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Pilebro, Björn
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Publications (10 of 26) Show all publications
Harms, H. J., Clemmensen, T., Rosengren, S., Tolbod, L., Pilebro, B., Wikström, G., . . . Sorensen, J. (2023). Association of right ventricular myocardial blood flow with pulmonary pressures and outcome in cardiac amyloidosis. JACC Cardiovascular Imaging
Open this publication in new window or tab >>Association of right ventricular myocardial blood flow with pulmonary pressures and outcome in cardiac amyloidosis
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2023 (English)In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591Article in journal (Refereed) In press
Abstract [en]

Background: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied.

Objectives: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA.

Methods: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA.

Results: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, New York Heart Association functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with hazard ratio 9.0 (95% CI: 4.2-14.5), P < 0.0001).

Conclusions: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
cardiac amyloidosis, myocardial blood flow, positron emission tomography, pulmonary hypertension, right ventricle
National Category
Cardiac and Cardiovascular Systems Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-208226 (URN)10.1016/j.jcmg.2023.01.024 (DOI)37052560 (PubMedID)2-s2.0-85153887935 (Scopus ID)
Available from: 2023-05-12 Created: 2023-05-12 Last updated: 2023-06-19
Anan, I., Suhr, O. B., Liszewska, K., Baranda, J. M., Pilebro, B., Wixner, J. & Ihse, E. (2022). Amyloid fibril composition type is consistent over time in patients with Val30Met (p. Val50Met) transthyretin amyloidosis. PLOS ONE, 17(3), Article ID e0266092.
Open this publication in new window or tab >>Amyloid fibril composition type is consistent over time in patients with Val30Met (p. Val50Met) transthyretin amyloidosis
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2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0266092Article in journal (Refereed) Published
Abstract [en]

Background: We have previously shown that transthyretin (TTR) amyloidosis patients have amyloid fibrils of either of two compositions; type A fibrils consisting of large amounts of C-terminal TTR fragments in addition to full-length TTR, or type B fibrils consisting of only full-length TTR. Since type A fibrils are associated with an older age in ATTRVal30Met (p.Val50Met) amyloidosis patients, it has been discussed if the TTR fragments are derived from degradation of the amyloid deposits as the patients are aging. The present study aimed to investigate if the fibril composition type changes over time, especially if type B fibrils can shift to type A fibrils as the disease progresses.

Material and methods: Abdominal adipose tissue biopsies from 29 Swedish ATTRVal30Met amyloidosis patients were investigated. The fibril type in the patients initial biopsy taken for diagnostic purposes was compared to a biopsy taken several years later (ranging between 2 and 13 years). The fibril composition type was determined by western blot.

Results: All 29 patients had the same fibril composition type in both the initial and the follow-up biopsy (8 type A and 21 type B). Even patients with a disease duration of more than 12 years and an age over 75 years at the time of the follow-up biopsy had type B fibrils in both biopsies.

Discussion: The result clearly shows that the amyloid fibril composition containing large amounts of C-terminal fragments (fibril type A) is a consequence of other factors than a slow degradation process occurring over time.

Place, publisher, year, edition, pages
Public Library of Science, 2022
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-193805 (URN)10.1371/journal.pone.0266092 (DOI)000799828800066 ()35358243 (PubMedID)2-s2.0-85127435798 (Scopus ID)
Funder
Erik, Karin och Gösta Selanders Foundation
Available from: 2022-05-06 Created: 2022-05-06 Last updated: 2023-09-05Bibliographically approved
Unéus, E. I., Wilhelmsson, C., Bäckström, D., Anan, I., Wixner, J., Pilebro, B., . . . Sundström, T. (2022). Cerebellar and Cerebral Amyloid Visualized by [18F]flutemetamol PET in Long-Term Hereditary V30M (p.V50M) Transthyretin Amyloidosis Survivors. Frontiers in Neurology, 13, Article ID 816636.
Open this publication in new window or tab >>Cerebellar and Cerebral Amyloid Visualized by [18F]flutemetamol PET in Long-Term Hereditary V30M (p.V50M) Transthyretin Amyloidosis Survivors
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2022 (English)In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 13, article id 816636Article in journal (Refereed) Published
Abstract [en]

Introduction: Hereditary transthyretin (ATTRv) amyloidosis caused by the V30M (p. V50M) mutation is a fatal, neuropathic systemic amyloidosis. Liver transplantation has prolonged the survival of patients and central nervous system (CNS) complications, attributed to amyloid angiopathy caused by CNS synthesis of variant transthyretin, have emerged. The study aimed to ascertain amyloid deposition within the brain in long-term ATTRv amyloidosis survivors with neurological symptoms from the CNS.

Methods: A total of 20 patients with ATTR V30M having symptoms from the CNS and a median disease duration of 16 years (8–25 years) were included in this study. The cognitive and peripheral nervous functions were determined for 18 patients cross-sectionally at the time of the investigation. Amyloid brain deposits were examined by [18F]flutemetamol PET/CT. Five patients with Alzheimer's disease (AD) served as positive controls.

Result: 60% of the patients with ATTRv had a pathological Z-score in the cerebellum, compared to only 20% in the patients with AD. 75% of the patients with transient focal neurological episodes (TFNEs) displayed a pathological uptake only in the cerebellum. Increased cerebellar uptake was related to an early age of onset of the ATTRv disease. 55% of the patients with ATTRv had a pathological Z-score in the global cerebral region compared to 100% of the patients with AD.

Conclusion: Amyloid deposition within the brain after long-standing ATTRv amyloidosis is common, especially in the cerebellum. A cerebellar amyloid uptake profile seems to be related to TFNE symptoms.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
amyloid angiopathy, amyloidosis-hereditary, positron emission tomography, transthyretin, [18F]flutemetamol
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-193803 (URN)10.3389/fneur.2022.816636 (DOI)000773941500001 ()35317351 (PubMedID)2-s2.0-85127418033 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20160787Region VästerbottenThe Swedish Brain Foundation
Available from: 2022-05-06 Created: 2022-05-06 Last updated: 2023-08-28Bibliographically approved
Henein, M. Y., Pilebro, B. & Lindqvist, P. (2022). Disease progression in cardiac morphology and function in heart failure: ATTR cardiac amyloidosis versus hypertensive left ventricular hypertrophy. Heart and Vessels, 37, 1562-1569
Open this publication in new window or tab >>Disease progression in cardiac morphology and function in heart failure: ATTR cardiac amyloidosis versus hypertensive left ventricular hypertrophy
2022 (English)In: Heart and Vessels, ISSN 0910-8327, E-ISSN 1615-2573, Vol. 37, p. 1562-1569Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is today more frequently recognized but the rate of progression of cardiac dysfunction is not well established. The aim of this study is to investigate the nature of cardiac structure and function changes, over time, in a retrospective cohort of ATTR-CA patients.

METHODS: Fifty-one patients with ATTR-CA (mean age 78 ± 7 years, 30 females) were compared with 20 patients with heart failure but no amyloidosis (HFnCA) (mean age 76 ± 7 years, 5 females), all with septal thickness >  = 14 mm. All patients underwent DPD scintigraphy and an echocardiogram (Echo 2) which was compared with a previous echocardiographic examination (Echo 1), performed at least 3 years before.

RESULTS: Over the follow-up period, the interventricular septal thickness (IVST) and relative wall thickness (RWT) in ATTR-CA increased from 16 (4) to 18 (5) mm and from 0.51 (0.17) to 0.62 (0.21) respectively, p < 0.001 for both, by a mean increase of 0.4 mm/year and 0.03 mm/year, (p = 0.009 and p = 0.002 compared with HFnCA), respectively. RWT > 0.45 (AUC = 0.77) and RELAPS > 2.0 (AUC 0.86) both predicted positive DPD diagnosis for ATTR-CA.

CONCLUSION: In ATTR-CA patients, the overtime-increase in RWT and IVST was worse than that seen in patients with heart failure but no cardiac amyloidosis. Also, RWT and relative apical sparing predicted diagnosis of ATTR-CA, thus could strengthen the use of follow-up echocardiographic findings as red flag for the diagnosis of ATTR-CA.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Cardiac amyloidosis, DPD scintigraphy, Echocardiography, Prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-193208 (URN)10.1007/s00380-022-02048-5 (DOI)000767750300001 ()35275264 (PubMedID)2-s2.0-85126085900 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20160787Swedish Heart Lung Foundation, 20200160Swedish Research Council, 2019–01338
Available from: 2022-03-21 Created: 2022-03-21 Last updated: 2022-11-28Bibliographically approved
Schmidt, H. H., Wixner, J., Planté-Bordeneuve, V., Muñoz-Beamud, F., Lladó, L., Gillmore, J. D., . . . Adams, D. (2022). Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. American Journal of Transplantation, 22(6), 1646-1657
Open this publication in new window or tab >>Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation
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2022 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 22, no 6, p. 1646-1657Article in journal (Refereed) Published
Abstract [en]

Hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis, is a progressive disease, for which liver transplantation (LT) has been a long-standing treatment. However, disease progression continues post-LT. This Phase 3b, open-label trial evaluated efficacy and safety of patisiran in patients with ATTRv amyloidosis with polyneuropathy progression post-LT. Primary endpoint was median transthyretin (TTR) reduction from baseline. Twenty-three patients received patisiran for 12 months alongside immunosuppression regimens. Patisiran elicited a rapid, sustained TTR reduction (median reduction [Months 6 and 12 average], 91.0%; 95% CI: 86.1%–92.3%); improved neuropathy, quality of life, and autonomic symptoms from baseline to Month 12 (mean change [SEM], Neuropathy Impairment Score, −3.7 [2.7]; Norfolk Quality of Life-Diabetic Neuropathy questionnaire, −6.5 [4.9]; least-squares mean [SEM], Composite Autonomic Symptom Score-31, −5.0 [2.6]); and stabilized disability (Rasch-built Overall Disability Scale) and nutritional status (modified body mass index). Adverse events were mild or moderate; five patients experienced ≥1 serious adverse event. Most patients had normal liver function tests. One patient experienced transplant rejection consistent with inadequate immunosuppression, remained on patisiran, and completed the study. In conclusion, patisiran reduced serum TTR, was well tolerated, and improved or stabilized key disease impairment measures in patients with ATTRv amyloidosis with polyneuropathy progression post-LT (www.clinicaltrials.gov NCT03862807).

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
clinical research/practice, clinical trial, liver allograft function/dysfunction, liver transplantation/hepatology, molecular biology: small interfering RNA, neurology, patient survival, pharmacology
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-193692 (URN)10.1111/ajt.17009 (DOI)000780378600001 ()35213769 (PubMedID)2-s2.0-85127222590 (Scopus ID)
Available from: 2022-05-02 Created: 2022-05-02 Last updated: 2023-05-29Bibliographically approved
Arnberg, E., Eldhagen, P., Löfbacka, V., Venkateshvaran, A., Pilebro, B. & Lindqvist, P. (2022). RWT/SaVR-A Simple and Highly Accurate Measure Screening for Transthyretin Cardiac Amyloidosis. Journal of Clinical Medicine, 11(14), Article ID 4120.
Open this publication in new window or tab >>RWT/SaVR-A Simple and Highly Accurate Measure Screening for Transthyretin Cardiac Amyloidosis
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2022 (English)In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, no 14, article id 4120Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Cardiac amyloidosis is an underdiagnosed condition and simple methods for accurate diagnosis are warranted. We aimed to validate a novel, dual-modality approach to identify transthyretin cardiac amyloidosis (ATTR-CA), employing echocardiographic relative wall thickness (RWT), and ECG S-wave from aVR (SaVR), and compare its accuracy with conventional echocardiographic approaches.

MATERIAL AND METHODS: We investigated 102 patients with ATTR-CA and 65 patients with left ventricular hypertrophy (LVH), all with septal thickness &gt; 14 mm. We validated the accuracy of echocardiographic measures, including RWT, RWT/SaVR, posterior wall thickness (PWT), LV mass index (LVMI), left atrial volume index (LAVI), global longitudinal strain (GLS), and relative apical sparing (RELAPS) to identify ATTR-CA diagnosed using DPD-scintigraphy or abdominal fat biopsy.

RESULTS: PWT, RWT, RELAPS, troponin, and RWT/SaVR were significantly higher in ATTR-CA compared to LVH. RWT/SaVR &gt; 0.7 was the most accurate parameter to identify ATTR-CA (sensitivity 97%, specificity 90% and accuracy 91%). RELAPS was found to have much less accuracy (sensitivity 74%, specificity 76% and accuracy 73%).

CONCLUSION: We can confirm the very strong diagnostic accuracy of RWT/SaVR to identify ATTR-CA in patients with septal thickness &gt; 14 mm. Given its high sensitivity and specificity, RWT/SaVR &gt; 0.7 has the potential to implement as a non-invasive, simple, and widely available diagnostic tool when screening for ATTR-CA.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
ECG, cardiac amyloidosis, left ventricular hypertrophy, relative wall thickness, transthyretin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-198312 (URN)10.3390/jcm11144120 (DOI)000831448600001 ()35887882 (PubMedID)2-s2.0-85137207829 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20160787Swedish Heart Lung Foundation, 20200160Swedish Research Council, 2019–01338
Available from: 2022-07-28 Created: 2022-07-28 Last updated: 2022-11-03Bibliographically approved
Löfbacka, V., Axelsson, J., Pilebro, B., Suhr, O. B., Lindqvist, P. & Sundström, T. (2021). Cardiac transthyretin amyloidosis 99mTc-DPD SPECTcorrelates with strain echocardiography and biomarkers. European Journal of Nuclear Medicine and Molecular Imaging, 48, 1822-1832
Open this publication in new window or tab >>Cardiac transthyretin amyloidosis 99mTc-DPD SPECTcorrelates with strain echocardiography and biomarkers
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2021 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 48, p. 1822-1832Article in journal (Refereed) Published
Abstract [en]

Purpose: Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters.

Methods: Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers.

Results: Statistically significant correlations were seen in VOIs between DPD uptakes and the corresponding echocardiographic strain values. Furthermore, DPDload had a strong correlation with echocardiographic strain parameters and also correlated with biomarkers troponin T and logarithmic NT-ProBNP.

Conclusions: In patients with ATTRv cardiomyopathy, DPD SPECT/CT measures the amyloid distribution and provides information on cardiac amyloid load. DPD amyloid load correlates with functional cardiac parameters.

Place, publisher, year, edition, pages
Springer, 2021
Keywords
Amyloidosis-hereditary, Cardiomyopathy, Transthyretin amyloidosis, Tc-99m-DPD scintigraphy, 2D speckle tracking strain, SPECT
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-178531 (URN)10.1007/s00259-020-05144-8 (DOI)000602293500001 ()33367948 (PubMedID)2-s2.0-85098069527 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20160787
Available from: 2021-01-15 Created: 2021-01-15 Last updated: 2023-03-24Bibliographically approved
Löfbacka, V., Suhr, O. B., Pilebro, B., Wixner, J., Sundström, T., Lindmark, K., . . . Lindqvist, P. (2021). Combining ECG and echocardiography to identify transthyretin cardiac amyloidosis in heart failure. Clinical Physiology and Functional Imaging, 41(5), 408-416
Open this publication in new window or tab >>Combining ECG and echocardiography to identify transthyretin cardiac amyloidosis in heart failure
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2021 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 41, no 5, p. 408-416Article in journal (Refereed) Published
Abstract [en]

AIMS/BACKGROUND: Transthyretin amyloid (ATTR) amyloidosis cardiomyopathy is an underdiagnosed, causatively treatable cause of heart failure. The aim of this study was to evaluate the efficacy of electrocardiography (ECG) and echocardiography on patients with increased interventricular septum diameter (IVSd) to identify ATTR cardiac amyloidosis (ATTR-CA) patients.

METHODS: We investigated 58 patients with heart failure and an IVSd >14mm. Included were 33 ATTR-CA patients and 25 controls that consisted of non-amyloidosis heart failure (HF) patients with negative 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy. We used echocardiography including 2D speckle tracking strain and a 12-lead ECG to test the accuracy to differentiate the groups.

RESULTS: We found high diagnostic accuracy (98%) for differentiating ATTR-CA from HF controls using a combination of R amplitude in -aVR from ECG and relative wall thickness acquired from echocardiography. With this combined model (RWT/ R in -aVR), the sensitivity was 100% and specificity was 95% using a cut off value of 0.90. Furthermore, the area under the curve was 99% and the negative predictive value was 100%.

CONCLUSION: We found that a simple combination of ECG and echocardiographic parameters used in clinical settings was able to differentiate ATTR-CA from other etiologies of HF with increased interventricular septum thickness. The high sensitivity and negative predictive value render the algorithm useful for selection of patients for further diagnostic procedures for ATTR-CA.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
Cardiac amyloidosis, ECG, Echocardiography, Heart failure, Transthyretin amyloidosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-183897 (URN)10.1111/cpf.12715 (DOI)000661468500001 ()34033209 (PubMedID)2-s2.0-85107933221 (Scopus ID)
Funder
Swedish Heart Lung Foundation, 20160787Swedish Heart Lung Foundation, 20200160Swedish Research Council, 2019-01338
Available from: 2021-06-03 Created: 2021-06-03 Last updated: 2022-03-04Bibliographically approved
Lindmark, K., Pilebro, B., Sundström, T. & Lindqvist, P. (2021). Prevalence of wild type transtyrethin cardiac amyloidosis in a heart failure clinic. ESC Heart Failure, 8(1), 745-749
Open this publication in new window or tab >>Prevalence of wild type transtyrethin cardiac amyloidosis in a heart failure clinic
2021 (English)In: ESC Heart Failure, E-ISSN 2055-5822, Vol. 8, no 1, p. 745-749Article in journal (Refereed) Published
Abstract [en]

Aims: Wild type transthyretin amyloidosis (ATTRwt) has gained interest during recent years due to better diagnostic tools and the emergence of treatment options. Little is known about the prevalence of the disease. We aimed to investigate the prevalence in a heart failure population with myocardial hypertrophy.

Methods and results: All patients with an ICD code of heart failure living within the catchment area of Umeå University hospital and intraventricular septum >14 mm were offered screening with 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scan and a clinical work up. Out of 2238 patients with heart failure, 174 patients were found to have a septum >14 mm. Ten patients were already diagnosed with hereditary ATTR cardiomyopathy, 12 patients had ATTRwt cardiomyopathy, 12 patients had known HCM, one patient had AL amyloidosis, and four patients had already undergone a negative DPD scan (DPD uptake grade 0 and 1) within the last 3 years. This left 134 patients who we tried to contact for screening, but 48 patients had either died or declined to participate. Out of 86 screened patients, 13 had a DPD uptake of grade 2 or 3 without other amyloid disease making the total number of patients with ATTRwt in this population 25.

Conclusions: Approximately 20% of investigated patients in a cohort with heart failure and increased myocardial wall thickness has ATTRwt. Calculated for the whole population of heart failure patients, the prevalence is just over 1.1%. Comparing this number to the total population would give an estimated prevalence of 1:6000.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
ATTRwt, Cardiac amyloidosis, Amyloidosis, Heart failure, Transthyretin amyloidosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-177241 (URN)10.1002/ehf2.13110 (DOI)000589923100001 ()33205581 (PubMedID)2-s2.0-85096650668 (Scopus ID)
Available from: 2020-12-14 Created: 2020-12-14 Last updated: 2022-05-03Bibliographically approved
Paulsson Rokke, H., Sadat Gousheh, N., Westermark, P., Suhr, O. B., Anan, I., Ihse, E., . . . Wixner, J. (2020). Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis. Orphanet Journal of Rare Diseases, 15(1), Article ID 278.
Open this publication in new window or tab >>Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis
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2020 (English)In: Orphanet Journal of Rare Diseases, E-ISSN 1750-1172, Vol. 15, no 1, article id 278Article in journal (Refereed) Published
Abstract [en]

Background: The diagnostic accuracy of histopathological detection of transthyretin amyloid (ATTR) by Congo red staining of abdominal fat samples has been questioned since low sensitivity has been reported, especially for patients with ATTR cardiomyopathy. However, the outcome of surgically obtained fat pad biopsies has not yet been evaluated. The aim was to evaluate the diagnostic accuracy of skin punch biopsies from abdominal fat in patients with suspected ATTR amyloidosis.

Material and methods: Data were evaluated from patients who had undergone abdominal fat pad biopsies using a skin punch due to suspected amyloidosis from 2006 to 2015. The biopsies had been analysed using Congo red staining to determine the presence of amyloid, and immunohistochemistry or Western blot to determine the type of amyloidosis. The final diagnosis was based on the clinical picture, biopsy results and DNA sequencing. Minimum follow-up after the initial biopsy was 3 years.

Results: Two hundred seventy-four patients (61% males) were identified, and in 132 (48%), a final diagnosis of amyloidosis had been settled. The majority (93%) had been diagnosed with hereditary transthyretin (ATTRv) amyloidosis, and therefore subsequent analyses were focused on these patients. Overall, our data showed a test specificity of 99% and a sensitivity of 91%. Ninety-eight (94%) of the patients had neuropathic symptoms at diagnosis, whereas 57 (55%) had signs of amyloid cardiomyopathy. Subgroup analyses showed that patients with merely neuropathic symptoms displayed the highest test sensitivity of 91%, whereas patients with pure cardiomyopathy displayed the lowest sensitivity of 83%. However, no significant differences in sensitivity were found between patients with or without cardiomyopathy or between the sexes.

Conclusions: Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspect ATTRv amyloidosis, including patients presenting with cardiomyopathy. In addition, the method enables typing not only of the precursor protein but also of the amyloid fibril type, which is related to the phenotype and to the outcome of the disease.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2020
Keywords
Adipose tissue, Amyloid polyneuropathy, Amyloidosis, hereditary, Biopsy, Cardiomyopathy, restrictive, Techniques and procedures, diagnostic, Transthyretin
National Category
Gastroenterology and Hepatology Clinical Laboratory Medicine
Identifiers
urn:nbn:se:umu:diva-176302 (URN)10.1186/s13023-020-01565-8 (DOI)000578596700002 ()33032630 (PubMedID)2-s2.0-85092555541 (Scopus ID)
Available from: 2020-11-05 Created: 2020-11-05 Last updated: 2024-03-14Bibliographically approved
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