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Amyloid Fibril Composition as a Predictor of Development of Cardiomyopathy After Liver Transplantation for Hereditary Transthyretin Amyloidosis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
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2012 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 10, 1017-1023 p.Article in journal (Refereed) Published
Abstract [en]

Background. Liver transplantation (LTx) is an accepted treatment for hereditary transthyretin (TTR) amyloidosis (ATTR). However, unforeseen heart complications, especially a rapid development of cardiomyopathy after LTx has affected mortality and morbidity. Recently, a relationship between ATTR-fibril composition and cardiomyopathy has been noted. The aim of this study was to investigate whether development of cardiomyopathy and heart failure in LTx ATTR amyloid patients is related to amyloid fibril composition. Methods. Twenty-four patients with hereditary ATTR amyloidosis who had undergone LTx and have had their amyloid fibril type tested were available for the study. They had been examined by echocardiography including tissue Doppler and speckle tracking echocardiography before and after LTx. Patients were divided into two groups according to fibril composition, 10 patients with type A fibrils (a mixture of truncated and full-length TTR) and 14 patients with type B fibrils (full-length TTR fibrils only). There was no difference in time to the follow-up echocardiography between the two groups. Results. After LTx, the group consisting of type A patients developed symptoms of heart failure and with reduced systolic and diastolic ventricular function as shown by echocardiography, whereas no similar deterioration was noted for the group of patients with type B fibrils. Conclusion. Patients with type A fibrils deteriorate an already existing cardiomyopathy and heart failure after LTx, in contrast to patients with type B fibrils. These results might have significant clinical implications in optimizing best patients selection criteria for LTx.

Place, publisher, year, edition, pages
2012. Vol. 93, no 10, 1017-1023 p.
National Category
Clinical Medicine
URN: urn:nbn:se:umu:diva-56994DOI: 10.1097/TP.0b013e31824b3749ISI: 000304866100012OAI: diva2:539519
Available from: 2012-07-04 Created: 2012-07-02 Last updated: 2016-01-07Bibliographically approved
In thesis
1. Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study
Open this publication in new window or tab >>Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Hjärtfunktion vid ärftlig transtyretin-amyloidos : en ekokardiografisk studie
Abstract [en]

Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.

Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.

Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.

Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. 56 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1774
Amyloid, echocardiography, ECG, HCM, fibril type, strain, ATTR, cardiomyopathy, speckle tracking
National Category
Cardiac and Cardiovascular Systems Other Clinical Medicine
urn:nbn:se:umu:diva-113891 (URN)978-91-7601-399-1 (ISBN)
Public defence
2016-01-29, Hörsal Betula Unod L0, Umeå, 09:00 (Swedish)
Available from: 2016-01-08 Created: 2016-01-04 Last updated: 2016-01-07Bibliographically approved

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Gustafsson, SandraHenein, Michael Y.Lindqvist, PerSuhr, Ole B.
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