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Nghiên cứu đặc điểm tổn thương và kết quả can thiệp đặt stent chỗ chia nhánh động mạch vành thủ phạm ở bệnh nhân hội chứng mạch vành cấp TT TIENG ANH

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VIETNAM MILITARY MEDICAL UNIVERSITYLE THANH BINH RESEARCH ON CULPRIT CORONARY ARTERY BIFURCATION LESION CHARACTERISTICS AND STENTING IN PATIENTS WITH ACUTE CORONARY SYNDROME Speciality :

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VIETNAM MILITARY MEDICAL UNIVERSITY

LE THANH BINH

RESEARCH ON CULPRIT CORONARY ARTERY BIFURCATION LESION CHARACTERISTICS AND STENTING

IN PATIENTS WITH ACUTE CORONARY SYNDROME

Speciality : Internal Medicine

ABSTRACT OF MEDICAL DOCTORAL THESIS

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The thesis has been completed at:

VIETNAM MILITARY MEDICAL UNIVERSITY

Supervisor:

1 Prof PhD Pham Manh Hung

2 Prof PhD Nguyen Oanh Oanh

Reviewer 1: Prof PhD Pham Nguyen Son

Reviewer 2: Prof PhD Pham Thi Kim Lan

Reviewer 3: Prof PhD Ta Manh Cuong

The thesis will be present in front of board of university examiner and reviewer hold at Military Medical University

At on / / 2022

The thesis can be found at:

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- Library of Military Medical University

LIST OF SCIENTIFIC WORKS PUBLISHED RELATED TO THE THESIS

1 Lê Thanh Bình, Phạm Mạnh Hùng, Nguyễn Oanh Oanh

(2021) Investigation the Clinical, Laboratory, and LesionCharacteristics in Patients with Acute Coronary Syndrome and

Bifurcation Lesion Stenting, Vietnam Medical Journal, 504(1):

61-65

2 Lê Thanh Bình, Phạm Mạnh Hùng, Nguyễn Oanh Oanh

(2021) Patients with Coronary Artery Bifurcation Lesions

Treated by Axxess Stent Implantation, Journal of Military

Pharmaco – medicine, 46(6): 216-226.

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Acute coronary syndrome (ACS) is one of the serious events ofcoronary artery disease and is a medical emergency Except for somediseases that cause pandemics (such as COVID-19), ACS is currentlystill the leading cause of death in the world Today, along withadvances in diagnosis and combination drugs, percutaneous coronaryintervetion (PCI) is an effective treatment for ACS, which hassignificantly reduced mortality

The prevalence of coronary artery bifurcation lesions is reported

to be between 15% and 20% of all performed coronary angiogramsand despite progressive development of coronary percutaneoustechniques, still those lesions represent a challenge for interventionalcardiologists, especially in patients with ACS Complex coronarybifuraction lesions make PCI more challenging and are linked tohigher rates of procedural complications, such as side branch loss, aswell as higher rates of long-term Major Adverse CardiovascularEvents (MACE) compared to non-bifurcation lesions

The use of a provisional side branch (SB) stenting strategy isone of the fundamental philosophies of the European BifurcationClub (EBC) and consequently the use of a second stent duringbifurcation treament is madated only under specific circumstances.However, despite these efforts, the gold-standard technique,especially during ACS, has not been yet defined and there is nogeneral consensus on how to restore coronary branches flow due tothe presence of complex double coronary bifurcation lesions occurredduring ACS In those complex cases, probably most operators wouldopt for fast coronary flow restoration in the main vessel (MV) withprovisional stenting, treating the close major branch only if required

by limited flow or residual significant disease after this fistprovisional strategy However, the disadvantage of this approach isthe difficulty in accessing the SB and the rate of intraprocedural SBclosure can be from 7% to 20%

The AXXESS stent (Biosensors Europe SA, Morges,Switzerland) is a self-expanding biolimus-A9 eluting stent designed

to treat easily the complex anatomy of bifurcation lesions With aconical V shape, the device is positioned at the level of the

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bifurcation carina without the need for stent recrossing, allowing thetreatment of both distal branches with minimum carina strutcoverage.

In order to contribute to understanding the bifucation lesioncharacteristics as well as the results of stenting at the cuprit lesion inthe patients with ACS, we conducted a study on the topic: “Research

on coronary artery bifurcation lesion characteristics and stenting inpatients with acute coronary syndrome”

Objectives of the thesis

1 Investigate some clinical, laboratory and culprit coronary bifurcation lesion characteristics in patients with ACS.

2 Evaluate short-term PCI outcomes in culprit coronary bifurcation lesions using provisional stenting technique or dedicated AXXESS stent based on the lesion morphology in patients with ACS.

The necessity of the study

ACS is a common medical emergency today Culprit coronarybifurcation lesions remain one of the most challenging lesions ininterventional cardiology, especially in patients with ACS Despitethe fast growing scientific literature related to ACS, its optimalmanagement remain a subject of considerable debate One of themain concerns when dealing with ACS is the potential increased risk

of late stent thrombosis associated with treatment complexity

The use of a provisional side branch (SB) stenting strategy isone of the fundamental philosophies of the European BifurcationClub (EBC) However, the major drawback of this strategy is thedifficulty in accessing the SB (especially in true bifurcation lesions)and the higher rates of long-term MACE The AXXESS stent(Biosensors Europe SA, Morges, Switzerland) is a self-expandingbiolimus-A9 eluting stent designed to treat easily the complexanatomy of bifurcation lesions With a conical V shape, the device ispositioned at the level of the bifurcation carina without the need for

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stent recrossing, allowing the treatment of both distal branches withminimum carina strut coverage Published results from internationallong-term studies have confirmed the safety and efficacy ofAXXESS stent in patients with bifurcation lesions Therefore, it isnecessary to conduct a study to evaluate the results of PCI incoronary bifurcation lesions using provisional stenting technique orAXXESS stent based on lesion morphology in Vietnamese patients.

New Contribution of the thesis

Results of the thesis have shown that coronary arterybifurcation lesions were common in the left anterior descending(LAD) (79.4%) Medina 1.1.1 bifurcation and Medina 1.1.0bifurcation were the most common with 48.2% and 30.5%,respectively The majority of the patients (79.4%) had abifurcation angle < 700

Culprit coronary bifurcation lesion treatment with usingprovisional stenting technique or dedicated bifurcation AXXESSstent based on lesion morphology in patients with ACS is feasibleand highly successful The short-time clinical outcome are verypromising

Structure of the thesis

The thesis consists of 132 pages with 4 main chapters:Introduction (02 pages); Overview (34 pages); Methodology (24pages); Results (31 pages); Discussion (37 pages); limitation (1page);Conclusions (2 pages) and proposal (1 page) The thesis contains 45tables, 4 charts and graphs, 32 figures and 2 diagrams The thesis alsoincludes 124 references; 13 of them are written in Vietnamese while

114 are in English

CHAPTER 1: LITERATURE REVIEW

1.1 Definition of coronary artery bifurcation lesion

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According to the EBC consensus, a bifurcation coronary lesion is alesion occurring at, or adjacent to, a significant division of a major epicardialcoronary artery, being “significant” usually referred to a SB of  2 mm indiameter, is often arbitrarily defined based upon the subjectiveangiographic judgement of the operator.

1.2 Coronary artery bifurcation classifications

Figure 1.4 The Medina classification for bifurcation lesions

The Medina classification:

- Type 1.1.1: lesions located in the PMV, DMV, and SB.

- Type 1.1.0: lesions located in the PMV and DMV.

- Type 1.0.1: lesions located in the PMV and SB.

- Type 0.1.1: lesions located in the DMV and SB.

- Type 1.0.0: lesions located only in the PMV.

- Type 0.1.0: lesions located only in the DMV.

- Type 0.0.1: lesions located only in the SB.

1.3 Coronary artery bifurcation lesion intervention

1.3.1 Interventional techniques in the treament of bifurcation lesions with drug eluting stent

*Provisional stenting technique

Indication:

- Nontrue bifurcation lesions (Medina classification: Type1.1.0; Type 1.0.0; Type 0.1.0; Type 0.0.1)

- True bifurcation lesions:

+ SB is not suitable for stenting, or

+ The lesions on the SB is very focal, localized within 5 mmfrom the ostium of the SB, or

+ Patient’s condition is severe

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1.3.2 Interventional technique with using AXXESS stent in the treament of bifurcation lesions

*The AXXESS Self-Expanding Bifurcation DES:

AXXESS consists of a conical-shape self-expanding nitinol(nickel/titanium) stent flatform, especially designed to conform to theshape of the bifurcation anatomy It has been tailored to reconstructthe bifurcation without creating a false carina, lowering the risk ofuncovered struts at the flow divider The stent is coated with anabluminal-applied biodegradable poly-lactic acid polymer thatreleases Biolimus A9TM, an anti-restenotic drug designed byBiosensors specifically for use with DES

Indication:

- De novo bifurcation lesions, and

- PMV reference diameter  2.75 mm, and

- SB reference diameter  2.5 mm, and

- Bifurcation angle < 70, and

- The patient’s condition is stable

1.4 Summary of studies on coronary artery bifurcation lesion intervention

Internationally, there have been many studies on coronary arterybifurcation lesion interventions using the provisional stentingtechnique or dedicated bifurcation AXXESS stent However therehave been no Vietnamese studies on coronary artery bifurcationlesion interventions in patients with ACS

CHAPTER 2: SUBJECTS AND METHODOLOGY 2.1 RESEARCH SUBJECTS

Patients who were clinically diagnosed with ACSadmitted

to Vietnam National Heart Institute, Bach Mai Hospital, and Hanoi Medical University Hospital from 5/2014 to 12/2017

2.1.1 Patient inclusion criteria

Clinical:

- Patients with ACS (including ST-segment elevationmyocardial infarction, non-ST segment elevation myocardialinfarction and Unstable Angina) who were underwent

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percutaneous coronary angiography as stated by the

AHA/ACC 2014 Guidelines

Coronary angiography:

- Culprit de novo bifurcation lesions

- MV reference diameter  2.75 mm (by QCA)

- SB reference diameter ≥ 2.5 mm (by QCA)

Coronary artery bifurcation lesion intervention: by 2014

Consensus from the EBC, patients were selected into 2 groups:

- Group 1: using provisional stenting technique with

second-generation DES Selection criteria:

+ Nontrue bifurcation lesions, or

+ True bifurcation lesions with: SB is not suitable for stenting,

or the lesions on the SB were very focal, or the patient’scondition is severe

- Group 2: using AXXESS stent, plus 2nd-generation DES (if

needed) Selection criteria:

+ Large difference in diameter of PMV and DMV.

+ Bifurcation angle < 70°.

+ The patient’s condition is stable

2.1.2 Patient exclusion criteria:

- Patients with cardiogenic shock

- Acute pulmonary edema

- Left main disease (stenosis > 50%, by QCA)

- Culprit coronary lesions with severe tortuosity or heavy calcification.SYNTAX score ≥ 33 (except in case of refusal of CABG).Contraindications to prolonged dual-antiplatelet therapy

- Life expectancy < 1 year

2.2 RESEARCH METHODS

2.2.1 Study design: Prospective, non-randomized, interventional

study

2.2.2 Sample selection and sample size

All consecutive patients with ACS and culprit de novobifurcation lesions, who were suitable for inclusion/exclusion criteriawere categorized into 2 groups

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Sample size: 141 patients including 90 patients in Group 1 and

51 patients in Group 2 (calculated according to the sample sizeformula)

2.2.3 Technical protocol and standard in study

2.2.3.1 Medical treatment: Patients were treated adopting the 2014

AHA/ACC Guideline for the Management of Patients With Elevation Acute Coronary Syndromes

Non-ST-2.2.3.2 PCA and culprit coronary artery bifurcation lesion intervention: : Through adhering to the 2014 AHA/ACC Guidelines

and 2014 Consensus from the EBC

Provisional stenting technique

1 Placement of two wires (MV and SB)

2 Predilatation, when needed

3 Stent the MV leaving a wire in the SB

4 Proximal optimal technique (POT) in the proximal MV stent

5 Rewire the SB passing through the struts of the MV stent

6 Remove the jailed wire and dilate in the SB

7 Performance of kissing balloon inflation with moderatepressure (8 atm) in the SB, until the balloon is fullyexpanded

8 POT in the proximal MV stent

9 Placement of a second stent in the SB only if the result isinadequate (dissection, TIMI flow < 3)

Figure 2.5 Provisional stenting technique

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Figure 2.6 Placement of a second stent in the SB

Stenting technique using the dedicated bifurcation AXXESS stent

1 Guiding catheter: 7 Fr

2 Wire both branches (MV and SB)

3 Predilatation in the MV or both, when needed

4 The AXXESS stent is advanced onto the wire of the distalvessel with the sharpest bend to the proximal MV This can

be either branch, but it is often positioned on the MV wire.The distal markers of the AXXESS stent are advancedbeyond the carina in the distal vessel

5 The whole device is then gently retracted, alongsidesimultaneous gradual pullback of the actuato, slowlyretracting the sheath This allows progressive flaring of thethree distal markers across the carina Angiographically, this

is visualized when one marker appears to be in either MV or

SB, with the other two marker positioned in the other vessel,spaning the carina While the cover sheath contains morethan half the stent length (identified by the deploymentmarker on the delivery catheter), further adjustment of thestent position is possible It is often helpful to confirmadequate carina spanning by gently advancing the deviceforward while the cover sheath remains in this position, asadjustments can still be made at this point This should bevisualized in two orthogonal radiographic projections toensure separation of three markers into the MV and SB Itshould be stressed, however, that the device cannot berecaptured and the cover sheath cannot be re-advanced overthe expanded stent

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6 The final positioning maneuvre occurs with gentle forwardpressure applied with the device spanning the carina, and fullretraction of the covered sheath using the actuator.Ideally,the device should be placed 2-3 mm distal to the carina tomaximize distal vessel stent coverage.

7 Rewire the SB (no need pasing through the struts of the MVstent)

8 Performance of kissing balloon inflation with moderatepressure (8 atm) in the SB

9 Further DES can then be advanced if required and deployed

in the distal MV (stenosis > 75%, dissection, TIMI flow <3) or SB (dissection, TIMI flow < 3)

Figure 2.7 AXXESS stenting technique

Figure 2.8 Stent distribution patterns 2.2.3.3 Clinical standards: by 2014 AHA/ACC Guidelines.

2.2.3.4 Subclinical standards: Criteria for identifying increased

myocardial biomarkers and localizing myocardial ischemia

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2.2.3.5 Definitions of PCI Success and Complications: By 2011

ACCF/AHA/SCAI Guideline for Percutaneous CoronaryIntervention

2.4 RESEARCH DATA STATISTICAL ANALYSIS:

Using data analysis software SPSS 24.0 The comparisons are

considered significantly significant at p < 0.05.

2.5 Ethical aspect

No violation of ethical regulations The topic was approved

by the Ethics Council of Military Medical University

CHAPTER 3: RESEARCH RESULTS

Between May 2014 and December 2017, we analyzed 141patients with ACS and culprit de novo bifurcation lesions who weresuitable for inclusion/exclusion criteria were divided into 2 groupsfor study Group 1 (90 patients) was treated with second-generationDES using the provisional stenting technique On the other hand, Group

2 (51 patients) was treated with the AXXESS stent, plus generation DES (if needed)

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second-3.1 General characteristics of research subjects

3.1.1 Gender

Table 3.1 Gender characteristics

Parameter All patients n=141 Group 1 n=90 Group 2 n=51 p

0.05

There were 103 male (73.0%) and 38 female (27.0%) The male/

female ratio was 2.7/1

3.1.2 Age

Table 3.2 Age characteristics

Parameter patients All

n=141

Group 1 n=90 Group 2 n=51 p

Mean ± SD 66.1 ± 9.4 67.3 ± 10.4 64.0 ± 7.1 < 0.05 < 60 n (%) 31 (22.0) 19 (21.1) 12 (23.5) > 0.05  60 n (%) 110 (78.0) 71 (78.9) 39 (76.5)

The average age is 66.1  9.4 years, the oldest is 90 years old,

and the youngest is 47 years old

The percentage of patients aged 60 and over accounts for 78.0%

3.2 Clinical, subclinical and bifurcation lesions characteristics 3.2.1 Clinical characteristics

Table 3.3 Characteristics of cardiovascular risk factors

Parameter All patients n=141 Group 1 n=90 Group 2 n=51 p

Hypertension n

38(74.5) > 0.05Diabetic n

n (%) 7 (5.0) 5 (5.6) 2 (3.9) > 0.05Obesity n (%) 10 (7.1) 6 (6.7) 4 (7.8) > 0.05

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