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Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway is disturbed in heart failure, leading to increased formation of reactive oxygen species and reduced NO bioavailability, and resultant myocardial dysfunction, adverse left ventricular remodeling, and cardiorenal syndrome. Restoration of sufficient NO-sGC–cGMP signaling has been proposed as an important treatment target in heart failure, beyond neurohormonal blockage and afterload reduction. Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO. VICTORIA was a Phase 3 trial that compared vericiguat, at a target dose of 10 mg, with placebo in 5050 patients with HFrEF (ejection fraction < 45%) on top of guideline-indicated therapy. The composite endpoint was the first occurrence of cardiovascular death or hospitalization for heart failure. The median follow up was 10.8 months. The included patients had to have had a heart failure-related hospitalization or need of IV diuretic therapy in the past 6 months, making it a particularly high risk and vulnerable patient population. The composite endpoint occurred less frequently with vericiguat than with placebo (35.5% vs 38.5%, p = 0.02). Adverse events were common in both groups, syncope was more common with vericiguat than with placebo (4% vs 3.5%, p = 0.03). Compared to the other recent large trials in HFrEF, PARADIGM-HF and DAPA-HF, patients in VICTORIA were older, more symptomatic (up to 40% NYHA IIIIV class), had higher N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels, and were more vulnerable since 84% had been hospitalized for heart failure in the previous 6 months. While drugs involving the neurohormonal pathways are effective in slowing down the progression of disease in more stable HFrEF, vericiguat may be a drug of choice particularly in the highest risk patients with recent or recurrent hospitalizations despite full background medication. The drug has also shown safety in patients with reduced renal function. This article discusses the place in therapy of vericiguat in patients with HFrEF, which is a heterogenous group in terms of etiology, clinical profiles, and comorbidities.

Biomarkers are useful for diagnosis, disease monitoring and risk stratification in cardiovascular disease. Cardiogenic shock (CS) is a medical emergency caused by a primary cardiac insult resulting in inadequate cardiac output, hypoperfusion and organ injury. The pathophysiology of CS is complex involving hemodynamic and circulatory disturbances, inflammation and organ dysfunction. CS is associated with high short-term mortality. Biomarkers such as lactate, cardiac troponins and markers of renal function are established in the diagnosis and monitoring of CS. Evaluation of organ injury and dysfunction is essential for the management. Biomarkers of inflammation and novel biomarkers such as growth differentiating factor-15 (GDF-15), sST2 and dipeptidyl dipeptidase 3 (DPP) may improve our understanding of pathophysiology and clinical course. The prognostic properties of these biomarkers aids in risk stratification and are incorporated as clinical tools for mortality risk prediction in CS. In this review, the role of biomarkers in CS will be discussed. Markers of organ injury and dysfunction, metabolism and novel biomarkers will be covered from a clinical perspective.

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis. Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCTmax >= and < 0.5 mu g/L, and IL-6 and CRPmax above/below median. Results: PCT peaked already at 24 h [median PCTmax 0.71 mu g/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRPmax 137mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCTmax >= 0.5 mu g/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRPmax. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCTmax >= 0.5 mu g/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRPmax showed no prognostic significance. The association of inflammatory markers with clinical infections was modest. Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis. (C) 2020 Elsevier B.V. All rights reserved.

Aseta käsikirjoitukselle embargo, kun julkaistu. Heart failure (HF) is one of the most life-threatening diseases globally. HF is an under-diagnosed condition, and more screening tools are needed to detect it. A few recent studies have suggested that HF also affects the functioning of the speech production mechanism by causing generation of edema in the vocal folds and by impairing the lung function. It has not yet been studied whether these possible effects of HF on the speech production mechanism are large enough to cause acoustically measurable differences to distinguish speech produced in HF from that produced by healthy speakers. Therefore, the goal of the present study was to compare speech production between HF patients and healthy controls by focusing on the excitation signal generated at the level of the vocal folds, the glottal flow. The glottal flow was computed from speech using the quasi-closed phase glottal inverse filtering method and the estimated flow was parameterised with 12 glottal parameters. The sound pressure level (SPL) was measured from speech as an additional parameter. The statistical analyses conducted on the parameters indicated that most of the glottal parameters and SPL were significantly different between the HF patients and healthy controls. The results showed that the HF patients generally produced a more rounded glottal pulse and a lower SPL level compared to the healthy controls, indicating incomplete glottal closure and inappropriate leakage of air through the glottis. The results observed in this preliminary study indicate that glottal features are capable of distinguishing speakers with HF from healthy controls. Therefore, the study suggests that glottal features constitute a potential feature extraction approach which should be taken into account in future large-scale investigations in studying the automatic detection of HF from speech.

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., The "Heart failure specialists of Tomorrow" (HoT) group gathers young researchers, physicians, basic scientists, nurses and many other professions under the auspices of the Heart Failure Association of the European Society of Cardiology. After its foundation in 2014, it has quickly grown to a large group of currently 925 members. Membership in this growing community offers many advantages during, before, and after the 'Heart Failure and World Congress on Acute Heart Failure'. These include: eligibility to receive travel grants, participation in moderated poster sessions and young researcher and clinical case sessions, the HoT walk, the career café, access to the networking opportunities, and interaction with a large and cohesive international community that constantly seeks multinational collaborations.

Heart failure (HF) is a major global health concern and is increasing in prevalence. It affects the larynx and breathing - thereby the quality of speech. In this article, we propose an approach for the automatic detection of people with HF using the speech signal. The proposed method explores mel-frequency cepstral coefficient (MFCC) features, glottal features, and their combination to distinguish HF from healthy speech. The glottal features were extracted from the voice source signal estimated using glottal inverse filtering. Four machine learning algorithms, namely, support vector machine, Extra Tree, AdaBoost, and feed-forward neural network (FFNN), were trained separately for individual features and their combination. It was observed that the MFCC features yielded higher classification accuracies compared to glottal features. Furthermore, the complementary nature of glottal features was investigated by combining these features with the MFCC features. Our results show that the FFNN classifier trained using a reduced set of glottal + MFCC features achieved the best overall performance in both speaker-dependent and speaker-independent scenarios. (C) 2021 The Author(s). Published by Elsevier Ltd.

Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway is disturbed in heart failure, leading to increased formation of reactive oxygen species and reduced NO bioavailability, and resultant myocardial dysfunction, adverse left ventricular remodeling, and cardiorenal syndrome. Restoration of sufficient NO-sGC-cGMP signaling has been proposed as an important treatment target in heart failure, beyond neurohormonal blockage and afterload reduction. Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO. VICTORIA was a Phase 3 trial that compared vericiguat, at a target dose of 10 mg, with placebo in 5050 patients with HFrEF (ejection fraction45%) on top of guideline-indicated therapy. The composite endpoint was the first occurrence of cardiovascular death or hospitalization for heart failure. The median follow up was 10.8 months. The included patients had to have had a heart failure-related hospitalization or need of IV diuretic therapy in the past 6 months, making it a particularly high risk and vulnerable patient population. The composite endpoint occurred less frequently with vericiguat than with placebo (35.5% vs 38.5%, p = 0.02). Adverse events were common in both groups, syncope was more common with vericiguat than with placebo (4% vs 3.5%, p = 0.03). Compared to the other recent large trials in HFrEF, PARADIGM-HF and DAPA-HF, patients in VICTORIA were older, more symptomatic (up to 40% NYHA IIIIV class), had higher N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels, and were more vulnerable since 84% had been hospitalized for heart failure in the previous 6 months. While drugs involving the neurohormonal pathways are effective in slowing down the progression of disease in more stable HFrEF, vericiguat may be a drug of choice particularly in the highest risk patients with recent or recurrent hospitalizations despite full background medication. The drug has also shown safety in patients with reduced renal function. This article discusses the place in therapy of vericiguat in patients with HFrEF, which is a heterogenous group in terms of etiology, clinical profiles, and comorbidities.

Nitric oxide (NO)-soluble guanylate cyclase(sGC)-cGMP signalling is impaired in HF syndromes, which could predispose to vascular oxidative stress. Nitrates directly stimulate cGMP, but are limited by tolerance. Therapeutic targets that aim at increasing cGMP concentrations have therefore been explored. Recently, two classes of drugs have been discovered, the sGC activators and the sGC stimulators, which target two different redox states of sGC: the NO-sensitive reduced (ferrous) sGC and NO-insensitive oxidized (ferric) sGC, respectively. Cinaciguat is an activator and riociguat and vericiguat are sGC stimulators. Vericiguat is the most advanced agent in its clinical trial programme with two completed phase IIb studies, SOCRATES -REDUCED in HFrEF and SOCRATES-PRESERVED in HFpEF, with mixed results on NT-proBNP. The ongoing VICTORIA trial in HFrEF will study 4,872 participants with a mortality/morbidity end-point and VITALITY HFpEF trial will study 735 participants, with a quality of life end-point.

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p &lt, 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018, adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.

Aims To investigate the incidence, haemodynamic alterations and 90-day mortality of acute kidney injury (AKI) in patients with cardiogenic shock. We assessed the utility of creatinine, urine output (UO) and cystatin C (CysC) definitions of AKI in prognostication. Methods and results Cardiogenic shock patients with serial plasma samples (n = 154) from the prospective multicenter CardShock study were included in the analysis. Acute kidney injury was defined and staged according to the KDIGO criteria by creatinine (AKI(crea)) and/or UO (AKI(UO)). CysC-based AKI (AKI(CysC)) was defined similarly to AKI(crea). Changes in haemodynamic parameters were assessed over time from baseline until 96 h. Mean age of the study population was 66 +/- 12 years and 74% were men. Median baseline creatinine was 1.12 [interquartile range (IQR) 0.87-1.54] mg/dL and CysC 1.19 (IQR 0.90-1.69) mg/L. The 90-day mortality was 38%. The incidences for AKI were: AKI(crea) 31%, AKI(UO) 50%, and AKI(Cysc) 33%. AKI(crea) [odds ratio (OR) 12.2, 95% confidence interval (CI) 4.1-36.0] and AKI(CysC) (OR 2.5, 95% CI 1.1-6.1), but not AKI(UO), were independent predictors of mortality. However, a stricter UO cut-off of < 0.3 mL/kg/h for 6 h was independently associated with 90-day mortality (OR 3.6, 95% CI 1.4-9.3). Development of AKI was associated with persistently elevated central venous pressure and decreased cardiac index and mean arterial pressure. Conclusions Acute kidney injury is frequent in patients with cardiogenic shock and especially AKI(crea) predicts poor outcome. The KDIGO UO criterion seems, however, rather liberal and a stricter AKI definition of UO

BACKGROUND Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF. METHODS In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years. RESULTS The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years. CONCLUSIONS Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.

Background: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC). Methods: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes. Results: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices ( P < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], P = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score. Conclusions: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.

Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS). Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-15(0h) level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P=.002). Adding GDF-15(12h) >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality. Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS.

Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery. Some of these changes influence normal biochemical values while others may mimic symptoms of medical disease. It is important to differentiate between normal physiological changes and disease pathology. This review highlights the important changes that take place during normal pregnancy.

WOS: 000374984300007, PubMed ID: 27812386, AimsAcute heart failure (AHF) is one of the leading causes of unscheduled hospitalization and is associated with frequent readmissions and substantial mortality. Precipitating factors of AHF influence short-term mortality, but their effect on outcome after hospital discharge is unknown. The present study assessed the effect of precipitating factors on readmission and long-term survival in the overall population and in patients aged 75years or younger. Methods and resultsPatients admitted with AHF (n=755) included in the multicentre cohort Biomarcoeurs' were included in the study. Precipitating factors of AHF were classified in four main groups: acute coronary syndrome, atrial fibrillation, acute pulmonary disease and other causes. Hospital readmission during 90days after discharge and survival at 1year were analysed. Precipitating factors influenced readmissions and survival. Acute pulmonary disease was associated with fewer readmissions (HR 0.61, 95% confidence interval (CI) 0.37-0.99, P=0.049), especially in patients aged 75years or younger (HR 0.20, 95% CI 0.06-0.63, P=0.006), whereas atrial fibrillation (HR 2.23, 95% CI 1.29-3.85, P=0.004) and acute coronary syndrome (HR 2.23, 95% CI 1.02-4.86, P=0.044) were associated with more readmissions. Patients with acute pulmonary disease at admission showed higher mortality (HR 1.59, 95% CI 1.04-2.43, P=0.034), especially in subjects aged 75years or younger (HR 2.52, 95% CI 1.17-5.41, P=0.018). ConclusionsPrecipitating factors of AHF substantially influenced outcome after hospitalization. In particular, patients with AHF precipitated by acute pulmonary disease showed fewer readmissions and higher 1year mortality, especially in patients aged 75years or younger.

Changes in QRS duration and pattern are regarded to reflect severe ischemia in acute coronary syndromes (ACS), and ventricular conduction blocks (VCBs) are recognized high-risk markers in both ACS and acute heart failure. Our aim was to evaluate the prevalence, temporal evolution, association with clinical and angiographic parameters, and impact on mortality of VCBs in ACS-related cardiogenic shock (CS). Data of 199 patients with ACS-related CS from a prospective multinational cohort were evaluated with electrocardiogram data from baseline and day 3. VCBs including left or right bundle branch block, right bundle branch block and hemiblock, isolated hemiblocks, and unspecified intraventricular conduction delay were assessed. Fifty percent of patients had a VCB at baseline; these patients were older, had poorer left ventricular function and had more often left main disease compared with those without VCB. One-year mortality was over 2-fold in patients with VCB compared with those without VCB (68% vs 32%, p

BackgroundThe most common aetiology of cardiogenic shock (CS) is acute coronary syndrome (ACS), but even up to 20%-50% of CS is caused by other disorders. ST-segment deviations in the electrocardiogram (ECG) have been investigated in patients with ACS-related CS, but not in those with other CS aetiologies. We set out to explore the prevalence of different ST-segment patterns and their associations with the CS aetiology, clinical findings and 90-day mortality. MethodsWe analysed the baseline ECG of 196 patients who were included in a multinational prospective study of CS. The patients were divided into 3 groups: (a) ST-segment elevation (STE). (b) ST-segment depression (STDEP). (c) No ST-segment deviation or ST-segment impossible to analyse (NSTD). A subgroup analysis of the ACS patients was conducted. ResultsST-segment deviations were present in 80% of the patients: 52% had STE and 29% had STDEP. STE was associated with the ACS aetiology, but one-fourth of the STDEP patients had aetiology other than ACS. The overall 90-day mortality was 41%: in STE 47%, STDEP 36% and NSTD 33%. In the multivariate mortality analysis, only STE predicted mortality (HR 1.74, CI95 1.07-2.84). In the ACS subgroup, the patients were equally effectively revascularized, and no differences in the survival were noted between the study groups. ConclusionST-segment elevation is associated with the ACS aetiology and high mortality in the unselected CS population. If STE is not present, other aetiologies must be considered. When effectively revascularized, the prognosis is similar regardless of the ST-segment pattern in ACS-related CS.

Aims Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long‐term survival in patients with de novo AHF and acutely decompensated chronic heart failure (ADCHF). Methods and Results We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow‐up. Half (51.5%, n = 506) of the patients had de novo AHF. LBBB, and IVCD were more common in ADCHF than in de novo AHF: 17.2% vs. 8.7% (P

AimsThe aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. Methods and resultsThe CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85). ConclusionAlthough most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials.

Objectives: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock. Design: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality. Setting: Nine tertiary care university hospitals. Patients: Patients with cardiogenic shock caused by acute coronary syndrome (n=145). Interventions: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement. Measurements and Main Results: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, >= 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, >= 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients. Conclusions: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

Background The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5–10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score (P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS., published version, peerReviewed

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over noninvasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. Methods: 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24 h into MV (n= 137; 63%), NIV(n= 26; 12%), and supplementary oxygen (n= 56; 26%) groups. We compared the clinical characteristics and 90-day outcome between the MV and the NIV groups. Results: Mean age was 67 years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO2/FiO(2) ratio, baseline hemodynamics or LVEF. MV patients predominantly presented with hypoperfusion, with more severe metabolic acidosis, higher lactate levels and greater need for vasoactive drugs, whereas NIV patients tended to be more often congestive. 90-day outcome was significantly worse in the MV group (50% vs. 27%), but after propensity score adjustment, mortality was equal in both groups. Confusion, prior CABG, ACS etiology, higher lactate level, and lower baseline PaO2 were independent predictors of mortality, where as ventilation strategy did not have any influence on outcome. Conclusions: Although MV is generally recommended mode of ventilatory support in CS, a fair number of patients were successfully treated with NIV. Moreover, ventilation strategy was not associated with outcome. Thus, NIV seems a safe option for properly chosen CS patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS.Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P.001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P.01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P.001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03).Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality.

Aims: Cardiac resynchronization therapy (CRT) induces reverse cardiac remodelling in heart failure (HF), but many patients receiving CRT remain non-responders. This study assessed the role of amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide (MR-proANP), and mid-regional-pro-adrenomedullin (MR-proADM) at the time of device implantation to predict favourable clinical course (CRT response and/or risk of MACE) in HF patients receiving CRT. Methods and results: A total of 137 HF patients were prospectively included. Blood was drawn from the coronary sinus (CS) at CRT implantation, and from a peripheral vein (PV) simultaneously and after 6 months. Clinical CRT response at 6 months and major adverse cardiovascular events (MACE) at 2 years were assessed. Baseline PV-levels of MR-proANP (202 vs. 318 pmol/L, P = 0.009) and MR-proADM (843 vs. 1112 pmol/L, P = 0.02) were lower in CRT responders compared with non-responders. At 6 months, CRT responders showed a decrease in MR-proANP levels, compared with an increase in non-responders (-32 vs. +7 pmol/L, P = 0.02). During the same period, NT-proBNP decreased by a similar way in responders and non-responders, while MR-proADM was unchanged in both groups. High baseline MR-proANP, either in PV (OR 0.41, 95% CI 0.24-0.71, P = 0.002) or CS (OR 0.32, 95% CI 0.15-0.70, P = 0.005) was associated with reduced likelihood of CRT response. Furthermore, PV and CS levels of NT-proBNP, MR-proANP, and MR-proADM were all associated with increased risk of 2-year MACE (all P < 0.01). Conclusion: Mid-regional-pro-atrial natriuretic peptide may assist prediction of clinical course in HF patients undergoing CRT implantation. Low circulating MR-proANP at the time of device implantation is associated with CRT response and more favourable outcome.

Acute heart failure (AHF) is the most common cause of unplanned hospital admissions, and is associated with high mortality rates. Over the next few decades, the combination of improved cardiovascular disease survival and progressive ageing of the population will further increase the prevalence of AHF in developed countries. New recommendations on the management of AHF have been published recently, but as elderly patients are under-represented in clinical trials, and scientific evidence is often lacking, the diagnosis and management of AHF in this population is challenging. The clinical presentation of AHF, especially in patients aged>85years, differs substantially from that in younger patients, with unspecific symptoms, such as fatigue and confusion, often overriding dyspnoea. Older patients also have a different risk profile compared with younger patients: often heart failure with preserved ejection fraction, and infection as the most frequent precipitating factor of AHF. Moreover, co-morbidities, disability and frailty are common, and increase morbidity, recovery time, readmission rates and mortality; their presence should be detected during a geriatric assessment. Diagnostics and treatment for AHF should be tailored according to cardiopulmonary and geriatric status, giving special attention to the patient's preferences for care. Whereas many elderly AHF patients may be managed similarly to younger patients, different strategies should be applied in the presence of relevant co-morbidities, disability and frailty. The option of palliative care should be considered at an early stage, to avoid unnecessary and harmful diagnostics and treatments.

WOS: 000368722000002, PubMed ID: 26370690, Purpose: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. Results: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. Conclusion: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF., Research Council of Lithuania [MIP-049/2015], The work of G. Baksyte was supported by the grant MIP-049/2015 from the Research Council of Lithuania.

Introduction: CD146 is a component of the endothelial junction. We previously showed that its soluble form (sCD146) is as powerful as plasma natriuretic peptides to detect cardiac origin of acute dyspnea. The source of plasma sCD146 in heart failure (HF) is however unknown. Hypothesis: We make the hypothesis that peripheral venous congestion (VC), a typical sign of global ventricular failure, might be the source of increased sCD146. Methods: A total of 44 outpatients with heart failure, NYHA functional class II or III, and LVEF Results: The age of the study cohort was 54±2 years, 32% were female, 32% had an ischemic etiology and the LVEF was 22±1%. The induction of VC was associated with an increase in circulating levels of sCD146 in the congested arm when compared to baseline (506±33 vs 463±33 ng/ml, p=0.001) and to control arm (476±32 ng/ml, p=0.035). In contrast, no significant increase occurred in the control arm when compared to baseline values (Figure). Conclusions: Plasma sCD146 acutely increases in response to experimental peripheral VC. sCD146 could be particularly useful to titrate diuretic treatment in HF patients with global heart failure, possibly preventing end-organ dysfunction and damage from severe and/or long-standing peripheral VC.

The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality.The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate2 mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85).Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials.NCT01374867.

The short-term mortality in cardiogenic shock (CS) is high, and risk stratification is needed for rational use of advanced therapies. The aim was to evaluate the prognostic value of bioactive adrenomedullin (bio-ADM) and lactate in CS. CardShock was a prospective, observational, European

The short-term mortality in cardiogenic shock (CS) complicating acute coronary syndromes (ACS) is high, and risk stratification is needed for rational use of advanced therapies. The aim of this study was to evaluate the added value of NT-proBNP and ST2 to clinical variables for risk stratification

Supplemental Digital Content is available in the text, Red blood cell distribution width (RDW) may serve as an integrative marker of pathological processes that portend worse prognosis in heart failure (HF). The prognostic value of RDW variation (ΔRDW) during hospitalization for acute heart failure (AHF) has yet to be studied. We retrospectively analyzed 2 independent cohorts: Centro Hospitalar do Porto (derivation cohort) and Lariboisière hospital (validation cohort). In the derivation cohort a total of 170 patients (age 76.2 ± 10.3 years) were included and in the validation cohort 332 patients were included (age 76.4 ± 12.2 years). In the derivation cohort the primary composite outcome of HF admission and/or cardiovascular death occurred in 78 (45.9%) patients during the 180-day follow-up period. Discharge RDW and ΔRDW were both increased when hemoglobin levels were lower; peripheral edema was also associated with increased discharge RDW (all P 15% at discharge was associated with a 2-fold increase in event rate, HR = 1.95 (1.05–3.62), P = 0.04, while a ΔRDW >0 also had a strong association with outcome, HR = 2.47 (1.35–4.51), P = 0.003. The addition of both discharge RDW > 15% and ΔRDW > 0 to hemoconcentration was associated with a significant improvement in the net reclassification index, NRI = 18.3 (4.3–43.7), P = 0.012. Overlapping results were found in the validation cohort. As validated in 2 independent AHF cohorts, an in-hospital RDW enlargement and an elevated RDW at discharge are associated with increased rates of mid-term events. RDW variables improve the risk stratification of these patients on top of well-established prognostic markers.

Aims Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. [GRAPHICS] .