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Pang N, Tian Y, Chi H, Fu X, Li X, Wang S, Pan F, Wang D, Xu L, Luo J, Liu A, Liu X. Development and validation of an early prediction model for cardiac death risk in patients with light chain amyloidosis: a multicenter study. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2025; 11:45. [PMID: 40375306 PMCID: PMC12079809 DOI: 10.1186/s40959-025-00342-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 04/23/2025] [Indexed: 05/18/2025]
Abstract
BACKGROUND Cardiac involvement is the primary driver of death in systemic light chain (AL) amyloidosis. However, the early prediction of cardiac death risk in AL amyloidosis remains insufficient. OBJECTIVES We aimed to develop a novel prediction model and prognostic scoring system that enables early identification of these high-risk individuals. METHODS This study enrolled 235 patients with confirmed AL cardiac amyloidosis from three hospitals. Patients from the first hospital were randomly assigned to the training and internal validation sets in an 8:2 ratio, while the external validation set comprised patients from the other two hospitals. Participants were categorized into a cardiac death group and a non-cardiac death group (including survivors and those who died from other causes). Five different machine learning models were used to train model, and model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS All five models showed excellent performance on the training and internal validation sets. In external validation, both the Logistic Regression (LR) and Random Forest models achieved an area under the ROC curve of 0.873 and 0.877, respectively, and exhibited superior calibration and decision curve analysis. Considering the comprehensive performance and clinical applicability, the LR model was selected as the final prediction model. The visualization results are ultimately presented in a nomogram. Further analyses were performed on the newly identified predictors. CONCLUSIONS This prediction model enables early identification and risk assessment of cardiac death in patients with AL amyloidosis, exhibiting considerable predictive ability.
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Affiliation(s)
- Naidong Pang
- Department of Cardiology, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ying Tian
- Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- Multiple Myeloma Clinical Research Center of Beijing, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hongjie Chi
- Department of Cardiology, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xiaohong Fu
- Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xin Li
- Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Shuyu Wang
- The Third Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Feifei Pan
- Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Dongying Wang
- Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Lin Xu
- Department of Cardiology, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jingyi Luo
- Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- Multiple Myeloma Clinical Research Center of Beijing, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Aijun Liu
- Department of Hematology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
- Multiple Myeloma Clinical Research Center of Beijing, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
| | - XingPeng Liu
- Department of Cardiology, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
- Department of Cardiology, HTRM Cardiovascular Hospital, Dezhou, Shandong, China.
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McCallinhart PE, Chade AR, Bender SB, Trask AJ. Expanding landscape of coronary microvascular disease in co-morbid conditions: Metabolic disease and beyond. J Mol Cell Cardiol 2024; 192:26-35. [PMID: 38734061 PMCID: PMC11340124 DOI: 10.1016/j.yjmcc.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/26/2024] [Accepted: 05/08/2024] [Indexed: 05/13/2024]
Abstract
Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that CMD is an independent predictor of cardiac morbidity and mortality in patients with obesity and metabolic disease. CMD is comprised of functional, structural, and mechanical impairments that synergize and ultimately reduce coronary blood flow in metabolic disease and in other co-morbid conditions, including transplant, autoimmune disorders, chemotherapy-induced cardiotoxicity, and remote injury-induced CMD. This review summarizes the contemporary state-of-the-field related to CMD in metabolic and these other co-morbid conditions based on mechanistic data derived mostly from preclinical small- and large-animal models in light of available clinical evidence and given the limitations of studying these mechanisms in humans. In addition, we also discuss gaps in current understanding, emerging areas of interest, and opportunities for future investigations in this field.
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Affiliation(s)
- Patricia E McCallinhart
- Center for Cardiovascular Research, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America
| | - Alejandro R Chade
- Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, United States of America; Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States of America
| | - Shawn B Bender
- Department of Biomedical Sciences, University of Missouri, Columbia, MO, United States of America; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States of America; Research Service, Harry S Truman Memorial Veterans Hospital, Columbia, MO, United States of America.
| | - Aaron J Trask
- Center for Cardiovascular Research, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States of America.
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İrgi T, Baycan ÖF, Güvenç TS, Özcan FB, Atıcı A, Yılmaz Y, Çalişkan M. Concomitant amyloidosis is the primary cause of endothelial and coronary microvascular dysfunction in carpal tunnel syndrome. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 41:100393. [PMID: 38655035 PMCID: PMC11035090 DOI: 10.1016/j.ahjo.2024.100393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 04/09/2024] [Accepted: 04/11/2024] [Indexed: 04/26/2024]
Abstract
Study objectives Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself. Design Prospective observational study. Setting Medeniyet University Goztepe Hospital. Participants 61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls. Interventions Subjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT). Main outcome measures Comparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis. Results Patients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, p < 0.05 for both) and CFVR (2.4 (2.1-2.8) in CTS and 1.8 (1.6-2.1) in CTS-A groups, p < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60-0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A. Conclusion Most arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis.
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Affiliation(s)
- Tuğçe İrgi
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Ömer Faruk Baycan
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Tolga Sinan Güvenç
- Istinye University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Fatma Betül Özcan
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Adem Atıcı
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Yusuf Yılmaz
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
| | - Mustafa Çalişkan
- Istanbul Medeniyet University School of Medicine, Department of Cardiology, Istanbul, Turkey
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De Michieli L, Cipriani A, Iliceto S, Dispenzieri A, Jaffe AS. Cardiac Troponin in Patients With Light Chain and Transthyretin Cardiac Amyloidosis: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol 2024; 6:1-15. [PMID: 38510286 PMCID: PMC10950441 DOI: 10.1016/j.jaccao.2023.12.006] [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: 08/31/2023] [Revised: 12/27/2023] [Accepted: 12/29/2023] [Indexed: 03/22/2024] Open
Abstract
Cardiac amyloidosis (CA) is an infiltrative disease caused by amyloid fibril deposition in the myocardium; the 2 forms that most frequently involve the heart are amyloid light chain (AL) and amyloid transthyretin (ATTR) amyloidosis. Cardiac troponin (cTn) is the biomarker of choice for the detection of myocardial injury and is frequently found to be elevated in patients with CA, particularly with high-sensitivity assays. Multiple mechanisms of myocardial injury in CA have been proposed, including cytotoxic effect of amyloid precursors, interstitial amyloid fibril infiltration, coronary microvascular dysfunction, amyloid- and non-amyloid-related coronary artery disease, diastolic dysfunction, and heart failure. Regardless of the mechanisms, cTn values have relevant prognostic (and potentially diagnostic) implications in both AL and ATTR amyloidosis. In this review, the authors discuss the significant aspects of cTn biology and measurement methods, potential mechanisms of myocardial injury in CA, and the clinical application of cTn in the management of both AL and ATTR amyloidosis.
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Affiliation(s)
- Laura De Michieli
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
- Cardiovascular Department, Mayo Clinic and Medical School, Rochester, Minnesota, USA
| | - Alberto Cipriani
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
- Cardiology Unit, University Hospital of Padua, Padua, Italy
| | - Sabino Iliceto
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
- Cardiology Unit, University Hospital of Padua, Padua, Italy
| | | | - Allan S. Jaffe
- Cardiovascular Department, Mayo Clinic and Medical School, Rochester, Minnesota, USA
- Department of Laboratory Medicine and Pathology, Mayo Clinic and Medical School, Rochester, Minnesota, USA
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Gharbin J, Winful A, Alebna P, Grewal N, Brgdar A, Rhodd S, Taha M, Fatima U, Mehrotra P, Onwuanyi A. Trends in incidence and clinical outcome of non-ST elevation myocardial infarction in patients with amyloidosis in the United States, 2010-2020. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2023; 35:100336. [PMID: 38511180 PMCID: PMC10945973 DOI: 10.1016/j.ahjo.2023.100336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 03/22/2024]
Abstract
Study objective To assess temporal changes in clinical profile and in-hospital outcome of patients with amyloidosis presenting with non-ST elevation myocardial infarction, NSTEMI. Design/setting We conducted a retrospective observational study using the National Inpatient Sample (NIS) database from January 1, 2010, to December 31, 2020. Main outcomes Primary outcome of interest was trend in adjusted in-hospital mortality in patients with amyloidosis presenting with NSTEMI from 2010 to 2020. Our secondary outcomes were trend in rate of coronary revascularization, and trend in duration of hospitalization. Results We identified 272,896 hospitalizations for amyloidosis. There was a temporal increase in incidence of NSTEMI among patients aged 18-44 years from 15.5 % to 28.0 %, a reverse trend was observed in 45-64 years: 22.1 % to 17.7 %, p = 0.043. There was no statistically significant difference in rate of coronary revascularization from 2010 to 2020; 16.3 % to 14.2 %, p = 0.86. We observed an increased odds of all-cause in-hospital mortality in patients with NSTEMI compared to those without NSTEMI (aOR = 2.2, 95 % CI: 1.9-2.6, p < 0.001) but there was a decrease trend in mortality from 21.5 % to 11.3 %, p = 0.013 for trend. Hospitalization duration was also observed to decreased from 14.1 days to 10.9 days during the study period (p = 0.055 for trend). Conclusion In patients with amyloidosis presenting with NSTEMI, there was increased incidence of NSTEMI among young adults, a steady trend in coronary revascularization, and a decreasing trend of adjusted all-cause in-hospital mortality and length of hospitalization from 2010 to 2020 in the United States.
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Affiliation(s)
- John Gharbin
- Department of Internal Medicine, Howard University, Washington, DC, USA
| | - Adwoa Winful
- Medical University of South Carolina Health, Orangeburg, SC, USA
| | - Pamela Alebna
- Division of Cardiology, Virginia Commonwealth University, Virginia, USA
| | - Niyati Grewal
- Department of Internal Medicine, Howard University, Washington, DC, USA
| | - Ahmed Brgdar
- Division of Cardiology, Howard University, Washington, DC, USA
| | - Suchelis Rhodd
- Division of Cardiology, Howard University, Washington, DC, USA
| | - Mohammed Taha
- Division of Cardiology, Virginia Commonwealth University, Virginia, USA
| | - Urooj Fatima
- Division of Cardiology, Howard University, Washington, DC, USA
| | | | - Anekwe Onwuanyi
- Division of Cardiology, Morehouse School of Medicine, Atlanta, GA, USA
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Huisl JP, Herrmann EJ, Aßmus B. [Systemic forms of amyloidosis with cardiac manifestation]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:340-350. [PMID: 36627390 DOI: 10.1007/s00108-022-01449-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/28/2022] [Indexed: 01/11/2023]
Abstract
The term amyloidosis summarizes heterogeneous diseases in which a misfolding of protein structures occurs. These misfolded proteins can fundamentally be deposited anywhere in the body and lead to malfunction of the affected organ. There are preferential sites of deposition depending on which protein is misfolded. Cardiac transthyretin (ATTR) amyloidosis is a rare cause of cardiomyopathy and part of an underdiagnosed systemic disease. For cardiac ATTR amyloidosis, which involves deposition of misfolded tranthyretin either as a wild type (wtATTR) or as a mutated form (mATTR or hATTR), evidence-based treatment options have recently become available with slowing of the progression of the cardiomyopathy and a significant reduction of hospitalization rates. Therefore, it is important to diagnose this severe disease at an early stage and to differentiate it from other forms of amyloidosis. A clinical screening is easily possible by determination of free light chains using imaging examinations (cardiac magnetic resonance imaging or scintigraphic procedures) and immunofixation before the definitive diagnosis is made based on a biopsy and/or genetic tests. An interdisciplinary work-up involving hemato-oncology, nephrology, neurology and other disciplines, is indispensable when cardiac amyloidosis is suspected.
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Affiliation(s)
- Jan Philipp Huisl
- Med. Klinik I, Kardiologie/Angiologie, UKGM, Universitätsklinikum Gießen, Klinikstr. 33, 35392, Gießen, Deutschland
| | - Ester J Herrmann
- Med. Klinik I, Kardiologie/Angiologie, UKGM, Universitätsklinikum Gießen, Klinikstr. 33, 35392, Gießen, Deutschland
| | - Birgit Aßmus
- Med. Klinik I, Kardiologie/Angiologie, UKGM, Universitätsklinikum Gießen, Klinikstr. 33, 35392, Gießen, Deutschland.
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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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Acquasaliente L, De Filippis V. The Role of Proteolysis in Amyloidosis. Int J Mol Sci 2022; 24:ijms24010699. [PMID: 36614141 PMCID: PMC9820691 DOI: 10.3390/ijms24010699] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 01/04/2023] Open
Abstract
Amyloidoses are a group of diseases associated with deposits of amyloid fibrils in different tissues. So far, 36 different types of amyloidosis are known, each due to the misfolding and accumulation of a specific protein. Amyloid deposits can be found in several organs, including the heart, brain, kidneys, and spleen, and can affect single or multiple organs. Generally, amyloid-forming proteins become prone to aggregate due to genetic mutations, acquired environmental factors, excessive concentration, or post-translational modifications. Interestingly, amyloid aggregates are often composed of proteolytic fragments, derived from the degradation of precursor proteins by yet unidentified proteases, which display higher amyloidogenic tendency compared to precursor proteins, thus representing an important mechanism in the onset of amyloid-based diseases. In the present review, we summarize the current knowledge on the proteolytic susceptibility of three of the main human amyloidogenic proteins, i.e., transthyretin, β-amyloid precursor protein, and α-synuclein, in the onset of amyloidosis. We also highlight the role that proteolytic enzymes can play in the crosstalk between intestinal inflammation and amyloid-based diseases.
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Affiliation(s)
- Laura Acquasaliente
- Correspondence: (L.A.); (V.D.F.); Tel.: +39-0498275703 (L.A.); +39-0498275698 (V.D.F.)
| | - Vincenzo De Filippis
- Correspondence: (L.A.); (V.D.F.); Tel.: +39-0498275703 (L.A.); +39-0498275698 (V.D.F.)
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Maisuradze N, Ghanie N, Kurnick A, Gooden M, Ahmed R. Decompensated Heart Failure as the Initial Presentation of Multiple Myeloma: A Case Report. Cureus 2022; 14:e29658. [PMID: 36320971 PMCID: PMC9612592 DOI: 10.7759/cureus.29658] [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] [Accepted: 09/27/2022] [Indexed: 11/24/2022] Open
Abstract
Amyloid deposition in the setting of multiple myeloma (MM) is a well-documented phenomenon. In this paper, we present the rare case of a 62-year-old male who presented with decompensated heart failure in the setting of cardiac amyloid deposition as the initial presentation of MM. The patient presented to the emergency department with two weeks of worsening lower extremity edema. Laboratory exam revealed elevated troponin I, elevated B-type natriuretic peptide (BNP), macrocytosis, increased urine protein/creatinine ratio, and a monoclonal peak on both serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP). Transthoracic echocardiogram (TTE) revealed findings suggestive of amyloidosis. Abdominal fat pad biopsy confirmed amyloid deposition. The patient did not have other symptoms typically seen in multiple myeloma, such as fatigue or weakness, bone pain, or weight loss. In conclusion, we present a rare case of decompensated heart failure in the setting of amyloidosis as the initial presentation of multiple myeloma.
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Lisi DD, Di Caccamo L, Damerino G, Portelli MC, Comparato F, Stefano VD, Brighina F, Corrado E, Galassi AR, Novo G. Effectiveness and Safety of oral anticoagulants in cardiac amyloidosis: lights and shadows. Curr Probl Cardiol 2022:101188. [DOI: 10.1016/j.cpcardiol.2022.101188] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 03/22/2022] [Indexed: 12/18/2022]
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Saeed S, Saad JM, Ahmed AI, Han Y, Al-Mallah MH. The utility of positron emission tomography in cardiac amyloidosis. Heart Fail Rev 2021; 27:1531-1541. [PMID: 34743267 DOI: 10.1007/s10741-021-10183-w] [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] [Accepted: 10/14/2021] [Indexed: 10/19/2022]
Abstract
Cardiac amyloidosis, characterized by progressive restrictive cardiomyopathy, presents unusual diagnostic challenges. Conventional cardiac scintigraphy has shown limited utility in the quantification of disease burden and serial follow-up of cardiac amyloidosis. The advent of specialized positron emission tomography with specific amyloid-binding radiotracers has the potential to change currently employed diagnostic algorithms for the imaging of cardiac amyloidosis. This review aims to discuss the diagnostic utility of amyloid-binding radiotracers, including Pittsburg compound B, florbetapir, florbetapan, and sodium fluoride. These tracers have promising potential for the early detection of the particular type of cardiac amyloidosis, pursuing relevant medical intervention, assessing amyloid burden, monitoring treatment response, and overall prognostication.
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Affiliation(s)
- Subha Saeed
- Crozer Keystone Health System, Upland, PA, USA
| | - Jean Michel Saad
- Houston Methodist Debakey Heart & Vascular Center, Houston, TX, USA
| | | | - Yushui Han
- Houston Methodist Debakey Heart & Vascular Center, Houston, TX, USA
| | - Mouaz H Al-Mallah
- Houston Methodist Debakey Heart & Vascular Center, Houston, TX, USA. .,Weill Cornell Medical College, New York City, NY, USA.
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Pidello S, Simonato E, Orzan F, Frea S, Barreca A, Rinaldi M, Boffini M. Interventricular Septal Rupture in a 62-Year-Old Man With Familial Amyloid Polyneuropathy. Tex Heart Inst J 2021; 47:302-305. [PMID: 33472226 DOI: 10.14503/thij-18-6799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Cardiac involvement in familial amyloid polyneuropathy consists of arrhythmias, conduction disturbances, and heart failure. To our knowledge, heart rupture has never been described in association with this condition. We report the case of a 62-year-old man with a 6-year history of refractory familial amyloid polyneuropathy who underwent liver transplantation. The operation was complicated by severe hypotension because the neuropathy involved the autonomic system. Perioperatively, the patient had a myocardial infarction, and during the next 10 days, a complete interventricular septal rupture developed, resulting in a systemic-to-pulmonary shunt. Coronary angiographic findings were normal. However, the shunt caused unstable hemodynamics, resulting in cardiogenic shock. An attempt to close the rupture percutaneously failed. The patient underwent successful heart transplantation 50 days later. Macroscopic examination of the explanted heart showed thickening of both ventricles, septal rupture, and a gray scar in the interventricular septum around the cavity. Histopathologic examination revealed intramural amyloid angiopathy. Our case shows that heart rupture can occur in patients with familial amyloid polyneuropathy who have no history of obstructive coronary artery disease, perhaps as a result of tissue fragility caused by amyloid angiopathy. Therefore, autonomic disturbances should be regarded with concern and promptly treated in the perioperative period.
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Affiliation(s)
- Stefano Pidello
- Division of Cardiology, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Erika Simonato
- Division of Cardiac Surgery, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Fulvio Orzan
- Division of Cardiology, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Simone Frea
- Division of Cardiology, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Antonella Barreca
- Division of Pathology, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Mauro Rinaldi
- Division of Cardiac Surgery, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
| | - Massimo Boffini
- Division of Cardiac Surgery, Città della Salute e della Scienza, University Hospital of Torino, 10126 Torino, Italy
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Gudkova AY, Lapekin SV, Bezhanishvili TG, Trukshina MA, Davydova VG, Krutikov AN, Kulikov AN, Streltsova AA, Andreeva SE, Grozov RV, Poliakova AA, Kostareva AA, Salogub GN, Shlyakhto EV. AL-amyloidosis with cardiac involvement. Diagnostic capabilities of non-invasive methods. TERAPEVT ARKH 2021; 93:487-496. [DOI: 10.26442/00403660.2021.04.200689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 01/15/2023]
Abstract
There are presented the literature data and a description of the clinical course of the disease in isolated/predominant cardiac amyloidosis. Amyloid cardiomyopathy is the most common phenocopy of hypertrophic cardiomyopathy. The modern possibilities of non-invasive diagnostics using osteoscintigraphy for the differential diagnosis between amyloid cardiomyopathy caused by AL- and transthyretin amyloidosis are described in detail.
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14
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Lin XY, Pan D, Sang LX, Chang B. Primary localized gastric amyloidosis: A scoping review of the literature from clinical presentations to prognosis. World J Gastroenterol 2021; 27:1132-1148. [PMID: 33828390 PMCID: PMC8006099 DOI: 10.3748/wjg.v27.i12.1132] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 01/10/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023] Open
Abstract
Localized gastric amyloidosis (LGA) is a rare disease characterized by abnormal extracellular deposition of amyloid protein restricted to the stomach and it is confirmed by positive results of Congo red staining. Over decades, only a few cases have been reported and studies or research focusing on it are few. Although LGA has a low incidence, patients may suffer a lot from it and require proper diagnosis and management. However, the pathology of LGA remains unknown and no overall review of LGA from its presentations to its prognosis has been published. Patients with LGA are often asymptomatic or manifest atypical symptoms, making it difficult to differentiate from other gastrointestinal diseases. Here, we report the case of a 70-year-old woman with LGA and provide an overview of case reports of LGA available to us. Based on that, we conclude current concepts of clinical manifestations, diagnosis, treatment, and prognosis of LGA, aiming at providing a detailed diagnostic procedure for clinicians and promoting the guidelines of LGA. In addition, a few advanced technologies applied in amyloidosis are also discussed in this review, aiming at providing clinicians with a reference of diagnostic process. With this review, we hope to raise awareness of LGA among the public and clinicians.
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Affiliation(s)
- Xin-Yu Lin
- Department of Neurology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Yilmaz A, Bauersachs J, Bengel F, Büchel R, Kindermann I, Klingel K, Knebel F, Meder B, Morbach C, Nagel E, Schulze-Bahr E, Aus dem Siepen F, Frey N. Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK). Clin Res Cardiol 2021; 110:479-506. [PMID: 33459839 PMCID: PMC8055575 DOI: 10.1007/s00392-020-01799-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022]
Abstract
Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.
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Affiliation(s)
- A Yilmaz
- Sektion für Herzbildgebung, Klinik für Kardiologie, Universitätsklinikum Münster, Von-Esmarch-Str. 48, 48149, Münster, Germany.
| | - J Bauersachs
- Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - F Bengel
- Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Hannover, Germany
| | - R Büchel
- Klinik für Nuklearmedizin, Universitätsspital Zürich, Zurich, Switzerland
| | - I Kindermann
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Germany
| | - K Klingel
- Institut für Pathologie und Neuropathologie, Universität Tübingen, Tübingen, Germany
| | - F Knebel
- Medizinische Klinik m.S. Kardiologie und Angiologie, Charite Universitätsmedizin Berlin Campus Mitte, Berlin, Germany
| | - B Meder
- Klinik für Innere Medizin III, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - C Morbach
- Klinik für Innere Medizin III, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - E Nagel
- Interdisziplinäres Amyloidosezentrum Nordbayern, Deutsches Zentrum für Herzinsuffizienz, Medizinische Klinik I der Universität Würzburg, Würzburg, Germany
| | - E Schulze-Bahr
- Institut für Experimentelle und translationale kardiovaskuläre Bildgebung, Universitätsklinikum Frankfurt, Frankfurt, Germany
| | - F Aus dem Siepen
- Institut für Genetik von Herzerkrankungen (IfGH), Universitätsklinikum Münster, Münster, Germany
| | - N Frey
- Klinik für Innere Medizin III, Schwerpunkt Kardiologie und Angiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.,Kommission für Klinische Kardiovaskuläre Medizin, Deutsche Gesellschaft für Kardiologie, Düsseldorf, Germany
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16
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Sharma S, Sonny A, Dalia AA, Karamchandani K. Acute heart failure after liver transplantation: A narrative review. Clin Transplant 2020; 34:e14079. [PMID: 32941661 DOI: 10.1111/ctr.14079] [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: 06/30/2020] [Revised: 08/06/2020] [Accepted: 08/27/2020] [Indexed: 11/27/2022]
Abstract
Acute heart failure (AHF) is an under recognized yet potentially lethal complication after liver transplantation (LT) surgery. The increase in incidence of liver transplantation amongst high-risk patients and the leniency in the criteria for transplantation, predisposes these patients to postoperative AHF and the antecedent morbidity and mortality. The inability of conventional preoperative cardiovascular testing to accurately identify patients at risk for post-LT AHF poses a considerable challenge to clinicians caring for these patients. Even if high-risk patients are identified, there is considerable ambiguity in the candidacy for transplantation as well as optimization strategies that could potentially prevent the development of AHF in the postoperative period. The intraoperative and postoperative management of patients who develop AHF is also challenging and requires a well-coordinated multidisciplinary approach. The use of mechanical circulatory support in patients with refractory heart failure has the potential to improve outcomes but its use in this complex patient population can be associated with significant complications and requires a stringent risk-benefit analysis on a case-by-case basis.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA
| | - Abraham Sonny
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Adam A Dalia
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kunal Karamchandani
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA
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17
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Hoffman JE, Dempsey NG, Sanchorawala V. Systemic Amyloidosis Caused by Monoclonal Immunoglobulins: Soft Tissue and Vascular Involvement. Hematol Oncol Clin North Am 2020; 34:1099-1113. [PMID: 33099427 DOI: 10.1016/j.hoc.2020.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Clinical features of soft tissue amyloid light-chain (AL) amyloidosis include macroglossia, arthropathy, muscle pseudohypertrophy, skin plaques, and carpal tunnel syndrome. Vascular manifestations of AL amyloid include periorbital ecchymosis, jaw or limb claudication, and even myocardial infarction caused by occlusion of small vessel coronary arteries. Some of these features, such as macroglossia, periorbital ecchymosis, and the so-called shoulder-pad sign, are pathognomonic for AL amyloidosis. These findings may be the initial presenting features of the disease, and the recognition of these red flag symptoms is very important for the diagnosis and early intervention on the underlying plasma cell disease.
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Affiliation(s)
- James E Hoffman
- Department of Medicine, Division of Hematology, University of Miami/Sylvester Comprehensive Cancer Center, 1475 Northwest 12th Avenue, Miami, FL 33136, USA
| | - Naomi G Dempsey
- Department of Medicine, Division of Hematology, University of Miami/Sylvester Comprehensive Cancer Center, 1475 Northwest 12th Avenue, Miami, FL 33136, USA
| | - Vaishali Sanchorawala
- Boston University School of Medicine and Boston Medical Center, 72 East Concord Street, K-503, Boston, MA 02118, USA.
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18
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Gatti M, Carisio A, D'Angelo T, Darvizeh F, Dell'Aversana S, Tore D, Centonze M, Faletti R. Cardiovascular magnetic resonance in myocardial infarction with non-obstructive coronary arteries patients: A review. World J Cardiol 2020; 12:248-261. [PMID: 32774777 PMCID: PMC7383353 DOI: 10.4330/wjc.v12.i6.248] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/13/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
The diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) necessitates documentation of an acute myocardial infarction (AMI), non-obstructive coronary arteries, using invasive coronary angiography or coronary computed tomography angiography and no clinically overt cause for AMI. Historically patients with MINOCA represent a clinical dilemma with subsequent uncertain clinical management. Differential diagnosis is crucial to choose the best therapeutic option for ischemic and non-ischemic MINOCA patients. Cardiovascular magnetic resonance (CMR) is able to analyze cardiac structure and function simultaneously and provides tissue characterization. Moreover, CMR could identify the cause of MINOCA in nearly two-third of patients providing valuable information for clinical decision making. Finally, it allows stratification of patients with worse outcomes which resulted in therapeutic changes in almost half of the patients. In this review we discuss the features of CMR in MINOCA; from exam protocols to imaging findings.
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Affiliation(s)
- Marco Gatti
- Faletti Riccardo, Department of Surgical Sciences, University of Turin, Turin 10126, Italy.
| | - Andrea Carisio
- Faletti Riccardo, Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Tommaso D'Angelo
- Department of Biomedical Sciences and Morphological and Functional Imaging, "G. Martino" University Hospital Messina, Messina 98100, Italy
| | - Fatemeh Darvizeh
- Faletti Riccardo, Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Serena Dell'Aversana
- Department of advanced biomedical sciences, University of Naples Federico II, Naples 80138, Italy
| | - Davide Tore
- Faletti Riccardo, Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Maurizio Centonze
- Department of Diagnostic Imaging, APSS di Trento, Trento 38123, Italy
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Suleiman S, Coughlan JJ, Moore D. Cardiac amyloidosis presenting with recurrent ischaemic strokes. BMJ Case Rep 2020; 13:e231910. [PMID: 32094234 PMCID: PMC7046391 DOI: 10.1136/bcr-2019-231910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2020] [Indexed: 01/03/2023] Open
Abstract
A 72-year-old man presented to our service with sudden onset right-sided weakness, aphasia and gaze palsy with diplopia. CT angiogram demonstrated an acute thrombotic occlusion of the distal basilar artery, a basilar infarct and the patient underwent successful thrombectomy. ECG and telemetry demonstrated slow atrial fibrillation (AF). His transthoracic echocardiogram (TTE) showed a reduced ejection fraction of 25% with global hypo-kinesis, a dilated left ventricle (LV) and LV hypertrophy (LVH). Repeat TTE appeared suspicious for an infiltrative cardiomyopathy with LVH and a speckled appearance to the myocardium. Approximately 10 months later, he suffered another ischaemic stroke post-elective cardioversion for AF while on anticoagulation. Cardiac MRI demonstrated areas of delayed gadolinium enhancement consistent with amyloidosis. Fat pad biopsy was positive for amyloidosis. Our patient has made an excellent recovery from the ischaemic strokes and is being managed in our heart failure clinic.
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Affiliation(s)
- Suleiman Suleiman
- Department of Cardiology, Tallaght University Hospital, Dublin, Ireland
| | | | - David Moore
- Department of Cardiology, Tallaght University Hospital, Dublin, Ireland
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20
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Di Giovanni B, Gustafson D, Adamson MB, Delgado DH. Hiding in Plain Sight: Cardiac Amyloidosis, an Emerging Epidemic. Can J Cardiol 2019; 36:373-383. [PMID: 32145865 DOI: 10.1016/j.cjca.2019.12.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/09/2019] [Accepted: 12/09/2019] [Indexed: 12/13/2022] Open
Abstract
Amyloidosis is a term used to describe a group of rare heterogeneous diseases that ultimately result in the deposition and accumulation of misfolded proteins. These misfolded proteins, known as amyloids, are associated with a variety of precursor proteins that have amyloidogenic potential. Ultimately, the specific type of amyloidosis is dependent on multiple factors including genetic variability of precursor proteins and the tissue or organ in which the amyloid accumulates. Several types of amyloid have a predilection for the heart and thus contribute to cardiac amyloidosis, a major cause of restrictive cardiomyopathy. Individuals with cardiac amyloidosis present clinically with heart failure with preserved ejection fraction. Although improved diagnostics and increased awareness of cardiac amyloidosis have led to a relative increase in diagnosis, cardiac amyloidosis remains an underrecognized and underdiagnosed cause of heart failure with preserved ejection fraction. It is essential to properly identify cases of cardiac amyloidosis and determine the pathology responsible for the formation of amyloid to appropriately provide management. This review aims to encourage physician awareness of cardiac amyloidosis by focusing on clinical presentation and the distinctions between types. Furthermore, epidemiology is central to understanding the affected demographics and sometimes hereditary nature of the disease. Improved understanding of cardiac amyloidosis will ideally lead to earlier diagnosis and interventions to improve patient outcomes.
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Affiliation(s)
- Bennett Di Giovanni
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
| | - Dakota Gustafson
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Mitchell B Adamson
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Diego H Delgado
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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22
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Taiwo AA, Alapati L, Movahed A. Cardiac amyloidosis: A case report and review of literature. World J Clin Cases 2019; 7:742-752. [PMID: 30968039 PMCID: PMC6448069 DOI: 10.12998/wjcc.v7.i6.742] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/12/2019] [Accepted: 02/18/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cardiac amyloidosis, a disease caused by the precipitation of amyloid proteins in the myocardial extracellular matrix has been historically difficult to diagnose due to lack of specific clinical manifestations and necessity of biopsy to demonstrate amyloid deposition. However, advances in cardiovascular imaging techniques have facilitated earlier recognition of this disease. In addition, while once thought of as incurable, treatment strategies are emerging for cardiac amyloidosis, making early diagnosis essential. CASE SUMMARY We outline the case of a 73 years old African American female who was admitted with sudden onset shortness of breath and found to be in cardiogenic shock. Cardiac amyloidosis was suspected due to discordance between electrocardiogram and echocardiogram findings and this was subsequently confirmed with the aid of scintigraphy and an endomyocardial biopsy. CONCLUSION Our objective is to highlight the diagnostic evaluation and clinical implications of cardiac amyloidosis.
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Affiliation(s)
- Adeyemi Adedamola Taiwo
- Department of Internal Medicine, East Carolina University, Greenville, NC 27834, United States
| | - Lavanya Alapati
- Department of Cardiovascular Sciences, East Carolina Heart Institute, East Carolina University, Greenville, NC 27834, United States
| | - Assad Movahed
- Department of Cardiovascular Sciences, East Carolina Heart Institute, East Carolina University, Greenville, NC 27834, United States
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23
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Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 2017; 28:10-21. [PMID: 28739313 DOI: 10.1016/j.tcm.2017.07.004] [Citation(s) in RCA: 227] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 07/06/2017] [Accepted: 07/07/2017] [Indexed: 12/20/2022]
Abstract
The amyloidoses are a group of systemic diseases characterized by organ deposition of misfolded protein fragments of diverse origins. The natural history of the disease, involvement of other organs, and treatment options vary significantly based on the protein of origin. In AL amyloidosis, amyloid protein is derived from immunoglobulin light chains, and most often involves the kidneys and the heart. ATTR amyloidosis is categorized as mutant or wild-type depending on the genetic sequence of the transthyretin (TTR) protein produced by the liver. Wild-type ATTR amyloidosis mainly involves the heart, although the reported occurrence of bilateral carpal tunnel syndrome, spinal stenosis and biceps tendon rupture in these patients speaks to more generalized protein deposition. Mutant TTR is marked by cardiac and/or peripheral nervous system involvement. Cardiac involvement is associated with symptoms of heart failure, and dictates the clinical course of the disease. Cardiac amyloidosis can be diagnosed noninvasively by echocardiography, cardiac MRI, or nuclear scintigraphy. Endomyocardial biopsy may be needed in the case of equivocal imaging findings or discordant data. Treatment is aimed at relieving congestive symptoms and targeting the underlying amyloidogenic process. This includes anti-plasma cell therapy in AL amyloidosis, and stabilization of the TTR tetramer or inhibition of TTR protein production in ATTR amyloidosis. Cardiac transplantation can be considered in highly selected patients in tandem with therapy aimed at suppressing the amyloidogenic process, and appears associated with durable long-term survival.
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Affiliation(s)
- Omar K Siddiqi
- Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, 88 East Newton Street, Boston, MA; Amyloidosis Center, Boston University School of Medicine, Boston Medical Center, Boston, MA
| | - Frederick L Ruberg
- Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, 88 East Newton Street, Boston, MA; Amyloidosis Center, Boston University School of Medicine, Boston Medical Center, Boston, MA; Department of Radiology, Boston University School of Medicine, Boston Medical Center, Boston, MA.
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24
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Li R, Yang ZG, Wen LY, Liu X, Xu HY, Zhang Q, Guo YK. Regional myocardial microvascular dysfunction in cardiac amyloid light-chain amyloidosis: assessment with 3T cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2016; 18:16. [PMID: 27048459 PMCID: PMC4822254 DOI: 10.1186/s12968-016-0240-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 03/29/2016] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Coronary microvascular dysfunction is highly prevalent in patients with amyloid light-chain (AL) cardiac amyloidosis (AL-CA). The aim of this study was to clarify the feasibility of first-pass perfusion imaging using 3 T cardiovascular magnetic resonance (CMR) for evaluating the difference in left ventricular (LV) regional myocardial microvascular function among normal subjects and in patients with AL-CA. The amyloidosis patients were classified into those with impaired systolic function [LV ejection fraction (LVEF) < 50 %] and those with preserved systolic function. METHODS In total, 32 patients with biopsy-proven AL-CA, including 11 AL-CA patients with systolic dysfunction, 21 AL-CA patients with preserved systolic function, and 25 healthy subjects, underwent CMR examination. LV regional myocardial perfusion parameters included upslope, time to maximum signal intensity (TTM) and max signal intensity (MaxSI) were compared among the three patient groups. Receiver operating characteristic analysis was performed to determine whether perfusion parameters could be used in discriminating regional myocardial microvascularity between AL-CA patients and normal subjects. RESULTS The patients with AL-CA had significantly reduced first-pass perfusion upslope and MaxSI, and increased TTM compared with the normal subjects (all P < 0.01). Compared with the patients with AL-CA and preserved LVEF, the patients with AL-CA and impaired systolic function had a longer TTM in the basal (47.05 ± 16.59 vs. 39.68 ± 19.11; P = 0.002) and mid-ventricular (44.61 ± 16.34 vs. 37.74 ± 18.25; P = 0.002) segments; lower upslope in the basal (2.41 ± 1.32 vs. 3.60 ± 1.68; P < 0.0001), mid-ventricular (2.82 ± 1.34 vs. 4.15 ± 2.02; P < 0.0001), and apical (3.71 ± 1.38 vs. 4.97 ± 2.55; P = 0.004) segments; and lower MaxSI (31.67 ± 15.23 vs. 37.96 ± 11.15; P < 0.0001) in the basal segment. The ROC curve analysis revealed that the first-pass upslope, TTM, and MaxSI may be used as indicators for differentiating microcirculation between AL-CA patients with preserved or impaired systolic function and normal subjects. CONCLUSIONS The differences in LV regional myocardial microvascular function among normal subjects, AL-CA patients with systolic dysfunction, and AL-CA patients with preserved systolic function can be monitored using first-pass perfusion CMR.
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Affiliation(s)
- Rui Li
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
- />Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Shunqing District, Nanchong, Sichuan 637000 China
| | - Zhi-gang Yang
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
- />National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 17# Section 3 South Renmin Road, Chengdu, Sichuan 610041 China
| | - Lin-yi Wen
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
| | - Xi Liu
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
| | - Hua-yan Xu
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
- />National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 17# Section 3 South Renmin Road, Chengdu, Sichuan 610041 China
| | - Qin Zhang
- />Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 China
| | - Ying-kun Guo
- />Department of Radiology, West China Second University Hospital, Sichuan University, 20# Section 3 South Renmin Road, Chengdu, Sichuan 610041 China
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Current indications, strategies, and outcomes with cardiac transplantation for cardiac amyloidosis and sarcoidosis. Curr Opin Organ Transplant 2015; 20:584-92. [DOI: 10.1097/mot.0000000000000229] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
Amyloidosis refers to a group of rare but potentially fatal, protein misfolding diseases. The heart is frequently involved in the most common types, that is, immunoglobulin light chain and transthyretin amyloidosis and is the single most important predictor of patient outcomes. A major limitation in improving patient outcomes, in addition to developing novel therapeutics, is the late diagnosis of the disease. Once suspected, an organ for biopsy should be targeted and the amyloid type should be identified by mass spectrometry. An endomyocardial biopsy should be offered if cardiac involvement is in doubt. Echocardiography, MRI and nuclear imaging can provide valuable diagnostic and prognostic information and can secure the diagnosis if amyloid has been identified in an extracardiac tissue.
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Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia. Heart Vessels 2015; 31:990-5. [PMID: 25794983 DOI: 10.1007/s00380-015-0658-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 03/06/2015] [Indexed: 12/27/2022]
Abstract
Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient.
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Dorbala S, Vangala D, Bruyere J, Quarta C, Kruger J, Padera R, Foster C, Hanley M, Di Carli MF, Falk R. Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis. JACC-HEART FAILURE 2014; 2:358-67. [PMID: 25023822 DOI: 10.1016/j.jchf.2014.03.009] [Citation(s) in RCA: 155] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Revised: 02/24/2014] [Accepted: 03/07/2014] [Indexed: 11/18/2022]
Abstract
OBJECTIVES The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. BACKGROUND Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD). METHODS Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product. RESULTS Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function. CONCLUSIONS Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.
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Affiliation(s)
- Sharmila Dorbala
- Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Divya Vangala
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - John Bruyere
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Christina Quarta
- Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jenna Kruger
- Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Robert Padera
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Courtney Foster
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Michael Hanley
- Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Marcelo F Di Carli
- Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Rodney Falk
- Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Mohty D, Damy T, Cosnay P, Echahidi N, Casset-Senon D, Virot P, Jaccard A. Cardiac amyloidosis: updates in diagnosis and management. Arch Cardiovasc Dis 2013; 106:528-40. [PMID: 24070600 DOI: 10.1016/j.acvd.2013.06.051] [Citation(s) in RCA: 166] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2013] [Revised: 06/24/2013] [Accepted: 06/24/2013] [Indexed: 12/15/2022]
Abstract
Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment.
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Affiliation(s)
- Dania Mohty
- Service de cardiologie, pôle cœur-poumon-rein, hôpital Dupuytren, CHU de Limoges, 87042 Limoges, France; Service d'hématologie clinique et de thérapie cellulaire, pôle onco-hématologie, centre national de référence pour l'amylose AL et autres maladies de dépôts d'immunoglobulines monoclonales, CHU de Limoges, Limoges, France.
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Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjö L, Kero T, Långström B, Granstam SO, Rosengren S, Vedin O, Wassberg C, Wikström G, Westermark P, Sörensen J. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med 2012; 54:213-20. [PMID: 23238792 DOI: 10.2967/jnumed.111.102053] [Citation(s) in RCA: 195] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-(11)C]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole ((11)C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of (11)C-PIB PET in systemic amyloidosis affecting the heart. METHODS Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type-and healthy volunteers (n = 5) were investigated with PET/CT using (11)C-PIB to study cardiac amyloid deposits and with (11)C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. RESULTS Myocardial (11)C-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in (11)C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with (11)C-PIB. No correlation between (11)C-PIB retention index and myocardial blood flow as measured with (11)C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient. CONCLUSION (11)C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.
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Affiliation(s)
- Gunnar Antoni
- Platform for Preclinical PET, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
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Luigetti M, Papacci M, Bartoletti S, Marcaccio A, Romano A, Sabatelli M. AL amyloid neuropathy mimicking a chronic inflammatory demyelinating polyneuropathy. Amyloid 2012; 19:53-5. [PMID: 22292918 DOI: 10.3109/13506129.2011.650247] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Cardiac Amyloidosis: Evolving Approach to Diagnosis and Management. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2011; 13:528-42. [DOI: 10.1007/s11936-011-0147-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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