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Rietz M, Weber T, Schaller T, Luitjens JH, Uhrmacher L, Messmann H, Probst A. Severe gastroparesis complicated by gastric perforation caused by lightchain amyloidosis. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:387-392. [PMID: 39586808 DOI: 10.1055/a-2442-7944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
AL-Amyloidosis is a rare systemic disease that can occur in patients with monoclonal gammopathy or multiple myeloma. As multiple organs may be affected by deposition of amyloid fibrils, the clinical presentation varies considerably, and the diagnostic process may be challenging.We report on a 59-year-old female who suffered from gastroesophageal reflux symptoms, nausea, epigastric pain, and meteorism over several years. Repeated upper GI endoscopies including biopsies and CT scans were unremarkable except for unspecific enlargement of mesenterial lymph nodes.A few weeks after a surgical hiatal hernia repair with fundoplication, the patient developed massive distension of the stomach and the proximal duodenum resulting in gastric perforation. Histopathological staining of gastric biopsies and mesenterial lymph nodes using hematoxylin and eosin was unremarkable. Because of endoscopic findings (submucosal hematomas, and ulcerations) and the unexplained severe motility disorder, histopathological staining was performed using Congo red. Extensive amyloid deposits were seen. Further workup confirmed AL amyloidosis caused by monoclonal gammopathy. Specific oncological treatment was started.The rare differential diagnosis of amyloidosis should be taken into account in patients with unexplained motility disorders, unspecific gastrointestinal symptoms, and abdominal lymphadenopathy. In the presented case, delayed diagnosis of AL amyloidosis in the gastrointestinal tract led to severe gastroparesis resulting in gastric perforation. Specific histopathologic staining can confirm the diagnosis.
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Affiliation(s)
- Michael Rietz
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
| | - Tobias Weber
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
| | - Tina Schaller
- Institute of Pathology and Molecular Diagnostics, University Hospital Augsburg, Augsburg, Germany
| | - Jan Hendrik Luitjens
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
| | - Luise Uhrmacher
- Department of Hematology and Oncology, University Hospital Augsburg, Augsburg, Germany
| | - Helmut Messmann
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
| | - Andreas Probst
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany
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Obara K, Baba K. A Skin Biopsy of the Abdominal Wall Without a Rash Is Safe and Effective in the Diagnosis of Systemic Amyloidosis. Am J Dermatopathol 2025; 47:251-259. [PMID: 40086071 DOI: 10.1097/dad.0000000000002862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
ABSTRACT The diagnosis of systemic amyloidosis is decided through histologic materials from biopsy from different organs. This is a retrospective study from the institutional database of our hospital and consisted of patients to being judged to need skin biopsy for the purpose of diagnosing systemic amyloidosis visiting dermatology between April 2005 and August 2022. A total of 30 patients underwent the skin biopsy of dermis and fatty tissue on abdominal wall without rash and a total of 36 specimens were obtained. A total of 14 of these specimens showed amyloid deposition histologically. Among the 14 specimens, amyloid immunoglobin light chain amyloidosis in 8 samples (57.1%) was the most diagnosed, the others being wild-type amyloid transthyretin amyloidosis in 5 samples (35.8%) and amyloid A amyloidosis in 1 sample (7.1%). The skin biopsy has an 87.5% (14 of 16) sensitivity and 100% (20 of 20) specificity, with 12.5% (2 of 16) false negatives and 0% (0 of 20) false positives in diagnosis of systemic amyloidosis. Skin biopsy from normal abdominal wall skin to evaluate dermis and fatty tissue is a safe, sensitive, and specific procedure to the diagnosis of systemic amyloidosis.
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Affiliation(s)
- Koya Obara
- Dermatologist, Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan; and
| | - Kyoko Baba
- Medical Doctor, Department of Plastic and Aesthetic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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Oubari S, Papathanasiou M, Michel L, Rassaf T, Thimm A, Hagenacker T, Ehling D, Wieczorek S, Naser E, Hegenbart U, Schönland S, Dührsen U, Reinhardt HC, Carpinteiro A. Gain or amplification of 1q21 in systemic light chain amyloidosis is associated with advanced Mayo stage, plasma cell disease and worse overall survival. Ann Hematol 2025:10.1007/s00277-025-06256-7. [PMID: 40119178 DOI: 10.1007/s00277-025-06256-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 02/10/2025] [Indexed: 03/24/2025]
Abstract
Systemic light-chain amyloidosis (AL) is an acquired protein misfolding disease characterized by deposition of immunoglobulin light-chain fibrils most often secreted from clonal plasma cells. In this retrospective study we analyzed the impact of iFISH aberrations on clinical characteristics and outcomes in 175 AL patients presented between 2015 and 2024. The most common aberrations were t(11;14) (57%), deletion 13q14 (33%), +1q21 (21%), hyperdiploidy (21%) and deletion 16q23 (17%). Significant elevations in dFLC levels were observed in patients with + 1q21 (median 407 vs. 213 mg/l, p = 0.04) and deletion 16q23 (median 476 vs. 204, p = 0.006). Only + 1q21 was associated with increased levels of cardiac biomarkers NTproBNP (median 9945 vs. 3538 pg/ml, p = 0.002) and hsTnT (median 110 vs. 53 ng/l, p = 0.002). This resulted in an increased proportion of patients with Mayo stage IIIb (53% vs. 26%, p = 0.01). Patients with + 1q21 had more advanced plasma cell disease (p = 0.0004). Our study highlights for the first time + 1q21 as the key aberration associated with advanced cardiac and plasma cell disease. After 17 months of follow-up, overall survival was significantly worse in patients with + 1q21 treated with daratumumab (7.2 months vs. not reached, p = 0.006). Alternative therapeutic approaches such as CAR-T therapies or bispecific antibodies should be further investigated.
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Affiliation(s)
- Sara Oubari
- Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, 45147, Germany
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Maria Papathanasiou
- Department of Cardiology and Angiology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Lars Michel
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Tienush Rassaf
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Andreas Thimm
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Department of Neurology and Center for Translational Neuro- and Behavioral Science, University Hospital Essen, Essen, Germany
| | - Tim Hagenacker
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Department of Neurology and Center for Translational Neuro- and Behavioral Science, University Hospital Essen, Essen, Germany
| | - Daniela Ehling
- Department of Medical Genetics, MVZ Dr. Eberhard & Partner Dortmund, Dortmund, Germany
| | - Stefan Wieczorek
- Department of Medical Genetics, MVZ Dr. Eberhard & Partner Dortmund, Dortmund, Germany
| | - Eyad Naser
- Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany
| | - Ute Hegenbart
- Department of Internal Medicine V, Amyloidosis Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan Schönland
- Department of Internal Medicine V, Amyloidosis Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Ulrich Dührsen
- Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, 45147, Germany
| | - Hans Christian Reinhardt
- Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, 45147, Germany
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
| | - Alexander Carpinteiro
- Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, 45147, Germany.
- Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
- Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
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Usuku H, Oike F, Kuyama N, Hirakawa K, Takashio S, Izumiya Y, Tsujita K. Echocardiographic findings of patients with transthyretin amyloid cardiomyopathy. J Echocardiogr 2025; 23:1-9. [PMID: 39729212 DOI: 10.1007/s12574-024-00672-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/10/2024] [Accepted: 11/13/2024] [Indexed: 12/28/2024]
Abstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is becoming increasingly recognized with the aging population, advancements in understanding of disease pathobiology and the potential benefits of emerging therapies. Bone scintigraphy, including 99mTc-labeled pyrophosphate scintigraphy, is currently considered the first-line modality for identifying ATTR-CM. Therefore, it is important to increase the preset probability using inexpensive and simple tests including echocardiography. Although there were a lot of typical echocardiographic findings of amyloid cardiomyopathy, unexplained left ventricular (LV) wall thickness, LV apical sparing, and a discrepancy between LV wall thickness and QRS voltage were selected as red flags/clues for ATTR-CM in various current diagnostic algorithms. Although echocardiography is useful for ATTR-CM screening, there are several limitations. Therefore, it is important to perform echocardiography and combine it with physical examination, laboratory findings, and other imaging data.
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Affiliation(s)
- Hiroki Usuku
- Department of Laboratory Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
| | - Fumi Oike
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Naoto Kuyama
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kyoko Hirakawa
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Seiji Takashio
- Department of Internal Medicine and Cardiovascular Medicine, Takashio Heart Clinic, Kumamoto, Japan
| | - Yasuhiro Izumiya
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Center of Metabolic Regulation of Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Salimi Y, Shiri I, Mansouri Z, Sanaat A, Hajianfar G, Hervier E, Bitarafan A, Caobelli F, Hundertmark M, Mainta I, Gräni C, Nkoulou R, Zaidi H. Artificial intelligence-based cardiac transthyretin amyloidosis detection and scoring in scintigraphy imaging: multi-tracer, multi-scanner, and multi-center development and evaluation study. Eur J Nucl Med Mol Imaging 2025:10.1007/s00259-025-07117-1. [PMID: 39907796 DOI: 10.1007/s00259-025-07117-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 01/24/2025] [Indexed: 02/06/2025]
Abstract
INTRODUCTION Providing tools for comprehensively evaluating scintigraphy images could enhance transthyretin amyloid cardiomyopathy (ATTR-CM) diagnosis. This study aims to automatically detect and score ATTR-CM in total body scintigraphy images using deep learning on multi-tracer, multi-scanner, and multi-center datasets. METHODS In the current study, we employed six datasets (from 12 cameras) for various tasks and purposes. Dataset #1 (93 patients, 99mTc-MDP) was used to develop the 2D-planar segmentation and localization models. Dataset #2 (216 patients, 99mTc-DPD) was used for the detection (grade 0 vs. grades 1, 2, and 3) and scoring (0 and 1 vs. grades 2 and 3) of ATTR-CM. Datasets #3 (41 patients, 99mTc-HDP), #4 (53 patients, 99mTc-PYP), and #5 (129 patients, 99mTc-DPD) were used as external centers. ATTR-CM detection and scouring were performed by two physicians in each center. Moreover, Dataset #6 consisting of 3215 patients without labels, was employed for retrospective model performance evaluation. Different regions of interest were cropped and fed into the classification model for the detection and scoring of ATTR-CM. Ensembling was performed on the outputs of different models to improve their performance. Model performance was measured by classification accuracy, sensitivity, specificity, and AUC. Grad-CAM and saliency maps were generated to explain the models' decision-making process. RESULTS In the internal test set, all models for detection and scoring achieved an AUC of more than 0.95 and an F1 score of more than 0.90. For detection in the external dataset, AUCs of 0.93, 0.95, and 1 were achieved for datasets 3, 4, and 5, respectively. For the scoring task, AUCs of 0.95, 0.83, and 0.96 were achieved for these datasets, respectively. In dataset #6, we found ten cases flagged as ATTR-CM by the network. Out of these, four cases were confirmed by a nuclear medicine specialist as possibly having ATTR-CM. GradCam and saliency maps showed that the deep-learning models focused on clinically relevant cardiac areas. CONCLUSION In the current study, we developed and evaluated a fully automated pipeline to detect and score ATTR-CM using large multi-tracer, multi-scanner, and multi-center datasets, achieving high performance on total body images. This fully automated pipeline could lead to more timely and accurate diagnoses, ultimately improving patient outcomes.
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Affiliation(s)
- Yazdan Salimi
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Isaac Shiri
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Zahra Mansouri
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Amirhossein Sanaat
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Ghasem Hajianfar
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Elsa Hervier
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Ahmad Bitarafan
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Federico Caobelli
- Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Moritz Hundertmark
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ismini Mainta
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Christoph Gräni
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - René Nkoulou
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland
| | - Habib Zaidi
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, CH-1211, Switzerland.
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
- Department of Nuclear Medicine, University of Southern Denmark, Odense, Denmark.
- University Research and Innovation Center, Óbuda University, Budapest, Hungary.
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Christoffersen M, Greve AM, Hornstrup LS, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A. Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol 2025; 10:155-163. [PMID: 39630472 PMCID: PMC11618624 DOI: 10.1001/jamacardio.2024.4102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 08/30/2024] [Indexed: 12/08/2024]
Abstract
Importance Transthyretin tetramer destabilization is the rate-limiting step in the development of transthyretin cardiac amyloidosis, an underrecognized contributor to mortality in older adults. Objective To test the hypothesis that transthyretin tetramer destabilization is associated with all-cause and cardiovascular mortality in the general population. Design, Setting, and Participants In this cohort study including individuals aged 20 to 80 years, genetic data were analyzed from 2 similar prospective studies of the Danish general population, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). Observational data from a subsample of the same studies where transthyretin was measured consecutively were also analyzed. In both studies, individuals were followed up from the examination date (1991-1994 in CCHS and 2003-2015 in CGPS) until death or the end of follow-up in December 2018. Data were analyzed from November 1, 2023, to August 15, 2024. Exposures Missense variants in TTR associated with increasing transthyretin tetramer destabilization in primary genetic analyses, and plasma transthyretin level in secondary observational analyses. Main Outcomes and Measures All-cause and cardiovascular mortality identified from the national Danish Civil Registration System and the national Danish Register of Causes of Death. Results A total of 102 204 individuals (median [IQR] age, 57 [47-66] years; 56 445 [55%] female) were included. Median follow-up was 10 years (range, <1-27 years). In genetic analyses, p.T139M, a transthyretin tetramer stabilizing variant that is more stable than noncarriers' tetramer stability, was used as the reference. For noncarriers who have intermediate tetramer stability and for heterozygotes for amyloidogenic variants (p.V142I, p.H110N, and p.D119N) who have the lowest tetramer stability, respective hazard ratios (HRs) were 1.37 (95% CI, 1.06-1.77) and 1.65 (95% CI, 0.95-2.88) for all-cause mortality (P for trend = .01), and 1.63 (95% CI, 0.92-2.89) and 2.23 (95% CI, 0.78-6.34) for cardiovascular mortality (P for trend = .06). Furthermore, compared with p.T139M, plasma transthyretin decreased stepwise by TTR genotype: -18% for noncarriers and -29% for heterozygotes for amyloidogenic variants (p.V142I, p.H110N, p.D119N; P for trend < .001). Therefore, genetically determined, increasingly lower plasma transthyretin could be considered a surrogate marker for transthyretin tetramer destabilization. Observationally, among 19 619 individuals, noncarriers with plasma transthyretin concentrations less than 20 mg/dL vs 20 to 40 mg/dL had HRs of 1.12 (95% CI, 1.02-1.23) for all-cause mortality and 1.16 (95% CI, 0.97-1.39) for cardiovascular mortality. Conclusions and Relevance Transthyretin tetramer destabilization was associated with all-cause and cardiovascular mortality in the Danish general population. These findings may suggest a need for large-scale assays to measure transthyretin destabilization for detection of transthyretin amyloidosis before clinical manifestations emerge, since early treatment improves the prognosis.
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Affiliation(s)
- Mette Christoffersen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Anders Møller Greve
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Louise Stig Hornstrup
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
| | - Ruth Frikke-Schmidt
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Børge Grønne Nordestgaard
- Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
- Copenhagen City Heart Study, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Copenhagen City Heart Study, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
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Das P, Thakur D, Borah GJ, Wodeyar NK, Mohindra S. Hepatic Amyloidosis Manifesting as Budd-Chiari Syndrome: An Unusual Presentation. Cureus 2025; 17:e76719. [PMID: 39897254 PMCID: PMC11785456 DOI: 10.7759/cureus.76719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/31/2024] [Indexed: 02/04/2025] Open
Abstract
Amyloidosis is a rare infiltrative multisystemic disorder characterized by protein misfolding, leading to progressive organ failure. It can be either acquired or hereditary. Very few case reports regarding hepatic amyloidosis with Budd-Chiari syndrome have been reported up to date. We report the case of a 45-year-old man presenting with abdominal distension, pain in the abdomen, and jaundice. Through right hepatic vein cannulation, HVPG (hepatic venous pressure gradient) was found to be 10 mmHg. The liver biopsy revealed near-total replacement of hepatic parenchyma by amorphous congophilic deposits with obliteration of sinusoids. Hepatic amyloidosis with hepatic venous occlusion is a rare entity.
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Affiliation(s)
- Pritam Das
- Gastroenterology and Hepatology, King George's Medical University, Lucknow, IND
| | - Dhruv Thakur
- Gastroenterology, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, IND
| | - Gourav Jyoti Borah
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Naganath K Wodeyar
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Samir Mohindra
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
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Li X, Guo Y, Shen K, Huang S, Gao Y, Lin L, Wang J, Cao J, Cao X, Jin Z, Zhang Z, Varga-Szemes A, Schoepf UJ, Li J, Wang Y. Comprehensive prognosis assessment of cardiovascular magnetic resonance parametric mapping in light chain amyloidosis. J Cardiovasc Magn Reson 2024; 27:101135. [PMID: 39675480 PMCID: PMC11773017 DOI: 10.1016/j.jocmr.2024.101135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/07/2024] [Accepted: 12/10/2024] [Indexed: 12/17/2024] Open
Abstract
BACKGROUND Recent evidence underscores the importance of cardiovascular magnetic resonance (CMR) in light chain amyloidosis (AL amyloidosis). We aimed to comprehensively assess the prognostic significance of CMR parametric mapping in AL amyloidosis. METHODS This prospective study consecutively included AL amyloidosis patients who underwent CMR imaging before therapy. The statistical analyses included T2, extracellular volume, and native T1 as variates under investigation, adjusted for well-established prognostic markers. The outcome was death from any cause. RESULTS In total, 195 patients (age, 57.2 ± 9.1 years; male/female, 123/72) were recruited. At the median follow-up time (19 months), the survival probability was approximately 67.2% (131/195). T >44 ms, extracellular volume fraction (ECV) >47%, and native T1 >1468 ms were significantly prognostic (all, P < 0.05) but non-significant after adjustment for N-terminal pro-B-type natriuretic peptide (all, P > 0.05) in AL amyloidosis. T2 >44 ms was independently prognostic after correcting for left ventricle (LV) late gadolinium enhancement, LV ejection fraction, LV longitudinal strain, and therapeutic response (all, P < 0.05). In patients achieving deep hematologic response, T2 >44 ms (hazard ratios [HR] 6.611, 95% confidence interval [CI] 1.723-25.361, P = 0.006) was significantly prognostic for mortality after adjustment for cardiac response. Accordingly, T2 >44 ms was significantly associated with mortality (HR 5.734, 95% CI 1.189-27.656, P = 0.030) and remained independently prognostic after correcting for LV late gadolinium enhancement and LV longitudinal strain (both, P < 0.05) in patients who achieved both deep hematologic response and cardiac response. CONCLUSION This study highlights that T2 is a valuable independent predictor of mortality in an AL amyloidosis population, additive to common CMR risk factors. Moreover, myocardial edema assessment identified patients in need of adjunctive therapies, which is of particular prognostic significance in patients with deep therapeutic response.
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Affiliation(s)
- Xiao Li
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yubo Guo
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kaini Shen
- Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Sisi Huang
- Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yajuan Gao
- Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Lu Lin
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jian Wang
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jian Cao
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xinxin Cao
- Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zhengyu Jin
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zhuoli Zhang
- Department of Radiological Sciences, University of California, Irvine, California, USA
| | - Akos Varga-Szemes
- Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA
| | - U Joseph Schoepf
- Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jian Li
- Department of Hematology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Yining Wang
- Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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Tang L, Zhao W, Li K, Tian L, Zhou X, Guo H, Zeng M. Assessing microvascular dysfunction and predicting long-term prognosis in patients with cardiac amyloidosis by cardiovascular magnetic resonance quantitative stress perfusion. J Cardiovasc Magn Reson 2024; 27:101134. [PMID: 39675481 PMCID: PMC11761856 DOI: 10.1016/j.jocmr.2024.101134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 12/09/2024] [Accepted: 12/09/2024] [Indexed: 12/17/2024] Open
Abstract
BACKGROUND Cardiac involvement in light chain amyloidosis (AL) is the main determinant of prognosis. Amyloid can be deposited in the extracellular space and cause an increase in extracellular volume fraction (ECV). At the same time, amyloid can also be deposited in the wall of small vessels and cause microvascular dysfunction. This study sought to investigate the extent of microvascular dysfunction and its incremental prognostic value in cardiac light-chain amyloidosis (AL-CA) by quantitative stress perfusion. METHODS A total of 126 AL amyloidosis patients (61.13 ± 8.46 years, 81 male) confirmed by pathology were prospectively recruited. All subjects underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE), T1 mapping, and stress perfusion on a 3T scanner. ECV and myocardial perfusion reserve (MPR) were measured semi-automatically using a dedicated CMR software. Clinical, laboratory, and CMR parameters were analyzed for their prognostic value in the assessment of AL-CA patients. Mortality-associated markers were analyzed by univariate and multivariable Cox regression. RESULTS The median follow-up time was 37 (33.6-40.4) months, and 62 patients died. The ECV of survivors was significantly reduced, but the stress myocardial blood flow and MPR were higher (P < 0.001). The MPR of the transmural LGE group was significantly lower than that of the no LGE and subendocardial LGE groups (P < 0.001). In multivariable analysis, ECV, MPR, and LGE were independently predictive. MPR of >1.5 and ECV of ≤53.6% were associated with improved overall survival, both of which provided predictive incremental value in patients with advanced disease. With equal Mayo staging and degree of ECV, MPR improves assessment of patient survival. CONCLUSION ECV and MPR showed additive incremental values and further discriminated prognosis of patients in advanced stages. CMR phenotypes with higher ECV and lower MPR had a worse prognosis.
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Affiliation(s)
- Leting Tang
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Wenjin Zhao
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Kang Li
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Lin Tian
- Circle Cardiovascular Imaging Inc., Changsha, China
| | - Xiaoyue Zhou
- MR Collaboration, Siemens Healthineers Ltd., Shanghai, China
| | - Hu Guo
- MR Application, Siemens Healthineers Ltd., Changsha, China
| | - Mu Zeng
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China.
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10
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Hughes MS, Lentzsch S. PRIMARY SYSTEMIC AMYLOIDOSIS: A BRIEF OVERVIEW. Presse Med 2024:104267. [PMID: 39672504 DOI: 10.1016/j.lpm.2024.104267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/14/2024] [Indexed: 12/15/2024] Open
Abstract
Primary systemic amyloidosis, or light chain (AL) amyloidosis, is a rare lymphoproliferative disorder in which aberrant light-chain immunoglobulins secreted into the bloodstream aggregate into fibrils and deposit into tissues, causing widespread organ damage and, if not treated, death. This review provides a comprehensive summary of the pathophysiology and manifestations of AL amyloidosis; standard-of-care diagnostic approach; typical treatment regimens; and areas of active investigation.
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Affiliation(s)
- Michael Sang Hughes
- Department of Hematology/Oncology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 6GN-435, New York, NY 10032.
| | - Suzanne Lentzsch
- Department of Hematology/Oncology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 6GN-435, New York, NY 10032
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11
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Sabri S, Bachir H, Hamaz S, Bennesser HA, Serraj K. Ascites revealing peritoneal amyloidosis and IgG kappa multiple myeloma: A case report. Radiol Case Rep 2024; 19:5465-5470. [PMID: 39285976 PMCID: PMC11403892 DOI: 10.1016/j.radcr.2024.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/02/2024] [Accepted: 08/04/2024] [Indexed: 09/19/2024] Open
Abstract
AL amyloidosis is a rare systemic disease characterized by the deposition of amyloid protein in various organs, including the kidneys, heart, peripheral nervous system, digestive tract, skin, and muscles. Peritoneal involvement in AL amyloidosis is exceptionally rare. We present a unique case of AL amyloidosis with concurrent cardiac, cutaneous, and peritoneal manifestations. The patient initially presented with ascites and respiratory symptoms. An etiological workup revealed multiple myeloma as the underlying cause. This case highlights the importance of considering AL amyloidosis in the differential diagnosis of peritoneal ascites, providing valuable insights for radiologists in recognizing atypical presentations of this disease.
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Affiliation(s)
- Samia Sabri
- Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, Morocco
- Department of Internal Medicine, Univeristy Hospital Mohammed Vl, Oujda, Morocco
| | - Houda Bachir
- Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, Morocco
- Department of Internal Medicine, Univeristy Hospital Mohammed Vl, Oujda, Morocco
| | - Siham Hamaz
- Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, Morocco
- Department of Internal Medicine, Univeristy Hospital Mohammed Vl, Oujda, Morocco
| | - Habiba Alaoui Bennesser
- Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, Morocco
- Department of Internal Medicine, Univeristy Hospital Mohammed Vl, Oujda, Morocco
| | - Khalid Serraj
- Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, Morocco
- Department of Internal Medicine, Univeristy Hospital Mohammed Vl, Oujda, Morocco
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12
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Salzillo C, Franco R, Ronchi A, Quaranta A, Marzullo A. Cardiac Amyloidosis: State-of-the-Art Review in Molecular Pathology. Curr Issues Mol Biol 2024; 46:11519-11536. [PMID: 39451564 PMCID: PMC11506355 DOI: 10.3390/cimb46100684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/05/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024] Open
Abstract
Amyloidosis refers to a group of diseases caused by extracellular deposits of misfolded proteins, which alter tissue function and structure, potentially affecting any organ. The term "amyloid" was introduced in the 19th century and later associated with pathological protein deposits. Amyloid fibrils, which are insoluble and resistant to degradation, originate from soluble proteins that undergo misfolding. This process can be triggered by several factors, such as aging, elevated protein concentrations, or pathogenic variants. Amyloid deposits damage organs both by disrupting tissue architecture and through direct cytotoxic effects, leading to conditions such as heart failure. Amyloidosis can be classified into acquired or inherited forms and can be systemic or localized. Diagnosing cardiac amyloidosis is complex and often requires tissue biopsies, which are supported by Congo Red dye staining. In some cases, bisphosphonate bone scans may provide a less invasive diagnostic option. In this state-of-the-art review, we focus on the most common forms of cardiac amyloidosis, from epidemiology to therapy, emphasizing the differences in molecular mechanisms and the importance of pathological diagnosis for appropriate treatment using a multidisciplinary approach.
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Affiliation(s)
- Cecilia Salzillo
- Department of Experimental Medicine, PhD Course in Public Health, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Department of Precision and Regenerative Medicine and Ionian Area, Pathology Unit, University of Bari “Aldo Moro”, 70121 Bari, Italy;
| | - Renato Franco
- Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (R.F.); (A.R.)
| | - Andrea Ronchi
- Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (R.F.); (A.R.)
| | - Andrea Quaranta
- Department of Precision and Regenerative Medicine and Ionian Area, Pathology Unit, University of Bari “Aldo Moro”, 70121 Bari, Italy;
| | - Andrea Marzullo
- Department of Precision and Regenerative Medicine and Ionian Area, Pathology Unit, University of Bari “Aldo Moro”, 70121 Bari, Italy;
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13
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Singh A, Khanna T, Mahendru D, Kahlon J, Kumar V, Sohal A, Yang J. Insights into renal and urological complications of inflammatory bowel disease. World J Nephrol 2024; 13:96574. [PMID: 39351187 PMCID: PMC11439091 DOI: 10.5527/wjn.v13.i3.96574] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 09/19/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India
| | - Diksha Mahendru
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Jasraj Kahlon
- Department of Internal Medicine, Abrazo Medical Center, Phoenix, AZ 85015, United States
| | - Vikash Kumar
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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14
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Badwan O, Berglund F, Rosenzveig A, Persits I, Gharaibeh A, Kumar A, Agrawal A, Sul L, Chan N, Wang TKM, Hanna M, Klein AL. Pericardial Disease in Cardiac Amyloidosis: A Comprehensive Review. Am J Cardiol 2024; 223:100-108. [PMID: 38740164 DOI: 10.1016/j.amjcard.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 05/02/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
In patients with cardiac amyloidosis, pericardial involvement is common, with up to half of patients presenting with pericardial effusions. The pathophysiological mechanisms of pericardial pathology in cardiac amyloidosis include chronic elevations in right-sided filling pressures, myocardial and pericardial inflammation due to cytotoxic effects of amyloid deposits, and renal involvement with subsequent uremia and hypoalbuminemia. The pericardial effusions are typically small; however, several cases of life-threatening cardiac tamponade with hemorrhagic effusions have been described as a presenting clinical scenario. Constrictive pericarditis can also occur due to amyloidosis and its identification presents a clinical challenge in patients with cardiac amyloidosis who concurrently manifest signs of restrictive cardiomyopathy. Multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, is useful in the evaluation and management of this patient population. The recognition of pericardial effusion is important in the risk stratification of patients with cardiac amyloidosis as its presence confers a poor prognosis. However, specific treatment aimed at the effusions themselves is seldom indicated. Cardiac tamponade and constrictive pericarditis may necessitate pericardiocentesis and pericardiectomy, respectively.
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Affiliation(s)
- Osamah Badwan
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Felix Berglund
- Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Akiva Rosenzveig
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ian Persits
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ahmad Gharaibeh
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ashwin Kumar
- Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ankit Agrawal
- Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Lidiya Sul
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Nicholas Chan
- Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Tom Kai Ming Wang
- Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Mazen Hanna
- Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Allan L Klein
- Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell, and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio.
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15
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Sanchorawala V. Systemic Light Chain Amyloidosis. N Engl J Med 2024; 390:2295-2307. [PMID: 38924733 DOI: 10.1056/nejmra2304088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/28/2024]
Affiliation(s)
- Vaishali Sanchorawala
- From the Amyloidosis Center, Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston
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16
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Grazzini G, Pradella S, Bani R, Fornaciari C, Cappelli F, Perfetto F, Cozzi D, Giovannelli S, Sica G, Miele V. The Role of T2 Mapping in Cardiac Amyloidosis. Diagnostics (Basel) 2024; 14:1048. [PMID: 38786346 PMCID: PMC11120592 DOI: 10.3390/diagnostics14101048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/14/2024] [Accepted: 05/17/2024] [Indexed: 05/25/2024] Open
Abstract
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy divided into two types: light-chain (LA) and transthyretin (ATTR) CA. Cardiac magnetic resonance (CMR) has emerged as an important diagnostic tool in CA. While late gadolinium enhancement (LGE), T1 mapping and extracellular volume (ECV) have a consolidate role in the assessment of CA, T2 mapping has been less often evaluated. We aimed to test the value of T2 mapping in the evaluation of CA. This study recruited 70 patients with CA (51 ATTR, 19 AL). All the subjects underwent 1.5 T CMR with T1 and T2 mapping and cine and LGE imaging. Their QALE scores were evaluated. The myocardial T2 values were significantly (p < 0.001) increased in both types of CA compared to the controls. In the AL-CA group, increased T2 values were associated with a higher QALE score. The myocardial native T1 values and ECV were significantly (p < 0.001) higher in the CA patients than in the healthy subjects. Left ventricular (LV) mass, QALE score and ECV were higher in ATTR amyloidosis compared with AL amyloidosis, while the LV ejection fraction was lower (p < 0.001). These results support the concept of the presence of myocardial edema in CA. Therefore, a CMR evaluation including not only myocardial T1 imaging but also myocardial T2 imaging allows for more comprehensive tissue characterization in CA.
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Affiliation(s)
- Giulia Grazzini
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Silvia Pradella
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Rossella Bani
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Chiara Fornaciari
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Francesco Cappelli
- Regional Amyloid Center, Azienda Ospedaliero Universitaria Careggi, Largo Piero Palagi 1, 50134 Florence, Italy
| | - Federico Perfetto
- Regional Amyloid Center, Azienda Ospedaliero Universitaria Careggi, Largo Piero Palagi 1, 50134 Florence, Italy
| | - Diletta Cozzi
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Simona Giovannelli
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Giacomo Sica
- Department of Radiology, Monaldi Hospital, Azienda Ospedaliera dei Colli, 80131 Naples, Italy
| | - Vittorio Miele
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
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17
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Harris JC, Zhang Q, Tondon R, Alipour Z, Stashek K. Characterization of Amyloidosis in the Gastrointestinal Tract With an Emphasis on Histologically Distinct Interstitial Patterns of Deposition and Misinterpretations. Am J Surg Pathol 2024; 48:302-308. [PMID: 38145407 DOI: 10.1097/pas.0000000000002173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2023]
Abstract
Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195 biopsies) with amyloid involvement of the luminal tract were reviewed. Amyloid subtyping by mass spectrophotometry was available for 59 patients. Immunoglobulin light chain (AL) was the most commonly identified subtype (60%), followed by serum amyloid A (AA; 19%) and transthyretin (ATTR; 16%). 150/195 biopsies (77%) were positive for amyloid deposition, with an average of 2.4 positive biopsies per every 3.1 taken per patient. The sites with the highest yield were duodenum (37/37, 100%) and colon (63/74, 85%). Gastric biopsies were most likely to involve the lamina propria (41/45, 91%, P < 0.001), with the background mucosa showing reactive epithelial changes in almost half of the biopsies (20/45, 44%). Several distinct histologic patterns of interstitial deposition were identified, including muscularis mucosae deposition (n = 40, 27% of positive biopsies), peri-Brunner gland (n = 6, 17% of duodenal biopsies), mass-forming (n = 4, 2.7% of positive biopsies, including 3 suspected cases with localized involvement), collagenous colitis-like (n = 3, 4.8% of positive colonic biopsies), and globular (n = 19, 12.7% of positive biopsies). Congo Red was ordered in 81% of cases in which it was requested clinically, with a positivity rate of 30%. Of the 34 cases in which an amyloid workup was requested (but Congo Red was not performed), 14 were positive on reevaluation. Several missed cases had deposition in multiple biopsies, and almost half were missed by subspecialist GI pathologists. Nine misinterpretations were from the stomach, with seven initially diagnosed as chemical or reactive gastropathy. Additional discrepant cases were identified from the duodenum (n = 2) and colon (n = 3), with the vascular-only deposition pattern (n = 3), muscularis mucosae-only deposition (n = 3), and globular pattern (n = 1) identified. Given the challenges of identifying amyloid on hematoxylin and eosin staining, Congo Red ordering percentage should be 100% in clinically suspicious cases unless deposition is definitively seen on hematoxylin and eosin staining.
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Affiliation(s)
- Jaryse Carol Harris
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
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18
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Norisyam Y, Zairul Anuar KB, Ohn KM, Moharzudi M. Rare vertebral pathological fracture in primary amyloidosis. BMJ Case Rep 2024; 17:e258973. [PMID: 38388204 PMCID: PMC10884212 DOI: 10.1136/bcr-2023-258973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2024] Open
Abstract
Spinal involvement in primary amyloidosis is an exceedingly rare condition, presenting with typical pathological fracture symptoms that are often indistinguishable from other pathologies such as bone metastasis, metabolic disorders and infections. Histopathological studies for tissue diagnosis are the cornerstone of a definitive diagnosis, leading to successful treatment. Early diagnosis and intervention play a pivotal role in the care of patients with amyloidosis. Here, we present a unique case of a pathological fracture in the L4 vertebra following minor trauma. This fracture manifested with pain, instability and limitations in daily activities in a patient who had already been diagnosed with systemic amyloidosis and was undergoing chemotherapy. This case represents a distinct instance of vertebral involvement in amyloidosis and was managed with both chemotherapy and surgical intervention to address the spinal pathology, resulting in favourable outcomes.
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Affiliation(s)
- Yusoff Norisyam
- Department of Orthopaedic, Hospital Sultan Ismail, Johor Bharu, Johor Darul Ta'zim, Malaysia
| | | | - Khin Maung Ohn
- Orthopaedic Surgery, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia
| | - Mohamed Moharzudi
- Department of Pathology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia
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19
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Wang J, Zhao Y, Liao P, Huang S, Huang Y, Chen S, Li Y, Zhong L. Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets. BLOOD SCIENCE 2024; 6:e00181. [PMID: 38226018 PMCID: PMC10789457 DOI: 10.1097/bs9.0000000000000181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 12/21/2023] [Indexed: 01/17/2024] Open
Abstract
Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.
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Affiliation(s)
- Jinghua Wang
- Department of Hematology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yujie Zhao
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Pengjun Liao
- Department of Hematology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Shuxin Huang
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Youxue Huang
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Shaohua Chen
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Yangqiu Li
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Liye Zhong
- Department of Hematology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
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20
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Ghosh S, Villacorta-Martin C, Lindstrom-Vautrin J, Kenney D, Golden CS, Edwards CV, Sanchorawala V, Connors LH, Giadone RM, Murphy GJ. Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures. Amyloid 2023; 30:379-393. [PMID: 37439769 DOI: 10.1080/13506129.2023.2224494] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 06/04/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND In ATTR amyloidosis, transthyretin (TTR) protein is secreted from the liver and deposited as toxic aggregates at downstream target tissues. Despite recent advancements in treatments for ATTR amyloidosis, the mechanisms underlying misfolded TTR-mediated cellular damage remain elusive. METHODS In an effort to define early events of TTR-associated stress, we exposed neuronal (SH-SY5Y) and cardiac (AC16) cells to wild-type and destabilized TTR variants (TTRV122I (p.V142I) and TTRL55P (p.L70P)) and performed transcriptional (RNAseq) and epigenetic (ATACseq) profiling. We subsequently compared TTR-responsive signatures to cells exposed to destabilized antibody light chain protein associated with AL amyloidosis as well as ER stressors (thapsigargin, heat shock). RESULTS In doing so, we observed overlapping, yet distinct cell type- and amyloidogenic protein-specific signatures, suggesting unique responses to each amyloidogenic variant. Moreover, we identified chromatin level changes in AC16 cells exposed to mutant TTR that resolved upon pre-incubation with kinetic stabilizer tafamidis. CONCLUSIONS Collectively, these data provide insight into the mechanisms underlying destabilized protein-mediated cellular damage and provide a robust resource representing cellular responses to aggregation-prone proteins and ER stress.
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Affiliation(s)
- Sabrina Ghosh
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
- Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA
| | | | | | - Devin Kenney
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Carly S Golden
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Camille V Edwards
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
- Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA
- Amyloidosis Center, Alan and Sandra Gerry Amyloid Research Laboratory, Boston University School of Medicine, Boston, MA, USA
| | - Vaishali Sanchorawala
- Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA
- Amyloidosis Center, Alan and Sandra Gerry Amyloid Research Laboratory, Boston University School of Medicine, Boston, MA, USA
| | - Lawreen H Connors
- Amyloidosis Center, Alan and Sandra Gerry Amyloid Research Laboratory, Boston University School of Medicine, Boston, MA, USA
| | - Richard M Giadone
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
- Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA
| | - George J Murphy
- Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, USA
- Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA, USA
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21
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Napolitano A, De Michieli L, Sinigiani G, Berno T, Cipriani A, Spiezia L. Thromboembolic and Bleeding Events in Transthyretin Amyloidosis and Coagulation System Abnormalities: A Review. J Clin Med 2023; 12:6640. [PMID: 37892778 PMCID: PMC10607836 DOI: 10.3390/jcm12206640] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/18/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy.
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Affiliation(s)
- Angela Napolitano
- General Internal Medicine & Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy;
| | - Laura De Michieli
- Department of Cardiothoracic and Vascular Sciences & Public Health, Padova University Hospital, 35128 Padova, Italy; (L.D.M.); (G.S.); (A.C.)
| | - Giulio Sinigiani
- Department of Cardiothoracic and Vascular Sciences & Public Health, Padova University Hospital, 35128 Padova, Italy; (L.D.M.); (G.S.); (A.C.)
| | - Tamara Berno
- Haematology Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy;
| | - Alberto Cipriani
- Department of Cardiothoracic and Vascular Sciences & Public Health, Padova University Hospital, 35128 Padova, Italy; (L.D.M.); (G.S.); (A.C.)
| | - Luca Spiezia
- General Internal Medicine & Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, 35128 Padova, Italy;
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Oli SS, Jha A, Karki A, Sapkota S, Adhikari L. Primary Systemic Amyloidosis: A Case Report. JNMA J Nepal Med Assoc 2023; 61:822-824. [PMID: 38289775 PMCID: PMC10579773 DOI: 10.31729/jnma.8297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Indexed: 02/01/2024] Open
Abstract
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease. Keywords cardiomyopathies; case reports; primary amyloidosis.
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Affiliation(s)
- Saurav Sen Oli
- Kathmandu Medical College and Teaching Hospital, Sinamangal, Kathmandu, Nepal
| | - Abhishek Jha
- Kathmandu Medical College and Teaching Hospital, Sinamangal, Kathmandu, Nepal
| | - Anisha Karki
- Kathmandu Medical College and Teaching Hospital, Sinamangal, Kathmandu, Nepal
| | - Shova Sapkota
- Kathmandu Medical College and Teaching Hospital, Sinamangal, Kathmandu, Nepal
| | - Laxman Adhikari
- Department of Nephrology, Kathmandu Medical College and Teaching Hospital, Sinamangal, Kathmandu, Nepal
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23
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Singh RB, Singhal S, Sinha S, Cho J, Nguyen AXL, Dhingra LS, Kaur S, Sharma V, Agarwal A. Ocular complications of plasma cell dyscrasias. Eur J Ophthalmol 2023; 33:1786-1800. [PMID: 36760117 PMCID: PMC10472748 DOI: 10.1177/11206721231155974] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 01/21/2023] [Indexed: 02/11/2023]
Abstract
Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.
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Affiliation(s)
- Rohan Bir Singh
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Great Ormond Street Institute of Child Health, University College London, London, UK
- Discipline of Ophthalmology and Visual Sciences, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Sachi Singhal
- Department of Internal Medicine, Crozer-Chester Medical Center, Upland, PA, USA
| | - Shruti Sinha
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Junsang Cho
- Department of Ophthalmology, Vanderbilt Eye Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Lovedeep Singh Dhingra
- Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA
| | - Snimarjot Kaur
- Department of Pediatrics, Yale-New Haven Hospital, New Haven, CT, USA
| | - Vasudha Sharma
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Aniruddha Agarwal
- Department of Ophthalmology, University of Maastricht, Maastricht, the Netherlands
- Department of Ophthalmology, The Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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24
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Tahara S, Kohyama M, Nakamitsu A, Sugiyama Y, Tazaki T, Taogoshi H, Komo T, Yamaguchi T, Ueda M, Ishikawa A, Takahashi S, Sasaki M. Surgical strategies for localized colorectal amyloidosis. Surg Case Rep 2023; 9:66. [PMID: 37103609 PMCID: PMC10140200 DOI: 10.1186/s40792-023-01649-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 04/13/2023] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND Localized colorectal amyloidosis has a good prognosis, but cases involving bleeding or perforation may require surgery. However, there are few case reports discussing the differences in the surgical strategy between the segmental and pan-colon types. CASE PRESENTATION A 69-year-old woman with a history of abdominal pain and melena was diagnosed with amyloidosis localized in the sigmoid colon by colonoscopy. Since preoperative imaging and intraoperative findings could not rule out malignancy, we performed laparoscopic sigmoid colectomy with lymph-node dissection. Histopathological examination and immunohistochemical staining revealed a diagnosis of AL amyloidosis (λ type). We diagnosed localized segmental gastrointestinal amyloidosis, because there was no amyloid protein in the margins, and the tumor was localized. There were no malignant findings. CONCLUSIONS Unlike systemic amyloidosis, localized amyloidosis has a favorable prognosis. Localized colorectal amyloidosis can be classified into the segmental type, in which amyloid protein is deposited locally, and the pan-colon type, in which amyloid protein is deposited extensively in the colon. Amyloid protein causes ischemia due to vascular deposition, weakening of the intestinal wall due to muscle layer deposition, and decreased peristalsis due to nerve plexus deposition. No amyloid protein should remain outside the resection area. The pan-colon type is often reported to cause complications such as anastomotic leakage, and primary anastomosis should be avoided. On the other hand, if there is no contamination or tumor remnants in the margin, the segmental type may be considered for primary anastomosis.
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Affiliation(s)
- Shunya Tahara
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Mohei Kohyama
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan.
| | - Atsushi Nakamitsu
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Yoichi Sugiyama
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Tatsuya Tazaki
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Hiroyuki Taogoshi
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Toshiaki Komo
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Takuro Yamaguchi
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
| | - Mitsuharu Ueda
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjou, Chuo Ward, Kumamoto, Kumamoto, 860-8556, Japan
| | - Akira Ishikawa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami Ward, Hiroshima, Hiroshima, 734-0037, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami Ward, Hiroshima, Hiroshima, 734-0037, Japan
| | - Masaru Sasaki
- Department of Surgery, JA Hiroshima General Hospital, 1-3-3 Jigozen, Hatsukaichi, Hiroshima, 738-8503, Japan
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Budweg J, Al-Ani M, Assaf Y, Parker A, Aranda J. Amyloid transthyretin cardiac amyloidosis with different manifestations, test findings and types. BMJ Case Rep 2023; 16:e250972. [PMID: 37080632 PMCID: PMC10124201 DOI: 10.1136/bcr-2022-250972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023] Open
Abstract
Amyloid transthyretin amyloidosis usually presents with cardiac amyloidosis manifestations, most commonly with a heart failure syndrome. The history and physical examination offer clues of other cardiac and extracardiac manifestations. Taking a detailed history is essential in elucidating pertinent family and medical history that may increase suspicion for amyloidosis. Further, certain findings on electrocardiogram and imaging should raise suspicion and trigger further workup that can confirm the diagnosis, since treatment is evolving.
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Affiliation(s)
- Jeffery Budweg
- Medicine, University of Florida, Gainesville, Florida, USA
| | - Mohammad Al-Ani
- Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA
| | - Yazan Assaf
- Medicine, University of Florida, Gainesville, Florida, USA
- Medicine, Division of Cardiology, Baylor College of Medicine, Houston, Texas, USA
| | - Alex Parker
- Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA
| | - Juan Aranda
- Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA
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26
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Lee HJ, Kim JS, Mun YC, Lee JK. Ultrasound-guided percutaneous core needle biopsy of abdominal subcutaneous fat for diagnosing amyloidosis: comparison with bone marrow biopsy. Acta Radiol 2023; 64:1770-1774. [PMID: 36748104 DOI: 10.1177/02841851231151369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with underlying hematologic malignancy have a higher risk of developing systemic amyloidosis, which worsens their prognosis. Histopathologic detection of amyloid deposits in tissue biopsy specimens is the only diagnostic method for amyloidosis. PURPOSE To compare the efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of abdominal subcutaneous fat with that of bone marrow biopsy (BMB) for diagnosing amyloidosis. MATERIAL AND METHODS A total of 90 consecutive patients with underlying hematologic disorders who underwent both USPCB of abdominal subcutaneous fat and BMB for suspicion of amyloid deposition during a 10-year period were included in this retrospective study. RESULTS The sensitivity and specificity of detecting amyloid deposition were 85.7% and 100%, respectively, with USPCB as opposed to 4.8% and 100%, respectively, with BMB, and the sensitivity was significantly higher with USPCB (P < 0.001). The mean number of times USPCB was performed was 3.3. There were no major complications associated with USPCB. The sensitivity of detecting amyloidosis was not different between the 18-G needle group and the 14-G group (100% vs. 80%; P = 0.623). Logistic regression analysis revealed that acquiring more cores from USPCB and thinner fat tissues were statistically significant factors that affected the diagnostic accuracy of USPCB for amyloid detection. CONCLUSION The sensitivity of amyloid deposition was significantly higher with USPCB of abdominal subcutaneous fat than BMB. Acquiring more cores by multiple biopsies instead of using a larger bore needle and thin subcutaneous fat pad may be a favorable factor for the diagnostic accuracy of USPCB.
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Affiliation(s)
- Hyo Jeong Lee
- Department of Radiology, College of Medicine, 26717Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea
| | - Jin Sil Kim
- Department of Radiology, College of Medicine, 26717Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea
| | - Yeung-Chul Mun
- Department of Hematology and Oncology, College of Medicien, 26717Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea
| | - Jeong Kyong Lee
- Department of Radiology, College of Medicine, 26717Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea
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Mora V, Roldán I, Romero E, Saad A, Gil C, Contreras MB, Trainini J, Escribano P, Gimeno P, Arbucci R, Valls A, Lowenstein J. Myocardial Wringing and Rigid Rotation in Cardiac Amyloidosis. CJC Open 2023; 5:128-135. [PMID: 36880078 PMCID: PMC9984891 DOI: 10.1016/j.cjco.2022.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background The motion of the heart is a result of the helicoidal arrangement of the myofibers in the organ's wall. We aimed to study the relationship between the wringing motion state and the degree of ventricular function in patients with cardiac amyloidosis (CA). Methods Fifty patients with CA and decreased global longitudinal strain (LS) were evaluated using 2-dimensional speckle-tracking echocardiography. We have expressed LS as positive values to facilitate understanding. Normal twist, which occurs when basal and apical rotations occur in opposite directions, was coded as positive. When the apex and base rotate in the same direction (rigid rotation), twist was coded as negative. Left ventricular (LV) wringing (calculated as twist/LS, which takes into account actions that occur simultaneously during LV systole [ie, longitudinal shortening and twist]) was evaluated according to LV ejection fraction (LVEF). Results Most of the patients (66%) who participated in the study were diagnosed with transthyretin amyloidosis. A positive relationship was observed between wringing and LVEF (r = 0.75, P < 0.0001). In advanced stages of ventricular dysfunction, rigid rotation appeared in 66.6% of patients with LVEF ≤ 40%, in whom negative values of twist and wringing were observed. LV wringing proved to be a good discriminator of LVEF (area under the curve 0.90, P < 0.001, 95% confidence interval 0.79-0.97); for example, wringing < 1.30°/% detected LVEF < 50% with 85.7% sensibility and 89.7% specificity. Conclusions Wringing, which integrates twist and simultaneous LV longitudinal shortening, is a conditioning rotational parameter of the degree of ventricular function in patients with CA.
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Affiliation(s)
- Vicente Mora
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Ildefonso Roldán
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Elena Romero
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Ariel Saad
- Cardiodiagnosis Department, Medical Research, Buenos Aires, Argentina
| | - Celia Gil
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - M Belen Contreras
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Jorge Trainini
- Cardiodiagnosis Department, Medical Research, Buenos Aires, Argentina
| | - Pablo Escribano
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Pau Gimeno
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Rosina Arbucci
- Cardiodiagnosis Department, Medical Research, Buenos Aires, Argentina
| | - Amparo Valls
- Department of Cardiology, Hospital Universitario Dr Peset. Valencia, Spain
| | - Jorge Lowenstein
- Cardiodiagnosis Department, Medical Research, Buenos Aires, Argentina
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Cardiac Amyloidosis: A Rare TTR Mutation Found in an Asian Female. J Cardiovasc Dev Dis 2023; 10:jcdd10010013. [PMID: 36661908 PMCID: PMC9863331 DOI: 10.3390/jcdd10010013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Transthyretin cardiac amyloidosis (ATTR) is a life-threatening, debilitating disease caused by abnormal formation and deposit of transthyretin (TTR) protein in multiple tissues, including myocardial extracellular matrix. It can be challenging to diagnose due to the myriad of presenting signs and symptoms. Additionally, numerous TTR mutations exist in certain ethnicities. Interestingly, our patient was discovered to have a very rare Gly67Ala TTR mutation typically not found in individuals of Asian descent. Recent advances in cardiovascular imaging techniques have allowed for earlier recognition and, therefore, management of this disease. Although incurable, there are now new, emerging treatments that are available for symptom control of cardiac amyloidosis, making early diagnosis vital for these patients, specifically their quality of life. CASE SUMMARY We outline a case of a 50-year-old Asian female who was initially hospitalized for nausea and vomiting and persistent orthostatic hypotension. She underwent a multitude of laboratory and imaging tests, resulting in a diagnosis of cardiac amyloidosis, which was confirmed to be due to a rare TTR mutation via genetic testing. CONCLUSIONS Our objective is to describe various TTR mutations, existing diagnostic imaging modalities, and available treatments, as well as highlight the importance of early screening and awareness of cardiac amyloidosis, allowing for quicker diagnosis and treatment of this disease.
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Alraawi Z, Banerjee N, Mohanty S, Kumar TKS. Amyloidogenesis: What Do We Know So Far? Int J Mol Sci 2022; 23:ijms232213970. [PMID: 36430450 PMCID: PMC9695042 DOI: 10.3390/ijms232213970] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/01/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.
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Affiliation(s)
- Zeina Alraawi
- Department of Chemistry and Biochemistry, Fulbright College of Art and Science, University of Arkansas, Fayetteville, AR 72701, USA
| | - Nayan Banerjee
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A & 2B Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Srujana Mohanty
- Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata 741246, India
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ABRANTES AR, LUZ IA, SANTOS PA, BARRETO P, FERRER FA, LOBOS AV. Kappa chain amyloidosis: a deadly entity not to forget in patients with nondiabetic proteinuria. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2022. [DOI: 10.23736/s0393-3660.20.04539-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Wang J, Yang S, Liao P, Zeng L, Ling W, Wan L, Weng J, Zhong L. Incidence and effect of secondary cardiac amyloidosis on outcomes of patients with t(11;14) multiple myeloma. Front Cardiovasc Med 2022; 9:994384. [PMID: 36119749 PMCID: PMC9479066 DOI: 10.3389/fcvm.2022.994384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 08/16/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe t(11;14)(q13;32) is a common chromosome translocation in multiple myeloma (MM), but its prognostic value remains controversial. Immunoglobulin light chain amyloidosis is commonly secondary to multiple myeloma, which can rapidly cause heart failure and high mortality. We aimed to investigate the prevalence of secondary cardiac amyloidosis in MM patients with t(11;14) and to evaluate its impact on survival outcomes.MethodsWe retrospectively identified 52 MM patients with t(11;14) in our center between October 2015 and April 2022. The associations between cardiac amyloidosis and clinical and biological parameters were statistically analyzed, and the impacts of concomitant of cardiac amyloidosis on survival and prognosis of MM patients with t(11;14) were also assessed.ResultsConcomitant presence of cardiac amyloidosis was observed in 15 (28.8%) of all cases. Patients with cardiac amyloidosis had significantly higher NT-proBNP (p = 0.002) and higher hs-cTnT (p < 0.001), while the patients without cardiac amyloidosis had higher percentage of bone marrow plasma cells (p = 0.027), higher incidence of hemoglobin <80 g/L (p = 0.021) and bone destruction (p < 0.001). The median overall survival (OS) for all patients was 33.4 months after a median follow-up of 23.8 months. The amyloidosis group showed a significantly shorter OS than the non-amyloidosis group (15.3 vs. 41.8 months, p < 0.001). Besides, patients harboring NT-proBNP >1,800 pg/ml (p < 0.001) or hs-cTnT ≧40 pg/ml (p = 0.001) or light chain (LC) only isotype (p = 0.033) had a significantly shorter mean OS compared with patients with lower NT-proBNP or hs-cTnT or other M-protein isotype. Univariate analyses showed that NT-proBNP >1,800 pg/ml, hs-cTnT ≧40 pg/ml, LC only isotype, and concomitant presence of cardiac amyloidosis were independently associated with shorter OS, while NT-proBNP >1,800 pg/ml still retained the prognostic value for OS in multivariate analyses.ConclusionThe t(11;14) MM patients with coexisting cardiac amyloidosis may represent a distinct clinical entity that confers a poor outcome. These findings may have important clinical and biological implications.
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Affiliation(s)
- Jinghua Wang
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Shuo Yang
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Pengjun Liao
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Lingji Zeng
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Wei Ling
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Li Wan
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jianyu Weng
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- *Correspondence: Liye Zhong
| | - Liye Zhong
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Jianyu Weng
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Bezerra HKF, de França TRT, Prado JD, Saint-Gerons RS, de Amorim Carvalho EJ, da Cruz Perez DE. Oral localized amyloidosis. Head Neck Pathol 2022; 16:818-822. [PMID: 35296978 PMCID: PMC9424412 DOI: 10.1007/s12105-022-01436-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 11/30/2022]
Abstract
This report describes two cases of oral localized amyloidosis (LA). In case 1, a 52-year-old man appeared with painful slightly, yellowish multiple nodules located on the dorsum of the tongue, of unknown duration. Incisional biopsy was performed, and the histopathologic analysis revealed a homogeneous, eosinophilic, and extracellular material. Congo red stain showed salmon pink coloration at light microscopy and apple-green birefringence at polarized light. In case 2, a 74-year-old man presented asymptomatic nodular lesions on the labial commissures with duration of several months. An excisional biopsy was performed in both lesions, and microscopically the specimen demonstrated the same histopathologic features of the case 1. Furthermore, amyloidosis with systemic involvement was excluded after investigations for both patients. Thus, the final diagnosis for both cases was LA. The patient 1 refused the surgical excision of the residual lesion, and in both cases, no signs of clinical and systemic progression were observed after 24 and 84 months of follow up. Although it is rare, LA should be considered in the differential diagnosis of multiple or single yellowish nodules on the oral cavity.
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Affiliation(s)
- Hélen Kaline Farias Bezerra
- Department of Clinical and Preventive Dentistry, Oral Pathology Unit, Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | | | - José Divaldo Prado
- Department of Stomatology, A. C. Camargo Cancer Center, São Paulo, São Paulo, Brazil
| | - Rafael Segura Saint-Gerons
- Andalusian Healthcare Service, Department of Medical and Surgical Specialties, University of Córdoba, Córdoba, Spain
| | - Elaine Judite de Amorim Carvalho
- Department of Clinical and Preventive Dentistry, Oral Pathology Unit, Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | - Danyel Elias da Cruz Perez
- Department of Clinical and Preventive Dentistry, Oral Pathology Unit, Federal University of Pernambuco, Recife, Pernambuco, Brazil. .,Department of Clinical and Preventive Dentistry, Oral Pathology Unit, Universidade Federal de Pernambuco, 4ª Travessa Professor Artur de Sá, s/n, CEP: 50740-521, Recife, PE, Brazil.
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Cuddy SAM, Chetrit M, Jankowski M, Desai M, Falk RH, Weiner RB, Klein AL, Phelan D, Grogan M. Practical Points for Echocardiography in Cardiac Amyloidosis. J Am Soc Echocardiogr 2022; 35:A31-A40. [PMID: 36064258 DOI: 10.1016/j.echo.2022.06.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Affiliation(s)
- Sarah A M Cuddy
- Amyloidosis Program, Brigham and Women's Hospital, Boston, Massachusetts
| | - Michael Chetrit
- Department of Cardiovascular Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Madeline Jankowski
- Division of Cardiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Milind Desai
- Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Rodney H Falk
- Amyloidosis Program, Brigham and Women's Hospital, Boston, Massachusetts
| | - Rory B Weiner
- Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Allan L Klein
- Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio
| | - Dermot Phelan
- Sanger Heart & Vascular Institute, Atrium Health, Charlotte, North Carolina
| | - Martha Grogan
- Cardiac Amyloid Clinic, Division of Circulatory Failure, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
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34
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Lewis E, Fine N, Miller RJH, Hahn C, Chhibber S, Mahe E, Tay J, Duggan P, McCulloch S, Bahlis N, Neri P, Jimenez-Zepeda VH. Amyloidosis and COVID-19: experience from an amyloid program in Canada. Ann Hematol 2022; 101:2307-2315. [PMID: 36028582 PMCID: PMC9417080 DOI: 10.1007/s00277-022-04964-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/18/2022] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.
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Affiliation(s)
- Ellen Lewis
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Nowell Fine
- Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
| | - Robert J H Miller
- Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
| | - Christopher Hahn
- Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - Sameer Chhibber
- Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - Etienne Mahe
- Department of Pathology and Lab Medicine, University of Calgary, Calgary, AB, Canada
| | - Jason Tay
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Charbonneau Cancer Research Institute, Calgary, AB, Canada
| | - Peter Duggan
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Sylvia McCulloch
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Nizar Bahlis
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Charbonneau Cancer Research Institute, Calgary, AB, Canada
| | - Paola Neri
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Charbonneau Cancer Research Institute, Calgary, AB, Canada
| | - Victor H Jimenez-Zepeda
- Division of Hematology, Department of Medicine, University of Calgary, Calgary, AB, Canada. .,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. .,Charbonneau Cancer Research Institute, Calgary, AB, Canada. .,Department of Medical Oncology and Hematology, Tom Baker Cancer Centre, 1331 29th St, NW, Calgary, AB, T2N 4N2, Canada.
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35
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Bharati J, Lahoud OB, Jhaveri KD, Izzedine H. AA Amyloidosis associated with cancers. Nephrol Dial Transplant 2022; 38:1366-1374. [PMID: 35867878 DOI: 10.1093/ndt/gfac217] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Indexed: 11/12/2022] Open
Abstract
Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentation and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.
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Affiliation(s)
- Joyita Bharati
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.,Glomerular Center at Northwell Health, Division of Kidney Diseases and Hypertension, Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
| | - Oscar B Lahoud
- Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, NY, NY, USA
| | - Kenar D Jhaveri
- Glomerular Center at Northwell Health, Division of Kidney Diseases and Hypertension, Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
| | - Hassan Izzedine
- Department of Nephrology, Peupliers Private Hospital, Ramsay Générale de Santé, Paris, France
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Tjahjadi C, Fortuni F, Stassen J, Debonnaire P, Lustosa RP, Marsan NA, Delgado V, Bax JJ. Prognostic Implications of Right Ventricular Systolic Dysfunction in Cardiac Amyloidosis. Am J Cardiol 2022; 173:120-127. [PMID: 35369931 DOI: 10.1016/j.amjcard.2022.02.048] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/22/2022]
Abstract
Left ventricular (LV) systolic dysfunction in cardiac amyloidosis (CA) is associated with poor prognosis. This study aimed to investigate the prognostic implications of right ventricular (RV) systolic dysfunction in CA. A total of 93 patients diagnosed with CA who underwent standard and speckle-tracking echocardiography were included. During a median follow-up of 17 (5 to 38) months, 42 patients (45%) died. Nonsurvivors were more likely to present with immunoglobulin light-chain amyloidosis and New York Heart Association class III to IV heart failure symptoms. Regarding the echocardiographic characteristics, nonsurvivors had a higher LV apical ratio, worse LV diastolic function, and worse RV systolic function (evaluated with both tricuspid annular plane systolic excursion and RV free wall strain). RV free wall strain was independently associated with all-cause mortality in several multivariable Cox regression models and had incremental prognostic value over conventional parameters of RV function when added to a basal model (including heart failure symptoms, amyloidosis phenotype, and LV global longitudinal strain). Based on spline curve analysis and Youden index, a value of 16% for RV free wall strain was identified as the optimal cutoff to predict outcome and patients with RV free wall strain <16% had a significantly worse short- and long-term survival during follow-up (1- and 3-year cumulative survival: 81% vs 31% and 67% vs 20%, respectively, p <0.001). In conclusion, RV systolic dysfunction is independently associated with poor outcome in patients with CA and the use of advanced echocardiographic parameters, such as RV free wall strain, may be of aid for better risk stratification.
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Affiliation(s)
- Catherina Tjahjadi
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Federico Fortuni
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, San Giovanni Battista Hospital, Foligno, Italy
| | - Jan Stassen
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Jessa Hospital, Hasselt, Belgium
| | - Philippe Debonnaire
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Sint-Jan Hospital Bruges, Bruges, Belgium
| | - Rodolfo P Lustosa
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Nina Ajmone Marsan
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Victoria Delgado
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jeroen J Bax
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
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37
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Ikura H, Endo J, Kitakata H, Moriyama H, Sano M, Fukuda K. Molecular Mechanism of Pathogenesis and Treatment Strategies for AL Amyloidosis. Int J Mol Sci 2022; 23:6336. [PMID: 35683015 PMCID: PMC9181426 DOI: 10.3390/ijms23116336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 11/17/2022] Open
Abstract
In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free light chains (FLCs), which form amyloid fibrils that deposit in the interstitial tissue, resulting in organ injury and dysfunction. AL amyloidosis progresses much faster than other types of amyloidosis, with a slight delay in diagnosis leading to a marked exacerbation of cardiomyopathy. In some cases, the resulting heart failure is so severe that chemotherapy cannot be administered, and death sometimes occurs within a few months. To date, many clinical studies have focused on therapeutics, especially chemotherapy, to treat this disease. Because it is necessary to promptly lower FLC, the causative protein of amyloid, to achieve a hematological response, various anticancer agents targeting neoplastic plasma cells are used for the treatment of this disease. In addition, many basic studies using human specimens to elucidate the pathophysiology of AL have been conducted. Gene mutations associated with AL, the characteristics of amyloidogenic LC, and the structural specificity of amyloid fibrils have been clarified. Regarding the mechanism of cellular and tissue damage, the mass effect due to amyloid deposition, as well as the toxicity of pre-fibrillar LC, is gradually being elucidated. This review outlines the pathogenesis and treatment strategies for AL amyloidosis with respect to its molecular mechanisms.
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Affiliation(s)
| | - Jin Endo
- Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-City, Tokyo 160-8582, Japan; (H.I.); (H.K.); (H.M.); (M.S.); (K.F.)
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38
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Ng PLF, Lim YC, Evangelista LKM, Wong RCC, Chai P, Sia CH, Loi HY, Yeo TC, Lin W. Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis. Ann Noninvasive Electrocardiol 2022; 27:e12967. [PMID: 35567784 PMCID: PMC9296797 DOI: 10.1111/anec.12967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/25/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this "classical" finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non-invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium-pyrophosphate imaging. CONCLUSIONS Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.
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Affiliation(s)
- Perryn Lin Fei Ng
- Department of Cardiology, National University Heart Centre, Singapore, Singapore
| | - Yoke Ching Lim
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Raymond Ching Chiew Wong
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ping Chai
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ching Hui Sia
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hoi Yin Loi
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Diagnostic Imaging, National University Hospital, Singapore, Singapore
| | - Tiong Cheng Yeo
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Weiqin Lin
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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39
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Liu XH, Shi JY, Zhang DD, Jia FW, Lin X, Zhu YL, Zhuang JL, Fang LG, Chen W. Prognostic value of left atrial mechanics in cardiac light-chain amyloidosis with preserved ejection fraction: a cohort study. BMC Cardiovasc Disord 2022; 22:175. [PMID: 35428181 PMCID: PMC9013068 DOI: 10.1186/s12872-022-02589-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 03/27/2022] [Indexed: 12/05/2022] Open
Abstract
Background Light-chain amyloidosis is a plasma cell disorder associated with poor outcomes, especially when the heart is involved. The characteristics of left atrial (LA) function and its prognostic implications in cardiac amyloidosis (CA) have not been fully investigated. Methods Between April 2014 and June 2019, 93 patients with a diagnosis of CA, normal left ventricular ejection fraction (LVEF) and sinus rhythm were included. Their clinical, baseline echocardiographic and follow-up data were investigated. LA function, including LA strain and strain rate, was assessed using 2D speckle tracking echocardiography in different LA functional phases. Results Among all patients, 38 (40.9%) died. Multivariate Cox regression analyses showed that LA mechanics regarding LA reservoir and booster pump functions were independent predictors for overall survival. Traditional echocardiographic parameters for LA structure like LA volume index and LA width were not associated with mortality. Moreover, LA strain and strain rate in reservoir and contractile phases improved the discrimination and goodness of fit of the conventional prognostic model, the Mayo criteria 2004 and 2012, in our study population. Decreased LA mechanics were associated with impaired left ventricular (LV) systolic and diastolic function, and LA reservoir and contractile functions were associated with LA structure. Conclusions Assessment of LA reservoir and contractile functions via 2D speckle tracking echocardiographic LA mechanical indices provide clinical and prognostic insights into cardiac light-chain amyloidosis patients, especially those with preserved EF and sinus rhythm. Emphasizing the monitoring of LA function may be beneficial for the prognosis prediction of CA. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-022-02589-7.
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40
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Cuddy SAM. Editorial: 18F-Fluoride PET/MR in cardiac amyloid; simple addition versus synergy? J Nucl Cardiol 2022; 29:750-752. [PMID: 33205329 DOI: 10.1007/s12350-020-02437-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 10/15/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Sarah A M Cuddy
- Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, USA.
- CV Imaging Program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, USA.
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41
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Baker KR. Light Chain Amyloidosis: Epidemiology, Staging, and Prognostication. Methodist Debakey Cardiovasc J 2022; 18:27-35. [PMID: 35414848 PMCID: PMC8932379 DOI: 10.14797/mdcvj.1070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/02/2022] [Indexed: 12/19/2022] Open
Abstract
Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment.
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42
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Gołębiowski T, Kuźniar J, Porażko T, Wojtala R, Konieczny A, Krajewska M, Klinger M. Multisystem Amyloidosis in a Coal Miner with Silicosis: Is Exposure to Silica Dust a Cause of Amyloid Deposition? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19042297. [PMID: 35206498 PMCID: PMC8871531 DOI: 10.3390/ijerph19042297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 02/12/2022] [Accepted: 02/13/2022] [Indexed: 02/04/2023]
Abstract
The over-secretion of monoclonal immunoglobulin light chains by clonal B cells followed by the aggregation and extracellular deposition of fibrillar deposits are responsible forthe clinical course AL amyloidosis. It is well documented that silica significantly increases the number of immunoglobulin-secreting cells. In the present paper, we report on a coal miner with silicosis and fast progressing primary amyloidosis with predominantly heart, kidney, and lung manifestations. Severeheart failure due to myocardial hypertrophy resulted in the patient’s death. We conclude that long-term environmental silica exposure and silica deposition may contribute to the development of monoclonal gammopathy and amyloidosis due to chronic stimulus and the dysregulation of the immune system.
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Affiliation(s)
- Tomasz Gołębiowski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.K.); (A.K.); (M.K.)
- Correspondence: ; Tel.: +48-717332546
| | - Jakub Kuźniar
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.K.); (A.K.); (M.K.)
| | - Tomasz Porażko
- Department of Internal Medicine and Nephrology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland; (T.P.); (M.K.)
| | - Renata Wojtala
- Departament of Patomorphology, Wroclaw Medical University, 50-556 Wroclaw, Poland;
| | - Andrzej Konieczny
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.K.); (A.K.); (M.K.)
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland; (J.K.); (A.K.); (M.K.)
| | - Marian Klinger
- Department of Internal Medicine and Nephrology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland; (T.P.); (M.K.)
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43
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Stelmach-Gołdyś A, Zaborek-Łyczba M, Łyczba J, Garus B, Pasiarski M, Mertowska P, Małkowska P, Hrynkiewicz R, Niedźwiedzka-Rystwej P, Grywalska E. Physiology, Diagnosis and Treatment of Cardiac Light Chain Amyloidosis. J Clin Med 2022; 11:jcm11040911. [PMID: 35207184 PMCID: PMC8880759 DOI: 10.3390/jcm11040911] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/27/2022] [Accepted: 02/02/2022] [Indexed: 02/04/2023] Open
Abstract
AL (light-chain) amyloidosis is a systemic disease in which amyloid fibers are formed from kappa or lambda immunoglobulin light chains, or fragments thereof, produced by a neoplastic clone of plasmocytes. The produced protein is deposited in tissues and organs in the form of extracellular deposits, which leads to impairment of their functions and, consequently, to death. Despite the development of research on pathogenesis and therapy, the mortality rate of patients with late diagnosed amyloidosis is 30%. The diagnosis is delayed due to the complex clinical picture and the slow progression of the disease. This is the type of amyloidosis that most often contributes to cardiac lesions and causes cardiac amyloidosis (CA). Early diagnosis and correct identification of the type of amyloid plays a crucial role in the planning and effectiveness of therapy. In addition to standard histological studies based on Congo red staining, diagnostics are enriched by tests to determine the degree of cardiac involvement. In this paper, we discuss current diagnostic methods used in cardiac light chain amyloidosis and the latest therapies that contribute to an improved patient prognosis.
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Affiliation(s)
- Agnieszka Stelmach-Gołdyś
- Department of Immunology, Faculty of Health Sciences, Jan Kochanowski University, 25-317 Kielce, Poland; (A.S.-G.); (B.G.); (M.P.)
- Department of Hematology, Holy Cross Cancer Centre, 25-734 Kielce, Poland
| | - Monika Zaborek-Łyczba
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (M.Z.-Ł.); (J.Ł.); (P.M.); (E.G.)
| | - Jakub Łyczba
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (M.Z.-Ł.); (J.Ł.); (P.M.); (E.G.)
| | - Bartosz Garus
- Department of Immunology, Faculty of Health Sciences, Jan Kochanowski University, 25-317 Kielce, Poland; (A.S.-G.); (B.G.); (M.P.)
- Department of Hematology, Holy Cross Cancer Centre, 25-734 Kielce, Poland
| | - Marcin Pasiarski
- Department of Immunology, Faculty of Health Sciences, Jan Kochanowski University, 25-317 Kielce, Poland; (A.S.-G.); (B.G.); (M.P.)
- Department of Hematology, Holy Cross Cancer Centre, 25-734 Kielce, Poland
| | - Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (M.Z.-Ł.); (J.Ł.); (P.M.); (E.G.)
| | - Paulina Małkowska
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland; (P.M.); (R.H.)
| | - Rafał Hrynkiewicz
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland; (P.M.); (R.H.)
| | | | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland; (M.Z.-Ł.); (J.Ł.); (P.M.); (E.G.)
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Anandh U, Vaswani B, Gowrishankar S. Acute interstitial nephritis following lenalidomide therapy in a patient with AL amyloidosis. Indian J Nephrol 2022; 32:390-391. [PMID: 35967521 PMCID: PMC9364991 DOI: 10.4103/ijn.ijn_101_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/01/2022] [Accepted: 05/08/2022] [Indexed: 11/04/2022] Open
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Gibbons CH, Silvestri NJ. Autonomic Dysfunction in Neuromuscular Disorders. Neuromuscul Disord 2022. [DOI: 10.1016/b978-0-323-71317-7.00005-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Howard ER. George Budd and His Contribution to the Early History of Amyloid Disease. Clin Liver Dis (Hoboken) 2021; 20:1-20. [PMID: 36518786 PMCID: PMC9742754 DOI: 10.1002/cld.1187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Content available: Audio Recording.
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Inoue G, Matsumori T, Uza N. Diagnosis of AL-type amyloidosis from bile duct wall thickening. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 29:e71-e72. [PMID: 34919336 DOI: 10.1002/jhbp.1098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/13/2021] [Accepted: 11/23/2021] [Indexed: 11/05/2022]
Affiliation(s)
- Genki Inoue
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Department of Gastroenterology, Kobe City Nishi-Kobe Medical Center, Kobe, Japan
| | - Tomoaki Matsumori
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Asadian S, Farzin M, Tabesh F, Rezaeian N, Bakhshandeh H, Hosseini L, Toloueitabar Y, Hemmati Komasi MM. The Auxiliary Role of Cardiac Magnetic Resonance Feature-Tracking Parameters in the Differentiation between Cardiac Amyloidosis and Constrictive Pericarditis. Cardiol Res Pract 2021; 2021:2045493. [PMID: 34725571 PMCID: PMC8557086 DOI: 10.1155/2021/2045493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/30/2021] [Accepted: 10/18/2021] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVES Cardiac amyloidosis (CA) and constrictive pericarditis (CP) are described as the differential diagnoses of restrictive hemodynamic alterations of the heart. We aimed to explain cardiac magnetic resonance (CMR) imaging findings (especially feature tracking (FT)) of CA and CP cases and compare them with healthy controls. Moreover, we evaluated the role of biventricular FT parameters in differentiating CA from CP. METHODS Thirty-eight patients who underwent CMR between February 2016 and January 2018 with the ultimate diagnosis of CA (19 patients) or CP (19 patients) were enrolled. We included biopsy-proven light-chain amyloidosis patients. The data of 28 healthy controls were utilized for comparison. The patients were followed up for 8-23 months to register mortality and their surveillance. All CMR morphological and functional data, including FT parameters, were recorded and analyzed. RESULTS Of only 13/19 (68.4%) CA patients who had the follow-up data, 11/13 (84.6%) died. One of The CP patients (5.3%) expired during the follow-up. Significant between-group differences were noted concerning the biventricular ejection fraction as well as global longitudinal, circumferential, and radial strain values (Ps < 0.001). The left ventricular (LV) global longitudinal strain (GLS) ≤10% was detected in 13/19 (68.4%) of the CA and 1/19 (5.3%) of CP cases (P < 0.001). A significant difference between the mean value of the LVGLS and LV global circumferential strain (GCS) of the basal LV level compared to the mid and apical levels was observed (Ps < 0.001) in the CA patients. The differences between the mean LVGLS and the GCS measures of the mid and apical LV levels were not significant (P=1 and P=0.06, respectively). CONCLUSIONS In our study, CA and CP severely disrupted ventricular strains. Biventricular GLS was meaningfully lower in the CA subjects. Therefore, strain analysis, especially in the longitudinal direction, could be helpful to differentiate CA from CP.
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Affiliation(s)
- Sanaz Asadian
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahta Farzin
- Iran University of Medical Sciences, Tehran, Iran
| | - Faezeh Tabesh
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Rezaeian
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hooman Bakhshandeh
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Leila Hosseini
- North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Yaser Toloueitabar
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
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Trzeciak P, Herbet M, Dudka J. Common Factors of Alzheimer's Disease and Rheumatoid Arthritis-Pathomechanism and Treatment. Molecules 2021; 26:6038. [PMID: 34641582 PMCID: PMC8512006 DOI: 10.3390/molecules26196038] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/20/2021] [Accepted: 09/29/2021] [Indexed: 11/17/2022] Open
Abstract
The accumulation of amyloid plaques, or misfolded fragments of proteins, leads to the development of a condition known as amyloidosis, which is clinically recognized as a systemic disease. Amyloidosis plays a special role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and rheumatoid arthritis (RA). The occurrence of amyloidosis correlates with the aging process of the organism, and since nowadays, old age is determined by the comfort of functioning and the elimination of unpleasant disease symptoms in the elderly, exposure to this subject is justified. In Alzheimer's disease, amyloid plaques negatively affect glutaminergic and cholinergic transmission and loss of sympathetic protein, while in RA, amyloids stimulated by the activity of the immune system affect the degradation of the osteoarticular bond. The following monograph draws attention to the over-reactivity of the immune system in AD and RA, describes the functionality of the blood-brain barrier as an intermediary medium between RA and AD, and indicates the direction of research to date, focusing on determining the relationship and the cause-effect link between these disorders. The paper presents possible directions for the treatment of amyloidosis, with particular emphasis on innovative therapies.
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Affiliation(s)
| | - Mariola Herbet
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090 Lublin, Poland; (P.T.)
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Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis. J Clin Med 2021; 10:jcm10194427. [PMID: 34640445 PMCID: PMC8509415 DOI: 10.3390/jcm10194427] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/18/2022] Open
Abstract
Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology-and progression-of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
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