New and revisited approaches to preserving the reperfused myocardium

Key Points Mortality after acute ST-segment elevation myocardial infarction (STEMI) has plateaued in the past decade, after a period of continual decline Beyond early reperfusion, a variety of adjunctive agents to reduce myocardial infarction after reperfusion have been tested in clinical settings, and have yielded largely disappointing results Before clinical testing, candidate cardioprotective agents should be tested in animal models with comorbidities similar to that in patients, and in combination with P2Y 12 inhibitors Approaches for improving cardiac function following STEMI that have been promising in preclinical studies include those that target mitochondrial bioenergetics, pyroptosis, autophagy, and no-reflow and anaesthetic preconditioning Strategies to reduce myocardial infarct size beyond early reperfusion have thus far yielded disappointing results in clinical trials. In this Review, Kloner and co-workers discuss several new approaches to preserve the reperfused myocardium, including those that target mitochondrial bioenergetics and autophagy. Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.