umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)Alternativ titel
Hjärtfunktion vid ärftlig transtyretin-amyloidos : en ekokardiografisk studie (Svenska)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet , 2016. , s. 56
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1774
Nyckelord [en]
Amyloid, echocardiography, ECG, HCM, fibril type, strain, ATTR, cardiomyopathy, speckle tracking
Nationell ämneskategori
Kardiologi Annan klinisk medicin
Identifikatorer
URN: urn:nbn:se:umu:diva-113891ISBN: 978-91-7601-399-1 (tryckt)OAI: oai:DiVA.org:umu-113891DiVA, id: diva2:890771
Disputation
2016-01-29, Hörsal Betula Unod L0, Umeå, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2016-01-08 Skapad: 2016-01-04 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
Delarbeten
1. Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?
Öppna denna publikation i ny flik eller fönster >>Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?
Visa övriga...
2015 (Engelska)Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 22, nr 3, s. 163-170Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. Methods: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. Results: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). Conclusion: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

Nyckelord
cardiac amyloidosis, classification tree, echocardiography, electrocardiography, hypertrophic rdiomyopathy, hypertrophy
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Kardiologi
Identifikatorer
urn:nbn:se:umu:diva-109962 (URN)10.3109/13506129.2015.1037831 (DOI)000361295200004 ()26104852 (PubMedID)
Tillgänglig från: 2015-10-09 Skapad: 2015-10-09 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
2. Right ventricular involvement in transthyretin amyloidosis
Öppna denna publikation i ny flik eller fönster >>Right ventricular involvement in transthyretin amyloidosis
Visa övriga...
2018 (Engelska)Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, nr 3, s. 160-166Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: The extent of right ventricular (RV) involvement in transthyretin amyloidosis (ATTR) is unknown.

Objectives: This study sought to establish the degree of RV involvement in ATTR amyloidosis, and compare findings with RV involvement in hypertrophic cardiomyopathy (HCM).

Methods: Forty-two patients with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were included in this study. Echocardiographic measurements for conventional parameters, as well as RV global and segmental strain, were recorded.

Results: When comparing RV structure and function between cardiac ATTR amyloidosis and HCM patients, only segmental strain differed between the two groups. In cardiac ATTR amyloidosis, we found an RV apex-to-base strain gradient with highest deformation in the apex. This pattern was reversed in patients with HCM.

Conclusions: RV involvement is common in cardiac ATTR patients. The present study also detected an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to what has previously been described for the left ventricle in these patients. This pattern was not seen in HCM patients. Further studies are needed to assess the clinical importance of these findings.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2018
Nyckelord
Hypertrophic cardiomyopathy, apical sparing, strain, amyloid cardiomyopathy, right ventricle
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:umu:diva-113889 (URN)10.1080/13506129.2018.1493989 (DOI)000451980700004 ()30193533 (PubMedID)
Anmärkning

Originally included in thesis in manuscript form.

Tillgänglig från: 2016-01-04 Skapad: 2016-01-04 Senast uppdaterad: 2019-05-17Bibliografiskt granskad
3. Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition
Öppna denna publikation i ny flik eller fönster >>Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition
Visa övriga...
2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikel-id e0143456Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

PURPOSE: Transthyretin V30M (ATTR V30M) amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.

MATERIAL AND METHODS: Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV) dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.

RESULTS: There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007) and posterior wall thicknesses (p = 0.010), lower median LV mass indexed to height (p = 0.008), and higher septal strain (p = 0.037), as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.

CONCLUSION: This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.

Nyckelord
gender, fibril, ATTR, transthyretin, cardiac amyloidosis, age
Nationell ämneskategori
Kardiologi
Identifikatorer
urn:nbn:se:umu:diva-113831 (URN)10.1371/journal.pone.0143456 (DOI)000365853900127 ()
Tillgänglig från: 2016-01-04 Skapad: 2016-01-04 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
4. Amyloid Fibril Composition as a Predictor of Development of Cardiomyopathy After Liver Transplantation for Hereditary Transthyretin Amyloidosis
Öppna denna publikation i ny flik eller fönster >>Amyloid Fibril Composition as a Predictor of Development of Cardiomyopathy After Liver Transplantation for Hereditary Transthyretin Amyloidosis
Visa övriga...
2012 (Engelska)Ingår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, nr 10, s. 1017-1023Artikel i tidskrift (Refereegranskat) 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.

Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:umu:diva-56994 (URN)10.1097/TP.0b013e31824b3749 (DOI)000304866100012 ()
Tillgänglig från: 2012-07-04 Skapad: 2012-07-02 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

Open Access i DiVA

fulltext(1803 kB)525 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 1803 kBChecksumma SHA-512
872cbcae08ad56d6cdf1e410ce1431ca1fffe3dadd340fbbf967aac72fac27a9e2164fe3ee6abfd5d57ad8f0c2208b0f127771a34cbc87f2f7fa05c6e0806879
Typ fulltextMimetyp application/pdf
Spikblad(98 kB)16 nedladdningar
Filinformation
Filnamn SPIKBLAD01.pdfFilstorlek 98 kBChecksumma SHA-512
72c49c2517487c7208fade4e70ba839996136a9892fc91b90bf89cdccc518a1da3dba9eddec2612eb5acc0e9b301f4f04604bd871a6a7860e04816e87610bc20
Typ spikbladMimetyp application/pdf

Personposter BETA

Arvidsson, Sandra

Sök vidare i DiVA

Av författaren/redaktören
Arvidsson, Sandra
Av organisationen
Institutionen för folkhälsa och klinisk medicin
KardiologiAnnan klinisk medicin

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 525 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 856 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf