Wojta, Johann

Abstract Inflammation is a key driver of coronary syndromes across the continuum from chronic coronary syndromes to acute coronary syndromes. It contributes to atherogenesis, plaque destabilization, and ischaemic events and influences myocardial injury, repair, and remodelling. Inflammatory activity is further amplified by metabolic and autoimmune comorbidities such as diabetes, obesity, and connective tissue diseases, with obesity representing a major driver of chronic low-grade inflammation through adipose tissue dysfunction and cytokine activation, while psychosocial stress and environmental exposures including air pollution serve as additional triggers. Genetic variations, including human leucocyte antigen genotypes, modulate individual susceptibility to vascular inflammation and myocardial injury. This expert consensus from the European Society of Cardiology’s Association for Acute CardioVascular Care summarizes the current understanding of inflammation across the full spectrum of coronary syndromes, including underlying mechanisms, relevant biomarkers, and imaging approaches that characterize vascular inflammation, and integrates insights from experimental and clinical studies. Importantly, this document provides explicit consensus-based guidance on when, how, and in whom inflammation should be assessed and treated in routine clinical practice. While the causal association between inflammation and atherosclerotic cardiovascular disease is well established, pharmacological modification of inflammation has produced conflicting evidence. Some agents, such as low-dose colchicine, have demonstrated modest reductions in cardiovascular events, although results across trials have been inconsistent. Other anti-inflammatory therapies have not shown clinical benefit, whereas selective cytokine inhibition with canakinumab has reduced cardiovascular risk at the cost of increased infection rates. The present manuscript also focuses on the evaluation of inflammatory activity in cardiovascular patients in routine clinical practice. It further discusses criteria for patient selection and clinical decision-making regarding the introduction of anti-inflammatory therapy in individuals with established atherosclerotic cardiovascular disease.

Abstract Metabolic disorders such as obesity, type 2 diabetes, and dyslipidaemia are major drivers of cardiovascular risk and have reached epidemic levels in Western populations. Recent advances in clinical research have uncovered unexpected and often beneficial effects of pharmacological classes of metabolic drugs on cardiovascular outcomes, revealing complex interactions between metabolism and cardiac pathology. Despite their clinical efficacy, the molecular and cellular mechanisms through which many of these agents act remain only partially understood. This gap in knowledge underscores the urgent need for fundamental research that not only dissects the biology of metabolic disorders and cardiovascular disease but also reveals the mechanistic basis of existing and emerging therapies, thereby enabling rational therapeutic development. This scientific statement, developed by researchers from the European Society of Cardiology (ESC) Council on Basic Cardiovascular Science and several ESC Working Groups, provides a state-of-the-art overview of the emerging molecular and cellular pathways linking metabolic abnormalities with vascular and cardiac disease. By illuminating these critical connections and unresolved questions, this article aims to catalyse innovation in the prevention and management of cardiovascular disease in the context of metabolic dysfunction and to suggest new directions for future research.

Abstract The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.

Background: The efficacy of remote ischaemic conditioning in clinical trials of ST-segment elevation myocardial infarction (STEMI) or elective percutaneous coronary intervention is controversial. We aimed to systematically review and meta-analyse whether remote ischaemic conditioning reduces myocardial damage in those patients. Methods: We searched PubMed, Embase and Web of Science from inception until December 2017 for randomised clinical trials evaluating remote ischaemic conditioning versus a control group. Two independent reviewers extracted data of 23 trials (2118 patients with STEMI; 2048 patients undergoing elective percutaneous coronary intervention) which were meta-analysed using random-effects models. Results: Remote ischaemic conditioning reduced infarct size in STEMI patients when assessed by imaging (mean difference of infarct size as percentage of left ventricle −2.43, 95% confidence interval (CI) –4.37 to −0.48; P=0.01; I2=44%; n=925) or biomarkers related to myocardial injury (peak values of cardiac biomarker release reported as standardised mean difference −0.19, 95% CI −0.37 to −0.02; P=0.03; I2=58%; n=1483) and increased myocardial salvage index (mean difference 0.07, 95% CI 0.01 to 0.13; P=0.02; I2=49%; n= 636). Left ventricular ejection fraction was increased when assessed during the first days after STEMI (mean difference 1.53, 95% CI 0.23 to 2.83; P=0.02; I2=28%; n=1192). Remote ischaemic conditioning had no influence on biomarker values after elective percutaneous coronary intervention (standardised mean difference 0.06, 95% CI −0.17 to 0.30; P=0.59). Conclusions: Despite a statistically significant reduction of myocardial damage in STEMI patients, the magnitude of the reduction was small and a significant impact on clinical events is unlikely. With respect to elective percutaneous coronary intervention, remote ischaemic conditioning had no influence on myocardial injury and its use is not supported by our analysis.