Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy
BackgroundThe aim of the study was to determine the prevalence of rare disease-causing variants in cardiomyopathy-associated genes in a cohort of patients with ischemic and non-ischemic dilated cardiomyopathy undergoing heart transplant.MethodsWe conducted a single-center cohort study of 60 adult pa...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1542653/full |
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| author | Louie Cao Joshua Rushakoff Ian Williamson Anja Karlstaedt Michelle Kittleson Lawrence Czer Evan P. Kransdorf |
| author_facet | Louie Cao Joshua Rushakoff Ian Williamson Anja Karlstaedt Michelle Kittleson Lawrence Czer Evan P. Kransdorf |
| author_sort | Louie Cao |
| collection | DOAJ |
| description | BackgroundThe aim of the study was to determine the prevalence of rare disease-causing variants in cardiomyopathy-associated genes in a cohort of patients with ischemic and non-ischemic dilated cardiomyopathy undergoing heart transplant.MethodsWe conducted a single-center cohort study of 60 adult patients with left ventricular ejection fraction ≤50% and left ventricular end-diastolic dimension ≥95th percentile for sex/height who underwent heart transplant between January 2017 and December 2023 and consented to participate in a cardiac tissue biobank. We evaluated the prevalence of rare (minor allele frequency <0.1%) disease-causing (pathogenic or likely pathogenic by American College of Genetics and Genomics criteria) variants in cardiomyopathy-associated genes.ResultsA total of 60 individuals fulfilled the inclusion criteria: 16 with ischemic dilated cardiomyopathy [88% men, median age 65 years, interquartile range (IQR) 64–68 years] and 44 with non-ischemic dilated cardiomyopathy (80% men, median age 53 years, IQR 39–65 years). We found that the prevalence of disease-causing variants was similar between patients with ischemic dilated cardiomyopathy (3/16 or 19%; 95% credible interval 6%–36%) and those with non-ischemic dilated cardiomyopathy (10/44 or 23%; 95% credible interval 12%–33%). Variants in the ischemic dilated cardiomyopathy group were found in the TTN and DMD genes. Variants in the non-ischemic dilated cardiomyopathy group were found in the TTN, FLNC, LMNA, MYH7, and RBM20 genes.ConclusionsPatients with ischemic dilated cardiomyopathy undergoing heart transplant possessed a similar burden of rare disease-causing variants as those with non-ischemic dilated cardiomyopathy. Our results suggest that genetic testing may be beneficial in patients with advanced heart failure requiring heart transplant due to ischemic dilated cardiomyopathy to detect disease-causing variants in cardiomyopathy-associated genes. |
| format | Article |
| id | doaj-art-b401979a7e8042d6b067eb8aac8e7148 |
| institution | Kabale University |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-b401979a7e8042d6b067eb8aac8e71482025-08-20T03:53:27ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-04-011210.3389/fcvm.2025.15426531542653Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathyLouie CaoJoshua RushakoffIan WilliamsonAnja KarlstaedtMichelle KittlesonLawrence CzerEvan P. KransdorfBackgroundThe aim of the study was to determine the prevalence of rare disease-causing variants in cardiomyopathy-associated genes in a cohort of patients with ischemic and non-ischemic dilated cardiomyopathy undergoing heart transplant.MethodsWe conducted a single-center cohort study of 60 adult patients with left ventricular ejection fraction ≤50% and left ventricular end-diastolic dimension ≥95th percentile for sex/height who underwent heart transplant between January 2017 and December 2023 and consented to participate in a cardiac tissue biobank. We evaluated the prevalence of rare (minor allele frequency <0.1%) disease-causing (pathogenic or likely pathogenic by American College of Genetics and Genomics criteria) variants in cardiomyopathy-associated genes.ResultsA total of 60 individuals fulfilled the inclusion criteria: 16 with ischemic dilated cardiomyopathy [88% men, median age 65 years, interquartile range (IQR) 64–68 years] and 44 with non-ischemic dilated cardiomyopathy (80% men, median age 53 years, IQR 39–65 years). We found that the prevalence of disease-causing variants was similar between patients with ischemic dilated cardiomyopathy (3/16 or 19%; 95% credible interval 6%–36%) and those with non-ischemic dilated cardiomyopathy (10/44 or 23%; 95% credible interval 12%–33%). Variants in the ischemic dilated cardiomyopathy group were found in the TTN and DMD genes. Variants in the non-ischemic dilated cardiomyopathy group were found in the TTN, FLNC, LMNA, MYH7, and RBM20 genes.ConclusionsPatients with ischemic dilated cardiomyopathy undergoing heart transplant possessed a similar burden of rare disease-causing variants as those with non-ischemic dilated cardiomyopathy. Our results suggest that genetic testing may be beneficial in patients with advanced heart failure requiring heart transplant due to ischemic dilated cardiomyopathy to detect disease-causing variants in cardiomyopathy-associated genes.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1542653/fullischemic cardiomyopathydilated cardiomyopathyheart transplantationgenetic testingischemic dilated cardiomyopathy |
| spellingShingle | Louie Cao Joshua Rushakoff Ian Williamson Anja Karlstaedt Michelle Kittleson Lawrence Czer Evan P. Kransdorf Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy Frontiers in Cardiovascular Medicine ischemic cardiomyopathy dilated cardiomyopathy heart transplantation genetic testing ischemic dilated cardiomyopathy |
| title | Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy |
| title_full | Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy |
| title_fullStr | Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy |
| title_full_unstemmed | Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy |
| title_short | Similar burden of rare genetic variants in ischemic and non-ischemic dilated cardiomyopathy |
| title_sort | similar burden of rare genetic variants in ischemic and non ischemic dilated cardiomyopathy |
| topic | ischemic cardiomyopathy dilated cardiomyopathy heart transplantation genetic testing ischemic dilated cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1542653/full |
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