ATTR Amyloid Cardiomyopathy: Characterization of Extracellular Vesicles as Potential Disease Stratifiers and Prognostic Biomarkers
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Wild-type ATTR Amyloidosis, Amyloidosis Cardiac, Amyloidosis, Hereditary, Amyloidosis Transthyretin. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Brazil
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This study explores whether extracellular vesicles (EVs) tiny particles released into the bloodstream by cells can serve as early and minimally invasive biomarkers for transthyretin amyloid cardiomyopathy (ATTR-CM). Because ATTR-CM is often diagnosed only after significant heart damage has occurred, there is an urgent need for earlier detection methods. The study will enroll individuals with different clinical presentations of transthyretin amyloidosis, along with healthy controls. Participants will undergo blood sampling, cardiac imaging (including echocardiography, cardiac MRI, and scintigraphy when indicated), and molecular EV analysis. By comparing EV profiles across groups, the study aims to determine whether these vesicles reflect early cardiac involvement, track disease progression, and support more accurate and timely diagnosis. Ultimately, this research seeks to improve clinical decision-making and patient outcomes in ATTR cardiomyopathy.
Detailed description
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative disease caused by the deposition of misfolded transthyretin protein in the myocardium. Despite advances in imaging and treatment, early detection and accurate risk stratification remain major challenges, often resulting in delayed diagnosis and worse clinical outcomes.
This prospective observational study will enroll 70 adult participants, distributed into four predefined groups:
* ATTR-CM with myocardial dysfunction (n = 20) * Hereditary ATTR with predominant neurologic involvement (n = 20) * Genotype-positive individuals without clinical manifestation (n = 10) * Healthy controls (n = 20)
All participants will undergo blood collection for extracellular vesicle (EV) isolation and molecular profiling. EVs are nanoscale particles released by cells that carry proteins, lipids, and nucleic acids reflective of their cellular origin and physiological state, potentially serving as minimally invasive biomarkers.
Participants with cardiac involvement will additionally undergo standardized cardiac evaluations, including echocardiography, cardiac MRI, and nuclear imaging when indicated. Clinical data, functional status, and laboratory parameters will be correlated with EV characteristics to assess their association with disease severity and progression.
By integrating EV profiling with clinical and imaging findings across different phenotypes and disease stages, this study aims to identify biomarkers capable of improving diagnostic accuracy, tracking disease evolution, and supporting personalized care strategies in ATTR amyloidosis.
Primary outcome measures
- Serum concentration of circulating extracellular vesicles (EVs) [Time frame: baseline]
- Circulating extracellular vesicle protein profile [Time frame: baseline]
Secondary outcome measures (3)
- Correlation between circulating extracellular vesicle concentration and echocardiographic parameters [Time frame: baseline]
- Correlation between extracellular vesicle molecular profile and cardiac magnetic resonance findings [Time frame: baseline]
- Correlation between extracellular vesicle characteristics and myocardial uptake on scintigraphy [Time frame: baseline]
Eligibility criteria
Inclusion criteria
- Adult patients aged 18 years or older;
- Confirmed diagnosis of transthyretin cardiac amyloidosis (TTR-CA), with or without myocardial dysfunction, according to established diagnostic criteria;
- Willingness to comply with study procedures and requirements;
- Ability to provide written informed consent.
Exclusion criteria
- Presence of other significant cardiac conditions that may interfere with study outcomes, such as severe coronary artery disease or major valvular disease;
- Inability to provide informed consent or to participate in the required clinical assessments and examinations.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Brazil · 1 center
- Instituto do Coracao, HCFMUSP — São Paulo
Publications
- Perez-Gonzalez R, Kim Y, Miller C, Pacheco-Quinto J, Eckman EA, Levy E. Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes. FASEB J. 2020 Sep;34(9):12922-12931. doi: 10.1096/fj.202000823R. Epub 2020 Aug 9. PMID 32772431
- Moreno CR, Ramires JAF, Lotufo PA, Soeiro AM, Oliveira LMDS, Ikegami RN, Kawakami JT, Pereira JJ, Reis MM, Higuchi ML. Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients. Front Cardiovasc Med. 2021 Aug 5;8:694851. doi: 10.3389/fcvm.2021.694851. eCollection 2021. PMID 34422924
- Roura S, Gamez-Valero A, Lupon J, Galvez-Monton C, Borras FE, Bayes-Genis A. Proteomic signature of circulating extracellular vesicles in dilated cardiomyopathy. Lab Invest. 2018 Oct;98(10):1291-1299. doi: 10.1038/s41374-018-0044-5. Epub 2018 Mar 14. PMID 29540862
- Bakhshandeh B, Kamaleddin MA, Aalishah K. A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors. Curr Stem Cell Res Ther. 2017;12(1):31-36. doi: 10.2174/1574888x11666160709211528. PMID 27396390
- van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost. 2010 Dec;8(12):2596-607. doi: 10.1111/j.1538-7836.2010.04074.x. PMID 20880256
- Ridger VC, Boulanger CM, Angelillo-Scherrer A, Badimon L, Blanc-Brude O, Bochaton-Piallat ML, Boilard E, Buzas EI, Caporali A, Dignat-George F, Evans PC, Lacroix R, Lutgens E, Ketelhuth DFJ, Nieuwland R, Toti F, Tunon J, Weber C, Hoefer IE. Microvesicles in vascular homeostasis and diseases. Position Paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Bi PMID 28569921
- Sunkara V, Woo HK, Cho YK. Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics. Analyst. 2016 Jan 21;141(2):371-81. doi: 10.1039/c5an01775k. PMID 26535415
- Roy S, Hochberg FH, Jones PS. Extracellular vesicles: the growth as diagnostics and therapeutics; a survey. J Extracell Vesicles. 2018 Feb 26;7(1):1438720. doi: 10.1080/20013078.2018.1438720. eCollection 2018. PMID 29511461
Identifiers
NCT: NCT07314268 · 83160124.2.0000.0068