Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from six months after heart transplantation: the randomized MANDELA study.

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64.1mL/min/1.73m2 versus 52.9mL/min/1.73m2 ; difference +11.3mL/min/1.73m2 (p<0.001). By month 18, estimated GFR had increased by ≥10mL/min/1.732 in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by ≥25 mL/min/1.73m2 in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI versus the CNI-free regimen (p=0.015); 6/15 episodes in CNI-free patients occurred with EVR concentration <5ng/mL. Rates of adverse events and associated discontinuations were comparable EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. This article is protected by copyright. All rights reserved.

Impact of Elevated Donor Troponin I as Predictor of Adverse Outcome in Adult Heart Transplantation: A Single-center Experience.

BACKGROUND: Due to globally increasing donor organ shortage, investigation of previously described risk factors for utilizing marginal donor hearts is needed. The aim of this study was to determine the impact of elevated donor serum troponin I (TnI) levels on outcome after heart transplantation (HTx). METHODS: Between January 1996 and August 2013, 161 patients were reviewed for donor TnI serum levels (>0.3 ng/mL was considered elevated), postoperative outcome parameters, 30-day mortality, and 1-, 3-, and 5-year survival. RESULTS: TnI levels were elevated in 45 (28.0%) donors. Recipients of hearts with elevated TnI had higher incidence of postoperative systolic dysfunction, prolonged inotropic support, prolonged mechanical ventilation, and longer intensive care unit (ICU) stay (p < 0.001). This group had higher 30-day mortality (22.2% vs 8.6%, p = 0.03) and lower 1-, 3-, and 5-year survival (56%, 53%, and 50% versus 82%, 76%, and 69%, p = 0.032). Elevated TnI was the only independent risk factor for 30-day mortality (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.28-10.27, p = 0.015). CONCLUSIONS: Elevated donor TnI serum concentration seems to be a marker for adverse outcome and increased short- and long-term mortality after HTx. Nevertheless, many other perioperative variables and parameters can be associated with outcome.

The activity of nintedanib in an animal model of allogenic left lung transplantation resembling aspects of allograft rejection.

AIM OF THE STUDY: The prevention and treatment of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) remain unsatisfactory. Growth factors may play an important role in the development of CLAD. This study evaluated the effects of nintedanib, a receptor tyrosine kinase inhibitor, in the treatment of CLAD after experimental LTx. MATERIALS AND METHODS: A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the effect of nintedanib (50 mg/kg per day) on the development of CLAD. Therapy with nintedanib began 2 days before LTx and ended on postoperative day (POD) 20 (n = 6) or 60 (n = 6). Nontreated animals who underwent LTx (n = 12) were used as controls, whereas naïve lungs (n = 24) served as reference for physiological healthy organs without transplantation damage or medical effects. Acute and chronic rejection were evaluated on POD 20 and 60, respectively. RESULTS: Immunohistologic analysis showed a decrease in growth factors/receptors on POD 60 (nintedanib-treated vs. nontreated controls: platelet-derived growth factor (PDGF) A: [P ≤ 0.001]; PDGF receptor-α: [P ≤ 0.001]; vascular endothelial growth factor (VEGF) A: [P ≤ 0.001]; VEGF receptor-2: [P ≤ 0.001]). However, no reductions in fibrotic changes were observed in nintedanib-treated allografts compared with nontreated allografts. Although nintedanib treatment started before LTx none of the animals showed impaired wound healing. No dehiscence of the sutures of the bronchus, vessels or skin, or stenosis of the bronchus was found. CONCLUSION: In conclusion, while nintedanib reduced the expression of growth factors/receptors in a rat LTx model, a reduction in fibrotic alterations was not observed at POD 60.

Minimized extracorporeal circulation is improving outcome of coronary artery bypass surgery in the elderly.

Advanced age is a known risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). Minimized extracorporeal circulation (MECC) has been shown to reduce the negative effects associated with conventional extracorporeal circulation (CECC). This trial assesses the impact of MECC on the outcome of elderly patients undergoing CABG. Eight hundred and seventy-five patients (mean age 78.35 years) underwent isolated CABG using CECC (n=345) or MECC (n=530). The MECC group had a significantly shorter extracorporeal circulation time (ECCT), cross-clamp time and reperfusion time and lower transfusion needs. Postoperatively, these patients required significantly less inotropic support, fewer blood transfusions, less postoperative hemodialysis and developed less delirium compared to CECC patients. In the MECC group, intensive care unit (ICU) stay was significantly shorter and 30-day mortality was significantly reduced [2.6% versus 7.8%; p<0.001]. In conclusion, MECC improves outcome in elderly patients undergoing CABG surgery.

Re-exploration for bleeding or tamponade after cardiac surgery: impact of timing and indication on outcome.

OBJECTIVES: Re-exploration after cardiac surgery remains a frequent complication with adverse outcomes. The aim of this study was to evaluate the impact of timing and indication of re-exploration on outcome. METHODS: A retrospective, observational study on a cohort of 209 patients, who underwent re-exploration after cardiac surgery between January 2005 and December 2011, was performed. The cohort was matched for age, gender, and procedure with patients who were not re-explored during the same period. RESULTS: The intraoperative and postoperative transfusion requirements were higher in the re-exploration group (p < 0.01). Patients in the re-exploration group had significantly higher incidences of postoperative acute renal injury (10.0 vs. 3.3%), sternal wound (9.1 vs. 2.4%) and pulmonary (13.4 vs. 4.3%) infections, longer ventilation time (22 [range, 14-52] vs. 12 [range, 9-16] hours) and intensive care unit stay (5 [range, 3-7] vs. 2 [range, 2-4] days), and higher mortality rate (9.6 vs. 3.3%). However, the multivariate logistic regression analysis demonstrated that not the re-exploration itself, but the deleterious effects of re-exploration (blood loss and transfusion requirement) were independent risk factors for mortality. Mortality was 5.3% for patients who were re-explored within the first 12 hours and 20.3% for patients who were re-explored after 12 hours (p = 0.003). Mortality was 3.6% for patients with bleeding and 31.4% for patients with cardiac tamponade for indication of re-exploration (p < 0.001). CONCLUSIONS: This study suggests that re-exploration after cardiac surgery is associated with increased mortality and morbidity. Patients with delayed re-exploration and suffering from cardiac tamponade have adverse outcome.

Synergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats.

Chronic lung allograft dysfunction (CLAD) still remains a major drawback in the outcome following lung transplantation (LTx). New therapeutic strategies are warranted. Growth factors and their receptors like platelet-derived growth factor-receptor (PDGFR) and vascular endothelial growth factor-receptor (VEGFR), may play a crucial role in the development of CLAD, especially bronchiolitis obliterans (BO) and vasculopathy. In this study, we used an orthotopic left lung transplantation model from Fischer (F344) to Wystar Kyoto (WKY) rats to investigate the effect of the receptor tyrosine kinase inhibitor (RTKI) vatalanib alone, the dual combination of vatalanib and imatinib and a triple therapy consisting of vatalanib, imatinib and the mammalian target of rapamycin inhibitor (mTORI) everolimus on the development of CLAD after LTx in rats. With this trial we demonstrated that monotherapy with vatalanib attenuated mild and severe chronic vascular rejection, whereas dual therapy (vatalanib and imatinib) after LTx also showed a significant reduction of chronic bronchiolar rejection and interstitial fibrosis. By adding everolimus, the effect of vatalanib and imatinib could additionally be increased. In conclusion, the combination of mTORI and RTKIs might be a possible strategy in the prevention of CLAD and BO.

The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

Everolimus's influence on persistent acute rejection after experimental lung transplantation.

BACKGROUND: In lung transplantation, acute rejection episodes increase the risk of chronic rejection. Therefore treatment of acute rejection needs to be optimized for better long-term outcome of lung-transplantation and patient survival. OBJECTIVES: The aim was to verify whether an inhibitor of the mammalian target of rapamycin (Everolimus) contained the extent of persistent acute rejection after left lung allo-transplantation in rats. MATERIAL AND METHODS: Rats (F344-to-WKY) with a high grade of acute rejection were treated with methylprednisolone (10mg/kg, postoperative days 14-16) alone or in combination with everolimus (2.5 mg/kg, postoperative days 14-30). The rats were killed on postoperative day 20 and 30. Infiltration of inflammatory cells (ED1, CD11a, CD18) and activation of endothelial cells (ICAM-1) were measured by immunohistochemistry RESULTS: Everolimus treatment significantly reduced the number of ICAM-1 positive small vessels (66%; p<0.05) and suppressed the infiltration of leucocytes (CD11a (64%), CD18 (42%); p<0.05) and macrophages (ED1; 22%) in the allografts on POD 30. Despite this clear anti-inflammatory effects, lung allografts still showed severe acute vascular rejection in combination with high grade small airway inflammation. CONCLUSIONS: The shown anti-inflammatory effects of Everolimus could not delay the progression of acute rejection in rat lung allografts.

Suppression of bronchiolitis obliterans in allogeneic rat lung transplantation--effectiveness of everolimus.

BACKGROUND: Chronic rejection (CR) after lung transplantation (LTX) manifests pathologically by fibrotic airway remodelling and bronchiolitis obliterans (BO). The role of the mammalian target of rapamycin inhibitor everolimus in preventing this process is poorly understood. METHODS: A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to analyze the effect of everolimus (2.5 mg/kg/day) on the development of CR. Drug therapy began on postoperative day (POD) 0, 7 and 14 characterizing different grade of acute rejection (AR) of the allograft before drug treatment. RESULTS: Non-treated recipients developed severe acute rejection (AR) and first signs of CR on POD 20 and a pronounced CR on POD 60. On POD 20, only application of everolimus from POD 0 to 60 significantly reduced acute inflammatory infiltration (p<0.001). Independent of treatment scheme, everolimus suppressed the development of early signs of chronic alterations (POD 20). However, neither early (POD 7-60) nor late (POD 14-60) application of everolimus affected the progression of CR (POD 60). Only its initial treatment (POD 0-60) inhibited the development of BO and vasculopathy (p<0.001). An additional finding was a decrease in body weight after drug application. CONCLUSION: The effectiveness of everolimus after rat LTX depended on the grade of inflammation of the allograft before initiation of drug treatment. Only allografts with no or low grade AR benefit from long-term treatment with everolilmus in the prevention of BO after LTX. It could be speculated that conversion to an everolimus-based immunosuppression after LTX might only be successful in patients free of BO.

Pharmacokinetics of a self-microemulsifying drug delivery system of tacrolimus.

This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf®) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration-time curve in the SEDDM Tac group and the Prograf® group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15 min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf® group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac.

Impact of minimized extracorporeal circulation on outcome in patients with preoperative anemia undergoing coronary artery bypass surgery.

Preoperative anemia and low hematocrit during cardiopulmonary bypass have been associated with worse outcome in patients undergoing cardiac surgery. The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of anemic patients after coronary artery bypass grafting (CABG) was assessed. Between January 2004 and December 2011, 1,945 consecutive patients with preoperative anemia underwent isolated CABG using CECC (44.8%) or MECC (55.2%). The cutoff point for anemia was 13 g/dl for men and 12 g/dl for women. The postoperative creatine kinase and lactate levels were significantly lower in the MECC group (p < 0.001). There was no difference in postoperative blood loss between the groups. However, the intraoperative and postoperative transfusion requirements were significantly lower in the MECC group (p < 0.05). Furthermore, MECC patients had lower incidences of postoperative acute renal failure, and low cardiac output syndrome, shorter intensive care unit lengths of stay and reduced 30-day mortality (p < 0.05). In conclusion, a reduced postoperative mortality, lower transfusion requirements, and less renal and myocardial damage encourage the use of MECC for CABG, especially in the specific high-risk subgroup of patients with anemia.

Everolimus in heart transplantation: an update.

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

Temporary percutaneous right ventricular support using a centrifugal pump in patients with postoperative acute refractory right ventricular failure after left ventricular assist device implantation.

OBJECTIVE: Acute right ventricular (RV) failure is a life-threatening condition with a poor prognosis, and sometimes the use of mechanical circulatory support is inevitable. In this article, we describe our experience using a centrifugal pump as a temporary percutaneous right ventricular assist device (RVAD) in patients with postoperative acute refractory RV failure after left ventricular assist device (LVAD) implantation. METHODS: We retrospectively reviewed eight consecutive patients with acute RV failure who underwent temporary percutaneous RVAD implantation using a centrifugal pump after LVAD implantation between April 2008 and February 2011. A Dacron graft was attached to the main pulmonary artery and passed through a subxiphoid exit, where the outflow cannula was inserted. The inflow cannula was percutaneously cannulated using Seldinger's technique in the femoral vein. The chest was definitely closed. The technique allowed bedside removal, avoiding chest re-opening. RESULTS: The median patient age was 52 years (range: 41-58). The median duration of support was 14 days (range: 12-14). RV systolic function improved; central venous pressure and mean pulmonary artery pressure decreased significantly after RVAD support. In three patients, an oxygenator was integrated into the RVAD due to impaired pulmonary function. Six patients were successfully weaned. Five patients survived to hospital discharge. Technical problems or serious complications concerning decannulation were not observed. CONCLUSION: This report suggests that implantation of temporary percutaneous RVAD using a centrifugal pump is a safe alternative in the treatment of postoperative acute refractory RV failure. Ease of device implantation, weaning, explantation, and limited number of complications justify a liberal use.

Impact of the severity of acute rejection in the early phase after rat lung transplantation on the effectiveness of mycophenolate mofetil to treat chronic allograft rejection.

OBJECTIVES: Prevention and treatment of bronchiolitis obliterans (BO) after lung transplantation (LTX) remains disappointing. The high prevalence and the critical detection of early mild acute lung rejection aggravated optimum immunosuppressive therapy. In this study, two hypotheses were investigated: (i) mycophenolate mofetil (MMF) prevented the development of BO after rat LTX. (ii) The effectiveness of MMF depended on the degree of acute rejection (AR) at the time of drug initiation. METHODS: A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the basic effect of MMF (30 mg/kg body weight per day) on the development BO. MMF therapy began on Days 0, 7 and 14 after transplantation characterizing different degree of AR of the allograft at the time of drug initiation and ended on Day 60 after transplantation. Non-treated animals were used as controls. Histopathological alterations were analysed according to the International Society for Heart and Lung Transplantation (ISHLT). RESULTS: MMF treatment of allografts with high-grade AR (ISHLT-A3-4/B2R; from Day 14 to 60) failed. All animals developed vascular fibrosis and BO. Promising long-term outcome was shown after treatment of mild to moderate acute rejecting of allografts (MMF from Day 7 to 60). The proportion of animals with high grade acute airway inflammation was significantly reduced (33%; P<0.05). All animals were free of BO and chronic vascular alterations (90%). MMF (Day 0-60) significantly reduced the proportion of animals with severe acute vascular rejection and high grade airway inflammation (17 and 0%, respectively; P<0.05, each). None of the animals treated with MMF from Day 0 to 60 developed chronic rejection (CR). CONCLUSIONS: MMF significantly reduced AR and CR after rat LTX. However, only allografts with no or mild AR at the time of drug initiation benefited from MMF treatment. In addition, the appearance of early signs of fibroproliferative alterations in the airway structures might prevent a successful long-term outcome.

Ventricular assist device implantation in patients on percutaneous extracorporeal life support without switching to conventional cardiopulmonary bypass system.

OBJECTIVES: Ventricular assist device (VAD) implantation using cardiopulmonary bypass (CPB) is an established procedure. However, the well-described complications of CPB may exacerbate multiple organ failure and increase blood product transfusions especially in end-stage heart failure patients. METHODS: We describe our successful experience in six consecutive patients with profound cardiogenic shock, who were provided on an emergency basis with a percutaneous extracorporeal life support (ECLS) system via the peripheral vessels. After stabilization, a VAD was implanted using ECLS without switching to a conventional CPB system to reduce its side effects. We compared the data with those of 11 patients in whom the VAD was placed with the aid of an additional CPB system. RESULTS: The six patients demonstrated a shorter duration of operating room time compared with the patients requiring CPB for device placement. During and after surgery, blood loss and blood product transfusions were lower in these patients. The need for mechanical ventilation and inotropic support was shorter and the survival rate (100% at 30 days, 83.3% at 3 months and 83.3% at 6 months) was higher when compared with patients who were operated upon with CPB. Two patients were successfully bridged to transplantation. One patient died due to cerebral bleeding after 7 weeks. CONCLUSIONS: Our experience suggests that VAD implantation using percutaneous ECLS without switching to conventional CPB is a safe alternative in the bridge to bridge concept, especially in high-risk patients with cardiogenic shock who would benefit from the avoidance of the adverse sequels associated with conventional CPB.

Successful coronary artery bypass grafting with the aid of a portable minimized extracorporeal life support system.

Extracorporeal life support system has been successfully used in patients with cardiac failure after open heart surgery, as a bridge to transplantation, and in patients with prolonged cardiogenic shock or cardiopulmonary arrest. This report presents our early experience with the new system Cardiohelp in coronary artery bypass grafting (CABG). Between August 2010 and June 2011, 50 patients underwent CABG with the aid of Cardiohelp. This subgroup was matched for sex and logistic EuroSCORE with 100 patients, who underwent CABG using two different extracorporeal circulation systems, a minimized (MECC) (n = 50) and a conventional (CECC) (n = 50) during the same period. Because of less hemodilution, the intraoperative blood transfusion was significantly lower in the Cardiohelp group (36%) and MECC group (40%) compared with the CECC group (64%). Postoperative release of creatinine kinase and lactate was lower in the Cardiohelp and MECC groups (p < 0.001). Furthermore, these patients had shorter duration of ventilation and lengths of stay at the intensive care unit (p < 0.05). Device-related complications were not observed. A conversion to CECC was not necessary. In conclusion, the Cardiohelp is a safe alternative for CABG surgery. Valid technical innovations and limited number of side effects support its employment as a highly effective device for coronary surgery.

Successful use of temporary right ventricular support to avoid implantation of biventricular long-term assist device: a transcutaneous approach.

Severe right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is a serious complication with a poor prognosis. The most effective therapy for these patients is an upgrade to biventricular mechanical support. However, it is well recognized that primary and secondary biventricular ventricular assist device implantation is associated with higher mortality rates. We report on three patients with cardiogenic shock, who were provided on an emergency basis with a percutaneous extracorporeal life support (ECLS) system by the femoral vessels. After stabilization, a LVAD was implanted. To avoid secondary RV failure, the ECLS was switched to a transcutaneous RV assist device (RVAD) as a temporary RV support. The arterial cannula was removed from the femoral artery, and a prosthesis-supported cannula was sutured to the pulmonary artery and passed through a subxiphoid exit. The femoral vein cannula was left in situ. Both cannulae were connected to a centrifugal pump. Two patients could be weaned from the RVAD; the system was explanted under local anesthesia. One patient died due to internal bleeding. In conclusion, the ease of device implantation, weaning, and explantation justifies a liberal use of temporary RV support to avoid implantation of the problematic long-term biventricular assist devices.

Coronary artery bypass grafting in patients with type 2 diabetes mellitus: a comparison between minimized and conventional extracorporeal circulation.

Diabetes mellitus (DM) is an established independent risk factor for significant morbidity and mortality after coronary artery bypass grafting (CABG). The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of diabetic patients after CABG was assessed. Between January 2002 and December 2009, 1,184 patients with DM underwent elective isolated CABG using CECC (54.6%) or MECC (45.4%). All analysis was performed retrospectively. The extracorporeal circulation time was significantly reduced during MECC procedure. The postoperative increase of creatine kinase and lactate levels was significantly weaker in the MECC group (p < 0.001). Also, the transfusion requirements were significantly lower (p < 0.001). Furthermore, MECC patients had lower incidences of postoperative acute renal failure and sternal wound infections and shorter ICU and hospital lengths of stay (p < 0.05). Moreover, 30-day mortality was significantly reduced in the MECC group (p < 0.05). In conclusion, CABG surgery using MECC system is a safe alternative in patients with DM. A reduced postoperative mortality and lengths of stay, lower transfusion requirements, less renal and myocardial damage, and lower incidence of sternal wound infections encourage the usage of MECC system, especially in high-risk patients.

Successful use of hirudin during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.

In this case series, we describe our successful use of a reduced hirudin dosage as an anticoagulant during cardiac surgery using minimized extracorporeal circulation in patients with heparin-induced thrombocytopenia.