Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction (CHIP in STEMI)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: ST-elevation Myocardial Infarction (STEMI); Clonal Hematopoiesis of Indeterminate Potential (CHIP)
• Intervention / Treatment: Diagnostic test: Clonal hematopoiesis assessment and cardiac magnetic resonance imaging

Detailed Description

Background and Rationale:

CHIP mutations - particularly in TET2 and DNMT3A - promote a pro-inflammatory state in hematopoietic cells. Preclinical data demonstrate that TET2-deficient macrophages exhibit exaggerated NLRP3 inflammasome activation and IL-1β secretion, while DNMT3A mutations impair immune resolution after myocardial ischemia. This enhanced inflammatory signaling may worsen myocardial ischemia-reperfusion injury (IRI), thereby increasing MVO, IMH, and infarct size in CHIP carriers presenting with STEMI.

Study Design:

Prospective, observational, single-center cohort study. No intervention beyond standard of care.

Study Population:

350 patients aged 18-75 years with STEMI undergoing primary PCI at the University Clinic of Internal Medicine III - Cardiology and Angiology, Medical University of Innsbruck. A minimum of 90 female participants will be enrolled.

Key Inclusion Criteria:

• Age 18-75 years
• STEMI with symptom onset ≤12 hours before PCI
• Successful primary PCI of culprit lesion
• Written informed consent

Key Exclusion Criteria:

• Prior myocardial infarction or known cardiomyopathy
• Known hematological malignancy
• Contraindication to CMR (pacemaker, severe claustrophobia, eGFR <30 mL/min/1.73m²)
• Cardiogenic shock requiring mechanical circulatory support
• Life expectancy <12 months due to non-cardiac cause
• Pregnancy

Assessments:

1. Cardiac MRI (CMR) at 5±2 days post-PCI: MVO, IMH, infarct size (%LVMM), LV/RV ejection fraction, volumes, mass
2. Targeted next-generation sequencing (NGS) for CHIP mutations (VAF ≥2%): DNMT3A, TET2, ASXL1, and other driver genes
3. Single-cell RNA sequencing (scRNA-seq) of PBMCs at baseline and 12-month follow-up
4. Serial blood biomarkers: hsCRP, IL-6, IL-18, NT-proBNP, troponin T, complete blood count
5. Clinical follow-up visits at 12, 24, and 48 months

Primary Endpoint:

Presence of microvascular obstruction (MVO) and/or intramyocardial hemorrhage (IMH) on CMR at 5±2 days post-PCI in CHIP carriers versus non-carriers.

Secondary Endpoints:

• Infarct size (% left ventricular myocardial mass, %LVMM)
• LV and RV ejection fraction, end-diastolic/systolic volumes, myocardial mass
• MACE: all-cause mortality, non-fatal reinfarction, hospitalization for heart failure at 12, 24, and 48 months
• Changes in CHIP mutation variant allele frequency (VAF) over time
• Differential gene expression in immune cell subsets by scRNA-seq
• Biomarker trajectories (NT-proBNP, hsCRP, IL-6)

Ethics and Regulatory:

The study protocol has been approved by the Research Ethics Committee of the Medical University of Innsbruck and is conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines. All participants provide written informed consent prior to study inclusion. The study is funded by the KLiF (Klinisch-Interne Forschung) program of the Medical University of Innsbruck.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Ivan Lechner, MD, PhD; Phone Number: +43 512 504 83772; Email: ivan.lechner@tirol-kliniken.at
• Study Contact Backup: Name: Sebastian J Reinstadler, MD, PhD; Phone Number: +43 512 504 83772

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University of Innsbruck
      • Contact: Ivan Lechner, MD, PhD; Phone Number: +43 512 504 83772; Email: ivan.lechner@tirol-kliniken.at
      • Contact: Sebastian J Reinstadler, MD, PhD; Phone Number: +43 512 504 83772

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 ± 2 days after primary percutaneous coronary intervention
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.	5 ± 2 days, 4 months, and 12 months after primary percutaneous coronary intervention
All-cause mortality	eath from any cause after study inclusion.	Within 12 months after study inclusion.
Hospitalization for heart failure	Hospitalization due to new or worsening heart failure after study inclusion.	Within 12 months after study inclusion.

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 20, 2029
• Study Completion (Estimated): June 20, 2030

Study Registration Dates

• First Submitted: May 22, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: STEMI; cardiac MRI; microvascular obstruction; CHIP
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction
• Other Study ID Numbers: 1195/2024; KLP1365525 (Other Grant/Funding Number: Austrian Science Fund)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No