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.

Our interest in the mechanisms of atherosclerosis progression (ATHp) has led to the recent identification of 13 miRNAs and 1285 mRNAs whose expression was altered during ATHp. Here, we deepen the functional relationship among these 13 miRNAs and genes associated to oxidative stress, a crucial step in the onset and progression of vascular disease. We first compiled a list of genes associated to the response to oxidative stress (Oxstress genes) by performing a reverse Gene Ontology analysis (rGO, from the GO terms to the genes) with the GO terms GO0006979, GO1902882, GO1902883 and GO1902884, which included a total of 417 unique Oxstress genes. Next, we identified 108 putative targets of the 13 miRNAs among these unique Oxstress genes, which were validated by an integrated miRNA/mRNA counter-expression analysis with the 1285 mRNAs that yielded 14 genes, Map2k1, Mapk1, Mapk9, Dapk1, Atp2a2, Gata4, Fos, Egfr, Foxo1, Ccr7, Vkorc1l1, Rnf7, Kcnh3, and Mgat3. GO enrichment analysis and a protein–protein-interaction network analysis (PPI) identified most of the validated Oxstress transcripts as components of signaling pathways, highlighting a role for MAP signaling in ATHp. Lastly, expression of these Oxstress transcripts was measured in PBMCs from patients suffering severe coronary artery disease, a serious consequence of ATHp. This allowed the identification of FOXO1 and CCR7 as blood markers downregulated in CAD. These results are discussed in the context of the interaction of the Oxstress transcripts with the ATHp-associated miRNAs.

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BackgroundIschemic postconditioning (IPostC), has been proposed as a useful approach to reduce infarct size in all species, but its clinical utility remains unclear.ObjectiveTo investigate the role played by the protocol used on the efficacy of IPostC in protecting the diseased human myocardium.MethodsMyocardial atrial samples from patients were subjected to a 90 min ischemia/120 min reoxygenation followed by different IPostC protocols to investigate the role of the time of ischemia (30, 60, 90 and 120 s) and the number of cycles (1, 2, 3 and 4) with 60 and 120 s of total ischemic time. Muscles were also subjected to ischemic preconditioning (IPreC). The release of lactate dehydrogenase (LDH) and the measurement of tetrazolium bromide (MTT) were determined.ResultsIPostC increased the LDH and decreased the MTT values from those of control, independently of the duration of the conditioning ischemia. LDH and MTT values also worsened by augmenting the number of IPostC cycles whereas they were significantly improved by IPreC. However, analysis of individual results indicated that in approximately 1/3 of the cases IPostC exhibited some degree of protection especially in the presence of increased ischemic injury.ConclusionsThe present findings show that IPostC of the human myocardium may be influenced by the protocol used and also by the degree of the preceding ischemic injury. IPostC was beneficial in approximately 1/3 of the cases; however in the remaining cases it increased ischemic damage and, therefore, these results raise a word of caution on its broad clinical use.

Cardiovascular mortality increases with decreasing renal function although the cause is yet unknown. Here, we have investigated whether low chronic inflammation in chronic kidney diseases (CKD) could contribute to increased risk for coronary artery diseases (CAD). Thus, a prospective case–control study was conducted in patients with CAD and CKD undergoing coronary artery bypass graft surgery with the aim of detecting differences in cardiovascular outcomes, epicardial adipose tissue volume, and inflammatory marker activity associated with renal dysfunction. Expression of membrane CD14 and CD16, inflammatory cytokines and chemokines, mitogen-activated protein (MAP) kinases and hsa-miR-30a-5p were analyzed in peripheral blood mononuclear cells (PBMCs). Epicardial fat volume and tissue inflammation in perivascular adipose tissue and in the aorta were also studied. In the present study, 151 patients were included, 110 with CAD (51 with CKD) and 41 nonCAD controls (15 with CKD). CKD increased the risk of cardiac surgery–associated acute kidney injury (CSA-AKI) as well as the 30-day mortality after cardiac surgery. Higher counts of CD14++CD16+ monocytes were associated with vascular inflammation, with an increased expression of IL1β, and with CKD in CAD patients. Expression of hsa-miR-30a-5p was correlated with hypertension. We conclude that CKD patients show an increased risk of CSA-AKI and mortality after cardiovascular surgery, associated with the expansion of the CD14++CD16+ subset of proinflammatory monocytes and with IL1β expression. We propose that inflammation associated with CKD may contribute to atherosclerosis (ATH) pathogenesis.

The P-Magna prosthesis showed significantly better overall and cardiac-related survival than the Mitroflow LX. The higher early SVD and reoperation rates seen with the Mitroflow LX prosthesis did not impact negatively on valve-related survival.

BackgroundThe diseased human myocardium is highly susceptible to ischemia/reoxygenation (I/R)-induced injury but its response to protective interventions such as ischemic preconditioning (IPreC) is unclear. Cardiac and other pre-existing clinical conditions as well as previous or ongoing medical treatment may influence the myocardial response to I/R injury and protection. This study investigated the effect of both on myocardial susceptibility to I/R-induced injury and the protective effects of IPreC.Methods and resultsAtrial myocardium from cardiac surgery patients (n = 300) was assigned to one of three groups: aerobic control, I/R alone, and IPreC. Lactate dehydrogenase leakage, as a marker of cell injury, and cell viability were measured. The basal redox status was determined in samples from 90 patients.The response to I/R varied widely. Myocardium from patients with aortic valve disease was the most susceptible to injury whereas myocardium from dyslipidemia patients was the least susceptible. Tissue from females was better protected than tissue from males. Myocardium from patients with mitral valve disease was the least responsive to IPreC. The basal redox status was altered in the myocardium from patients with mitral and aortic valve disease.ConclusionsThe response of the myocardium to I/R and IPreC is highly variable and influenced by the underlying cardiac pathology, dyslipidemia, sex, and the basal redox status. These results should be taken into account in the design of future clinical studies on the prevention of I/R injury and protection.