-
European Journal of Heart Failure Dec 2022An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for... (Meta-Analysis)
Meta-Analysis
AIMS
An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data.
METHODS AND RESULTS
We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non-cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%-1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%-20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%-15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%-4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%-10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%-9%); severe aortic stenosis (n = 7), 8% (95% CI 5%-13%); autopsy series of 'unselected' elderly individuals (n = 4), 21% (95% CI 7%-39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR-CA, but the average percentage of patients with amyloid light-chain (AL) CA was up to 18%.
CONCLUSIONS
Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR-CA accounts for many cases of CA across the different settings, but AL-CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women.
Topics: Female; Male; Humans; Heart Failure; Amyloidosis; Amyloid; Phenotype; Ventricular Dysfunction, Left; Cardiomyopathies
PubMed: 35509173
DOI: 10.1002/ejhf.2532 -
Journal of the American College of... Apr 2022Over the last year, 5 national or international scientific societies have issued documents regarding cardiac amyloidosis (CA) to highlight the emerging clinical science,... (Review)
Review
Over the last year, 5 national or international scientific societies have issued documents regarding cardiac amyloidosis (CA) to highlight the emerging clinical science, raise awareness, and facilitate diagnosis and management of CA. These documents provide useful guidance for clinicians managing patients with CA, and all include: 1) an algorithm to establish a diagnosis; 2) an emphasis on noninvasive diagnosis with the combined use of bone scintigraphy and the exclusion of a monoclonal protein; and 3) indications for novel disease-modifying therapies for symptomatic CA, either with or without peripheral neuropathy. Nonetheless, the documents diverge on specific details of diagnosis, risk stratification, and treatment. Highlighting the similarities and differences of the documents by the 5 scientific societies with respect to diagnosis, risk stratification, and treatment offers useful insight into the knowledge gaps and unmet needs in the management of CA. An analysis of these documents, therefore, highlights "gray zones" requiring further investigation.
Topics: Amyloidosis; Humans; Societies, Scientific
PubMed: 35361352
DOI: 10.1016/j.jacc.2022.01.036 -
Archivos de Cardiologia de Mexico 2020La amiloidosis cardíaca es una entidad que permanece infradiagnosticada, a pesar de los avances recientes en su diagnóstico y tratamiento. El objetivo de este estudio...
ANTECEDENTES Y OBJETIVO
La amiloidosis cardíaca es una entidad que permanece infradiagnosticada, a pesar de los avances recientes en su diagnóstico y tratamiento. El objetivo de este estudio es revisar una serie de casos de amiloidosis cardíaca para describir los principales datos clínicos y los hallazgos en las pruebas de imagen.
MATERIALES Y MÉTODOS
Estudio retrospectivo de pacientes con diagnóstico principal o secundario de amiloidosis cardíaca en los informes de alta de pacientes hospitalizados en este centro desde 2006 hasta 2016. Se revisaron los datos clínicos de los pacientes, así como las pruebas de imagen (ECG, ecocardiograma, gammagrafía cardíaca, resonancia magnética cardíaca). Se realizó seguimiento de los pacientes hasta enero de 2018.
RESULTADOS
Se analiza a 30 pacientes (20 varones) con media de 65 años. Los principales datos ecocardiográficos fueron dilatación biauricular, disfunción diastólica e hipertrofia ventricular izquierda (HVI) en un 97%. Sólo el 6.7% cumplía criterios de HVI en el electrocardiograma. Hasta un 33% tenía disfunción sistólica. Se realizó gammagrafía y resonancia magnética cardíaca en un 33%. La supervivencia a los 12 meses fue de 61%.
CONCLUSIÓN
La presencia de insuficiencia cardíaca, fibrilación auricular o trastornos de conducción junto a datos ecocardiográficos indicativos debe alertar al clínico. Otros datos como disfunción sistólica o sexo femenino no deben disminuir la sospecha. El estudio debe completarse con gammagrafía y resonancia magnética cardíaca, ya que el diagnóstico temprano tiene implicaciones pronósticas y terapéuticas.
BACKGROUND AND OBJECTIVE
Cardiac amyloidosis is an entity that remains underdiagnostic, despite recent advances in its diagnosis and treatment. The aim of this study is to review a series of diagnosed cases of cardiac amyloidosis to describe the main clinical data and the findings in the imaging tests.
MATERIALS AND METHODS
Retrospective study of patients with primary or secondary diagnosis of cardiac amyloidosis in discharge reports of patients hospitalized in our center from 2006 to 2016. The clinical data of the patients were reviewed, as well as the imaging tests (ECG, echocardiogram, cardiac scintigraphy, cardiac magnetic resonance). Patients were followed until January 2018.
RESULTS
We analyze 30 patients (20 men) with an average of 65 years. The main echocardiographic data were biatrial dilatation, diastolic dysfunction and left ventricular hypertrophy (LVH) in 97%. Only 6.7% met criteria for LVH in the electrocardiogram. Up to 33% had systolic dysfunction. Scintigraphy and cardiac magnetic resonance were performed in 33%. Survival at 12 months was 61%.
CONCLUSION
The presence of heart failure, atrial fibrillation or conduction disorders with suggestive echocardiographic data should alert the clinician. Other data such as systolic dysfunction or female sex should not decrease the suspicion. The study should be completed with gammagraphy and cardiac magnetic resonance since early diagnosis has prognostic and therapeutic implications.
Topics: Aged; Amyloidosis; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Diseases; Humans; Magnetic Resonance Imaging; Male; Radionuclide Imaging; Retrospective Studies
PubMed: 32952176
DOI: 10.24875/ACM.19000238 -
Ugeskrift For Laeger Jan 2023Amyloidosis is a severe disease caused by protein misfolding and deposition in tissues and organs. Thirty-eight different proteins are known to be amyloidogenic.... (Review)
Review
Amyloidosis is a severe disease caused by protein misfolding and deposition in tissues and organs. Thirty-eight different proteins are known to be amyloidogenic. Amyloidosis is categorized into inherited or acquired, and systemic or localized. Light-chain (AL)- and transthyretin (ATTR) amyloidosis are the two most common subtypes. Awareness, early diagnosis, accurate subtyping and relevant treatment are crucial for the management. Novel therapies of systemic AL and ATTR amyloidosis have considerably improved outcome and survival. The aim of this review is to increase awareness and knowledge on diagnosing amyloidosis.
Topics: Humans; Amyloidosis
PubMed: 36629291
DOI: No ID Found -
The New England Journal of Medicine Oct 2023Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin.
METHODS
In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months.
RESULTS
A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group.
CONCLUSIONS
In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).
Topics: Humans; Cardiomyopathies; Prealbumin; RNA, Small Interfering; Amyloidosis, Familial; Liver; Double-Blind Method; Amyloidosis
PubMed: 37888916
DOI: 10.1056/NEJMoa2300757 -
Methodist DeBakey Cardiovascular Journal 2022Amyloidosis encompasses a collection of disorders of pathological protein folding. The extracellular location where these "amyloid fibril" proteins are deposited... (Review)
Review
Amyloidosis encompasses a collection of disorders of pathological protein folding. The extracellular location where these "amyloid fibril" proteins are deposited determines the clinical presentation of the disease. The abnormal architecture of these fibrils makes them insoluble and not easily removed, leading to disruption of normal tissue structure and interference with normal physiology. Amyloidosis of the heart and kidney can be inherited, secondary to unrelated diseases, or due to a plasma cell disorder. This review will focus on immunoglobulin light chain amyloidosis, which is life-threatening and must be diagnosed as early as possible by employing precise and accurate typing to ensure timely and frequently curative therapy.
Topics: Amyloid; Amyloidosis; Heart; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney
PubMed: 36132587
DOI: 10.14797/mdcvj.1150 -
Aging Oct 2019
Topics: Amyloidosis; Heart Diseases; Humans; Middle Aged
PubMed: 31631062
DOI: 10.18632/aging.102383 -
Hematology/oncology Clinics of North... Dec 2020Opportunities and challenges in the field of systemic amyloidosis can be grouped into 4 categories. First, a deeper understanding of the pathogenesis of the disease is... (Review)
Review
Opportunities and challenges in the field of systemic amyloidosis can be grouped into 4 categories. First, a deeper understanding of the pathogenesis of the disease is required. Second, a greater awareness of the disease, which will lead to an earlier diagnosis, is imperative. Third, end points for interventional trials are required to convey us to our fourth aspirations, which are novel therapies for patients with light chain amyloidosis.
Topics: Clinical Trials as Topic; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 33099434
DOI: 10.1016/j.hoc.2020.08.009 -
Journal of Advanced Research Feb 2022Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The... (Review)
Review
INTRODUCTION
Protein aggregation and deposition of uniformly arranged amyloid fibrils in the form of plaques or amorphous aggregates is characteristic of amyloid diseases. The accumulation and deposition of proteins result in toxicity and cause deleterious effects on affected individuals known as amyloidosis. There are about fifty different proteins and peptides involved in amyloidosis including neurodegenerative diseases and diseases affecting vital organs. Despite the strenuous effort to find a suitable treatment option for these amyloid disorders, very few compounds had made it to unsuccessful clinical trials. It has become a compelling challenge to understand and manage amyloidosis with the increased life expectancy and ageing population.
OBJECTIVE
While most of the currently available literature and knowledge base focus on the amyloid inhibitory mechanism as a treatment option, it is equally important to organize and understand amyloid disaggregation strategies. Disaggregation strategies are important and crucial as they are present innately functional in many living systems and dissolution of preformed amyloids may provide a direct benefit in many pathological conditions. In this review, we have compiled the known amyloid disaggregation mechanism, interactions, and possibilities of using disaggregases as a treatment option for amyloidosis.
METHODS
We have provided the structural details using protein-ligand docking models to visualize the interaction between these disaggregases with amyloid fibrils and their respective proposed amyloid disaggregation mechanisms.
RESULTS
After reviewing and comparing the different amyloid disaggregase systems and their proposed mechanisms, we presented two different hypotheses for ATP independent disaggregases using L-PGDS as a model.
CONCLUSION
Finally, we have highlighted the importance of understanding the underlying disaggregation mechanisms used by these chaperones and organic compounds before the implementation of these disaggregases as a potential treatment option for amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Molecular Chaperones; Protein Aggregates
PubMed: 35127169
DOI: 10.1016/j.jare.2021.05.007 -
Circulation. Cardiovascular Imaging Jul 2021
Review
ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.
Topics: Amyloidosis; Biopsy; Cardiomyopathies; Consensus; Echocardiography; Evidence-Based Medicine; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Myocardium; Predictive Value of Tests; Prognosis; Radionuclide Imaging
PubMed: 34196223
DOI: 10.1161/HCI.0000000000000029