University of Oulu

Jääskeläinen, P., Vangipurapu, J., Raivo, J., Kuulasmaa, T., Heliö, T., Aalto‐Setälä, K., Kaartinen, M., Ilveskoski, E., Vanninen, S., Hämäläinen, L., Melin, J., Kokkonen, J., Nieminen, M. S., The FinHCM Study Group, Laakso, M., and Kuusisto, J. ( 2019) Genetic basis and outcome in a nationwide study of Finnish patients with hypertrophic cardiomyopathy, ESC Heart Failure, 6: 436– 445.

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

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Author: Jääskeläinen, Pertti1,2; Vangipurapu, Jagadish3; Raivo, Joose3;
Organizations: 1Heart Center, Kuopio University Hospital, Kuopio, Finland
2Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland, Kuopio University Hospital, P.O. Box 100, FIN-70029 KYS, Kuopio, Finland
3Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
4Helsinki University Central Hospital, Helsinki, Finland
5Heart Center Co., Institute of Biomedical Technology, Tampere University Hospital, University of Tampere, Tampere, Finland
6Savonlinna Central Hospital, Savonlinna, Finland
7Heart Center Co., Tampere University Hospital, Tampere, Finland
8Vaasa Central Hospital, Vaasa, Finland
9Central Finland Central Hospital, Jyväskylä, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2019
Publish Date: 2020-03-31


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.

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The FinHCM Study Group: Helena Kervinen10 (Hyvinkää Hospital, Hyvinkää, Finland), Juha Mustonen11 (North Karelia Central Hospital, Joensuu, Finland), Jukka Juvonen12 (Kainuu Central Hospital, Kajaani, Finland), Mari Niemi13 (Kokkola Central Hospital, Kokkola, Finland), Paavo Uusimaa14 (Oulu University Hospital, Oulu, Finland), Juhani Junttila14 (Oulu University Hospital, Oulu, Finland), Matti Kotila15 (Seinäjoki Central Hospital, Seinäjoki, Finland), Mikko Pietilä16 (Turku University Hospital, Turku, Finland), Heini Jyrkilä17 (University of Eastern Finland, Kuopio, Finland), Ilkka Mähönen18 (University of Tampere, Tampere, Finland), Paula Vartia19 (University of Helsinki, Helsinki, Finland).

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Series: ESC heart failure
ISSN: 2055-5822
ISSN-E: 2055-5822
ISSN-L: 2055-5822
Volume: 6
Issue: 2
Pages: 436 - 445
DOI: 10.1002/ehf2.12420
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Academy of Finland, the Finnish Foundation for Cardiovascular Research, and the Kuopio University Hospital (EVO grants to J.K.).
Copyright information: © 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. ESC HEART FAILURE ESC Heart Failure 2019; 6: 436–445 Published online 18 February 2019 in Wiley Online Library ( DOI: 10.1002/ehf2.12420. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.