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Amyloid heart disease mimicking hypertrophic cardiomyopathy.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
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2005 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, no 3, 225-230 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate the importance of transthyretin (TTR) gene mutations in explaining the phenotypic expression in patients diagnosed with hypertrophic cardiomyopathy (HCM) in northern Sweden. BACKGROUND: Hypertrophic cardiomyopathy is relatively common and often caused by mutations in sarcomeric protein genes. Mutations in the TTR gene are also common, one of which causes familial amyloid polyneuropathy (FAP), with peripheral polyneuropathy and frequently, cardiac hypertrophy. These circumstances were highlighted by the finding of an index case with amyloidosis, presenting itself as HCM. Initial rectal and fat biopsies did not show amyloid deposits. Later on, the patient was shown to carry a TTR gene mutation, and cardiac amyloidosis was confirmed by myocardial biopsy. Only then was a repeated fat biopsy positive for amyloid deposits. DESIGN: Cross-sectional study. SETTING: Cardiology tertiary referral centre. SUBJECTS: Forty-six unrelated individuals with HCM and the index case were included. Common diagnostic criteria for HCM were used. The 46 patients with HCM were previously analysed for mutations in eight sarcomeric protein genes and the TTR gene was now analysed by denaturing high-performance liquid chromatography and direct sequencing. RESULTS: One mutation in the TTR gene (Val30Met) was found in three individuals and the index case. CONCLUSIONS: Three of the 46 cases with HCM carried the Val30Met mutation, and were considered likely to have cardiac amyloidosis, like the index case. As a correct diagnosis of cardiac amyloidosis is mandatory for a potentially life-saving treatment, TTR mutation analysis should be considered in cases of HCM not explained by mutations in sarcomeric protein genes.

Place, publisher, year, edition, pages
2005. Vol. 258, no 3, 225-230 p.
Keyword [en]
Adult, Aged, Aged, 80 and over, Amyloid Neuropathies, Familial/diagnosis/*genetics, Cardiology Service, Hospital, Cardiomyopathy, Hypertrophic/diagnosis/*genetics, Cross-Sectional Studies, DNA Mutational Analysis, Diagnosis, Differential, Humans, Male, Middle Aged, Point Mutation, Prealbumin/*genetics
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-14815DOI: 10.1111/j.1365-2796.2005.01522.xPubMedID: 16115295OAI: diva2:154487
Available from: 2007-06-18 Created: 2007-06-18 Last updated: 2012-06-21Bibliographically approved
In thesis
1. Hypertrophic cardiomyopathy in Northern Sweden: with special emphasis on molecular genetics
Open this publication in new window or tab >>Hypertrophic cardiomyopathy in Northern Sweden: with special emphasis on molecular genetics
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of this thesis was to identify the genotypes causing HCM in northern Sweden, to characterize the disease phenotypes and correlate these findings.

Forty-six patients were recruited for the genetic studies (21 women), 11 familial and 35 sporadic cases. Eight sarcomeric protein genes were screened for mutations. A total of 11 different disease causing mutations were found in four genes. Six of the mutations were previously not described. A novel mutation (a 33 base pair deletion) in the troponin I gene was found in one HCM family. Despite the severe genetic defect, the associated phenotype displayed only mild cardiac hypertrophy and few symptoms. Most mutations (64%) were identified in the myosin binding protein C gene, a gene considered to have a low penetrance. Mutations were identified in 10 of 11 familial HCM cases, but only in three of the 35 sporadic cases.

It was found that cardiac amyloidosis can sometimes present itself as HCM. Three HCM patients (7%) carried the ATTR Val30Met mutation, also found in Swedish patients with familial amyloid polyneuropathy (FAP). The patients had no symptoms of polyneuropathy, but cardiac amyloidosis as the cause of hypertrophy was verified by myocardial biopsy in an index case. Amyloid heart disease should therefore be considered as a differential diagnosis in patients with HCM.

By studying heart rate variability (HRV), it was found that young patients with HCM had signs of autonomic dysfunction, expressed as a reduced HRV. Treatment with beta-blockade attenuated these effects. Abnormal autonomic function might be a substrate for lethal arrhythmias, most often encountered in younger patients with HCM. The results suggest a possible protective effect of beta-blockade, remaining to be studied further.

Ventricular function is frequently abnormal in HCM. In particular, diastolic dysfunction has been demonstrated. The recently described myocardial performance index allows the assessment of cardiac function by combining systolic and diastolic performance. We found that patients with hypertrophic cardiomyopathy had evidence of global and regional right ventricular dysfunction, besides left ventricular dysfunction. Hypertrophic cardiomyopathy is traditionally considered to be a disease of the left ventricle. The results show that hypertrophic cardiomyopathy should more be regarded as a biventricular disease.

In conclusion, the myosin binding protein C gene is the most common gene causing familial HCM in northern Sweden. This disease gene is considered to be associated with a mild, late-onset disease with ≈50% penetrance at 30 years of age. The low disease penetrance emphasizes the importance of adequate family screening when evaluating patients with HCM, since the familial nature of the disease might easily be overlooked. These particular disease features in northern Sweden contrast to most previous reports, which indicate another disease gene as the most frequent in HCM, associated with a much higher penetrance. Amyloid heart disease, requiring different treatment than HCM, should be kept in mind as a differential diagnosis in the management of patients with HCM.

Key words: Hypertrophic cardiomyopathy, genetics, autonomic nervous system, familial amyloid polyneuropathy, echocardiography.

Umeå University medical dissertations, ISSN 0346-6612 ; 894
Hypertrophic cardiomyopathy, genetics, autonomic nervous system, familial amyloid polyneuropathy, echocardiography
Research subject
urn:nbn:se:umu:diva-274 (URN)91-7305-660-X (ISBN)
Public defence
2004-05-28, Sal E04, Byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2004-05-10 Created: 2004-05-10 Last updated: 2010-08-10Bibliographically approved

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Mörner, StellanHellman, UrbanSuhr, Ole BKazzam, ElsadigWaldenström, Anders
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