O. Chioncel et al. Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.

Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients.

Background-Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function. Methods and Results-In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg SC) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein.In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde Ϫ25% versus 9%; nitrotyrosine Ϫ38% versus Ϫ11%; interleukin-6 Ϫ29% versus 0.9%; endothelin-1 Ϫ36% versus Ϫ11%; flow-mediated dilation 45% versus Ϫ9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; PϽ0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (PϽ0.05). Conclusions

In terms of in-hospital survival, a vasodilator in combination with a diuretic fared better than treatment with only a diuretic. Catecholamine inotropes should be used cautiously as it has been seen that they actually increase the risk for in-hospital mortality.

AimsLittle is known regarding temporal trends in mortality attributed to heart failure (HF) from a population perspective. The aim of this study was to assess the mortality related to HF as an underlying cause during the last 20 years in seven European countries. Methods and resultsThe number of deaths with HF as the underlying cause was collected in seven European states: Germany, Greece, England and Wales, Spain, France, Finland, and Sweden from 1987 to 2008. Disease coding for HF was based on the International Classification of Diseases (ICD 9th and 10th versions). We computed age-standardized death rates (SDRs) per 100 000 inhabitants. Mean age at death from HF was also calculated for the same period. In the seven studied countries, the HF SDR decreased continuously from 54.2 (1987) to 32.6 (2008). Despite differences in the early 1990s, SDRs related to HF seemed to converge, in these seven European countries, to 30 deaths per 100 000 population in the near future, for both men and women. During the study period, the mean age at death increased from 80.0 to 82.7 years. Half of the deaths from HF occurred in hospital, without change over time. ConclusionThere has been a 40% reduction of the SDR due to HF in seven European countries during two decades and a concomitant increase in the mean age at death from HF. We hypothesize that these results may be related to a better management of chronic and acute HF patients over the past 20 years.--

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps.

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Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.