
Tobias Lerchner and Stephane Heymans discuss the study that provided seminal evidence linking genetic variation to susceptibility to acute myocarditis.
Ludmila Caceva discusses the 1970s studies that revealed that the plasma lipid prolife of the Inuit population of Greenland, who had a low incidence of cardiovascular disease, was characterized by low levels of cholesterol, lipoproteins and triglycerides and high levels of omega-3 fatty acids and how these findings shaped dietary guidelines worldwide.
In the setting of myocardial ischaemia-reperfusion injury, ischaemia induces severe myocardial hypoxia, whereas the abrupt reintroduction of oxygen during reperfusion further amplifies tissue injury through redox imbalance. This dynamic stabilizes hypoxia-inducible factors (HIFs), which become transcriptionally active and induce hypoxia-responsive gene networks. In turn, HIF-dependent programmes orchestrate adaptive responses to acute hypoxia, including metabolic reprogramming towards glycolysis, promotion of extracellular adenosine signalling, induction of epidermal growth factor pathways and integration with circadian regulatory circuits. Collectively, these programmes increase myocardial resistance to ischaemic stress and limit ischaemia-reperfusion injury. In this Review, we examine the functional roles of HIFs in cardioprotection, with a particular focus on their contributions to ischaemic preconditioning or remote preconditioning and the HIF-dependent pathways that drive these cardioprotective effects. Given that pharmacological HIF stabilizers are already in clinical use for the treatment of renal anaemia, these insights provide a clear translational framework, positioning HIF activation as a plausible and immediately actionable therapeutic approach to prevent or treat myocardial ischaemia-reperfusion injury.
The introduction of intracoronary imaging (ICI) into clinical practice has been one of the major advances in percutaneous coronary intervention (PCI) for patients with atherosclerotic coronary artery disease. However, because the procedural advantages of ICI in routine clinical practice can be offset by higher costs and longer procedural times, high-quality evidence demonstrating the net clinical benefits of ICI guidance has long been awaited. The publication of eight large (n > 1,000 patients), international, randomized studies (the ILUMIEN IV, IVUS-ACS, IVUS-CHIP, IVUS-XPL, OCCUPI, OCTOBER, RENOVATE-COMPLEX-PCI and ULTIMATE trials) has provided substantial data on the clinical use of ICI guidance to improve the safety and outcomes of patients undergoing PCI. However, the heterogeneity of the study populations, lack of standardized criteria across ICI protocols and the mixed results of randomized trials have left uncertainty about why and when the use of ICI confers a benefit in real-world settings. In this Review, by discussing the study characteristics and procedural aspects that contributed to the consistency and heterogeneity across trials, we provide a practical and comprehensive appraisal of the appropriateness - why, when, how and which - of ICI guidance in the clinical decision-making process for contemporary PCI, with the overall aim of improving clinical outcomes.
In this Tools of the Trade, Ackers-Johnson and Pavlovic describe a Langendorff-free approach to isolate cardiomyocytes without the technical hurdles associated with the conventional Langendorff perfusion procedure.