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Clinical Cardiology Sep 2022Transthyretin amyloid cardiomyopathy (ATTR-CM) is a debilitating and life-threatening condition with a heterogeneous clinical presentation. Recent guidelines from the... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a debilitating and life-threatening condition with a heterogeneous clinical presentation. Recent guidelines from the United States and Europe have been published to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies for patients with ATTR-CM. These guidelines highlight the importance of an early diagnosis to optimize therapeutic outcomes, specifying the use of tests and imaging techniques to allow accurate, noninvasive diagnosis of ATTR-CM. However, as regional practice variations across Asia may limit access to healthcare, availability of specific tests, and expertise in assessing diagnostic images, there is an ongoing need to provide an Asian perspective on these clinical guidelines. This review article provides practical recommendations for the diagnosis and monitoring of patients with ATTR-CM in Asia, highlighting the need for additional guidelines to support a broad and diverse population, consider differing healthcare systems and diagnostic testing availability, and provide a flexible yet robust algorithm.
Topics: Amyloid Neuropathies, Familial; Asia; Cardiomyopathies; Early Diagnosis; Humans; Monitoring, Physiologic; Prealbumin
PubMed: 35795903
DOI: 10.1002/clc.23882 -
Future Cardiology Jan 2023This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study... (Review)
Review
WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?
This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results.
WHAT DID RESEARCHERS FIND OUT?
In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study.
WHAT DO THE RESULTS MEAN?
Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. : NCT01994889 (ClinicalTrials.gov) : NCT02791230 (ClinicalTrials.gov).
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Benzoxazoles; Cardiomyopathies
PubMed: 36715498
DOI: 10.2217/fca-2022-0096 -
European Journal of Internal Medicine May 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) has been traditionally considered a rare and inexorably fatal condition. ATTR-CM now is an increasingly recognized cause... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) has been traditionally considered a rare and inexorably fatal condition. ATTR-CM now is an increasingly recognized cause of heart failure (HF) and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CM, which is now possible without recourse to endomyocardial biopsy in ≈70 % of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CM and more accurate prognostic stratification. Although radionuclide scintigraphy with 'bone' tracers has an established diagnostic value, the diagnostic performance of the bone tracers validated for non-invasive confirmation of ATTR-CM may not be equal. Characterising the wider clinical phenotype of patients with ATTR-CM has enabled identification of features with potential for earlier diagnosis such as carpal tunnel syndrome. Therapies able to slow or halt ATTR-CM progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional HF medications. Cutting-edge research in the field of antibody-mediated removal of ATTR deposits compellingly suggest that ATTR-CM is a truly reversible disorder, bringing hope for patients even with advanced disease. A wide horizon of possibilities is unfolding and awaits discovery.
Topics: Humans; Cardiomyopathies; Amyloid Neuropathies, Familial; Heart Failure; Echocardiography; Prealbumin; Magnetic Resonance Imaging
PubMed: 38184468
DOI: 10.1016/j.ejim.2024.01.001 -
Circulation Nov 2022
Topics: Humans; Prealbumin; Amyloidosis; Cognition
PubMed: 36441817
DOI: 10.1161/CIRCULATIONAHA.122.062532 -
Current Problems in Cardiology Jan 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is a mutation-based genetic disorder due to the accumulation of unstable transthyretin protein and presents with symptoms... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a mutation-based genetic disorder due to the accumulation of unstable transthyretin protein and presents with symptoms of congestive heart failure (CHF) and numerous extracardiac symptoms like carpal tunnel syndrome and neuropathy. Two subtypes of ATTR-CM are hereditary and wild-type, both of which have different risk factors, gender prevalence and major clinical symptoms. Timely usage of imaging modalities like echocardiography, cardiac magnetic imaging resonance, and cardiac scintigraphy has made it possible to suspect ATTR-CM in patients presenting with CHF. Management of ATTR-CM includes appropriate treatment for heart failure for symptomatic relief, prevention of arrhythmias and heart transplantation for nonresponders. With the recent approval of tafamidis in the successful management of ATTR-CM, numerous potential therapeutic points have been identified to stop or delay the progression of ATTR-CM. This article aims to provide a comprehensive review of ATTR-CM and insights into its novel therapeutics and upcoming treatments.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Heart Failure; Echocardiography; Cardiomyopathies
PubMed: 37640179
DOI: 10.1016/j.cpcardiol.2023.102057 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
European Journal of Heart Failure Sep 2022
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Echocardiography; Heart Failure; Humans; Prealbumin
PubMed: 35906799
DOI: 10.1002/ejhf.2639 -
Minerva Cardiology and Angiology Apr 2022Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold... (Review)
Review
Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Amyloid transthyretin cardiac amyloidosis (ATTR-CA) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction and is an underdiagnosed disorder affecting quality of life and prognosis. This justifies the current search for novel tools for early diagnosis and accurate risk prediction, as well as for safe and effective therapies. In this review we will provide an overview of the main unsolved issues and the most promising research lines on ATTR-CA, ranging from the mechanisms of amyloid formation to therapies.
Topics: Amyloid; Amyloid Neuropathies, Familial; Amyloidogenic Proteins; Cardiology; Humans; Prealbumin; Quality of Life
PubMed: 35412035
DOI: 10.23736/S2724-5683.21.05926-3 -
Biomolecules Aug 2022The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type...
The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca-bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop.
Topics: Amyloidosis; Calcium; Humans; Prealbumin; Proteolysis
PubMed: 36008960
DOI: 10.3390/biom12081066 -
PloS One 2022Acute phase reactants (APRs) are proteins altered by inflammation and are regarded as surrogate markers representing inflammatory status. This study evaluated changes of...
OBJECTIVES
Acute phase reactants (APRs) are proteins altered by inflammation and are regarded as surrogate markers representing inflammatory status. This study evaluated changes of albumin (Alb), prealbumin (Palb), and ischemia-modified albumin (IMA) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in response to alterations in disease activity and the correlation between disease activity and Alb, Palb, and IMA.
METHODS
Fifty-nine patients with AAV registered in the prospective SHAVE cohort, who had available serial blood samples at least three months apart were included (indicated as pre and post). Correlation analysis and linear regression were carried out to determine the relationship between continuous variables. Alb, Palb, and IMA levels in 40 healthy controls (HCs) were compared with patients with AAV.
RESULTS
Comparison of Alb, Palb, and IMA levels in HCs and in patients at initial (pre) and follow-up (post) time points revealed that Alb levels significantly increased following the improvement of disease activity and were comparable between HCs and patients at follow-up (post). Meanwhile, there was no significant difference noted in Palb and IMA levels after the decrease of disease activity. While initial (pre) Alb and Palb were significantly associated with BVAS, a subgroup analysis of patients with new-onset disease showed Palb was no longer significantly associated with Birmingham Vasculitis Activity Score (BVAS). Multivariate linear regression showed Alb level (standardized β = -0.377; 95% confidence interval: -5.623, -1.260; p = 0.003) was an independent predictor of BVAS at baseline.
CONCLUSIONS
Among Alb, Palb, and IMA, we found that Alb could be a useful marker indicating disease activity in patients with AAV.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Humans; Prealbumin; Prospective Studies; Serum Albumin; Serum Albumin, Human
PubMed: 35797397
DOI: 10.1371/journal.pone.0271055