This topic is researched for two goals: Examine clinical and laboratory characteristics, coronary artery injury, coronary artery intervention in patients with acute ST-elevation myocardial infarction who receive PPCI association with TA. Assess the results, safety and the relationship between clinical, laboratory characteristics and major cardiovascular events within 12 months in patients with acute ST-elevation myocardial infarction who receive PPCI association with TA.
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE CLINICAL RESEARCH INSTITUTE OF MEDICINE AND PHARMACY SCIENCE 108 LÊ CAO PHƯƠNG DUY THE RESULTS OF PRIMARY PERCUTANEOUS CORONARY INTERVENTION ASSOCIATION WITH THROMBUS ASPIRATION ON PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION Major: Cardiovascular Internal Medicine ID: 62720141 SUMMARY OF THE DISSERTATION OF DOCTOR OF PHILOSOPHY IN MEDICINE Hà Nội - 2019 The research is completed at: CLINICAL RESEARCH INSTITUTE OF MEDICINE AND PHARMACY SCIENCE 108 Science advisors: Prof PhD Nguyễn Quang Tuấn Assoc Prof PhD Phạm Thái Giang Reviewers: This thesis will be defended at the meeting of the Dissertation Review Committee at: Clinical Research Institute of Medicine and Pharmacy science 108 At The thesis can be accessed at: National Library of Vietnam Library of Clinical Medicine Research Institute 108 LIST OF RESEARCH WORKS RELATED TO THE THESIS Lê Cao Phương Duy, Phạm Thái Giang (2018), "The early effect of thrombus aspiration during primary percutaneous coronary intervention on patients with acute ST-elevation myocardial infarction", Journal of Clinical Medicine and Pharmacy 108, (13), p 57-65 Lê Cao Phương Duy, Phạm Thái Giang (2018), "Results of primary percutaneous coronary intervention on patients with acute ST-elevation myocardial infarction at Nguyen Tri Phuong Hospital", Journal of Clinical Medicine and Pharmacy 108, (13), p 183-188 INTRODUCTION Coronary heart disease is the most common cause of morbidity and mortality alongside with heavy burden on treatment cost in developed countries, and is growing rapidly in developing countries Acute myocardial infarction is the necrosis on an area of the cardiac muscle, result of myocardial ischemia, which is a very common clinical emergency Several clinical trials have demonstrated that urgent recovery of the flow of narrowed or blocked coronary arteries is a major determinant for short-term as well as long-term survival Many studies have shown the efficacy and benefits of early percutaneous coronary intervention (PCI) as well as the subsequent combination of fibrinolytic agents (FA) and PCI in patients with acute ST-elevation myocardial infarction based on some criteria such as overall mortality, secondary MI and stroke However, in primary percutaneous coronary intervention (PPCI), microvascular embolism due to atherosclerotic fragments from culprit lesion on distal blood vessels occurs in most patients Blockage of these blood vessels causes blockage in the microcirculation and can lead to suboptimal reperfusion in different areas of the heart muscle Thrombosis in the coronary artery is an important step to re-circulate clogged coronary arteries, improve microcirculation and myocardial perfusion Some studies have shown that TA prior to stent insertion in PCI in patients with acute ST-elevation myocardial infarction can improve several events such as all-cause mortality, cardiovascular death, non-fatal MI at one year, and two years; improve myocardial perfusion and mortality during the procedure; improve microvascular perfusion, improve left ventricular remodeling and reduce infarct size at 90 days and months However, data on the role of cardiomyopathy in PCI is currently not consistent on patients with acute ST-elevation myocardial infarction In Vietnam, there are not many studies on this issue To contribute in improving the quality of diagnosis and treatment of cardiovascular disease in general and MI patients in specific, we conducted the study: “The results of primary percutaneous coronary intervention association with thrombus aspiration on patients with acute STelevation myocardial infarction” with objectives: Examine clinical and laboratory characteristics, coronary artery injury, coronary artery intervention in patients with acute ST-elevation myocardial infarction who receive PPCI association with TA Assess the results, safety and the relationship between clinical, laboratory characteristics and major cardiovascular events within 12 months in patients with acute ST-elevation myocardial infarction who receive PPCI association with TA New contributions of the thesis: Clinical, laboratory, coronary injury and intervention characteristics in patients with acute ST-elevation myocardial infarction who receive PPCI association with TA PPCI association with TA in patients with acute ST-elevation myocardial infarction showed effectiveness on myocardial reperfusion criteria but has not shown short-term effectiveness (within 12 months) based on major cardiovascular events It is not recommended to systematically TA during PPCI, the intervention should based on specific clinical situation Dissertation layout: The thesis consists of 132 pages Introduction (2 pages), Conclusions (2 pages), Recommendations (1 page) The thesis has chapters including: Chapter 1: Literature review of 37 pages; Chapter 2: Materials and Methods of 24 pages; Chapter 3: Results of 29 pages; Chapter 4: Discussion of 37 pages The thesis consists of 50 tables, charts, 10 pictures, and 120 references (Vietnamese: 13; English: 107) Chapter LITERATURE REVIEW 1.1 Outline of acute coronary syndrome (ACS) and acute STelevation myocardial infarction (STEMI) ACS is a term refer to symptoms associated with acute ischemic heart disease, often due to a sudden reduction in coronary artery blood flow (coronary artery) STEMI is a clinical syndrome defined by specific symptoms of ischemia accompanied by changes of ST elevation could be observed on electrocardiogram and a significant increase of several biomarkers due to myocardial necrosis afterward Diagnosis of ST elevation in the absence of left ventricular hypertrophy and associated left bundle branch block were agreed by the ESC, ACCF, AHA and World Heart Federation, and were considered as global consensus in diagnosis of acute MI ST elevation can be summarized as follows: ST elevation: ST elevation ≥ mm in men or 1.5 mm in women on V2 V3 leads and/or ≥ mm in other chest leads and limb leads New occurrence of left bundle branch block or considered as new is equal to ST elevation ST depression of ≥ mm in V1-V4: posterior myocardial infarction ST depression in multiple leads alongside with ST elevation in aVR: occlusion of the left coronary artery or the proximal ventricular branch ST elevation in V3R - V5R: Right ventricular infarction 1.2 Treatment of STEMI 1.2.1 Internal medical treatment Medicine have been proven effective in many studies including: heparin, dual antiplatelet therapy, statins, beta blockers, angiotensinconverting enzyme inhibitors or receptor inhibitors 1.2.2 Reperfusion strategies * Fibrinolytic agents (FA): is prescribed when the time from the first medical exposure to possible coronary intervention is more than 120 minutes FA should be used as soon as possible with the golden time of less than 12 hours * Primary percutaneous coronary intervention (PPCI): PPCI is preferred over FA when the delay in treatment is short, large hospital, adequate equipment, a team of experienced doctors and staffs The indication of PPCI is based on the guideline from ACCF / AHA 2013: including all patients diagnosed with STEMI within 12 hours of onset of chest pain, or after 12 hours if there are still symptoms of myocardial ischemia (much elevated chest pain and / or ST elevation on diabetes), or clinical cardiogenic shock * Coronary artery bypass grafting (CABG): CABG used to be one of the main treatments of coronary artery disease Today, this technique is gradually replaced by FA and PCI treatment Emergency CABG in STEMI is indicated in the following cases: - Mechanical complications (perforation of ventricular septal wall, muscle breakage ) - Coronary anatomy is not suitable for PPCI 1.2.3 Thrombus aspiration (TA) technique in PPCI on STEMI patients Theoretical basis of TA in PPCI PPCI has been shown to be highly effective in the treatment of STEMI However, the problem is that normal PCI with balloons and stents can lead to rupture of a blood clot or atheroma, forming debris, drifting to distal coronary vessels, causing distal embolism and reduces myocardial perfusion of these parts Distal embolization in coronary artery contributes significantly to vascular dysfunction and the phenomenon of "no-reflow" flow Therefore, in addition to pharmacological treatment and direct stent placement, some TA devices have been developed to reduce thrombotic burden, reduce distal thromboembolism, improve myocardial perfusion, and have the potential to improve clinical outcomes Assign TA in the PPCI In current clinical practice, TA is indicated after assessing coronary artery flow and thrombotic morphology After passing the guidewire through the lesion, the surgeon will take a coronarography before deciding whether or not to have a TA If the coronary arterial flow has TIMI of or 1, the surgeon will perform TA with a catheter If the coronary arterial flow has TIMI of or 3, the surgeon will conduct TA when the thrombotic state is G4 grade Evaluate the TA results TA is rated as successful when: The thrombus pumped into the filter could be seen The flow after suction improves TIMI degrees, allowing a clear determination of atherosclerotic lesions and distal segments of coronary arteries 1.3 Current research related to the thesis topic Many studies assessing the effectiveness of TA during PPCI have been published in peer reviewed journals, but the results were not consistent Three large and scientifically valuable studies on this issue are: TAPAS (Tone Svilaas et al.), TASTE (Frobert O et al.) and TOTAL (Jolly SS et al.) The TAPAS study showed that TA improved myocardial perfusion, improved ST segment recovery and improved major cardiovascular events at 30 days However, TASTE and TOTAL studies have shown the opposite results The TASTE study consisted of 7244 patients showed mortality and other clinical outcomes such as stent thrombosis, and myocardial infarction did not differ between the two groups The TOTAL study also showed similar results, with no difference in cardiovascular death, myocardial infarction, cardiogenic shock or IV NYHA heart failure between the two study groups Chapter METHODS AND MATERIALS 2.1 RESEARCH SAMPLE 2.1.1 Inclusion criteria - STEMI patients with indications of TA during PPCI who visit and treated at Nguyen Tri Phuong Hospital during the study period from June 2014 to June 2016 - Patients agree to participate in the study 2.1.2 Exclusion criteria - Contraindications for use of antiplatelet agents such as aspirine, clopidogrel - Patient who had already taken fibrinolytic drugs - New stroke, or gastrointestinal hemorrhage within months - Severe renal failure, severe liver failure - Severe comorbidities such as: late stage cancer, diabetic coma 2.1.3 Sample size and research groups: all patients were divided into two groups: - Group 1: including all STEMI patients who have successfully received TA during PPCI - Group 2: including all STEMI patients who received TA but did not succeed during PPCI 2.1.4 Study site Department of Interventional Cardiology at Nguyen Tri Phuong Hospital, Ho Chi Minh City 2.2 RESEARCH METHODS 2.2.1 Research design: clinical trial, longitudinal 2.2.2 Research facilities and equipment - Philip CV20 for digital circuit imaging - Intervention device: intervention catheter, conductor, balloon, stent We used the Export TA catheter, size 6F from Medtronic - Other equipment: echocardiography, temporary pacemaker, electric shock device to switch the rhythm, breathing machine for emergency aids 2.2.3 Steps to conduct research 2.2.3.1 Before implementing PCI Doctors directly ask for history, medical history and clinical examination of patients when hospitalized We recorded the following clinical features: age, sex, body mass index (BMI), time of admission, history of cardiovascular disease, cardiovascular risk factors, accompanying diseases, symptoms of angina, heart rate and blood pressure at admission, assessment of heart failure level in acute MI according to Killip classification Patients were recorded basic laboratory tests such as cardiac enzymes (CK-MB, troponin I), blood tests, blood sugar, electrolytes in the blood, blood lipid complexes, urea , blood creatinine, electrocardiogram, cardiac Doppler ultrasound Troponin I is performed by luminescent immunization on Architect i2000 systems (Abbott) with the 99th percentile for the upper threshold in men of 0.034 ng/ml and in women of 0.017 ng/ml Clinical and laboratory characteristics are documented through a standard research record for all patients 2.2.3.2 PPCI procedure - Anesthesia method: local anesthesia with Lidocaine 2% - Access path: right radial artery or right femoral artery - Treatment drugs before performing the procedure: Anticoagulant: use one of the following two types: Low molecular weight heparin: intravenous enoxaparin 0.5 mg/kg before intervention Then maintain mg/kg subcutaneously every 12 hours Unfractionated heparin: 70 - 100 units/kg intravenous dose before coronary intervention, then repeat 1000 - 1500 units (or 1/4 first dose) intravenously after each hour if the intervention lasts more than hour Dual antiplatelet therapy: 10 Doppler echocardiography is performed within 24 hours after admission Early evaluation after PCI based on: Hemodynamic condition The level of heart failure according to Killip The relief of chest pain Flow level according to TIMI The level of myocardial perfusion according to TMP Recovery of ST elevation Major cardiovascular events include: all-cause mortality, reinfarction, thrombosis in the stent, and brain stroke Medical treatment at discharge All patients after coronary intervention were re-examined at Nguyen Tri Phuong Hospital's Interventional Cardiology once a month Indications for post-PCI treatment were as follows: Aspirin: all patients after coronary artery intervention continue to take aspirin 81 mg daily, indefinitely unless contraindicated Clopidogrel: if a patient has a stent that is not covered, indicated for at least months and optimal for year, except for patients at high risk of bleeding If stent-coated interventions were performed, indicated for at least year with a dose of 75 mg/day Beta blockers: if there are no contraindications Appropriate dose adjustment: starting with low doses and increase the dose slowly, especially in patients with heart failure ACE inhibitors: indicated for patients with heart failure, left ventricular dysfunction (EF < 40%), hypertension or diabetes Angiotensin receptor inhibitors: indicated when the patient is not tolerated with angiotensin-converting enzyme inhibitors Aldosteron resistance: indicated for patients with heart failure but without kidney failure 11 Evaluate short-term effectiveness (within 12 months): Follow up clinically by direct examination The variables collected included: chronic heart failure based on NYHA classification Evaluation of major cardiovascular complications including: all-cause mortality, stent thrombosis, myocardial infarction, and brain stroke at 30 days and 12 months for both study groups The collected data is included in the patient's medical record 2.2.4 Standards used in research - Classification of acute heart failure according to Killip - The door-to-balloon time beginning from the moment a patient was hospitalized until the first balloon was performed - TIMI blood clotting standard - Method of assessing flow in coronary arteries according to TIMI scale - Assess the level of myocardial perfusion according to TMP - TIMI frame count: The number of TIMI calculated by the number of frames on the vein taken from the moment contrast materials entered the coronary artery until it reached the distant end of the coronary artery - Technically successful coronary intervention standards: defined as non-existent stenosis above 20% and normal intravascular artery flow back to normal (TIMI = 3) and no distal filling thrombosis - Clinically successful coronary intervention criteria: Surgical success, improvement in clinical cardiovascular symptoms and no cardiovascular events including myocardial infarction, stroke, cardiac shock and all causes mortality - Criteria for evaluating the recovery of ST elevation: The ST segment returns to normal: the ST segment deflects to ≥ 70% compared to before The ST segment partially improves: the ST segment recovers of 30-70% compared to before ST segment does not change: ST differs by 0,05 Recurrent acute myocardial infarction 0 Thrombosis in stent 0 Events p Comment: There was no difference in major cardiovascular events between the two study groups during the time of hospitalization Table 3.14 The effect of successful TA on the disappearance of chest pain after PCI No chest pain Characteristics Yes (n %) No (n %) Successful TA 59 (86,8) (13,2) Unsuccessful TA 10 (43,5) 13 (56,5) OR (95% CI) p 8,52 (2,96 – 26,24)