Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Diagnostic and prognostic contribution of DPD scintigraphy in transthyretin V30M cardiac amyloidosis.","authors":"Maria C Azevedo Coutinho, Nuno Cortez-Dias, Guilhermina Cantinho, Susana Gonçalves, Nelson Cunha, Tiago Rodrigues, Laura Santos, Isabel Conceição, João Agostinho, Fausto J Pinto","doi":"10.1080/13506129.2023.2239987","DOIUrl":"10.1080/13506129.2023.2239987","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis and prognostic stratification of cardiac transthyretin amyloidosis are crucial. Although ^99mTc 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy is the preferred method for the non-invasive diagnosis, its accuracy appears to be limited in transthyretin amyloidosis protein (ATTR) V30M mutation. Furthermore, its prognostic value in this mutation is unknown. This study investigated the diagnostic value of DPD scintigraphy to detect ATTR cardiomyopathy in V30M mutation and explored its prognostic value regarding mortality.</p><p><strong>Methods: </strong>A total of 288 ATTR V30M mutation carriers (median age: 46 years; 49% males) without myocardial thickening (defined as septal thickness ≥13mm) attributable to other causes and who underwent DPD scintigraphy were enrolled. ATTR cardiomyopathy was defined by septal thickness ≥13mm and at least one of the criteria: late heart-to-mediastinum (H/M) ¹²³I-metaiodobenzylguanidine (MIBG) uptake ratio <1.60; electrical heart disease or biopsy-documented amyloidosis.</p><p><strong>Results: </strong>ATTR cardiomyopathy was identified in 41 (14.2%) patients and cardiac DPD uptake in 34 (11.8%). During a mean follow-up of 33.6 ± 1.2 months, 16 patients died (5.6%). Mortality was 14 times higher in patients with ATTR cardiomyopathy, 13 times higher in those with DPD uptake and 10 times higher in those with late H/M MIBG <1.60. The combined assessment of septal thickness and cardiac DPD uptake improved risk stratification: patients without septal thickening and without DPD retention had an excellent prognosis while those who presented either or both of them had a significantly worse prognosis, with 5-year mortality rates ranging from 39.9 to 53.3%.</p><p><strong>Conclusions: </strong>DPD scintigraphy is useful for prognostic stratification of ATTR V30M mutation carriers. Patients without septal thickening and no DPD uptake present the best prognosis compared to those with any signs of cardiac involvement.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inappropriate use of technetium-99m pyrophosphate scanning for the evaluation of transthyretin amyloidosis.","authors":"Crystal Lihong Yan, Nina Thakkar Rivera, James Hoffman","doi":"10.1080/13506129.2023.2267162","DOIUrl":"10.1080/13506129.2023.2267162","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AA amyloidosis in a father and daughter as complication of <i>PSTPIP1</i>-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.","authors":"Anne F Brunger, Hans L A Nienhuis, Johan Bijzet, Evelien Zonneveld-Huijssoon, Jan S F Sanders, Geertje E Legger, Reinold O B Gans, Bouke P C Hazenberg","doi":"10.1080/13506129.2023.2272556","DOIUrl":"10.1080/13506129.2023.2272556","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment response and neurofilament light chain levels with long-term patisiran in hereditary transthyretin-mediated amyloidosis with polyneuropathy: 24-month results of an open-label extension study.","authors":"Simina Ticau, Emre Aldinc, Michael Polydefkis, David Adams, Teresa Coelho, Mitsuharu Ueda, Cecilia Hale, John Vest, Paul Nioi","doi":"10.1080/13506129.2023.2232520","DOIUrl":"10.1080/13506129.2023.2232520","url":null,"abstract":"<p><strong>Background: </strong>Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy.</p><p><strong>Methods: </strong>All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.</p><p><strong>Results: </strong>Patients receiving patisiran in the parent study (APOLLO-patisiran, <i>n</i> = 137; phase II OLE-patisiran, <i>n</i> = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran -4.8 (-8.9, -0.6); phase II OLE-patisiran -5.8 (-10.5, -1.2)) and Norfolk QOL-DN (APOLLO-patisiran -2.4 (-7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (<i>n</i> = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.</p><p><strong>Conclusions: </strong>Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The way to a man's heart: prostate samples for the early detection of transthyretin cardiomyopathy.","authors":"Lawrence Zeldin, Karan Wats, Kathleen M O'Toole, Fabrizio Remotti, Mathew S Maurer","doi":"10.1080/13506129.2023.2268812","DOIUrl":"10.1080/13506129.2023.2268812","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction in ^99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.","authors":"René Rettl, Raffaella Calabretta, Franz Duca, Christina Binder, Christina Kronberger, Robin Willixhofer, Michael Poledniczek, Carolina Donà, Christian Nitsche, Dietrich Beitzke, Christian Loewe, Michaela Auer-Grumbach, Diana Bonderman, Stefan Kastl, Christian Hengstenberg, Roza Badr Eslam, Johannes Kastner, Jutta Bergler-Klein, Marcus Hacker, Andreas Kammerlander","doi":"10.1080/13506129.2023.2247136","DOIUrl":"10.1080/13506129.2023.2247136","url":null,"abstract":"<p><p><b>Aims:</b> Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.<b>Methods and results:</b> ATTRv-CM patients underwent [^99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: <i>n</i> = 5, inotersen: <i>n</i> = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, <i>p</i> = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, <i>p</i> < .001) in ATTRwt-CM patients (historical control cohort: <i>n</i> = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.<b>Conclusions:</b> RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial ^99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10088979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported outcome measures for transthyretin cardiac amyloidosis: the ITALY study.","authors":"Alberto Aimo, Lucio Teresi, Vincenzo Castiglione, Anna Lisa Picerni, Martina Niccolai, Silvia Severino, Assunta Agazio, Anna Carnevale Baraglia, Laura Obici, Giovanni Palladini, Lucia Ponti, Alessia Argirò, Francesco Cappelli, Federico Perfetto, Matteo Serenelli, Giancarlo Trimarchi, Roberto Licordari, Gianluca Di Bella, Olena Chubuchna, Filippo Quattrone, Sabina Nuti, Sabina De Rosis, Claudio Passino, Claudio Rapezzi, Giampaolo Merlini, Michele Emdin, Giuseppe Vergaro","doi":"10.1080/13506129.2023.2254451","DOIUrl":"10.1080/13506129.2023.2254451","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin cardiac amyloidosis (ATTR-CA) has a deep impact on the quality of life (QoL), yet no specific patient-reported outcome measures (PROMs) for ATTR-CA exist.</p><p><strong>Methods: </strong>The ITALY study involved 5 Italian referral centres (Pisa, Pavia, Ferrara, Florence, Messina) enrolling consecutive outpatients with ATTR-CA.</p><p><strong>Results: </strong>Two 30-item questionnaires were created for wild-type (wt) and variant (v) ATTR-CA. Scores ranged from 100 (best condition) to 0 (worst condition). Out of 140 patients enrolled (77% with ATTRwt-CA), 115 repeated the re-evaluation at 6 months. At baseline, only 30% of patients needed help to fill out the questionnaires. Among baseline variables, all KCCQ and SF-36 domains were univariate predictors of ITALY scores in ATTRwt-CA patients, with the KCCQ Symptom Summary score (beta coefficient 0.759), Social Limitations (0.781), and Overall summary score (0.786) being the strongest predictors. The SF-36 Emotional well-being score (0.608), the KCCQ Overall summary score (0.656), and the SF-36 Energy/fatigue score (0.669) were the strongest univariate predictors of ITALY scores in ATTRv-CA. Similar results were found at 6 months.</p><p><strong>Conclusions: </strong>The ITALY questionnaires are the first specific PROMs for ATTRwt- and ATTRv-CA. Questionnaire completion is feasible. ITALY scores display close relationships with non-ATTR-specific measures of QoL.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.","authors":"Guillaume Fargeot, Andoni Echaniz-Laguna, Céline Labeyrie, Juliette Svahn, Jean-Philippe Camdessanché, Pascal Cintas, Jean-Baptiste Chanson, Florence Esselin, Céline Piedvache, Céline Verstuyft, Steeve Genestet, Emmeline Lagrange, Laurent Magy, Yann Péréon, Sabrina Sacconi, Aissatou Signate, Aleksandra Nadaj-Pakleza, Frédéric Taithe, Karine Viala, Céline Tard, Vianney Poinsignon, Cécile Cauquil, Shahram Attarian, David Adams","doi":"10.1080/13506129.2023.2270661","DOIUrl":"10.1080/13506129.2023.2270661","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from <i>TTR</i> gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available.</p><p><strong>Methods: </strong>In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the <i>TTR</i> gene in French patients with age >50 years with a progressive idiopathic polyneuropathy.</p><p><strong>Results: </strong>553 patients (70% males) with a mean age of 70 years were included. A <i>TTR</i> gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met <i>TTR</i> variation in 10 cases. In comparison with patients with no <i>TTR</i> gene pathogenic variants (<i>n</i> = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, <i>p</i> = .007), significant weight loss (33 vs 11%, <i>p</i> = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, <i>p</i> = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives.</p><p><strong>Conclusion: </strong>In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.","authors":"Grégoire Albenque, Mélanie Bézard, Mounira Kharoubi, Shirley Odouard, Ariane Lunati, Elsa Poullot, Amira Zaroui, Emmanuel Teiger, Luc Hittinger, Vincent Audard, Khalil El Karoui, Benoît Funalot, Pascale Fanen, Thibaud Damy, Silvia Oghina","doi":"10.1080/13506129.2023.2227322","DOIUrl":"10.1080/13506129.2023.2227322","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.</p><p><strong>Material and methods: </strong>This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.</p><p><strong>Results: </strong>Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, <i>p</i> < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, <i>p</i> < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, <i>p</i> = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, <i>p</i> = .018).</p><p><strong>Conclusion: </strong>This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How well does liver span as part of the consensus criteria for liver involvement in AL amyloidosis perform?","authors":"Anne F Brunger, Ronald van Rheenen, Reinold O B Gans, Bouke P C Hazenberg, Hans L A Nienhuis","doi":"10.1080/13506129.2023.2222878","DOIUrl":"10.1080/13506129.2023.2222878","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}