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Objectives Calcium sensitizers have been shown to improve outcomes in patients with low cardiac output syndrome (LCOS) after cardiac surgery. We assessed the effects of levosimendan on LCOS in cardiac surgical patients to identify outcome predictors. Methods A total of 106 patients in whom LCOS persisted despite conventional therapy additionally received 0.1 µg/kg/min of levosimendan for 24 hours according to a defined treatment algorithm. Baseline and treatment data as well as hemodynamic and outcome parameters were compared between survivors and nonsurvivors, and a multivariate correlation and regression tree analysis was implemented. Results The ejection fraction significantly increased from 27% ± 4% to 38% ± 8% within 24 hours and to 45% ± 10% within 48 hours of starting levosimendan. These changes were accompanied by a significant increase in cardiac output from 5.2 ± 0.6 to 6.2 ± 0.7 L/min within 24 hours and significant dose reductions in vasopressors and inotropes. In contrast to nonsurvivors, survivors’ need for inotropic support decreased after the addition of levosimendan to the therapy. Conclusion In our patients, all of whom were treated according to the same algorithm, the response to levosimendan in terms of the post-levosimendan need for inotropes and vasopressors predicted survival.

Background: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients. Methods: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed. The data were collected from the patients’ medical files, and included duration of mechanical ventilation, antibiotics, microbiological test results and neurological outcome. The outcome was the effect of early bronchoscopy (≤48 h after administration) on the rate of intubated patients on day five and day seven. Results: From January 2013 to December 2018, 190 patients were admitted with OHCA. Bronchoscopy was performed in 111 patients out of the 164 patients who survived the first day. Late bronchoscopy &gt, 48 h was associated with higher rates of intubation on day five (OR 4.94, 95% CI 1.2–36.72, 86.7% vs. 55.0%, p = 0.036) and day seven (OR 4.96, 95% CI 1.38–24.69, 80.0% vs. 43.3%, p = 0.019). Conclusion: This study shows that patients who suffered from OHCA might have a better outcome if they receive a bronchoscopy early after hospital admission. Our data suggests an association of early bronchoscopy with a shorter intubation period.

Purpose To evaluate myocardial viability assessment with hybrid 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG-PET/MR) in predicting left ventricular (LV) wall motion recovery after percutaneous revascularisation of coronary chronic total occlusion (CTO). Methods and results Forty-nine patients with CTO and corresponding wall motion abnormality (WMA) underwent [18F]FDG-PET/MR imaging for viability assessment prior to percutaneous revascularisation. After 3–6 months, 23 patients underwent follow-up MR to evaluate wall motion recovery. In total, 124 segments were assigned to the CTO territories, while 80 segments displayed impaired wall motion. Of these, 68% (54) were concordantly viable in PET and MR; conversely, only 2 segments (2%) were assessed non-viable by both modalities. However, 30% showed a discordant viability pattern, either PET non-viable/MR viable (3 segments, 4%) or PET viable/MR non-viable (21 segments, 26%), and the latter revealed a significant wall motion improvement at follow-up (p = 0.033). Combined imaging by [18F]FDG-PET/MR showed a fair accuracy in predicting myocardial recovery after CTO revascularisation (PET/MR area under ROC curve (AUC) = 0.72, p = 0.002), which was superior to LGE-MR (AUC = 0.66) and [18F]FDG-PET (AUC = 0.58) alone. Conclusion Hybrid PET/MR imaging prior to CTO revascularisation predicts more accurately the recovery of dysfunctional myocardium than PET or MR alone. Its complementary information may identify regions of viable myocardium with increased potential for functional recovery.

BACKGROUND Patients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx. OBJECTIVE This trial evaluates the effect of hydrocortisone on glycocalyx integrity in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS In a prospective, randomized interventional pilot trial, 30 patients received either hydrocortisone (100 mg over 10 min) or placebo (saline control) before surgery. Plasma concentrations of glycocalyx constituents (syndecan-1, heparan sulfate) and various clinical parameters (respiratory and renal function, inflammatory markers, use of vasopressors, length of stay at the intensive care unit) were measured. Primary endpoint was a significant difference of glycocalyx constituents in plasma. Comparisons were made with Friedman's and Wilcoxon tests (paired data), or the Kruskal-Wallis and Mann-Whitney U tests (unpaired data). Holm-Bonferroni method was used for post-hoc corrections. RESULTS Heparan sulfate and syndecan-1 increased significantly during and after cardiac surgery with cardiopulmonary bypass in both groups. Whereas the maximum increase of heparan sulfate was 12.3-fold in the control vs. 3.8-fold in the pretreated group (p

We are presenting the case of a 76-year-old female scheduled for major abdominal surgery. Her past medical history was remarkable for a three-vessel coronary artery disease, with a severely impaired left ventricular function. She had already undergone complex coronary artery bypass surgery. Currently, she presented with the rare constellation of a hemodynamic relevant and interventionally intractable stenosis of the left subclavian artery proximal to a crucial coronary bypass from left internal mammary artery to the left anterior descending. To protect this patient from perioperative myocardial infarction, an intra-aortic balloon pump was successfully used.

Purpose To evaluate the role of plasma disappearance rate of indocyanine green (PDR-ICG) as an outcome prediction tool in cardiac surgery. Patients and Methods One hundred ninety patients undergoing coronary artery bypass grafting, valve surgery or combined procedures were enrolled. PDR-ICG measurements along with standard lab values were performed preoperative and on postoperative days 1, 2, and on discharge from the intensive care unit. Adverse outcomes were defined as prolonged length of stay in the intensive care unit and/or mortality. Two groups were defined according to length of stay in the intensive care unit (≤ 3 days vs > 3 days). Results PDR-ICG values differed significantly for all time points between the groups. In a multivariate model, in patients over 65 years with a EuroSCORE below 8.5, a preoperative PDR-ICG value below 12.85%/min was the strongest independent predictor for prolonged intensive care unit stay (> 3 days). A preoperative PDR-ICG value below 8.2%/min was the strongest independent predictor for mortality in a multivariate analysis including age, cardiac function, and EuroSCORE. Conclusions In addition to the established scores, PDR-ICG may provide valuable information for the assessment of perioperative morbidity and mortality in cardiac surgery. Pre- and early postoperative measurements may help to identify patients at risk for developing perioperative complications.

Background Adiponectin is an anti-inflammatory adipocytokine believed to be involved in the pathogenesis of chronic heart failure (CHF). We aimed to characterize the expression of adiponectin and its receptors in CHF and to assess the impact of microRNAs on the cardiac adiponectin system. Methods Expression of adiponectin and adiponectin receptors (ADIPOR1 and ADIPOR2) was studied by qPCR and immunohistochemistry in myocardial tissues of patients with end-stage CHF and control subjects. MicroRNA binding was evaluated by cloning of an ADIPOR2 3´-untranslated-region reporter construct and subsequent transfection experiments. Effects of miRNA transfection were analyzed in cardiomyocyte cell cultures by qPCR and Western blotting. Gene silencing of ADIPOR2 was performed by siRNA transfection, and the effects of hypoxia/serum starvation were analyzed by flow cytometry. Results Although CHF patients displayed elevated plasma adiponectin levels, myocardial adiponectin expression generally was very low. In CHF, cardiac ADIPOR1 expression increased by >4-fold, whereas the increase in ADIPOR2 was less than 2-fold. Reporter gene assays on constructs containing the ADIPOR2-3′-untranslated region suggest that microRNA-150 specifically repressed ADIPOR2 expression. Transfection of cardiomyocytes with premiR-150 precursor molecules resulted in 60% down-regulation of ADIPOR2 mRNA and a significant reduction of ADIPOR2 protein expression. MicroRNA-150 was substantially expressed in both normal and CHF myocardium, with a 1.7-fold higher expression in CHF. Finally, knock-down experiments elucidated a stress-protective role of ADIPOR2 in cardiomyocytes. Conclusions MicroRNA-150 counteracts ADIPOR2 up-regulation in CHF and thus may contribute to adiponectin resistance. Targeting microRNA-150 may be a future strategy to restore cardioprotective adiponectin effects.

Zweck dieser Studie war es, die Wirksamkeit, Effizienz und Vertraglichkeit von Daptomycin bei der Behandlung grampositiver Infektionen nach herzchirurgischen Eingriffen zu analysieren. Diese retrospektive Analyse wurde bei 49 erwachsenen Patienten durchgefuhrt, welche nach herzchirurgischen Eingriffen eine grampositive Infektion aufwiesen und mindestens mit einer einmaligen Dosis Daptomycin behandelt worden waren. Die Diagnose einer grampositiven Infektion wurde mittels klinischer Parameter, laborchemischer Befunde und mikrobiologischer Ergebnisse gestellt. 94% aller Patienten konnten erfolgreich mittels Daptomycin therapiert werden. Es kam zu keinem Todesfall, welcher mit einer grampositiven Infektion assoziiert gewesen sein konnte. Als Therapieerfolg wurden dabei ein Ruckgang der Entzundungszeichen und eine Verbesserung des klinischen Zustands des Patienten gewertet, der uber das Absetzen der Therapie hinaus anhielt. Daptomycin stellt als erster Vertreter einer neuen Antibiotikaklasse einen vielversprechenden Kandidaten dar. Nach erfolgreicher Anwendung bei komplizierten Haut und Weichteilinfektionen, Bakteriamien und rechtsseitiger Endokarditis zeigte Daptomycin in unserer retrospektiven Analyse eine sehr gute Wirksamkeit bei guter Vertraglichkeit und fehlenden relevanten Nebenwirkungen bei grampositiven Infektionen nach herzchirurgischen Eingriffen.

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.

Levosimendan is a calcium sensitizer with positive inotropic and vasodilating properties. It increases the sensitivity of troponin C for calcium, opens adenosine triphosphate-dependent potassium (K + ) channels and inhibits phosphodiesterase III. Levosimendan is approved for use in cardiac failure but large clinical trials have raised doubts whether levosimendan is superior to β-adrenergic agonists regarding long-term survival of patients. Despite this controversy, there is growing evidence of beneficial effects of levosimendan in ischemia/reperfusion (I/R) injury due to its effect on K + channels. As a consequence, patents on K + channel agonists have been granted recently for reducing injury in organs or tissue in transplants and trauma therapy. Moreover, experimental studies and clinical trials have shown that levosimendan effectively inhibits cardiomyocyte apoptosis. The underlying molecular mechanism is currently unclear. However, it is tempting to assume that levosimendan inhibits cardiomyocyte apoptosis due to its beneficial effect on I/R injury. However, the link between these two phenomena has not been well established. This review summarizes experimental studies and clinical trials on the effects of levosimendan in I/R injury and apoptosis also discussing recent patents.

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with activation of the complement system, platelets, neutrophils, monocytes, and macrophages which may lead to systemic inflammatory response syndrome in several cases. Despite modification of surgical techniques, biocompatibility of the bypass circuit and intensive care procedures after operation, CPB is still associated with post-operative morbidity including reduced cardiac function, capillary leak or multi-organ dysfunction. Corticosteroids are known for their anti-inflammatory effects and therefore, they are beneficial in selected trauma or septic patients. Prophylaxis with corticosteroids in cardiac surgery has been used since decades. The studies for methylprednisolone and hydrocortisone, the most commonly used corticosteroids, show conflicting results. For hydrocortisone, which is the mainstream of corticosteroid treatment in septic patients, the number of studies is low, but will increase in the next years. This article reviews the data concerning its use in patients undergoing cardiac surgery, its contraindications, adverse effects, risks, and benefits.

Acute coronary syndrome is one of the major health problems worldwide and accounts for a great number of cardiac hospitalizations in the Western world. Atherosclerotic plaque rupture or erosion followed by platelet activation and total occlusion of a coronary artery is involved in the pathogenesis of acute coronary syndrome and myocardial infarction. The glycoprotein IIb/IIIa receptor, a platelet surface integrin, plays a key role in platelet aggregation once it has been activated. In order to improve myocardial tissue reperfusion, platelet inhibition with glycoprotein IIb/IIIa inhibitors (in combination with aspirin, clopidogrel, and heparin) has been shown as beneficial adjuvant therapy in patients with acute myocardial infarction. Tirofiban is a glycoprotein IIb/IIIa inhibitor. This article reviews the data concerning its use in patients with ST elevation myocardial infarction, the pharmacokinetic profile, contraindications, an adjuvant anticoagulation therapy and the surveillance.

Peri-operative acute renal failure requiring renal replacement therapy is common (5-30%) after cardiac surgery and associated with a mortality of approximately 50%. Pre-operative renal impairment seems to be the most important risk factor for frank postoperative renal failure. To help evaluate the risk factors, we conducted a prospective observational trial of 1574 consecutive patients with normal pre-operative renal function (creatinine110 micromol.l(-1)). Renal failure was defined as the need for renal replacement therapy. After univariate analysis of previously described risk factors, those who differed significantly between patients with or without renal failure were enrolled into a multivariate classification and regression tree (CART) statistical model that identifies the most 'predictive' risk factors and creates a ranked list of these. In patients with pre-operatively normal renal function, a serum level of lactate1.1 mmol.l(-1) in the first 24 h after the operation was the strongest predictor for the development of renal failure.

Primary graft dysfunction after heart transplantation is a severe complication generally related to prolonged ischemia time, size mismatch, or poor quality of the organ. Current therapeutic options include pharmacologic inotropic support with catecholamines or phosphodiesterase inhibitors, and mechanical circulatory support. We report 12 patients who received levosimendan, a new Ca(2+) sensitizer, as adjunctive inotropic support. The patients showed a rapid reduction of the doses of inotropic drugs, and no patient needed mechanical support. Levosimendan may be a useful, adjunctive inotropic drug in the treatment of patients with primary graft dysfunction after heart transplantation.

Die extrakorporale Membranoxigenation (ECMO) bildet neben einer Vielzahl anderer, konservativer Therapieansatze eine Behandlungsalternative beim schweren, akuten Lungenversagen (veno-venose Systeme) und in Ausnahmefallen auch beim akuten Herz-Kreislaufversagen (veno-arterielle Systeme). Beide Methoden kommen bei hochselektierten Patienten in spezialisierten Zentren zur Anwendung, in Ausnahmefallen ist aber auch ein mobiler Einsatz und auch Transport von Patienten unter ECMO moglich. Kontrollierte Studien konnten bisher keinen Uberlebensvorteil bei Anwendung dieser Technik nachweisen, sie kann jedoch in Einzelfallen lebensrettend sein. Langzeituberlebende Patienten nach Einsatz dieser Technik zeigen signifikante Einschrankungen ihrer gesundheitsbezogenen Lebensqualitat (HRQL), wobei es aber uber Jahre nach Verlassen der Intensivstation zu einer langsamen Normalisierung kommt und schwere Einschrankungen selten sind. Chronische Post-Traumatische Belastungsstorungen (PTSD) und andere stress-assoziierte Erkrankungen finden sich bei Patienten nach ECMO Therapie in bis zu 30% der Falle. Chronische Stresserkrankungen haben einen signifikant negativen Effekt auf die erreichte HRQL und sind im Gesamtverlauf der Rehabilitationsphase zu berucksichtigen.

Heutzutage gilt die Herztransplantation (HTX) als Goldstandard der Therapie der chronischen und terminalen Herzinsuffizienz. Das akute Transplantatversagen (ATV) nach HTX ist eine dramatische Komplikation, die mit einer hohen Morbiditat und Mortalitat einhergeht. Als Risikofaktoren konnten bisher eine verlangerte Ischamiezeit, eine schlechte Organqualitat und eine akuten Abstosungsreaktion identifiziert werden. Folge des ATV ist nicht selten ein Multiorganversagen (MOV). Als therapeutische Optionen stehen primar konservative Masnahmen, wie die Behandlung mit Katecholaminen und Phosphodiesterasehemmern zur Verfugung, die jedoch selbst mit Nebenwirkungen und potentiellen Komplikationen vergesellschaftet sind. Bei Versagen konservativer Masnahmen muss haufig auf mechanische Kreislaufunterstutzungssysteme zuruckgegriffen werden, die sich von der intraaortalen Ballonpumpe bis zur Implantation eines biventrikularen Assist-devices erstrecken. Kalziumsensitizer steigern die kardiale Kontraktilitat, ohne die intrazellulare Kalziumkonzentration zu beeinflussen und umgehen somit die Nebenwirkungen eines Kalziumuberangebots. Wir berichten von zwei Fallen ATV nach HTX, das sich jeweils nach der Gabe von Levosimendan, einem Kalziumsensitizer, rasch erholte.

Stroke volume variation as measured by the analysis of the arterial pressure waveform enables prediction of volume responsiveness in ventilated patients with normal cardiac function. The aim of this study was to investigate the ability of monitoring stroke volume variation to predict volume responsiveness and to assess changes in preload in patients with reduced left ventricular function after cardiac surgery.Prospective study.University hospital.Fifteen mechanically ventilated patients with a left ventricular ejection fraction0.35 (study group) and 15 patients with an ejection fraction0.50 (control group) after coronary artery bypass grafting following admission to the intensive care unit.Volume loading with 10 mL of hetastarch 6% times body mass index. If stroke volume index increased5%, successive volume loading was performed until no further increase in stroke volume index was reached.Stroke volume variation, central venous pressure, pulmonary artery occlusion pressure (PAOP), and left ventricular end-diastolic area index (LVEDAI) were measured at baseline and immediately after each volume loading step. In both groups, stroke volume variation at baseline correlated significantly with changes in stroke volume index caused by volume loading (p.01). Further, changes in stroke volume variation as a result of volume loading correlated significantly with the concomitant changes in stroke volume index in both groups (p.01). Using receiver operating characteristic analysis, in the study group areas under the curve for stroke volume variation, PAOP, central venous pressure, and LVEDAI did not differ significantly. In the control group, the area under the curve for stroke volume variation was statistically larger than for PAOP, central venous pressure, and LVEDAI.Continuous and real-time monitoring of stroke volume variation by pulse contour analysis can predict volume responsiveness and allows real-time assessment of the hemodynamic effect of volume expansion in patients with reduced left ventricular function after cardiac surgery.

Real-time measurement of stroke volume variation by arterial pulse contour analysis (SVV) is useful in predicting volume responsiveness and monitoring volume therapy in mechanically ventilated patients. This study investigated the influence of the depth of tidal volume (V(t)) on SVV both during the state of fluid responsiveness and after fluid loading in mechanically ventilated patients.Prospective study in a university hospital, adult cardiac surgery intensive care unit.20 hemodynamically stable patients immediately after cardiac surgery.Stepwise fluid loading using colloids until stroke volume index (SVI) did not increase by more than 10%. Before and after fluid loading V(t) was varied (5, 10, and 15 ml/kg body weight) in random order.Pulse contour SVV was measured before and after volume loading at the respective V(t) values. Thirteen patients responded to fluid loading with an increase in SVI greater than 10%, which confirmed volume responsiveness at baseline measurements. These were included in further analysis. During volume responsiveness SVV at V(t) of 5 ml/kg (7+/-0.7%) and SVV at V(t) of 15 ml/kg (21+/-2.5%) differed significantly from that at V(t) of 10 ml/kg (15+/-2.1%). SVV was correlated significantly with the magnitude of V(t). After volume resuscitation SVV at the respective V(t) was significantly reduced; further, SVV at V(t) of 5 ml/kg(-1) (5.3+/-0.6%) and 15 ml/kg (16.2+/-2.0%) differed significantly from that at V(t) of 10 ml/kg (10.2+/-1.0%). SVV and depth of V(t) were significantly related.In addition to intravascular volume status SVV is affected by the depth of tidal volume under mechanical ventilation. This influence must be regarded when using SVV for functional preload monitoring.

Primary graft failure (PGF) is a severe complication responsible for 42% of the in-hospital mortality after heart transplantation. It has been postulated that once 30-day survival is achieved, patients with PGF have no increased risk of death. Levosimendan increases the 30-day survival among patients with PGF. Herein we have reported a 3-year follow-up at a single center of a patient cohort including PGF cases treated with levosimendan.From September 2005 to December 2006 53 patients underwent heart transplantation at our institution, including 12 patients (22.6%) who presented with PGF and were treated with levosimendan using a 24-hour continuous infusion (0.10 μg/kg/min). Risk factors for 1-year and three-year mortality were analyzed using 30-day as well as 1 and 3-year survivals comparing patients with versus without PGF (n = 41).There were no significant differences in donor age, weight, height, and serum sodium between the groups. However, the ischemia time (259 ± 53 vs 227 ± 50 min; P = .06) and recipient age (51.6 ± 15 vs 41.5 ± 21 years; P = .07) were greater among the PGF patients. The 30-day survival rate was 92% in both groups. After 1 and 3 years, the survival rate was significantly lower among the PGF cohort (50% vs 80.6% and 41.7% vs 80.6%; P.05) with 86.5% of PGF patients succunding due to non cardiac reasons, predominantly infections.Although treatment of PGF with levosimendan increased the 30-day survival, the 1 year and 3-year rates were reduced among this cohort of patients. PGF was associated with poor long-term outcomes, which may be a consequence of systemic malperfusion during the stage of cardiac low-output after transplantation.

Background . The purpose of this study was to evaluate the course of serum markers of myocardial tissue damage after two different types of minimally invasive coronary surgical procedures (MICS) as compared with conventional coronary artery bypass grafting (CABG). Methods . We enrolled 87 patients with one- or two- vessel disease scheduled for one of the three procedures: minimally invasive direct coronary artery bypass grafting (MIDCABG) by lateral thoracotomy (n = 29), the OCTOPUS method by median sternotomy (n = 27), and CABG (n = 31). Creatine kinase activity (CK), creatine kinase MB activity (CK-MB act), creatine kinase MB mass concentration (CK-MB mass), myoglobin concentration (MG), and cardiac troponin I concentration (cTnI) were measured perioperatively until the second postoperative day. Results . Creatine kinase-MB, CK-MB mass, and cTnI were significantly higher after CABG and were nearly maintained within the normal range in MICS. Creatine kinase and MG were significantly lower in the OCTOPUS group than in the MIDCABG or CABG groups. Conclusions . Minimally invasive coronary surgical procedures cause less myocardial injury than CABG as indicated by specific serum markers. However, higher CK and MG reflect more substantial skeletal muscle trauma during MIDCABG operation compared with Octopus procedures.

A patient with severe dilated cardiomyopathy developed heparin-induced thrombocytopenia type II (HIT II) after implantation of a biventricular assist device (biVAD). Because the patient showed mild renal dysfunction but severe hepatic impairment, the management of anticoagulation was switched from heparin to the direct thrombin inhibitor hirudin, which was administered by continuous infusion of 0.6 to 1 mg/h. This protocol was monitored by measuring the plasma hirudin level, which ranged from 0.5 to 1.5 microg/mL. Unfortunately, the patient died on day 22 after implantation from fulminant sepsis caused by Aspergillus fumigatus. Neither thromboembolic events nor thrombocytopenia was observed after hirudin administration. The explanted biVAD showed no thrombotic material in the arterial/venous lines or on the polyurethane valves. We discuss the challenges posed by HIT II complicating VAD support as well as its clinical management with direct thrombin inhibitors.

Objectives The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. Methods We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. Results We studied nine patients (eight males, one female), of overall mean age of 51 ± 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 ± 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. Conclusions Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.

A young woman suffering from congenital hypertrophic obstructive cardiomyopathy (HOCM) received a transcoronary ablation of the septal hypertrophy (TASH) and an automated Cardioverter/Defibrillator (AICD) for the relief of progressive symptoms of heart failure. She developed an acute heart failure in the perioperative period and had to be put on veno-arterial extracorporeal membrane oxygenation. Following this the patient developed a nearly complete thrombosis of the left-sided cardiac chambers, despite successful laboratory anticoagulation.

Primary pheochromocytomas located outside the adrenal glands account for only 10% of all pheochromocytomas. Mediastinal pheochromocytomas are even rarer and usually represent a therapeutic challenge as they often infiltrate adjacent structures. We report the case of a large primary mediastinal pheochromocytoma in a 65-year-old patient presenting with a sudden angina-like chest pain and dyspnea. Thoracic multislice computed tomography showed an 8 x 5 x 6-cm retrocardiac mass causing compression of both atria and infiltrating the left superior pulmonary vein. The tumor was highly vascularized and presented a blood supply derived from the circumflex artery. The mass was successfully removed by open heart surgery, and the patient was discharged 10 days postoperatively.

Heart transplantation is considered nowadays the gold standard in the therapy of chronic and terminal heart insufficiency. Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or acute rejection. All these factors can potentially lead to multiorgan failure. Pharmacological and mechanical support for these patients is limited and often related to side effects. Ca 2+ sensitizers have been proposed to increase cardiac contractility without altering intracellular Ca 2+ levels, thus avoiding the side effects of Ca 2+ overload. We report two cases of heart transplanted patients suffering from acute graft failure in the early postoperative period who recovered after intravenous administration of levosimendan, a Ca 2+ sensitizer.

BACKGROUND Galectins are a family of soluble lectins expressed in a variety of tissues, which play many important regulatory roles in inflammation, immunity, and cancer. The up-regulation of galectin-3 in hypertrophied hearts and the development of fibrosis have been shown in experimental studies. Increased galectin-3 levels are associated with poor long-term survival in end-stage heart failure (HF). We examined the relationship between plasma galectin-3 levels and the myocardial tissue expression of galectin-3 in patients with end-stage HF. MATERIAL AND METHODS Expression of galectin-3 was assessed by real-time PCR and immunohistochemistry in left ventricle and atrial myocardium of patients (n=12) with end-stage HF undergoing heart transplantation. All patients gave informed consent. Serum expression of galectin-3 was assessed by ELISA in serum from 20 patients with end-stage HF and in 20 healthy volunteers who served as controls. RESULTS Expression of galectin-3 was similar in the myocardium of patients in comparison to the control group, independently of the anatomical area (HF vs. healthy ventricle: 1.73E-02 vs. 1.50 E-02; HF vs. healthy atrium: 1.32E-02 vs. 1.16E-02). However, serum expression of galectin-3 was significantly higher in the end-stage HF patients compared to the healthy controls (13.02±10.6 vs. 3.7±1.3 ng/ml; p

Infections due to multidrug-resistant pathogens have an increasing impact on patients undergoing cardiac surgery. Preoperative infections, such as endocarditis, and postoperative infections, including wound and device infection, influence patient outcomes. Special interest needs to be taken in patients admitted to cardiac surgical intensive care units, as these patients are at high risk for infections, particularly nosocomial pneumonia, catheter-related and wound infections. The increasing numbers of infections due to Gram-positive multidrug-resistant pathogens underline the necessity for newer antibiotics with bactericidal effects and a more favorable profile of side effects. Daptomycin, a lipopeptide antimicrobial agent with bactericide activity against Gram-positive organisms, has been successfully used in the treatment of complicated infections due to Gram-positive multidrug-resistant pathogens, especially regarding endocarditis, wound infections, device and catheter-related infections in intensive care units. In this review, the authors will summarize therapeutic potential of daptomycin in cardiac surgery and postoperative intensive care.

Female gender is an established risk factor for worse outcomes after cardiac surgery, and women are more likely to experience postoperative complications. Our aim was to analyze the influence of gender on outcome and postoperative complications after the use of intra-aortic balloon counter-pulsation (IABP) in cardiac surgery patients.Fifty-seven consecutive female patients (mean age: 73 ± 9 years) requiring an IABP at our department from January 2007 to January 2010 were retrospectively analyzed and compared with 182 male patients receiving IABP support within the same period. The collected data included patient demographics, preoperative state, operative details, postoperative pharmacological treatment, IABP-associated complications, and inhospital mortality. Preoperative mortality risk was calculated by logistic EuroSCORE.There were no differences regarding the type of operation, preoperative renal or hepatic failure, though the prevalence of peripheral artery occlusive disease was higher in men. Furthermore, female patients receiving an IABP were significantly older (73 ± 9 vs. 67 ± 10 years), had a higher ejection fraction (EF) (45% ± 24% vs. 36% ± 14%), and had a higher EuroSCORE (25% ± 20% vs. 19% ± 17%; p 0.05). Postoperative catecholamine support was significantly higher in the female patients. Women had a prolonged length of stay (LOS) at the ICU (10.64 ± 9.7 vs. 7.6 ± 7.6 days), higher incidence of renal replacement therapy, and a higher mortality (19 [19.4%] vs. 35 [33.9%]; p 0.05) after the use of IABP.Women have a worse outcome after the use of IABP, including LOS at the ICU, postoperative renal failure, and inhospital mortality, despite higher EF, when compared with men.

sensitizing effect in the cardiac myofilaments.Pleiotropic effects include activation of adenosine triphospha-te–sensitive sarcolemmal K channels of smooth muscle cells(linked to vasodilation) and activation of adenosine triphospha-te–sensitive K channels in cardiovascular mitochondria (in-volved in a cardioprotective effect). The active long-lived me-tabolite OR-1896, also an inodilator

Cardiac surgery, especially if it involves cardiopulmonary bypass, is associated with a severe systemic inflammatory response. It is characterized by complement activation and initiation of coagulation, fibrinolysis and kallikrein cascades. Consecutive activation of immunoregulatory cells results in an extensive release of pro- and anti-inflammatory cytokines. This inflammatory storm is related to organ dysfunction or failure and correlates with postoperative morbidity. In order to attenuate this deleterious inflammatory response in the perioperative period alternative surgical techniques, novel extracorporeal circulation devices and immunomodulatory pharmacological strategies are in focus of contemporary research. Since decades corticosteroids have been used and studied in patients undergoing cardiac surgery. Although it could be shown that glucocorticoids seem to change the pro-inflammatory cytokine profile in a favourable manner, it still remains controversial if this effect translates into a better clinical outcome. Several clinical trials have proclaimed an association between this inflammatory response and the incidence of major complications i.e, myocardial infarction and pulmonary complications, but until now they have failed to show conclusive results. This article describes the different types and recommended dose schemes of corticosteroids in the perioperative period of cardiac surgery along with the discussion of few patents. It will comment on potential side effects and review the effect on the postoperative outcome.

Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related to altered expression profiles of glucocorticoid receptor isoforms glucocorticoid receptor-α (mediating anti-inflammatory effects) and glucocorticoid receptor-β (acting as a dominant negative inhibitor). We investigated the impact of glucocorticoid receptor isoforms on glucocorticoid effects in human T-cells. We hypothesized that 1) changes of the ratio of glucocorticoid receptor isoforms impact glucocorticoid resistance and 2) glucocorticoid receptor-α expression is controlled by microRNA-mediated gene silencing.Laboratory-based study.University research laboratory.Healthy volunteers, sepsis patients.First, T-cells from healthy volunteers (native and CD3/CD28-stimulated cells with or without addition of hydrocortisone) were analyzed for the expression of glucocorticoid receptor-isoforms by quantitative polymerase chain reaction. Additionally, effects of gene silencing of glucocorticoid receptor-β by siRNA transfection were determined. Secondly, microRNA-mediated silencing was evaluated by cloning of a glucocorticoid receptor-α-specific 3'-untranslated-region reporter construct and subsequent transfection experiments in cell cultures. Effects of miRNA transfection on glucocorticoid receptor-α expression were analyzed in Jurkat T-cells and in T-cells from healthy volunteers (quantitative polymerase chain reaction and Western blotting). Finally, expression of glucocorticoid receptor-α, glucocorticoid receptor-β, and miR-124 was tested in T-cells of sepsis patients (n=24).Stimulation of T-cells induced a significant upregulation of glucocorticoid receptor-α (not glucocorticoid receptor-β) thereby possibly rendering T-cells more sensitive to glucocorticoids; this T-cell response was hindered by hydrocortisone. Silencing of glucocorticoid receptor-β doubled the inhibitory effects of glucocorticoids on interleukin-2 production. MicroRNA-124 was proved to specifically downregulate glucocorticoid receptor-α. Furthermore, a glucocorticoid-induced three-fold upregulation of microRNA-124 was found. T-cells of sepsis patients exhibited slightly decreased glucocorticoid receptor-α and slightly increased miR-124 expression levels, whereas glucocorticoid receptor-β expression was two-fold upregulated (p.01) and exhibited a remarkable interindividual variability.Glucocorticoid treatment induces expression of miR-124, which downregulates glucocorticoid receptor-α thereby limiting anti-inflammatory effects of glucocorticoids. Steroid treatment might aggravate glucocorticoid resistance in patients with high glucocorticoid receptor-β levels.

BACKGROUND Left atrial cardiac myxomas are among the most common cardiac masses. However, occurrence of left atrial myxomas in post-transplant patients is very rare and often misdiagnosed as left atrial thrombus formation. CASE REPORT We report the case of a 67-year old female, who was referred due to suspected left atrial thrombus but was found to have a pediculated mass at the suture line of the left atrium on cardiac MRI. After resection, the diagnosis myxoma was confirmed histologically and the donor origin of the myxoma was proven by tissue typing. CONCLUSIONS Despite a rare entity, atrial myxomas may occur in post cardiac transplant patients and may therefore support the role of advanced imaging techniques in patients with suspected left atrial masses.

Vasodilatory shock frequently occurs after cardiac surgery, particularly after cardiac assist device implantation. This complication is often associated with high mortality, especially if refractory to conventional vasoconstrictor treatment. Methylene blue, a guanylate cyclase inhibitor, has been successfully used in the management of vasodilatory shock associated with cardiopulmonary bypass. We present four successive cases after implantation of cardiac assist devices suffering from norepinephrine and vasopressin refractory severe vasodilatory shock. In all patients, administration of a single dose of methylene blue (2 mg/kg body weight) resulted in an immediate and persistent decrease in vasoconstrictor dosages and serum lactate concentrations. Despite of this benefit, all patients deceased during hospital stay, however, this was not related to the methylene blue treatment. Methylene blue seems to be a promising therapeutical option in patients with otherwise resistant vasodilatory shock after cardiac assist device implantation. However, controlled clinical trials are necessary to substantiate safety and efficacy.

Background: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations. They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone in a prospective, randomized, placebo-controlled double-blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression. Methods: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group (n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS (n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV). Results: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed delirium on POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3 ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70; specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95% confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period. Conclusions: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship.

Cushing's syndrome is associated with excessive cortisol secretion by the adrenal gland or ectopic tumours and may result in diabetes, hypertension, and life-threatening infections with high mortality rates especially in the case of surgical resection. Although surgical resection is the treatment of choice, patients may benefit from preceding medical therapy. This may especially be useful as an adjunctive approach in emergency settings, if patients cannot undergo surgery, if surgery or radiotherapy fails, or if the tumour recurs. Medical therapy can be categorized in three different groups-inhibition of steroidogenesis, suppression of adrenocorticotropic hormone, and antagonism of the glucocorticoid receptor. However, the majority of common drugs are not available for parenteral administration, which may evoke a management problem in emergency settings or in patients unable to tolerate oral medication. The carboxylated imidazole etomidate is a well known parenteral induction agent for general anaesthesia. Besides its hypnotic properties, etomidate also has α-adrenergic characteristics and inhibits the enzyme 11-deoxycortisol s-hydroxylase, which catalyzes the final step of the conversion of cholesterol to cortisol. Adverse outcomes have been reported when used for sedation in septic or trauma patients probably by its interference with steroid homeostasis. However, its capability of inhibition of the 11-deoxycortisol s-hydroxylase leads to suppression of cortisol secretion which has been demonstrated to be a useful tool in severe and complicated hypercortisolemia. Within this article, we review the data concerning different pharmacological approaches with particular consideration of etomidate in order to suppress steroidogenesis in patients with Cushing's syndrome.

Objective: Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. They act through the glucocorticoid receptor, for which, in humans, several polymorphisms have been described. In particular, the BclI single-nucleotide polymorphism is associated with hypersensitivity to glucocorticoids and with susceptibility to development of major depression. Furthermore, in patients with posttraumatic stress disorder carrying the BclI GG genotype, cortisol levels were lower and showed an inverse relationship to posttraumatic stress disorder symptom intensity. Here, we studied the association of the BclI polymorphism with plasma cortisol levels, traumatic memories, posttraumatic stress disorder symptoms, and health-related quality of life outcomes in 126 patients undergoing cardiac surgery and intensive care unit therapy.Design: Prospective observational study.Setting: Cardiovascular intensive care unit in a university hospital.Patients: A total of 126 patients undergoing cardiac surgery and intensive care unit treatmentInterventions: No interventions were performed.Measurements and Main Results: Validated questionnaires were used to quantify end points. Measurements were taken 1 day before and 1 wk and 6 months after cardiac surgery. Homozygous carriers of the BclI G allele (n = 21) had significantly lower preoperative plasma cortisol levels and more long-term traumatic memories from intensive care unit therapy at 6 months after cardiac surgery than heterozygous carriers or noncarriers (1.9 +/- 1.4 vs. 1.0 +/- 1.2, p = .01). Anxiety was significantly more common as a long-term traumatic memory in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers (57% vs. 35%, p = .03). Posttraumatic stress disorder symptom scores were significantly higher at discharge from the intensive care unit in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers. Only heterozygous carriers or BclI G allele noncarriers had a significant gain in health-related quality of life physical function at 6 months after cardiac surgery (p Conclusion: Homozygous BclI G allele carriers are at risk for traumatic memories, posttraumatic stress disorder symptoms, and lower health-related quality of life after cardiac surgery and intensive care unit therapy. The BclI single-nucleotide polymorphism may help to identify individuals at need for tailored medical care. (Crit Care Med 2011; 39: 643-650)

The aim of this review is to summarize the historical background of drug resistance of Gram-positive pathogens as well as to describe in detail the novel lipopeptide antibiotic daptomycin. Pharmacological and pharmacokinetic aspects are reviewed and the current clinical use of daptomycin is presented. Daptomycin seems to be a reliable drug in the treatment of complicated skin and skin structure infections, infective right-sided endocarditis, and bacteremia caused by Gram-positive agents. Its unique mechanism of action and its low resistance profile, together with its rapid bactericidal action make it a favorable alternative to vancomycin in multi-drug resistant cocci. The role of daptomycin in the treatment of prosthetic material infections, osteomyelitis, and urogenital infections needs to be evaluated in randomized clinical trials.

Ghrelin is a peptide hormone mainly produced by the stomach, which strongly stimulates the release of growth hormone (GH) via the GH secretagogue receptor 1a (GHSR-1a) located in the hypothalamus. It has been reported to exert performance-enhancing effects on myocardial function, and as both ghrelin and GHSR-1a are expressed in myocardial tissues, the ghrelin system may have a direct GH-independent impact on cardiac function. We intended to investigate the expression of ghrelin and its receptor GHSR-1a in different myocardial areas of patients with chronic heart failure (CHF) as compared to heart-healthy subjects to better define the role of the ghrelin signaling system in the networks regulating cardiac function and its potential as a target for diagnosis and/or treatment of CHF. Myocardium biopsies of 12 patients undergoing heart transplantation and suffering from CHF were obtained. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Expression of ghrelin was significantly decreased in CHF hearts both in atrium and ventricles in comparison to the control hearts (p

The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB).We studied 30 patients undergoing CS with CPB. All patients received midazolam and sufentanil for induction and isoflurane and sufentanil for maintenance of general anaesthesia. Blood samples were drawn before and after induction of general anaesthesia, after the beginning of surgery, during and after weaning from CPB, and after admission to intensive care unit (ICU) after surgery. Endocannabinoid measurements were performed by HPLC-tandem mass spectrometry.Induction of general anaesthesia led to a significant decline in plasma AEA concentrations [from mean (sd) 0.39 (0.03) to 0.27 (0.03) ng ml(-1), P0.01]. CPB induced a pronounced increase in 2-AG concentrations [from 112.5 (163.5) to 321.0 (120.4) ng ml(-1), P0.01], whereas AEA concentrations remained persistently low until admission to the ICU. 2-AG concentrations returned to preoperative values after surgery.General anaesthesia with isoflurane significantly reduces plasma AEA concentrations. This could be a consequence of stress reduction after loss of consciousness. The significant increase in 2-AG after initiation of CPB may be part of an inflammatory response. These findings suggest that anaesthesia and surgery have differential effects on the ECS which could have substantial clinical consequences.