Prosthesis–patient mismatch is less frequent and more clinically indolent in patients operated for aortic insufficiency

ObjectiveTo date, no study has focused on the incidence and effects of prosthesis–patient mismatch in patients requiring aortic valve replacement for aortic insufficiency. We hypothesized that the incidence and implications of prosthesis–patient mismatch in patients with aortic insufficiency might be different than for aortic stenosis or mixed disease because the annulus is generally larger in aortic insufficiency and left ventricular remodeling might differ.MethodsNinety-eight patients with lone aortic insufficiency (≥3+ with a preoperative mean gradient <30 mm Hg) were followed over 7.7 ± 4.3 years (maximum, 17.5 years) with clinical and echocardiographic assessments. They were compared with 707 patients who had aortic valve replacement for aortic stenosis or mixed disease. Prosthesis–patient mismatch was defined as an in vivo indexed effective orifice area of 0.85 cm2/m2 or less.ResultsCompared with patients with aortic stenosis/mixed disease, patients with aortic insufficiency had approximately half the incidence of prosthesis–patient mismatch (P = .003). Patients with prosthesis–patient mismatch had significantly higher transprosthesis gradients postoperatively. An independent detrimental effect of prosthesis–patient mismatch on survival was observed in patients with aortic stenosis/mixed disease who had preoperative left ventricular dysfunction (hazard ratio, 2.3; P = .03) but not in patients with aortic insufficiency, irrespective of left ventricular function (hazard ratio, 0.7; P = .7). In patients with aortic stenosis/mixed disease with left ventricular dysfunction, prosthesis–patient mismatch predicted heart failure symptoms by 3 years after aortic valve replacement (odds ratio, 6.0; P = .002), but there was no such effect in patients with aortic insufficiency (P = .8). Indexed left ventricular mass regression occurred to a greater extent in patients with aortic insufficiency than in patients with aortic stenosis/mixed disease (by an additional 29 ± 5 g/m2, P < .001), and there was a trend for prosthesis–patient mismatch to impair regression in patients with aortic insufficiency (by 30 ± 17 g/m2, P = .1).ConclusionsThe incidence and significance of prosthesis–patient mismatch differs in patients with aortic insufficiency compared with those with aortic stenosis or mixed disease. In patients with aortic insufficiency, prosthesis–patient mismatch is seen less frequently and has no significant effect on survival and freedom from heart failure but might have a negative effect on left ventricular mass regression

Results of the minimally invasive coronary artery bypass grafting angiographic patency study

ObjectiveMinimally invasive coronary artery bypass grafting is safe and widely applicable, and may be associated with fewer transfusions and infections, and better recovery than standard coronary artery bypass grafting. However, graft patency rates remain unknown. The Minimally Invasive Coronary Artery Bypass Grafting Patency Study prospectively evaluated angiographic graft patency 6 months after minimally invasive coronary artery bypass grafting.MethodsIn this dual-center study, 91 patients were prospectively enrolled to undergo minimally invasive coronary artery bypass grafting via a 4- to 7-cm left thoracotomy approach. The left internal thoracic artery, the ascending aorta for proximal anastomoses, and all coronary targets were directly accessed without endoscopic or robotic assistance. The study primary outcome was graft patency at 6 months, using 64-slice computed tomography angiography. Secondary outcomes included conversions to sternotomy and major adverse cardiovascular events (Clinical Trial Registration Unique identifier: NCT01334866).ResultsThe mean age of patients was 64 ± 8 years, the mean ejection fraction was 51% ± 11%, and there were 10 female patients (11%) in the study. Surgeries were performed entirely off-pump in 68 patients (76%). Complete revascularization was achieved in all patients, and the median number of grafts was 3. There was no perioperative mortality, no conversion to sternotomy, and 2 reopenings for bleeding. Transfusion occurred in 24 patients (26%). The median length of hospital stay was 4 days, and all patients were followed to 6 months, with no mortality or major adverse cardiovascular events. Six-month computed tomography angiographic graft patency was 92% for all grafts and 100% for left internal thoracic artery grafts.ConclusionsMinimally invasive coronary artery bypass grafting is safe, feasible, and associated with excellent outcomes and graft patency at 6 months post-surgery

Comparative Analysis Following Implementation of Two Types of Y‐Composite Multiarterial Revascularization Strategies at a Single Academic Institution

Background We compared early outcomes, at a single academic institution, of implementing full coronary revascularization in coronary artery bypass grafting using multiarterial Y‐composite grafts with multiple sequential anastomoses. Methods and Results Clinical records of 425 consecutive patients who underwent coronary artery bypass grafting using Y‐grafting with left internal mammary artery and radial artery (Y‐RA group) or right internal mammary artery (Y‐RIMA group) from 2015 to 2019, were reviewed. These were compared with the institutional experience of isolated coronary artery bypass grafting cases (in situ on pump/off pump) for the same period of time. When comparing the 4 groups, the Y‐RIMA/RA groups revealed a higher number of distal anastomosis than the in situ on‐ or off‐pump groups. When the number of distal arterial anastomosis was analyzed, there was a superiority of using the Y‐configuration compared with the in situ approach. Moreover, there were no significant differences among groups for mortality and/or major adverse cardiac and cerebrovascular events in hospital or at 30‐day follow‐up. A subanalysis comparing the Y‐RIMA group with the Y‐RA group showed that complementary grafts to the Y‐construct were required to accomplish full revascularization more frequently in the Y‐RIMA group. Full‐arterial revascularization was achieved in 92.2% of the Y‐RA group and 72.0% of the Y‐RIMA group (P<0.001). In 82.8% of the Y‐RA group and 30.8% of the Y‐RIMA group, revascularization was completed as an anaortic procedure (P<0.001). Conclusions The 2 types of arterial Y‐composite grafting were able to be introduced in the routine practice of our institution showing comparable results to the established institutional practice. This procedure allowed for more arterial distal anastomosis to be performed safely without compromising outcomes

Clinical-grade generation of active NK cells from cord blood hematopoietic progenitor cells for immunotherapy using a closed-system culture process

Contains fulltext : 97724.pdf (publisher's version ) (Open Access)Natural killer (NK) cell-based adoptive immunotherapy is a promising treatment approach for many cancers. However, development of protocols that provide large numbers of functional NK cells produced under GMP conditions are required to facilitate clinical studies. In this study, we translated our cytokine-based culture protocol for ex vivo expansion of NK cells from umbilical cord blood (UCB) hematopoietic stem cells into a fully closed, large-scale, cell culture bioprocess. We optimized enrichment of CD34(+) cells from cryopreserved UCB units using the CliniMACS system followed by efficient expansion for 14 days in gas-permeable cell culture bags. Thereafter, expanded CD34(+) UCB cells could be reproducibly amplified and differentiated into CD56(+)CD3(-) NK cell products using bioreactors with a mean expansion of more than 2,000 fold and a purity of >90%. Moreover, expansion in the bioreactor yielded a clinically relevant dose of NK cells (mean: 2x10(9) NK cells), which display high expression of activating NK receptors and cytolytic activity against K562. Finally, we established a versatile closed washing procedure resulting in optimal reduction of medium, serum and cytokines used in the cell culture process without changes in phenotype and cytotoxic activity. These results demonstrate that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials