Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning

Matej Pičulin, Tim Smole, Bojan Žunkovič, Enja Kokalj, Marko Robnik-Šikonja, Matjaž Kukar, Dimitrios I. Fotiadis, Vasileios C. Pezoulas, Nikolaos S. Tachos, Fausto Barlocco, Francesco Mazzarotto, Dejana Popović, Lars S. Maier, Lazar Velicki, Iacopo Olivotto, Guy A. MacGowan, Djordje G. Jakovljević, Nenad Filipović, Zoran Bosnić

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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Background: Cardiovascular disorders in general are responsible for 30% of deaths worldwide. Among them, hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that is present in about 1 of 500 young adults and can cause sudden cardiac death (SCD). Objective: Although the current state-of-the-art methods model the risk of SCD for patients, to the best of our knowledge, no methods are available for modeling the patient's clinical status up to 10 years ahead. In this paper, we propose a novel machine learning (ML)-based tool for predicting disease progression for patients diagnosed with HCM in terms of adverse remodeling of the heart during a 10-year period. Methods: The method consisted of 6 predictive regression models that independently predict future values of 6 clinical characteristics: left atrial size, left atrial volume, left ventricular ejection fraction, New York Heart Association functional classification, left ventricular internal diastolic diameter, and left ventricular internal systolic diameter. We supplemented each prediction with the explanation that is generated using the Shapley additive explanation method. Results: The final experiments showed that predictive error is lower on 5 of the 6 constructed models in comparison to experts (on average, by 0.34) or a consortium of experts (on average, by 0.22). The experiments revealed that semisupervised learning and the artificial data from virtual patients help improve predictive accuracies. The best-performing random forest model improved R2 from 0.3 to 0.6. Conclusions: By engaging medical experts to provide interpretation and validation of the results, we determined the models' favorable performance compared to the performance of experts for 5 of 6 targets.

Original languageEnglish
Article numbere30483
Number of pages18
JournalJMIR Medical Informatics
Issue number2
Publication statusPublished - 2 Feb 2022
Externally publishedYes

Bibliographical note

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Medical Informatics, is properly cited. The complete bibliographic information, a link to the original publication on https://medinform.jmir.org/, as well as this copyright and license information must be included.


Horizon 2020 Framework Programme: 777204


  • AI
  • Artificial intelligence
  • Cardiomyopathy
  • Cardiovascular disease
  • Disease progression
  • Hypertrophic cardiomyopathy
  • Machine learning
  • ML
  • Prediction
  • Prediction model
  • SCD
  • Sudden cardiac death
  • Validation

ASJC Scopus subject areas

  • Health Informatics
  • Health Information Management


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