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Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy.
Eur J Med Genet 2019; :103754EJ

Abstract

Knowledge on the influence of specific genotypes on the phenotypic expression of hypertrophic cardiomyopathy (HCM) is emerging. The objective of this study was to evaluate the genotype-phenotype relation in HCM patients and to construct a score to predict the genetic yield based to improve counseling. Unrelated HCM patients who underwent genetic testing were included in the analysis. Multivariate logistic regression was performed to identify variables that predict a positive genetic test. A weighted score was constructed based on the odds ratios. In total, 378 HCM patients were included of whom 141 carried a mutation (global yield 37%), 181 were mutation negative and 56 only carried a variant of unknown significance. We identified age at diagnosis <45 years, familial HCM, familial sudden death, arrhythmic syncope, maximal wall thickness ≥20 mm, asymmetrical hypertrophy and the absence of negative T waves in the lateral ECG leads as significant predictors of a positive genetic test. When we included these values in a risk score we found very high correlation between the score and the observed genetic yield (Pearson r = 0.98). MYBPC3 mutation carriers more frequently suffered sudden cardiac death compared to troponin complex mutations carriers (p = 0.01) and a similar trend was observed compared to MYH7 mutation carriers (p = 0.08) and mutation negative patients (p = 0.11). To conclude, a simple score system based on clinical variables can predict the genetic yield in HCM index patients, aiding in counseling HCM patients. MYBPC3 mutation carriers had a worse outcome regarding sudden cardiac death.

Authors+Show Affiliations

Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Belgium; The University Hospitals of Leuven are Member of the European Reference Network for Rare and Complex Diseases of the Heart (ERN GUARD-HEART), European Union. Electronic address: Tomas.Robyns@uzleuven.be.Center for Human Genetics, University Hospitals Leuven, Belgium.Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium.Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Belgium.Center for Human Genetics, University Hospitals Leuven, Belgium.Center for Human Genetics, University Hospitals Leuven, Belgium.Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Belgium.Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Belgium.Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium; Department of Cardiovascular Sciences, University of Leuven, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31513939

Citation

Robyns, Tomas, et al. "Clinical and ECG Variables to Predict the Outcome of Genetic Testing in Hypertrophic Cardiomyopathy." European Journal of Medical Genetics, 2019, p. 103754.
Robyns T, Breckpot J, Nuyens D, et al. Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy. Eur J Med Genet. 2019.
Robyns, T., Breckpot, J., Nuyens, D., Vandenberk, B., Corveleyn, A., Kuiperi, C., ... Willems, R. (2019). Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy. European Journal of Medical Genetics, p. 103754. doi:10.1016/j.ejmg.2019.103754.
Robyns T, et al. Clinical and ECG Variables to Predict the Outcome of Genetic Testing in Hypertrophic Cardiomyopathy. Eur J Med Genet. 2019 Sep 9;103754. PubMed PMID: 31513939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy. AU - Robyns,Tomas, AU - Breckpot,Jeroen, AU - Nuyens,Dieter, AU - Vandenberk,Bert, AU - Corveleyn,Anniek, AU - Kuiperi,Cuno, AU - Van Aelst,Lucas, AU - Van Cleemput,Johan, AU - Willems,Rik, Y1 - 2019/09/09/ PY - 2018/11/08/received PY - 2019/08/23/revised PY - 2019/09/08/accepted PY - 2019/9/13/pubmed PY - 2019/9/13/medline PY - 2019/9/13/entrez KW - Genetic testing KW - Genotype phenotype relation KW - Hypertrophic cardiomyopathy SP - 103754 EP - 103754 JF - European journal of medical genetics JO - Eur J Med Genet N2 - Knowledge on the influence of specific genotypes on the phenotypic expression of hypertrophic cardiomyopathy (HCM) is emerging. The objective of this study was to evaluate the genotype-phenotype relation in HCM patients and to construct a score to predict the genetic yield based to improve counseling. Unrelated HCM patients who underwent genetic testing were included in the analysis. Multivariate logistic regression was performed to identify variables that predict a positive genetic test. A weighted score was constructed based on the odds ratios. In total, 378 HCM patients were included of whom 141 carried a mutation (global yield 37%), 181 were mutation negative and 56 only carried a variant of unknown significance. We identified age at diagnosis <45 years, familial HCM, familial sudden death, arrhythmic syncope, maximal wall thickness ≥20 mm, asymmetrical hypertrophy and the absence of negative T waves in the lateral ECG leads as significant predictors of a positive genetic test. When we included these values in a risk score we found very high correlation between the score and the observed genetic yield (Pearson r = 0.98). MYBPC3 mutation carriers more frequently suffered sudden cardiac death compared to troponin complex mutations carriers (p = 0.01) and a similar trend was observed compared to MYH7 mutation carriers (p = 0.08) and mutation negative patients (p = 0.11). To conclude, a simple score system based on clinical variables can predict the genetic yield in HCM index patients, aiding in counseling HCM patients. MYBPC3 mutation carriers had a worse outcome regarding sudden cardiac death. SN - 1878-0849 UR - https://www.unboundmedicine.com/medline/citation/31513939/Clinical_and_ECG_variables_to_predict_the_outcome_of_genetic_testing_in_hypertrophic_cardiomyopathy L2 - https://linkinghub.elsevier.com/retrieve/pii/S1769-7212(18)30833-4 DB - PRIME DP - Unbound Medicine ER -