Beating-heart patch closure of muscular ventricular septal defects under real-time three-dimensional echocardiographic guidance: A preclinical study

ObjectivesSafe and effective device closure of ventricular septal defects remains a challenge. We have developed a transcardiac approach to close ventricular septal defects using a patch delivery and fixation system that can be secured under real-time three-dimensional echocardiographic guidance.MethodsIn Yorkshire pigs (n = 8) a coring device was introduced into the left ventricle through a purse-string suture placed on the left ventricular apex, and a muscular ventricular septal defect was created. The patch deployment device containing a 20-mm polyester patch was advanced toward the ventricular septal defect through another purse-string suture on the left ventricular apex, and the patch was deployed under real-time three-dimensional echocardiographic guidance. The anchor delivery device was then introduced into the left ventricle through the first purse-string suture. Nitinol anchors to attach the patch around the ventricular septal defect were deployed under real-time three-dimensional echocardiographic guidance. After patch attachment, residual shunts were sought by means of two-dimensional and three-dimensional color Doppler echocardiography. The heart was then excised, and the septum with the patch was inspected.ResultsA ventricular septal defect was created in the midventricular (n = 4), anterior (n = 2), and apical (n = 2) septum. The mean size was 9.8 mm (8.2–12.0 mm), as determined by means of two-dimensional color Doppler scanning. The ventricular septal defects were completely closed in 7 animals. In one a 2.4-mm residual shunt was identified. No anatomic structures were compromised.ConclusionsBeating-heart perventricular muscular ventricular septal defect closure without cardiopulmonary bypass can be successfully achieved by using a catheter-based patch delivery and fixation system under real-time three-dimensional echocardiographic guidance. This approach might be a better alternative to cardiac surgery or transcatheter device closure

Myocardial hypoxic stress mediates functional cardiac extracellular vesicle release

AIMS: Increased shedding of extracellular vesicles (EVs)-small, lipid bilayer-delimited particles with a role in paracrine signalling-has been associated with human pathologies, e.g. atherosclerosis, but whether this is true for cardiac diseases is unknown. METHODS AND RESULTS: Here, we used the surface antigen CD172a as a specific marker of cardiomyocyte (CM)-derived EVs; the CM origin of CD172a+ EVs was supported by their content of cardiac-specific proteins and heart-enriched microRNAs. We found that patients with aortic stenosis, ischaemic heart disease, or cardiomyopathy had higher circulating CD172a+ cardiac EV counts than did healthy subjects. Cellular stress was a major determinant of EV release from CMs, with hypoxia increasing shedding in in vitro and in vivo experiments. At the functional level, EVs isolated from the supernatant of CMs derived from human-induced pluripotent stem cells and cultured in a hypoxic atmosphere elicited a positive inotropic response in unstressed CMs, an effect we found to be dependent on an increase in the number of EVs expressing ceramide on their surface. Of potential clinical relevance, aortic stenosis patients with the highest counts of circulating cardiac CD172a+ EVs had a more favourable prognosis for transcatheter aortic valve replacement than those with lower counts. CONCLUSION: We identified circulating CD172a+ EVs as cardiac derived, showing their release and function and providing evidence for their prognostic potential in aortic stenosis patients