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The AVSD repair surgery was first performed in 1951 by Clarence Dennis at the University of Minnesota and cardiopulmonary technology was also first applied in the world.There are many ca

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PATIENTS WITH PARTIAL ATRIOVENTRICULAR

SEPTAL DEFECT BEFORE AND AFTER SURGERY

Specialize d: Inte rnal Cardiology

Code: 62.72.01.41

SUMMARY OF DOCTORAL DISSERTATION

Ha Noi – 2019

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CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

Scie nce supe rvisor:

1 Associate Professor, PhD: Pham Nguye n Son

Revie we r 1: Associate Professor, PhD Pham Thi Hong Thi Revie we r 2: Associate Professor, PhD Hoang Dinh Anh

Revie we r 3: Associate Professor, PhD Luong Cong Thuc

The dissertation will be defended in front of the Council Evaluation at:

The dissertation can be found at library of:

1 Vietnam National Library

2 108 Institute of clinica l medical and pharmaceutical sciences

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INTRODUCTION OF THE DISSERTATIONPREAMBLE

AVSD (atrioventricular septal defect) is an anomal characterized by a lack of atrioventricular septal wall with a variety

of abnormalities of the atrioventricular valves The cause of this abnormality is the incomplete connection of the endothelium during pregnancy.AVSD accounts for to 3–5% of CHD (congenital heart defects), and 60% of these cases are partial AVSD

The AVSD repair surgery was first performed in 1951 by Clarence Dennis at the University of Minnesota and cardiopulmonary technology was also first applied in the world.There are many categories of AVSD, but currently AVSD is classified into two groups: complete and partial form The appropriate time for surgical treatment as well as long-term results are issues that have been interested and studied by many authors around the world

The rate of reoperation is still high of 10-25%, depending on each the center, mainly due to the progression of MR (mitral valve regurgitation) or LVOTO (left ventricular ouflow tract obstruction) Therefore, long-term follow-up after surgerywith echocardiography

is a mandatory indication for patients with AVSD

There are many major cardiac surgery centers performed partial AVSD surgery in Vietnam however there have not been yet many general studies on the diagnosis, the diagnostic means, the role

of echocardiography in diagnosis, prognosis and indications for surgery, treatment methods as well as preoperative characteristics affecting treatment results, changes in cardiac morphology and function after surgery of Vietnamese patients

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Therefore, we performed the study "Study on clinical, subclinica l and echocardiographic characteristis of patients with partial AVSD before and after the surgery"

1 Objectives of the study

a Investigate the clinical, subclinical characteristics and Doppler

echocardiography of patients with partial AVSD

b Evaluate clinical, subclinical and morphologica l, fuctional

cardiac changes after surgery in patients with partial AVSD

2 Scie ntific and practical significance and ne w contributions

of the study

This study is a significant scientific and practical research, provides new contributions to the cardiovascular profession in general and to echocardiography in particular:

– This study gives a relatively comprehensive view of partial AVSD in Vietnamese in the following aspects:

+ Clinical: the main symptoms are dyspnea (NYHA II 56,7%), systolic murmur of MR and TR (88.1% and 53.7%, respectively) + Chest X-ray: increased cardiothoracic ratio and increased pulmonary circulation suggestive of left to right shunt flow + ECG: there are some typical signs such as left axis (62.7%), incomplete right bundle branch block (67.2%)

+ Echocardiography: characterized by the presence of the primum ASD (100%) in combination with cleft of anterior mitral valve (97%) The increase in pulmonary pressure was proportional to the diameter of the ASD and the degree of pulmonary pressure was closely related to the time of mechanical ventilation after surgery The percentage of moderate to severe mitral valve rergurgitation was 86.6% and that ofmoderate to severe tricuspid

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valve regurgitation was 79,1% The degree of valve regurgitation

is proportional to number of valve repair techniques

– The study also showed that the efficacy and safety of pAVSD repair surgery vary due to patient’s age, weight as well as the generalcondition.The efficacy and safety of the surgery revealed through the improvement of clinical indexes, the assessment of morphology and cardiac function by echocardiography (decreased pulmonary pressure, decreased MR grade, decreased TR grade, preserved systolic function after surgery, reduce the diameter of RV ) Transthoracic echocardiography is a simple, inexpensive, easy-to-use diagnostic tool to evaluate treatment results and long-term follow-up

3 The layout of the disse rtation

– The dissertation has 136 pages including sections: Introduction (3 pages), chapter I: Overview (33 pages), chapter II: Objects and research methods (26 pages), chapter III: Results (39 pages), Chapter IV: Discussion (32 pages), Conclusion (2 pages), Recommendations (1 page) – The dissertation has 52 tables, 8 charts, 31 pictures, 2 diagrams Use 123 references (20 Vietnamese documents, 97 English documents, 6 French documents)

CHAPTER I OVERVIEW 1.1 Basic knowle dge about partial AVSD

1.1.1 History of research and embryology, anatomical abnormalities of partial AVSD

In 1846, AVSD was first described by Peacock, the lesion identification was incomplete atrial and ventricular septal wall In

1875, Rokitansky was the one who used the term "complete" and

"partial" to describe this pathology

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The anatomical standard of partial AVSD is primum ASD and cleft of anterior leaf mitral valve (few cases do not have) Partial AVSD has separated mitral valve and tricuspide valve with separated and complete valve rings

1.1.3 Pathophysiology of partial AVSD

Because of anatomical abnormalities, many patients with AVSD have one or more of the following disorders: shunt via ASD, left and right atrioventricular valve regurgitation Without surgery, about 15% of untreated patients will develop pulmonary vascular disease and atrial fibrillation in adolescence

1.1.4 Diagnosis of partial AVSD

1.1.4.1 Diagnosis of partial AVSD

The clinical manifestations of the partial AVSD change and are related to hemodynamic changes

Clinical symptoms often appear late with the symptoms such

as shortness of breath, palpitations, and fatigue

Physical signs: a systolic murmur due to increased flow through the pulmonary valve, the seconde sound of pulmonary valve

is loud and splited (prolonging the pulmonary component of the T2)

In addition, the systolic murmur of MR or TR can be heard

1.1.4.2 Paraclinical partial AVSD

Chest X ray

Right ventricular and pulmonary arterylobes are usuallydilated and there is signs of increased pulmonary perfusion

ECG

Classically, the ECG has a left axis with angles from 0 to –

900 Signs of right ventricular hypertrophy w ith rsR'in the precordial leads Left precordial leads or qRs or qRS reflect the degree of right

ventricular hypertrophy Right bundle branch block is also common

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Doppler echocardiography

Echocardiography allows to identify and classify the AVSD morphology In addition to assess morphological changes, echocardiography also evaluates changes in hemodynamic adn functional parameters

Atrioventricular valve morphology: mitral valve and tricuspide

valve are on the same plane, mitral valve leaves and tricuspide leaves cling to the tip of the ventricular septum, with 2 separate atrioventricular valve holes

Cleft of atrioventricular valve: the subcostal view, the

parasternal short axis view and apical four-chamber view provide a clear view of the atrioventricular valves Cleft of anterior mitral valve directly toward to the inlet ventricular septum

Variation in the left ventricular outlet:the anteriorly aortic

shift, not “wedged” between the MV and TV loop, causes the aorta anterior to the atrioventricular junction which may cause LVOTO

Characteristics of the primum ASD: Focal are seen extending

to the atrioventricular valve, no atrioventricular segment, size varies

but often is wide

Several other combined characteristics:

The extension of the LVOT with the ratio of outlet/inlet > 1 Counter-clockwise displacement of the MV chordare The balance/imbalance of the two ventricles and the two atriums There might have inlet VSD without shunt or trivial flow And some other abnormalities can be seen (ventricular dysplasia, stenosis of the RVOT)

Hemodynamic and functional parameters

Echocardiographic parameters include: left ventricular size and function, right ventricular size, degree of MR, TR, ASD shunt, PAP and pulmonary flow (Qp), aortic flow (Qs)

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The above parameters can be assessed simply and accurately

by Doppler echocardiography and can be repeated many times, safely and inexpensively

In the world, the basic knowledge about the disease as well as the treatment of surgery have been studied for a long time In 1954, Lillehei and co-workers successfully carried out the first partial AVSD repair surgery with the good results

The study of Hani K Najm collected data of 180 childrens who had surgery to repair of partial AVSD from 7/1982 to 12/1996

in Canada, the average age was 3.6 years (1 month - 16.4 years) The short term death rate is 1.6% Other complications: atrial arrhythmia, transient atrioventricular block soon after surgery The average postoperative follow up time with echocardiography was 4.6 ± 3.6 years (2 months - 13.7 years) showed that ASD residual shunts accounted for 1%, mild (or no), moderate and severe MR were 85%, 14% and 1% respectively

Research of Krupickova et al (2000 – 2015) on 51 symptomatic patients with partial and transitional AVSD with mean age of 179 days (0 - 357 days), of which 31% of patients had severe valve anomalies The in hospital death rate was 5.9%, 22% of patients had to undergo re-surgery (4 days - 5.1 years), 1 patient had

to replace mechanical valve Multivariate analysis showed that unfavorable anatomical status of MV is an independent risk factor for reoperation MV

Besides, the study of Barnett and colleagues on adult patients (from 13 - 65 years old, the average age is 48 years old), with a Qp/Qs ratio of 3.9 (from 2.4 to 4.4) showed no deaths during hospital stay, improved heart failure through NYHA postoperative evaluation

of patients This suggests the safety and the effect of partial AVSD

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surgeryand should be recommended for all patients to prevent changes in morphology and cardiac function

1.2.2 Studies in Vietnam

In Vietnam, there is a lot of difficulty in early diagnosistherefore many patients come for treatment at high age compared to the recommended age of operation

Le Thi Thanh Xuan and Nguyen Tan Vien published research results on ehocardiography of morphology and hemodynamics in children with AVSD The results showed that the complete AVSD accounted for 71.6%, the rest was partial AVSD; 44% had atrioventricular valve regurgitation, of which none had severe atrioventricular valve regurgitation, 48% had pulmonary hypertesion, 11% had other combined heart defects

Research of Bui Duc Phu and Le Ba Minh Du at Hue Central Hospital on surgical results of 17 cases of AVSD from 1/2000 to 6/2005 There are no death related surgery, the atrioventricular valve regurgitation improved

Most recently (in 2015), Dao Quang Vinh conducted a study

to evaluate the results of partial AVSD surgery The study included

89 patients, the early and first 6-month mortality rate accounted for 1.1%, 1.1% severe MR need to be reoperated The severity of MR decreased and heart failure improved

CHAPTER 2 SUBJECTS AND METHODS OF THE STUDY

2.1 Object of rese arch

Including 67 patients, diagnosed with partial AVSD and had indication for operation at Hanoi Heart Hospital The period was from January 2011 to December 2014

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 Inclusion criteria: Patients were recruited when the following

criteria were met:

a The patient was diagnosed of partial AVSD based on echocardiography results in Ha Noi Heart Hospital:

+ Primum atrial septal atrial (or unique atrial form)

+ MV and TV are separate and located on the same plane + There are cleft(s) of anterior MV leaflet (few do not have)

b The patient was indicated surgery and had surgery to repair partial AVSD at Hanoi Heart Hospital

c Patients agreed to participate in the study

 Exclusion criteria:

a The patient was accompanied by another complex CHD

b Partial AVSD with manifestations of Eisenmenger syndrome (patients with frequent cyanosis, echocardiogrphy showing bidirectional or right to left shunt mainly, cardiac catheterization w ith pulmonary resistance > 10 Wood)

c The patient was operated

d Patients with severe medical illness accompanied

e Patient and family members did not agree to participate in the study

f Patients did not come for follow-up visits or later than 2 weeks

 Sample s ize se lection method: Due to the low proportion of

patients with partial AVSD, we selected a convenient method

2.2 Rese arch methodology

2.2.2 Rese arch design: prospective

2.2.3 Steps to conduct research: We conducted data on patient's

medical history, clinica l examination, subclinical tests, etc according

to the pre-designed study sample The patient evaluation follow up times included: before surgery (time M-1), after surgery and before

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discharge (usually about 1 week after surgery - time M0), 1 month after surgery (time M1), 3 months after surgery (time of M3) and 6 months after surgery (time of M6)

2.2.3.1 Clinical parameters

– General characteristics

– Clinical characteristics: general and local signs

2.2.3.2 Subclinical parameters

Chest X ray: measured cardiothoracic ratio and evaluate

status of pulmonary circulation

ECG: analyzed by standard ECG reading

2.2.3.3 Echocardiography: performed at all the times of

examination, according to ESC 2010 guideline

The diagnostic criteria for partial AVSD and morphological, functional and hemodynamic parameters

2.2.3.4 Surgical parameters and surgical techniques: recorded

parameters related to surgica l procedures (identification of structural abnormalities), performed surgical techniques, time-based parameters surgery and complications

We also offered a number of criteria to evaluate short-term treatment results: early mortality after surgery, the rate of severe patients discharge, the proportion of patients requiring permanent pacemaker implant, the rate of early reoperated within 30 days, the reduction of MR and PAP degree and some other parameters

2.2.4 Data processing

Data entry: information cards of subjects were extracted from

medical records, encoded with passcodes to ensure confidential information The answers were cleaned manually, then entered using Microsoft Excel software

Data analysis

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 The data was processed, converted and analyzed by Stata 12.0 software

 In the process of processing, cleaning the missing values, entered incorrectly, unreasonably, less clearly than comparing with paper questionnaire

 Descriptive statistics are performed by calculating frequencies, averages, and ratios to find the distribution of demographic variables (age, gender), clinica l and subclinica l characteristics

 Inference statistics are shown by the Fisher - Exact test (because there are> 20% of cells have expected frequency <5) when testing the difference between 4 patient groups by 4 age groups in proportion Clinica l and subclinical characteristics Use ANOVA statistical tests (normal distribution and uniform variance) or Krusal - Wallis test (if non-standard distribution) to compare the differences between quantitative indicators by 4 age groups

 Student Use the Student’s t – test paired test (with standard distribution) or Wilcoxon signed - rank test (without standard distribution) to compare the difference before and after in terms

of quantitative indicators from time to time For qualitative variables, compare the ratios before and after using the Chi square test of McNemar (with table 2x2) and McNemar - Bowker test (with table 2xn) to evaluate at the above times compared to the time of admission

 Statistical significance level α = 0.05 is applied

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Calculate the value of echocardiography in diagnosis:

Sensitivity = a/(a+b); Specificity = d/(c+d)

Positive predictive value = a / (a + c);

Negative predictive value = d / (b + d)

The results were presented in tables and charts

2.3 Rese arch ethics

The study did not violate ethical regulations when studying biomedical research Before recruited in this study, patients were fully explained about the purpose, requirements and content of the study After that, those patients who voluntarily participated would

be included in the research, had full corrective surgery when indicated and consulted with the whole hospital, the report of the consultation and the patients agree to surgery The patient's condition and other personal information is kept confidential The study was approved by the hospital-level ethics committee Do not take patients

to test unrecognized treatments The purpose of the study is to protect and improve public health

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