Dataset Information

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

ABSTRACT:

Objective

To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar.

Background

Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed.

Methods

MI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated.

Results

The AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (p = 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (p < 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (p = 0.002), the number of deceleration zones (p = 0.029), and the area of fractionated electrograms (p = 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (p = 0.021, p = 0.018, p = 0.051, respectively).

Conclusion

AGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.

SUBMITTER: Adelino R

PROVIDER: S-EPMC9530287 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Adeliño Raquel R Martínez-Falguera Daina D Curiel Carolina C Teis Albert A Marsal Roger R Rodríguez-Leor Oriol O Prat-Vidal Cristina C Fadeuilhe Edgar E Aranyó Júlia J Revuelta-López Elena E Sarrias Axel A Bazan Víctor V Andrés-Cordón Joan F JF Roura Santiago S Villuendas Roger R Lupón Josep J Bayes-Genis Antoni A Gálvez-Montón Carolina C Bisbal Felipe F

Frontiers in cardiovascular medicine 20220920

<h4>Objective</h4>To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar.<h4>Background</h4>Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed.<h4>Methods</h4>MI was induced in 20 swine. Contrast-enhanced magneti ...[more]

PMID: 36204562

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Project description: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.

Project description:BackgroundIn infarct-related ventricular tachycardia (VT), the circuit often corresponds to a location characterized by activation slowing during sinus rhythm (SR). However, the relationship between activation slowing during SR and vulnerability for reentry and correlation to components of the VT circuit are unknown. This study examined the relationship between activation slowing during SR and vulnerability for reentry and correlated these areas with components of the circuit.MethodsIn a porcine model of healed infarction, the spatial distribution of endocardial activation velocity was compared between SR and VT. Isthmus sites were defined using activation and entrainment mapping as areas exhibiting diastolic activity within the circuit while bystanders were defined as areas displaying diastolic activity outside the circuit.ResultsOf 15 swine, 9 had inducible VT (5.2±3.0 per animal) while in 6 swine VT could not be induced despite stimulation from 4 RV and LV sites at 2 drive trains with 6 extra-stimuli down to refractoriness. Infarcts with VT had a greater magnitude of activation slowing during SR. A minimal endocardial activation velocity cutoff ≤0.1 m/s differentiated inducible from noninducible infarctions (P=0.015). Regions of maximal endocardial slowing during SR corresponded to the VT isthmus (area under curve=0.84 95% CI, 0.78-0.90) while bystander sites exhibited near-normal activation during SR. VT circuits were complex with 41.7% exhibiting discontinuous propagation with intramural bridges of slow conduction and delayed quasi-simultaneous endocardial activation. Regions forming the VT isthmus borders had faster activation during SR while regions forming the inner isthmus were activated faster during VT.ConclusionsEndocardial activation slowing during SR may differentiate infarctions vulnerable for VT from those less vulnerable for VT. Sites of slow activation during SR correspond to sites forming the VT isthmus but not to bystander sites.

Dataset Information

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

Objective

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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