Details

Autor(en) / Beteiligte

• Aronis, Konstantinos N
• Prakosa, Adityo
• Bergamaschi, Teya
• Berger, Ronald D
• Boyle, Patrick M
• Chrispin, Jonathan
• Ju, Suyeon
• Marine, Joseph E
• Sinha, Sunil
• Tandri, Harikrishna
• Ashikaga, Hiroshi
• Trayanova, Natalia A

Titel

Characterization of the Electrophysiologic Remodeling of Patients With Ischemic Cardiomyopathy by Clinical Measurements and Computer Simulations Coupled With Machine Learning

Ist Teil von

• Frontiers in physiology, 2021-07, Vol.12, p.684149-684149

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Patients with ischemic cardiomyopathy (ICMP) are at high risk for malignant arrhythmias, largely due to electrophysiological remodeling of the non-infarcted myocardium. The electrophysiological properties of the non-infarcted myocardium of patients with ICMP remain largely unknown. To assess the pro-arrhythmic behavior of non-infarcted myocardium in ICMP patients and couple computational simulations with machine learning to establish a methodology for the development of disease-specific action potential models based on clinically measured action potential duration restitution (APDR) data. We enrolled 22 patients undergoing left-sided ablation (10 ICMP) and compared APDRs between ICMP and structurally normal left ventricles (SNLVs). APDRs were clinically assessed with a decremental pacing protocol. Using genetic algorithms (GAs), we constructed populations of action potential models that incorporate the cohort-specific APDRs. The variability in the populations of ICMP and SNLV models was captured by clustering models based on their similarity using unsupervised machine learning. The pro-arrhythmic potential of ICMP and SNLV models was assessed in cell- and tissue-level simulations. Clinical measurements established that ICMP patients have a steeper APDR slope compared to SNLV (by 38%, < 0.01). In cell-level simulations, APD alternans were induced in ICMP models at a longer cycle length compared to SNLV models (385-400 vs 355 ms). In tissue-level simulations, ICMP models were more susceptible for sustained functional re-entry compared to SNLV models. Myocardial remodeling in ICMP patients is manifested as a steeper APDR compared to SNLV, which underlies the greater arrhythmogenic propensity in these patients, as demonstrated by cell- and tissue-level simulations using action potential models developed by GAs from clinical measurements. The methodology presented here captures the uncertainty inherent to GAs model development and provides a blueprint for use in future studies aimed at evaluating electrophysiological remodeling resulting from other cardiac diseases.