Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery

Background: Cardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) and are aimed at functionally repairing the myocardium that suffers from or is damaged by ischemia. This non-randomized open-label study assessed the safety and feasibility of epicardial transplantation of atrial appendage micrografts (AAMs) in patients undergoing CABG surgery.Methods: Twelve consecutive patients destined for CABG surgery were included in the study. Six patients received AAMs during their operation and six patients were CABG-operated without AAMs transplantation. Data from 30 elective CABG patients was collected for a center- and time-matched control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially onto the infarct scar site identified in preoperative late gadolinium enhancement cardiac magnetic resonance imaging (CMRI). The primary outcome measures at the 6-month follow-up were (i) patient safety in terms of hemodynamic and cardiac function over time and (ii) feasibility of therapy administration in a clinical setting. Secondary outcome measures were left ventricular wall thickness, change in myocardial scar tissue volume, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide levels, NYHA class, number of days in hospital and changes in the quality of life.Results: Epicardial transplantation of AAMs was safe and feasible to be performed during CABG surgery. CMRI demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment.Conclusions and Relevance: Transplantation of AAMs shows good clinical applicability as performed during cardiac surgery, shows initial therapeutic effect on the myocardium and has the potential to serve as a delivery platform for cardiac gene therapies.Trial Registration:ClinicalTrials.gov, identifier: NCT02672163.

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Autologous cardiac micrografts as support therapy to coronary artery bypass surgery

10.1101/2021.03.05.21252995 ◽

2021 ◽

Author(s):

Annu Nummi ◽

Severi Mulari ◽

Juhani A. Stewart ◽

Sari Kivistö ◽

Kari Teittinen ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Bypass ◽

Outcome Measures ◽

Coronary Artery Bypass Surgery ◽

Bypass Surgery ◽

Artery Bypass ◽

Left Ventricular ◽

Atrial Appendage ◽

Cabg Surgery ◽

Link Type

AbstractObjectivesCardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) for treating the myocardium suffering from or damaged by ischemia. This phase 1, open-label study assessed the safety and feasibility of epicardial transplantation of atrial appendage micrografts (AAMs) in patients undergoing CABG surgery.MethodsTwelve consecutive patients destined for CABG surgery were included in the study. Six patients received AAMs during their operation and six patients were CABG-operated without AAMs treatment. Data from 30 elective CABG patients was collected for a conjunctive control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially on the infarct scar site identified in preoperative CMR. The primary outcome measures at six-months follow-up were i) patient safety in terms of hemodynamic and cardiac function over time and ii) feasibility of therapy administration in a clinical setting. Secondary outcome measures were left ventricular wall thickness, change in myocardial scar tissue volume, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, NYHA class, number of days in hospital and changes in the quality of life.ResultsEpicardial transplantation of AAMs was safe and feasible to be performed in conjunction with CABG surgery. CMR demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment.ConclusionTransplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can additionally serve as a delivery platform for cardiac gene therapies.Trial RegistrationClinicalTrials.gov identifier NCT02672163

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Abstract 233: Cardiac Dysfunction Is Associated with Diminished Cardiac Neuropeptide Expression in Patients Undergoing Coronary Artery Bypass Surgery

Circulation Research ◽

10.1161/res.111.suppl_1.a233 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Leena Pradhan-Nabzdyk ◽

Asma Ejaz ◽

Frank W LoGerfo

Keyword(s):

Coronary Artery ◽

Coronary Artery Bypass ◽

Coronary Artery Bypass Surgery ◽

Bypass Surgery ◽

Artery Bypass ◽

Left Ventricular ◽

Right Atrial ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

The Relationship

Background: Neuropeptide Y (NPY) and its receptors, NPY1R, NPY2R, and NPY5R, Substance P (SP) and its receptor Neurokinin 1R (NK1R) and calcitonin gene related peptide (CGRP), are important regulators of cardiac physiology, including: vasomodulation, cardiomyocyte hypertrophy, ischemia-induced angiogenesis, modulation of Protein Kinase C activity and calcium homeostasis.[[Unable to Display Character: ]] Objective: To determine the relationship between cardiac function and neuropeptide expression in human subjects. Methods: 38 consecutive patients undergoing elective, on pump, coronary artery bypass surgery (CABG) for coronary artery occlusive disease were studied. A Transesophageal Echo was performed immediately following induction of anesthesia and Left Ventricular Ejection Fraction (LVEF) was determined by AHA criteria as Normal, >55% (NLVEF, n = 26) or Low, <50% (LLVEF, n = 12). Patients with HbA1c>6.0 were considered diabetic. Right atrial tissue was obtained at the time of cannulation and the mRNA expression of Pre-Pro-NPY, NPY1R, NPY2R, NPY5R, Pre-Pro-SP, NK1R and CGRP was determined with qRT-PCR. Data are expressed as fold change relative to the NLVEF group. Results: The results of this study are summarized in the table below. Conclusions: 1. There is a strong association of LLVEF with diminished expression of SP, NK1R and NPY5R, with a similar trend for NPY2R. 2. LLVEF was not associated with HbA1c or diabetes status. 3. The consequences of diminished cardiac neuropeptide expression, the mechanisms involved, the relationship to cardiac autonomic neuropathy, with or without diabetes, warrant priority as an investigational initiative.

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