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

The impact of patient–prosthesis mismatch on late outcomes after mitral valve replacement

ObjectivesThe incidence of patient–prosthesis mismatch after mitral valve replacement and its effect on late outcomes have remained unclear. This study was conducted to determine the impact of patient–prosthesis mismatch on recurrent congestive heart failure, postoperative pulmonary hypertension, and late survival after mitral valve replacement.MethodsBetween 1985 and 2005, 884 patients, with a mean age 63 ± 12 years, underwent mitral valve replacement (657 mechanical, 227 bioprosthesis) with contemporary prostheses. Mean clinical and echocardiographic follow-up was 5.1 ± 4.1 years (4344 patient-years). Patient–prosthesis mismatch was defined as an indexed effective orifice area of 1.25 cm2/m2 or less. Parametric and nonparametric analyses were used to determine predictors of outcomes.ResultsThe incidence of patient–prosthesis mismatch was 32%. Predictors of recurrent congestive heart failure included low indexed effective orifice area, low ejection fraction, elevated postoperative mean mitral gradient, and use of a bioprosthesis (P ≤ .05). Postoperative pulmonary hypertension was associated with small mitral size, elevated mean mitral gradient, low ejection fraction, and atrial fibrillation (P ≤ .05); indexed effective orifice area did not predict postoperative pulmonary hypertension (P = .89). Poor late survival was predicted by low indexed effective orifice area (≤1.25 cm2/m2), New York Heart Association class 3 or 4, elevated right ventricular pressure, stroke, older age, coronary artery disease, and bioprosthesis use (P ≤ .05). Survival for patients with patient–prosthesis mismatch versus those without patient–prosthesis mismatch at 1, 3, 5, and 10 years was 91% versus 95%, 85% versus 90%, 78% versus 86%, and 65% versus 75%, respectively (P = .05).ConclusionsPatient–prosthesis mismatch after mitral valve replacement is not uncommon; it is associated with recurrence of congestive heart failure and postoperative pulmonary hypertension and independently affected late survival. This study emphasizes the importance of implanting a sufficiently large prosthesis in adult patients undergoing mitral valve replacement

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

Design of a 3D printer head for additive manufacturing of sugar glass for tissue engineering applications

Additive manufacturing is now considered as a new paradigm that is foreseen to improve progress in many fields. The field of tissue engineering has been facing the need for tissue vascularization when producing thick tissues. The use of sugar glass as a fugitive ink to produce vascular networks through rapid casting may offer the key to vascularization of thick tissues produced by tissue engineering. Here, a 3D printer head capable of producing complex structures out of sugar glass is presented. This printer head uses a motorized heated syringe fitted with a custom made nozzle. The printer head was adapted to be mounted on a commercially available 3D printer. A mathematical model was derived to predict the diameter of the filaments based on the printer head feed rate and extrusion rate. Using a 1 mm diameter nozzle, the printer accurately produced filaments ranging from 0.3 mm to 3.2 mm in diameter. One of the main advantages of this manufacturing method is the self-supporting behaviour of sugar glass that allows the production of long, horizontal, curved, as well as overhanging filaments needed to produce complex vascular networks. Finally, to establish a proof of concept, polydimethylsiloxane was used as the gel matrix during the rapid casting to produce various “vascularized” constructs that were successfully perfused, which suggests that this new fabrication method can be used in a number of tissue engineering applications, including the vascularization of thick tissues

Insulin treatment enhances the myocardial angiogenic response in diabetes

ObjectiveGrowth factor and cell-based angiogenesis are attractive therapeutic options for diabetic patients with end-stage coronary disease. Reduced collateral vessel formation observed in diabetes is associated with increased expression of anti-angiogenic proteins, angiostatin and endostatin. The aim of this study was to determine the effects of insulin treatment on the diabetic angiogenic response to chronic myocardial ischemia.MethodsYucatan miniswine were treated with alloxan (pancreatic β-cell specific toxin, 150 mg/kg) and divided into two groups. In the diabetic group (DM, n = 8), blood glucose levels were kept greater than 250 mg/dL, and in the insulin-treated group (IDM, n = 6), intramuscular insulin was administered daily to keep blood glucose less than 150 mg/dL. A third group of age-matched swine served as nondiabetic controls (ND; n = 8). Eight weeks later, all animals underwent circumflex artery ameroid constrictor placement to induce chronic ischemia. Myocardial perfusion was assessed at 3 and 7 weeks after ameroid placement using microspheres. Microvascular function, capillary density, and myocardial expression of anti-angiogenic mediators were evaluated.ResultsDiabetic animals exhibited significant impairments in endothelium-dependent microvessel relaxation to adenosine diphosphate and substance P, which were reversed in insulin-treated animals. Collateral-dependent perfusion in the ischemic circumflex territory, which was profoundly reduced in diabetic animals (−0.18 ± 0.02 vs +0.23 ± 0.07 mL · min−1 · g−1; P < .001), improved significantly with insulin treatment (0.12 ± 0.05 mL · min−1 · g−1; P < .01). Myocardial expression of anti-angiogenic proteins, angiostatin and endostatin, showing a 4.3- and 3.6-fold increase in diabetic animals respectively (both P < .01 vs ND), was markedly reduced in insulin-treated animals (2.3- and 1.8-fold vs ND; both P < .01).ConclusionsInsulin treatment successfully reversed diabetic coronary endothelial dysfunction and significantly improved the endogenous angiogenic response. These pro-angiogenic effects may be mediated through downregulation of anti-angiogenic mediators. Insulin therapy appears to be a promising modality to enhance the angiogenic response in diabetic patients

A nanoparticle ink allowing the high precision visualization of tissue engineered scaffolds by MRI

Hydrogels are widely used as cell scaffolds in several biomedical applications. Once implanted in vivo, cell scaffolds must often be visualized, and monitored overtime. However, cell scaffolds appear poorly contrasted in most biomedical imaging modalities such as magnetic resonance imaging (MRI). MRI is the imaging technique of choice for high-resolution visualization of low-density, water-rich tissues. Attempts to enhance hydrogel contrast in MRI are performed with “negative” contrast agents that produce several image artifacts impeding the delineation of the implant’s contours. In this study, a magnetic ink based on ultra-small iron oxide nanoparticles (USPIONs; <5 nm diameter cores) is developed and integrated into biocompatible alginate hydrogel used in cell scaffolding applications. Relaxometric properties of the magnetic hydrogel are measured, as well as biocompatibility and MR-visibility (T1-weighted mode; in vitro and in vivo). A 2-week MR follow-up study is performed in the mouse model, demonstrating no image artifacts, and the retention of “positive” contrast overtime, which allows very precise delineation of tissue grafts with MRI. Finally, a 3D-contouring procedure developed to facilitate graft delineation and geometrical conformity assessment is applied on an inverted template alginate pore network. This proof-of-concept establishes the possibility to reveal precisely engineered hydrogel structures using this USPIONs ink high-visibility approach

BEaTS-β: an open-source electromechanical bioreactor for simulating human cardiac disease conditions

Heart disease remains the leading cause of worldwide mortality. Although the last decades have broadened our understanding of the biology behind the pathologies of heart disease, ex vivo systems capable of mimicking disease progression and abnormal heart function using human cells remain elusive. In this contribution, an open-access electromechanical system (BEaTS-β) capable of mimicking the environment of cardiac disease is reported. BEaTS-β was designed using computer-aided modeling to combine tunable electrical stimulation and mechanical deformation of cells cultured on a flexible elastomer. To recapitulate the clinical scenario of a heart attack more closely, in designing BEaTS-β we considered a device capable to operate under hypoxic conditions. We tested human induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and coronary artery endothelial cells in our simulated myocardial infarction environment. Our results indicate that, under simulated myocardium infarction, there was a decrease in maturation of cardiomyocytes, and reduced survival of fibroblasts and coronary artery endothelial cells. The open access nature of BEaTS-β will allow for other investigators to use this platform to investigate cardiac cell biology or drug therapeutic efficacy in vitro under conditions that simulate arrhythmia and/or myocardial infarction