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European Journal of Heart Failure Feb 2021
Topics: Amyloid Neuropathies, Familial; Heart Failure; Humans; Prealbumin
PubMed: 33342016
DOI: 10.1002/ejhf.2080 -
Romanian Journal of Internal Medicine =... Mar 2023Transthyretin cardiac amyloidosis is a progressive disease known to cause heart failure, conduction anomalies, and arrythmias. Due to poor outcomes and mortality from... (Review)
Review
Transthyretin cardiac amyloidosis is a progressive disease known to cause heart failure, conduction anomalies, and arrythmias. Due to poor outcomes and mortality from severe cardiomyopathy, prevalence and incident rates are often underreported. As global longevity is increasing and rates of amyloidosis are also increasing, there is a need to improve diagnostic and therapeutic interventions. Previously, symptom management and transplantation were the mainstay of treatment for heart failure symptoms, but studies using RNAi and siRNA technologies have shifted the paradigm of therapeutic strategy in amyloid cardiomyopathy management. Additionally, early detection and clinical monitoring with numerous imaging and non-imaging techniques are being increasingly investigated. Here, we review the epidemiology, pathophysiology, diagnosis, and management of transthyretin amyloid cardiomyopathy.
Topics: Humans; Amyloidosis; Arrhythmias, Cardiac; Cardiomyopathies; Heart Failure; Prealbumin
PubMed: 36278951
DOI: 10.2478/rjim-2022-0018 -
Heart Failure Reviews Mar 2024Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease characterized by the deposition of abnormal transthyretin protein fibrils in the heart, leading to... (Review)
Review
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease characterized by the deposition of abnormal transthyretin protein fibrils in the heart, leading to cardiac dysfunction. Recent evidence suggests that sex differences may play a significant role in various steps of ATTR-CA, including clinical presentation, diagnostic challenges, disease progression, and treatment outcomes. ATTR-CA predominantly affects men, whereas women are older at presentation. Women generally present with a history of heart failure with preserved ejection fraction and/or carpal tunnel syndrome. When indexed, left ventricular (LV) wall thickness is equal, or even increased, than men. Women also have smaller LV cavities, more preserved ejection fractions, and apparently a slightly worse right ventricular and diastolic function. Given the under-representation on women in clinical trials, no data regarding sex influence on the treatment response are currently available. Finally, it seems there are no differences in overall prognosis, even if premenopausal women may have a certain level of myocardial protection. Genetic variations, environmental factors, and hormonal changes are considered as potential contributors to observed disparities. Understanding sex differences in ATTR-CA is vital for accurate diagnosis and management. By considering these differences, clinicians can improve diagnostic accuracy, tailor treatments, and optimize outcomes for both sexes with ATTR-CA.
Topics: Humans; Female; Male; Cardiomyopathies; Prealbumin; Sex Characteristics; Amyloidosis; Heart; Amyloid Neuropathies, Familial
PubMed: 37566193
DOI: 10.1007/s10741-023-10339-w -
Current Heart Failure Reports Oct 2022Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial... (Review)
Review
PURPOSE OF REVIEW
Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role.
RECENT FINDINGS
Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain. Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis.
Topics: Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Heart Failure; Humans; Prealbumin; Troponin
PubMed: 35930129
DOI: 10.1007/s11897-022-00570-1 -
Circulation Jan 2019Despite the availability of proven treatments for some patients with heart failure (HF), many patients—particularly those with HF and preserved ejection fraction...
Despite the availability of proven treatments for some patients with heart failure (HF), many patients—particularly those with HF and preserved ejection fraction (HFpEF)—remain difficult to treat, resulting in persistently high morbidity and mortality in the majority of HF patients. The lack of effective treatments, disappointing results of many HF randomized clinical trials (RCT), and variable treatment responses even for proven therapies are all possible reasons for the poor prognosis of HF patients. In the context of this backdrop, it is not surprising that there has been growing interest and enthusiasm for “precision medicine” in order to improve outcomes for patients who suffer from the HF syndrome.
Topics: Amyloidosis; Heart; Humans; Prealbumin; RNA Interference; RNA, Small Interfering
PubMed: 30664380
DOI: 10.1161/CIRCULATIONAHA.118.037593 -
Journal of the American College of... Jul 2019
Topics: Amyloidosis; Cardiomyopathies; Humans; Prealbumin
PubMed: 31319911
DOI: 10.1016/j.jacc.2019.05.031 -
Global Heart 2023Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of...
Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of heart failure 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-CA, which is now possible without recourse to endomyocardial biopsy in around 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-CA and more accurate prognostic stratification. Therapies able to slow or halt ATTR-CA progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional heart failure medications. A wide horizon of possibilities is unfolding and awaits discovery.
Topics: Humans; Prealbumin; Amyloidosis; Heart Failure; Prognosis; Cardiomyopathies
PubMed: 38028963
DOI: 10.5334/gh.1275 -
Pharmacology & Therapeutics Dec 2017Amyloidosis refers to a range of protein misfolding disorders that can cause organ dysfunction through progressive fibril deposition. Cardiac involvement often leads to... (Review)
Review
Amyloidosis refers to a range of protein misfolding disorders that can cause organ dysfunction through progressive fibril deposition. Cardiac involvement often leads to significant morbidity and mortality and increasingly has been recognized as an important cause of heart failure. The two main forms of cardiac amyloidosis, light chain (AL) and transthyretin (ATTR) amyloidosis, have distinct mechanisms of pathogenesis. Recent insights have led to the development of novel pharmacotherapies with the potential to significantly impact each disease. This review will summarize the preclinical and clinical data for these emerging treatments for AL and ATTR amyloidosis.
Topics: Amyloid; Amyloidosis; Animals; Antibodies; Heart Diseases; Humans; Plasma Cells; Prealbumin
PubMed: 28648829
DOI: 10.1016/j.pharmthera.2017.06.011 -
Arquivos Brasileiros de Oftalmologia 2022Transthyretin familial amyloidosis is the most common form of inherited systemic amyloidosis worldwide. The condition develops secondary to more than 100 different point... (Review)
Review
Transthyretin familial amyloidosis is the most common form of inherited systemic amyloidosis worldwide. The condition develops secondary to more than 100 different point mutations in the transthyretin gene (18q12.1). The mutations lead to abnormal amyloid deposits, mainly in the heart and peripheral nerves. Leptomeningeal and mainly ocular involvement is common. Although there are several different types of treatment available, ocular involvement, which occurs also in liver transplant recipients, remains a major challenge, progressing even in liver transplant recipients. Patients with ocular involvement require efficient ophthalmological follow-up to prevent vision loss. In this review, different forms of ocular involvement characterizing the subtypes of transthyretin mutations were described, and the effects of different treatments were summarized. Further research is necessary to fully elucidate these issues.
Topics: Amyloid Neuropathies, Familial; Humans; Mutation; Prealbumin
PubMed: 35417510
DOI: 10.5935/0004-2749.20220099 -
Nature Communications Jun 2023Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here,...
Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake Ttr mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.
Topics: Mice; Male; Animals; Choroid Plexus; Blood-Brain Barrier; Brain; Thyroid Hormones; Prealbumin; Biological Transport
PubMed: 37349305
DOI: 10.1038/s41467-023-39326-3