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Introduction Heart failure places a significant economic burden on health care. Acute heart failure requires hospitalization and often frequent re-hospitalization in expensive wards where vasoactive rescue therapy is often added on top of standard medications. In these lean times, there is a growing need for cost-effective therapeutic options that supply superior support and in addition shorten the length of stay in hospital and reduce re-hospitalization rates. The inodilator levosimendan represents the latest addition to the vasoactive treatments of acute heart failure patients, and it appears to meet these expectations. Our aim was to answer the question whether the treatment efficacy of levosimendan – when selected as therapy for patients hospitalized for acute heart failure – brings savings to hospitals in various European countries representing different economies. Methods and results We took a conservative approach and selected some a fortiori arguments to simplify the calculations. We selected seven European countries to represent different economies: Italy, Spain, Greece, Germany, Sweden, Finland and Israel. Data on the costs of medications and on the cost per day were collected and fed in a simple algorithm to detect savings. These saving varied from country to country, from a minimum of €0.50 in Germany to a maximum of €354.64 in Sweden. Conclusions The use of levosimendan as a therapy for patients hospitalized for acute heart failure provides a net saving to hospitals driven by a reduction in the length of hospital stay. This finding is true in each of the countries considered in this study. [ABSTRACT FROM AUTHOR]

Perioperative detection of cardiac biomarkers may help to identify patients at risk. Whether detection of these markers will be recommended in the preoperative setting for patients with cardiac diseases in the future has to be discussed as large prospective trials on this topic are missing. For preoperative evaluation of cardiac insufficiency quantification of brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are useful markers. Troponin is the marker of choice for detection of myocardial ischemia/infarction in the postoperative setting. In unstable patients coronary angiography and/or percutaneous coronary intervention (PCI) are indicated. However, in stable patients the decision for coronary angiography and/or PCI has to be made in each patient individually after interdisciplinary discussion between anesthesiologists, cardiologists and surgeons. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Acute Heart Failure and Cardiogenic Shock: A Multidisciplinary Practical Guidance," by A. Mebazaa et al. in a 2015 issue.

OBJECTIVE:: In sepsis, cardiac function is frequently depressed. Microcirculatory disturbances as evidenced in most organs may extend to the coronary circulation and may play a role in the occurrence of cardiac dysfunction. Staphylococcal alpha-toxin and Escherichia coli hemolysin (ECH), pore-forming exotoxins of clinically relevant bacteria, have recently been demonstrated to evoke cardiac dysfunction in isolated rat hearts by activating myocardial eicosanoid metabolism. alpha-Toxin activates synthesis of thromboxane (Tx) A2, ECH of cysteinyl-leukotrienes (Sibelius U, Grandel U, Buerke M, et al: Leukotriene-mediated coronary vasoconstriction and loss in myocardial contractility evoked by low doses of Escherichia coli hemolysin in perfused reat hearts. Crit Care Med 2003; 3:683-688, Sibelius U, Grandel U, Buerke M, et al: Staphylococcal alpha-toxin provokes coronary vasoconstriction and loss in myocardial contractility in perfused rat hearts-Role of Tx formation. Circulation 2000; 101:78-85). We now investigated whether cardiac dysfunction in response to alpha-toxin and ECH is caused by disturbances of regional cardiac perfusion. DESIGN:: A prospective, experimental study. SETTING:: A research laboratory at a university hospital. SUBJECTS:: Isolated hearts from male Wistar rats. INTERVENTIONS:: Changes of regional perfusion were investigated by using colored microspheres in isolated rat hearts perfused with alpha-toxin or ECH either at constant coronary perfusion pressure or constant coronary flow rate. Significance of toxin-activated eicosanoid generation was evaluated by pharmacologic interventions. MEASUREMENTS AND MAIN RESULTS:: By eliciting eicosanoid formation, both toxins caused an increase in coronary vascular resistance and a loss in contractile function. In ECH-perfused hearts, reduction of regional perfusion predominantly occurred in subendocardial sections in either perfusion mode (coronary perfusion pressure or coronary flow rate). When synthesis of cysteinyl-leukotrienes was blocked by the 5-lipooxygenase inhibitor MK-886, disturbances of regional perfusion and the associated cardiac dysfunction were largely prevented. Coronary perfusion of alpha-toxin caused a decrease of regional perfusion that was more pronounced in subepicardial layers. Inhibiting the release of TxA2 by blocking the cyclooxygenase with indomethacin attenuated the perfusion abnormalities and the cardiodepression in response to alpha-toxin. CONCLUSIONS:: Bacterial exotoxins of clinically relevant bacteria may impair cardiac function by eliciting distinct coronary perfusion abnormalities via release of vasoactive eicosanoids. [ABSTRACT FROM AUTHOR]

Objective: Staphylococcal alpha-toxin and Escherichia coli hemolysin (ECH) evoke cardiac dysfunction in isolated rat hearts by provoking myocardial synthesis of arachidonic acid-derived thromboxane A2 or the cysteinyl-leukotrienes, LTC4, LTD4, and LTE4, respectively. We investigated whether low doses of either toxin, which fail to induce cardiac depression by themselves, induce cardiac dysfunction when combined with free arachidonic acid.Design: Prospective, experimental study.Setting: Research laboratory at a university hospital.Subjects: Isolated hearts from male Wistar rats.Interventions: Hearts were perfused with low doses of ECH or alpha-toxin in the absence or presence of arachidonic acid or the alternative eicosanoid precursor eicosapentaenoic acid (EPA).Measurements and Main Results: Application of low-dose ECH with arachidonic acid increased coronary perfusion pressure, depressed left ventricular contractile function, provoked electrical instability, and induced a release of creatine kinase concomitant with the liberation of LTC4, LTD4, and LTE4 into the perfusate. All events were abolished when formation of cysteinyl-leukotrienes was blocked by the 5-lipoxygenase activity inhibitor MK-886, targeting 5-lipoxygenase activating protein. In the presence of arachidonic acid, low doses of alpha-toxin caused an increase in cerebral perfusion pressure and a decline of contractile performance, attributable to the release of thromboxane A2, as both events were mitigated by the cyclooxygenase-inhibitor indomethacin. High doses of ECH caused cardiac dysfunction even in the absence of arachidonic acid. However, in the presence of EPA, the cardiodepressant effect of ECH was blunted. Release of EPA-derived LTE5 at the expense of arachidonic acid-derived LTC4, LTD4, and LTE4 was noted in these hearts.Conclusions: The potency of the bacterial exotoxins ECH and alpha-toxin to cause coronary vasoconstriction and myocardial depression is dependent on the availability of free arachidonic acid and may be influenced by supplying omega-3 fatty acids as alternative lipid precursors. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate the efficacy of the combination of clopidogrel and aspirin in the prevention of thrombus formation on artificial heart valves in an experimental rabbit model as compared to anticoagulation with warfarin. Methods: Studies were performed after oral administration of clopidogrel and aspirin in group I (n=9) for 5 days, after 5±2 days treatment with warfarin in group II (n=9) and without medication in group III (n=9). Leaflets from Sulzer Carbomedics bileaflet valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein. Results: In group III, the flow chamber was clotted after a median of 15 min of circulation. Weight analysis before and after 1 h of perfusion showed that the median thrombus weight was 9.1 mg in group I, 14.4 mg in group II and 33.7 mg in group III. Further analysis by electron microscopy showed fewer platelets and erythrocytes on leaflets in group I than on leaflet surfaces in group II. Conclusion: Clopidogrel and aspirin were more effective than warfarin in preventing thrombus formation on artificial heart valve leaflets in our investigation. This rabbit model with a high dosage of clopidogrel and aspirin, and a short-time exposure of the heart valve leaflets to rabbit blood under laminar flow, should be further evaluated with respect to whether it can give information about antithrombotic regimens in patients after mechanical heart valve replacement. [Copyright &y& Elsevier]

Background: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects.Methods: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions.Results: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment. [ABSTRACT FROM AUTHOR]

Perioperative detection of cardiac biomarkers may help to identify patients at risk. Whether detection of these markers will be recommended in the preoperative setting for patients with cardiac diseases in the future has to be discussed as large prospective trials on this topic are missing. For preoperative evaluation of cardiac insufficiency quantification of brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are useful markers. Troponin is the marker of choice for detection of myocardial ischemia/infarction in the postoperative setting. In unstable patients coronary angiography and/or percutaneous coronary intervention (PCI) are indicated. However, in stable patients the decision for coronary angiography and/or PCI has to be made in each patient individually after interdisciplinary discussion between anesthesiologists, cardiologists and surgeons. [ABSTRACT FROM AUTHOR]

Abstract: The synthetic arginine-derived direct thrombin inhibitor argatroban is an attractive anticoagulant for percutaneous coronary intervention (PCI), because of its rapid onset and offset, and its hepatic elimination. Argatroban was approved for PCI in patients with heparin-induced thrombocytopenia (HIT). However, there are limited data about argatroban in non-HIT patients. The objective of this open-label, multiple-dose, controlled study was to examine the safety and efficacy of argatroban in patients undergoing elective PCI. Methods and results: Of 140 patients randomized to three argatroban dose groups (ARG250, ARG300, and ARG350 with 250, 300, or 350μg/kg bolus, followed by 15, 20, or 25μg/kg/min infusion) and one unfractionated heparin (UFH) group (70–100IU/kg bolus), 138 patients were analyzed. Argatroban dose-dependently prolonged activated clotting time (ACT) with more patients reaching the minimum target ACT after the initial bolus injection (ARG250: 86.1%, ARG300: 89.5%, and ARG350: 96.8%) compared to 45.5% in UFH (p <0.001). The patient proportion who did not require additional bolus injections to start PCI was significantly higher in argatroban than in UFH (p ≤0.002). Consequently, the time to start of PCI was shortened in argatroban groups. Composite incidences of death, myocardial infarction, and urgent revascularization until day 30 were not significantly different between the groups (ARG250: 2.8%, ARG300: 0.0%, ARG350: 3.2% vs. UFH: 3.0%). Major bleeding was observed only in UFH (3.0%), while minor bleeding occurred in ARG350 (3.2%) and UFH (6.1%, n.s.). Conclusion: Argatroban dose-dependently increases coagulation parameters and, compared to UFH, demonstrates a superior predictable anticoagulant effect in patients undergoing elective PCI. [Copyright &y& Elsevier]

Background and purpose:Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage.Experimental approach:We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10 000 Ukg−1) or its vehicle were injected 5 min prior to the start of reperfusion.Key results:Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11±2.7% necrosis as percentage of area at risk after aprotinin; 24±3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2±1.5 and 17.3±2.3 IU g−1 protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44±15 vs 102±2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R.Conclusions and implications:Inhibition of serine proteases by aprotinin inhibits an inflammatory cascade initiated by MI+R. The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis.British Journal of Pharmacology (2008) 155, 93–102; doi:10.1038/bjp.2008.223; published online 9 June 2008 [ABSTRACT FROM AUTHOR]

Background and purpose:The Na+/H+ exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca2+ overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects.Experimental approach:An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 μ ml−1) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min).Key results:Treatment with cariporide (10 mg kg−1 i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54±6.2 to 2.4±1.0 cells min−1, P<0.01), adherence (6.3±1.9 to 1.2±0.4 cells 100 μm−1, P<0.01) and extravasation (9.1±2.1 to 2.4±1.1 cells per 20 × 100 μm perivascular space, P<0.05), following haemorrhagic shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P-selectin showed a profound decrease in endothelial expression following cariporide administration in both thrombin and I/R stimulated groups (35.4±3.2 vs 14.2±4.1% P-selectin positive cells per tissue section, P<0.01).Conclusions and implications:The NHE inhibitor cariporide is known to limit reperfusion injury by controlling Ca2+ overload but these data are novel evidence for a vasculoprotective effect of NHE inhibition at all levels of leukocyte activation, an effect which is likely to be mediated at least in part by a reduction of P-selectin expression.British Journal of Pharmacology (2008) 153, 1678–1685; doi:10.1038/sj.bjp.0707647; published online 10 March 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Multiple organ dysfunction syndrome (MODS) is a disease entity that carries a high mortality rate. It is characterized by a sequential failure of several organ systems after a trigger event, most commonly sepsis. There is increasing evidence that autonomic dysfunction may substantially contribute to the development of MODS. We recently characterized the spectrum of autonomic dysfunction by using heart rate variability in critically ill MODS patients and were able to show that autonomic dysfunction predicts 28-day mortality in MODS. The aim of the present study was evaluate whether autonomic dysfunction is also a predictor of 180-day and 365-day mortalities. DESIGN:: Prospective cohort study. SETTING:: Twelve-bed medical intensive care unit in a university center. PATIENTS:: Ninety consecutively admitted score-defined MODS patients. INTERVENTIONS:: We assessed heart rate variability as a marker of autonomic dysfunction. The patients were followed for 180- and 365-day mortalities. MEASUREMENTS AND MAIN RESULTS:: We prospectively used the heart rate variability variable lnVLF, which predicted 28-day mortality best in the entire cohort of patients, for analysis of longer term mortality. The variable lnVLF was found to be useful for risk prediction for about 60 days, and then the survival curves became nearly parallel. CONCLUSIONS:: Autonomic function of critically ill MODS patients is blunted, and this attenuation has prognostic implications not merely concerning 28-day mortality but also concerning longer term (about 2-month) mortality. [ABSTRACT FROM AUTHOR]

Objective: Multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, like sepsis or cardiogenic shock. Mortality rate is high, up to 70%. Autonomic dysfunction may substantially contribute to the development of MODS. Our study aimed to characterize a) the spectrum of autonomic dysfunction of critically ill MODS patients; b) whether autonomic dysfunction is different in patients receiving sedation, mechanical ventilation, or catecholamines; c) the age dependency of autonomic dysfunction in MODS; and d) whether autonomic dysfunction predicts mortality in MODS.Design: Prospective cohort study.Setting: Twelve-bed medical intensive care unit in a university center.Patients: Ninety consecutively admitted score-defined MODS patients.Interventions: Assessment of heart rate variability, baroreflex sensitivity, and chemoreflex sensitivity as markers of autonomic dysfunction. The patients were followed for 28-day mortality.Measurements and Main Results: Baroreflex sensitivity, chemoreflex sensitivity, and almost all indexes of heart rate variability were attenuated in comparison to normal range data. There was no association between the assessed heart rate variability variables, baroreflex sensitivity or chemoreflex sensitivity, and the presence of sedation or catecholamine therapy. Except for frequency-domain variables, pNN50 (percentage of differences of successive RR intervals differing >50 msecs) and rMSSD (root mean square of successive difference of N-N intervals), none of the measured variables were related to the presence of mechanical ventilation. Age dependency was detected for baroreflex sensitivity but not for heart rate variability indexes or chemoreflex sensitivity (across ages 24-96 yrs). lnVLF predicted 28-day mortality best in the entire cohort of patients and in a subgroup of patients with cardiogenic-triggered MODS.Conclusions: Autonomic function of MODS patients is blunted, and this attenuation has prognostic implications. The extensive influence of MODS on autonomic function overwhelms and masks the well-known age dependency of autonomic function seen in healthy persons. [ABSTRACT FROM AUTHOR]

An abstract of the article "The soluble guanylate cyclase activator BAY 58-2667 has a favourable safety profile and improves cardiopulmonary haemodynamics in acute decompensated heart failure," by V. Mitrovic and colleagues is presented.