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Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophy...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584370/ https://www.ncbi.nlm.nih.gov/pubmed/37851708 http://dx.doi.org/10.7554/eLife.88865 |
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author | Zhang, Yingnan Zhang, Kelly Prakosa, Adityo James, Cynthia Zimmerman, Stefan L Carrick, Richard Sung, Eric Gasperetti, Alessio Tichnell, Crystal Murray, Brittney Calkins, Hugh Trayanova, Natalia A |
author_facet | Zhang, Yingnan Zhang, Kelly Prakosa, Adityo James, Cynthia Zimmerman, Stefan L Carrick, Richard Sung, Eric Gasperetti, Alessio Tichnell, Crystal Murray, Brittney Calkins, Hugh Trayanova, Natalia A |
author_sort | Zhang, Yingnan |
collection | PubMed |
description | Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophysiological (EP) remodeling. Here, we developed a novel genotype-specific heart digital twin (Geno-DT) approach to investigate the role of pathophysiological remodeling in sustaining VT reentrant circuits and to predict the VT circuits in ARVC patients of different genotypes. This approach integrates the patient’s disease-induced structural remodeling reconstructed from contrast-enhanced magnetic-resonance imaging and genotype-specific cellular EP properties. In our retrospective study of 16 ARVC patients with two genotypes: plakophilin-2 (PKP2, n = 8) and gene-elusive (GE, n = 8), we found that Geno-DT accurately and non-invasively predicted the VT circuit locations for both genotypes (with 100%, 94%, 96% sensitivity, specificity, and accuracy for GE patient group, and 86%, 90%, 89% sensitivity, specificity, and accuracy for PKP2 patient group), when compared to VT circuit locations identified during clinical EP studies. Moreover, our results revealed that the underlying VT mechanisms differ among ARVC genotypes. We determined that in GE patients, fibrotic remodeling is the primary contributor to VT circuits, while in PKP2 patients, slowed conduction velocity and altered restitution properties of cardiac tissue, in addition to the structural substrate, are directly responsible for the formation of VT circuits. Our novel Geno-DT approach has the potential to augment therapeutic precision in the clinical setting and lead to more personalized treatment strategies in ARVC. |
format | Online Article Text |
id | pubmed-10584370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-105843702023-10-19 Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins Zhang, Yingnan Zhang, Kelly Prakosa, Adityo James, Cynthia Zimmerman, Stefan L Carrick, Richard Sung, Eric Gasperetti, Alessio Tichnell, Crystal Murray, Brittney Calkins, Hugh Trayanova, Natalia A eLife Computational and Systems Biology Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophysiological (EP) remodeling. Here, we developed a novel genotype-specific heart digital twin (Geno-DT) approach to investigate the role of pathophysiological remodeling in sustaining VT reentrant circuits and to predict the VT circuits in ARVC patients of different genotypes. This approach integrates the patient’s disease-induced structural remodeling reconstructed from contrast-enhanced magnetic-resonance imaging and genotype-specific cellular EP properties. In our retrospective study of 16 ARVC patients with two genotypes: plakophilin-2 (PKP2, n = 8) and gene-elusive (GE, n = 8), we found that Geno-DT accurately and non-invasively predicted the VT circuit locations for both genotypes (with 100%, 94%, 96% sensitivity, specificity, and accuracy for GE patient group, and 86%, 90%, 89% sensitivity, specificity, and accuracy for PKP2 patient group), when compared to VT circuit locations identified during clinical EP studies. Moreover, our results revealed that the underlying VT mechanisms differ among ARVC genotypes. We determined that in GE patients, fibrotic remodeling is the primary contributor to VT circuits, while in PKP2 patients, slowed conduction velocity and altered restitution properties of cardiac tissue, in addition to the structural substrate, are directly responsible for the formation of VT circuits. Our novel Geno-DT approach has the potential to augment therapeutic precision in the clinical setting and lead to more personalized treatment strategies in ARVC. eLife Sciences Publications, Ltd 2023-10-18 /pmc/articles/PMC10584370/ /pubmed/37851708 http://dx.doi.org/10.7554/eLife.88865 Text en © 2023, Zhang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Zhang, Yingnan Zhang, Kelly Prakosa, Adityo James, Cynthia Zimmerman, Stefan L Carrick, Richard Sung, Eric Gasperetti, Alessio Tichnell, Crystal Murray, Brittney Calkins, Hugh Trayanova, Natalia A Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title | Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title_full | Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title_fullStr | Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title_full_unstemmed | Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title_short | Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
title_sort | predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584370/ https://www.ncbi.nlm.nih.gov/pubmed/37851708 http://dx.doi.org/10.7554/eLife.88865 |
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