SYNOPSIS FOR MS.

CARDIAC SURGERY

Impact of LA Appendage Occlusion on Thromboembolic event in Mitral

Valve Surgery

By
Dr.FarhanEjaz
M.B.B.S

SUPERVISOR
Prof. Dr. ZafarTufail
Head of Cardiac Surgery Department,
Punjab Institute of Cardiology, Lahore
 LIST OF ABBREVIATION

ABBREVIATIONS USED FOR

AF Atrial Fibrillation

CABG Coronary Artery Bypass Grafting

CPB Cardiopulmonary By Pass

CT Computed tomography

ECG Electrocardiogram

GLUT Glucose type receptor

ICU Intensive Care Unit

ICAM Intra adhesive cellular molecule

IL Interleukin

IIT Intensive Insulin therapy

LA Left atrium

LAA Left atrial appendage

PIC Punjab institute of cardiology

SD Standard deviation

SPSS Statistical Package for Social Sciences

PROJECT SUMMARY:

The study “Impact of LA Appendage Occlusion on Thromboembolic event in Mitral

Valve Surgery” will be conducted at Punjab Institute of Cardiology under the supervision

of Prof. Dr. Zafar Tufail. In south Asian population a large number of people are exposed

to recurrent attacks of rheumatic fever which results in severe rheumatic heart disease

involving and the mitral valve being the most frequently involved. The lack of available

medical facilities, these patients present with heart palpitations, coughing, fatigue,

shortness of breath and chest pain. Study will conducted to find out the impact of LA

Appendage Occlusion on thromboembolic event in Mitral Valve Surgery.

All consecutive patients of mitral valve disease requiring surgery will be enrolled in this

study after informed consent. Clinical and postoperative variables will be entered in the

predesigned proforma and patients will be followed for difference in mortality and

morbidity in both groups during hospital stay.

Statistical analysis will be performed using the SPSS (Statistical Package for Social

Sciences) system for Windows. Postoperative outcomes will be compared with two

groups by applying Chi Square test and independent sample T test and p values will be

calculated as<0.05 will be taken as significant.The result drawn from the statistical

analysis will help to formulate guidelines and recommendations for undergoing mitral

valve surgery for better management of patient care.

INTRODUCTION:

Mitral valve surgery is surgery to either repair or replace the mitral valve of heart.Mitral

regurgitation (MR) is the second most frequent indication for valve surgery in Europe. It is

essential to distinguish the cause of mitral regurgitation, particularly in relation to management.

In primary MR, one or several components of the mitral valve apparatus are directly affected.

The common causes of organic (primary) MR include prolapse syndrome, flail leaflet, rheumatic

heart disease, coronary artery disease (CAD), infective endocarditis, certain drugs (some

anorectic drugs), and collagen vascular disease. In some cases, such as ruptured chordae

tendineae, ruptured papillary muscle, or infective endocarditis, MR may be acute and severe.

Alternatively, MR may worsen gradually over a prolonged period of time. It is important to

know the causes of MR because the management and treatment differ according to the aetiology.

(Atti et. al., 2018)

The purpose of mitral valve surgery is to exclude a major source of thromboembolism from the

rest of the circulation in patients with dilated and poorly contracting atria, without the need for

long-term antithrombotic therapy. The advantages would be two fold: prevention of ischaemic

events caused by emboli originating from thrombi in the LAA and discontinuation of

antithrombotic therapy within a few months of the procedure, avoiding the bleeding risk

associated with the long-term use of antithrombotic drugs

The left atrial appendage (LAA) is a trabeculated structure with variable anatomy comprised of

pectinate muscle, which grows out of the primary atrium before the left atrium (LA) develops.

This outcropping joins the venous component of the LA by way of a bottlenecked junction, in
contrast to the anatomy of the right atrial appendage which, although trabeculated, joins the

atrium via a wider neck

Atrial fibrillation, the most common cardiac arrhythmia worldwide, is becoming increasingly

prevalent because of the longevity of an aging population (Ahmad2013)..Atrial fibrillation is

associated with up to a five-fold increased risk of ischemic stroke because of its potential to

cause thrombus formation in the left atrium, which in turn can embolize to the cerebral

circulation. Atrial fibrillation accounts for 15% to 20% of all ischemic strokes (Crystal. and

Connolly2004).
LITERATURE REVIEW:

The left atrial appendage (LAA) is considered to be the dominant source of embolism (> 90%) in

patients with non-valvular atrial fibrillation (AF). Occlusion or resection of the left atrial

appendage occlusion (LAAO) remains an important intervention for prevention of recurrent

emboli in patients who are at risk of stroke. LAAO provides an opportunity to avoid systemic

anticoagulation, thereby minimizing the risk of bleeding.

Surgical LAAO (s-LAAO) usually involves LAA closure while performing other cardiac

surgeries. With the increasing prevalence of AF, there is a growing interest in the surgical

community for s-LAAO. s-LAAO was associated with lower risk of embolic events (OR: 0.63,

95%CI: 0.53-0.76; P < 0.001) and a lower risk of stroke (OR: 0.68, 95%CI: 0.57-0.82; P <

0.0001). There was no significant difference in all-cause mortality between the two groups (OR:

0.83, 95%CI: 0.51-1.36; P = 0.46). There was no significant difference in the incidence of

follow-up AF between the two groups (OR: 1.41, 95%CI: 0.79-2.52, P = 0.24. (Atti et.al., 2018 )

LAA exclusion group (n = 188) had a lower prevalence of female gender, hypertension, and

diabetes mellitus compared with the non-LAA exclusion group (n = 93). The CHA 2DS2VASc

scores were comparable between groups (2.6 vs 2.9, P = .11), as was anticoagulant use (82.4% vs

85.0%, P = .60). Concomitant surgical ablation was performed in 73.9% of patients who

underwent LAA exclusion. Nine cerebrovascular events occurred in the LAA exclusion group

and 13 in the non-LAA exclusion group (HR 0.30 [0.12-0.75], P = .01). There was no difference

in all-cause mortality between groups. On multivariate analysis of the primary end point of

strokes or transient ischemic attacks, significant variables were LAA exclusion (HR 0.31 [0.12-

0.76], P = .01). (Abrich et. al., 2018)

Gong et. al., (2014) were divided into two groups as LAA closure group (n = 521) and non-LAA

closure group (n = 339).Early mortality, postoperative cerebral ischemic stroke and the risk

factors for cerebral ischemic stroke were assessed. Compared with non-LAA closure group,

LAA closure group had higher proportion of female gender, higher percentage of patients with

cardiac insufficiency, pulmonary hypertension and left atrial thrombus, higher incidence of

mechanical valve implantation and concurrent tricuspid surgery, and larger preoperative

diameter of left atrium, but lower proportion of hypertension and patients undergoing coronary

artery bypass surgery, and shorter aorta cross clamping time (χ² = 6.807 to 122.576, t = -2.818

and 3.756, all P < 0.05). There were no differences in exploratory thoracotomy for bleeding and

in-hospital mortality between the two groups. Postoperative cerebral ischemic stroke occurred in

12 patients (1.4%). The incidence of cerebral ischemic stroke in LAA closure group was

significantly lower than in non-LAA closure group (0.6% vs.2.7%, χ² = 6.452, P =

0.011).Logistic regression analysis showed that LAA closure was a significant protective factor

for postoperative cerebral ischemic stroke (OR = 0.189, 95% CI: 0.039 to 0.902, P = 0.037)

while history of cerebrovascular disease (OR = 4.326, 95% CI:1.074 to 17.418, P = 0.039) and

preoperative diameter of left atrium (OR = 1.509, 95% CI: 1.022 to 1.098, P = 0.002) being the

independent risk factors for postoperative cerebral ischemic stroke. The subgroup analysis

showed that, for atrial fibrillation patients, LAA closure was a strong protective factor (OR =

0.064, 95% CI: 0.006 to 0.705, P = 0.025), but LAA closure was not a significant predictive

factor (OR = 1.902, 95% CI: 0.171 to 21.191, P = 0.601) in non-atrial fibrillation patients. They

find out that concurrent LAA closure during mitral valve replacement is safe and effective to

reduce the early postoperative risk of cerebral ischemic stroke in atrial fibrillation patients. Gong

et. al., (2014)

Objective:

o To compare the impact of LA appendage occlusion on outcomes in patients undergoing

mitral valve surgery.

Operational Definitions:
Thromboembolism:-

Formation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood

stream to plug another vessel. The clot may plug a vessel in the lungs (pulmonary embolism),

brain (stroke), gastrointestinal tract or kidneys. Thromboembolism is a significant cause of

morbidity (disease) and mortality (death), especially in adults.

Mortality: - Death due to any cause within 7 days after operation including intraoperational
mortality

Post-operative stroke: If there was evidence of new neurological deficit with

morphological substrate confirmed by computed tomography within 7 days.

New focal neurologic deficit or comatose state occurring postoperatively that persisted for more

then 24 hours after its onset. Excluding confused states, transient events and intellectual

impairment

Post-operative pulmonary dysfunction

Require more than 24 hours of mechanical ventilation.

Hypothesis:

o There is no difference in the impact of LA appendage occlusion on outcome in patients

undergoing mitral valve surgery.

Alternative Hypothesis:

o There is a difference in the impact of LA appendage occlusion on outcome in patients

undergoing mitral valve surgery.

Materials and Methods:
Study design: It will be a Non-Randomized Controlled Trial.

Setting: Study will be conducted at the Cardiac Surgery Department, Punjab Institute of

Cardiology, Jail Road, Lahore. It is a 540 bedded tertiary care hospital dedicated to cardiac

patients only.

Duration of study: It will be 12 months study after date of approval of synopsis.

Sample Size:

The sample size 158 (79 in each group) calculated by the following formula keeping the power
of study equal to 90% and level of significance equal to 5%. (Zheng et al., 2020)

Where, α = level of significance (5%)

β = power of study (90%)

P1 = Anticipated proportion of Mitral Stenosis in Group with LAA= 91.2%

P2 = Anticipated proportion of Mitral Stenosis in Group with LAA= 78.3%

n = 79 in each group

Sampling technique: Convenient sampling technique.

Selection criteria:
Inclusion criteria
1. Patients of age 15-80 years,

2. Rheumatic Heart Disease

3. Planned to undergo Mitral Valve Surgery under general anesthesia.

Exclusion criteria

4. Previous history of cardiac surgery

5. Prior Pulmonary dysfunction and stroke

6. Patients withsignificant mitral stenosis and aortic valve surgery (DVR)

Methodology:

After fulfilling inclusion criteria 312 patients will enroll and two groups will be formed using the

criteria of Friedman et al., (2017) group A will be labeled as patients undergoing surgery with LA

Appendage and group B will be labeled as patients undergoing surgery without LA Appendage

Patients will be included after taking consent on a consent form (Appendix l).A Proforma

(Appendix ll) will be used for data collection, which will include parameters of study.

All the information will be collected on a specially designed Proforma. It will include history,

general physical and systemic examination along with information regarding operative variables

of mitral valve surgery and follow up during hospital stay till discharge. Proforma is attached

with the synopsis.

Surgical Techniques
LAA closure will be performed through a median sternotomy using cardiopulmonary bypass.

When left atrial appendage closure will be performed as part of a mitral valve operation, the
ostium of the left atrial appendage will usually sutured in 2 layers of polypropylene suture from

inside the left atrium. When LAA closure will performed as part of other cardiac procedures, the

LAA will be amputated and its opening will be sutured in 2 layers of polypropylene suture from

the outside of the heart. In a minority of cases, the LAA will be stapled or suture closed from

inside the LA depending on the patient tissue quality.

Statistical analysis: All the data will be entered and analyzed through SPSS version 21.

Quantitative variables like age, BMI, increase in serum creatinine will be presented as mean and

standard deviation, median and interquartile intervals, and range. Qualitative variables like

gender, ARF and in-hospital mortality will be presented as frequency and percentage.Both

groups will be compared for qualitative variables like, (ARF and in-hospital mortality) by using

chi-square test (if cell frequency < 5 then Fisher exact test) and for quantitative variables like,

(increase in serum creatinine) by using independent sample t-test.P-value≤0.05 will be

considered as significant. To identify the independent predictors of CPB duration regression

analysis will be applied.Data will be stratified for age, gender, BMI and diagnosis. Post-

stratification, chi-square test and independent sample t-test will be applied to compare study

groups in different stratified groups for outcome with p-value≤0.05 taken as significant.
Outcome and Utilization

The result of this study will help us generating information as well as enable us to confirm the

evidence in local population. Then in future, we will be able to implement the results of this

study and suggest to shorten the duration of cardiopulmonary bypass to prevent the hazardous

consequences of longer cardiopulmonary bypass time. This will improve our practice as well as

reduce the burden on surgeons and hospital by reducing the post-operative complications.

Estimated Cost of the Project:

S# Modality Cost per patient Cost for 312 patients

1 Cardiac Biomarkers Rs. 250 Rs. 80,000/-

2 Chest Radiograph Rs.140 Rs. 44,800/-

3 Echocardiography Rs. 1000 Rs. 3,20,000/-

4 Stationeries Rs. 100 Rs. 32,000/-

5 Photocopyand miscellaneous Rs. 100 Rs. 32,000/-

Total Rs. 1590/- Rs. 5,08,800/-

All this cost will be provided by Punjab Institute of Cardiologythrough Government of Punjab.

Work Plan
Months 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th

Synopsis
writing

Synopsis
approval from
review and
advanced
committee
Data
collection

Data analysis

Thesis writing

Thesis
submission
Reference
Abrich, V.A., Narichania, A.D., Love, W.T., Lanza, L.A., Shen, W.K. and Sorajja, D., 2018.

Left atrial appendage exclusion during mitral valve surgery and stroke in atrial

fibrillation. Journal of Interventional Cardiac Electrophysiology, 53(3), pp.285-292.

Ahmad, Y., Lip, G.Y. and Lane, D.A., 2013. Recent developments in understanding

epidemiology and risk determinants of atrial fibrillation as a cause of stroke. Canadian

Journal of Cardiology, 29(7), pp.S4-S13.

Atti, V., Anantha-Narayanan, M., Turagam, M.K., Koerber, S., Rao, S., Viles-Gonzalez, J.F.,

Suri, R.M., Velagapudi, P., Lakkireddy, D. and Benditt, D.G., 2018. Surgical left atrial

appendage occlusion during cardiac surgery: A systematic review and meta-analysis. World

Journal of Cardiology, 10(11), p.242.

Crystal, E. and Connolly, S.J., 2004. Role of oral anticoagulation in management of atrial

fibrillation. Heart, 90(7), pp.813-817.

Engel, M.E., Stander, R., Vogel, J., Adeyemo, A.A. and Mayosi, B.M., 2011. Genetic

susceptibility to acute rheumatic fever: a systematic review and meta-analysis of twin

studies. PloS one, 6(9), p.e25326.

Friedman, D.J., Piccini, J.P. and Wang, T., 2017, March. Comparative effectiveness of left

atrial appendage occlusion among atrial fibrillation patients undergoing cardiac surgery: a

report from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. In Presented

at: Annual meeting of the American College of Cardiology.

Gong, Z., Jiang, S., Li, B., Ren, C., Wang, M., Wang, Y., Chen, T., Zhang, T. and Gao, C.,

2014. Early results of left atrial appendage closure in cerebral ischemic stroke reduction in

patients with mitral valve replacement. Zhonghuawaikezazhi [Chinese Journal of

Surgery], 52(12), pp.934-938.

Lee, C.H., Kim, J.B., Jung, S.H., Choo, S.J., Chung, C.H. and Lee, J.W., 2014. Left atrial

appendage resection versus preservation during the surgical ablation of atrial fibrillation. The

Annals of thoracic surgery, 97(1), pp.124-132.

Zühlke, L.J. and Steer, A.C., 2013. Estimates of the global burden of rheumatic heart

disease. Global heart, 8(3), pp.189-195.

 PROFORMA

Impact of LA Appendage Occlusion on Thromboembolic event in Mitral

Valve Surgery

Case no: Reg. No.: Date: / /

Name:
Age: Gender: Male □ Female□
Height (cm) Weight(kg)
NYHA class I II III IV
Group: A (Group with LAA)
Group B ((Group without LAA)

Risk Factors :
 Smoking Yes □ No □

 Diabetes Mellitus Yes □ No □

 Hypertension Yes □ No □

 Previous history of mitral valve surgery Yes □ No □

 Hyperlipidemia Yes □ No □

 A,.Fib Yes □ No □

 LA size _________________

Outcomes

 ICU stay (No of days)____________Total Hospital stay (No of days)____________

 Intr-operative stroke Yes □ No □
 Post-operative stroke Yes □ No □
 Post-operative pulmonary dysfunction Yes □ No □
 Mortality Yes □ No □

APPENDIX I

CONSENT FORM

I…………………………………..…S/O or D/O……………………………………….

Suffering from Coronary artery disease hereby give consent for inclusion in the study, “Impact

of LA Appendage Occlusion on Thromboembolic event in Mitral Valve Surgery ”I have

been told about the study protocol.

I shall fully co-operate with Dr. Farhan Ejazin when I will be called for.

………………………
NAME/Signatures
Address:
Telephone Numbers: