Identification of Genetic Determinants of the Coronary Microvascular Obstruction Development in Percutaneous Coronary Interventions
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Hospital Mortality Rate
研究概览
简要总结
Myocardial infarction (MI) remains one of the most common causes of death. Percutaneous coronary intervention (PCI) is the main treatment option to restore blood flow through the infarction-related coronary artery (IRA) in MI patients. Performing PCI significantly reduces mortality, but in 5-10% cases, PCI is complicated by the development of coronary microvascular obstruction (CMVO, "no-reflow"). CMVO is defined as the absence of adequate myocardial perfusion, despite the restoration of the IRA lumen. The development of CMVO significantly worsens the prognosis and increases mortality.
CMVO has a complex pathogenesis and is development due to following mechanisms: distal microembolism, ischemia-reperfusion injury, persistent endothelial dysfunction, and individual predisposition. These mechanisms can be implemented simultaneously and have different severity. The most significant predictors of CMVO occurrence are: age, time from pain onset to reperfusion, severity of acute heart failure, ineffective thrombolytic therapy, collateral blood flow according to the Rentrop classification, severity of IRA thrombosis according to Thrombolysis in Myocardial Infarction (TIMI) thrombus grade, initial IRA blood flow according to TIMI flow grade, implantation of 3 or more stents, direct IRA stenting, neutrophil and blood glucose levels.
Difficulties in CMVO predicting are caused by the pathogenetic heterogeneity of this complication. Even the best models are moderately accurate. This can be explained by the fact that the models don't use genetic factors that determine endothelial function, microcirculation, hemostasis, and inflammation. Identification of the genetic determinants of the CMVO development can help create a new diagnostic system for CMVO predicting.
详细描述
The aim of the study to identify the genetic determinants of the coronary microvascular obstruction development during percutaneous coronary interventions in myocardial infarction patients. The study investigates the role of some variants of single nucleotide polymorphism (SNP) as predictors of CMVO development. Selected SNPs that are associated with the mechanisms of CMVO development (according to literature). Hypothesis: selected SNPs are independent genetic predictors of the development of CMVO during PCI in MI patients.
Study design: matched case-control study. Sample size: 80 patients. Patients must have inclusion criteria, haven't exclusion criteria, and sign an informed consent. Division into 2 groups in the ratio 1:1. Group 1 (CMVO+): 40 patients with MI who were detected the CMVO after PCI. The second group (CMVO-, control): 40 patients with MI who weren't detected CMVO after PCI. Groups are matched by sex and age. The sample size (80 patients) was determined in accordance with the following parameters: alpha error - 5%, study power - 80%, group size ratio - 1:1, minimum odds ratio for detection - 4.0, prevalence SNP in the population - 12-69% (average 50%).
CMVO (no-reflow) is defined as inadequate myocardial perfusion after successful mechanical restoration of blood flow through the IRA (according to the 2017 European Society of Cardiology STEMI guidelines). CMVO criteria (there must be at least one criterion): 1) IRA blood flow is less than 3 points according to TIMI flow grade; 2) myocardial perfusion less than 2 points according to Myocardial blush grade (MBG). Other causes of IRA obstruction (spasm, dissection, thromboembolism) must be excluded.
Research stages: 1) assessment of inclusion / exclusion criteria; 2) signing informed consent; 3) taking blood for genetic analysis (performed in the operating room immediately after PCI); 4) processing of blood samples and their transportation to the laboratory; 5) filling out the patient's register card (contains information about the treatment and outcomes); 6) performing genetic analysis; 7) statistical processing of the obtained results.
The registration card is filled in at the end of hospitalization. Purpose: 1) comparison of SNP variants and outcomes; 2) multivariate analysis of SNP variants and other CMVO predictors. The card contains the following data: information about PCI, risk factors for the CMVO development, laboratory data (general blood count, biochemical blood test, etc.), examination data (ECG, ECG monitoring, echocardiography, six-minute walk test), information about complications and outcomes. These laboratory tests and instrumental studies are used in accordance with routine hospital protocols for the treatment of MI patients (the using is not associated with the investigation).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •informed consent to participate in the study;
- •male or female 18 years of age or older;
- •type 1 ST-segment elevation MI (according to the criteria of the fourth universal definition of myocardial infarction and current clinical guidelines);
- •blood sampling in the operating room (immediately after PCI) and signing the informed consent;
- •for the "CMVO+" group: CMVO because of PCI (CMVO is registered according to the criteria from the European Society of Cardiology clinical guidelines);
- •for the "CMVO-" group: absence of CMVO after PCI; patient should compliance by sex and age (±5 years) with pair in the "CMVO+" group.
排除标准
- •late admission (more than 48 hours from the onset of anginal pain) or early post-infarction angina pectoris;
- •not 1 type MI;
- •complications during PCI (dissection, perforation or acute intraoperative thrombosis of the IRA);
- •death during PCI, not due to the CMVO development;
- •concomitant terminal pathology (not associated with MI) with a life expectancy less than 1 month.
研究组 & 干预措施
"CMVO+" (patients has presented CMVO in PCI)
Patients with 1 type MI that has presented CMVO in emergency PCI.
干预措施: different variants of SNPs that may be associated with the coronary microvascular obstruction development (Genetic)
"CMVO-" (patients hasn't presented CMVO in PCI)
Patients with 1 type MI that hasn't presented CMVO in emergency PCI.
干预措施: different variants of SNPs that may be associated with the coronary microvascular obstruction development (Genetic)
结局指标
主要结局
Hospital Mortality Rate
时间窗: up to 7-15 days after PCI
Death during index hospitalization.
次要结局
- Six-minute Walk Test(7-10 day after PCI)
- N-terminal Pro-brain Natriuretic Peptide(7-10 day after PCI)
- Ventricular Fibrillation(up to 7-15 days after PCI)
- Left Ventricle Ejection Fraction(7-10 day after PCI)