Taha, K; van de Leur, RR; Vessies, M; Mast, TP; Cramer, MJ; Cauwenberghs, N; Verstraelen, TE; ... van Es, R; + view all Taha, K; van de Leur, RR; Vessies, M; Mast, TP; Cramer, MJ; Cauwenberghs, N; Verstraelen, TE; de Brouwer, R; Doevendans, PA; Wilde, A; Asselbergs, FW; van den Berg, MP; D’hooge, J; Kuznetsova, T; Teske, AJ; van Es, R; - view fewer (2023) Deep neural network-based clustering of deformation curves reveals novel disease features in PLN pathogenic variant carriers. The International Journal of Cardiovascular Imaging 10.1007/s10554-023-02924-9. (In press).

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Abstract

Echocardiographic deformation curves provide detailed information on myocardial function. Deep neural networks (DNNs) may enable automated detection of disease features in deformation curves, and improve the clinical assessment of these curves. We aimed to investigate whether an explainable DNN-based pipeline can be used to detect and visualize disease features in echocardiographic deformation curves of phospholamban (PLN) p.Arg14del variant carriers. A DNN was trained to discriminate PLN variant carriers (n = 278) from control subjects (n = 621) using raw deformation curves obtained by 2D-speckle tracking in the longitudinal axis. A visualization technique was used to identify the parts of these curves that were used by the DNN for classification. The PLN variant carriers were clustered according to the output of the visualization technique. The DNN showed excellent discriminatory performance (C-statistic 0.93 [95% CI 0.87–0.97]). We identified four clusters with PLN-associated disease features in the deformation curves. Two clusters showed previously described features: apical post-systolic shortening and reduced systolic strain. The two other clusters revealed novel features, both reflecting delayed relaxation. Additionally, a fifth cluster was identified containing variant carriers without disease features in the deformation curves, who were classified as controls by the DNN. This latter cluster had a very benign disease course regarding development of ventricular arrhythmias. Applying an explainable DNN-based pipeline to myocardial deformation curves enables automated detection and visualization of disease features. In PLN variant carriers, we discovered novel disease features which may improve individual risk stratification. Applying this approach to other diseases will further expand our knowledge on disease-specific deformation patterns. Graphical abstract: [Figure not available: see fulltext.] Overview of the deep neural network-based pipeline for feature detection in myocardial deformation curves. Firstly, phospholamban (PLN) p.Arg14del variant carriers and controls were selected and a deep neural network (DNN) was trained to detect the PLN variant carriers. Subsequently, a clustering-based approach was performed on the attention maps of the DNN, which revealed 4 distinct phenotypes of PLN variant carriers with different prognoses. Moreover, a cluster without features and a benign prognosis was detected.

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