Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy

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http://hdl.handle.net/10138/301568

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FinHCM Study Grp , Jääskeläinen , P , Vangipurapu , J , Raivo , J , Kuulasmaa , T , Helio , T , Aalto-Setala , K , Kaartinen , M , Ilveskoski , E , Vanninen , S , Hämäläinen , L , Melin , J , Kokkonen , J , Nieminen , M S , Laakso , M , Kuusisto , J , Kervinen , H , Mustonen , J , Juvonen , J , Niemi , M , Uusimaa , P , Junttila , J , Kotila , M , Pietila , M , Jyrkila , H , Mahonen , I & Vartia , P 2019 , ' Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy ' , ESC Heart Failure , vol. 6 , no. 2 , pp. 436-445 . https://doi.org/10.1002/ehf2.12420

Title: Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy
Author: FinHCM Study Grp; Jääskeläinen, Pertti; Vangipurapu, Jagadish; Raivo, Joose; Kuulasmaa, Teemu; Helio, Tiina; Aalto-Setala, Katriina; Kaartinen, Maija; Ilveskoski, Erkki; Vanninen, Sari; Hämäläinen, Liisa; Melin, John; Kokkonen, Jorma; Nieminen, Markku S.; Laakso, Markku; Kuusisto, Johanna; Kervinen, Helena; Mustonen, Juha; Juvonen, Jukka; Niemi, Mari; Uusimaa, Paavo; Junttila, Juhani; Kotila, Matti; Pietila, Mikko; Jyrkila, Heini; Mahonen, Ilkka; Vartia, Paula
Contributor: University of Helsinki, Department of Medicine
University of Helsinki, Clinicum
Date: 2019-04
Language: eng
Number of pages: 10
Belongs to series: ESC Heart Failure
ISSN: 2055-5822
URI: http://hdl.handle.net/10138/301568
Abstract: Aims Nationwide large-scale genetic and outcome studies in cohorts with hypertrophic cardiomyopathy (HCM) have not been previously published. Methods and results We sequenced 59 cardiomyopathy-associated genes in 382 unrelated Finnish patients with HCM and found 24 pathogenic or likely pathogenic mutations in six genes in 38.2% of patients. Most mutations were located in sarcomere genes (MYBPC3, MYH7, TPM1, and MYL2). Previously reported mutations by our study group (MYBPC3-Gln1061Ter, MYH7-Arg1053Gln, and TPM1-Asp175Asn) and a fourth major mutation MYH7-Val606Met accounted for 28.0% of cases. Mutations in GLA and PRKAG2 were found in three patients. Furthermore, we found 49 variants of unknown significance in 31 genes in 20.4% of cases. During a 6.7 +/- 4.2 year follow-up, annual all-cause mortality in 482 index patients and their relatives with HCM was higher than that in the matched Finnish population (1.70 vs. 0.87%; P <0.001). Sudden cardiac deaths were rare (n = 8). Systolic heart failure (hazard ratio 17.256, 95% confidence interval 3.266-91.170, P = 0.001) and maximal left ventricular wall thickness (hazard ratio 1.223, 95% confidence interval 1.098-1.363, P <0.001) were independent predictors of HCM-related mortality and life-threatening cardiac events. The patients with a pathogenic or likely pathogenic mutation underwent an implantable cardioverter defibrillator implantation more often than patients without a pathogenic or likely pathogenic mutation (12.9 vs. 3.5%, P <0.001), but there was no difference in all-cause or HCM-related mortality between the two groups. Mortality due to HCM during 10 year follow-up among the 5.2 million population of Finland was studied from death certificates of the National Registry, showing 269 HCM-related deaths, of which 32% were sudden. Conclusions We identified pathogenic and likely pathogenic mutations in 38% of Finnish patients with HCM. Four major sarcomere mutations accounted for 28% of HCM cases, whereas HCM-related mutations in non-sarcomeric genes were rare. Mortality in patients with HCM exceeded that of the general population. Finally, among 5.2 million Finns, there were at least 27 HCM-related deaths annually.
Subject: Hypertrophic cardiomyopathy
Genetics
Targeted sequencing
Mutation
Mortality
Outcome
HEAVY-CHAIN GENE
ALPHA-TROPOMYOSIN
ASP175ASN MUTATION
MAGNETIC-RESONANCE
FOUNDER MUTATIONS
DISEASE
IMPAIRMENT
MORTALITY
INSIGHTS
3121 General medicine, internal medicine and other clinical medicine
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