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Aims: Women continue to have a worse prognosis following ST-elevation myocardial infarction (STEMI) compared to men, despite advancements in treatment. This study investigates whether neurohormonal biomarker differences contribute to sex-related disparities in mortality., Methods and Results: A total of 1892 consecutive STEMI patients from two tertiary heart centres were included. Admission neurohormonal activation defined as pro-atrial natriuretic peptide (proANP) and mid-regional pro-adrenomedullin (MR-proADM) was measured in blood drawn prior to acute coronary angiography (CAG). The primary endpoint was 1-year mortality stratified according to sex and biomarker level. Of 1782 (94%) with biomarkers available, 476 (27%) of patients were women. They were older (68 vs. 62 years), had longer symptom-to-angiography delay (211 vs. 181 min), and displayed a higher one-year mortality rate (12% vs. 7.4%, P < 0.001) compared to men. The neurohormonal response was higher in women compared to men [median (interquartile range) proANP 1050 (671-1591) vs. 772 (492-1294) pmol/L, P < 0.001); MR-proADM 0.80 (0.63-1.03) vs. 0.70 (0.58-0.89) nmol/L, P < 0.001]. In women, a level at or above the median was independently associated with a significantly higher mortality risk when adjusting for age, left ventricular ejection fraction, diabetes, heart failure, symptom onset to CAG, left-sided culprit lesion, obesity, renal dysfunction, primary percutaneous intervention, admission systolic blood pressure, and multivessel disease (HR proANP 6.05, 95% CI 1.81-20.3, P = 0.004; HR MR-proADM 3.49, 95% CI 1.42-8.62, P = 0.007). In men, there was an independent prognostic association for proANP but not for MR-proADM (HR proANP 2.38, 95% CI 1.18-4.81, P = 0.015; HR MR-proADM 1.74, 95% CI 0.89-3.40, P = 0.11)., Conclusion: Increased neurohormonal activation (MR-proADM and proANP) is associated with higher mortality in women compared to men. Neurohormonal activation may contribute to the observed sex-related differences in mortality., Competing Interests: Conflict of interest: Manufacturers of assays did not provide support by financial or any other means., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Out-of-hospital cardiac arrest is a leading cause of death worldwide. Establishing vascular access is critical for administering guideline-recommended drugs during cardiopulmonary resuscitation. Both the intraosseous route and the intravenous route are used routinely, but their comparative effectiveness remains unclear., Methods: We conducted a randomized clinical trial to compare the effectiveness of initial attempts at intraosseous or intravenous vascular access in adults who had nontraumatic out-of-hospital cardiac arrest. The primary outcome was a sustained return of spontaneous circulation. Key secondary outcomes were survival at 30 days and survival at 30 days with a favorable neurologic outcome, defined by a score of 0 to 3 on the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability)., Results: Among 1506 patients who underwent randomization, 1479 were included in the primary analysis (731 in the intraosseous-access group and 748 in the intravenous-access group). The successful establishment of vascular access within two attempts occurred in 669 patients (92%) assigned to the intraosseous-access group and in 595 patients (80%) assigned to the intravenous-access group. Sustained return of spontaneous circulation occurred in 221 patients (30%) in the intraosseous-access group and in 214 patients (29%) in the intravenous-access group (risk ratio, 1.06; 95% confidence interval [CI], 0.90 to 1.24; P = 0.49). At 30 days, 85 patients (12%) in the intraosseous-access group and 75 patients (10%) in the intravenous-access group were alive (risk ratio, 1.16; 95% CI, 0.87 to 1.56); a favorable neurologic outcome at 30 days occurred in 67 patients (9%) and 59 patients (8%), respectively (risk ratio, 1.16; 95% CI, 0.83 to 1.62). Prespecified adverse events were uncommon., Conclusions: There was no significant difference in sustained return of spontaneous circulation between initial intraosseous and intravenous vascular access in adults who had out-of-hospital cardiac arrest. (Funded by the Novo Nordisk Foundation and others; IVIO EU Clinical Trials Register number, 2022-500744-38-00; ClinicalTrials.gov number, NCT05205031.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties., Methods: This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24-48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB)., Discussion: Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints., Trial Registration: Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021-002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277-8523., (© 2024. The Author(s).)

Background: Cardiogenic shock (CS) occurs in 5-10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development., Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24-48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed., Discussion: Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up., Trial Registration: The Regional Ethics Committee : H-21045751. EudraCT: 2021-002028-19., Clinicaltrials: gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277-8523., (© 2024. The Author(s).)