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.

Efficacy of extracorporeal membrane oxygenation in a congenital heart surgery program.

BACKGROUND: To report our experience with extracorporeal membrane oxygenation (ECMO) in a congenital heart surgery program. METHODS: Since 12/1996, 24 patients (8 newborns, 9 infants, 3 children, 4 adolescents/ adults 17-23 years), mean age 4.0+/-7.4 years (2 days-23 years), body weight 2.7-87 kg had ECMO as circulatory support. Indication was failure to wean from cardiopulmonary bypass in the majority of cases. RESULTS: Mean duration of support was 3.8+/-2.9 d (12 h-13 d). Fourteen patients were weaned from ECMO (9 discharged), three successfully transplanted (one after switching to a pulsatile assist device). One patient on left-ventricular support required ECMO for sudden right ventricular failure (decreased). There were six deaths on ECMO due to multiorgan failure (MOV) (3) or no myocardial recovery (3). Six patients died after weaning (3 MOV, 2 myocardial failure, 1 fungal sepsis). Overall, twelve patients (50%) were discharged and are clinically well after 3.4+/-2.4 years (0.8-7.2 years). CONCLUSION: In our series, ECMO markedly reduces mortality in patients who would otherwise not survive either open heart surgery or myocardial failure of any origin and was not associated with discernible morbidity in the midterm.

Normative angiographic data relating to the dimensions of the aorta and pulmonary trunk in children and adolescents.

BACKGROUND: Definition of normative data of the great arteries from neonatal to adult ages may aid in assessment of the growth of cardiovascular structures, thus guiding the timing and type of intervention in patients with congenital cardiac disease. METHODS: We calculated the cross-sectional areas of the arterial roots at the basal attachment of the valvar leaflets, the sinuses, and standardized distal sites using cineangiograms of 59 normal children and adolescents with mean age of 5.4 plus or minus 4.7 years and a range from 0.1 to 16 years, the children having a mean weight of 21.2 plus or minus 15.7 kilograms, with a range from 2.2 to 68 kilograms, and mean height of 108 plus or minus 35 centimetres, with a range from 43 to 184 centimetres. Values at each site were calculated averaging end-diastolic and end-systolic measurements, and indexed to body surface area. Results are expressed as the mean plus or minus the standard deviation. RESULTS: The diameter of the aortic root at the basal attachment of the leaflets was 249 plus or minus 26, the midpoint of the sinuses 379 plus or minus 59, the sinutubular junction 290 plus or minus 58, the isthmus 158 plus or minus 36, the postisthmic region 152 plus or minus 33, and the descending aorta at the level of diaphragm 130 plus or minus 18 millimetres squared per metre squared. The pulmonary root measured at the basal attachment of the leaflets was 253 plus or minus 28, the midpoint of the sinuses 352 plus or minus 58, the sinutubular junction 293 plus or minus 58, the right pulmonary artery 176 plus or minus 25, the left pulmonary artery 153 plus or minus 20, and sum of right and left pulmonary arteries 330 plus or minus 37 millimetres squared per metre squared. All indexes were consistent over a wide range for body surface areas. CONCLUSIONS: Definition of normative data of the great vessels may aid in the evaluation of congenital or acquired abnormalities, serving as guidelines for intervention during medical or surgical management and follow-up.