{"doi":"10.1016/j.jacc.2022.08.804","title":"Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies","abstract":"BACKGROUND: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. OBJECTIVES: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. METHODS: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). RESULTS: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. CONCLUSIONS: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing.","journal":"Journal of the American College of Cardiology","year":2022,"id":234295,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":102,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":849694,"name":"Matteo Dal Ferro","orcid":"0000-0002-2310-0448","position":1,"is_corresponding":false},{"id":706427,"name":"Davide Stolfo","orcid":"0000-0002-4538-6811","position":2,"is_corresponding":false},{"id":55325,"name":"Ilaria Gandin","orcid":"0000-0003-3196-2491","position":3,"is_corresponding":false},{"id":849695,"name":"Kristen Medo","orcid":"0009-0007-9785-4668","position":4,"is_corresponding":false},{"id":501641,"name":"Sharon Graw","orcid":"0000-0003-4577-1493","position":5,"is_corresponding":false},{"id":849696,"name":"Marta Gigli","orcid":"0000-0002-3856-937X","position":6,"is_corresponding":false},{"id":328472,"name":"Giulia Gagno","orcid":"0000-0001-5796-4247","position":7,"is_corresponding":false},{"id":849697,"name":"Denise Zaffalon","orcid":"0000-0001-5938-4000","position":8,"is_corresponding":false},{"id":849698,"name":"Matteo Castrichini","orcid":"0000-0002-2405-3364","position":9,"is_corresponding":false},{"id":849699,"name":"Marco Masè","orcid":"0000-0003-0457-9489","position":10,"is_corresponding":false},{"id":849700,"name":"Antonio Cannatà","orcid":"0000-0001-7609-6297","position":11,"is_corresponding":false},{"id":850355,"name":"Francesca Brun","orcid":null,"position":12,"is_corresponding":false},{"id":849701,"name":"Garrett Storm","orcid":"0000-0003-1248-1449","position":13,"is_corresponding":false},{"id":849702,"name":"Giovanni Maria Severini","orcid":"0000-0002-5790-2000","position":14,"is_corresponding":false},{"id":55338,"name":"Stefania Lenarduzzi","orcid":"0000-0001-8450-1694","position":15,"is_corresponding":false},{"id":502820,"name":"Giorgia Girotto","orcid":"0000-0003-4507-6589","position":16,"is_corresponding":false},{"id":55732,"name":"Paolo Gasparini","orcid":"0000-0002-0859-0856","position":17,"is_corresponding":false},{"id":849703,"name":"Francesca Bortolotti","orcid":"0000-0002-3014-6989","position":18,"is_corresponding":false},{"id":520975,"name":"Mauro Giacca","orcid":"0000-0003-2927-7225","position":19,"is_corresponding":false},{"id":849704,"name":"Serena Zacchigna","orcid":"0000-0001-6705-3076","position":20,"is_corresponding":false},{"id":688441,"name":"Marco Merlo","orcid":"0000-0002-1022-3131","position":21,"is_corresponding":false},{"id":10989,"name":"Matthew R.G. 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