Role of presence of ramus branch on left anterior descending artery dimensions and clinical consequences in anterior wall myocardial infarction.

**1. Title of the project:**Role of presence of ramus branch on left anterior descending artery dimensions and clinical consequences in anterior wall myocardial infarction.

2. Type of Study:   Prospective, Observational study.

3. Aims & objectives***:***

Aim:

To assess the role of vessel in Ramus territory on Left anterior descending artery dimensions, ejection fraction and clinical outcomes in patients with Anterior Myocardial Infraction

Objectives

Primary objective

To compare the dimensions of LAD and LMCA between the patients with and without vessel in ramus territory.

Secondary objective

1. To compare extended Major Adverse cardiovascular events (MACE) at 1 month follow up for those with and without Ramus Intermedius.

2. To compare Ejection Fraction and Improvement in Ejection fraction at 1 month follow-up for those with and without Ramus Intermedius

4.Justification for study (whether of national significance with rationale): If it can be shown that presence of RI impacts LAD size and therefore EF or clinical outcomes in AWMI, it can act as a prognostic marker which is easily available in all patients with MI undergoing CAG. Therefore, it may then be used as an add-on in risk scores to provide better prognostic information.

5. Departments involved:

Department of Cardiology, Kasturba hospital, Manipal.

Department of CVT, MCHP, MAHE, Manipal.

6. Study period: 2 years

7. Sample size :  Sample size was retrospectively obtained from a previously conducted study.

Sample size was based on LMCA Area

Sample size evaluation: For 2 independent samples

n=2[(Zα/2 + Zβ)2 σ 2]/d2

Zα/2 =1.96(5% Level of significance)

Z β = 0.95(95% power value)

σ = 3.60( Pooled standard deviation)

d= 2 (clinically significant difference in LMCA area between 2 groups )

n= 120 in each group

Attrition of 10%

n= 132 in each group

8. Materials and methods:

a) Inclusion and exclusion criteria:

Inclusion criteria:

1. Patients with ECG showing Anterior wall MI.

2. Patients undergoing coronary angiogram for coronary artery disease evaluation.

3. Above Individuals undergoing IVUS during PCI to rule out lesion characteristics and dimensions of LAD.

Exclusion criteria:

1. Previous coronary artery bypass grafting (CABG)

2. Acute LAD occlusion with underlying etiology other than coronary atherosclerotic plaque with superimposed thrombosis (as dissection or embolism)

3. Previous angioplasty at the site of the culprit lesion.

Tools used: Philips Intrasight and Boston Scientific machine for calculating Vessel Area and diameter through IVUS and QCA analysis is done using Philips Azurion Version 2.2

9. Detailed description of procedure / processes:

The study will be conducted after departmental presentation, hospital permission IRC, IEC approval and CTRI registration will be done. After IRC and IEC approval and CTRI registration the patients with Anterior wall myocardial infarction visiting to the emergency triage will be enrolled in the study as per inclusion criteria. Details of the study are explained to the patient party and informed consent will be taken. Participants will undergo Angiogram and IVUS as a part of standard care for AWMI. LMCA, LAD and Ramus diameter, area would be measured on IVUS and QCA for comparison. One month follow up is considered as per treating doctor’s advice.

10. Outcome measures:

Intravascular ultrasound and quantitative coronary analysis

Lumen diameter (mm)

Lumen area (mm2)

Vessel wall diameter(mm)

Vessel wall area (mm2)

Major adverse cardiovascular events

Acute MI (%)

Acute coronary syndrome (IHD) (%)

Heart failure (%)

Stroke (%)

Cardiovascular death (%)

Revascularization (%)

11. Potential risks and benefits:This is an observational study. Primary percutaneous coronary angioplasty is as diagnostic procedure used as a standard care unit for AWMI patients*.*

Benefits: Helpful to understand potential variations in coronary arteries among people with or without ramus intermedius. This includes observing alterations in left ventricular ejection fraction, the incidence of significant cardiac complications and overall clinical outcomes. Risk: Minimal risk12. Ethical considerations and methods to address issues : This is a prospective observational study. Approval from institutional ethics committee will be taken prior to patient recruitment. Written informed consent will be taken from all participants and only those giving consent will be included in the study. Information from the study records including your name, address, medical records, results of tests, study results will be kept confidential and will be received only by authorized personnel from the sponsor or their representative, Ethics committee or regulatory bodies. The data will not be made available to another individual unless you specifically give permission in writing. Information and results from this study may be presented at meetings or published in journals without including your name and personnel identifications. No reference will be made in oral or written reports which could link you to the study.13. Budget (give details) and proposed funding source:  Nil

14. Review of literature

Anatomy of Coronary Artery

The coronary arteries run through the coronary sulcus within the myocardium of the heart. Their main function is to supply vital blood to the heart, essential for myocardial function and maintaining overall body homeostasis. The configuration of coronary arteries differs significantly among people. The two main arteries are the right coronary artery (RCA) and the left main coronary artery (LMCA).

In coronary artery disease there will be decreased blood flow through coronary arteries which result in altered myocardial function. Most common aetiology of CAD include atherosclerosis followed by prinzmetal angina and congenital abnormality of coronary artery.[1]

Coronary Dominance

Coronary artery which gives rise to PDA and supplies the inferior wall of the heart is considered as coronary dominance. If the PDA arises from RCA, then it is considered as right dominance (70%). If the Inferior wall of heart is supplied by branch of LCX then it is considered as Left dominance (10%) If both RCA and LCX give rise to PDA then it is referred to as codominance. (20%).[2]

Ramus Intermedius

The ramus intermedius artery is one of the epicardial coronary artery branches. It is thought to be a common anatomical variation that results in an appearance of trifurcation in the LMCA.

The presence of ramus intermedius (RI) has several advantages. It reduces left main impedance by allowing blood to drain into three ostia rather than two. A large RI usually supplies a bigger area in the angle between the LAD and the LCX. This is thought to reduce LV dysfunction and provide electrical stability, which may help prevent ventricular fibrillation following ACS. [3]

Intravascular Ultrasound

In the suspecting and treatment of coronary disease, Intravascular ultrasound (IVUS) serves as a significant complement to angiography, offering fresh perspectives. The use of IVUS guidance proves particularly beneficial in intricate lesion types, such as left main and bifurcation lesions, with studies indicating potential mortality reduction through IVUS-guided interventions.[4]

Quantitative Coronary Analysis

The QCA approach, which is derived from contrast coronary angiography, provides parameters that objectively and interval-measure the significance of a coronary stenosis. It also aids in the estimation of the short- and long-term outcomes of percutaneous coronary procedures.[5]

Galbraith et al. conducted a study from 2006 to 2008 seeking to investigate the theory that the existence of a RI exacerbates flow disruptions in the proximal LAD, leading to more extensive proximal LAD lesions and larger STEMI.

This retrospective study involved the recruitment of 3,644 patients, among whom 608 presented with STEMI. Within the STEMI group, 386 patients had LAD culprit lesions, among whom 150 had a RI while 106 did not. The assessment of infarct size utilized creatinine kinase-MB, peak troponin-I and LVEF as markers.

The study revealed that LAD lesions tended to occur more proximally in patients with RI, accounting for 43% and 63% of lesions within the first 10 and 20 mm of the LAD, respectively, in contrast to 10% and 32% in those without RI. Patients with RI exhibited higher peak troponin-I and peak creatinine kinase-MB levels. Additionally, patients with RI showed a trend towards a decreased left ventricular ejection fraction.

Consequently, the study concluded that the presence of RI correlated with increased proximity of LAD lesions and larger anterior infarctions, suggesting that anatomy-related flow disruptions hold significant clinical consequences.[6]

2) Between 2016 and 2018, Separham A and Jodi S et al. conducted a study to evaluate how the presence of RI impacts the clinical outcomes in anterior STEMI with LAD as culprit lesion. The study encompassed 105 patients undergoing PPCI for acute anterior STEMI, among whom 53 patients had RI. Notably, RI presence was more prevalent among male patients compared to their female counterparts. Additionally, individuals with RI exhibited a lower occurrence of single-vessel disease and a higher frequency of proximal LAD involvement.

Post-intervention, patients with RI demonstrated a greater than 50% reduction in the ST segment, significantly surpassing those without RI. However, there were no noteworthy differences observed between the groups in terms of cardiac enzyme levels, EF, heart failure, cardiogenic shock, or in-hospital and one-year mortality rates.

The study concluded that RI presence correlated with increased proximity of LAD lesions and a reduced occurrence of single-vessel disease. Despite these associations, the presence of RI did not appear to significantly impact hospitalizations or one-year outcomes.[7]

3. Between 2016 and 2019, S. Reddy et al. conducted a study aiming to establish the normal dimensions of disease-free segments in coronary arteries by utilizing intravascular ultrasound. The research involved 303 patients with ACS undergoing PCI along with IVUS and QCA. Analysis was performed on 492 proximal coronary segments: 221 associated with the LM, 164 with the LAD, 45 with LCX, and 62 with the RCA.

The conclusion drawn was that coronary artery dimensions assessed IVUS were significantly larger than those determined by QCA. The study did not find any gender differences in coronary artery size. However, age was highlighted as an independent predictor of coronary artery size in the left main and LAD. The study also suggests that coronary artery size may not be a risk factor for acute coronary syndrome.[8]

4. A study conducted by P.K. Goel, P. Liladhar Vora, A. Kumar Sahu et al. from 2008 to 2017 aimed to establish the correlation between quantitative angiographic coronary diameter (DQCA) and intravascular ultrasound-derived coronary diameter (DIVUS). The retrospective analysis included 202 patients who had undergone IVUS-guided left main percutaneous coronary intervention (LM-PCI). Specifically, 186 LM, 177 ostio-proximal LAD (op-LAD), and 44 ostio-proximal LCX (op-LCX) cases were examined.

The study identified a linear correlation between DIVUS and DQCA, providing equations for estimating vessel size: LM DIVUS = 1.68 + 0.69 x DQCA, op-LAD DIVUS = 1.91 + 0.53 x DQCA, and op-LCX DIVUS = 1.93 + 0.49 x DQCA. As a result, the study suggests that these equations could serve as an approximate estimation of true vessel size in situations where IVUS assessment is unavailable.[9]

15. References:

1. Villa AD, Sammut E, Nair A, Rajani R, Bonamini R, Chiribiri A. Coronary artery anomalies overview: The normal and the abnormal. World J Radiol. 2016 Jun 28;8(6):537-55

2)A study of coronary dominance and its clinical significance D.P. Aricatt et al. Folia Morphol 2023;82(1):102-107

3)Angiographical study of ramus intermedius coronary artery in Basrah Saja M. Ali1 MJBU, Vol. 35, No.2, 2017

4. Intravascular Ultrasound Assessment of Lumen Size and Wall Morphology in Normal Subjects and Patients With Coronary artery disease Nissen et al; Vol 84, No 3 September 1991

5. Quantitative coronary angiogram in current era; Principles and applications Garrone et.al J interven cardiol;22:527-536

6)Galbraith et al ,Comparison of Location of “Culprit Lesions” in Left Anterior Descending Coronary Artery Among Patients With Anterior Wall ST-Segment Elevation Myocardial Infarction Having Ramus Intermedius Coronary Arteries Versus Patients Not Having Such Arteries . (Am J Cardiol 2010;106:162–166)

7. Separham A, Jodi S. Comparison of in-Hospital Outcome after Percutaneous Coronary Intervention Between Patients with Anterior Myocardial Infarction and Those With or Without Ramus Intermedius.. J Cardiothoracic Med. 2019; 7(4):518-522

8)S. Reddy et al ., Coronary artery size in North Indian population  Intravascular ultrasound-based study . Indian Heart Journal 71 (2019) 412-417

9)P.K. Goel, P. Liladhar Vora, A. Kumar Sahu et al., Left main coronary artery diameter : A correlation between intravascular ultrasound and quantitative coronary angiography. Indian Heart Journal 73 (2021) 660-663