Clonal Hematopoiesis of Indeterminate Potential (CHIP) refers to the age-related expansion of hematopoietic stem cell clones carrying somatic mutations in leukemia-associated driver genes (e.g., DNMT3A, TET2, ASXL1) in the absence of a hematological malignancy. CHIP has been identified as an independent cardiovascular risk factor associated with increased rates of myocardial infarction, stroke, and cardiovascular mortality, likely mediated through enhanced inflammatory signaling in mutant macrophages and monocytes.
ST-elevation myocardial infarction (STEMI) is a life-threatening emergency requiring immediate reperfusion by primary percutaneous coronary intervention (PCI). Despite successful reperfusion, adverse cardiac remodeling and heart failure may occur depending on myocardial injury severity, microvascular obstruction (MVO), and intramyocardial hemorrhage (IMH) - phenomena substantially driven by ischemia-reperfusion injury and the inflammatory response.
The CHIP in STEMI study is a prospective, observational, single-center cohort study at the Medical University of Innsbruck investigating whether CHIP - detected by targeted next-generation sequencing - is associated with greater infarct severity and worse cardiac outcomes in STEMI patients undergoing primary PCI. The primary endpoint is the presence of MVO and/or IMH on cardiac MRI (CMR) at 5±2 days post-PCI. Secondary endpoints include infarct size, left and right ventricular function, major adverse cardiovascular events (MACE), and immune cell transcriptome profiling by single-cell RNA sequencing.
350 patients (18-75 years, minimum 90 female) will be enrolled over 36 months and followed for 4 years (2026-2030).
Diagnosis of first acute ST-elevation myocardial infarction according to current European Society of Cardiology guidelines
Symptoms consistent with ST-elevation myocardial infarction lasting more than 30 minutes and less than 12 hours before primary percutaneous coronary intervention
Treatment with primary percutaneous coronary intervention
Age 18 to 75 years
Prior myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention
Persistent hemodynamic instability, Killip class greater than 2 including cardiogenic shock, or resuscitated cardiac arrest not allowing cardiac magnetic resonance imaging
Known active or prior malignancy, including hematologic malignancies or myelodysplastic syndromes
Prior oncologic treatment with chemotherapy, radiotherapy, or radioisotopes
The study population will consist of adult female and male patients aged 18 to 75 years with a first acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention within 12 hours after symptom onset. Patients will be screened at the coronary care unit of the Medical University of Innsbruck. Eligible patients will be invited to participate after primary percutaneous coronary intervention and after assessment of inclusion and exclusion criteria. Standard clinical care and secondary prevention will be performed according to current guideline recommendations.
Cohort
Prospective
Clonal hematopoiesis assessment and cardiac magnetic resonance imaging
Diagnostic testParticipants will undergo blood sampling for assessment of clonal hematopoiesis of indeterminate potential by targeted next-generation sequencing and cardiac magnetic resonance imaging for assessment of myocardial injury, including microvascular obstruction, intramyocardial hemorrhage, infarct size, ventricular function, and myocardial tissue characteristics. Additional biomarker and inflammatory profiling will be performed according to the study protocol.
Occurrence of microvascular injury
Presence of microvascular injury, defined as microvascular obstruction and/or intramyocardial hemorrhage, assessed by cardiac magnetic resonance imaging in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. The outcome will be analyzed according to the presence or absence of clonal hematopoiesis of indeterminate potential.
Infarct size
Infarct size expressed as percentage of left ventricular myocardial mass, assessed by cardiac magnetic resonance imaging in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. The outcome will be analyzed according to the presence or absence of clonal hematopoiesis of indeterminate potential.
Left ventricular ejection fraction
Left ventricular ejection fraction assessed by cardiac magnetic resonance imaging in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.
All-cause mortality
eath from any cause after study inclusion.
Hospitalization for heart failure
Hospitalization due to new or worsening heart failure after study inclusion.
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