpEF) guides therapy but echocardiography may be delayed or unavailable. We developed and validated machine learning models using routine 12-lead ECG data to classify HF phenotypes. METHODS: In this retrospective cohort of hospitalised patients with HF, predictors available at or before the index ECG were used. HFmrEF was pooled with HFrEF (left ventricular ejection fraction <50%) for model development. Data were split 70/30 into training and held-out test sets. Random forest (RF), Extreme Gradient Boosting and support vector machine models were trained and tuned using fivefold cross-validation in the training set. Boruta was used to select key ECG features. Test-set performance was evaluated by area under the curve (AUC) and accuracy; AUCs were compared using DeLong's test. RESULTS: Overall, 495 patients were included (254 HFmr/rEF; 241 HFpEF). RF consistently performed best. Using ECG features alone, RF achieved an AUC of 0.821 (95% CI 0.752 to 0.890) and accuracy of 75.7%. A parsimonious RF model using 12 Boruta-selected ECG variables achieved an AUC of 0.832 (95% CI 0.766 to 0.899) and accuracy of 76.4%, with no significant AUC difference versus a comprehensive RF model using clinical/laboratory/ECG predictors (AUC 0.804, 95% CI 0.734 to 0.875; p=0.288) or the model using all ECG features (p=0.092). Adding X-ray cardiomegaly did not improve performance. CONCLUSION: A parsimonious RF model based on a small set of standard ECG measurements differentiates HFmr/rEF from HFpEF with good discrimination, supporting ECG as an adjunct for phenotyping when echocardiography is not immediately available.

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