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Background: Pulmonary venous hypertension (PVH) is very common. The mechanism of PVH is still under discussion and might constitute a 'hyperactive' form of pulmonary vascular remodelling which leads to an inappropriate increase in pulmonary vascular resistance and subsequent significant right heart dysfunction. According to current opinion, the oral dual endothelin (ETA/ETB) antagonist bosentan is not indicated for PVH. We investigated prospectively bosentan in two patients with postcapillary venous hypertension (PVH) to resolve right heart failure.Methods: One patient presented with high-grade aortic stenosis, judged inoperable due to severe congestive liver, pancreatic and bowel disease; the other had a mitral valve replacement 14 years ago. Invasive evaluation of reversibility of pulmonary hypertension with intravenous epoprostenol was performed, and subsequently a test administration of bosentan was given to exclude a significant increase in left ventricular filling pressure. Thereafter bosentan therapy twice daily was administered. Clinical and echocardiographic follow-up was for 5 months.Results: In patient 1, PVH decreased dramatically over 5 months of bosentan treatment. 6-minute walk distance improved from 225 to 525 meters. In patient 2 right ventricular pressure decreased from 60 to 40 mmHg + right atrial pressure (echocardiographic measurements) and his 6-minute walk distance increased from 242 m to 477 m during follow-up of 5 months.Conclusion: Bosentan might lead to improvement in patients with PVH. Invasive haemodynamic testing to confirm pulmonary reagibility and exclude increasing pulmonary capillary wedge pressure is warranted before administration of bosentan. [ABSTRACT FROM AUTHOR]

An abstract of the study "Cardiac Hepatopathy Before and After Heart Transplantation," by W. Dichtl and colleagues is presented.

Irisin is a myokine involved in adipocyte transformation. Its main beneficial effects arise from increased energy expenditure. Irisin production is particularly stimulated by physical exercise. The present study investigates the changes of plasma irisin in type 2 diabetic patients performing 2 different training modalities. Fourteen type 2 diabetic patients underwent 4 week of supervised high-intensity interval training (HIT; n=8) or continuous moderate-intensity training (CMT; n=6), with equivalent total amounts of work required. Plasma samples were collected in the resting state atbaseline and one day after the exercise intervention to analyse resting plasma irisin, blood lipids, blood glucose, hsCRP, Adiponectin, Leptin and TNF-α concentrations. In addition, body composition and VO 2peak were determined Resting plasma irisin increased after HIT (p=0.049) and correlated significantly with plasma fasting glucose at follow-up (r=0.763; p=0.006). CMT did not significantly change the amount of plasma irisin, although follow-up values of plasma irisin correlated negatively with fat-free mass (r=-0.827, p=0.002) and with fasting plasma glucose (r = - 0.934, p=0.006). Plasma irisin was found to increase with higher training intensity, confirming the assumption that exercise intensity, in addition to the type of exercise, may play an important role in the stimulation of the irisin response., Competing Interests: The authors declare no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Chronic inflammation, even at subclinical levels, is associated with adverse long-term outcome., Patients and Methods: In this prospective, observational study, 66 critically ill patients surviving to hospital discharge were included. C-reactive protein (CRP) levels were determined at hospital discharge, 1, 2, and 6 weeks after hospital discharge. All the patients were repeatedly screened for adverse events resulting in rehospitalization or death for 1.5 years., Results: After hospital discharge, over two-thirds of the patients exhibited elevated CRP levels (>2.0 mg/L). During the first week, CRP decreased compared with hospital discharge (P < 0.001) but did not change after week 1 (P = 0.67). Age (P = 0.24), surgical status (P = 0.95), or sepsis (P = 0.77) did not influence the CRP course. The latter differed between patients with (n = 15) and without (n = 51) adverse events (P = 0.003). CRP levels of patients without adverse events persistently decreased after hospital discharge (P = 0.03), whereas those of patients with adverse events did not (P = 0.86) but rebounded early., Conclusions: Plasma CRP levels in critically ill patients decreased during the first week after hospital discharge but remained unchanged during the subsequent 5 weeks. Over two-thirds of the patients exhibited elevated CRP levels compatible with chronic sub-clinical inflammation. Persistently elevated CRP levels after hospital discharge are associated with higher risk of rehospitalization.

Background: In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults., Methods: In this prospective, randomized, controlled open-label study, we evaluated the influence of in-line microfilters on systemic immune activation in 504 critically ill adults with a central venous catheter in place and an expected length of stay in the intensive care unit >24 h. Patients were randomized to have in-line microfilters placed into all intravenous lines (intervention group) or usual care (control group). The primary endpoint was the number of intensive care unit days with SIRS. Secondary endpoints were the incidence of SIRS, SIRS criteria per day, duration of invasive mechanical ventilation, intensive care unit length of stay, the incidence of acute lung injury, maximum C-reactive protein, maximum white blood cell count, incidence of new candida and/or central-line-associated bloodstream infections, incidence of new thromboembolic complications, cumulative insulin requirements and presence of hyper- or hypoglycemia., Results: The study groups did not differ in any baseline variable. There was no difference in the number of days in the intensive care unit with SIRS between microfilter and control patients [2 (0.8-4.7) vs. 1.8 (0.7-4.4), p = 0.62]. Except for a higher incidence of SIRS in microfilter patients (99.6 vs. 96.8 %, p = 0.04), no difference between the groups was observed in any secondary outcome parameter. Results did not change when only patients with an intensive care unit length of stay of greater than 7 days were included in the analysis. The rate of adverse events was comparable between microfilter and control patients. In two patients allocated to the microfilter group, the study intervention was discontinued for technical reasons. Use of in-line microfilters was associated with additional costs., Conclusions: The use of in-line microfilters failed to modulate systemic inflammation and clinical outcome parameters in critically ill adults., Trial Registration: Clinical Trials NCT01534390.

Background: Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients., Methods: In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13)., Findings: We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001)., Interpretation: During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke., Funding: Reformpool of the Tyrolean Health Care Fund., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Heart failure (HF) is approaching epidemic proportions worldwide and is the leading cause of hospitalization in the elderly population. High rates of readmission contribute substantially to excessive health care costs and highlight the fragmented nature of care available to HF patients. Disease management programs (DMPs) have been implemented to improve health outcomes, patient satisfaction, and quality of life, and to reduce health care costs. Telemonitoring systems appear to be effective in the vulnerable phase after discharge from hospital to prevent early readmissions. DMPs that emphasize comprehensive patient education and guideline-adjusted therapy have shown great promise to result in beneficial long-term effects. It can be speculated that combining core elements of the aforementioned programs may substantially improve long-term cost-effectiveness of patient management.We introduce a collaborative post-discharge HF disease management program (HerzMobil Tirol network) that incorporates physician-controlled telemonitoring and nurse-led care in a multidisciplinary network approach.

Purpose: A heart rate >90 bpm serves as one of four characteristics defining the systemic inflammatory response syndrome and is used in scoring systems to predict in-hospital mortality of intensive care unit (ICU) patients. Despite its central role in critical illness, specific data regarding the relationship between heart rate and outcome are rare., Methods: In this post hoc analysis of a prospectively collected database, we analyzed the value of heart rate averaged from four predefined time points during the last 24 h before ICU discharge as a predictor of post-ICU in-hospital and post-hospital mortality in medical ICU patients. Furthermore, the relationship between heart rate and inflammation, as well as the influence of rate control medications on the association between heart rate and outcome were identified., Results: Among the 702 ICU patients discharged from the ICU, 7.1 % died before hospital discharge. At 4 years of follow-up, post-hospital mortality was 14.4 %. Multivariate Cox proportional hazards models revealed heart rate before ICU discharge (HR 5.95; 95 % CI 1.24-28.63; p = 0.03) as an independent predictor of post-ICU in-hospital mortality. Both heart rate (HR 2.56; 95 % CI, 1.05-6.34; p = 0.04) and the C-reactive protein serum concentration before ICU discharge (HR, 1.26; 95 % CI, 1.09-1.46; p = 0.002) were independently associated with post-hospital mortality. Heart rate control therapy reduced the risk of post-ICU in-hospital (HR 0.38; 95 % CI, 0.18-0.81; p = 0.01) and post-hospital (HR, 0.47; 95 % CI, 0.22-1.00; p = 0.05) mortality., Conclusion: Heart rate evaluated 24 h before ICU discharge was independently associated with post-ICU in-hospital and post-hospital mortality. Pharmacological interventions to control heart rate may beneficially influence post-ICU mortality.

Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the "gold standard." In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests.

Background: Exercise capacity in patients with dilated cardiomyopathy has low correlation to resting left ventricular function. Dysfunctional autonomic activity, cardiomechanics and inflammation are associated with exercise capacity but were investigated under inhomogeneous situations. It remains essentially unclear which factor mainly determines exercise capacity in dilated cardiomyopathy., Methods: In a prospective, observational study in a narrow time frame we assessed clinically, inflammatory, hemodynamic and, autonomic parameters as well as echocardiographic measures to explore independent determinants of exercise capacity in 28 treated patients with dilated cardiomyopathy., Results: Right ventricular end-diastolic diameter, tricuspid regurgitation velocity, and sympathovagal balance were independent determinants of exercise capacity (B coefficient, 69; CI 95 %, 15-122; p = 0.004); (B coefficient, - 226; CI 95 %, - 374 to - 79; p = 0.007) and (B coefficient, - 104; CI 95 %, - 172 to - 37), respectively. C-reactive protein, serum creatinin and body mass index were independently associated with right ventricular end-diastolic diameter (B coefficient, 0.34; CI 95 %, 0.12-0.56; p = 0.004); (B coefficient, 0.9; CI 95 %, 0.34-1.455; p = 0.003); and (B coefficient, 0.09; CI 95 %, 0.02-0.15; p = 0.01), respectively., Conclusions: In stable patients with dilated cardiomyopathy, autonomic modulation, and right ventricular dysfunction may be the most important determinants of exercise capacity, whereas inflammation, kidney dysfunction, and body mass index are independently associated with right ventricle remodeling.

The ongoing conflict in the Eastern Republic of the Congo (DRC) has claimed up to 5.4 million lives by 2008. Whereas few deaths were directly due to violence, most victims died from medical conditions such as infectious diseases. This survey investigates the availability of resources required to provide adequate sepsis care in Eastern DRC. The study was conducted as a self-reported, questionnaire-based survey in four Eastern provinces of the DRC. Questionnaires were sent to a cluster of 80 urban-based hospitals in the North Kivu, South Kivu, Maniema and Orientale provinces. The questionnaire contained 74 questions on the availability of resources required to adequately treat sepsis patients as suggested by the latest Surviving Sepsis Campaign (SSC) guidelines. Sixty-six questionnaires were returned (82.5%) and analyzed. Crystalloid solutions and intravenous fluid giving sets were the only resources constantly available in all hospitals. None of the respondents reported to have constant access to piperacillin, carbapenems, fresh frozen plasma, platelets, dobutamine, activated protein C, echocardiography or equipment to measure lactate levels, invasive blood pressure, central venous pressure, cardiac output, pulmonary artery pressure or endtidal carbon dioxide. No respondent stated that a mechanical ventilator, syringe pump, fluid infuser, peritoneal dialysis or haemodialysis/hemofiltration machine was constantly available at his/her hospital. Resources required for consistent implementation of the SSC guidelines were not available in any hospital. care and implement the SSC guidelines in a cluster of hospitals in the Eastern DRC.

Purpose: To describe the mechanics and possible clinical importance of left ventricular (LV) rotation, exemplify techniques to quantify LV rotation and illustrate the temporal relationship of cardiac pressures, electrocardiogram and LV rotation., Materials and Methods: Review of the literature combined with selected examples of echocardiographic measurements., Results: Rotation of the left ventricle around its longitudinal axis is an important but thus far neglected aspect of the cardiac cycle. LV rotation during systole maximizes intracavitary pressures, increases stroke volume, and minimizes myocardial oxygen demand. Shearing and restoring forces accumulated during systolic twisting are released during early diastole and result in diastolic LV untwisting or recoil promoting early LV filling. LV twist and untwist are disturbed in a number of cardiac diseases and can be influenced by several therapeutic interventions by altering preload, afterload, contractility, heart rate, and/or sympathetic tone., Conclusions: The concept of LV twisting and untwisting closely linking LV systolic and diastolic function may carry potential diagnostic and therapeutic importance for the management of critically ill patients. Future clinical studies need to address the feasibility of assessing LV twist and untwist as well as the relevance of its therapeutic modulation in critically ill patients.

Background: Plasma copeptin levels before and during exogenous arginine vasopressin infusion (AVP) were evaluated, and the value of copeptin levels before AVP therapy to predict complications during AVP therapy and outcome in vasodilatory shock patients was determined., Methods: This prospective, observational study was nested in a randomized, controlled trial investigating the effects of two AVP doses (0.033 vs. 0.067 IU/min) on the hemodynamic response in patients with advanced vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery. Clinical data, plasma copeptin levels and adverse events were recorded before, 24 hours after and 48 hours after randomization., Results: Plasma copeptin levels were elevated before AVP therapy. During AVP, copeptin levels decreased (P<0.001) in both groups (P=0.73). Copeptin levels at randomization predicted the occurrence of ischemic skin lesions (AUC ROC, 0.73; P=0.04), a fall in platelet count (AUC ROC, 0.75; P=0.01) during AVP and intensive care unit mortality (AUC ROC, 0.67; P=0.04). Twenty-five patients (64.1%) exhibited a decrease in copeptin levels. Patients experiencing a decrease in copeptin levels were older (P=0.04), had a higher Sequential Organ Failure Assessment score count before (P=0.03) and during AVP therapy (P=0.04), had a longer intensive care unit stay (P<0.001) and required AVP therapy longer (P=0.008) than patients without a decrease in copeptin levels during AVP., Conclusion: Plasma copeptin levels are elevated in patients with advanced vasodilatory shock. During exogenous AVP therapy, copeptin levels decrease, suggesting suppression of the endogenous AVP system.

Objective: To assess if secondary and tertiary hospitals in Mongolia have the resources needed to implement the 2008 Surviving Sepsis Campaign (SSC) guidelines., Methods: To obtain key informant responses, we conducted a nationwide survey by sending a 74-item questionnaire to head physicians of the intensive care unit or department for emergency and critically ill patients of 44 secondary and tertiary hospitals in Mongolia. The questionnaire inquired about the availability of the hospital facilities, equipment, drugs and disposable materials required to implement the SSC guidelines. Descriptive methods were used for statistical analysis. Comparisons between central and peripheral hospitals were performed using non-parametric tests., Findings: The response rate was 86.4% (38/44). No Mongolian hospital had the resources required to consistently implement the SSC guidelines. The median percentage of implementable recommendations and suggestions combined was 52.8% (interquartile range, IQR: 45.8-67.4%); of implementable recommendations only, 68% (IQR: 58.0-80.5%) and of implementable suggestions only, 43.5% (IQR: 34.8-57.6%). These percentages did not differ between hospitals located in the capital city and those located in rural areas., Conclusion: The results of this study strongly suggest that the most recent SSC guidelines cannot be implemented in Mongolia due to a dramatic shortage of the required hospital facilities, equipment, drugs and disposable materials. Further studies are needed on current awareness of the problem, development of national reporting systems and guidelines for sepsis care in Mongolia, as well as on the quality of diagnosis and treatment and of the training of health-care professionals.

Background: There are no data on the association between acute inflammation during critical illness and long-term mortality in ICU patients., Methods: Nonsurgical patients with an ICU length of stay > 24 h surviving until ICU discharge were included into this prospective, observational, follow-up study. Demographics, chronic diseases, admission diagnosis, the Simplified Acute Physiology Score (SAPS) II, length of ICU stay, maximum C-reactive protein (CRP) levels during the ICU stay (CRPmax), and CRP levels at ICU discharge (CRPdis) were documented. After a follow-up time of 1.88 ± 1.16 years (range, 0.5-4 years), the survival status was determined., Results: Seven hundred sixty-five patients were enrolled into the study protocol. One hundred fifty-eight patients (20.7%) died within 0.62 ± 0.88 years after ICU discharge. Cumulative survival rates differed between patients grouped into the CRPmax and CRPdis quartiles. Patients in the first and second CRPmax quartiles had better cumulative survival rates than those in higher CRPmax quartiles (all P < .001). Patients in the first CRPdis quartile had better cumulative survival rates than those in higher CRPdis quartiles (all P < .001). Using adjusted Cox proportional hazards models, both CRPmax and CRPdis were independently associated with post-ICU mortality (both P < .001). Furthermore, the number of chronic diseases (P < .001), age (P < .001), and the SAPS II (P = .03) were associated with post-ICU mortality in both Cox models., Conclusions: CRP levels during critical illness seem independently associated with post-ICU survival in nonsurgical ICU patients. Future research focusing on the association between acute systemic inflammation and post-ICU outcome is warranted in order to improve long-term survival of critically ill patients.

Study Objective: To evaluate the current status of anesthesia and its allied disciplines in Mongolia., Design: Nationwide questionnaire survey., Setting: Two university hospitals., Measurements: A total of 44 hospitals that include a department of surgery and that were registered at the Mongolian Ministry of Health were queried. The questionnaire included 44 questions in two sections. The first section consisted of 6 general questions about the hospital, and the second section included 40 questions on anesthesia and perioperative patient care. The Mann-Whitney U-test, Chi²-tests, and a bivariate correlation analysis were used for statistical analysis., Main Results: 44 (100%) questionnaires were returned. Twenty-two (50%) hospitals were located in the capital city of Ulaanbaatar. Nine hundred (median; interquartile range: 413-1,468) surgical interventions were performed annually in the study hospitals. Physician anesthesiologists delivered anesthesia in all hospitals. Techniques for general anesthesia included endotracheal intubation (95.5%), laryngeal mask ventilation (13.6%), mask ventilation (27.3%), dissociative ketamine anesthesia (84.1%), and combined general/regional anesthesia (63.6%). Regional anesthetic techniques included spinal (97.7%), epidural (43.2%), axillary plexus (40.9%), peripheral nerve (13.6%), and local anesthesia (15.9%). The most frequently used hypnotics were ketamine (86.4%) and thiopental sodium (70.5%). Halothane was available in all hospitals. Oxygen was available during anesthesia in 95.5% of hospitals. The most widely available intraoperative monitoring equipment were a stethoscope (84.1%), oximeter (81.8%), and sphygmomanometer (84.1%). A recovery room was available in 22 (50%) hospitals., Conclusions: Anesthesia is an underdeveloped and under-resourced medical specialty in Mongolia., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection., Methods: A medical database was retrospectively searched for critically ill patients admitted because of septic shock from abdominal infection (n = 194). Demographic, clinical, and laboratory data; FO supplementation (10 g/d) (n = 42); rate, degree, and number of organ failures assessed by the Sequential Organ Failure Assessment (SOFA) score; and secondary outcome variables were recorded. A propensity score-based model was used to establish 2 comparable groups (FO, n = 29; control, n = 29). Mann-Whitney rank sum test, Fisher exact test, and logistic regression analyses were used to compare variables between groups., Results: There were no differences in the rate of single organ failures, the maximum SOFA score (median [interquartile range (IQR)], 12 [8-15] vs 11 [9-14]; P = .99), or the number of organ failures (median [IQR], 2 [1-3] vs 2 [1-3]; P = .54] between patients receiving FO supplementation and those not receiving supplementation. There were no group differences in the maximum C-reactive protein levels (P = .1), duration of mechanical ventilation (P = .65) or hemofiltration (P = .21), intensive care unit-acquired infections, intensive care unit length of stay (P = .59), and intensive care unit (P = 1) or hospital mortality (P = 1)., Conclusions: Early intravenous FO may not decrease the number and degree of organ failures in patients with septic shock from abdominal infection. Future trials are needed before FO supplementation in septic shock from abdominal infection can be recommended.

Despite successful intensive care a substantial portion of critically ill patients dies after discharge from the intensive care unit or hospital. Observational studies investigating long-term survival of critically ill patients reported that most deaths occur during the first months or year after discharge. Only limited data on the causes of impaired quality of life and post-intensive care unit deaths exist in the current literature. In this manuscript we hypothesize that the acute inflammatory response which characteristically accompanies critical illness is ensued by a prolonged imbalance or activation of the immune system. Such a chronic low-grade inflammatory response to critical illness may be sub-clinical and persist for a variable period of time after discharge from the intensive care unit and hospital. Chronic inflammation is a well-recognized risk factor for long-term morbidity and mortality, particularly from cardiovascular causes, and may thus partly contribute to the impaired quality of life as well as increased morbidity and mortality following intensive care unit and hospital discharge of critically ill patients. Assuming that critical illness is indeed followed by a prolonged inflammatory response, important implications for treatment would arise. An interesting and potentially beneficial therapy could be the administration of immune-modulating drugs during the time after intensive care unit or hospital discharge until chronic inflammation has subsided. Statins are well-investigated and effective drugs to attenuate chronic inflammation and could potentially also improve long-term outcome of critically ill patients after intensive care unit or hospital discharge. Future studies evaluating the course of inflammation during and after critical illness as well as its response to statin therapy are required., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Purpose: To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock., Methods: In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6 microg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067 IU/min (n = 25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48 h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period., Results: Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067 IU/min required less norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P < 0.001), but were higher in the 0.067 IU/min group (P < 0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033 IU/min, 52%; 0.067 IU/min, 52%; P = 1)., Conclusions: A supplementary AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033 IU/min.

Background: It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock., Methods: The database of a multidisciplinary intensive care unit (ICU) was retrospectively screened for adult patients with septic shock. BMI, demographic, clinical and laboratory variables together with outcome measures were collected in all patients. Subjects were categorized as follows: underweight, BMI < 18.5; normal weight, BMI 18.5-24.9; overweight, BMI 25-29.9; obesity, BMI >or= 30. Bivariate and multivariate logistic regression models were used to evaluate the association between BMI and outcome parameters., Results: In total, 301 patients with septic shock were identified. BMI was bivariately associated with ICU mortality (OR 0.91; 95% CI 0.86-0.98; P = 0.007). There was no significant association between BMI and ICU mortality in the multivariate model but an increasing BMI tended to be associated with lower ICU mortality (OR 0.93; 95% CI 0.86-1.01; P = 0.09). Although overweight (OR 0.43; 95% CI 0.19-0.98; P = 0.04) and obese (OR 0.28; 95% CI 0.08-0.93; P = 0.04) patients had an independently lower risk of ICU death than those with normal weight, there was no difference in the risk of ICU death between normal weight and underweight patients (P = 0.22). A high BMI was independently associated with a lower frequency of acute delirium (P = 0.04) and a lower need for ICU re-admission (P = 0.001) but with a higher rate of ICU-acquired urinary tract infections (P = 0.02)., Conclusions: BMI up to 50 does not appear to be associated with worse ICU and hospital mortality in patients with septic shock. In contrast, a high BMI may reduce the risk of death from septic shock.

Background: Telemonitoring of patients with chronic heart failure (CHF) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization., Objective: The goal of the MOBIle TELemonitoring in Heart Failure Patients Study (MOBITEL) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation., Methods: Patients were randomly allocated to pharmacological treatment (control group) or to pharmacological treatment with telemedical surveillance for 6 months (tele group). Patients randomized into the tele group were equipped with mobile phone-based patient terminals for data acquisition and data transmission to the monitoring center. Study physicians had continuous access to the data via a secure Web portal. If transmitted values went outside individually adjustable borders, study physicians were sent an email alert. Primary endpoint was hospitalization for worsening CHF or death from cardiovascular cause., Results: The study was stopped after randomization of 120 patients (85 male, 35 female); median age was 66 years (IQR 62-72). The control group comprised 54 patients (39 male, 15 female) with a median age of 67 years (IQR 61-72), and the tele group included 54 patients (40 male, 14 female) with a median age of 65 years (IQR 62-72). There was no significant difference between groups with regard to baseline characteristics. Twelve tele group patients were unable to begin data transmission due to the inability of these patients to properly operate the mobile phone ("never beginners"). Four patients did not finish the study due to personal reasons. Intention-to-treat analysis at study end indicated that 18 control group patients (33%) reached the primary endpoint (1 death, 17 hospitalizations), compared with 11 tele group patients (17%, 0 deaths, 11 hospitalizations; relative risk reduction 50%, 95% CI 3-74%, P = .06). Per-protocol analysis revealed that 15% of tele group patients (0 deaths, 8 hospitalizations) reached the primary endpoint (relative risk reduction 54%, 95% CI 7-79%, P= .04). NYHA class improved by one class in tele group patients only (P< .001). Tele group patients who were hospitalized for worsening heart failure during the study had a significantly shorter length of stay (median 6.5 days, IQR 5.5-8.3) compared with control group patients (median 10.0 days, IQR 7.0-13.0; P= .04). The event rate of never beginners was not higher than the event rate of control group patients., Conclusions: Telemonitoring using mobile phones as patient terminals has the potential to reduce frequency and duration of heart failure hospitalizations. Providing elderly patients with an adequate user interface for daily data acquisition remains a challenging component of such a concept.

The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

Background and Purpose: Levosimendan is a new calcium sensitizer that enhances the contractile force of the myocardium and exhibits additional vasodilating properties. The present study describes the hemodynamic effects of levosimendan in patients with acute predominant right heart failure in need of inotropic therapy., Patients and Methods: 18 patients (15 male, age 60 +/- 17 years) with acute heart failure, predominant right ventricular dysfunction, left ventricular ejection fraction (LVEF) < or = 30%, cardiac index (CI) < or = 2.5 l/min/m(2), right atrial pressure (RAP) > or = 10 mmHg, and pulmonary capillary wedge pressure (PCWP) > or = 15 mmHg were investigated. Following a loading dose, levosimendan was administered intravenously for 24 h., Results: After 24 h, CI and left ventricular stroke work index increased from 1.7 +/- 0.4 to 2.3 +/- 0.6 l/min/m(2) (p < 0.001) and 14 +/- 6 to 17.3 +/- 8 g-m/m(2)/beat (p < 0.05), respectively. PCWP and systemic vascular resistance decreased from 25 +/- 7 to 21 +/- 5 mmHg (p < 0.01) and 1,724 +/- 680 to 1,096 +/- 312 dyne * s * cm(-5) (p < 0.0001), respectively. RAP was reduced from 15 +/- 5 to 10 +/- 3 mmHg (p < 0.001), whereas decreases in mean pulmonary artery pressure and pulmonary vascular resistance were not significant. Right ventricular stroke work index (RVSWI) increased from 4.8 +/- 1.8 to 7.6 +/- 3.4 g-m/m(2)/beat (p < 0.01)., Conclusion: Levosimendan therapy is feasible and improves hemodynamics in patients with acute predominant right heart failure. Augmentation in RVSWI indicates an increase in right ventricular contractility rather than reduction in afterload as a possible pathophysiological mechanism.

Background and Aim of the Study: Aortic valve calcification may be an independent risk factor for adverse clinical outcome. The study aim was to assess the predictive value of possible risk factors, including the severity of aortic valve calcification as quantified with 16-multislice computed tomography (MSCT) for adverse short-term clinical outcome in patients with asymptomatic, degenerative aortic stenosis (AS)., Methods: Possible risk factors for adverse short-term clinical outcome were prospectively tested in 34 consecutive patients with asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated with continuity equation, mean and maximal transvalvular pressure gradients, end-diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic peptide (BNP), C-reactive protein (CRP))., Results: Within 18-24 months of follow up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients suffered from onset of symptoms accompanied by hemodynamic progression, and one patient died from sudden cardiac death. Six of these 10 patients underwent aortic valve replacement, one patient declined surgery, and three patients were not accepted for surgery (one of these died suddenly shortly afterwards). The aortic valve calcium score was the strongest predictor of a major adverse clinical event (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409 Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse clinical outcome., Conclusion: The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS. In patients with severe aortic valve calcification, close follow up examinations are mandatory, and early elective surgery may be considered even in the absence of symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS.

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.

Aims: This study compared the efficacy and safety of intravenous flecainide and ibutilide for immediate cardioversion of atrial fibrillation (AF)., Methods and Results: We conducted a prospective, randomised trial, including 207 patients with AF of recent onset (< or = 48 h). Flecainide was given over 20 min at a dose of 2 mg/kg body weight (maximum 200 mg), ibutilide was infused at a dose of 1 mg (or 0.01 mg/kg if less than 60 kg) over 10 min, followed by a 10 min observation period and an identical second dose if AF did not convert to sinus rhythm (SR). Treatment was considered successful if SR occurred within 90 min of starting medication. The conversion rates were 56.4% in patients given flecainide and 50.0% in patients given ibutilide (P=0.34). Multivariate analysis revealed that a lower age for women independently increased the probability of conversion. None of the other variables, including left atrial size, left ventricular systolic function, presence of left ventricular hypertrophy, plasma levels of potassium or magnesium at baseline, or concomitant use of digoxin, beta-blocker, diltiazem or verapamil were predictors of conversion. The frequency of adverse events was comparable in the two treatment groups., Conclusions: There was no significant difference in the cardioversion efficacy or in the risk of adverse events between flecainide and ibutilide in patients with AF of recent onset. In patients without contraindications to both medications, the physician's choice has to be governed by other factors.

Background: Both vascular inflammation as determined by C-reactive protein (CRP) and extrinsic coagulation as measured by factor VII activity (F VII) may predict clinical restenosis rate in patients with stable angina pectoris undergoing elective percutaneous coronary intervention (PCI)., Hypothesis: The primary objective of this study was to investigate the associations between baseline CRP levels, F VII activity, and restenosis rate after elective PCI in a 6-month follow-up period., Methods: This prospective study included 81 patients aged > or = 19 years undergoing PCI for angiographically significant (> or = 70%) stenosis, with or without stenting, and 49 controls. Factor VII activity and CRP were measured in samples collected at angiography and 16-24 h post procedure after overnight fast. Successful PCI was defined as final diameter of < 50% with TIMI 3 flow and no complication within 1 h. After 6 months all patients who had undergone PCI were evaluated via a standardized questionnaire. Clinical restenosis was defined as the occurrence of a major adverse coronary events (MACE), within the follow-up period., Results: Diagnostic angiography led to a significant increase in CRP levels after 16-20 h in patients with discrete CAD (n = 22) but not in patients without any signs of coronary atherosclerosis (n = 27). During a 6-month follow-up after PCI, 17 of 81 (21%) patients developed MACE. Tertiles of CRP levels independently predicted clinical restenosis, as it developed in 33.3% of patients with the highest CRP levels (0.7-4.8 mg/dl), in 16.6% of patients with second tertile CRP levels (0.23-0.69 mg/dl), and in 7.4% of patients with lowest tertile CRP levels (0.0-0.22 mg/dl). There was a significant difference in the restenosis rate between patients from the first and the third tertiles (p = 0.018). Successful PCI was associated with a significant decrease of mean CRP levels after 6 months, whereas PCI in patients suffering from MACE led to no change in CRP levels. There was no association between factor VII activity and clinical outcome after PCI, and F VII activity did not change over a 6-month period., Conclusions: In patients with stable angina pectoris undergoing elective PCI, increased preprocedural and 6-month follow-up CRP plasma levels are associated with clinical restenosis. Factor VII plasma activity lacks such correlations.