View clinical trials related to Cardiac Allograft Vasculopathy.
Filter by:The goal of this clinical trial is to test if SGLT2 inhibitors could prevent or delay the development of Cardiac Allograft Vasculopathy (CAV) post-heart transplantation (TxC). The main questions it aims to answer are: Primary outcome: CAV, according to ISHLT grading system diagnosed by CCTA; Secondary outcomes: cardiovascular death, all-cause mortality, hospitalization, worsening glomerular filtration rate, fasting glucose, weight, and blood pressure. Exploratory and safety outcomes: Rejection, hypoglycemia, urinary tract infection, hypovolemia, and limb amputation. HYPOTHESIS The null hypothesis is that SGLT2 inhibitors do not reduce the incidence of CAV in transplanted patients. The alternative hypothesis is that SGLT2 inhibitors reduce the incidence of CAV in transplanted patients.METHODOLOGY Study Design A randomized clinical trial of superiority with active control (2 arms), with central randomization and blinded evaluation of outcomes, to evaluate the efficacy and safety of adding dapagliflozin or empagliflozin 10 mg once daily to conventional post-TxC treatment compared with the treatment of isolated conventional post-TxC for 6-8 months. Study Sample Sample: All adult patients undergoing a heart transplant between January 2017 and December 2023 at Hospital de Messejana. Inclusion Criteria Included: Patients of both sexes, aged ≥ 18 years, who have undergone heart transplantation between January 2017 and December 2023 and are under the care of the Heart Transplant and Heart Failure Unit at Hospital de Messejana.
Cardiac allograft vasculopathy (CAV) is a common complication affecting heart transplant patients. This condition causes narrowing of the heart arteries leading to graft dysfunction. Surveillance for CAV is vital; however an ideal approach has not been established. The goal of this study is to assess whether noninvasive positron emission tomography (PET) based surveillance is non-inferior to invasive coronary angiography (ICA) surveillance.
The aim of the mCAV study is a comprehensive characterization of the genetic, morphological and functional phenotype of isolated microvascular graft vasculopathy (mCAV) after orthotopic heart transplantation (OHT). The utilized methods include dynamic echocardiography, magnetic resonance imaging, invasive microvascular resistance measurements, histology, cellular calcium-signaling and magnetocardiography as well as molecular genetic expression analysis.
The goal of this research study is to understand if a blood test in people who have had heart transplants can detect and predict the following: - Blockages in the small blood vessels of the heart. - Whether small blockages can turn into more severe blockages in the future. Participants will undergo blood draws once every 3 months in the first year of the study (4 blood draws total, taking 15 minutes each) and their medical records will be reviewed for 3 years after the date they are enrolled in the study.
Many patients with end-stage heart failure, a condition in which the heart fails to pump enough blood to support the body's other organs, are fortunate enough to receive a heart transplant. However, despite taking medicines aimed at blunting the immune system's response to the donor heart, some of them will develop transplant-related disease in the coronary arteries supplying their hearts. Fifty years after the first human-to-human heart transplant, this disorder-cardiac allograft vasculopathy (CAV)-remains a leading cause of long-term death and has been coined the 'Achilles' Heel' of heart transplantation. Indeed, a better understanding of how CAV occurs and improved therapies to prevent and/or slow its development are desperately needed to meaningfully impact patient outcomes. Endothelin-1 (ET-1) is a key molecular regulator of arterial health, and our prior data suggests that it is associated with accelerated CAV. In this particular study of recent heart transplant recipients, we are asking: Does ET-1 contribute to the coronary artery's capacity to dilate/constrict? To answer this question, during the cardiac catheterization at 1 year post-transplant (standard of care), we will measure blood levels of ET-1 and perform an invasive evaluation of coronary vasomotor function inn a consecutive subset of patients who will have received a 1-week course of the oral endothelin receptor antagonist (macitentan) prior this catheterization, which will allow us to test how much ET-1 contributes to coronary responsiveness. The findings from this study may provide the necessary foundation to study whether endothelin receptor antagonists are able to effectively reduce the rate of accelerated CAV.
Cross-sectional study. We will prospectively obtain ddcf-DNA levels in all patients who undergo routine coronary angiography > 1 year after HT. Our main goal is to evaluate the performance of Donor-derived Cell Free DNA (ddcf-DNA) as a biomarker of CAV.
Cardiac allograft vasculopathy is a common complication affecting heart transplant patients. This condition causes narrowing of the heart arteries leading to graft dysfunction. The research team is investigating whether early antiplatelet therapy post heart transplant can prevent the development of CAV. This study will determine the feasibility of a large multicenter randomized placebo-controlled trial to answer this question.
Heart transplantation is a golden standard for the treatment of terminal heart failure. The major cause of death in late posttransplant period is cardiac allograft vasculopathy (CAV). This posttransplant complication develops slowly over several years, and when diagnosed either by conventional coronary angiography or due to graft failure, it is often too advanced and difficult to treat since it is diffuse coronary artery disease. Therefore, early prevention of CAV is a subject of major interest in the transplant cardiology. Since CAV is associated with immune factors, immunomodulatory therapeutic options, like extracorporeal photopheresis are lately being investigated. Unlike conventional coronary angiography, optical coherence tomography (OCT) is able to detect the development of CAV in the earliest phase, i.e. even in the first post-transplant year. In our study, we plan to investigate the prophylactic effect of extracorporeal photopheresis in the early development of cardiac graft vasculopathy detected by OCT.
Cardiac allograft vasculopathy (CAV) represents the leading cause of late morbidity and mortality in heart transplant recipients as the second most frequent cause of all deaths at 3 years. In distinction from general coronary atherosclerosis, CAV affects diffusely the entire coronary vasculature with marked intimal proliferation and concentric vascular thickening and fibrosis. It was demonstrated that most of the intimal thickening due to CAV occurs during the first year after transplantation. Furthermore, the severity of the CAV appears to correlate with lipid abnormalities and elevated low-density lipoprotein cholesterol (LDL-C) is very common after transplantation with nadir of LDL levels occurring at 6 months. Because of drug-drug interactions, heart transplant recipients cannot be treated with adequate doses of statins to achieve desirable reduction of LDL-C levels (reduction ˂ 60% of LDL-C). The use of alternative lipid-lowering drugs including bile acid sequestrates, fibrates, nicotinic acid or ezetimibe is not recommended in post-transplant scenario. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) increase availability has emerged as a novel drug tool for LDL-C lowering, capable to lower LDL-C by more than 60% even in statin-treated patients with very good safety profile. Although heart transplant recipients fulfill approved indication and standard clinical guidelines of a PCSK9 inhibitor, alirocumab, there are no available data on use of PCSK9 inhibitor in post-transplant situation. The purpose of the ACAV study is to clarify efficacy and safety of alirocumab compared to placebo administered during the first year after transplantation in heart transplant recipients in addition to background atorvastatin therapy. Except lipid profile, optical coherence tomography (OCT) will be performed as the objective efficacy endpoint to examine thickness and lumen of coronary vessels. It is expected that inhibition of PCSK9 in heart transplant recipient will dramatically improve post-transplant lipoprotein levels and perhaps slow down development of CAV in the most critical period of the first year after transplantation.
Studies have shown that cardiac function is affected immediately after heart transplantation (HTx), but seems to recover to some extent over the first year. This immediate effect is associated with lack of oxygen in the tissue and reperfusion injury causing cellular energy depletion, mitochondrial failure and cellular damage. This condition may progress into full blown primary graft failure (PGF), characterized as deterioration of the transplanted heart, which is seen in 3-30 % of HTx patients. In addition to PGF, chronic rejection owing to cardiac allograft vasculopathy (CAV) may develop. PGF and CAV remain the major heart related mortality causes, and additional assessment and treatments are therefore needed. Acute cellular rejection (ACR) is diagnosed based on endomyocardial biopsies (EMB), which are routinely performed to ensure prober immunosuppression in HTx patients. ACR occur in approximately 25% of HTx patients, and is associated with PGF and CAV. However, mitochondrial function and integrity may prove to be a more sensitive marker of allograft rejection than endomyocardial biopsies. Therefore, assessment of mitochondrial function may allow for earlier detection of allograft rejection and dysfunction. This may be of particular importance as emerging treatments are targeting both energy substrate supply for adenosine-triphosphate generation produced by the mitochondria and mitochondrial function in the failing heart. Despite the association between graft rejection and mitochondrial function, it remains unsettled whether mitochondrial function associate with PGF, ACR and CAV. Such findings may be of prognostic importance and even elucidate new treatment targets. Hence, we evaluate the mitochondrial status in HTx patients through four studies designed to assess different aspects of the interplay between cardiac function and mitochondrial integrity and function. Hypotheses: Study 1: Primary graft pump function is correlated to mitochondrial function in the first myocardial biopsy taken from the donor heart during the operation. Study 2: Cardiac mitochondrial function improves over the first 3 months after a heart transplantation. Study 3: Heart transplant patients with moderate to severe coronary graft vasculopathy has impaired mitochondrial function. Study 4: Myocardial external energy efficiency by positron-emission tomography can be used as a marker of mitochondrial function and chronic rejection in HTx patients.