Clinical Research Directory

Genetic Testing of CYP2C19 in Prognostic Evaluation of Long-Term Major Adverse Cardiac and Vascular Events

Several studies have shown that the efficacy of clopidogrel for secondary prevention of major adverse cardiovascular events (MACE), including acute coronary syndrome, depends on the polymorphism of the CYP2C19 gene. However, studies with large sample sizes and long-term follow-up are missing. Moreover, the impact of this polymorphism on the risk of major adverse limb events (MALE), particularly in patients with peripheral artery disease of the lower limb, is unexplored. Additionally, the impact of CYP2C19 gene polymorphism on clopidogrel effectiveness in preventing recurrent stroke in diverse populations is unknown since most of the data are from Asian ancestry populations. We hypothesize that patients with CYP2C19 gene loss of function alleles are at high risk of MACE and MALE compared to those without loss of function alleles at long-term follow-up. We propose to assess MACE and MALE in a large cohort of patients with available CYP2C19 genotypes treated at the University of Florida Health to evaluate the impact of CYP2C19 gene polymorphisms on the risk of new or recurrent events at long-term follow-up. Our specific aims are Aim 1) to determine the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MACE (a composite of all-cause death, non-fatal MI, and non-fatal stroke) at long-term follow-up; Aim 2) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MALE (a composite of limb amputations, chronic threatening limb ischemia, acute limb ischemia, and limb revascularization) at long-term follow-up; and Aim 3) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of cerebrovascular events (CVE, a composite of any stroke and transient ischemic attack) at long-term follow-up.

Safety and Clinical Performance of the Freesolve Resorbable Magnesium Scaffold System in the Treatment of Subjects With Long de Novo Lesions

The study objective is the assessment of safety and clinical performance of Freesolve 35- and 40-mm in de novo coronary artery lesions up to 38 mm length.

Comparison of Moderate-Intensity Statin Plus Ezetimibe vs. High-Intensity Statin for Coronary Plaque Stabilization

This study is a prospective, multicenter, randomized clinical trial aimed at comparing the effects of moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy on coronary plaque stabilization. Using advanced imaging techniques such as near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), the trial evaluates whether the combination therapy is non-inferior to monotherapy in stabilizing coronary plaques over 52 weeks. The primary endpoint is the percentage change in coronary atheroma volume (PAV) assessed by grayscale IVUS, with secondary outcomes including changes in lipid core burden, inflammatory markers, and clinical events like myocardial infarction and ischemic stroke. The study plans to enroll 408 patients undergoing coronary intervention across 7 domestic institutions, with rigorous follow-up protocols and adherence to international research guidelines.

Imaging Markers of High-Risk Plaque Phenotype for Predicting Post-PCI Outcomes

Despite the widespread use of stents, previous studies have shown that stent implantation mainly relieves symptoms but may not significantly improve long-term outcomes in patients with stable coronary artery disease. Identifying the types of plaques that are most likely to benefit from stenting is essential for improving personalized treatment. This study explores whether coronary computed tomography angiography (CCTA)-derived imaging biomarkers of coronary plaques are associated with increased risk of adverse outcomes after percutaneous coronary intervention (PCI). Around 2,000 patients who underwent CCTA followed by stent placement were included. Advanced software was used to quantify plaque inflammation and composition. Findings from this research may help guide personalized treatment strategies in patients undergoing PCI.

"Immunoregulation in Atherosclerosis: A Single-Cell RNA Sequencing Study"

Atherosclerosis is the leading cause of acute cardiovascular events, such as myocardial infarction and stroke, and is a significant risk factor for cardiovascular mortality. The detailed understanding of the immune mechanisms and cellular transformations involved in the pathogenesis of atherosclerosis is still limited, and the use of single-cell RNA sequencing (scRNAseq) has revealed new cellular functions and subpopulations associated with disease progression. This study aims to identify cellular subpopulations, molecular pathways, and changes in gene expression related to the development of atherosclerosis in human coronary arteries. Using scRNAseq, the study seeks to characterize the transcriptomic landscape of cells present in atherosclerotic plaques and identify molecular signatures that reveal individual predispositions to specific phenotypes, such as disease susceptibility and response to therapies. The research will be conducted at the Albert Einstein Israeli Hospital in São Paulo and will involve samples from coronary arteries and atherosclerotic plaques of the explanted hearts of patients who have undergone heart transplants as well as from discarded material of coronary artery bypass graft surgery (CABG). With an estimated sample size of 20-30 plaques, the data obtained will allow for a detailed analysis of the molecular mechanisms involved in atherosclerosis, contributing to the development of specific therapeutic targets.