Computer versus Cardiologist: Is a machine learning algorithm able to outperform an expert in diagnosing phospholamban (PLN) p.Arg14del mutation on ECG?

Abstract Background Phospholamban (PLN) p.Arg14del mutation carriers are known to develop dilated and/or arrhythmogenic cardiomyopathy and typical electrocardiographic (ECG) features have been identified for diagnosis. Machine learning is a powerful tool used in ECG analysis and has shown to outperform cardiologists. Objective We aimed to develop machine learning and deep learning models to diagnose PLN p.Arg14del cardiomyopathy using ECGs and evaluate their accuracy compared to an expert cardiologist. Methods We included 155 adult PLN mutation carriers and 155 age- and sex matched control subjects. 21 (13.4%) PLN mutation carriers were classified as symptomatic (symptoms of heart failure or malignant ventricular arrhythmias). The dataset was split into training and testing sets using 4-fold cross-validation. Multiple models were developed to discriminate between PLN mutation carrier or control subject. For comparison, expert cardiologists classified the same dataset. The best performing models were validated using an external PLN p.Arg14del mutation carriers dataset from Murcia, Spain (n= 50). We applied occlusion maps to visualize the most contributing ECG regions. Results In terms of specificity, the expert cardiologists (0.99) outperformed all models (range 0.53-0.81). In terms of accuracy and sensitivity the experts (0.28 and 0.64) was outperformed by all models (sensitivity range 0.65-0.81). T-wave morphology was most important for classification of PLN p.Arg14del. External validation showed comparable results, with the best model outperforming the experts. Conclusion This study shows that ML can outperform experienced cardiologists in the diagnosis of PLN p.Arg14del cardiomyopathy and suggests that the shape of the T-wave is of added importance to this diagnosis.