The cardiac valvular endothelial cells (VECs) are an ideal cell source that could be used for making the valve organoids. However, few studies have been focused on the derivation of this important cell type. Here we describe a two-step chemically defined xeno-free method for generating VEC-like cells from human pluripotent stem cells (hPSCs). HPSCs were specified to KDR+/ISL1+ multipotent cardiac progenitors (CPCs), followed by differentiation into valve endothelial-like cells (VELs) via an intermediate endocardial cushion cell (ECC) type. Mechanistically, administration of TGFb1 and BMP4 may specify VEC fate by activating the NOTCH/WNT signaling pathways and previously unidentified targets such as ATF3 and KLF family of transcription factors. When seeded onto the surface of the de-cellularized porcine aortic valve (DCV) matrix scaffolds, hPSC-derived VELs exhibit superior proliferative and clonogenic potential than the primary VECs and human aortic endothelial cells (HAEC). Our results show that hPSC-derived valvular cells could be efficiently generated from hPSCs, which might be used as seed cells for construction of valve organoids or next generation tissue engineered heart valves.

Background: The optimal choice of the valve prosthesis in mitral valve replacement (MVR) for infective endocarditis (IE) is controversial and challenging, particularly for younger patients. Hypothesis: The postoperative outcomes of mechanical and biological MVR in IE patients aged 50 to 69 years are different. Methods: All IE patients aged 50 to 69 years with primary MVR in Hubei province hospitals from 2002 to 2018 were retrospectively reviewed. The median duration of follow-up was 8.7 years (IQR, 6.8-10.9 years). Propensity score matching (1:3 ratio) was used to yield 492 patients with comparable baseline features between bioprostheses and mechanical prosthetic valve groups. Outcomes were postoperative mid-to long-term survival, mitral valve reoperation, prosthetic valve endocarditis (PVE), stroke, and major bleeding events. Results: Fifteen-year survival after MVR was 80.6% in the mechanical valve group and 69.3% in the bioprostheses group (HR 0.545, P = .040). The cumulative incidence of mitral valve reoperation was 8.8% with mechanical valves and 21.4% with bioprostheses (HR 0.260, P = .002). The cumulative incidence of PVE was 5.6% with mechanical valves and 7.2% with bioprostheses (HR 0.629, P = .435). The cumulative incidence of stroke was 12.9% with mechanical valves and 10.5% with bioprostheses (HR 1.217, P = .647). The cumulative incidence of major bleeding was 12.0% with mechanical valves and 6.75% with bioprostheses (HR 1.579, P = .268). Conclusions: Mechanical valve prostheses were associated with better survival, lower rates of reoperation compared with bioprostheses within 15 years after MVR in IE patients aged 50 to 69. These findings suggest mechanical valve prostheses may be a more reasonable alternative to bioprostheses in this patient group.

Background: Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. A rare but fatal complication prosthetic valve endocarditis (PVE) could greatly influence the clinical outcomes of TAVR. This meta-analysis aims to pin down the predictors of PVE in TAVR patients. Methods: We performed a systematic search for studies that reported the incidence and risk factors of PVE after TAVR. Data on studies, patients, baseline characteristics, and procedural characteristics were abstracted. Crude risk ratios (RRs) and 95% confidence intervals for each predictor were calculated by the use of random-effects models. Heterogeneity assumption was assessed by an I2 test. Results: We obtained data from 8 studies that included 68,805 TAVR patients, of whom 1,256 (1.83%) were diagnosed with PVE after TAVR. 280 patients died within the 30-days of PVE diagnosis and the pooled in-hospital mortality was 22.3%. The summary estimates indicated an increased risk of PVE after TAVR for males (RR 1.53, P = .0001); for patients with orotracheal intubation (RR 1.65, P = .01), new pacemaker implantation (RR 1.46, P = .003), and residual aortic regurgitation (≥2 grade) (RR 1.62, P = .05); while older age (RR 0.97, P = .0007) and implantation of a self-expandable valve (RR 0.74, P = .02) were associated with a lower risk of PVE after TAVR. Conclusion: Clinical characteristics and peri-procedure factors including age, male sex, valve type, orotracheal intubation, pacemaker implantation, and residual regurgitation were proven to be associated with the occurrence of PVE-TAVR. Clinicians should pay particular attention to PVE when treating TAVR patients with these predictors.