Amyloidosis Cardiac, Amyloidosis, Hereditary, Amyloidosis Transthyretin, Wild-type ATTR Amyloidosis
Conditions
Keywords
Early Diagnosis, Serum Biomarkers, Transthyretin Amyloid Cardiomyopathy, ATTR, Vesicle Protein Signature
Brief summary
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.
Interventions
None listed
Sponsors
InCor Heart Institute
University of Sao Paulo General Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum concentration of circulating extracellular vesicles (EVs) | baseline | Quantification of the total concentration of circulating extracellular vesicles isolated from peripheral blood, expressed as number of particles per mL, measured by Nanoparticle Tracking Analysis (NTA - NanoSight), in participants with different clinical presentations of transthyretin amyloidosis (ATTR) and in healthy controls. |
| Circulating extracellular vesicle protein profile | baseline | Protein profiling of circulating extracellular vesicles isolated from peripheral blood, including protein identification and assessment of relative abundance by mass spectrometry, followed by targeted validation and quantification of selected proteins using Western blotting and/or ELISA. Results will be reported as relative protein expression intensity or, when applicable, as absolute concentration (ng/mL), in participants with transthyretin amyloidosis (ATTR) and healthy controls, assessed at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between circulating extracellular vesicle concentration and echocardiographic parameters | baseline | Correlation between plasma concentration of circulating extracellular vesicles, measured as particles/mL by Nanoparticle Tracking Analysis, and cardiac structure and function parameters assessed by transthoracic echocardiography, including interventricular septal thickness (mm), left ventricular ejection fraction (%), and global longitudinal strain (%), analyzed using Pearson or Spearman correlation coefficients as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls. |
| Correlation between extracellular vesicle molecular profile and cardiac magnetic resonance findings | baseline | Correlation between the molecular profile of circulating extracellular vesicles, including protein levels assessed by Western blotting and/or ELISA and microRNA expression assessed by RT-qPCR, and cardiac involvement parameters evaluated by cardiac magnetic resonance imaging, including extracellular volume fraction (ECV, %) and presence or absence of late gadolinium enhancement, analyzed using correlation methods as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls. |
| Correlation between extracellular vesicle characteristics and myocardial uptake on scintigraphy | baseline | Correlation between circulating extracellular vesicle concentration, measured as particles/mL by Nanoparticle Tracking Analysis, and extracellular vesicle molecular characteristics assessed by RT-qPCR and Western blotting, and the degree of myocardial uptake evaluated by bone scintigraphy using an appropriate radiotracer and visual scoring system (e.g., Perugini grade 0-3), analyzed using correlation methods as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls. |
Countries
Brazil
Contacts
Primary ContactFelix Jose A Ramires, MD, PhD
Backup ContactCamila R Moreno, PhD
Outcome results
None listed