Clinical Research Directory

Breisgau PHENO-HEART MI

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.

Prediction of Adverse Events From Non-PCI Coronary Plaques Using Machine Learning

The aim of our project is to predict, with the help of artificial intelligence (AI) and machine learning techniques, the natural history of non-flow-limiting coronary stenoses and to develop and validate a machine learning risk score able to estimate the risk of MACE during follow-up based on OCT findings observed on coronary plaques not subjected to percutaneous coronary intervention (PCI) and on the clinical characteristics of the patients. We will collect information on all non-PCI coronary lesions assessed by performing OCT in non-culprit vessels of patients presenting with ACS or Chronic Coronary Syndrome (CCS) at the index procedure. All OCT runs will be digitized and analyzed with the help of AI. The OCT appearance of coronary plaques will be analyzed with AI and correlated with the risk of MACE during follow-up (a composite of cardiac death, myocardial infarction, or target lesion revascularization). An AI predictive risk model based on coronary plaque OCT images and patient clinical characteristics will be developed to estimate the risk of MACE incidence at follow-up. Cutting-edge machine learning algorithms, including convolutional neural networks, random forests, and support vector machines, will be used.

Insulin Resistance and Its Association With no Reflow Phenomenon After Primary PCI in Type II Diabetic STEMI Patients.

To investigate the relationship between the TyG index, coronary lesion complexity assessed by the SYNTAX score, and the development of the no-reflow phenomenon in STEMI patients with T2DM.

Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome

This is a prospective, open-label, multicenter, randomized, phase IV clinical trial designed to evaluate the safety and efficacy of early aspirin discontinuation followed by potent P2Y12 inhibitor monotherapy after intravascular ultrasound (IVUS)-guided drug-eluting stent implantation in patients with acute coronary syndrome. A total of 1,900 patients who achieve complete revascularization after IVUS-guided percutaneous coronary intervention (PCI) and meet the predefined successful IVUS-guided PCI criteria will be randomized in a 1:1 ratio to either the early single antiplatelet therapy group (Early SAPT: ticagrelor or prasugrel monotherapy) or the standard dual antiplatelet therapy group (Standard DAPT: aspirin plus ticagrelor or prasugrel). Randomization will be performed within 96 hours after completion of PCI, and clinical follow-up will be conducted at 1 month, 3 months, 6 months, and 12 months after randomization. The primary endpoints are major adverse cardiovascular events, defined as a composite of all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis occurring up to 12 months after randomization, and clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding occurring up to 12 months after randomization. This study aims to determine whether early P2Y12 inhibitor monotherapy is non-inferior to standard dual antiplatelet therapy (DAPT) for ischemic events and is superior in reducing clinically relevant bleeding.

Intramyocardial Haemorrhage in Patients With Primary STEMI

The purpose of the study is to assess the frequency and intensity of intramyocardial haemorrhage in patients with primary STEMI and different reperfusion strategies.

Intravascular Ultrasound guidaNce versuS angIoGrapHy Guidance in Patients With ST-segment Elevation Myocardial Infarction

STEMI represents the subtype of ACS with the worst prognosis, associated with high mortality and an elevated risk of complications. The use of IVI guidance holds the potential to reduce the incidence of MACE. In previous studies, there has been limited research on intravascular imaging in the context of primary revascularization procedures for STEMI, and no large-scale cohort study has compared the differences in clinical outcomes between IVI-guided and angiography-guided primary revascularization. Therefore, we conducted this large-scale randomized controlled trial to compare IVI-guided primary PCI versus coronary angiography-guided primary PCI in patients with STEMI.

Effect of Guanxinning Tablet on Coronary Microcirculation After Primary Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction

①Research objective: In a small sample population, through the pre - experimental method, explore and evaluate the effect of Guanxinning tablets on the coronary microcirculation after primary percutaneous coronary intervention (PPCI) in patients with acute ST - segment elevation myocardial infarction (STEMI), with the change in the percentage of intramyocardial hemorrhage (IMH) in ventricular mass measured by cardiac magnetic resonance (CMR) imaging as the primary endpoint. ②Research significance: The research results of this project will provide preliminary theoretical basis and methodological support for the formal randomized controlled study on evaluating the effect of Guanxinning tablets on the coronary microcirculation after PPCI in STEMI patients. It will offer new ideas for the long - term clinical treatment of STEMI patients after PPCI, and provide important theoretical support for expanding the clinical indications of Guanxinning tablets and exploring the reasons for its improvement of cardiovascular outcomes.

Delivery SSO2 Therapy for 60 Min in Anterior MI Patients With PCI ≤ 6 Hours of Symptoms Onset Compared to Standard.

A multi-center randomized post-approval evaluation of delivery of intracoronary hyperoxemic supersaturated Oxygen therapy for 60 minutes in anterior AMI patients with successful reperfusion (via PCI) within 6 hours after onset of symptoms compared to standard therapy

Intraoperative Echocardiography in Low-Risk CABG Surgery

This goal of this study is to better understand when and where intraoperative transesophageal echocardiography (TEE) should (or should not) be used during coronary artery bypass graft (CABG) surgeries.

Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia

ACCURATE will test the hypothesis that opportunistic genetic testing for Familial Hypercholesterolemia (FH) in patients admitted to hospital with an acute coronary syndrome will increase the diagnosis of FH and will impact patient care and outcomes. The study will recruit patients admitted to hospital with an acute coronary syndrome, and research-based genetic testing will be conducted for known FH-causing genetic variants. The results will be returned to the patients' treating physicians. The primary endpoint will be the number of patients with a new diagnosis of definite FH. The secondary endpoints will be the proportion of patients who undergo intensification of lipid-lowering therapy, the lowest LDL cholesterol level achieved, and the proportion of patients reaching guideline recommended lipid targets in the 15 months after the index acute coronary syndrome.

Analysis of the Microbiota and STEMI

Hyperglycemia is a common finding in patients diagnosed with acute coronary syndrome (ACS), and an independent predictor of mortality in patients with and without diabetes. Though percutaneous coronary intervention (PCI) is the cornerstone of ST-segment elevation myocardial infarction (STEMI), the incidence of heart failure, re-infarction and death in hyperglycemic patients remains significant, with a mortality of more than 40% one year after the event. In these STEMI patients dual anti-aggregation therapy is currently the gold standard after PCI, but bleeding phenomena, and therapeutic resistance may reduce their therapeutic efficacy. Therefore, it is likely that the individual response to the dual anti-aggregation therapy, and the hyperglycemic stress, may influence resistance mechanisms, and/or lead to an increase in pharmacological functional deactivation by the microbiotic flora. The term microbiota indicates the totality of the genomes of microorganisms that reside in an ecological niche, and which constitute the "human microbiota". In this context, the analysis of the faecal microbiota before PCI, at hospital discharge and at follow-up, could be considered useful for identifying hyperglycaemic patients with alteration of metabolic-oxidative processes, and pro-thrombotic correlates with worse post procedural prognosis. Therefore, the analysis of faecal microbiota during the STEMI event could theoretically identify hyperglycemic patients with excessive inflammatory and oxidative tone caused by hyperglycemia, conditioning resistance to double anti-aggregation therapy and coronary stenting, and conditioning pro-thrombotic phenomena after coronary reperfusion by PCI. Therefore, authors will conduct a study to analyze the microbiota in patients with acute hyperglycaemic and normoglycemic coronary syndrome. The primary objective of this study will be to evaluate any changes in the microbiota and its activity on faecal material taken before PCI, and after 6 and 12 months in patients with hyperglycemic STEMI, and also evaluate if the changes in the microbiota can be related to the 12-month prognosis.

Can Escalation Reduce Acute Myocardial Infarction Mortality in Cardiogenic Shock

The CERAMICS study is designed to more clearly delineate the current care of acute myocardial infarction with cardiogenic shock (AMICS) patients who are treated with mechanical circulatory support (MCS) devices in the United States with significant experience in MCS, all of whom have the capability of MCS escalation on-site. Study enrollment is targeted at 120 patients at 20 hospital sites, evaluating clinical outcomes, and focusing on outcomes MCS escalation decision making and ICU level management.

Empagliflozin for No-reflow Phenomenon in PCI for STEMI

Myocardial infarction remains, in our current era, a leading cause of morbidity and mortality both domestically and globally. A significant contributor to this issue is reperfusion injury, which enlarges the infarction, deteriorates ventricular function, leads to poorer outcomes, and currently has no specific treatment. Originally developed as an antidiabetic, empagliflozin has shown significant benefits in other organs and systems. Recent years have seen the demonstration of its cellular and vascular effects in animal models, potentially contributing to the reduction of reperfusion damage. However, no human studies have yet confirmed these effects. Consequently, this randomized, parallel-arm clinical trial was designed to evaluate the effect of empagliflozin treatment, administered from the pre-intervention period through to 3 days post-intervention, on the incidence of the no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) undergoing coronary angioplasty compared to a placebo. Before entering the hemodynamics room, participants in the intervention group will receive a loading dose of 25 mg of empagliflozin or a standar treatment. In-hospital treatment will continue with 10 mg empagliflozin daily for 3 days for the intervention group. Patients will be monitored weekly during the first month and bi-weekly during the second and third months. The primary outcome will be the incidence of the no-reflow phenomenon, measured through the Thrombolysis in Myocardial infarction (TIMI) flow scale in the coronary angiography performed to treat the infarction. Secondary outcomes will include the reduction of ST segment on the electrocardiogram, troponin levels, differences in the longitudinal strain by echocardiogram, and infarct size by magnetic resonance imaging.

Pilot Study of IC14 (Atibuclimab), an Anti-CD14 Monoclonal Antibody, to Treat STEMI

Adults who have had an ST-elevation myocardial infarction and were treated with stent placement will receive an intravenous infusion of a monoclonal antibody in order to prevent further heart muscle damage. The goal is to learn if this treatment improves some measures of heart function and inflammation. The study treatment patients will be compared to patients who receive placebo (inactive treatment).

AI-Powered ECG Detecting Culprit Vessel Blood Flow Abnormality in ACS

AI ECG TIMI is an investigator-initiated, international, and multicenter registry of acute coronary syndrome patients aimed to identify electrocardiographic findings detected by an AI model predicting coronary blood flow alteration. The aim of the study is to identify electrocardiographic findings detected by an automated artificial intelligence (AI) model that can predict coronary blood flow alteration as assessed by the TIMI grade flow at the very moment of the invasive coronary angiography in patients with acute coronary syndromes.

Drug-Coated Balloon Primary PCI in ST-Segment Elevation Myocardial Infarction

Drug-eluting stent (DES)-based primary percutaneous intervention (pPCI) has been established as the standard of care for patients presenting with ST-segment elevation myocardial infarction (STEMI), having demonstrated superiority over thrombolysis, plain balloon angioplasty, and bare-metal stents. Recently, the use of drug-coated balloons (DCB) has expanded dramatically across a variety of anatomical and clinical settings, including de novo coronary lesions. A DCB-based pPCI strategy may simplify the procedure and mitigate the risks of inadequate stent sizing due to spasm or large thrombus burden, acute stent thrombosis, distal embolization, no reflow, and the relatively higher incidence of late stent-related adverse events compared with elective PCI. Despite these theoretical advantages, data on the safety and efficacy of DCB-based pPCI in STEMI remains limited. The aim of this registry is to explore procedural and clinical outcomes of patients with STEMI treated with a DCB-based pPCI strategy.

Anticoagulation Therapy in Non-device-related Intra-cardiac Thrombus

Left ventricular thrombus is found in 10 to 25% of patients with impaired left ventricular function following ST-segment elevation myocardial infarction and up to 20% in dilated cardiomyopathy in observational studies. Likewise, the incidence of atrial thrombus among atrial fibrillation patients treated by vitamin K antagonist (VKA) is between 0.25% and 7%. Despite anticoagulant therapy, intra-cardiac thrombus remains a severe complication associated with a high risk of systemic embolism and subsequent mortality but also bleeding events related to the anticoagulation therapy. The class of non-vitamin K antagonist direct oral anticoagulant (DOA) has emerged in the last decades and has systematically surpassed VKA in the different clinical settings by providing at minimum a similar efficacy and a better safety profile. In the absence of randomized study in the specific clinical setting of intracardiac thrombus, international Guidelines recommend, on the basis of expert opinion, the use of VKA for at least 3 to 6 months in case of left ventricular thrombus and there is no specific recommendation for thrombus management from other cardiac localizations. In comparison to VKA, the easier management and the large evidence of better safety of DOA make it an interesting anticoagulant strategy. Data for left ventricule thrombosis treatment are limited and only supported by observational cohorts. However, these recent cohorts have shown promising data in this indication reporting similar thrombus regression following DOA in comparison to VKA and similar ischemic outcomes although no head-to-head comparison would be powered. As a consequence, the multicentric randomized ARGONAUT trial aims to confirm these results and evaluate the impact of DOA compared to VKA on thrombus regression and clinical outcomes among patients with intracardiac thrombus, regardless of the thrombus localization and any underlying heart disease.

The Coronary Sinus Balloon Pump in STEMI

This study is a prospective, multicenter, randomized controlled clinical trial designed to evaluate the safety and efficacy of the coronary sinus balloon pump (manufactured by Shanghai MicroPort Rotapace Medical Technology Co., Ltd.) as an adjunctive therapy during percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). As a pivotal study, it aims to support the product registration application to the National Medical Products Administration (NMPA).

DAPAgliflozine to Attenuate Cardiac RemOdeling afTEr aCuTe myOcardial Infarction

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.

Impact of Cardio-Selective Beta-Blockers on Infarct Size After Acute Myocardial Infarction

Introduction: The effect of intravenous beta-blockers on the extent of the necrotic area, after primary percutaneous transluminal coronary angioplasty (PTCA), for acute myocardial infarction is not well established. Purpose: The present study aims to investigate, whether the early intravenous administration of landiolol, a highly cardioselective b-blocker, reduces the extent of the necrotic area after ST-elevation myocardial infarction (STEMI). Methods: This prospective observational cohort study will enroll patients presenting with STEMI, who undergo primary PCI and receive either intravenous landiolol or standard oral β-blocker therapy, in accordance with current European Society of Cardiology (ESC) guidelines. Eligibility will be determined by predefined inclusion and exclusion criteria. Treatment selection will be based solely on the clinical judgment of the attending cardiologist, without randomization. Results: Final infarct size will be quantified by cardiac magnetic resonance imaging (CMR) performed at least three months after the STEMI to minimize edema-related overestimation. Myocardial function will be assessed during hospitalization using transthoracic echocardiography, including measurement of global longitudinal strain (GLS). Additional data will include serial high-sensitivity troponin and creatine phosphokinase (CPK) measurements, 24-hour continuous electrocardiographic monitoring for arrhythmia burden, and predefined safety outcomes collected throughout hospitalization.

TIRANA-ACS: A Prospective Registry Study for the Targeted Investigation of Residual Inflammation After Non-ST/ ST Elevation Acute Coronary Syndrome

This prospective observational study aims to evaluate the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) as a predictor of mortality in patients following an episode of Acute Coronary Syndrome (ACS). Despite advancements in interventional cardiology and medical therapy, mortality remains significant in post-ACS patients, and early risk stratification is essential for optimizing outcomes. Recent studies have suggested that systemic inflammatory markers, such as NLR, are associated with adverse cardiovascular events. It is an easily obtainable and cost-effective laboratory parameter derived from a routine complete blood count. However, its value as an independent predictor of mortality post-ACS has not yet been fully established in our population. The study will include patients aged, admitted with a confirmed diagnosis of ACS (STEMI or Non-STEMI) and treated with percutaneous coronary intervention (PCI). NLR values will be measured from the first blood draw upon hospital admission, 24 and 48 hours post PCI. Patients will be followed up for up to 6 months after discharge through telephone interviews . First, primary outcomes of the study will be the association between NLR values and mortality (all cause mortality and cardiovascular mortality), MACE (MACE was defined as the composite of all-cause mortality, cardiac death, unplanned revascularization, non-fatal myocardial infarction that was attributable and not related to stent failure or unplanned revascularization not related to stent failure) within 6 months post-ACS. Secondary outcomes will include: 1. Differences in mean NLR between STEMI and NSTEMI patients. 2. Association between elevated NLR and the presence of multivessel coronary artery disease on angiography. 3. Correlation of NLR with other biomarkers, including the platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol, and maximum troponin levels (as an indicator of myocardial infarction size) This study aims to contribute to the identification of easily accessible and cost-efficient biomarkers that can aid clinicians in early risk stratification of ACS survivors. A strong correlation between high NLR values and increased post-discharge mortality would suggest that inflammation plays a key role in patient prognosis and could potentially influence post-ACS management strategies.

Inflammatory and Hematological Indices in Diabetic STEMI Patients Undergoing Primary PCI

ST-segment Elevation Myocardial Infarction (STEMI) remains a major cause of mortality despite the adoption of Primary Percutaneous Coronary Intervention (PPCI) as the standard treatment. However, outcomes still vary significantly among patients, especially between diabetic and non-diabetic cohorts. The research question driving this study is: Can hematologic, inflammatory, and thrombotic indices serve as reliable prognostic tools in predicting the no-reflow phenomenon and coronary artery disease (CAD) severity in STEMI patients, particularly among those with diabetes mellitus? Recent literature identifies inflammation as a key contributor to the pathogenesis and outcomes of Acute Coronary Syndrome (ACS), including the no-reflow phenomenon and Major Adverse Cardiovascular Events (MACE). Markers such as C-reactive protein (CRP), Neutrophil-to-Albumin Ratio (NAR), Red Cell Distribution Width (RDW), Platelet Distribution Width (PDW), Hemoglobin-to-Red Cell Distribution Width ratio (Hb/RDW), and the RDW/PDW ratio have shown individual correlations with poor outcomes. Emerging indices such as the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammatory Response Index (SIRI) further integrate immune and inflammatory components and have shown promise in early risk stratification. The current strategy in many cardiac centers relies on angiographic and clinical indicators, which may be insufficient for individualized risk prediction. Hence, incorporating accessible and cost-effective blood-based markers could significantly enhance prognostic accuracy. The rationale of this research lies in comparing these indices in diabetic versus non-diabetic STEMI patients, aiming to stratify risk, predict no-reflow, assess coronary artery disease burden using the SYNTAX score, and identify those at risk for early adverse outcomes.

The First-In-Man Use of Coronary Sinus Balloon Pump in STEMI Patients Treated by Primary PCI

This is a prospective, multicenter clinical investigation aiming to evaluate the safety and efficacy of the coronary sinus balloon pump in its first application in patients with acute ST-segment elevation myocardial infarction (STEMI).

ReModeling in ST-elevation myocARrdial Infarction: a Comparison of Left VEntricuLar Functions in Long-term Follow-up Among STEMI Patients

Patients diagnosed with STEMI who underwent pPCI were included in this study. The investigators collected comprehensive data on each patient's status, including laboratory findings such as NT-proBNP, troponin levels, and inflammatory profile assessed by leukocyte count, C-reactive protein, interleukin-1, and interleukin-6. Additionally, electrocardiographic and echocardiographic features, details of the coronary intervention procedure, hospital stay duration, complications, and medical treatments were recorded. Comprehensive transthoracic echocardiograms (TTE) were performed at admission and before discharge. Myocardial tissue characterization was conducted by cardiac magnetic resonance (CMR) imaging before discharge, assessing intramyocardial hemorrhage (IMH), microvascular obstruction (MVO), infarct size (IS), area at risk (AAR), salvaged myocardium, and salvage index. At the six-month follow-up, laboratory tests, CMR imaging, and TTE were repeated, along with a thorough clinical evaluation. LVR was defined by one of the following criteria: a 20% increase in end-diastolic volume by TTE or 12% by CMR, a 15% increase in end-systolic volume, a sphericity index greater than 42% (CMR only), the emergence of new concentric hypertrophy, or a reduction greater than 10% in left ventricular ejection fraction (LVEF).