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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 -
European Heart Journal Dec 2022To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological...
AIMS
To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors.
METHODS AND RESULTS
In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01).
CONCLUSIONS
Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.
Topics: Humans; Amyloidosis; Magnetic Resonance Imaging; Immunoglobulin Light-chain Amyloidosis; Heart; Prognosis; Magnetic Resonance Spectroscopy; Myocardium; Magnetic Resonance Imaging, Cine; Predictive Value of Tests
PubMed: 36239754
DOI: 10.1093/eurheartj/ehac363 -
Journal of the American College of... Nov 2021
Topics: Amyloidosis; Cardiomyopathies; Humans; Phenotype
PubMed: 34823662
DOI: 10.1016/j.jacc.2021.09.857 -
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 -
Annals of Palliative Medicine Jul 2023
Topics: Humans; Amyloidosis; Intestines
PubMed: 37038081
DOI: 10.21037/apm-23-115 -
Acta Haematologica 2020Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding... (Review)
Review
Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloid-osis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloid-osis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes, similar to patients with other indications. Kidney transplantation is associated with particularly favorable outcomes in patients with amyloidosis, especially if the precursor protein has been eliminated. Overall, outcomes of solid organ transplantation are improving, but more data are needed to refine the selection criteria and the timing for organ transplantation, which should be performed in highly experienced centers involving multidisciplinary teams with close patient follow-up to detect amyloid recurrence.
Topics: Amyloidosis; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Transplantation; Treatment Outcome
PubMed: 32535598
DOI: 10.1159/000508262 -
Annals of Clinical and Translational... Dec 2023Disease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of...
OBJECTIVE
Disease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of amyloidosis, we assessed detection and typing yield of skin biopsy for amyloid in patients with confirmed systemic amyloidosis and neuropathic symptoms.
METHODS
In this case-control study, patients with transthyretin and light chain amyloidosis (ATTRv, ATTRwt, and AL) were consecutively recruited. They were sex and age-matched to three control groups (1) non-neuropathic controls (NNC), (2) monoclonal gammopathy of undetermined significance (MGUS), and (3) other neuropathic disease controls (ONC). Patients underwent a double 3 mm skin biopsy in proximal and distal leg. Amyloid index and burden, protein typing by immuno-electron microscopy, intraepidermal nerve fiber density, electroneuromyography, and clinical characteristics were analyzed.
RESULTS
We studied 15 subjects with confirmed systemic amyloidosis, 20 NNC, 18 MGUS, and 20 ONC. Amyloid was detected in 100% of patients with amyloidosis (87% in ankle and 73% in thigh). It was not detected in any of the control groups. A small fiber neuropathy was encountered in 100% of amyloidosis patients, in 80% of MGUS, and in 78% of ONC. Amyloid burden was higher in ATTRv, followed by AL and ATTRwt. The ultrastructural examination allowed the identification of the precursor protein by immunotyping in most of the cases.
INTERPRETATION
Skin biopsy is a minimally invasive test with optimal sensitivity for amyloid. It allows amyloid typing by electron microscope to identify the precursor protein. The diagnostic work up of systemic amyloidosis should include a skin biopsy.
Topics: Humans; Case-Control Studies; Small Fiber Neuropathy; Amyloidosis; Amyloid; Polyneuropathies; Peripheral Nervous System Diseases; Biopsy
PubMed: 37849451
DOI: 10.1002/acn3.51924 -
Expert Review of Proteomics Sep 2019: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is... (Review)
Review
: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is essential in determining the causative protein and initiating proper treatment. Mass spectrometry-based proteomics is currently the most sensitive and accurate means of typing amyloid. : Amyloidosis can be systemic or localized, acquired or hereditary, and can affect any organ or tissue. Diagnosis requires biopsy, histological analysis, and typing of the causative protein to determine treatment. The kidneys are the most commonly affected organ in systemic disease. Fibrinogen alpha chain amyloidosis (AFib) is the most prevalent form of hereditary renal amyloidosis. Select mutations in the fibrinogen Aα (FGA) gene lead to AFib. : Mass spectrometry is currently the most specific and sensitive method for amyloid typing. Identification of the mutated fibrinogen alpha chain can be difficult in the case of 'private' frameshift mutations, which dramatically change the sequences of the expressed fibrinogen alpha chain. A combination of expert pathologist review, mass spectrometry, and gene sequencing can allow for confident diagnosis and determination of the fibrinogen alpha chain mutated sequence.
Topics: Amyloid; Amyloidosis; Fibrinogen; Humans; Kidney; Mass Spectrometry; Mutation; Proteomics
PubMed: 31443619
DOI: 10.1080/14789450.2019.1659137 -
JACC. Cardiovascular Imaging Nov 2019Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes... (Review)
Review
Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes a major source of heart failure with excess cardiac morbidity and mortality. Myocardial fibrosis (defined as excess myocardial collagen concentration that distorts myocardial architecture) is prevalent and causes cardiac symptoms and ultimately adverse cardiac events, such as heart failure, arrhythmia, and death. Conversely, cardiac amyloidosis is far less prevalent than myocardial fibrosis but represents a more extreme form of interstitial heart disease with marked interstitial expansion, profound architectural distortion, and then rapid clinical decline. Myocardial extracellular volume measures fundamentally advance the understanding of myocardium and specifically highlights the role of the interstitium. Rather than conceptualizing myocardium as a homogenous tissue, dichotomizing the myocardium into its interstitial (including the microvasculature) and cardiomyocyte phenotypes promotes additional understanding of heart failure pathophysiology that may spur the development of more effective therapies.
Topics: Amyloidosis; Cardiomyopathies; Disease Progression; Extracellular Space; Fibrosis; Heart Failure; Humans; Myocardium; Prognosis; Ventricular Remodeling
PubMed: 31422140
DOI: 10.1016/j.jcmg.2019.04.025 -
International Journal of Molecular... Oct 2022Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses,... (Review)
Review
Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis.
Topics: Humans; Amyloidosis; Amyloid; Immunoglobulin Light-chain Amyloidosis; Amyloidogenic Proteins; Biocompatible Materials
PubMed: 36293523
DOI: 10.3390/ijms232012662