Nghiên cứu kết quả phẫu thuật fontan trong điều trị bệnh nhân tim bẩm sinh có sinh lý tuần hoàn một thất TT TIENG ANH

MINISTRY OF EDUCATION AND MINISTRY OF TRAINING HEALTH HANOI MEDICAL UNIVERSITY TRAN DAC DAI OUTCOMES AFTER THE EXTRACARDIAC FONTAN PROCEDURE IN PATIENTS DIAGNOSED WITH SINGLE-VENTRICLE LESIONS SUMMARY OF PHD THESIS HANOI – 2021 MINISTRY OF EDUCATION AND MINISTRY OF TRAINING HEALTH HANOI MEDICAL UNIVERSITY OUTCOMES AFTER THE EXTRACARDIAC FONTAN PROCEDURE IN PATIENTS DIAGNOSED WITH SINGLE-VENTRICLE LESIONS Specialized : Pediatrics Code : 62720135 SUMMARY OF PHD THESIS HANOI – 2021 THIS STUDY WAS COMPLETED IN: HANOI MEDICAL UNIVERSITY Supervisor: Prof Dr LE NGOC THANH Dr DANG THI HAI VAN Reviewer 1: Reviewer 2: Reviewer 3: The thesis will be defended before the Examining Board at university level in Hanoi Medical University At o’clock Date Month Year THESIS INTRODUCTION Background Many various studies aimed to evaluate and determine factors associated with the outcome of Fontan surgery in congenital heart patients with single-ventricle lesions, but most of the single-center reports from developed countries, and there is no consensus on the results as well as the incompleteness of input data on research variables This requires the need for continued extensive research in many different centers, especially in countries with resource-scare conditions Therefore, we conducted this study, examining a range of the variables both before, during and after operation to identify risk factors that might be associated with the key outcomes in surgical treatment with Fontan operation The number of patients with single ventricle heart is still very large and requires more comprehensive studies evaluating this issue At E Hospital, several initial research results stopped at the pathological characteristics and results of the Bidirectional Glenn Procedure as well as the indication of extracardiac conduit Fontan procedure In the retrospective study of Pham Huu Minh Nhut and Tran Quyet Tien on 122 cases of Fontan surgery at the Heart Institute of Ho Chi Minh City (2015–2019), the authors compared the characteristics before, during and after Fontan surgery between the fenestration group and non-fenestration group in Fontan surgery, however, early, and late complications as well as risk factors have not been fully evaluated Hence, we conducted the study thesis titled “Outcomes after the Extracardiac Fontan Procedure in Patients Diagnosed with SingleVentricle Lesions” with the aims: To evaluate outcomes after the extracardiac Fontan procedure in patients diagnosed with single-ventricle lesions To analyse several associated factors with the outcomes after the extracardiac Fontan procedure in patients diagnosed with singleventricle lesions The topicality of thesis In resource-scare settings like Vietnam, it is difficult us to acquire all important data for a large cohort of consecutive patients with single-ventricle lesions that underwent an extracardiac Fontan operation Compared to developed nations, Vietnam is facing many challenges in delivering care for children with congenital heart disease (CHD) in general and single-ventricle lesions, known as late diagnosis, inadequate infrastructure, and personnel and inadequate supply of drugs In Vietnam, the patients who are diagnosed with CHD follow a stepwise sequence by which they are transferred from the district to provincial hospitals and then to city’ hospitals Few lucky chil- dren are benefited from the timely detection of CHD, and importantly, there may still be many more who die due to undetected CHD Scientific contributions of thesis This is the first study in Vietnam with the largest scale to comprehensively evaluate the outcomes of Fontan surgery in congenital heart patients with single-ventricle lesions, as well as its associated factors In the early postoperative period, the survival rate at the time of discharge was 91.0%, there were no more patients with grade III heart failure after surgery and the mean SpO2 improved from 81.2% before surgery to 95.2% after surgery The rate of early Fontan failure is 9.7% Early mortality rate was 9.0%, which was due to early Fontan failure Early complications included failing Fontan circulation (6.9%), acute renal failure (6.2%) and prolonged pleural effusion (20.0%) In the medium-term period, the mean postoperative follow-up time for re-examination was 44.9 ± 19.9 months The survival rate to the time of last follow-up was 91.6% The mortality rate in the medium term is 8.4% The proportion of patients with arrhythmia at the time of re-examination was 33.7%, higher compared to before surgery (7.6%) and at hospital discharge (5.3%) 7.4% those happened complications in the medium term In which, 4.2% of patients were diagnosed with protein-losing enteropathy (PLE) and 3.2% of those had neurological complications There were no cases of thrombosis in the Fontan tube at the time of re-examination There were independent risk factors that were statistically significantly associated with early Fontan failure, which was an increase in mean preoperative PAP (OR: 1.8; 95%CI: 1.1–3.0), atrioventricular valve repair at the same time as Fontan surgery (OR: 65.8; 95%CI: 1.9–2228.1), and the mean postoperative PAP (OR: 1.6; 95%CI: 1.1–2.3) There were independent risk factors associated with prolonged pleural effusion after Fontan surgery, including preoperative NYHA class III (OR: 4.9; 95%CI: 1.1–20.5), primary anatomical diagnosis of DORV with TGA (OR: 31.0; 95%CI: 1.3–711.6), pre-Fontan AV vale regurgitation (OR: 70.7; 95%CI: 3.2–1523.2), the existence of pre-Fontan ventricle-to-pulmonary artery shunt (OR: 8.2; 95% CI: 1.6–42.7), low pulmonary artery index (PAI) (OR: 0.98 ; 95%CI: 0.97–0.99) and high PAP in the operation (OR: 1.2; 95%CI: 1.01– 1.5) There were independent risk factors associated with atrial rhythm status after Fontan surgery, including low pulmonary artery diameter (OR: 0.99; 95%CI: 0.98–0.99) and high immediate PAP after surgery (OR: 1.3; 95%CI: 1.05–1.6) Thesis structure The thesis has 135 pages with (excluding appendices and references) Background (2 pages), Literature Review (36 pages), Subjects and methods of study (21 pages), Results (36 pages), Discussion (37 pages), Conclusion (2 pages) and Recommendations (1 page) There are 37 Tables, Figures and 12 Images The reference includes 185 references in which are Vietnamese and 178 are English CHAPTER 1: LITERATURE REVIEW 1.1 Heart single ventricle 1.1.1 Definition A single ventricle is defined as the presence of two atrio-ventricular valves with one ventricular chamber or a large dominant ventricle associated with a diminutive opposing ventricle 1.1.2 Pathophysiology With a single ventricle, mixed oxygenated blood circulates throughout the body Depending on the structural anomaly, a patent ductus arteriosus (PDA), atrial septal defect (ASD), ventricular septal defect (VSD), or communication in the great arteries may be required to maintain pulmonary and systemic circulations More information about anatomical requirements can be found under each disease's respective chapters 1.1.3 Treatment for single ventricle A series of operations are performed in the first few years of life that will re-route blood so that enough oxygen is added to the bloodstream to meet the child's needs Each operation is performed under general anesthesia Types of operations include the following: Blalock-Taussig shunt, Glenn Shunt and Fontan Procedure Long-term outlook after single ventricle surgical repair: Infants will remain cyanotic after the first two operations until the final operation (Fontan procedure) is performed Your child will likely grow and develop more slowly than the average baby because of the lower amounts of oxygen available for the body's needs Following the Fontan procedure, when oxygen levels improve, many children will see major improvements in growth and development, and can eventually catch up to normal children There is significant risk for progressive development of complications such as heart failure, dysrhythmias, thromboembolism, Fontan obstruction, cyanosis, venous insufficiency, liver disease, and protein-losing enteropathy (loss of protein in the stool from higher venous pressures in the Fontan) as these individuals become adults Pregnancy and non-cardiac surgeries pose major risks and require careful evaluation and discussion with a congenital cardiologist Regular follow-up care at a center offering adult congenital cardiac care should continue throughout the individual's lifespan Flu shots are recommended annually, and pneumococcal vaccine should be received according to the doctor's recommendation 1.2 Diagnosis of a single ventricle Echocardiography is the best modality for the diagnosis of a single ventricle Other techniques may aid in the diagnosis of a single ventricle, including electrocardiography, plain chest films, and pulse oximetry Physical exam findings may also support the diagnosis Computed tomography (CT), cardiac catheterization, magnetic resonance imaging (MRI), and cardiac magnetic resonance imaging might also reveal a single ventricle but are typically reserved for indeterminant investigations or treatment Key univentricular variations and typical features: - Hypoplastic left heart syndrome (HLHS): The left ventricle, mitral valve, aortic valve, and aorta are underdeveloped - Tricuspid atresia: The tricuspid valve fails to develop, leading to an underdeveloped right ventricle - Ebstein anomaly: Abnormal development of tricuspid valve leaflets causes right ventricular atrialization The anomaly is associated with various cardiac structural abnormalities, including pulmonary valve pathologies, septal defects, and electrical conduction lesions - Double outlet right ventricle: The aorta and the pulmonary artery exit from the right ventricle, leaving the left ventricle underdeveloped - Double inlet left ventricle: Both atria connect to the left ventricle, resulting in an underdeveloped right ventricle - Atrioventricular canal defect: An atrial or ventricular septal defect forms large enough to make a functionally single ventricle 1.3 Management of single ventricle Univentricular heart syndrome medical management is targeted to the underlying pathology Supplemental oxygen will help alleviate hypoxemia, and acid-base or metabolic disturbances should have correctable factors mended Inhaled nitric oxide is beneficial to reduce resistance in the pulmonary vasculature, allowing more blood to be oxygenated by the lungs In strained hearts, inotropes may assist contraction force, but catecholamines should be avoided due to arrhythmogenesis When a patent ductus arteriosus (PDA) is needed to maintain collateral flow, prostaglandin E1 prolongs the opening of the ductus arteriosus, providing a bridge to permanent interventions Non-steroidal anti-inflammatory medications should be avoided to maintain a patent ductus arteriosus Catheter-based management is also based on underlying etiology, time of discovery, and prognosis When discovered in utero, catheter-based structural interventions and valvuloplasty can mitigate sequala by correcting anomalies during the developmental process Many interventions can also be performed after delivery, though further development is less influenced In Ebstein anomaly, associated pulmonary arteriovenous malformations can be occluded using a transcatheter approach Surgical intervention can also correct any of the abovementioned anatomical variations, though technique varies by condition The Fontan procedure, a popular choice for intervention, works by delivering blood to the lungs utilizing central venous pressure, and reduced intrathoracic pressure.[39] Optimal pressure dynamics with low pulmonary flow resistance allows for anterograde circulation.[40] Though reliably successful, the Fontan procedure should not be the only option considered In patients with severe disease, palliative surgery may be the best option and is typically preferred over choosing strict comfort measures Data is unclear if the Fontan procedure is superior to palliative options Patients should be referred to tertiary care centers for specialized evaluation and treatment Cardiac transplantation may be considered, albeit associated with suboptimal outcomes due to comorbidities Cardiac transplantation may also be required despite previous alternative procedures 1.4 Outcomes after the Fontan procedure The impact of Fontan circulation on the functioning of the whole body varies over time There are two main stages of action with different pathological features, clinical symptoms and pathophysiological mechanisms: early period after Fontan surgery; The late period is after 30 days until the appear of early Fontan failure 1.4.1 Early complications and its risk factors 1.4.1.1 Pathological characteristics, complications and mortality Pathophysiological features appear in the early stage due to the acute nature of the disorder of fluid distribution in the body The main clinical manifestations are decreased peripheral perfusion and increased Fontan system pressure These symptoms are encountered in varying degrees depending on the individual patient's adaptability to the Fontan circulation - With well-adapted cases (due to low Fontan system resistance, and good cardiac function and heart valves): usually a relatively mild clinical presentation Pulmonary arterial pressure was slightly elevated, blood pressure and cardiac output remained approximately 80% of normal, edema was mild, and vasopressors were not maintained - With poorly adapted cases: clinical manifestations are very severe, anuria, low blood pressure, hepatomegaly, edema, prolonged effusion Requires large volumes of fluid and responds poorly to conventional vasopressors The progressive severity, unresponsiveness to therapies leads to irreversible multi-organ dysfunction, gradually leading to EFF status, which is the main cause of death in this period Early-stage disease includes issues: risk of pleural drainage, length of stay, mechanical ventilation, prolonged use of vasopressors In addition, another pathological phenomenon that can also be seen at an early stage, although the rate is quite low, is hypercoagulability and the risk of thrombosis Mortality rate: In the first decades of the implementation of Fontan surgery, reports of EFF occurred with a rate of about 10% and was the main cause of mortality ranging from - 15% Over time, along with the improvement of surgical technique as well as the progress of postoperative resuscitation strategies, the rate of EFF has gradually decreased, below 3% in many randomized reports And less than 1% in select reports 1.4.2 Early complications and its risk factors Due to the characteristics of prolonged circulatory failure and silent progression, increasing over time, late complications after Fontan surgery are divided into two groups: - “Failing Fontan circulation” includes symptoms that occur but still maintain the Fontan circulation in the body and at this stage interventions for assessment and treatment are still available can be improved 11 double-inlet single ventricle, Ebstein anomaly, PA with IVS, Corrected congenital TGA, DORV with TGA, Unbalanced AV septal defect, AV septal defect with TGA), visceroatrial situs, systemic ventricular morphology, number of AV valve, AV valve regurgitation, AV valve status, systemic ventricular outflow obstruction Subaortic stenosism, restricted VSD, cavopulmonary anastomosis stenosis - Measurements on pre-Fontan cardiac catheterization - Indicators in surgery and after surgery in ICU 2.5.2 Outcome variables - Early complications: postoperative Fontan circulatory failure, acute renal failure, early postoperative arrhythmia, persistent pleural effusion, thromboembolic neurovascular events, infective endocarditis, storm reduction hypoxemia, persistent infections other than endocarditis, Fontan failure, and death - Late complications: arrhythmia, PLE, risk of hypercoagulability and neurological complications, physical development, and death 2.6 Data analysis Data entry was using Epidata 3.1 software Data were cleaned, processed and analyzed using Stata 13.1 software We applied Mann-Whitney test, Fisher's exact test, Sign test, t test, univariate and multivariable logistic regression models with stepwise backward strategy with p-value < 0.2 A pvalue < 0.05 was considered to be statistically significant CHAPTER 3: STUDY RESULTS During the study period from August 2012 to December 2019, a total of 145 patients diagnosed with CHD with single-ventricular physiology underwent Fontan surgery at the Cardiovascular Center of E Hospital 3.1 General characteristics of the study patients 3.1.1 General characteristics of patients at the pre-Fontan Among study patients, men account for a higher percentage than women The male/female ratio is 1.4 The mean age was 68.1 ± 54.0 months The average height and weight were 103.2 ± 18.5 cm and 16.5 ± 8.1 kg, respectively The average SpO2 value is 81.2 ± 4.3 % 12 All patients had preoperative heart failure, mainly grade II and III heart failure, and no patients had severe heart failure Most patients had sinus rhythm on electrocardiogram (92.4%) Only 11 patients had arrhythmias (7.6%) 3.1.2 Characteristics on echocardiography of patients at the pre-Fontan With the use of Doppler echocardiography at the pre-Fontan, anatomical diagnosis was based on the morphological types of the cardiac struc- ture of patients The most common anatomical diagnosis was DORV with TGA (n = 43, 29.66%), followed by tricuspid atresia (n = 24, 16.55%), AVSD (n = 22, 15.17%), double- inlet single ventricle (n = 21, 14.48%), mitral atresia/hypo- plastic mitral valve (n = 10, 6.90%), and corrected congenital TGA (n = 10, 6.90%) Other forms included AV septal defect with TGA (n = 8, 5.52%), Ebstein anomaly (n = 4, 2.76%), and PA with IVS (n = 3, 2.07%) Situs solitus was the most common form (n = 108, 74.48%), followed by situs inver- sus (n = 22, 15.17%) and situs ambiguus (n = 15, 10.34%) Preoperatively, systemic right ventricle and systemic left ventricle both accounted for 24.00%, with 35 patients, while 58 patients (40.00%) had two-ventricle morphology The remaining 17 cases (11.72%) had an unidentified sys- temic ventricular morphology 69 patients (47.59%) with one AV valve and 76 those (52.41%) with two AV valves were recorded More than half of patients had mild AV valve regurgitation (n = 79, 54.48%), while the figure for moder- ate AV valve regurgitation was 20.00% (n = 29) patients (5.52%) had systemic ventricular outflow obstruction, of which subaortic stenosis was patients and restricted VSD was patients Doppler echocardiography revealed that one case had cavopulmonary anastomosis stenosis, and case had pulmonary artery distortion Patent ductus arteriosus remained among patients (1.38%) 15 patients (10.34%) had large aortapulmonary circulation, while 50 patients (34.48%) had ventricle-topulmonary artery shunt 3.1.3 Several main data in the cardiac catheterization at the pre-Fontan Preoperatively, the mean PAP was 11.42 ± 2.16 mmHg (measuring at 142 patients) The mean VEDP was 5.05 ± 1.62 mmHg (measuring at 129 13 patients) The mean PAI was 319.46 ± 124.27 mm2/m2 (measuring at 137 patients) The mean Rp was 1.91 ± 0.80 Wood Unit per m2 (measuring at 64 patients) Also in the cardiac catheterization, large aortapulmonary circulation was in 50 patients (34.48%) 3.2 Fontan surgery outcomes 3.2.1 Intraoperative characteristics Fenestration was performed in 145 study patients Pulmonary artery reconstruction was performed in 15 patients (10.34%) Atrial septostomy procedure was performed in 16 patients (11.03%) Other operative procedures included DKS in patients (2.76%), repair of AV valve in patients (2.76%), AV valve replacement in case (0.69%), dissection APCA in case (0.69%), and ligation APCA in case (0.69%) Aortic cross-clamping was used in 126 patients (86.90%) patients (4.83%) had surgical bleeding patients (6.21%) were happened with edema after surgery 3.2.2 Early results after Fontan surgery 3.2.2.1 Hemodynamic parameters and symptoms of edema immediately after surgery Immediately after surgery in the recovery room, the average SpO2 value was 95.2 ± 5.3 % There were patients with edema immediately after Fontan surgery, accounting for 6.2% 3.2.2.2 Early complications after Fontan surgery Complications encountered were mainly prolonged pleural effusion (20.0%) patients had complications of acute renal failure (6.2%) 10 patients had circulatory failure after Fontan surgery (6.9%) 3.2.2.3 Early Fontan failure The prevalence of early Fontan failure was 9.7% (14/145 patients) Of these, 13 died (92.9%) Compared to the total number of studies, the overall mortality rate was 9.0% A patient with early Fontan failure underwent surgery to terminate Fontan circulation, reverting to the preoperative bidirectional Glenn form, and did not need to use ECMO support The time from Fontan surgery to the end 14 of Fontan circulation was days The primary cause of Fontan circulatory failure in this patient was hemodynamic instability unresponsive to treatment 57.1% of the early Fontan circulatory failure group found cause, the rest were identified due to different causes 3.2.2.4 Time of mechanical ventilation, recovery time and hospital stay after Fontan surgery Thirteen patients died in the recovery period after Fontan surgery At the time of discharge, there were 132 patients The average number of days in resuscitation is 7.8 ± 9.5 days, the shortest is days, the longest is 70 days The average number of mechanical ventilation hours was 50.8 ± 130.2 hours The average number of days of pleural drainage was 13.9 ± 11.4 days The shortest number of days for pleural drainage is days The longest number of days of pleural drainage was 79 days 3.2.3 Medium-term results after Fontan surgery Among 145 patients who received Fontan surgery wihtin years, 13 of them died during the ICU period after Fontan surgery There were 132 patients at the time of discharge; however, we only analyzed data from 131 patients due to case underwent Fontan takedown 95 patients were reexamined after Fontan surgery The mean postoperative follow-up time was 44.9 ± 19.9 months The shortest follow-up time was month and the longest was 90.3 months after Fontan surgery 3.2.3.1 Number of re-hospitalizations after Fontan surgery 26 out of 95 patients need to be hospitalized for treatment after Fontan surgery, accounting for 27.4%, with the number of hospitalizations from to times 3.2.3.2 Percentage of patients with heart failure after Fontan surgery There is a difference in the proportion of patients with heart failure before and after surgery After surgery, only patient had heart failure grade II 3.2.3.3 Percentage of patients with cardiac arrhythmias at time points The proportion of patients with arrhythmia at the time of follow-up was 33.7% higher than before surgery (7.6%) and at hospital discharge (5.3%) 15 3.2.3.4 Remaining problems of patients after Fontan surgery on echocardiography There were patients with small thrombus attached to the wall of the Fontan tube, however, there was no case of thrombosis in the Fontan tube at the time of follow-up Although 16 patients had a Fontan window observed at discharge, only patient had a Fontan window at the time of postoperative follow-up There were no cases of thrombus in the apical apex at the time of discharge, however, at the time of re-examination we found patients with thrombosis in the coccygeal artery even though the patient was treated according to the antiretroviral regimen Platelet thrombolysis with Aspirin unified by Cardiovascular Center E Hospital 14 patients tended to have subaortic stenosis at the time of discharge as well as at the time of re-examination However, at the time of discharge, we did not record information about the narrow position At the time of re-examination, 10 patients had a tendency for ventricular septal defect (71.4%) and patients had a tendency for subvalvular stenosis (28.6%) 3.2.3.5 Techniques performed after Fontan surgery After Fontan surgery, a total of 10 procedures were performed The total number of procedures performed was 45 times Of which the most is the pulmonary artery occlusion intervention (12.6%) 10 patients diagnosed cardiac catheterization (10.5%) Thus, the problem of dealing with a pulmonary embolism after Fontan’s surgery needs further research 3.2.3.6 Protein-losing enteropathy During the follow-up period, 4/95 patients had intestinal protein loss syndrome, accounting for 4.2% Four patients were diagnosed with intestinal protein loss syndrome In which, there were deaths after that, the procedures performed with these two patients were diagnostic cardiac catheterization, surgery to reopen the Fontan window, and repeated pleural drainage 3.2.3.7 Risk of hypercoagulability and neurological complications During the study period, there were patients with neurological complications after Fontan surgery, accounting for 3.2% There were patients experiencing neurological complications after Fontan surgery; in which, the death was in case and cerebrovascular accident-causing hemiplegia were cases 3.2.3.8 Mortality rate after late-stage Fontan surgery Of the 95 patients who were followed up after surgery, there were deaths (8.4%) The main causes of late death after Fontan surgery were heart failure and 16 Fontan circulatory failure Of these, died at the hospital and died at home of unknown cause The earliest time of death was month after discharge, the patient had pericardial effusion detected late The latest time of death was 59 months after discharge The cohort of patients with Fontan survival at 36 months (3 years) at discharge was estimated by functional survival of 94.70% 3.2.3.9 Physical development of patients after Fontan surgery The mean preoperative weight was 14.3 ± 21.3 (the percentile), the percentage from under 5th was 51.5%, over 85th was 2% The mean postoperative weight was 28.0 ± 27.9 (percentile), the percentage below 5th decreased to 27%, over 85th was 4% The mean preoperative height was 19.5 ± 24.1 (percentile), the percentage from less than 5th was 37.6%, over 85th was 3% The mean postoperative height was 26.1 ± 27.4 (percentile), the rate below 5th decreased to 26.7%, above 85th was 5% 3.3 Factors associated with the outcomes after Fontan surgery 3.3.1 Factors associated with early Fontan failure There were prognostic factors that were statistically significantly associated with early Fontan circulatory failure: mean pulmonary arterial pressure elevation before surgery (OR: 1.8; 95%CI: 1.1–1) 3.0; p=0.016), the conduct of AV valve repair at the same time as Fontan surgery (OR: 65.8; 95%CI: 1.9–2228,1; p=0.020), and the increased mean pulmonary arterial pressure after surgery (OR: 1.6; 95%CI: 1.1–2.3; p=0.004) 3.3.2 Factors associated with prolonged pleural effusion There were independent risk factors associated with prolonged pleural effusion after Fontan surgery, including: the NYHA class III (OR 4.93, 95%CI: 1.19–20.50, p=0.028), double-outlet right ventricle (DORV) with transposition of great arteries (TGA) (OR 31.00, 95%CI: 1.35–711.63, p=0.032), AV valve regurgitation (OR 70.73, 95%CI: 3.28–1523.28, p=0.007), ventricle-to-pulmonary artery shunt (OR 8.29, 95%CI: 1.60–42.78, p=0.012), PAI (OR 0.98, 95%CI: 0.97–0.99, p=0.002) at pre-Fontan, while, at Fontan, high PAP (OR 1.24, 95%CI: 1.01–1.53, p=0.046) was an independent predictor for prolonged pleural effusion 3.3.3 Some factors associated with atrial rhythm status at follow-up visit 17 There were independent risk factors associated with arrhythmia complications (atrial rhythm status) after Fontan surgery at the time of followup, including: low pulmonary artery size index (OR: 0.99; 95%CI: 0.98 – 0.99; p=0.047) and high value of pulmonary artery pressure immediately after surgery (OR: 1.3; 95%CI: 1.05 – 1.6; p=0.019) factors in the model have the ability to explain 17.3% to the state of atrial rhythm at the time of followup after Fontan surgery Our prognostic model is statistically significant (p=0.0176) 3.3.4 Some factors associated with late mortality after Fontan surgery Persistent pleural effusion was found to be a risk factor for late mortality in patients after Fontan surgery Statistically significant associations were found in both univariate (OR: 7.8; 95%CI: 1.8 – 35.1; p=0.007) and multivariate (OR: 11.2; 95%CI: 2.2 – 57.9; p=0.004) CHAPTER 4: DISCUSSION Postoperative pulmonary artery pressure: the mean pulmonary artery pressure after surgery was 15.5 ± 3.8 mmHg, of which 63/145 patients had postoperative pulmonary artery pressure >15 mmHg, accounting for 43 4% All postoperative patients received the pulmonary arterial pressure lowering drug Milrinone with an initial dose of 0.2 µg/kg body weight/min immediately after cardiac arrest Postoperative edema immediately: patients were documented with edema immediately after surgery (6.2%) The cause of edema may be too much peripheral blood stasis, too much causing edema Manifested by increased pulmonary artery pressure or decreased cardiac function In the case of early edema, it is possible that the patient did not respond to treatment, which is an indicator of early failure of the Fontan circulation Postoperative Fontan circulatory failure The early-stage Fontan circulation failure rate was determined to be 9.7% This result is consistent with the reports of Fontan surgery in the early Fontan era, with most reports of early Fontan circulatory failure rates ranging above 10% and the rate of failure in the early Fontan circulation Mortality ranges from 9-15% However, the rate of early Fontan cycle failure in recent reports is much lower There are two main groups of reasons that we explain 18 for the higher rate of Fontan circulation failure at an early stage in the study than the current common ground First, these are the first years of implementing a surgical strategy for monoventricular cardiac patients in our hospital practice, and a time when cardiologists at the center are approach, monitoring, and direct treatment for this group of patients, therefore, experience in treatment and postoperative resuscitation is still limited Second, due to insufficient resources on basic conditions in developing countries like Vietnam, most patients are not detected early, not have strategies and early intervention right after Therefore, in the early stages of Fontan surgery, it was late, when the pulmonary vascular system and heart function were changed in a negative direction and difficult to recover This also contributes to the unsatisfactory post-operative results Postoperative arrhythmia: 7/145 patients after surgery accounted for 4.8% of patients with postoperative arrhythmia For Fontan surgery with pericardial anastomosis, almost patients have less damage to the sinus node because they not have to perform anastomosis in the lumen of the right atrium as well as not increase pressure in the atrial chamber, so there is no trauma sinoatrial node, so that most postoperative arrhythmias are temporary and respond to drug therapy or temporary pacemakers Postoperative acute renal failure: 9/145 patients accounted for 6.2%, including patients with acute renal failure with oliguria and patients with acute renal failure with anuria All these patients underwent peritoneal dialysis At present, the indications for peritoneal dialysis for patients after cardiac surgery in children are still unclear, peritoneal dialysis is usually placed in the following cases: increased systemic venous pressure and severe edema, patients Oliguria or anuria for hours despite high doses of diuretics and vasopressors, serum potassium > 5.5 mmol/L, metabolic acidosis (pH < 7.3; HCO3 < 18 mmol/) due to low cardiac output Postoperative prolonged pleural effusion: the incidence of prolonged pleural effusion after Fontan surgery was 29/145 patients (accounting for 20%), including patients with chylous effusion With the same definition of disease criteria, author Gupta reported the rate of persistent pleural effusion 19 after Fontan surgery was 37%; This number is according to recent reports Treatment of prolonged pleural effusion we apply according to the PORTLAND protocol In some cases, if ALP is >15 mmHg, it is necessary to reopen the artificial pulse window and the atrium Postoperative neurovascular thromboembolic events: we encountered cases of thromboembolic events, accounting for 1.4% Both patients presented with left hemiparesis, of which one patient had convulsions On the brain scan image, one case had right temporal lobe cerebral infarction and the other case had right lateral cerebral infarction We blocked the Fontan window for a right temporal lobe infarction; Meanwhile, in case of patient with right lateral cerebral infarction, we treat the patient against cerebral edema and practice rehabilitation Time of mechanical ventilation: the average time of mechanical ventilation is 50.8 ± 130.2 hours (1 - 1104 hours) The comparison of time to mechanical ventilation after surgery is higher in our study The explanation for this may be due to the limited condition as well as the level of resuscitation, so the time of mechanical ventilation is still long Physical improvement Preoperative weight and height were 14.3 ± 21.3 and 19.5 ± 24.1, respectively, while post-operative weight and height were 28, respectively ,0 ± 27.9 and 26.1 ± 27.4 (percentile), the difference has statistical significance p < 0.05 This result is consistent with many studies around the world when it is shown that the majority of children after Fontan surgery have more dominant growth than before Fontan surgery It is possible that the early establishment of the Fontan circulation allows the infant's body to catch up to the normal growth rate On the other hand, insufficient height gain leading to short stature in older children may be due to delayed bone age, which seems to be affected by chronic hypoxia in the preoperative period Blood oxygen saturation Most patients after Fontan surgery have manifestations of decreased oxygen saturation in circulating blood due to the following reasons: one is the existence of shunts of systemic venous origin, which drains blood to the coronary sinuses and veins pulmonary or atrial system; either primary or 20 secondary anatomical abnormalities that are not surgically corrected, such as coronary sinuses remaining connected to the common atrium, or the formation of arteriovenous fistulas in the lungs, particularly these manifestations may appear immediately after surgery or develop gradually over time Obstructing the Fontan system Of the 88 patients who have been re-examined up to now, patients have an obstruction to the Fontan system that requires intervention (4.6%) The interventions for each specific patient, there were patient with dilation of the Fontan duct stenosis and two pulmonary artery branches, patient with angioplasty at the junction between the Fontan tube and the pulmonary artery, patient with atrial valve replacement ventricular valve, and patient had a mechanical atrioventricular valve replaced Postoperative ultrasonography, 14 patients tend to have subaortic stenosis (16.1%) In which, patients underwent DKS surgery right after the stenosis was detected and died We recommend that problems related to subaortic stenosis should be treated in the first stages thoroughly before Fontan surgery Postoperative arrhythmias Two independent risk factors were associated with atrial arrhythmia complications after Fontan surgery during follow-up including low pulmonary artery size index and high postoperative pulmonary artery pressure values Risk factors for the development of atrial arrhythmias include the use of the classic Fontan procedure, a history of preoperative bradycardia, the absence of preoperative sinus rhythm; age at the time of major Fontan surgery; prolonged postoperative period; moderate or greater atrioventricular valve regurgitation; and Heterotaxy syndrome Because the incidence of atrial arrhythmias increases with the postoperative period, and these disorders are an important factor influencing the severity of the disease; Therefore, routine ECG monitoring, on a 24-hour Holter monitor, and on exercise training is important for ongoing evaluation and monitoring In our center, pharmacological ablation of atrial tachycardia and Fontan anatomic screening by cardiac catheterization-angiography However, we had 13.6% of patients with atrial rhythm, 4.6% of patients with sinus rhythm and junctional rhythm, 21 and patient with junctional rhythm requiring surgery for treatment In the future, many patients in our study will need intervention for arrhythmias PLE Four patients were diagnosed with PLE All patients had edema, in which, cases appeared ascites and multi-membrane effusion In of the subsequent deaths, the procedures performed with these two patients were diagnostic cardiac catheterization, re-opening of the Fontan window, and repeated pleural drainage These are also cases of pleural adhesions at the time of Glenn surgery patients had Fontan windows open, and patient had Fontan stenosis However, we think that the rate of latent PLE in our cohort is probably quite high, which requires that patients after Fontan surgery need periodic testing, to identify and promptly handle PLE cases Risk of hypercoagulability and neurological complications There were patients encountered this complication after Fontan surgery In which, case died, the remaining cases had a cerebrovascular accidentcausing hemiplegia For the location of thrombosis, we found patients with thrombus in the coccyx (anatomical structure located between the pulmonary valve annulus and the pulmonary trunk ligation site) out of 87 patients at followup We did not find thrombosis present in the Fontan system after surgery at the time of the most recent follow-up Thromboembolism originated from the pulmonary artery stump At the time of echocardiography at hospital discharge on 132 patients after surgery, 78 patients had blood into the coccyx of the pulmonary artery (59.1%) At the time of follow-up, the percentage of patients with blood entering the coccyx of the pulmonary artery did not change, there were 51/87 patients with blood entering the dead end of the pulmonary artery (58.6%) Notably, we found that patients had thrombosis in the coccyx of the pulmonary artery (5.8%) even though the patients were treated according to the unified aspirin antiplatelet regimen of the Center Cardiology Hospital E To date, there have been very few reports indicating thromboembolism originated from the pulmonary artery stump Factors associated with early Fontan failure and persistent pleural effusion 22 To identify the factors associated with early Fontan circulation and persistent pleural effusion, respectively, we used univariate logistic regression model to determine the association of the former variables, respectively, during and after surgery to the dependent variable Next, to determine the independent risk factors for the dependent variable, we used logistic multivariable regression analysis with valid independent variables To select the best multivariable regression model, the author started from the full model including valid independent variables Then stepwise backward strategy with p value < 0.2 is applied to obtain the simplest predictive model Odds ratios (ORs) and 95% confidence intervals of OR were calculated, respectively, to determine the relationship of independent variables before, during and after surgery to dependent variables including: Fontan circulatory failure, persistent pleural effusion, and atrial arrhythmia The study also used logistic multivariate regression to further analyze risk factors for late mortality There were independent risk factors that were statistically significantly associated with early Fontan circulatory failure: mean pulmonary artery pressure before surgery increased, atrioventricular valve repair was performed at the same time Fontan surgery, and mean pulmonary artery pressure after surgery There were independent risk factors associated with persistent pleural effusion after Fontan surgery, including preoperative NYHA class III heart failure, anatomic bi-outlet right ventricular heart disease with dynamic origin vascular regurgitation, atrioventricular regurgitation, existence of a ventricular-pulmonary shunt, low pulmonary artery size index and pulmonary artery pressure in increased surgery Factors associated with late mortality Only relatively few postoperative factors that influence late mortality can be identified The results of a systematic review by author Tarek Alsaied combined a number of significant factors including increased left atrial pressure, persistent pleural effusion after surgery, and increased Fontan pressure after surgery In both multivariate and univariate regression analysis, the study found persistent pleural effusion to be a risk factor for late mortality in patients after Fontan surgery A comprehensive and exhaustive assessment focused on causation as well as a full assessment of risk factors and confounders should be performed in a later study 23 CONCLUSIONS Outcomes after the extracardiac Fontan procedure in patients diagnosed with single-ventricle lesions - Early outcomes + The survival rate at the time of discharge was 91.0%, there were no more patients with grade III heart failure after surgery and the average SpO2 improved from 81.2% before surgery to 95.2% after surgery + The early Fontan failure rate was 9.7% + Early mortality was 9.0% and was due to Fontan circulatory failure + Early complications were documented commonly included circulatory failure after Fontan surgery (6.9%), acute renal failure (6.2%) and persistent pleural effusion (20.0%) + With 132 patients stable before discharge, several main results were documented as following The average number of days in recovery was 7.7 ± 9.5 days The average number of mechanical ventilation hours was 50.2 ± 127.3 hours The average number of days in hospital after surgery was 30.7 ± 19.0 days The average number of days of pleural drainage was 13.9 ± 11.4 days - Mid-term outcomes + 95 patients were re-examined after Fontan surgery, with an average postoperative follow-up time of 44.9 ± 19.9 months + The survival rate to the time of last follow-up was 91.6% + The mortality rate in the medium term was 8.4% + Complications in the medium term: o The proportion of patients with arrhythmia at the time of followup was 33.7% higher compared to before surgery (7.6%) and at hospital discharge (5.3%) o 7.4% of patients had complications in the medium term In which, 4.2% of patients were diagnosed with PLE and 3.2% of patients had neurological complications o There were no cases of thrombus in the Fontan tube at the time of follow-up 24 Associated factors with the outcomes after the extracardiac Fontan procedure in patients diagnosed with single-ventricle lesions - Factors associated with early Fontan failure Patients with a single ventricle physiology undergoing preoperative elevated PAP, AV valve repair at Fontan, and postoperative elevated PAP were identified as independent risk factors to predict EFF - Factors associated with prolonged pleural effusion The NYHA class III, primary anatomical diagnosis of DORV with TGA, pre-Fontan AV valve regurgitation, the existence of pre-Fontan ventricle-to-pulmonary artery shunt, low pulmonary artery index, and high PAP in the operation were identified as independent risk factors to predict PPE following a Fontan operation - Factors associated with atrial rhythm status at follow-up visit There were independent risk factors associated with arrhythmia complications (atrial rhythm status) after Fontan surgery at the time of followup, including low pulmonary artery size index and high value of pulmonary artery pressure immediately after surgery - Factors associated with late mortality after Fontan surgery Persistent pleural effusion was found to be a risk factor for late mortality in patients after Fontan surgery RECOMMENDATIONS Several recommendations were suggested from the current findings - Congenital heart patients with univentricular circulatory physiology need to be diagnosed and treated early in stage one, avoiding systemic ventricular overload and increased pressure and pulmonary vascular resistance as these are early risk of premature failure of the Fontan circulation - Patients after Fontan surgery are often at risk of complications in both the early and mid-term stages, so it is necessary to follow up closely to promptly handle complications when they occur - Further studies are needed to have a complete treatment protocol for thromboembolism originated from the pulmonary artery stump in patients with Fontan surgery to avoid potential complications PUBLICATIONS Dai Dac Tran, Thanh Ngoc Le & Van Hai Thi Dang, 2020 “Predictors of Prolonged Pleural Effusion After the Extracardiac Fontan Procedure: A 8-Year Single-Center Experience in Resource-Scare Setting” Pediatric Cardiology tr 1-11 Trần Đắc Đại, Lê Ngọc Thành, Đặng Thị Hải Vân & Đỗ Anh Tiến, 2020 “Yếu tố tiên lượng thất bại với tuần hoàn Fontan giai đoạn sớm: kết sau năm triển khai phẫu thuật Fontan” Tạp chí Phẫu thuật Tim mạch Lồng ngực Việt Nam Số 30, tr 104-109 ... Setting” Pediatric Cardiology tr 1-11 Trần Đắc Đại, Lê Ngọc Thành, Đặng Thị Hải Vân & Đỗ Anh Tiến, 2020 “Yếu tố tiên lượng thất bại với tuần hoàn Fontan giai đoạn sớm: kết sau năm triển khai phẫu. .. after Fontan surgery on echocardiography There were patients with small thrombus attached to the wall of the Fontan tube, however, there was no case of thrombosis in the Fontan tube at the time... different causes 3.2.2.4 Time of mechanical ventilation, recovery time and hospital stay after Fontan surgery Thirteen patients died in the recovery period after Fontan surgery At the time of discharge,