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Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients., Methods: STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes., Results: Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003)., Conclusions: Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Rationale: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock. Objectives: To assess the correlation of capillary refill time values with 90-day mortality in cardiogenic shock patients or the need for venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Also to assess the correlation between capillary refill time and hemodynamic parameters. Methods: All consecutive patients with cardiogenic shock admitted to the intensive care unit of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction, and cardiac index) and peripheral tissue perfusion signs, such as capillary refill time on the index fingertip, mottling, and Pv-aCO 2 (the difference between partial pressure of CO 2 between venous and arterial blood) were recorded at inclusion (0 hour), 6 hours, 12 hours, 24 hours, and 48 hours. The composite primary endpoint was the association between 90-day mortality or the need for VA-ECMO support. Measurements and Main Results: A total of 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time points in nonsurvivors or patients needing VA-ECMO support. In univariate analysis, capillary refill time > 3 seconds at inclusion was associated with 90-day all-cause mortality or VA-ECMO support (hazard ratio, 12.38; 95% confidence interval, 2.91-52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93. Conclusions: In patients with cardiogenic shock admitted to the ICU, our preliminary data suggest that a prolonged capillary refill time >3 seconds was associated with an early prediction of 90-day mortality or the need for VA-ECMO support.

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., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

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.

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 < 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.

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., (© 2020 European Society of Cardiology.)

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

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%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-15 12h cutoff >7000 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS., Methods and Results: Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins-CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA)., Conclusion: A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction: The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown., Materials and Methods: P-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality., Results: Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5-4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1-3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2-5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2-7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome., Conclusions: Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock., Trial Registration: NCT01374867 at ClinicalTrials.gov., Competing Interests: VPH: Advisory board fees from Roche Diagnostics, research grant from Abbott, speaker fees from Orion, all outside the present work. KP: Advisory board fees from Roche Diagnostics (Finland). AM: lecture fees from Novartis, Orion, and Abbott, research grants from Roche, and consultant fees from Servier and Sanofi, all outside the present work. JL: Speakers bureau and consultancy fees: AstraZeneca, Bayer, Boehringer-Ingelheim, Novartis, OrionPharma, Pfizer, Roche Diagnostics, and ViforPharma, all outside the present work. All other authors report that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR-423-5p level to predict mortality and associations of miR-423-5p with prognostic markers in cardiogenic shock., Methods and Results: We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR-423-5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all-cause mortality. Median miR-423-5p level was significantly higher in 90 day non-survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003-0.017) vs. 0.004 AU (0.002-0.009), P = 0.003]. miR-423-5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P < 0.001) as well as lower cardiac index (1.8 vs. 2.4, P = 0.04) and estimated glomerular filtration rate (56 vs. 70 mL/min/1.73 m 2 , P = 0.002). In Cox regression analysis, miR-423-5p level above median was associated with 90 day all-cause mortality independently of established risk factors of cardiogenic shock [adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), P = 0.01]., Conclusions: In cardiogenic shock patients, above median level of miR-423-5p at baseline is associated with markers of hypoperfusion and seems to independently predict 90 day all-cause mortality., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objectives: The aim was to assess the extent of coronary artery disease and revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was evaluated and assessed for additive value over clinical risk scores., Background: bSS and rSS have been proven to be useful in risk stratification in stable coronary artery disease as well as in acute coronary syndromes, but they have not been studied in STEMI related CS., Methods: Patients from a multinational prospective study of CS were analyzed. The study population was divided into tertiles according to bSS. The Cox regression and receiver operating characteristic (ROC) curves were used to assess the predictive power of SS., Results: Of the 61 studied patients, 85% were male and the mean age was 67 years. Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10). However, additive value over clinical risk scores was limited. rSS was not associated with mortality, whereas post-percutaneous coronary intervention (PCI) TIMI flow 3 of infarct-related artery (IRA) predicted better survival., Conclusions: In STEMI related CS, the added value of bSS and rSS over clinical assessment and risk scores is limited. Our results suggest that while immediate PCI in order to restore blood flow to the IRA is essential, deferring the treatment of residual lesions does not seem to be associated with worse prognosis., (© 2018 Wiley Periodicals, Inc.)

Background: The 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., Methods: We 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., Results: ST-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, CI 95 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., Conclusion: ST-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., (© 2018 Wiley Periodicals, Inc.)

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<0.001). All types of VCBs at baseline were associated with increased mortality, and the predictive value of a VCB was independent of baseline variables and coronary angiography findings. Interestingly, 37% of the VCBs were transient, i.e., disappeared before day 3. However, 1-year mortality was much higher in these patients (69%) compared to patients with persistent (38%) or no VCB (15%, p<0.001). Indeed, a transient VCB was a strong independent predictor of 1-year mortality. In conclusion, our findings propose that any VCB in baseline electrocardiogram, even if transient, identifies very early patients at particularly high mortality risk in ACS-related CS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Vasopressor agents could have certain specific effects in patients with cardiogenic shock (CS) after myocardial infarction, which may influence outcome. Although norepinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and intervention data are lacking., Objectives: The goal of this paper was to compare in a prospective, double-blind, multicenter, randomized study, the efficacy and safety of epinephrine and norepinephrine in patients with CS after acute myocardial infarction., Methods: The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyperlactatemia, and high inotrope and vasopressor doses., Results: Fifty-seven patients were randomized into 2 study arms, epinephrine and norepinephrine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epinephrine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remaining unchanged with norepinephrine (p < 0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double product (p = 0.0002) and lactic acidosis from H2 to H24 (p < 0.0001)., Conclusions: In patients with CS secondary to acute myocardial infarction, the use of epinephrine compared with norepinephrine was associated with similar effects on arterial pressure and cardiac index and a higher incidence of refractory shock. (Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock [OptimaCC]; NCT01367743)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Up to 10% of acute coronary syndromes are complicated by cardiogenic shock (CS) with contemporary mortality rates of 40-50%. The extent of ischemic myocardium has a profound impact on the initial, in-hospital, and post-discharge management and prognosis in this patient population. Individualized patient risk assessment plays an important role in determining appropriate revascularization, drug treatment with inotropes and vasopressors, mechanical circulatory support, intensive care support of other organ systems, hospital level of care triage, and allocation of clinical resources. This review will outline the underlying causes and diagnostic criteria, pathophysiology, and treatment of CS complicating acute coronary syndromes with a focus on (a) potential therapeutic issues from the perspective an interventional cardiologist, an emergency physician, and an intensive care physician, (b) the type of revascularization, and (c) new therapeutic advancements in pharmacologic and mechanical percutaneous circulatory support.

Objective: Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients., Design: We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality., Measurements and Results: Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0])., Conclusions: In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.

Background: Altered mental status is among the signs of hypoperfusion in cardiogenic shock, the most severe form of acute heart failure. The aim of this study was to investigate the prevalence of altered mental status, to identify factors associating with it, and to assess the prognostic significance of altered mental status in cardiogenic shock., Methods: Mental status was assessed at presentation of shock in 215 adult cardiogenic shock patients in a multinational, prospective, observational study. Clinical picture, biochemical variables, and short-term mortality were compared between patients presenting with altered and normal mental status., Results: Altered mental status was detected in 147 (68%) patients, whereas 68 (32%) patients had normal mental status. Patients with altered mental status were older (68 vs. 64 years, p=0.04) and more likely to have an acute coronary syndrome than those with normal mental status (85% vs. 74%, p=0.04). Altered mental status was associated with lower systolic blood pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, p<0.001) as well as higher levels of blood lactate (3.4 vs. 2.3 mmol/l, p<0.001) and blood glucose (11.4 vs. 9.0 mmol/l, p=0.01). Low arterial pH (adjusted odds ratio 1.6 (1.1-2.2), p=0.02) was the only factor independently associated with altered mental status. Ninety-day mortality was significantly higher (51% vs. 22%, p<0.001) among patients with altered mental status., Conclusions: Altered mental status is a common clinical sign of systemic hypoperfusion in cardiogenic shock and is associated with poor outcome. It is also associated with several biochemical findings that reflect inadequate tissue perfusion, of which low arterial pH is independently associated with altered mental status.

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (ΔALT>+20%) was observed in 24% of patients. ΔALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p <0.001). Multivariable regression analysis showed that ΔALT>+20% was associated with increased 90-day mortality independent of other known risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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: Mortality in cardiogenic shock (CS) remains high. Early risk stratification is crucial to make adequate treatment decisions., Objectives: This study sought to develop an easy-to-use, readily available risk prediction score for short-term mortality in patients with CS, derived from the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock) trial., Methods: The score was developed using a stepwise multivariable regression analysis., Results: Six variables emerged as independent predictors for 30-day mortality and were used as score parameters: age >73 years, prior stroke, glucose at admission >10.6 mmol/l (191 mg/dl), creatinine at admission >132.6 μmol/l (1.5 mg/dl), Thrombolysis In Myocardial Infarction flow grade <3 after percutaneous coronary intervention, and arterial blood lactate at admission >5 mmol/l. Either 1 or 2 points were attributed to each variable, leading to a score in 3 risk categories: low (0 to 2), intermediate (3 or 4), and high (5 to 9). The observed 30-day mortality rates were 23.8%, 49.2%, and 76.6%, respectively (p < 0.0001). Validation in the IABP-SHOCK II registry population showed good discrimination with an area under the curve of 0.79. External validation in the CardShock trial population (n = 137) showed short-term mortality rates of 28.0% (score 0 to 2), 42.9% (score 3 to 4), and 77.3% (score 5 to 9; p < 0.001) and an area under the curve of 0.73. Kaplan-Meier analysis revealed a stepwise increase in mortality between the different score categories (0 to 2 vs. 3 to 4: p = 0.04; 0 to 2 vs. 5 to 9: p = 0.008)., Conclusions: The IABP-SHOCK II risk score can be easily calculated in daily clinical practice and strongly correlated with mortality in patients with infarct-related CS. It may help stratify patient risk for short-term mortality and might, thus, facilitate clinical decision making. (Intraaortic Balloon Pump in Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over non-invasive 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 24h 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 67years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO 2 /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 PaO 2 were independent predictors of mortality, whereas 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS)., Methods: Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose <4.0mmol/L), normoglycemia (4.0-7.9mmol/L), mild (8.0-11.9mmol/L), moderate (12.0-15.9mmol/L), and severe (≥16.0mmol/L) hyperglycemia. Clinical presentation, biochemistry, and short-term mortality were compared between the groups., Results: Plasma glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (p<0.001 for all). In-hospital mortality was highest among hypoglycemic (60%) and severely hyperglycemic (56%) patients, compared with 22% in normoglycemic group (p<0.01). Severe hyperglycemia was an independent predictor of in-hospital mortality (OR 3.7, 95% CI 1.19-11.7, p=0.02), when adjusted for age, gender, LVEF, lactate, and DM., Conclusions: Admission blood glucose level has prognostic significance in CS. Mortality is highest among patients with severe hyperglycemia or hypoglycemia. Severe hyperglycemia is independently associated with high in-hospital mortality in CS. It is also associated with biomarkers of systemic hypoperfusion and stress response., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS., Methods: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling., Results: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan., Conclusion: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

Aims: 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., Methods and Results: 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 lactate >2 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)., Conclusion: 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., Trial Registration: NCT01374867., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)