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Seminars in Nuclear Medicine Jul 2020Systemic amyloidosis is a heterogeneous group of disorders where misfolded proteins deposit in the various organs as nonbranching fibrils with a β-pleated-sheet... (Review)
Review
Systemic amyloidosis is a heterogeneous group of disorders where misfolded proteins deposit in the various organs as nonbranching fibrils with a β-pleated-sheet structure called amyloid. Extensive extracellular deposition of these amyloid fibrils eventually leads to organ dysfunction. Involvement of the heart, termed as cardiac amyloidosis, leads to heart failure if left untreated and carries high morbidity and mortality. Current interest in cardiac amyloidosis is growing rapidly thanks to the recent development of effective targeted treatment options, driving the need for better and earlier detection of the condition, which is largely underdiagnosed and far commoner than recognized. Timely diagnosis of cardiac amyloidosis is challenging, but is poised to improve with emergence of newer noninvasive imaging techniques, potentially obviating the need for endomyocardial biopsy in some patients and providing prognostic information. With recent advances in the therapeutic options for cardiac amyloidosis, an area of immense interest is the adoption of imaging as biomarkers for longitudinal assessment of disease progression and treatment response. In this article, we provide an overview of cardiac amyloidosis, discuss the role of imaging modalities in cardiac amyloidosis, and explore future directions for imaging in cardiac amyloidosis.
Topics: Amyloidosis; Biomarkers; Heart Diseases; Humans; Multimodal Imaging
PubMed: 32540027
DOI: 10.1053/j.semnuclmed.2020.01.001 -
Journal of Medical Case Reports Apr 2023Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light... (Review)
Review
BACKGROUND
Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.
CASE PRESENTATIONS
In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.
CONCLUSIONS
Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.
Topics: Male; Female; Humans; Aged; Adult; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias; Heart
PubMed: 37081462
DOI: 10.1186/s13256-023-03886-1 -
Journal of the American College of... Sep 2022
Topics: Amyloidosis; Carpal Tunnel Syndrome; Heart; Humans; Membrane Proteins; Nerve Tissue Proteins; Upper Extremity
PubMed: 36049805
DOI: 10.1016/j.jacc.2022.06.025 -
Internal and Emergency Medicine Jun 2022Cardiac amyloidosis (CA) is due to extracellular myocardial deposition of misfolded proteins resulting in severe cardiac dysfunction and death. The precursors of amyloid... (Review)
Review
Cardiac amyloidosis (CA) is due to extracellular myocardial deposition of misfolded proteins resulting in severe cardiac dysfunction and death. The precursors of amyloid fibrils, able of determining a relevant cardiac infiltration, are immunoglobulin-free light chains (AL amyloidosis) and transthyretin (TTR) (both wild and mutated types). The diagnosis of amyloidosis represents a challenge for the clinician given its rarity and its protean clinical presentation, thus an early diagnosis remains a cornerstone for the prognosis of these patients, also in light of the growing available treatments. There is great interest in identifying and applying biomarkers to help diagnose, inform prognosis, guide therapy, and serve as surrogate endpoints in these patients. In AL amyloidosis, biomarkers such as free light chains, natriuretic peptides and troponins are the most extensively studied and validated; they have proved useful in risk stratification, guiding treatment choice and monitoring hematological and organ response. A similar biomarker-based prognostic score is also proposed for ATTR amyloidosis, although studies are small and need to be validated for wild-type and mutant forms.
Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Prognosis
PubMed: 35325395
DOI: 10.1007/s11739-022-02958-2 -
European Journal of Heart Failure Feb 2021Amyloidoses are characterized by the tissue accumulation of misfolded proteins into insoluble fibrils. The two most common types of systemic amyloidosis result from the... (Review)
Review
Amyloidoses are characterized by the tissue accumulation of misfolded proteins into insoluble fibrils. The two most common types of systemic amyloidosis result from the deposition of immunoglobulin light chains (AL) and wild-type or variant transthyretin (ATTRwt/ATTRv). Cardiac involvement is the main determinant of outcome in both AL and ATTR, and cardiac amyloidosis (CA) is increasingly recognized as a cause of heart failure. In CA, circulating biomarkers are important diagnostic tools, allow to refine risk stratification at baseline and during follow-up, help to tailor the therapeutic strategy and monitor the response to treatment. Among amyloid precursors, free light chains are established biomarkers in AL amyloidosis, while the plasma transthyretin assay is currently being investigated as a tool for supporting the diagnosis of ATTRv amyloidosis, predicting outcome and monitor response to novel tetramer stabilizers or small interfering RNA drugs in ATTR CA. Natriuretic peptides (NPs) and troponins are consistently elevated in patients with AL and ATTR CA. Plasma NPs, troponins and free light chains hold prognostic significance in AL amyloidosis, and are evaluated for therapy decision-making and follow-up, while the value of NPs and troponins in ATTR is less well established. Biomarkers can be usefully integrated with clinical and imaging variables at all levels of the clinical algorithm of systemic amyloidosis, from screening to diagnosis and prognosis, and treatment tailoring.
Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Heart Failure; Humans; Prealbumin
PubMed: 33527656
DOI: 10.1002/ejhf.2113 -
The American Journal of Medicine Apr 2022Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the...
Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the manifestations of clinical disease. Meanwhile, coronavirus disease 2019 (COVID-19) is a disease caused by infection with the severe acute respiratory syndrome coronavirus 2 virus, with the potential to cause severe systemic illness and death. There is significant overlap in the demographics and comorbidities observed in AL amyloidosis and those associated with highest risk for severe morbidity and mortality due to COVID-19. This overlap creates unique challenges in caring for patients with AL amyloidosis, which are further compounded by the immunosuppressive nature of anti-plasma cell therapies, the need for frequent clinical assessments, and the exclusion of AL amyloidosis patients from initial COVID-19 vaccine trials. Herein, we highlight many of the relevant concerns related to COVID-19 and the treatment of AL amyloidosis, summarize a general approach for AL amyloidosis management amidst the ongoing COVID-19 pandemic, and discuss current guidance about COVID-19 vaccination of patients with AL amyloidosis.
Topics: Amyloidosis; COVID-19; COVID-19 Vaccines; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Pandemics
PubMed: 35081378
DOI: 10.1016/j.amjmed.2022.01.005 -
Advances in Clinical and Experimental... Feb 2022A substantial increase in the interest in transthyretin cardiac amyloidosis (ATTR-CA) is a result of the constantly growing number of patients, the use of clear... (Review)
Review
A substantial increase in the interest in transthyretin cardiac amyloidosis (ATTR-CA) is a result of the constantly growing number of patients, the use of clear diagnostic protocols and the availability of the first selective drug for these patients. This has also raised the awareness of the disease among physicians of all specialties. The topic is particularly relevant to cardiologists, who use non-invasive multimodal imaging in their daily practice. The differential diagnosis of the causes of myocardial hypertrophy includes arterial hypertension, hypertrophic cardiomyopathy, aortic stenosis (AS), athletic heart syndrome, Fabry disease, and cardiac amyloidosis (CA). It turns out that in patients with myocardial hypertrophy >15 mm, amyloidosis is the most common cause of left ventricular (LV) hypertrophy. In parallel, CA is one of the most common infiltrative diseases leading to a clinical picture that may mimic heart failure with preserved ejection fraction (HFpEF). The accumulation of amyloid in the extracellular space impairs the diastolic function of the myocardium, which is observed as the restrictive cardiomyopathy phenotype. In advanced cases, the LV systolic function is also impaired. Moreover, protein deposits contribute to the disturbances of calcium metabolism and cell metabolism as well as to cardiotoxicity, leading to edema and damage to cardiomyocytes.
Topics: Amyloidosis; Cardiomyopathies; Heart Failure; Humans; Hypertrophy, Left Ventricular; Stroke Volume; Ventricular Function, Left
PubMed: 35195962
DOI: 10.17219/acem/142252 -
Prion Dec 2021The severe course of COVID-19 causes systemic chronic inflammation and thrombosis in a wide variety of organs and tissues. The nature of these inflammations remains a...
The severe course of COVID-19 causes systemic chronic inflammation and thrombosis in a wide variety of organs and tissues. The nature of these inflammations remains a mystery, although they are known to occur against the background of a high level of cytokine production. The high level of cytokines provokes overproduction of the Serum amyloid A (SAA) protein. Moreover, the number of studies has shown that the severe COVID-19 causes SAA overproduction. The authors of these works regard a high level of SAA exclusively as a biomarker of COVID-19. However, it should be borne in mind that overproduction of SAA can cause systemic AA amyloidosis. SAA forms cytotoxic amyloid deposits in various organs and induces inflammation and thrombosis. The consequences of COVID-19 infection are surprisingly similar to the clinical picture that is observed in AA amyloidosis. Here I present the hypothesis that AA amyloidosis is a factor causing systemic complications after coronavirus disease.
Topics: Amyloidosis; Biomarkers; COVID-19; Humans; Inflammation; Serum Amyloid A Protein
PubMed: 33876719
DOI: 10.1080/19336896.2021.1910468 -
BMJ Case Reports Aug 2019In this case report, we present a healthy man who was referred for removal of subconjunctival yellow lesions found during a routine eye examination. In histopathological...
In this case report, we present a healthy man who was referred for removal of subconjunctival yellow lesions found during a routine eye examination. In histopathological examination, an amyloidosis was found. There were no remnants or new lesions during 1-year follow-up. There was no systemic involvement. Conjunctival amyloidosis is a rare diagnosis that often is overlooked. Failure to recognise conjunctival amyloidosis might lead to late diagnosis of systemic amyloidosis. This case may rise the awareness to this rare diagnosis.
Topics: Amyloidosis; Conjunctival Diseases; Humans; Male; Middle Aged
PubMed: 31371336
DOI: 10.1136/bcr-2019-230370 -
Medicina (Kaunas, Lithuania) Oct 2021Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited... (Review)
Review
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.
Topics: Amyloidosis; Colchicine; Familial Mediterranean Fever; Humans; Kidney; Kidney Diseases
PubMed: 34684086
DOI: 10.3390/medicina57101049