Background Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. Methods We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. Results At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, −6.6 and −6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P = 0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P = 0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. Conclusions We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.)

Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.

Background Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. Methods We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). Results More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P = 0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P = 0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P = 0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. Conclusions The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.)

Cardiac surgery is the largest consumer of blood products in medicine; although believed life saving, transfusion carries substantial adverse risks. This study characterizes the relationship between transfusion and risk of major infection after cardiac surgery. 5,158 adults were prospectively enrolled to assess infections after cardiac surgery. The most common procedures were isolated coronary artery bypass grafting (31%) and isolated valve surgery (30%); 19% were reoperations. Infections were adjudicated by independent infectious disease experts. Multivariable Cox modeling was used to assess the independent effect of blood and platelet transfusions on major infections within 60±5 days of surgery. Red blood cells (RBCs) and platelets were transfused in 48% and 31% of patients, respectively. Each RBC unit transfused was associated with a 29% increase in crude risk of major infection (P<0.001). Among RBC recipients, the most common infections were pneumonia (3.6%) and bloodstream infections (2%). Risk factors for infection included postoperative RBC units transfused, longer duration of surgery, and transplant or ventricular assist device implantation, in addition to chronic obstructive pulmonary disease, heart failure, and elevated preoperative creatinine. Platelet transfusion decreased the risk of infection (P=.02). Greater attention to management practices that limit RBC use, including cell salvage, small priming volumes, vacuum-assisted venous return with rapid autologous priming, and ultrafiltration, and pre- and intraoperative measures to elevate hematocrit could potentially reduce occurrence of major postoperative infections.

In patients with angina refractory to medical treatment and coronary artery disease that precluded coronary-artery bypass surgery or percutaneous transluminal coronary angioplasty, transmyocardial revascularization improved cardiac perfusion and clinical status over a 12-month period.

Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Persistence of hyperacute rejection in Gal KO pigs due to elicited non Gal antibody response required further genetic modifications of donor pigs and better control of the B cell response to xeno antigens. We report significant prolongation of graft survival of 8 months when peri-transplant B-cell depletion was added to an established anti CD154 and MMF based immunosuppressive regimen. Specifically Galactosyl transferase “knock-out” and human CD46 transgenic (GTKO.CD46Tg) pig cardiac xenografts were heterotopically transplanted into specific pathogen free (SPF) baboons. The B cell numbers and non Gal antibody production remained suppressed for over 2 months after only 4 doses of induction treatment with an anti CD20 antibody. Continuous evaluation of the transplanted hearts and recipients by telemetry provided accurate assessment of graft function and aided post operative care, allowing prevention of several major complications. The significant difference in graft survival with the addition of anti CD20 antibody identifies a critical role for B cells in the mechanisms of delayed xenograft rejection and represents a significant advance toward clinical application.

Background Infections are the most common non-cardiac complication after cardiac surgery, but their incidence across a broad range of operations, as well as the management factors that shape infection risk, remain unknown. Objectives This study prospectively examines the frequency of postoperative infections and associated mortality, and modifiable management practices predictive of infections within 65 days from cardiac surgery. Methods This study enrolled 5,158 patients and analyzed independently adjudicated infections using a competing risk model (with death as the competing event). Results Nearly 5% of patients experienced major infections. Baseline characteristics associated with increased infection risk included chronic lung disease (hazard ratio [HR] 1.66; CI 1.21–2.26), heart failure (HR 1.47; CI 1.11–1.95), and longer surgery (HR 1.31; CI 1.21–1.41). Practices associated with reduced infection risk included prophylaxis with second-generation cephalosporins (HR 0.70; CI 0.52–0.94), whereas postoperative antibiotic duration >48 hours (HR 1.92; CI 1.28–2.88), stress hyperglycemia (HR 1.32; CI 1.01–1.73); intubation time of 24–48 hours (HR 1.49; CI 1.04–2.14); and ventilation >48 hours (HR 2.45; CI 1.66–3.63) were associated with increased risk. HRs for infection were similar with either <24 hours or <48 hours of antibiotic prophylaxis. There was a significant but differential effect of transfusion by surgery type (excluding left ventricular assist device procedures/transplant) (HR 1.13; CI 1.07–1.20). Major infections substantially increased mortality (HR 10.02; CI 6.12, 16.39). Conclusions Major infections dramatically affect survival and readmissions. Second-generation cephalosporins were strongly associated with reduced major infection risk, but optimal duration of antibiotic prophylaxis requires further study. Given practice variations, considerable opportunities exist for improving outcomes and preventing readmissions.

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