Study on clinical, subclinical, echocardiographic characteristics of patients with partial atrioventricular septal defect before and after surgery

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 knowledge 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. 4 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 with 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. 5 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). 6 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 7 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 research 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. 8  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 with 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 size se lection method: Due to the low proportion of patients with partial AVSD, we selected a convenient method. 2.2 Research methodology 2.2.2 Research 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 9 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 10  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. 11 Calculate the value of echocardiography in diagnosis: Diagnosis of surgery Total (+) (–) Diagnosis of echocardiography (+) a c a + c (–) b d b + d Total a + b c + d a + b + c + d 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. Research 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. 12 RESEARCH CHART 13 CHAPTER 3 RESEARCH RESULTS 3.1 General characteristics of the study patient group The median age was 192 months (16 years), the youngest of 4 months, the oldest of 64 years. We divided patients into 4 age groups, from 2 years old and younger (22.4%), from 2 to 5 years old (14.9%), from 5 to 16 years old (13.4%) and over 16 years old (49,3%). The distribution of patients by gender male/ female is 46.3% and 53.7%. 3.2 Clinical and subclinical characteristics of the subjects 3.2.1 Clinical characteristics of research subjects – Reasons for detecting the disease: various, dyspnea accounted for 22.4% and other reasons 29.9%. – Functional characteristics: the most common symptom is shortness of breath with 56.7% of patients at NYHA II, 1.5% at NYHA III, no patients at NYHA IV. – Physical characteristics:the splitted S2 at pulmonary valve location were 46.3% and 23.9%, respectively, systolic murmur of MR and TR were 88.1% and 53.7% respectively. – Patients with Down syndrome were 7.5%. – Children get often recurrent bronchitis and delayed weight (40% and 26.7% in children under 2 years, respectively). 3.2.2 Subclinical characteristics of research subjects 3.2.2.1 Some subclinical characteristics of the research subjects Chest X-ray: 94.0% with cardiothoracic ratio > 50%, 49.3% with signs of increased pulmonary circulation. ECG: – Some basic parameters: sinus rhythm was 91%, 5 patients with atrial fibrillation (7.5%) and 1 patient with BAV III (1.5%). ECG 14 axis was mainly left axis (62.7%). 01 case of WPW (1.5%), no other arrhythmias. – Some characteristics of conduction system: incomplete right bundle branch block was primary (67.2%). BAV I was also common (34.3%). 3.2.2.2 Some characteristics of the Doppler echocardiography of the research subjects Some basic parameters – The majority of patients had good systolic left ventricular (EF) function before surgery and there was no difference between age groups. There were 16.4% of cases with left ventricular dilatation, but up to 92.5% with right ventricular dilatation. – Heart valve anatomy characteristics: 97% with "cleft" on anterior leaf of MV. 89.6% of patients had 2 balanced papillary muscle (10.4% had 2 muscle columns but unbalanced). 22.4% had "cleft" on septal leaf of TV. 22.4% had dysplasia TV. – Valve regurgitation characteristics: 65,7% were severe regurgitation of mitral valve, and 47,8% were severe regurgitation of tricuspid valve. – Heart septal perforation: large primium ASD (100%) with median diameter of 22 mm, 94% left-right shunt, 6% had bidirectional shunt but not often. – Some hemodynamic characteristics: 13.6% of patients did not have pre-operated HTAP, the severity of HTAP was: 18.2% mild, 39.4% moderate and 28.8% severe. The highest PAP group (≥ 60 mmHg) was the oldest (median is 20 years old). 3.3 Clinical, subclinical and morphological changes, cardiac function after surgery in the study patient group 3.3.1 Clinical changes after surgery 15 The change of functional signs: 58,2% patients was dyspnea before surgery with NYHA II, III however, 100% patients had NYH I at the follow-up time of 1 month, 3 months, 6 months. Changes of physical signs – The rate of systolic murmur of MR and TR postop were much lower than preop (before surgery and after 6 months, MR murmur reduced from88.1% to 15.4%, TR murmur from 53.7% to 0%). – A strong and splited T2 sound is almost non-existent in patients after surgery. 3.3.2 Subclinical changes after surgery 3.3.2.1 Changes of some subclinical characteristics Chest x-ray: 94% patients hadcardiothoracicratio ≥ 50% before surgery which reduced to 32.7% one month after surgery, signs of increased pulmonary circulation decreased from 49.4% to 1.9%. ECG: There was no significant change with parameters such as heart rate pattern, ECG axis, bundle branch block, atrioventricular block. 3.3.2.2 Changes in echocardiography characteristics aftersurgery Some basic parameters: increased LV end – diastolic diameter, in contrast, decreased RV end – diastolic diameter compared to before surgery and no significant change in the EF index. Changes in regurgitation of atrioventricular valve: there was a significant improvement in the degree of MR and TR over time. 16 Table 3.31. The degree of ventricular valve regurgitation over time Characteristics M-1 (1) Mo (2) M1 (3) M3 (4) M6 (5) p n (%) n (%) n (%) n (%) n (%) Mitral regurgitation No - Mild 9 (13,4) 39 (58,2) 36 (69,2) 29 (70,7) 29 (74,4) p2-1: <0,001 p3-1: <0,001 p4-1: <0,001 p5-1: <0,001 Moderate 14 (20,9) 25 (37,3) 15 (28,9) 9 (22,0) 7 (17,9) Severe 44 (65,7) 3 (4,5) 1 (1,9) 3 (7,3) 3 (7,7) Tricuspide regurgitation No - Mild 14 (20,9) 46 (68,7) 48 (92,3) 37 (90,2) 34 (87,2) p2-1: <0,001 p3-1: <0,001 p4-1: <0,001 p5-1: <0,001 Moderate 21 (31,3) 17 (25,4) 4 (7,7) 4 (9,8) 5 (12,8) Severe 32 (47,8) 4 (6,0) 0 0 0 Evaluation of changes in PAP over time: Preop mean systolic PAP was 43.3 mmHg, 1 month - 3 months - 6 months after surgery were 25-26 and 25 mmHg respectively. 3.3.3 Surgical parameters and related to the preoperative condition Reconstruct some assessment of atrioventricular valve abnormalities at surgery compared with preoperative echocardiography – Surgeons agreed with the diagnosis of partial AVSD: 100%. – There was a high agreement on the rate of diagnosis of cleft of MR (97% ultrasound and 94% surgeon). The value of echocardiography in diagnosing some atrioventricular valve abnormalities 17 Table 3.36. Value of echocardiogram in the diagnosis of atrioventricular valve abnormalities Parameter Cleft of MV Dilatation ring of MV Cleft of TV Hypoplasia of septal TV Sensitivity 98 2,4 66.6 29,2 Specificity 25 96 79,7 88,5 Predictive positive value 98,4 50 13,3 80 Negative predictive value 50 38 98 44 The results show that: assessing MV abnormalities had high sensitivity and positive predictive value. The techniques used for repairing MV and repairing TV: close of cleft MV was the most common (94%), for TV, the most used techniquewas the De Vega method (49.3%). The relationship assessment showed that the degree of MR, TR before surgery was closely related to the number of methods used to repair valves. Analysis of the relationship of preoperative systolic PAP with the perioperative: there was a close relationship with the time of mechanical ventilation, the higher of pre-operative PAPs, the longer the mechanical ventilation would last. But no association was found between the degree of preoperative MR and the surgical period. Table 3.44. Summary of some short-term treatment results Parameters Patients (n) Percent (%) Discharge 67 100 Reoperation 2 3,0 18 Permanent pacemaker implant 1 1,5 Temporary pacemaker implant 4 6,0 Discharge to die at home 0 0 Death 0 0 Evaluation of treatment results based on criteria of reducing MR, PAPs or both: there was a clear improvement (comparing the time 1 week - 1 month after surgery with preoperation): the degree of MR well reduced after 1 week - 1 month surgery was 73.1% and 82.7%, respectively; similar to the reduction in systolic PAPs 1 week - 1 month of 89.4% and 90.4%, respectively; combining these two criteria, the ratio was 61.2% and 73.1%, respectively. Some complications during and after surgery: no premature death, BAV III rate was 11.9% but 6/8 cases recovered to sinus before discharge, in addition to the rate of pneumonia - bronchopneumonia accounting for 17.9%, heart failure 7.5% and some other complications. CHAPTER 4 DISCUSS 4.1 General characteristics of the study patient group Patient age: the late detection of congenital heart disease was a feature of our current socio-economic conditions. A study of 40 years of partial AVSD surgery at the Mayo Clinic, the median age of patients was 9.6 years, 6.1 years and 7.2 years, respectively during the 50s, 70s and 80s. 4.3 Clinical, subclinical and morphological changes, cardiac function after surgery in the study patient group 4.3.1 Clinical changes after surgery 19 4.3.1.1 Changes in functional signs: There was a statistically significant change in functional signs before and after surgery (dyspnea NYHA II, III before surgery accounted for 58.2%, 100% at NYHA I at any time postoperative), this result was similar to the result of the author Dao Quang Vinh and some other authors. This showed an improvement in patients after surgery regardless of age. 4.3.2.2 Change of physical signs: – There was a clear change in heart auscultation, the rate of systolic murmur of MR and TR were recorded to decrease much compared to before surgery. MR after surgery was the leading cause of the re-surgery of patients with partial AVSD, the new appearance or the increase of MR murmur would be a sign that suggested the next indications to be done for evaluation (echocardiography). – A strong, splitting T2 sound did not appear after surgery (showing a significant decrease in blood flow to the lungs, a significant reduction in PAP). 4.3.2 Subclinical changes after surgery 4.3.2.1 Change of some subclinical characteristics Chest X Ray Cardiothoracic ratio, signs of increased pulmonary circulation and significant decreased PAP after surgery indirectly showed that pulmonary vascular disease was not a problem of the patient in this study. ECG There were no significant changes with most of the basic parameters except for a significantly lower heart rate compared to before surgery. Particularly 5 cases of atrial fibrillation before surgery were over 40 years old, 2 patients had sinus rhythm after surgery. This wasreally important for the patient, as atrial fibrillation was the 20 premise of the risk of stroke. There were 2 cases of BAV III with permanent pacemaker (3%), lower than some other studies reported by Di Mambro et al. 7.5%. 4.3.2.2 Changes in echocardiography characteristics after surgery Some basic parameters Longitudinal follow-up showed a significant change in the LV end-diastolic diameter (Dd) which was greater than before surgery, in contrast, the RV end-diastolic diameter was smaller before surgery and there was no significant change in the EF index. Our results were similar to those reported by Nguyen Thi Mai Ngoc and author Dao Quang Vinh. There was no left-right shunt after surgery to help reduce the volume and pressure RV, so it did not affect ventricular septal and left ventricle. Left ventricular systolic function remained within normal range before surgery and along the time of follow-up, as the study of author Dao Quang Vinh showed that surgery did not adversely affect heart function. Characteristics of MR and TR after surgery The rate of MR severe was high before surgery and decreased significantly after surgery. Three patients with severe MR at 3 months, 6 months were> 50 years old and 2 of them had atrial fibrillation before surgery. This showed the relationship between age of surgery and the ability to succeed in terms of valve repair, author Sarisoy and colleagues also reached the same conclusion. The rate of reoperation through many studies ranged from 11- 16% (author El-Najdawi et al., O'Sullivan et al.) with the reason of MR, stenosis of LVOT. Stulak et al's study showed that the reoperation time was about 10 years. We therefore need to continue 21 monitoring and evaluating the progression of MR with echocardiography. Repair of TR also achieved good results, similar to the research results of author Dao Quang Vinh, author Waqar et al. Results in terms of hemodynamics In our study, it showed a significant decrease of PAP compared to before surgery at all times with median PAPs value at the time before surgery, 1 week, 1 month, 3 months after surgery and