Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 350
- 试验地点
- 1
研究概览
简要总结
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).
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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