Marianne Zeller

Background and Aims: Cardiogenic shock (CS) is the most dreadful complication of acute coronary syndromes (ACS). Endothelial dysfunction and vascular leakage are hallmarks of CS pathophysiology; however, biomarkers reflecting these early processes are lacking. The adrenomedullin (ADM) system—the inactive precursor glycine-extended ADM (ADM-Gly), the activating enzyme peptidylglycine α-amidating monooxygenase (PAM), and biologically active ADM (bio-ADM)—modulates vascular tone and permeability. This study investigated associations of ADM system components with CS and 1-year mortality risk after ACS. Methods: ADM-Gly, PAM, and bio-ADM were assessed in 4098 (Switzerland; SPUM-ACS) and 824 (France; FAST-MI) ACS patients without CS on admission. The primary endpoint was in-hospital CS; the secondary endpoint was 1-year mortality. Biomarker–outcome associations were analysed using multivariable-adjusted regression models, and the incremental predictive value beyond established risk scores was quantified. Results: Higher ADM-Gly and bio-ADM, but not PAM, were associated with systemic inflammation and haemodynamic compromise. ADM-Gly and bio-ADM independently predicted CS risk in Switzerland (adjusted odds ratio [aOR] per log2 increase, 1.44, 95% confidence interval [CI] 1.22–1.71, P < .001 and aOR 1.37, 95% CI 1.10–1.70, P = .004) and France (adjusted risk ratio [RR] per log2 increase, 1.82, 95% CI 1.34–2.48, P < .001 and aRR 1.55, 95% CI 1.15–2.10, P = .004), and were associated with 1-year mortality risk (adjusted hazard ratio [aHR] per log2 increase, 1.33, 95% CI 1.09–1.61, P = .005 and aHR 1.46, 95% CI 1.15–1.86, P = .002). Addition of ADM-Gly and bio-ADM to the ORBI risk score improved its discrimination (Δ area under the receiver operating characteristic curve 0.02), reclassification (net reclassification improvement 0.229), and model fit (Δ Akaike information criterion −26.9), with consistent results in external validation. Conclusions: ADM-Gly and bio-ADM, but not PAM, independently predict in-hospital CS and 1-year mortality risk in initially stable patients with ACS and improve early risk stratification.

Aims: The efficacy of omega-3 fatty acid supplementation in cardiovascular prevention remains debated. Observational data suggest that individual fatty acids may have distinct prognostic value after acute myocardial infarction (AMI). This study aims to analyse the association of plasma fatty acid (FA) levels including eicosapentaenoic acid (EPA) and the EPA/docosahexaenoic acid (DHA) ratio at the time of AMI with 1-year cardiovascular (CV) mortality. Methods and results: This prospective study included 572 patients hospitalized for AMI. Plasma FA levels were measured using gas chromatography coupled with mass spectrometry. The associations between FA profiles and CV mortality at 1-year follow-up were analysed using Cox proportional hazards models. At follow-up, 29 deaths were cardiovascular-related. Patients who died had lower relative levels of EPA [0.47% (0.28–0.73) vs. 0.73% (0.52–1.02), P < 0.001], a lower EPA/DHA ratio [0.33 (0.22–0.43) vs. 0.44 (0.33–0.61), P < 0.001], and more elevated levels of inflammatory biomarkers, including hs-CRP and interleukin-1β. In contrast, DHA levels were not associated with CV mortality. In multivariate analysis, the EPA/DHA ratio was associated with lower CV mortality, even after adjustment for confounding factors including GRACE risk score, left ventricular ejection fraction, and inflammatory biomarkers. Conclusion: Our study demonstrates that higher plasma levels of EPA and EPA/DHA ratio are associated with lower CV mortality one year after AMI.

Background/Objectives: Despite advances in personalized medicine, diabetes classification and management have remained widely unchanged for decades. The aims of the present study were to determine profiles of patients with type 2 diabetes at the time of their myocardial infarction and to assess 1-year cardiovascular events. Methods: All type 2 diabetic patients admitted for myocardial infarction in our Coronary Intensive Care Unit between 1 April 2021 and 30 June 2023 were included in this retrospective study. To identify patient profiles, we performed a data-driven cluster analysis based on the k-means method according to six characteristics considered as the most relevant in the literature (age at diabetes diagnosis, body mass index, glycated hemoglobin, glutamate decarboxylase antibodies, insulin resistance and beta-cell function). Cox multivariate models were used to identify predictors of 1-year cardiovascular event- and major adverse cardiovascular event-free survivals. Results: This study included 250 patients with a median age of 71 years. Our cluster repartition was as follows: 46% patients presented a severe insulin-deficient diabetes, 3% a severe insulin-resistant diabetes, 16% a mild obesity-related diabetes, 33% a mild age-related diabetes, and 2% patients suffered from a severe autoimmune diabetes. In multivariate analyses, the only independent factor for both longer cardiovascular event- and major adverse cardiovascular event-free survival was a higher glomerular function rate (hazard ratio of 0.97 and 0.98 per 1 mL/mn/1.73 m²; p = 0.01 and p = 0.03, respectively). Conclusions: This study suggests that the severe insulin-deficient diabetes and mild age-related diabetes pathophysiological phenotypes, easily estimated using insulin resistance and beta-cell function as well as age at diabetes diagnosis, body mass index, and glycated hemoglobin, were more frequent among diabetic patients at the time of their myocardial infarction. In daily clinical practice, caution is needed for patients with a low glomerular function rate, as this was associated with shorter cardiovascular event- and major adverse cardiovascular event-free survival at 1-year.

And aims: Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire Régional Breton sur l’Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (AUC [95% CI]: 0.78 [0.76-0.81] vs. 0.81 [0.79-0.83]; p=0.048) and French ACS patients (0.77 [0.74-0.81] vs. 0.84 [0.81-0.86]; p=0.002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78-0.83]; males: 0.83 [0.82-0.85]; p<0.001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79-0.85]; males: 0.88 [0.86-0.89]; p<0.001) and SPUM-ACS (females: 0.83 [0.77-0.90], p=0.004; males: 0.83 [0.80-0.87], p=0.001). The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management.

Background: From a large observational acute coronary syndrome registry in Côte d'Ivoire, we aimed to assess incidence, clinical presentation, management, and in‐hospital outcomes for type 2 myocardial infarction (T2MI) compared with type 1 MI. Methods and Results: We conducted a cross‐sectional monocentric study using data from REACTIV (Registre des Infarctus de Côte d'Ivoire) at the Abidjan Heart Institute. All patients hospitalized with MI between 2018 and 2022 who underwent coronary angiography were included. For each patient, sociodemographic data, cardiovascular risk factors and history, and clinical and paraclinical presentation were collected at admission. In‐hospital outcomes, including major adverse cardiovascular events and mortality, were reported. Among 541 consecutive patients hospitalized with MI, 441 met the definition of type 1 MI or T2MI. T2MI accounted for 14.1% of cases. Patients with T2MI showed a trend toward slightly younger age (54 versus 58 years, P =0.09). Patients with T2MI seemed to have less severe coronary artery disease, with less frequent multivessel disease ( P <0.001). Main triggering factors for T2MI were coronary embolism (24.2%), severe hypertension with or without left ventricular hypertrophy (22.6%), and tachyarrhythmia (16.1%). In‐hospital event rates were low in both MI types. Although the difference was nonsignificant, death rates for patients with type 1 MI tended to be higher than for patients with T2MI, as well as occurrence of major adverse cardiovascular events. Conclusions: Our study revealed disparities in clinical characteristics, angiographic features, cause, and in‐hospital outcomes in T2MI in our population compared with Western populations. These results suggest the heterogeneity of T2MI and the potential causative and demographic variability depending on geographical area.

Omega-3 fatty acids (n-3 FAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerging protective roles in cardiovascular (CV) diseases.¹ The Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial (REDUCE-IT) showed reduction, by 25%, in the risk of ischaemic events and CV death compared with placebo of high-dose icosapent ethyl (IPE) in statin-treated adults at high CV risk with elevated triglycerides.² Nevertheless, several issues regarding the efficacy of n-3 FAs are the subject of lively debate. The residual risk reduction with IPE goes beyond triglyceride lowering, suggesting the involvement of a broad panel of pleiotropic effects of EPA.¹ While other clinical trials with purified EPA also found positive results on major coronary events,³ mixed EPA/docosahexaenoic acid (DHA) formulations showed less effectiveness in large outcomes trials, despite similar degrees of triglyceride lowering.^4,5 Finally, mineral oil used as placebo in the control group of REDUCE-IT was associated with an increase in inflammation, whereas IPE-treated patients displayed only moderate improvement in biomarkers. These data underscore the need for more extensive information on the relationship between EPA, EPA/DHA ratio, and inflammatory biomarkers in high-risk patients.⁶

Underlying coronary artery disease (CAD) is increasingly considered to be a key issue in the pathophysiology of type 2 myocardial infarction (T2MI). In T2MI, which is attributable to a mismatch between oxygen supply/demand, CAD is common and appears to be more severe than in type 1 myocardial infarction (T1MI). Little is known about the heterogeneous mechanisms that cause supply/demand imbalance and non-coronary triggers leading to myocardial ischemia or about how they are potentially modulated by the presence and severity of CAD. CAD seems to be underrecognized and undertreated in T2MI, even though previous studies have demonstrated both the short and long-term prognostic value of CAD in T2MI. In this literature review, we attempt to address the prevalence and severity of CAD, challenges in the discrimination between T2MI and T1MI in the presence of CAD, and the prognostic value of CAD among patients with T2MI.