Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Publications (10 of 45) Show all publications
Gentile, L., Coelho, T., Dispenzieri, A., Conceição, I., Waddington-Cruz, M., Kristen, A., . . . Amass, L. (2023). A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Orphanet Journal of Rare Diseases, 18(1), Article ID 350.
Open this publication in new window or tab >>A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
Show others...
2023 (English)In: Orphanet Journal of Rare Diseases, E-ISSN 1750-1172, Vol. 18, no 1, article id 350Article in journal (Refereed) Published
Abstract [en]

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs.

Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry.

Results: This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5).

Conclusions: This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Amyloidosis, Cardiomyopathy, Polyneuropathy, Registry, Transthyretin
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-216787 (URN)10.1186/s13023-023-02962-5 (DOI)37946256 (PubMedID)2-s2.0-85176133271 (Scopus ID)
Available from: 2023-11-21 Created: 2023-11-21 Last updated: 2024-03-14Bibliographically approved
Coelho, T., Waddington Cruz, M., Chao, C.-C., Parman, Y., Wixner, J., Weiler, M., . . . Berk, J. L. (2023). Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. Neurology and Therapy, 12, 267-287
Open this publication in new window or tab >>Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen
Show others...
2023 (English)In: Neurology and Therapy, ISSN 2193-8253, Vol. 12, p. 267-287Article in journal (Refereed) Published
Abstract [en]

Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study.

Methods: Patients eligible for NEURO-TTRansform were 18–82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II.

Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0.

Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice. 

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Amyloid, ATTR, Cardiomyopathy, Eplontersen, Polyneuropathy, Transthyretin amyloidosis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-202005 (URN)10.1007/s40120-022-00414-z (DOI)000899886900001 ()36525140 (PubMedID)2-s2.0-85144143659 (Scopus ID)
Available from: 2022-12-29 Created: 2022-12-29 Last updated: 2023-06-20Bibliographically approved
González-Moreno, J., Dispenzieri, A., Grogan, M., Coelho, T., Tournev, I., Waddington-Cruz, M., . . . Amass, L. (2023). Clinical and genotype characteristics and symptom migration in patients with mixed phenotype transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey. Paper presented at the XVIII International Symposium on Amyloidosis,Heidelberg, Germany, September 4–8, 2022.. Cardiology and Therapy
Open this publication in new window or tab >>Clinical and genotype characteristics and symptom migration in patients with mixed phenotype transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey
Show others...
2023 (English)In: Cardiology and Therapy, ISSN 2193-8261Article in journal (Refereed) Epub ahead of print
Abstract [en]

Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described.

Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022).

Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1–2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis.

Trial Registration: ClinicalTrials.gov: NCT00628745.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Amyloidosis, Cardiomyopathy, Mixed phenotype, Polyneuropathy, THAOS, Transthyretin
National Category
Cardiac and Cardiovascular Systems Neurology
Identifiers
urn:nbn:se:umu:diva-218890 (URN)10.1007/s40119-023-00344-3 (DOI)2-s2.0-85180174220 (Scopus ID)
Conference
the XVIII International Symposium on Amyloidosis,Heidelberg, Germany, September 4–8, 2022.
Funder
Pfizer AB
Note

Prior presentation: These data were presented in part at the XVIII International Symposium on Amyloidosis, Heidelberg, Germany, September 4–8, 2022.

Available from: 2024-01-04 Created: 2024-01-04 Last updated: 2024-01-04
Rutegård, M., Häggström, J., Back, E., Holmgren, K., Wixner, J., Rutegård, J., . . . Sjöström, O. (2023). Defunctioning loop ileostomy in anterior resection for rectal cancer and subsequent renal failure: nationwide population-based study. BJS Open, 7(3), Article ID zrad010.
Open this publication in new window or tab >>Defunctioning loop ileostomy in anterior resection for rectal cancer and subsequent renal failure: nationwide population-based study
Show others...
2023 (English)In: BJS Open, E-ISSN 2474-9842, Vol. 7, no 3, article id zrad010Article in journal (Refereed) Published
Abstract [en]

Background: Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking.

Methods: This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported.

Results: A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes.

Conclusion: Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.

Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-211795 (URN)10.1093/bjsopen/zrad010 (DOI)37161674 (PubMedID)2-s2.0-85161657368 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Society of MedicineCancerforskningsfonden i Norrland
Available from: 2023-07-12 Created: 2023-07-12 Last updated: 2024-02-01Bibliographically approved
Coelho, T., Marques, W., Dasgupta, N. R., Chao, C.-C., Parman, Y., França, M. C., . . . Waddington Cruz, M. (2023). Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy. Journal of the American Medical Association (JAMA), 330(15), 1448-1458
Open this publication in new window or tab >>Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy
Show others...
2023 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 330, no 15, p. 1448-1458Article in journal (Refereed) Published
Abstract [en]

Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis.

Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy.

Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group.

Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60).

Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights.

Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P <.001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group.

Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo.

Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2023
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-216127 (URN)10.1001/jama.2023.18688 (DOI)001077079100001 ()37768671 (PubMedID)2-s2.0-85174751577 (Scopus ID)
Available from: 2023-11-06 Created: 2023-11-06 Last updated: 2023-11-06Bibliographically approved
Thörn, R., Hemmingsson, O., Danielsson Borssén, Å., Werner, M., Karling, P. & Wixner, J. (2023). Improved survival in at-risk patients undergoing surveillance for hepatocellular carcinoma: a nationwide Swedish register-based study. Journal of Hepatocellular Carcinoma, 10, 1573-1586
Open this publication in new window or tab >>Improved survival in at-risk patients undergoing surveillance for hepatocellular carcinoma: a nationwide Swedish register-based study
Show others...
2023 (English)In: Journal of Hepatocellular Carcinoma, E-ISSN 2253-5969, Vol. 10, p. 1573-1586Article in journal (Refereed) Published
Abstract [en]

Purpose: Surveillance for hepatocellular carcinoma (HCC) is recommended in at-risk patients, but its effectiveness in Western populations has been questioned. The purpose was to evaluate the effect of surveillance in patients with HCC in a Northern European setting.

Patients and Methods: Data on patients diagnosed with HCC between 2009 and 2019 were collected from the nationwide Swedish National Registry for Tumors of the Liver and Bile Ducts (SweLiv). Patients who had undergone HCC surveillance were compared to those who had not (but had an obvious indication for surveillance, ie, liver cirrhosis or hepatic porphyria and an age of ≥50 years) regarding etiology, tumor burden, presence of extrahepatic spread, treatment and lead-time adjusted overall survival.

Results: A total of 4979 patients with index HCC were identified and information regarding surveillance was available in 4116 patients. Among these, 1078 had got their HCC diagnosis during surveillance, whereas 1647 had been diagnosed without surveillance despite a presumed indication. The most common underlying etiologies for HCC were hepatitis C (28.2%) and alcoholic liver disease (26.9%), and 94.8% had cirrhosis. The surveillance cohort more frequently met the University of California San Francisco-criteria (79% vs 53%, p <0.001), more often received a potentially curative treatment (62% vs 28%, p <0.001) and had less extrahepatic spread (7.6% vs 22.4% p <0.001). After adjustment for lead-time bias (sojourn time of 270 days), the surveillance group had a significantly longer estimated median survival time than the non-surveillance group (34 months vs 11 months, p <0.001). A multivariable cox regression analysis showed an adjusted hazard ratio of 0.59 (95% CI 0.51–0.67) in favor of surveillance.

Conclusion: Surveillance for HCC in at-risk patients is associated with diagnosis at an earlier tumor stage, treatment with curative intent and with improved lead-time adjusted overall survival. These findings encourage HCC surveillance of at-risk patients also in a Western population.

Place, publisher, year, edition, pages
Dove Medical Press, 2023
Keywords
chronic liver disease, cirrhosis, hepatocellular carcinoma, surveillance, survival
National Category
Surgery Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-214985 (URN)10.2147/JHC.S420130 (DOI)001074270400001 ()37753268 (PubMedID)2-s2.0-85171845818 (Scopus ID)
Funder
Region Västerbotten
Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2024-01-25Bibliographically approved
Coelho, T., Dispenzieri, A., Grogan, M., Conceição, I., Waddington-Cruz, M., Kristen, A. V., . . . Amass, L. (2023). Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay [Letter to the editor]. Amyloid: Journal of Protein Folding Disorders, 30(4), 445-448
Open this publication in new window or tab >>Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay
Show others...
2023 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 30, no 4, p. 445-448Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2023
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-212404 (URN)10.1080/13506129.2023.2229484 (DOI)37459334 (PubMedID)2-s2.0-85165167640 (Scopus ID)
Available from: 2023-07-28 Created: 2023-07-28 Last updated: 2024-01-02Bibliographically approved
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
Show others...
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
Show others...
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
Barroso, F. A., Coelho, T., Dispenzieri, A., Conceição, I., Waddington-Cruz, M., Wixner, J., . . . Amass, L. (2022). Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Amyloid: Journal of Protein Folding Disorders, 29(3), 175-183
Open this publication in new window or tab >>Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS)
Show others...
2022 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 29, no 3, p. 175-183Article in journal (Refereed) Published
Abstract [en]

Background: Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood.

Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020).

Results: Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]).

Conclusions: Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis.

Trial registration: ClinicalTrials.gov: NCT00628745.

Place, publisher, year, edition, pages
Taylor & Francis, 2022
Keywords
Amyloidosis, autonomic nervous system, neuropathy, registry, transthyretin
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-194848 (URN)10.1080/13506129.2022.2043270 (DOI)000785923400001 ()35451899 (PubMedID)2-s2.0-85129754303 (Scopus ID)
Available from: 2022-06-07 Created: 2022-06-07 Last updated: 2023-05-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1536-1277

Search in DiVA

Show all publications