Search

Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months.A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events.Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Aims Cardiogenic shock (CS) is known to induce an inflammatory response. The prognostic utility of this remains unclear. To investigate the association between C-reactive protein (CRP) levels and leucocyte count and mortality in patients with acute myocardial infarction complicated by CS (AMICS). Methods and results Consecutive patients (N = 1716) admitted between 2010 and 2017 with an individually validated diagnosis of AMICS were included. The analysis was restricted to patients alive at 48 h after first medical contact and a valid CRP and leucocyte measurement at 48 ± 12 h from the first medical contact. A combined inflammatory score for each patient was computed by summing the CRP and leucocyte count z-scores to normalize the response on a standard deviation scale. Associations with mortality were analysed using a multivariable Cox proportional hazards model stratified by inflammatory response quartiles: Of the 1716 patients in the cohort, 1111 (64.7%) fulfilled inclusion criteria. The median CRP level at 48 h was 145 mg/dL [interquartile range (IQR) 96–211]. The median leucocyte count was 12.6 × 10−9/L (IQR 10.1–16.4). Patients with the highest inflammatory response (Q4) had lower median left ventricular ejection fractions and higher lactate levels at the time of diagnosis. The 30-day all-cause mortality rates were 46% in Q4 and 21% in Q1 (P < 0.001). In multivariable models, the inflammatory response remained associated with mortality [hazard ratio (HR)Q4 2.32, 95% confidence interval (CI) 1.59–3.39, P < 0.001]. The finding was also significant in AMICS patients presenting with out-of-hospital cardiac arrest following multivariable adjustment (HRQ4 3.37, 95% CI 2.02–4.64, P < 0.001). Conclusion Cardiogenic shock induces an acute inflammatory response, the severity of which is associated with mortality.

BACKGROUND The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODS In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days. RESULTS A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberaltarget group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberaltarget group. The incidence of adverse events was similar in the two groups. CONCLUSIONS Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma.

Aim: To investigate how the inflammatory response after out-of-hospital cardiac arrest (OHCA) is modulated by blocking IL-6-mediated signalling with tocilizumab, and to relate induced changes to clinical status, myocardial- and brain injury. Methods: This is a preplanned substudy of the IMICA trial (ClinicalTrials.gov, NCT03863015). Upon admission 80 comatose OHCA patients were randomized to infusion of tocilizumab or placebo. Inflammation was characterized by a cytokine assay, CRP, and leukocyte differential count; myocardial injury by TnT and NT-proBNP; brain injury by neuron-specific enolase (NSE) and Neurofilament Light chain (NFL), while sequential organ assessment (SOFA) score and Vasoactive-Inotropic Score (VIS) represented overall clinical status. Results: Responses for IL-5, IL-6, IL-17, neutrophil as well as monocyte counts, and VIS were affected by tocilizumab treatment (all p < 0.05), while there was no effect on levels of NFL. IL-5 and IL-6 were substantially increased by tocilizumab, while IL-17 was lowered. Neutrophils and monocytes were lower at 24 and 48 hours, and VIS was lower at 24 hours, for the tocilizumab group compared to placebo. Multiple correlations were identified for markers of organ injury and clinical status versus inflammatory markers; this included correlations of neutrophils and monocytes with TnT, NSE, NFL, SOFA- and VIS score for the tocilizumab but not the placebo group. NT-proBNP, NFL and SOFA score correlated with CRP in both groups. Conclusions: Treatment with tocilizumab after OHCA modulated the inflammatory response with notable increases for IL-5, IL-6, and decreases for neutrophils and monocytes, as well as reduced vasopressor and inotropy requirements.

Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited.In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months.A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups.Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P

Aims: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. Methods and Results: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI 2 (n = 453), overweight BMI 25–29.9 kg/m2 (n = 391), obese class 1 BMI 30–34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). Conclusions: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an “obesity paradox” was not observed in this contemporary cohort of patients with AMICS in Denmark.

Purpose: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal–(Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI). Methods: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0–2; 3/4; 5–9), and had blood sampled upon admission. Results: Plasma concentrations of Copeptin (median (pmol/L) score 0–2: 313; score 3/4: 682; score 5–9: 632 p < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0–2: 22%; score 4/3: 51%; score 5–9: 72%, area under the curve (AUC): 0.73, plogrank < 0.0001), while the tested biomarkers did not (AUC: 0.51

Background As existing results are diverging, and the patient population has changed significantly, this study sought to investigate the prognostic importance of the culprit lesion location in patients with cardiogenic shock due to myocardial infarction (AMICS), in a contemporary and unselected patient population. Methods From the recruitment area of two tertiary heart centres in Denmark, covering 3.9 million citizens corresponding to two-thirds of the Danish population, all AMICS patients in the period of 2010–2017 were individually identified and validated through patient records. Results A total of 1716 patients with AMICS were identified. Immediate revascularization was performed in 1482 patients (86%). Among these, a culprit lesion in the left main coronary artery (LM) was associated with the highest 30-day mortality rate (66%), plogrank Conclusions Among AMICS patients undergoing revascularization, a LM culprit lesion was associated with the highest short-term mortality, whereas patients with a culprit lesion in the remaining coronary arteries had comparable and lower mortality rates. Multivessel disease patients had similar prognoses irrespective of percutaneous coronary intervention approach and whether partial or complete revascularization was achieved.

Acute myocardial infarction complicated by cardiogenic shock (AMICS) comprises a heterogeneous population with high mortality. Insight in timing and cause of death may improve understanding of the condition and aid individualization of treatment. This was assessed in a retrospective, multicenter observational cohort study based on 1,716 patients with AMICS treated during the period of 2010 to 2017, of whom 904 died before hospital discharge. Patients with AMICS were identified through national registries and review of individual patients charts. In 904 patients with AMICS who died before hospital discharge (median age 72 years [interquartile range (IQR) 63 to 79], 70% men), 342 (38%) had suffered out-of-hospital cardiac arrest. The most frequent cause of death was primary cardiac (54%), whereas 24% died of neurologic injury, and 20% of multiorgan failure (MOF). Time to death was 13 hours (IQR 5 to 43) for heart failure; 140 hours (IQR 95 to 209) in neurologic injury; and 137 hours (IQR 59 to 321) in MOF, p

Contemporary management of cardiogenic shock (CS) with vasopressors is associated with increased cardiac workload and despite the use of unloading devices such as the Impella pump, concomitant vasopressors are often necessary. Therefore, we compared if cardiac workload could be reduced and end-organ perfusion preserved with biventricular support (Bipella) compared to ImpellaCP and norepinephrine in pigs with left ventricular (LV) CS caused by left main coronary microembolization. Cardiac workload was calculated from heart rate × ventricular pressure-volume area obtained from conductance catheters placed in the LV and right ventricle (RV), whereas organ perfusion was measured from venous oxygen saturation in the pulmonary artery (SvO2) and the kidney- and the cerebral vein. A cross-over design was used to access the difference after 30 minutes of ImpellaCP and norepinephrine 0.1 µg/kg/min versus Bipella for 60 minutes. Bipella treatment reduced LV workload (p = 0.0078) without significant difference in RV workload from ImpellaCP and norepinephrine, however a decrease in SvO2 (49[44-58] vs. 66[63-73]%, p = 0.01) and cerebral venous oxygen saturations (62[48-66] vs. 71[63-77]%, p = 0.016) was observed during Bipella compared to ImpellaCP and norepinephrine. We conclude that Bipella reduced LV workload but did not preserve end-organ perfusion compared to ImpellaCP and norepinephrine in short-term LV CS.

The aim was to translationally compare a pharmacologic strategy versus treatment with the Impella RP in profound RV cardiogenic shock (CS). The pigs were allocated to either vasoactive therapy with norepinephrine (0.10 μg/kg/min) for the first 30 min, supplemented by an infusion of milrinone (0.4 μg/kg/min) for additional 150 min, or treatment with the Impella RP device for 180 min. Total RV workload (Pressure-volume-area × heart rate*103(mmHg/min)) remained unaffected upon treatment with the Impella RP and increased in the vasoactive group (CS 179[147;228] to norepinephrine 268[247;306](p = 0.002 compared to Impella RP) and norepinephrine + milrinone 366[329;422] (p = 0.002 compared to Impella RP). A trend towards higher venous cerebral oxygen saturation was observed with norepinephrine than Impella RP (Impella RP 51[47;61]% vs norepinephrine 62[57;71]%; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45[32;63]% vs norepinephrine + milrinone 73[66;81]%; p = 0.002). The Impella RP unloaded the failing RV. In contrast, vasoactive treatment led to enhanced cerebral venous oxygen saturation.

Introduction: Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, the definition of CS varies between trials, which may comprise interstudy comparability. Aim: The aim of the current study was to review differences and similarities of CS definitions used in randomized clinical trials (RCT) assessing patients with AMI-related CS. Methods: From the electronic databases MEDLINE and EMBASE we identified 19 AMI-related CS trials comprising a total of 2674 unique patients with CS. Results: Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary interventions, and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints and mortality varied markedly between trials. Hypotension was the most frequent inclusion criterion (17 (90%) trials), with a systolic blood pressure value Conclusions: RCTs of AMI-related CS show marked heterogeneity in inclusion criteria and outcomes potentially hampering interstudy comparability. Consensus criteria for CS appear needed for future selection of patients.

Background: Acute myocardial infarction complicated by cardiogenic shock (AMICS) with or without out-of-hospital cardiac arrest (OHCA) have some pathophysiological differences and could potentially be considered as two individual clinical entities. Thus, there may also be differences in terms of blood borne biomarkers. Purpose: To explore potential differences in concentrations of the biomarkers lactate, mid-regional proadrenomedullin (MRproADM), Copeptin, pro-atrial natriuretic peptide (proANP), Syndecan-1, soluble thrombomodulin (sTM), soluble suppression of tumorigenicity 2 (sST2) and neutrophil gelatinase-associated lipocalin (NGAL), in patients with AMICS with or without OHCA. Method: Patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction were enrolled during a 1-year period. In the present study 86 patients with confirmed AMICS at admission were included. Results: In the adjusted analysis OHCA patients had higher levels of lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) while the level of sST2 was lower (p = 0.029). There was little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%). Conclusion: AMICS patients with or without OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels. These findings support that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities.

Background: Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, no international consensus of a CS definition exists. This may compromise interstudy comparability. Aims: The aim of the current study was to review differences and similarities of CS enrolment criteria in AMI-related CS randomized clinical trials (RCT). Methods: From the electronic databases MEDLINE and EMBASE we identified all AMI-related CS trials. Results: A total of 19 trials comprising a total of 2674 unique patients with CS were identified. Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary intervention (PCI), and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints, and mortality varied markedly between trials. Hypotension was the most frequent overall inclusion criterion (17 [90%] trials), and a systolic blood pressure

Background: Prognosis models based on stepwise regression methods show modest performance in patients with cardiogenic shock (CS). Automated variable selection allows data-driven risk evaluation by recognizing distinct patterns in data. We sought to evaluate an automated variable selection method (least absolute shrinkage and selection operator, LASSO) for predicting 30-day mortality in patients with acute myocardial infarction and CS (AMICS) receiving acute percutaneous coronary intervention (PCI) compared to two established scores.Methods and results: Consecutive patients with AMICS receiving acute PCI at one of two tertiary heart centres in Denmark 2010-2017. Patients were divided according to treatment with mechanical circulatory support (MCS); PCI-MCS cohort (n = 220) versus PCI cohort (n = 1180). The latter was divided into a development (2010-2014) and a temporal validation cohort (2015-2017). Cohort-specific LASSO models were based on data obtained before PCI. LASSO models outperformed IABP-SHOCK II and CardShock risk scores in discriminative ability for 30-day mortality in the PCI validation [receiver operating characteristics area under the curve (ROC AUC) 0.80 (95% CI 0.76-0.84) vs 0.73 (95% CI 0.69-0.77) and 0.70 (95% CI 0.65-0.75), respectively, P < 0.01 for both] and PCI-MCS development cohort [ROC AUC 0.77 (95% CI 0.70-0.83) vs 0.64 (95% CI 0.57-0.71) and 0.64 (95% CI 0.57-0.71), respectively, P < 0.01 for both]. Variable influence differed depending on MCS, with age being the most influential factor in the LASSO-PCI model, whereas haematocrit and estimated glomerular filtration rate were the highest-ranking factors in the LASSO-PCI-MCS model.Conclusion: Data-driven prognosis models outperformed established risk scores in patients with AMICS receiving acute PCI and exhibited good discriminative abilities. Observations indicate a potential use of machinelearning to facilitate individualized patient care and targeted interventions in the future. Background Prognosis models based on stepwise regression methods show modest performance in patients with cardiogenic shock (CS). Automated variable selection allows data-driven risk evaluation by recognizing distinct patterns in data. We sought to evaluate an automated variable selection method (least absolute shrinkage and selection operator, LASSO) for predicting 30-day mortality in patients with acute myocardial infarction and CS (AMICS) receiving acute percutaneous coronary intervention (PCI) compared to two established scores.Methods and results Consecutive patients with AMICS receiving acute PCI at one of two tertiary heart centres in Denmark 2010-2017. Patients were divided according to treatment with mechanical circulatory support (MCS); PCI-MCS cohort (n=220) versus PCI cohort (n=1180). The latter was divided into a development (2010-2014) and a temporal validation cohort (2015-2017). Cohort-specific LASSO models were based on data obtained before PCI. LASSO models outperformed IABP-SHOCK II and CardShock risk scores in discriminative ability for 30-day mortality in the PCI validation [receiver operating characteristics area under the curve (ROC AUC) 0.80 (95% CI 0.76-0.84) vs 0.73 (95% CI 0.69-0.77) and 0.70 (95% CI 0.65-0.75), respectively, PConclusion Data-driven prognosis models outperformed established risk scores in patients with AMICS receiving acute PCI and exhibited good discriminative abilities. Observations indicate a potential use of machinelearning to facilitate individualized patient care and targeted interventions in the future.[GRAPHICS]

Aim: We sought to describe the contemporary annual incidence of cardiogenic shock (CS) following acute myocardial infarction (AMICS), the proportion of patients developing CS following ST-elevation myocardial infarction (STEMI), and other temporal changes in AMICS in Denmark between 2010 and 2017. Methods and results: Medical records of patients suspected of having AMICS during 2010–2017 were reviewed to identify consecutive patients with AMICS in a cohort corresponding to two-thirds of the Danish population. Due to changes in recruitment area over the study period, population-based incidence could only be calculated from 2012 to 2017. A total of 1716 patients with AMICS were identified and an increase in the annual incidence was observed, from a nadir 65.3 per million person-years in 2013 to 80.0 per million person-years in 2017 (P-value for trend < 0.001). This trend corresponded to an increase in patients with non-STEMI and a decrease in patients developing CS after STEMI (10.0–6.6%, P-value for trend < 0.001) Also, mean arterial blood pressure at the time of AMICS was lower (63 ± 11 mmHg to 61 ± 13 mmHg, P-value for trend = 0.001) and the frequency of patients with left ventricular ejection fraction ≤ 30% increased (61.8%–71.4%, P-value for trend = 0.004). The annual 30-day mortality during the study period remained unchanged at about 50%. Conclusion: The incidence rate of AMICS increased in the Danish population between 2012 and 2017. Fewer patients with STEMI developed CS, and haemodynamic severity of CS increased during the study period; however, survival rates remained unchanged.

PURPOSE OF REVIEW: Acute revascularization is with some evidence the only intervention proven to improve the prognosis in myocardial infarction-related cardiogenic shock but several interventions are continuously being investigated in order to increase survival among these patients. In this review, several aspects related to the interventional treatment of cardiogenic shock are discussed chronologically from symptom debut to leaving the cardiac catheterization laboratory. RECENT FINDINGS: In the randomized CULPRIT-SHOCK trial, a culprit-only revascularization strategy was reported superior to immediate complete revascularization among patients with multivessel disease. Recent large-scale observational data underline the marked prognostic importance of time from medical contact to revascularization in acute myocardial infarction-related cardiogenic shock. Moreover, studies suggest a potential beneficial effect of a transradial vascular access as well as early initialization of mechanical circulatory support in carefully selected patients. This, however, needs further validation. SUMMARY: Acute revascularization remains a crucial part of the initial management of acute myocardial infarction-related cardiogenic shock. Among cardiogenic shock patients presenting with multivessel disease, a culprit-only approach should be the routine strategy. Time to revascularization plays a crucial role in the setting of cardiogenic shock, why prehospital optimization and triaging may be the most important factors in order to improve prognosis in AMI-related cardiogenic shock.

AIMS: Out-of-hospital cardiac arrest (OHCA) is highly prevalent among patients with myocardial infarction and cardiogenic shock (MI-CS). We aimed to examine the prognostic importance of OHCA in patients with MI-CS.METHODS: Using Danish nationwide registries, we identified first-time hospitalized MI-CS patients (2010-2015) by OHCA status. Cumulative incidence curves and adjusted Cox regression models were used to compare in-hospital mortality, and among hospital survivors we compared 5-year rates of heart failure hospitalization and mortality.RESULTS: We identified 3107 MI-CS patients of whom 979 presented with OHCA (32%). OHCA patients were younger (median age: 65 vs. 74 years) and had less comorbidity. In-hospital mortality was 57% in those with OHCA compared with 67% in those without, but after adjustment the hazard ratio (HR) was 0.99 [95% CI: 0.87-1.11]. Hospital survivors consisted of 1375 MI-CS patients including 531 OHCA patients (39%). Five-year mortality was 22% for OHCA patients and 42% for patients without OHCA (adjusted HR: 0.90 [95% CI: 0.70-0.1.17]). The HR for five-year cardiovascular mortality was 0.80 [95% CI: 0.62-0.98]. Lastly, 5-year rate of heart failure hospitalization was 17% for patients with OHCA compared with 34% in those without (HR: 0.44 [95% CI: 0.34-0.57]).CONCLUSION: Among patients hospitalized with MI-CS, OHCA did not influence all-cause in-hospital or long-term mortality but was a marker for reduced long-term rates of heart failure hospitalization and cardiovascular mortality. Future randomized studies are needed to improve prognosis of MI-CS, however, the importance of OHCA must be considered.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Lundbeck Foundation OnBehalf Critical Cardiac Care Research Group Background Approximately half of all patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) present with out-of-hospital cardiac arrest (OHCA). Cardiogenic shock due to OHCA is caused by abrupt cessation of circulation, whereas AMICS without OHCA is due to cardiac failure with low cardiac output. Thus, there may also be differences between the two conditions in terms of blood borne biomarkers. Purpose To explore the potential differences in the admission plasma concentrations of biomarkers reflecting tissue perfusion (lactate), neuroendocrine response (mid-regional proadrenomedullin [MRproADM], Copeptin, pro-atrial natriuretic peptide [proANP]), endothelial damage (Syndecan-1, soluble thrombomodulin [sTM]), inflammation (soluble suppression of tumorigenicity 2 [sST2]) and kidney injury (neutrophil gelatinase-associated lipocalin [NGAL]), in patients with AMICS presenting with or without OHCA. Method Consecutive patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction (STEMI) were enrolled during a 1-year period. A total of 2,713 patients were screened. In the present study 86 patients with confirmed STEMI and CS at admission were included. Results Patients with OHCA (had significantly higher median admission concentrations of Lactate (6,9 mmol/L vs. 3.4 mmol/L p Conclusion Patients with STEMI and CS at admission with or without concomitant OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels at the time of admission to catheterization laboratory. These findings propose that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities. Abstract Figure. Level of biomarkers OHCA vs. non-OHCA

Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Unrestricted research grant from Abiomed Background No strong evidence exists regarding the treatment of cardiogenic shock (CS) caused by acute right ventricular (RV) failure which has mainly consisted of vasoactive drugs. There is expert agreement that treatment with the recently developed Impella RP is feasible, but no previous studies have compared vasoactive treatment strategies with the Impella RP in terms of cardiac unloading and end-organ perfusion. Hypothesis Treatment with the Impella RP device will be associated with lower RV myocardial workload (pressure-volume area) compared to vasoactive treatment strategies and can furthermore be achieved without compromising organ perfusion. Methods CS was induced by a stepwise injection of polyvinyl alcohol microspheres into the right coronary artery in twenty adult female Danish landrace pigs weighing 75-80 kg. After induction of CS, the pigs were allocated to one of the two interventions for 180 minutes: 1) vasoactive therapy comprised a continuous infusion of norepinephrine (0.1 µg/kg/min) for the first 30 minutes, supplemented by an infusion of milrinone (0.4 µg/kg/min) for the remaining 150 minutes or 2) immediate insertion of and treatment with the Impella RP. The results are presented as median [Q1;Q3]. Results Treatment with the Impella RP was associated with a lower RV workload compared to the vasoactive group, while no difference was observed with regards to left ventricular workload among intervention groups, Figure 1. Renal venous oxygen saturation increased to a similar degree following both interventions compared to the state of CS. A trend towards a higher cerebral venous oxygen saturation was observed with norepinephrine compared to Impella RP (Impella RP 51 [47;61] % vs Norepinephrine 62 [57;71] % ; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45 [32;63] % vs Norepinephrine +Milrinone 73 [66;81] %; p = 0.002). Conclusion In this large animal model of profound CS caused by predominantly RV failure the Impella RP unloaded the failing RV. The vasoactive treatment, however, caused a higher cerebral venous oxygen saturation, while both interventions increased renal venous oxygen saturation to a similar degree. Abstract Figure 1

The aim was to translationally compare a pharmacologic strategy versus treatment with the Impella RP in profound RV cardiogenic shock (CS). The pigs were allocated to either vasoactive therapy with norepinephrine (0.10 μg/kg/min) for the first 30 min, supplemented by an infusion of milrinone (0.4 μg/kg/min) for additional 150 min, or treatment with the Impella RP device for 180 min. Total RV workload (Pressure-volume-area × heart rate*10

Background Cardiogenic shock (CS) is a heterogeneous syndrome with varied presentations and outcomes. We used a machine learning approach to test the hypothesis that patients with CS have distinct phenotypes at presentation, which are associated with unique clinical profiles and in‐hospital mortality. Methods and Results We analyzed data from 1959 patients with CS from 2 international cohorts: CSWG (Cardiogenic Shock Working Group Registry) (myocardial infarction [CSWG‐MI; n=410] and acute‐on‐chronic heart failure [CSWG‐HF; n=480]) and the DRR (Danish Retroshock MI Registry) (n=1069). Clusters of patients with CS were identified in CSWG‐MI using the consensus k means algorithm and subsequently validated in CSWG‐HF and DRR. Patients in each phenotype were further categorized by their Society of Cardiovascular Angiography and Interventions staging. The machine learning algorithms revealed 3 distinct clusters in CS: "non‐congested (I)", "cardiorenal (II)," and "cardiometabolic (III)" shock. Among the 3 cohorts (CSWG‐MI versus DDR versus CSWG‐HF), in‐hospital mortality was 21% versus 28% versus 10%, 45% versus 40% versus 32%, and 55% versus 56% versus 52% for clusters I, II, and III, respectively. The "cardiometabolic shock" cluster had the highest risk of developing stage D or E shock as well as in‐hospital mortality among the phenotypes, regardless of cause. Despite baseline differences, each cluster showed reproducible demographic, metabolic, and hemodynamic profiles across the 3 cohorts. Conclusions Using machine learning, we identified and validated 3 distinct CS phenotypes, with specific and reproducible associations with mortality. These phenotypes may allow for targeted patient enrollment in clinical trials and foster development of tailored treatment strategies in subsets of patients with CS.

Supplemental Digital Content is available in the text., Background: Patients experiencing out-of-hospital cardiac arrest who remain comatose after initial resuscitation are at high risk of morbidity and mortality attributable to the ensuing post–cardiac arrest syndrome. Systemic inflammation constitutes a major component of post–cardiac arrest syndrome, and IL-6 (interleukin-6) levels are associated with post–cardiac arrest syndrome severity. The IL-6 receptor antagonist tocilizumab could potentially dampen inflammation in post–cardiac arrest syndrome. The objective of the present trial was to determine the efficacy of tocilizumab to reduce systemic inflammation after out-of-hospital cardiac arrest of a presumed cardiac cause and thereby potentially mitigate organ injury. Methods: Eighty comatose patients with out-of-hospital cardiac arrest were randomly assigned 1:1 in a double-blinded placebo-controlled trial to a single infusion of tocilizumab or placebo in addition to standard of care including targeted temperature management. Blood samples were sequentially drawn during the initial 72 hours. The primary end point was the reduction in C-reactive protein response from baseline until 72 hours in patients treated with tocilizumab evaluated by mixed-model analysis for a treatment-by-time interaction. Secondary end points (main) were the marker of inflammation: leukocytes; the markers of myocardial injury: creatine kinase myocardial band, troponin T, and N-terminal pro B-type natriuretic peptide; and the marker of brain injury: neuron-specific enolase. These secondary end points were analyzed by mixed-model analysis. Results: The primary end point of reducing the C-reactive protein response by tocilizumab was achieved since there was a significant treatment-by-time interaction, P

Aims The objective was to describe patient characteristics, interventions, and outcome in acute myocardial infarction complicated by cardiogenic shock (AMICS), due to predominantly right ventricular (RV) failure after revascularization, in comparison with patients suffering from left ventricular (LV) failure as these patients remain sparsely characterized. Methods and results From 2010 to 2017, consecutive AMICS patients admitted to either of two tertiary heart centres, covering 3.9 million citizens, corresponding to two-thirds of the Danish population, were identified and individually reviewed through patient records. A total of 1716 AMICS patients were identified, of which 1482 underwent acute revascularization and included for analysis. Hereof, 101 (7%) patients developed cardiogenic shock due to predominantly RV failure, while 1381 (93%) had significant LV involvement. Female sex was the only demographic factor associated with RV failure (35% vs. 25%, P = 0.01). Despite having a preserved LV ejection fraction, patients with predominantly RV failure were comparable to patients with LV involvement, in terms of haemodynamic and metabolic profile, here among variables commonly used in the cardiogenic shock definition including blood pressure (82 mmHg vs. 83 mmHg, P = 0.90) and lactate level (5.7 mmol/L vs. 5.4 mmol/L, P = 0.70). Patients with RV AMICS had significantly lower 30-day mortality than LV AMICS, and this result persisted after multivariable adjustment (RV vs. LV; hazard ratio 0.61, 95% confidence interval 0.41–0.92, P = 0.01). Conclusion In contemporary AMICS patients undergoing revascularization, patients with predominantly RV failure had comparable haemodynamics and metabolic derangement on admission compared to patients with LV failure but was associated with female sex and a significantly lower 30-day mortality.

Background Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction, with short-term mortality of approximately 50%. Whether diabetes mellitus and high blood glucose levels are associated with mortality in contemporary patients with acute myocardial infarction complicated by cardiogenic shock is inadequately described. Purpose To investigate if diabetes mellitus and high admission blood glucose were associated with 30-day mortality in a large, contemporary population with acute myocardial infarction complicated by cardiogenic shock. Methods Patients with acute myocardial infarction complicated by cardiogenic shock admitted at two tertiary centres in Denmark from 2010 to 2017 were individually identified through patient charts, resulting in the inclusion of 1716 cardiogenic shock patients. Glucose level at admission to the intensive care unit was available in 1302 patients. Results There was no significant difference in 30-day mortality between diabetes mellitus types I and II (63% vs. 62%, NS). Thirty-day mortality was significantly higher in diabetes patients compared to non-diabetes patients (62% vs. 50%, P 16 mmol/L, 67%; P = 0.028) and non-diabetes patients (4–8 mmol/L, 32%; 8–12 mmol/L, 43%; 12–16 mmol/L, 57%; >16 mmol/l; 68%; P Conclusion Patients with acute myocardial infarction complicated by cardiogenic shock and concomitant diabetes mellitus type I or II had a significantly higher 30-day mortality in comparison to patients without diabetes mellitus, whereas no difference was found between diabetes mellitus types I and II. High glucose levels on admission to the intensive care unit were associated with increased 30-day mortality in diabetes mellitus and non-diabetes mellitus patients.

Introduction Cardiogenic shock (CS) due to myocardial infarction (MI) carries 30-day mortality rates as high as 50%. The vast majority of study cohorts assessing mortality in CS comprise both patients presenting with and without out-of-hospital cardiac arrest (OHCA). Patients with and without OHCA are likely to represent two distinctive entities, which may be problematic to combine in an intervention trial. Purpose The aim of the study was to compare CS due to MI patients presenting with and without OHCA in terms of patient characteristics and outcome. Methods In the period from 2010–2017 all patients admitted at two tertiary heart centres in Denmark with CS following MI were individually identified and validated through patient records. The two centres have a catchment area of 3.9 million citizens corresponding to two-thirds of the Danish population. Results A total of 1716 CS patients were identified, of which 42% presented with OHCA. OHCA patients were younger (mean 63 vs 67 years), more frequently male (85 vs 67%), had higher lactate concentration (median 6.2 vs 5.0 mmol/L) on admission and higher left ventricular ejection fraction (median 30 vs 25%) compared to patients without OHCA (p Figure 1 Conclusion Among patients with CS due to MI, overall 30-day mortality was significantly lower in patients presenting with OHCA. Anoxic brain damage was the main cause of in hospital death among OHCA patients, whereas fatal heart failure prevailed in patients without OHCA. Combining these two groups in a single trial with one specific intervention seems inappropriate and likely to cause an imbalance in the signal-to-noise ratio. Acknowledgement/Funding The Danish Heart Foundation and a research grant from Abiomed

Cardiogenic shock (CS) mortality remains unacceptably high. Predicting in-hospital mortality is a critical barrier. Using clinical variables, we applied a machine learning approach to improve the assessment of risk for in-hospital mortality among patients with CS. The Cardiogenic Shock Working

Background Early postoperative mobilization is essential for rapid recovery but may be impaired by orthostatic intolerance (OI) and orthostatic hypotension (OH), which are highly prevalent after major surgery. Pathogenic mechanisms include an insufficient postoperative vasopressor response. The oral α-1 agonist midodrine hydrochloride increases vascular resistance, and the authors hypothesized that midodrine would reduce the prevalence of OH during mobilization 6 h after total hip arthroplasty relative to placebo. Methods This double-blind, randomized trial allocated 120 patients 18 yr or older and scheduled for total hip arthroplasty under spinal anesthesia to either 5 mg midodrine hydrochloride or placebo orally 1 h before mobilization at 6 and 24 h postoperatively. The primary outcome was the prevalence of OH (decrease in systolic or diastolic arterial pressures of > 20 or 10 mmHg, respectively) during mobilization 6 h after surgery. Secondary outcomes were OI and hemodynamic responses to mobilization at 6 and 24 h. Results At 6 h, 14 (25%; 95% CI, 14 to 38%) versus 23 (39.7%; 95% CI, 27 to 53%) patients had OH in the midodrine and placebo group, respectively, relative risk 0.63 (0.36 to 1.10; P = 0.095), whereas OI was present in 15 (25.0%; 15 to 38%) versus 22 (37.3%; 25 to 51%) patients, relative risk 0.68 (0.39 to 1.18; P = 0.165). At 24 h, OI and OH prevalence did not differ between groups. Conclusions Preemptive use of oral 5 mg midodrine did not significantly reduce the prevalence of OH during early postoperative mobilization compared with placebo. However, further studies on dose and timing are warranted since midodrine is effective in chronic OH conditions.

Early postoperative mobilization is essential for rapid recovery but may be impaired by orthostatic intolerance (OI) and orthostatic hypotension (OH), which are highly prevalent after major surgery. Pathogenic mechanisms include an insufficient postoperative vasopressor response. The oral α-1 agonist midodrine hydrochloride increases vascular resistance, and the authors hypothesized that midodrine would reduce the prevalence of OH during mobilization 6 h after total hip arthroplasty relative to placebo.This double-blind, randomized trial allocated 120 patients 18 yr or older and scheduled for total hip arthroplasty under spinal anesthesia to either 5 mg midodrine hydrochloride or placebo orally 1 h before mobilization at 6 and 24 h postoperatively. The primary outcome was the prevalence of OH (decrease in systolic or diastolic arterial pressures of20 or 10 mmHg, respectively) during mobilization 6 h after surgery. Secondary outcomes were OI and hemodynamic responses to mobilization at 6 and 24 h.At 6 h, 14 (25%; 95% CI, 14 to 38%) versus 23 (39.7%; 95% CI, 27 to 53%) patients had OH in the midodrine and placebo group, respectively, relative risk 0.63 (0.36 to 1.10; P = 0.095), whereas OI was present in 15 (25.0%; 15 to 38%) versus 22 (37.3%; 25 to 51%) patients, relative risk 0.68 (0.39 to 1.18; P = 0.165). At 24 h, OI and OH prevalence did not differ between groups.Preemptive use of oral 5 mg midodrine did not significantly reduce the prevalence of OH during early postoperative mobilization compared with placebo. However, further studies on dose and timing are warranted since midodrine is effective in chronic OH conditions.