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JACC. Cardiovascular Imaging Nov 2019Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart... (Review)
Review
Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart failure, and it is the imaging modality that most often raises the suspicion of cardiac amyloidosis. Echocardiography can provide an assessment of the likelihood of cardiac amyloid infiltration versus other hypertrophic phenocopies and can assess the severity of cardiac involvement. Visualizing myocardial amyloid infiltration is challenging and, until recently, was restricted to the domain of the pathologist. Two tests are transforming this: cardiac magnetic resonance (CMR) imaging and bone scintigraphy. After the administration of contrast, CMR is highly sensitive and specific for the 2 main types of ventricular myocardial amyloidosis, light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). CMR structural and functional assessment combined with tissue characterization can redefine cardiac involvement by tracking different disease processes, ranging from amyloid infiltration, to the myocardial response associated with amyloid deposition, through the visualization and quantification of myocardial edema and myocyte response. Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies; it has transformed the diagnostic pathway for ATTR, allowing noninvasive diagnosis of ATTR without the need for a tissue biopsy in the majority of patients. CMR with tissue characterization and bone scintigraphy are rewriting disease understanding, classification, and definition, and leading to a change in patient care.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diagnosis, Differential; Extracellular Space; Fibrosis; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Radionuclide Imaging; Reproducibility of Results; Ventricular Remodeling
PubMed: 31422120
DOI: 10.1016/j.jcmg.2019.06.023 -
Hematology/oncology Clinics of North... Dec 2020Early diagnosis of AL amyloidosis and appreciation of the nutritional and coagulation abnormalities associated with liver and gastrointestinal involvement are critically... (Review)
Review
Early diagnosis of AL amyloidosis and appreciation of the nutritional and coagulation abnormalities associated with liver and gastrointestinal involvement are critically important in the treatment and management. In cases of severe malabsorption total parenteral nutrition can be extremely helpful as a bridge to organ improvement. Rarely the use of antifibrinolytic agents such as oral aminocaproic acid with transfusion support may control severe bleeding in patients with coagulation abnormalities. It is important to keep in mind that organ improvement should follow in lag phase after the reduction in the pathologic free light chain with treatment. Closely following light chain levels may permit brief holidays from treatment and enable periods of recovery before resuming therapy in patients with prompt early and deep hematologic responses.
Topics: Adult; Female; Gastrointestinal Diseases; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Liver Diseases; Male; Middle Aged
PubMed: 33099425
DOI: 10.1016/j.hoc.2020.09.001 -
Acta Haematologica 2020Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different... (Review)
Review
Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different organs. Prompt treatment directed to the underlying plasma cell clone is crucial in order to achieve a rapid, deep and durable hematologic response. The decrease in the production of the amyloidogenic light chains is a required condition to obtain the organ response, which is commonly delayed. Meanwhile, supportive treatment is aimed to maintain quality of life of these patients and preserve their involved organs' function. From simple measures, such as salt restriction or compressive stockings, to very complex interventions, such as heart transplantation in very selected patients with isolated severe cardiac involvement, this supportive care is essential and has to be necessarily included in the multidisciplinary management of this disease.
Topics: Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Specificity; Palliative Care
PubMed: 32235118
DOI: 10.1159/000506760 -
Journal of UOEH 2021A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24...
A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.
Topics: Aged; Amyloidosis; Biopsy; Hepatocyte Growth Factor; Humans; Immunoglobulin Light-chain Amyloidosis; Stomach
PubMed: 34092767
DOI: 10.7888/juoeh.43.227 -
Internal and Emergency Medicine Oct 2023Cardiac amyloidosis (CA) is an uncommon, progressive, and fatal disease; the two main forms that can affect the heart are transthyretin CA and light chain CA (AL-CA).... (Review)
Review
Cardiac amyloidosis (CA) is an uncommon, progressive, and fatal disease; the two main forms that can affect the heart are transthyretin CA and light chain CA (AL-CA). AL-CA is a medical urgency for which a diagnostic delay can be catastrophic for patients' outcome. In this manuscript, we focus on the pearls and pitfalls that are relevant to achieve a correct diagnosis and to avoid diagnostic and therapeutical delays. Through the aid of three unfortunate clinical cases, some fundamental diagnostic aspects are addressed, including the following: first, a negative bone scintigraphy does not exclude CA, with patients with AL-CA frequently showing no or mild cardiac uptake, and its execution should not delay hematological tests; second, fat pad biopsy does not have a 100% sensitivity for AL amyloidosis and, if negative, further investigations should be performed, particularly if the pre-test probability is high. Third, Congo Red staining is not sufficient to reach a definitive diagnosis and amyloid fibrils typing with mass spectrometry, immunohistochemistry, or immunoelectron microscopy is crucial. To achieve a timely and correct diagnosis, all the necessary investigations must be performed, always considering the yield and diagnostic accuracy of each examination.
Topics: Humans; Delayed Diagnosis; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Biopsy; Congo Red; Cardiomyopathies
PubMed: 37338717
DOI: 10.1007/s11739-023-03335-3 -
ESC Heart Failure Feb 2022The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review... (Review)
Review
The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review summarizes main evidence from literature with clinical perspective. The rate of thromboembolic events is as high as 5-10% amyloidosis patients, at least in patients with cardiac involvement, with deleterious impact on prognosis. The most known pro-thrombotic factors are heart failure, atrial fibrillation, and atrial myopathy. Atrial fibrillation could occur in 20% to 75% of systemic amyloidosis patients. Cardiac thrombi are frequently observed in patients, particularly in immunoglobulin light chains (AL) amyloidosis, up to 30%, and it is advised to look for them systematically before cardioversion. In AL amyloidosis, nephrotic syndrome and the use of immunomodulatory drugs also favour thrombosis. On the other hand, the bleeding risk increases because of frequent amyloid digestive involvement as well as factor X deficiency, renal failure, and increased risk of dysautonomia-related fall.
Topics: Amyloid; Amyloidosis; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Thromboembolism
PubMed: 34784656
DOI: 10.1002/ehf2.13701 -
Hematology/oncology Clinics of North... Dec 2020The spectrum of immunoglobulin paraprotein-associated diseases requiring therapy extends beyond multiple myeloma and AL amyloidosis. Awareness of these is essential in... (Review)
Review
The spectrum of immunoglobulin paraprotein-associated diseases requiring therapy extends beyond multiple myeloma and AL amyloidosis. Awareness of these is essential in ensuring timely accurate diagnosis and appropriate treatment. As most paraprotein-associated diseases are fairly uncommon, therapeutic decisions must often be made in the absence of data from randomized controlled trials. Treatment is generally directed at the underlying clonal cell population. This review focuses on the spectrum of the less common paraprotein-associated disorders. In most instances, the monoclonal immunoglobulin plays a direct role in the pathophysiology of the disease course; in a select few, the paraprotein may be a disease marker.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma
PubMed: 33099435
DOI: 10.1016/j.hoc.2020.07.002 -
Acta Haematologica 2020The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional... (Review)
Review
The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11;14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.
Topics: Biomarkers; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunoglobulin Light-chain Amyloidosis; Recurrence; Risk Factors; Treatment Outcome
PubMed: 32353854
DOI: 10.1159/000507072 -
Acta Haematologica 2020Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different... (Review)
Review
Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the importance of multidisciplinary care.
Topics: Amyloidosis; Cardiomyopathies; Combined Modality Therapy; Disease Management; Disease Susceptibility; Heart Function Tests; Humans; Immunoglobulin Light-chain Amyloidosis; Phenotype
PubMed: 32408301
DOI: 10.1159/000506919 -
Mayo Clinic Proceedings Jun 2021
Topics: Amyloidosis; Consensus; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 34088409
DOI: 10.1016/j.mayocp.2021.04.014