Last updated 6 days ago
Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis
20 patients around the world
Available in Brazil
Transthyretin cardiac amyloidosis (ATTR-CM) is characterized by the deposition of transthyretin amyloid fibrils within the myocardium. In addition to myocardial infiltration, amyloid deposition may involve intramyocardial vessels and contribute to coronary microvascular dysfunction. This may lead to impaired myocardial perfusion and reduced coronary flow reserve even in the absence of significant obstructive epicardial coronary artery disease.
Trimetazidine is a metabolic modulator that shifts myocardial energy metabolism from fatty acid oxidation toward glucose oxidation. This metabolic effect may improve myocardial energy efficiency and reduce oxygen requirements for adenosine triphosphate production. These properties provide the rationale for investigating whether trimetazidine may improve coronary microvascular function in people with ATTR-CM.
TACT-TTR is a prospective, open-label, single-center, single-arm pilot clinical trial conducted at the Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor-HCFMUSP). The study will enroll 20 participants with ATTR-CM who will receive trimetazidine and undergo approximately 6 months of follow-up.
Coronary physiology will be assessed using quantitative myocardial perfusion imaging with nitrogen-13 ammonia positron emission tomography/computed tomography (PET/CT). Myocardial blood flow will be measured at rest and during pharmacologic stress, allowing calculation of coronary flow reserve as the ratio of stress myocardial blood flow to resting myocardial blood flow. Participants will undergo assessments before and after the treatment period to investigate changes in coronary microvascular function. Additional clinical, imaging, laboratory, functional, and health-related quality-of-life assessments will be performed during follow-up.
This exploratory pilot study is intended to provide preliminary evidence on the potential role of trimetazidine as an adjunctive metabolic therapy targeting coronary microvascular dysfunction in ATTR-CM and to generate data that may support the design of future controlled clinical trials.
Fábio Fernandes
1Research sites
20Patients around the world
This study is for people with
Rare diseases
Amyloidosis
Requirements for the patient
From 18 Years
All Gender
Medical requirements
- Diagnosis of transthyretin cardiac amyloidosis confirmed by all protocol-specified diagnostic criteria or by Congo red-positive tissue biopsy with cardiac involvement. The diagnostic criteria listed in the current protocol include.Interventricular septal thickness >12 mm on echocardiography or cardiac magnetic resonance imaging, in the absence of other causes of hypertrophy (e.g., hypertension or aortic stenosis).History of signs or symptoms of heart failure consistent with cardiac amyloidosis.Cardiac scintigraphy with technetium-99m pyrophosphate showing grade II or III uptake according to the Perugini scale.Age >18 years.New York Heart Association (NYHA) functional class II, III, or IV.
- Previous adverse reaction, intolerance, or other contraindication to trimetazidine.Serum kappa/lambda ratio outside the normal range.Use of calcium channel blockers, beta-blockers, or nitrates.Obstructive coronary artery disease, defined as >50% stenosis in any major epicardial coronary artery, demonstrated by coronary computed tomography angiography.Active infection, inflammatory disease, or other systemic condition that may affect myocardial perfusion.Contraindication to dipyridamole or PET/CT imaging.Estimated glomerular filtration rate <30 mL/min/1.73 m², calculated using the CKD-EPI equation.Pregnancy or postpartum period.Presence of diseases other than cardiac amyloidosis that may impair functional capacity or limit ambulation during the 6-minute walk test.Other medical conditions or comorbidities that, in the investigator's opinion, may interfere with the course of the study or interpretation of the data.Refusal to provide written informed consent.
Sites
InCor - Instituto do Coração do HCFMUSP
StudyTACT-TTR
SponsorFábio Fernandes
Study typeInterventional
Conditions
Amyloidosis
Requirements
From 18 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT07836699
