Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction

NCT07615023 | Not Yet Recruiting

• 2 other identifiers: 1195/2024KLP1365525
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

ST-elevation Myocardial Infarction (STEMI); Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Keywords

CHIP; STEMI; cardiac MRI; microvascular obstruction

Outcome Measures

Primary Outcomes (1)

• 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.

  5 ± 2 days after primary percutaneous coronary intervention

Secondary Outcomes (4)

• Infarct size

  5 ± 2 days after primary percutaneous coronary intervention

• Left ventricular ejection fraction

  5 ± 2 days, 4 months, and 12 months after primary percutaneous coronary intervention

• All-cause mortality

  Within 12 months after study inclusion.

• Hospitalization for heart failure

  Within 12 months after study inclusion.

Study Arms (1)

STEMI Patients

Patients presenting with ST-elevation myocardial infarction (STEMI) who undergo successful primary percutaneous coronary intervention (PCI). All consecutive eligible patients are enrolled regardless of CHIP mutation status. This single cohort is analyzed based on CHIP presence/absence and specific CHIP mutation type (e.g., DNMT3A, TET2, ASXL1).

Diagnostic Test: Clonal hematopoiesis assessment and cardiac magnetic resonance imaging

Interventions

Clonal hematopoiesis assessment and cardiac magnetic resonance imaging DIAGNOSTIC_TEST

Participants 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.

STEMI Patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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
• Written informed consent

You may not qualify if:

• 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
• Abnormal baseline complete blood count with clinically significant cytopenia, defined as leukocytes less than 3.0 x 10\^9/L, platelets less than 100 x 10\^9/L, or hemoglobin less than 10 g/dL
• Chronic viral infection associated with systemic inflammation
• Active autoimmune disease or chronic systemic inflammatory disorder
• Chronic kidney disease with creatinine clearance less than 30 mL/min/1.73 m2
• Contraindication to cardiac magnetic resonance imaging
• Pre-ST-elevation myocardial infarction life expectancy of less than 1 year
• Participation in an interventional trial
• Limited possibility to attend follow-up examinations, for example residence abroad
• Pregnancy

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples for targeted next-generation sequencing (CHIP mutation detection, VAF ≥2%), single-cell RNA sequencing of PBMCs, and biomarker analysis (hsCRP, IL-6, IL-18, NT-proBNP, troponin T). DNA extracted from peripheral blood leukocytes.

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Ivan Lechner, MD, PhD

CONTACT

+43 512 504 83772; ivan.lechner@tirol-kliniken.at

Sebastian J Reinstadler, MD, PhD

CONTACT

+43 512 504 83772

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: May 29, 2026
• Study Start: June 20, 2026
• Primary Completion (Estimated): June 20, 2029
• Study Completion (Estimated): June 20, 2030
• Last Updated: May 29, 2026

Record last verified: 2026-05

Locations

AU (1)