Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1–182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.

Background: Current guidelines recommend emergency surgical correction in patients with post infarction ventricular septal rupture (PIVSR), but patients with multiorgan failure are commonly managed conservatively because of high surgical risk. We assessed characteristics and outcomes of operated PIVSR patients with or without the use of short-term ventricular assist devices (ST-VADs). We also assessed the impact of a ST-VAD on the performance of surgery Methods: We retrospectively analysed all consecutive patients with PIVSR between January 2004 and May 2017. Baseline clinical characteristics, use of ST-VAD and performance of surgery during admission were assessed. The main outcome measured was in-hospital mortality. Results: A total of 28 patients were included. Mean age was 69.2 years. Most patients (20/28, 71.4%) underwent surgical repair. ST-VADs were used in 11/28 patients (39.3%). This percentage progressively increased across the study period, from 22.2% (2/9) in 2004–2011 to 58.3% (7/12) in 2015–2017 ( p=0.091). Patients undergoing ST-VAD use had poorer INTERMACS status, higher values of creatinine, lactate and alanine aminotransferase and lower left ventricular ejection fraction as compared with operated patients without support. In-hospital mortality did not differ according to the use of ST-VADs in operated patients (27.3% without ST-VAD vs. 22.2% with ST-VAD, p=0.604). All five patients undergoing early preoperative venoarterial extracorporeal membrane oxygenator support and delayed surgery survived at hospital discharge. Conclusions: ST-VAD use increased in patients with PIVSR. Despite a higher risk profile in operated patients undergoing ST-VAD use, mortality was not significantly different in these patients. Early preoperative venoarterial extracorporeal membrane oxygenation should be considered for very high risk PIVSR patients.

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