NSTEMI

This is a prospective, multi-center, randomized controlled, open-label, blinded endpoint assessment study. The objective is to compare the 1-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE) between two treatment strategies-immediate complete revascularization and staged complete revascularization-in NSTE-ACS patients with multivessel disease (MVD). NSTE-ACS patients who meet other the inclusion and exclusion criteria will be randomized into the following two groups after signing an informed consent form: Intervention group Immediate Complete Revascularization: Emergency PCI for the culprit vessel is performed successfully, and simultaneous PCI is conducted for non-culprit vessels that meet the defined criteria (visually estimated diameter ≥2.5 mm, eligible for successful PCI, and visually estimated maximum diameter stenosis ≥ 70% or positive coronary physiology testing). Control group During emergency intervention, PCI is performed only on the culprit vessel. Elective PCI is then conducted for non-culprit vessels that meet the defined criteria (visually estimated diameter ≥ 2.5 mm, eligible for successful PCI, and visually estimated maximum diameter stenosis ≥ 70% or positive coronary physiology testing)-either during the current emergency hospitalization or within 6 weeks after the culprit vessel PCI.

Recent clinical trials have proven the cardiovascular benefits of new medications for patients with heart failure with reduced ejection fraction (HFrEF), especially sodium-glucose co-transporter 2 (SGLT2) inhibitors. There are no existing randomized clinical trials evaluating the efficacy and safety of dapagliflozin (nor any other SGLT2-inhibitor) to limit cardiac remodeling in patients with acute myocardial infarction (AMI) and left ventricular (LV) dysfunction. Preventing cardiac remodeling, an established predictor of subsequent heart failure (HF) and cardiovascular death, is likely to translate into benefit in reducing clinical events in post-MI patients.

Coronary heart disease and its acute complication, myocardial infarction (MI), represent the leading causes of death in Europe and the United States. Although novel treatment strategies have helped to improve survival in patients with MI, a large proportion of patients develops heart failure and is at risk of life-threatening arrhythmias. Complications arising after MI constitute a severe burden not only for the patients themselves, but also for health care systems worldwide. The likelihood of these complications depends on the area of myocardial tissue lost and the process of myocardial repair and scar tissue formation after MI ('remodeling') which are modified by the local and systemic immune response after MI. The immune response is critical after myocardial infarction. In particular, sustained overactive and prolonged inflammatory reactions lead to accentuated myocardial damage and dysfunction. Important mediators of the inflammatory reaction after MI are monocytes, T-cells, B-cells and hematopoietic stem and progenitor cells. Following MI, myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. T- and B-cells in particular act in response to specific antigens. Most of the data regarding the inflammatory response after MI, however, are derived from animal models. The immunological phenotypes after MI and their association with clinical outcome in humans are insufficiently characterized. Aims: The aim of this project is to provide establish clinically and immunologically well-characterized cohort of patients after MI This will aid in identifying novel prognostic cellular and humoral biomarkers that may be used to identify patients at a high inflammatory and immune risk and to guide clinical management. Furthermore, these mediators, in the future, may be targeted by novel antigen-specific immunomodulatory approaches. Patients with myocardial infarction (STEMI and NSTEMI) will be recruited after PCI within 24h and receive a structured follow-up. Clinical read-outs include a detailed and standardized patient history, clinical examination, standard blood work, coronary angiography, ECG, echocardiography and for subgroups, MRI. Patients will present for study visits at 6 weeks, 3 months and 12 months after the initial event. Blood will be sampled at the inclusion and during follow-up visits. Peripheral blood mononuclear cells and plasma will be stored at the Cardiovascular BioBank (CVBB) and FREEZE, both institutions at the University Hospital in Freiburg. Major adverse cardiac events (myocardial infarction, stroke, hospitalization for heart failure, cardiovascular death) will be recorded using telephone interviews and standardized queries to the local authorities. Several laboratory read-outs are planned including flow cytometry, mass cytometry, single cell RNA sequencing, T cell and B cell receptor sequencing and bulk-RNA-sequencing. In an initial approach we aim to recruit 400 patients with MI, of which we expect ≈40 to develop ischemic cardiomyopathy. Differences in immunological profiles between patients that develop MI and a propensity-matched control group will then be analyzed and correlated with clinical outcome data.

The purpose of the OPTIMISER Registry is to prospectively and retrospectively collect baseline, clinical and procedural data in patients who present with AMI and are treated with PCI as well as prospectively collect the clinical outcome data. Outcomes will be compared in different clinical subgroups. The impact of PCI in AMI in general as well as cardiovascular outcomes after AMI will be assessed.