ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy

Rutger R. van de Leur*, Remco de Brouwer, Hidde Bleijendaal, Tom E. Verstraelen, Belend Mahmoud, Ana Perez-Matos, Cathelijne Dickhoff, Bas A. Schoonderwoerd, Tjeerd Germans, Arjan Houweling, Paul A. van der Zwaag, Moniek G.P.J. Cox, J. Peter van Tintelen, Anneline S.J.M. te Riele, Maarten P. van den Berg, Arthur A.M. Wilde, Pieter A. Doevendans, Rudolf A. de Boer, René van Es

*Corresponding author for this work

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Abstract

Background: Phospholamban (PLN) p.(Arg14del) variant carriers are at risk for development of malignant ventricular arrhythmia (MVA). Accurate risk stratification allows timely implantation of intracardiac defibrillators and is currently performed with a multimodality prediction model. Objective: This study aimed to investigate whether an explainable deep learning–based approach allows risk prediction with only electrocardiogram (ECG) data. Methods: A total of 679 PLN p.(Arg14del) carriers without MVA at baseline were identified. A deep learning–based variational auto-encoder, trained on 1.1 million ECGs, was used to convert the 12-lead baseline ECG into its FactorECG, a compressed version of the ECG that summarizes it into 32 explainable factors. Prediction models were developed by Cox regression. Results: The deep learning–based ECG-only approach was able to predict MVA with a C statistic of 0.79 (95% CI, 0.76–0.83), comparable to the current prediction model (C statistic, 0.83 [95% CI, 0.79–0.88]; P = .054) and outperforming a model based on conventional ECG parameters (low-voltage ECG and negative T waves; C statistic, 0.65 [95% CI, 0.58–0.73]; P < .001). Clinical simulations showed that a 2-step approach, with ECG-only screening followed by a full workup, resulted in 60% less additional diagnostics while outperforming the multimodal prediction model in all patients. A visualization tool was created to provide interactive visualizations (https://pln.ecgx.ai). Conclusion: Our deep learning–based algorithm based on ECG data only accurately predicts the occurrence of MVA in PLN p.(Arg14del) carriers, enabling more efficient stratification of patients who need additional diagnostic testing and follow-up.

Original languageEnglish
Pages (from-to)1102-1112
Number of pages11
JournalHeart Rhythm
Volume21
Issue number7
DOIs
Publication statusE-pub ahead of print - 23 Feb 2024

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Publisher Copyright: © 2024 Heart Rhythm Society

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