Summary of the dissertation of doctor of philosophy in medicine: The results of primary percutaneous coronary intervention association with thrombus aspiration on patients with acute

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.

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

The research is completed at:

CLINICAL RESEARCH INSTITUTE OF MEDICINE AND

PHARMACY SCIENCE 108

Science advisors:

1 Prof PhD Nguyễn Quang Tuấn

2 Assoc Prof PhD Phạm Thái Giang

At

The thesis can be accessed at:

1 National Library of Vietnam

2 Library of Clinical Medicine Research Institute 108

LIST OF RESEARCH WORKS RELATED TO THE THESIS

1 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

2 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 6 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 ST- elevation myocardial infarction” with 2 objectives:

1 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

2 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 4 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, 5

charts, 10 pictures, and 120 references (Vietnamese: 13; English: 107)

Chapter 1 LITERATURE REVIEW

1.1 Outline of acute coronary syndrome (ACS) and acute elevation myocardial infarction (STEMI)

ST-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 ≥ 2 mm in men or 1.5 mm in women

on V2 V3 leads and/or ≥ 1 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 ≥ 2 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, angiotensin- converting 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 0 or 1, the surgeon will perform TA with a catheter If the coronary arterial flow has TIMI of 2 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 2 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 3 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

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 1 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 1 hour

Dual antiplatelet therapy:

Aspirin: first dose 162 - 325 mg before the intervention (4 tablets

81 mg orally or chewed), maintaining a dose of 75 - 162 mg/day (1

tablet of 81 mg/day) Combined with:

Clopidogrel: the first dose of 8 tablets of 75 mg (600 mg) for all patients with coronary intervention is first, maintaining 75 mg/day, or Ticargrelor: the first dose of 2 tablets of 90 mg (180 mg) taken

before the intervention, then maintained 180 mg daily (2 tablets of 90 mg), divided into 2 doses

Statin: 60 - 80 mg atorvastatin or 30 - 40 mg oral rosuvastatin just

before the intervention, then maintain atorvastatin 20 - 40 mg/day or rosuvastatin 10-20 mg/day Long-term treatment goals are LDL <70 mg/dL

Other drugs: Nitroglycerin, beta blockers, angiotensin inhibitors

or receptor inhibitors Specifies on case-by-case situation

Steps to perform the procedure

- Selective coronary angiography procedure: assessing culprit and

non-culprit artery damage including:

 Significant number of narrowed coronary arteries (narrow

≥ 70% of vascular diameter)

 The narrowing of coronary arteries and lesions include: calcification level, zigzag level, thrombotic morphology, and length of injury

 Evaluate collateral circulation and muscle bridge if available

 Determine the culprit coronary lesions based on changes

in electrocardiography and coronary angiography

 Evaluate flow in the coronary according to TIMI scale

 Evaluate TMP scale cardiac perfusion levels (TIMI myocardial perfusion grading)

- Coronary artery intervention procedure:

After assessing and determining coronary artery lesions, we proceeded to pass the intervention wire (guidewire) through the

coronary artery lesions We capture coronary coronary arteries in two orthogonal postures to re-evaluate lesions, TIMI thrombosis, TIMI flow levels and myocardial perfusion levels according to TMP If the patient has indicated of TA, we will conduct TA with a catheter before the standard coronary intervention includes: ballooning and/or stenting If the patient has no indication of TA, we would conduct standard coronary intervention and finish the procedure

- TA technique:

If the patient was indicated TA, surgeon will take TA catheter along the wire to approach the blood clot in the heart When the distal end of the catheter passes through the narrow position or obstruction, use a syringe attached to the catheter, creating negative pressure to suck the blood clot into the syringe The catheter can then be moved repeatedly and gently through the suction position or until the suction pressure is no longer felt, the catheter will be pulled out While pulling out the TA catheter out, the catheter tip was always attached to the starting hole of the coronary artery and always kept the TA syringe at negative pressure to avoid dropping the thrombus into the circulatory system Finally, inject blood in TA syringes into the filter, coronary angioplasty to evaluate the effectiveness of the TA The facilitator can perform TA multiple times if necessary After 3 times of TA, if there is

no improvement in thrombosis and TIMI flow classification on coronary angiography, the TA procedure would be stopped The patient will then be ballooned and put a stent if the injury is appropriate

2.2.3.3 Monitor patients after PPCI

 ECG and cardiac enzymes are performed at the following times: immediately after the intervention, after 6 hours, after 24 hours, and before discharge ECG is done in bed with 12 standard leads In case of suspicion of posterior myocardial infarction or right ventricular myocardial infarction, additional leads V3R, V4R, V5R, V7, V8, V9 will be measured

 All patients were given biochemical and hematological testing within 24 hours after the intervention Depending on the clinical result of each patient, some other specific tests may be performed if necessary, such as blood electrolytes, arterial blood gas, blood lactate,

 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, infarction, thrombosis in the stent, and brain stroke

re- 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 6 months and optimal for 1 year, except for patients at high risk of bleeding If stent-coated interventions were performed, indicated for at least 1 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