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.
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.
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.
This study will enroll adult participants aged 18 years or older, including patients with confirmed transthyretin cardiac amyloidosis (with or without myocardial dysfunction), as well as healthy volunteers without known cardiac disease. The population includes individuals with different clinical presentations of ATTR and matched controls for comparative analysis.
Cohort
Prospective
Not listed
Serum concentration of circulating extracellular vesicles (EVs)
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
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.
Correlation between circulating extracellular vesicle concentration and echocardiographic parameters
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
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
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.
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University of Sao Paulo General Hospital
Lead sponsor
InCor Heart Institute
Collaborator
