{"doi":"10.1161/circgen.123.004062","title":"Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation","abstract":"Background: Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases. Methods: We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity. Results: Fifty-four samples (44.3%) had pathogenic/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed ( P =8.30×10 -4 ). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases ( P <0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples. Conclusions: Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.","journal":"Circulation Genomic and Precision Medicine","year":2023,"id":345045,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1084005,"name":"Oddný Brattberg Gunnarsdóttir","orcid":"0000-0002-7625-0976","position":1,"is_corresponding":false},{"id":65103,"name":"Anissa Viveiros","orcid":"0000-0001-9452-1082","position":2,"is_corresponding":false},{"id":65099,"name":"Daniel Reichart","orcid":"0000-0002-8559-5888","position":3,"is_corresponding":false},{"id":415996,"name":"Daniel Quiat","orcid":"0000-0002-4224-7277","position":4,"is_corresponding":false},{"id":317865,"name":"Jon A. L. Willcox","orcid":"0000-0002-3782-4770","position":5,"is_corresponding":false},{"id":246655,"name":"Hao Zhang","orcid":"0000-0001-7043-5438","position":6,"is_corresponding":false},{"id":5572,"name":"Huachen Chen","orcid":"0000-0003-3542-0884","position":7,"is_corresponding":false},{"id":902493,"name":"Justin J. Curran","orcid":null,"position":8,"is_corresponding":false},{"id":1084006,"name":"Daniel Kim","orcid":"0000-0001-9673-5631","position":9,"is_corresponding":false},{"id":1084007,"name":"Simon Urschel","orcid":"0000-0003-0820-6815","position":10,"is_corresponding":false},{"id":5571,"name":"Barbara McDonough","orcid":"0000-0002-4257-8623","position":11,"is_corresponding":false},{"id":5570,"name":"Joshua M. Gorham","orcid":"0000-0001-5969-4690","position":12,"is_corresponding":false},{"id":251041,"name":"Steven R. DePalma","orcid":"0000-0002-0381-5016","position":13,"is_corresponding":false},{"id":5584,"name":"Jonathan G. Seidman","orcid":"0000-0002-9082-3566","position":14,"is_corresponding":false},{"id":5583,"name":"Christine E. Seidman","orcid":"0000-0001-6380-1209","position":15,"is_corresponding":false},{"id":5582,"name":"Gavin Y. Oudit","orcid":"0000-0002-9154-9028","position":16,"is_corresponding":false},{"id":65114,"name":"Yuri Kim","orcid":"0000-0001-5978-5779","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:35.133818Z","pmid":"37767697","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}