Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial

Abstract

IntroductionCardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial.Study designThe AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days.Ethics and disseminationThe institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings.Trial registration numberClinicalTrials.gov: NCT02798276, pre-results.

Electrophysiological effects of adipose graft transposition procedure (AGTP) on the post-myocardial infarction scar: A multimodal characterization of arrhythmogenic substrate

“…Our findings suggest that this reparative therapy is safe and may provide protective antiarrhythmic effects, adding a potential benefit against arrhythmic events on top of reducing scar size and heterogeneity and improving LV function. These findings provide additional safety information that will require further confirmation from the ongoing AGTP II randomized clinical trial (phase II-III; NCT02798276) ( 6 ). The AGTP is a simple technique that does not require exogenous cell therapy or cardiac tissue engineering products and avoids histocompatibility issues, making the procedure readily available to any patient with chronic MI undergoing cardiac surgery.…”

“…In the first-in-human phase I trial, this therapy proved to be safe in terms of arrhythmic events, hospital admissions, and mortality ( 5 ). Currently, AGTP efficacy is being tested in a multicenter, randomized, controlled phase II-III clinical trial (AGTP II Trial, NCT02798276) ( 6 ).…”

An immunohistochemical and biomechanical evaluation of the effect of fat graft on tendon healing

“…19,20 Thus, local adipose tissue grafting has been shown to be an easy-to-apply, low-cost method that provides successful results. 13 In the current study, for the first time in literature, the application of fat graft, which is a low-cost, easy-to-apply, and easily accessible method, was used in experimental tendon healing.…”

Epicardial Adipose Tissue: A Novel Potential Imaging Marker of Comorbidities Caused by Chronic Inflammation

“…A population of human adult mesenchymal-like cells derived from cardiac adipose tissue (cardiac adipose tissue mesenchymal stem cells—cATMSCs) was identified and characterized. These cells, despite residing in an adipocytic environment, have an inherent cardiac-like phenotype and may play a role in heart homeostasis and act as a cellular reservoir for myocardial tissue renewal promoting neovascularization, improving local microcirculation, metabolism, microenvironment at the scar site, and enhancing myocardial contractility [ 67 ]. Finally, metabolic and cardiovascular diseases are multifactorial disorders to which contributes the inflammation of the adipose tissue and EAT in our specific contest.…”