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1.
Heart Fail Clin ; 20(3): 307-316, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844301

RESUMO

Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.


Assuntos
Amiloidose , Cardiomiopatias , Compostos Radiofarmacêuticos , Humanos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Amiloidose/patologia , Cintilografia/métodos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Miocárdio/patologia , Miocárdio/metabolismo , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Pré-Albumina/metabolismo
2.
Heart Fail Clin ; 20(3): 271-282, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844298

RESUMO

Amyloidosis is a rare, heterogeneous group of diseases characterized by extracellular infiltration and deposition of misfolded fibrils in different organs and tissues. A timely diagnosis is important as it can improve outcome. Echocardiography has emerged as a powerful tool to prompt suspicion and refer patients to second-level evaluation to reach a definitive diagnosis. In this scenario, new echo techniques offer new insight into the cardiac amyloidosis (CA) pathophysiology and clinical course. The present review aims to describe the developments in echocardiographic assessment of patients with suspected CA and it summarizes new available echocardiographic scores able to guide a definite diagnosis.


Assuntos
Amiloidose , Cardiomiopatias , Ecocardiografia , Humanos , Amiloidose/diagnóstico por imagem , Amiloidose/terapia , Amiloidose/diagnóstico , Ecocardiografia/métodos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Medição de Risco , Gerenciamento Clínico
4.
Heart Fail Clin ; 20(3): 283-294, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844299

RESUMO

Amyloidosis is a systemic condition characterized by multiple organs involvement. A multidisciplinary and multimodal approach in assessing patients is pivotal and recommended by the international scientific societies. Biomarkers represent an essential noninvasive tool to increase the suspicion of disease and orient further workup and clinical management of patients. This review provides an updated contemporary focus on the clinical use of biomarkers in cardiac amyloidosis, emphasizing their role in both the diagnostic and prognostic setting and discussing future perspective of emerging biomarkers.


Assuntos
Amiloidose , Biomarcadores , Cardiomiopatias , Humanos , Biomarcadores/metabolismo , Amiloidose/diagnóstico , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Prognóstico
5.
Turk Kardiyol Dern Ars ; 52(4): 227-236, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38829635

RESUMO

OBJECTIVE: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients. METHODS: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features. RESULTS: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively. CONCLUSION: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Volume Sistólico , Humanos , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Masculino , Idoso , Volume Sistólico/fisiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Cardiomiopatias/fisiopatologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/diagnóstico por imagem , Amiloidose/fisiopatologia , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/diagnóstico por imagem , Neuropatias Amiloides Familiares/fisiopatologia , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/diagnóstico por imagem
6.
Res Vet Sci ; 175: 105315, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838511

RESUMO

Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis.


Assuntos
Amiloidose , Doenças dos Símios Antropoides , Pongo pygmaeus , Animais , Doenças dos Símios Antropoides/patologia , Amiloidose/veterinária , Amiloidose/patologia , Cadeias kappa de Imunoglobulina , Amiloidose de Cadeia Leve de Imunoglobulina/veterinária , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Linfonodos/patologia , Masculino , Proteômica , Feminino
11.
J Neuroimmune Pharmacol ; 19(1): 27, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829507

RESUMO

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aß42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.


Assuntos
Doença de Alzheimer , Amiloidose , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Doença de Alzheimer/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Prospectivos , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/metabolismo
12.
PLoS One ; 19(6): e0304891, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843135

RESUMO

ATTR amyloidosis is caused by deposition of large, insoluble aggregates (amyloid fibrils) of cross-ß-sheet TTR protein molecules on the intercellular surfaces of tissues. The process of amyloid formation from monomeric TTR protein molecules to amyloid deposits has not been fully characterized and is therefore modeled in this paper. Two models are considered: 1) TTR monomers in the blood spontaneously fold into a ß-sheet conformation, aggregate into short proto-fibrils that then circulate in the blood until they find a complementary tissue where the proto-fibrils accumulate to form the large, insoluble amyloid fibrils found in affected tissues. 2) TTR monomers in the native or ß-sheet conformation circulate in the blood until they find a tissue binding site and deposit in the tissue or tissues forming amyloid deposits in situ. These models only differ on where the selection for ß-sheet complementarity occurs, in the blood where wt-wt, wt-v, and v-v interactions determine selectivity, or on the tissue surface where tissue-wt and tissure-v interactions also determine selectivity. Statistical modeling in both cases thus involves selectivity in fibril aggregation and tissue binding. Because binding of protein molecules into fibrils and binding of fibrils to tissues occurs through multiple weak non-covalent bonds, strong complementarity between ß-sheet molecules and between fibrils and tissues is required to explain the insolubility and tissue selectivity of ATTR amyloidosis. Observation of differing tissue selectivity and thence disease phenotypes from either pure wildtype TTR protein or a mix of wildtype and variant molecules in amyloid fibrils evidences the requirement for fibril-tissue complementarity. Understanding the process that forms fibrils and binds fibrils to tissues may lead to new possibilities for interrupting the process and preventing or curing ATTR amyloidosis.


Assuntos
Amiloide , Pré-Albumina , Pré-Albumina/metabolismo , Pré-Albumina/química , Humanos , Amiloide/metabolismo , Amiloide/química , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Amiloidose/metabolismo , Modelos Moleculares , Conformação Proteica em Folha beta
13.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892061

RESUMO

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical for disease management. These technologies provide extensive insights into the specific proteins involved, allowing for more targeted treatment approaches and better patient results. Despite these advances, problems remain, owing to the heterogeneous composition of amyloid proteins and the varying efficacy of treatments based on amyloid type. Access to sophisticated diagnostics and therapy varies greatly, highlighting the global difference in renal amyloidosis management. Future research is needed to investigate next-generation sequencing and gene-editing technologies, like clustered regularly interspaced short palindromic repeats (CRISPR), which promise more profound insights into the genetic basis of amyloidosis.


Assuntos
Amiloidose , Nefropatias , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose/genética , Amiloidose/metabolismo , Nefropatias/diagnóstico , Nefropatias/terapia , Nefropatias/genética , Proteômica/métodos , Espectrometria de Massas/métodos
14.
Heart Fail Clin ; 20(3): 295-305, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844300

RESUMO

Cardiac magnetic resonance represents the gold standard imaging technique to assess cardiac volumes, wall thickness, mass, and systolic function but also to provide noninvasive myocardial tissue characterization across almost all cardiac diseases. In patients with cardiac amyloidosis, increased wall thickness of all heart chambers, a mildly reduced ejection fraction and occasionally pleural and pericardial effusion are the characteristic morphologic anomalies. The typical pattern after contrast injection is represented by diffuse areas of late gadolinium enhancement, which can be focal and patchy in very early stages, circumferential, and subendocardial in intermediate stages or even diffuse transmural in more advanced stages.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Miocárdio/patologia , Volume Sistólico/fisiologia
15.
Heart Fail Clin ; 20(3): 261-270, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844297

RESUMO

Amyloidosis refers to a heterogeneous group of disorders sharing common pathophysiological mechanisms characterized by the extracellular accumulation of fibrillar deposits consisting of the aggregation of misfolded proteins. Cardiac amyloidosis (CA), usually caused by deposition of misfolded transthyretin or immunoglobulin light chains, is an increasingly recognized cause of heart failure burdened by a poor prognosis. CA manifests with a restrictive cardiomyopathy which progressively leads to biventricular thickening, diastolic and then systolic dysfunction, arrhythmias, and valvular disease. The pathophysiology of CA is multifactorial and includes increased oxidative stress, mitochondrial damage, apoptosis, impaired metabolism, and modifications of intracellular calcium balance.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/fisiopatologia , Amiloidose/metabolismo , Cardiomiopatias/fisiopatologia , Cardiomiopatias/metabolismo , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Estresse Oxidativo , Miocárdio/patologia , Miocárdio/metabolismo
16.
Heart Fail Clin ; 20(3): 249-260, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844296

RESUMO

Amyloidosis is a heterogenous group of disorders, caused by the deposition of insoluble fibrils derived from misfolded proteins in the extracellular space of various organs. These proteins have an unstable structure that causes them to misfold, aggregate, and deposit as amyloid fibrils with the pathognomonic histologic property of green birefringence when viewed under cross-polarized light after staining with Congo red. Amyloid fibrils are insoluble and degradation-resistant; resistance to catabolism results in progressive tissue amyloid accumulation. The outcome of this process is organ disfunction independently from the type of deposited protein, however there can be organ that are specifically targeted from certain proteins.


Assuntos
Amiloide , Amiloidose , Humanos , Amiloidose/metabolismo , Amiloidose/patologia , Amiloide/metabolismo
17.
Heart Fail Clin ; 20(3): 325-331, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844303

RESUMO

Amyloidosis is a systemic disease due to the accumulation of misfolded amyloid fibrils that damage the heart and worsen the prognosis. Heart failure (HF), a condition frequently linked with an advanced stage of this disease, is the most prevalent clinical manifestation that leads to its diagnosis. However, due to the growing awareness of the occurrence of cardiac amyloidosis (CA), it is now possible to perform an early diagnosis and have a positive impact on its natural course. This study aims to highlight the most compelling issues concerning patients' clinical management with HF and CA.


Assuntos
Amiloidose , Cardiomiopatias , Insuficiência Cardíaca , Humanos , Amiloidose/terapia , Insuficiência Cardíaca/etiologia , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Prognóstico
18.
Anal Chem ; 96(23): 9460-9467, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38820243

RESUMO

Pathological cardiac hypertrophy is a complex process that often leads to heart failure. Label-free proteomics has emerged as an important platform to reveal protein variations and to elucidate the mechanisms of cardiac hypertrophy. Endomyocardial biopsy is a minimally invasive technique for sampling cardiac tissue, but it yields only limited amounts of an ethically permissible specimen. After regular pathological examination, the remaining trace samples pose significant challenges for effective protein extraction and mass spectrometry analysis. Herein, we developed trace cardiac tissue proteomics based on the anchor-nanoparticles (TCPA) method. We identified an average of 6666 protein groups using ∼50 µg of myocardial interventricular septum samples by TCPA. We then applied TCPA to acquire proteomics from patients' cardiac samples both diagnosed as hypertrophic hearts and myocarditis controls and identified significant alterations in pathways such as regulation of actin cytoskeleton, oxidative phosphorylation, and cGMP-PKG signaling pathway. Moreover, we found multiple lipid metabolic pathways to be dysregulated in transthyretin cardiac amyloidosis compared to other types of cardiac hypertrophy. TCPA offers a new technique for studying pathological cardiac hypertrophy and can serve as a platform toolbox for proteomic research in other cardiac diseases.


Assuntos
Miocárdio , Nanopartículas , Proteômica , Proteômica/métodos , Humanos , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/química , Nanopartículas/química , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/diagnóstico , Amiloidose/metabolismo , Amiloidose/patologia , Neuropatias Amiloides Familiares
20.
PLoS One ; 19(5): e0297182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768126

RESUMO

BACKGROUND: Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress. METHODS: Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program. RESULTS: 118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need. CONCLUSION: The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.


Assuntos
Amiloidose , Humanos , Feminino , Masculino , Idoso , Alemanha/epidemiologia , Amiloidose/terapia , Amiloidose/psicologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Qualidade de Vida , Cuidadores/psicologia , Diagnóstico Tardio
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