Are platelets a 'forgotten' source of sepsis-induced myocardial depressing factor(s)?

The mechanism of sepsis-induced cardiac failure was initially thought to be related to the presence of 'myocardial depressant' substances that directly alter heart function. Exosomes released by platelets and identified in the plasma are suggested to, at least partially, explain myocardial depression in sepsis. This hypothesis needs to be evaluated by clinical studies

Nitric oxide inhibition rapidly increases blood pressure with no change in outcome in cardiogenic shock: the TRIUMPH trial

The TRIUMPH study, recently published in Journal of the American Medical Association, was a prospective randomized placebo-controlled trial testing the hypothesis that tilarginine (a non-specific inhibitor of nitric oxide synthase), when compared with placebo, would reduce 30-day mortality by 25% in patients with myocardial infarction complicated by refractory cardiogenic shock despite successful revascularization of the infarct-related artery. Patients received an intravenous bolus of the drug followed by 5 hours of intravenous infusion of the drug or a matching placebo. Although tilarginine increased systolic blood pressure by 5 mmHg at 2 hours, no effect on mortality was observed at 30 days. There was, however, a 6% absolute increase in 30-day mortality in the tilarginine group (48%, versus 42% in the placebo). This definitive trial gave strong indications for stopping any further trial using non-specific inhibitors of nitric oxide synthase in cardiogenic shock and possibly also in any other cardiovascular area

In vivo and in vitro evidence for pleiotropic effects of levosimendan in the intensive care setting

Levosimendan, in addition to its inotropic properties, could have anti-inflammatory and anti-oxidative properties, and can potentially decrease the deleterious effects of reactive oxygen species on the tissues. In their study, Hasslacher and colleagues provided not only in vitro but also in vivo evidence that levosimendan could preserve organ function in acute heart failure and septic-shock-induced myocardial depression via cooling down the oxidative burst of circulating cells

Searching for an ideal hemodynamic marker to predict short-term outcome in cardiogenic shock

Cardiogenic shock is a lethal condition. Physicians are searching for hemodynamic markers which could help risk-stratification of patients in this picture. Torgersen and coworkers present an hourly time integral of the cardiac power index and cardiac index drops to predict outcomes in the setting of cardiogenic shock. Continuous monitoring of hemodynamic markers may have a role in prediction of outcomes

ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning

Acute Heart Failure Management

Acute heart failure (AHF) is a life-threatening medical condition, where urgent diagnostic and treatment methods are of key importance. However, there are few evidence-based treatment methods. Interestingly, despite relatively similar ways of management of AHF throughout the globe, mid-term outcome in East Asia, including South Korea is more favorable than in Europe. Yet, most of the treatment methods are symptomatic. The cornerstone of AHF management is identifying precipitating factors and specific phenotype. Multidisciplinary approach is important in AHF, which can be caused or aggravated by both cardiac and non-cardiac causes. The main pathophysiological mechanism in AHF is congestion, both systemic and inside the organs (lung, kidney, or liver). Cardiac output is often preserved in AHF except in a few cases of advanced heart failure. This paper provides guidance on AHF management in a time-based approach. Treatment strategies, criteria for triage, admission to hospital and discharge are described.Peer reviewe

The elusive task of biomarkers of renal injury

Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising candidate biomarkers of renal injury, with expression in renal tissue increasing dramatically after ischemia-reperfusion injury but not in the case of pure pre-renal failure. In a recent issue of Critical Care, Di Somma and colleagues reported that NGAL could improve the classification of acute kidney injury compared with clinical assessment and showed that NGAL was associated with poor prognosis. NGAL may therefore carry different information than biomarkers of renal function. This study finally provides additional evidence for the highly complex relationship between renal function and renal injury

Improving Postdischarge Outcomes in Acute Heart Failure

The global burden that acute heart failure (AHF) carries has remained unchanged over the past several decades (1). European registries (2–5) showed that 1-year outcome rates remain unacceptably high (Table 1) and confirm that hospitalization for AHF represents a change in the natural history of the disease process(6). As patients hospitalized for HF have a bad prognosis, it is crucial to utilize hospitalization as an opportunity to: 1) assess the individual components of the cardiac substrate; 2) identify and treat comorbidities; 3) identify early, safe endpoints of therapy to facilitate timely hospital discharge and outpatient follow-up; and 4) implement and begin optimization guideline-directed medical therapies (GDMTs). As outcomes are influenced by many factors, many of which are incompletely understood, a systematic approach is proposed that should start with admission and continues through post-discharge (7)

Possible joint pathways of early pre-eclampsia and congenital heart defects via angiogenic imbalance and potential evidence for cardio-placental syndrome Downloaded from

This editorial refers to 'Maternal and foetal angiogenic imbalance in congenital heart defects' † , by E. Llurba et al., on page 701 Foetal vasculogenesis and angiogenesis and maternal angiogenesis are essential requirements for a pregnancy. Decidua-associated vascular changes arise in the inner junctional zone myometrium in early pregnancy, followed by trophoblast invasion with associated remodelling. 1 Decidual natural killer and dendritic cells regulate key developmental processes at the human foetal -maternal interface via human leucocyte antigen (HLA)-C, HLA-E, and HLA-G. 3 In the past decade, extensive research has investigated the abnormalities that can occur in the first trimester of pregnancy that could lead to chorionic regression or small placenta, contributing to intrauterine growth restriction and early-onset pre-eclampsia. 5 This excessive systemic inflammatory response results in endothelial dysfunction and an associated increase in vascular reactivity, preceding onset of the clinical condition pre-eclampsia, which affects 2-8 % of all pregnancies. Flt-1 is expressed on endothelial cells and macrophages, and binds to VEGF and a platelet-derived protein called placental growth factor (PlGF), with a wide range of functions which are not completely understood. 6 A potential endogenous opponent of PlGF in the plasma is soluble fms-like tyrosine kinase (sFlt-1), which represents a type of Flt-1, without the transmembrane and intracellular tyrosine kinase domain. sFlt-1 and PlGF have comprehensive involvement not only in the development of atherosclerotic processes and myocardial infarction, but also in a wider range of other inflammatory processes such as sepsis, acute lung injury, and neoplasm, as recently reviewed by Hochholzer et al. 6 However, most work on this interesting biomarker has been performed in pre-eclampsia. sFlt-1 can be measured in the placenta and serum of pregnant women. In normotensive pregnancy, the sFlt-1 levels are stable up to the middle stages of gestation, followed by a steady increase from 33 weeks onwards. This increase corresponds to a late-gestational decrease in free PlGF levels. It is postulated that this serves to slow placental vascular growth by increasing antiangiogenic factors such as sFlt-1, and decreasing levels of proangiogenic factors such as VEGF and PlGF