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.

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.

ObjectivesTo describe the contemporary trends in the use of mechanical circulatory support (MCS) in patients with acute myocardial infarction and cardiogenic shock (AMICS). To evaluate survival benefit with early application of intra-aortic balloon pump (IABP) or Impella CP.MethodsA cohort study of all consecutive patients with AMICS undergoing percutaneous coronary intervention (PCI) <24 hours of symptom onset (early PCI) in southeastern Denmark from 2010 to 2017. A matched case–control study comparing 30-day mortality between patients receiving early-IABP or early-Impella CP and their respective control group. Controls were matched on age, left ventricular ejection fraction, arterial lactate, estimated glomerular filtration rate and cardiac arrest before PCI. Early-IABP/Impella CP was defined as applied before PCI if shock developed pre-PCI, or immediately after PCI if shock developed during PCI.Results903 patients with AMICS undergoing early PCI were identified. Use of MCS decreased from 50% in 2010 to 25% in 2017, p for trend of <0.001. The IABP was abandoned in 2012 and replaced mostly by Impella CP. Patients receiving MCS in 2013–2017 had more compromised haemodynamics compared with patients receiving MCS in 2010–2012. 40 patients received early IABP, and 40 patients received early Impella CP. Only the group receiving early Impella CP was associated with lower 30-day mortality compared with their matched control group (30-day mortality 40% vs 77.5%, plog-rank of<0.001).ConclusionUse of MCS decreased by 50% from 2010 to 2017. Patients receiving MCS had more compromised haemodynamics in recent years. Early application of Impella CP was associated with reduced 30-day mortality compared with a matched control group.

BACKGROUNDThe appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODSIn 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 (Pao 2 ) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao 2 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. RESULTSA 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. CONCLUSIONSTargeting 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. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials .gov number, NCT03141099.

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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.

Background: Out-of-hospital cardiac arrest (OHCA) patients who remain comatose after initial resuscitation are at high risk of morbidity and mortality due to the ensuing post cardiac arrest syndrome (PCAS). Systemic inflammation constitutes a major component of PCAS, and interleukin-6 (IL-6) levels are associated with PCAS severity. The IL-6 receptor antagonist tocilizumab could potentially dampen inflammation in PCAS. The objective of the present trial was to determine the efficacy of tocilizumab to reduce systemic inflammation after OHCA of presumed cardiac cause and thereby potentially mitigate organ injury. Methods: Eighty comatose OHCA patients were randomized 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 72h. Primary endpoint: reduction in C-reactive protein (CRP) response from baseline till 72h in patients treated with tocilizumab evaluated by mixed model analysis for a treatment-by-time interaction. Secondary endpoints (main): marker of inflammation: leukocytes, markers of myocardial injury: Creatine Kinase Myocardial Band (CKMB), Troponin T (TnT), and N-terminal pro B-type natriuretic peptide (NT-proBNP); marker of brain injury: neuron-specific enolase (NSE); these secondary endpoints were analyzed by mixed model analysis. Results: The primary endpoint of reducing the CRP response by tocilizumab was achieved as there was a significant treatment-by-time interaction, p<0.0001, and a profound effect on CRP levels. Systemic inflammation was reduced by treatment with tocilizumab as both CRP and leukocyte levels were markedly reduced, tocilizumab vs placebo at 24h: -84% [-90%;-76%] and -34% [-46%;-19%] respectively, both p<0.001. Myocardial injury was also reduced documented by reductions in CKMB and TnT; active vs. placebo at 12h: -36% [-54%;-11%] and -38% [-53%;-19%], respectively, both p<0.01. NT-proBNP was similarly reduced by active treatment; tocilizumab vs placebo at 48h: -65% [-80%;-41%], p<0.001. There were no differences in survival or neurological outcome. Conclusions: Treatment with tocilizumab resulted in a significant reduction in systemic inflammation and myocardial injury in comatose resuscitated OHCA patients. Clinical Trial Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT03863015

Background: Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). Objective: To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. Methods: CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO 2 ), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. Results: All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 10 3 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO 2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 10 3 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO 2 (p = 0.063) and increased arterial lactate levels (p = 0.002). Conclusion: Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.