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Marianna Fontana - One of the best experts on this subject based on the ideXlab platform.
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the value of screening biopsies in light chain al and transthyretin ATTR Amyloidosis
European Journal of Haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Faye Sharpley, Shameem Mahmood, Ana Martineznaharro, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P< .001), 59.7% and 42.2% for BM (P< .001), and 74.6% and 44.6% for GI biopsy (P< .001). ATTR amyloid deposits were detected in 35.4% BMs and 33.3% of GI biopsies when AFA did not demonstrate amyloid. In AL Amyloidosis, sensitivity of combined AFA and BM biopsy in AL Amyloidosis was 82.9%. There was a strong association between whole body amyloid burden and sensitivity of each screening biopsy method. The diagnostic sensitivity of screening biopsies ranged from 80.0% to 90.5% for patients with a large amyloid load on 123 I-SAP scintigraphy in comparison with 53.9%-79.0% in those with no visceral amyloid visible on imaging. CONCLUSION Performing both AFA and BM biopsy should be considered in suspected AL Amyloidosis to substantially reduce the clinical risk associated with critical organ biopsy. The sensitivity of screening biopsies in ATTR Amyloidosis is poor.
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The value of screening biopsies in light-chain (AL) and transthyretin (ATTR) Amyloidosis
European journal of haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Ana Martinez-naharro, Faye Sharpley, Shameem Mahmood, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P
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Quantitation of 99mTc-DPD uptake in patients with transthyretin-related cardiac Amyloidosis.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2018Co-Authors: James C. Ross, Philip N Hawkins, Julian D Gillmore, Ashutosh D. Wechalekar, David F. Hutt, Maria Burniston, Joanne Page, Jennifer A. Steeden, Marianna FontanaAbstract:Purpose: Transthyretin (ATTR) Amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. 99mTc-labelled 3,3-diphosphon...
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prognostic utility of the perugini grading of 99mtc dpd scintigraphy in transthyretin ATTR Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid
European Journal of Echocardiography, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martineznaharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A–associated ATTRm (n = 59) Amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). CONCLUSION: 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.
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Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.
European heart journal cardiovascular Imaging, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martinez-naharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P
Helen J. Lachmann - One of the best experts on this subject based on the ideXlab platform.
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the value of screening biopsies in light chain al and transthyretin ATTR Amyloidosis
European Journal of Haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Faye Sharpley, Shameem Mahmood, Ana Martineznaharro, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P< .001), 59.7% and 42.2% for BM (P< .001), and 74.6% and 44.6% for GI biopsy (P< .001). ATTR amyloid deposits were detected in 35.4% BMs and 33.3% of GI biopsies when AFA did not demonstrate amyloid. In AL Amyloidosis, sensitivity of combined AFA and BM biopsy in AL Amyloidosis was 82.9%. There was a strong association between whole body amyloid burden and sensitivity of each screening biopsy method. The diagnostic sensitivity of screening biopsies ranged from 80.0% to 90.5% for patients with a large amyloid load on 123 I-SAP scintigraphy in comparison with 53.9%-79.0% in those with no visceral amyloid visible on imaging. CONCLUSION Performing both AFA and BM biopsy should be considered in suspected AL Amyloidosis to substantially reduce the clinical risk associated with critical organ biopsy. The sensitivity of screening biopsies in ATTR Amyloidosis is poor.
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The value of screening biopsies in light-chain (AL) and transthyretin (ATTR) Amyloidosis
European journal of haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Ana Martinez-naharro, Faye Sharpley, Shameem Mahmood, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P
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prognostic utility of the perugini grading of 99mtc dpd scintigraphy in transthyretin ATTR Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid
European Journal of Echocardiography, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martineznaharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A–associated ATTRm (n = 59) Amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). CONCLUSION: 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.
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Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.
European heart journal cardiovascular Imaging, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martinez-naharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P
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Abstract 16030: Heterogeneity of Electrocardiographic Findings in Cardiac Transthyretin (ATTR) Amyloidosis and Impact on Survival
Circulation, 2014Co-Authors: Ketna Patel, Carol J Whelan, Marianna Fontana, Philip N Hawkins, Sajitha Sachchithanantham, Rabya Sayed, Ashutosh D. Wechalekar, Helen J. Lachmann, Julian D GillmoreAbstract:Introduction: Cardiac transthyretin (ATTR) Amyloidosis is an increasingly diagnosed cause of heart failure. Wild-type ATTR Amyloidosis (ATTRwt) is a disease of older Caucasian men. Hereditary (mutant) cardiac ATTR Amyloidosis (ATTRm) is most commonly associated with the V122I transthyretin (TTR) variant carried by 3-4% of African Americans or the T60A TTR variant in patients of Irish ancestry, the latter presenting with a mixed cardiac and neurologic phenotype. Most published data consider electrocardiographic (ECG) findings in ATTR Amyloidosis as a single entity. Prognostic factors for survival in cardiac ATTR Amyloidosis are poorly defined. Methods and Results: We analysed ECGs from 158 patients with cardiac ATTR Amyloidosis (ATTRwt=75; V122I=49; T60A=34) in a longitudinal retrospective study. Results are shown in Table 1. 63 patients died; 29 ATTRwt, 24 V122I, 10 T60A, during follow-up of 22.7±14.6, 23.8±12.8, and 31.3±20.4 months respectively. Overall median survival: ATTRwt 3.1yr (95%CI:2.2-4.0); V122I 2.6 yr (95%CI:2.2-3.0); T60A not reached. In ATTRwt, broad QRS (≥120ms) was associated with worse survival (1.6yr; 95%CI:1.3-1.9 vs not reached). No other ECG parameter in ATTRwt, and none in either ATTRm group affected survival. On univariate analysis of the ATTRwt cohort, broad QRS, age, systolic BP, TropT and NTproBNP were significant variables at the
Shuichi Ikeda - One of the best experts on this subject based on the ideXlab platform.
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Tafamidis dramatically improved severe proteinuria in a patient with TTR V30M hereditary ATTR Amyloidosis.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2019Co-Authors: Shuichi Ikeda, Akiyo Hineno, Tohru Ichikawa, Mutsuki MakinoAbstract:In hereditary ATTR Amyloidosis with a transthyretin (TTR) V30M mutation, TTR-related amyloid deposition in the kidney is a common postmortem finding [1]. However, the predominant clinical manifesta...
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Marked biochemical difference in amyloid proportion between intra- and extraocular tissues in a liver-transplanted patient with hereditary ATTR Amyloidosis.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2017Co-Authors: Tsuneaki Yoshinaga, Yoshiki Sekijima, Masahide Yazaki, Fuyuki Kametani, Yasuhiro Iesato, Teruyoshi Miyahara, Ayako Tsuchiya-suzuki, Kenji Sano, Keiichi Higuchi, Shuichi IkedaAbstract:In order to elucidate the pathomechanism of ocular amyloid formation in a liver-transplanted patient with hereditary ATTR Amyloidosis, we investigated detailed biochemical features of ocular amyloi...
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cerebral amyloid angiopathy in posttransplant patients with hereditary ATTR Amyloidosis
Neurology, 2016Co-Authors: Yoshiki Sekijima, Masahide Yazaki, Kazuhiro Oguchi, Naoki Ezawa, Tsuneaki Yoshinaga, Mitsunori Yamada, Hiroyuki Yahikozawa, Masahide Watanabe, Fuyuki Kametani, Shuichi IkedaAbstract:Objective: To investigate the prevalence and clinical features of posttransplant CNS symptoms in patients with hereditary ATTR Amyloidosis and their Pittsburgh compound B (PiB)–PET imaging correlates. Methods: We monitored prevalence and type of CNS symptoms in 53 consecutive posttransplant patients with hereditary ATTR Amyloidosis. 11 C-PiB-PET was performed in 15 patients with various disease durations. We also analyzed pathologic and biochemical characteristics of ATTR amyloid deposition in the brain of a posttransplant patient. Results: Transient focal neurologic episodes (TFNEs) ATTRibuted to ATTR-type cerebral amyloid angiopathy (CAA) were found in 11.3% of posttransplant hereditary ATTR Amyloidosis patients. TFNE occurred on average 16.8 years after onset of the disease. Patients with longer duration of illness (≥10 years) showed increased 11 C-PiB retention in the brain. The 11 C-PiB accumulation pattern in hereditary ATTR Amyloidosis was unique and different from those in Alzheimer disease or Aβ-type CAA. In the autopsy case, ATTR amyloid deposition was mainly localized to leptomeningeal vessels and leptomeninges of the brain. Amyloid fibrils in the brain were almost completely composed of variant transthyretin (TTR). Conclusions: TFNE due to ATTR-type CAA occurred frequently in posttransplant patients with long disease durations. 11 C-PiB-PET is a useful diagnostic tool for ATTR-type CAA. ATTR amyloid deposition in the CNS, as measured by PiB-PET, was detected approximately 10 years before onset of TFNE.
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Extremely early onset hereditary ATTR Amyloidosis with G47R (p.G67R) mutation.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2016Co-Authors: Yuya Kobayashi, Yoshiki Sekijima, Yuka Ogawa, Yasufumi Kondo, Daigo Miyazaki, Shuichi IkedaAbstract:Hereditary ATTR Amyloidosis (MIM 105210) is an autosomal dominant genetic disorder with systemic deposition of amyloid fibrils induced by transthyretin (TTR) gene mutation. To date, more than 120 p...
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safety and efficacy of long term diflunisal administration in hereditary transthyretin ATTR Amyloidosis
Amyloid, 2015Co-Authors: Yoshiki Sekijima, Kana Tojo, Hiroshi Morita, Jun Koyama, Shuichi IkedaAbstract:AbstractBackground: A recent 2-year randomized controlled trial indicated that the transthyretin (TTR) tetramer stabilizer, diflunisal, inhibits polyneuropathy progression and preserves quality of life in hereditary ATTR Amyloidosis. However, its long-term outcomes are unknown. Here, we report tolerance and efficacy of long-term diflunisal administration in hereditary ATTR Amyloidosis.Methods: Diflunisal was administered orally at 500 mg/day to 40 Japanese hereditary ATTR Amyloidosis patents who were not candidates for liver transplantation. The observation period ranged from 2 to 116 months (mean ± SD: 38.0 ± 31.2 months).Results: Diflunisal-related adverse events included deterioration of renal function and thrombocytopenia resulting in discontinuation of the drug in three patients. Orally administered diflunisal significantly increased serum TTR concentration (p = 0.001) and stabilized TTR tetramer structure in each patient. Longitudinal analyses of data collected at baseline, 24 months, and after 24 m...
Ashutosh D. Wechalekar - One of the best experts on this subject based on the ideXlab platform.
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the value of screening biopsies in light chain al and transthyretin ATTR Amyloidosis
European Journal of Haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Faye Sharpley, Shameem Mahmood, Ana Martineznaharro, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P< .001), 59.7% and 42.2% for BM (P< .001), and 74.6% and 44.6% for GI biopsy (P< .001). ATTR amyloid deposits were detected in 35.4% BMs and 33.3% of GI biopsies when AFA did not demonstrate amyloid. In AL Amyloidosis, sensitivity of combined AFA and BM biopsy in AL Amyloidosis was 82.9%. There was a strong association between whole body amyloid burden and sensitivity of each screening biopsy method. The diagnostic sensitivity of screening biopsies ranged from 80.0% to 90.5% for patients with a large amyloid load on 123 I-SAP scintigraphy in comparison with 53.9%-79.0% in those with no visceral amyloid visible on imaging. CONCLUSION Performing both AFA and BM biopsy should be considered in suspected AL Amyloidosis to substantially reduce the clinical risk associated with critical organ biopsy. The sensitivity of screening biopsies in ATTR Amyloidosis is poor.
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The value of screening biopsies in light-chain (AL) and transthyretin (ATTR) Amyloidosis
European journal of haematology, 2020Co-Authors: Oliver C Cohen, Carol J Whelan, Marianna Fontana, Janet A Gilbertson, Sajitha Sachchithanantham, Ashutosh D. Wechalekar, Ana Martinez-naharro, Faye Sharpley, Shameem Mahmood, Helen J. LachmannAbstract:INTRODUCTION Systemic Amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS All patients with systemic AL and ATTR Amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National Amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) Amyloidosis, respectively, was 73.2% and 27.3% for AFA (P
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Quantitation of 99mTc-DPD uptake in patients with transthyretin-related cardiac Amyloidosis.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2018Co-Authors: James C. Ross, Philip N Hawkins, Julian D Gillmore, Ashutosh D. Wechalekar, David F. Hutt, Maria Burniston, Joanne Page, Jennifer A. Steeden, Marianna FontanaAbstract:Purpose: Transthyretin (ATTR) Amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. 99mTc-labelled 3,3-diphosphon...
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prognostic utility of the perugini grading of 99mtc dpd scintigraphy in transthyretin ATTR Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid
European Journal of Echocardiography, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martineznaharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A–associated ATTRm (n = 59) Amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). CONCLUSION: 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.
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Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) Amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.
European heart journal cardiovascular Imaging, 2017Co-Authors: David F. Hutt, Marianna Fontana, Ashutosh D. Wechalekar, Maria Burniston, Ann-marie Quigley, Aviva Petrie, James C. Ross, Joanne Page, Ana Martinez-naharro, Helen J. LachmannAbstract:AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) Amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR Amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR Amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) Amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P
Ole B Suhr - One of the best experts on this subject based on the ideXlab platform.
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Expert consensus recommendations to improve diagnosis of ATTR Amyloidosis with polyneuropathy
Journal of Neurology, 2020Co-Authors: David Adams, Ole B Suhr, Philip N Hawkins, Julian D Gillmore, Morie A. Gertz, Yukio Ando, João Melo Beirão, Teresa Coelho, Isabelle Lousada, Giampaolo MerliniAbstract:Amyloid transthyretin (ATTR) Amyloidosis with polyneuropathy (PN) is a progressive, debilitating, systemic disease wherein transthyretin protein misfolds to form amyloid, which is deposited in the endoneurium. ATTR Amyloidosis with PN is the most serious hereditary polyneuropathy of adult onset. It arises from a hereditary mutation in the TTR gene and may involve the heart as well as other organs. It is critical to identify and diagnose the disease earlier because treatments are available to help slow the progression of neuropathy. Early diagnosis is complicated, however, because presentation may vary and family history is not always known. Symptoms may be mistakenly ATTRibuted to other diseases such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic axonal polyneuropathy, lumbar spinal stenosis, and, more rarely, diabetic neuropathy and AL Amyloidosis. In endemic countries (e.g., Portugal, Japan, Sweden, Brazil), ATTR Amyloidosis with PN should be suspected in any patient who has length-dependent small-fiber PN with autonomic dysfunction and a family history of ATTR Amyloidosis, unexplained weight loss, heart rhythm disorders, vitreous opacities, or renal abnormalities. In nonendemic countries, the disease may present as idiopathic rapidly progressive sensory motor axonal neuropathy or atypical CIDP with any of the above symptoms or with bilateral carpal tunnel syndrome, gait disorders, or cardiac hypertrophy. Diagnosis should include DNA testing, biopsy, and amyloid typing. Patients should be followed up every 6–12 months, depending on the severity of the disease and response to therapy. This review outlines detailed recommendations to improve the diagnosis of ATTR Amyloidosis with PN.
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The Swedish landscape of hereditary ATTR Amyloidosis.
Amyloid, 2017Co-Authors: Ole B Suhr, Bjorn Pilebro, Jonas Wixner, Hans-erik Lundgren, Intissar AnanAbstract:Northern Sweden is a well-known clustering area for hereditary transthyretin (TTR) amyloid (ATTR) Amyloidosis caused by the Val30Met mutation. However, several additional mutations have been found ...
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Phase 2 open-label extension study of patisiran, an investigational siRNA agent for hereditary ATTR Amyloidosis with polyneuropathy (hATTR-PN)
Neuromuscular Disorders, 2016Co-Authors: Isabel Conceição, John L. Berk, Ole B Suhr, Hartmut Schmidt, T Coelho, M. Waddington Cruz, Juan Buades, Josep M. Campistol, Jean Pouget, David H. AdamsAbstract:Hereditary ATTR Amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), is an inherited, progressive disease that can cause sensory, motor, and autonomi ...
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evolving landscape in the management of transthyretin Amyloidosis
Annals of Medicine, 2015Co-Authors: Philip N Hawkins, David Adams, Yukio Ando, Angela Dispenzeri, Alejandra Gonzalezduarte, Ole B SuhrAbstract:Transthyretin (TTR) Amyloidosis (ATTR Amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR Amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR Amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR Amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease.
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positron emission tomography pet utilizing pittsburgh compound b pib detects amyloid heart deposits in hereditary transthyretin Amyloidosis ATTR
Orphanet Journal of Rare Diseases, 2015Co-Authors: Bjorn Pilebro, Per Lindqvist, Torbjorn Sundstrom, Per Westermark, Gunnar Antoni, Ole B Suhr, Sandra Gustafsson, Jens Norkaer SorensenAbstract:Background DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR Amyloidosis. PET utilizing 11C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer’s disease. PIB was recently shown to identify cardiac Amyloidosis in both AL and ATTR Amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR Amyloidosis.
