Haifa Hong

Total Anomalous Pulmonary Venous Connection: The Current Management Strategies in A Pediatric Cohort of 768 Patients

Background: Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China. Methods: This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO. Results: The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035) TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time (P<0.001), and longer duration of ventilation (P=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1–112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time (P<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (P=0.038), except in newborn patients (P=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II. Conclusions: Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.

Cone reconstruction of the tricuspid valve in Ebstein anomaly with or without one and a half ventricle repair

OBJECTIVE We sought to review our institutional experience and midterm results with cone reconstruction in Ebstein anomaly with or without one and a half ventricle repair to evaluate these 2 important surgical methods for the treatment of Ebstein anomaly. METHODS From January 1, 2004, to October 1, 2009, 30 consecutive patients with Ebstein anomaly underwent cone reconstruction. All patients underwent cone reconstruction, and 20 patients with severe Ebstein anomaly had a bidirectional cavopulmonary shunt constructed. The median age was 60 months (range, 2-192 months). Our criteria to define severe Ebstein anomaly include a severely enlarged right-sided chamber, significant abnormality of the septal leaflet of the tricuspid valve, and hemodynamic instability after cardiopulmonary bypass. Clinical or echocardiographic characteristics were studied both preoperatively and postoperatively. RESULTS There was 1 (3.3%) hospital death. Before the operation, tricuspid incompetence was moderate in 8 and severe in 22 patients. Postoperative early echocardiographic analysis showed that tricuspid incompetence was mild in 26 patients, moderate in 3 patients, and severe in 1 patient. After a median follow-up time of 22 months, tricuspid incompetence of 20 patients with bidirectional cavopulmonary shunt was mild in 15 and moderate in 4. Tricuspid incompetence of 10 patients without a bidirectional cavopulmonary shunt from the latest echocardiogram (median follow-up time, 32 months) was mild in 4, moderate in 4, and severe in 2 patients. For patients whose postoperative tricuspid incompetence was beyond mild among the 10 patients without a bidirectional cavopulmonary shunt, preoperative echocardiographic analysis shows a severely dilated right ventricle. CONCLUSIONS Addition of a bidirectional cavopulmonary shunt to cone reconstruction of the tricuspid valve should be considered for young patients with severe Ebstein anomaly who are at high risk of right ventricular failure after the operation.

Label-free quantitative proteomic analysis of right ventricular remodeling in infant Tetralogy of Fallot patients.

Tetralogy of Fallot (TOF) results in chronic progressive right ventricular (RV) pressure overload and shunt hypoxemia. We investigated the global changes in the proteome of RV among infant patients with and without TOF to gain an insight into early RV remodeling. One hundred and thirty-six differentially expressed proteins were identified using label-free LC-ESI-MS/MS analysis. Western blot results revealed that the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) increased significantly in TOF patients; and levels of lysocardiolipin acyltransferase 1 (LCLAT1), lumican (LUM), and versican (VCAN) decreased significantly. QRT-PCR analysis showed that levels of PFKFB2 mRNA were markedly increased, but those of LCLAT1 and LUM were significantly decreased. VCAN mRNA showed no significant change in response to pathophysiology of TOF. The results of immunohistochemical staining were similar to those of Western blot analysis. Results of the proteomic analysis indicated that the level of glycolysis-related proteins had increased and levels of lipid-metabolism-related proteins had decreased. ECM proteins were found to be more down-regulated in TOF in the present study than in previous reports. Taken together, our findings may provide clues to both the metabolic inflexibility and ECM remodeling during the early RV remodeling, which occur in response to chronic hypoxia and long-term pressure overload in TOF patients.

Influence of antegrade pulmonary blood flow on the hemodynamic performance of bidirectional cavopulmonary anastomosis: A numerical study

The role and effect of preserved antegrade pulmonary blood flow (APBF) at the time of bidirectional cavopulmonary anastomosis (BCPA) in the management of single-ventricle physiology is controversial. We investigated the influence of APBF on the fluid dynamics of BCPA connection using computational fluid dynamics (CFD). Patient-specific, three-dimensional geometry of a BCPA connection with native pulmonary artery (PA) trunk was reconstructed and transient CFD simulations were done at four predetermined mean flow rates of PA trunk (0.5L/min, 1L/min, 1.5L/min and 2L/min). During a cardiac cycle, the flow ratio of left pulmonary artery (LPA)/right pulmonary artery (RPA) increased from 1.91 to 2.50, and average control volume power loss increased from 0.76 mW to 18.05 mW when the mean flow rate of PA trunk changed from 0.5L/min to 2L/min. The pulsatility of pressures in LPA, RPA and superior vena cava became more prominent as the amount of APBF increased. Local fluid structures in the connection area at four levels of APBF differed from each other.

Cardiomyocytes in Young Infants With Congenital Heart Disease: a Three-Month Window of Proliferation

Perinatal reduction in cardiomyocyte cell cycle activity is well established in animal models and humans. However, cardiomyocyte cell cycle activity in infants with congenital heart disease (CHD) is unknown, and may provide important information to improve treatment. Human right atrial specimens were obtained from infants during routine surgery to repair ventricular septal defects. The specimens were divided into three groups: group A (age 1–3 months); group B (age, 4–6 months); and group C (age 7–12 months). A dramatic fall in the number of Ki67 -positive CHD cardiac myocytes occurred after three months. When cultured in vitro, young CHD myocytes (≤3 months) showed more abundant Ki67-positive cardiomyocytes and greater incorporation of EdU, indicating enhanced proliferation. YAP1 and NICD—important transcript factors in cardiomyocyte development and proliferation—decreased with age and β-catenin increased with age. Compared with those of older infants, cardiomyocytes of young CHD infants (≤3 months) have a higher proliferating capacity in vivo and in vitro. From the perspective of cardiac muscle regeneration, CHD treatment at a younger age (≤3 months) may be more optimal.

Computational haemodynamic analysis of patient-specific virtual operations for total cavopulmonary connection with dual superior venae cavae

OBJECTIVES This study set out to design different types of total cavopulmonary connections (TCPC) with dual superior venae cavae (SVC), taking into account different sites for anastomosis from venae cavae to pulmonary arteries (PAs), and to compare haemodynamic features in these virtual operative designs. METHODS The geometries of bilateral bidirectional Glenn (BBDG) connection and inferior vena cava (IVC) connected extracardiac conduit were reconstructed to three-dimensional configurations according to the magnetic resonance images (MRIs) of two patients at the same age, and virtual operations were designed to create four possible TCPC models under the guidance of paediatric cardiac surgeons. Computational fluid dynamic (CFD) simulations were performed in each model at five predetermined pulmonary flow splits, to predict postoperative blood flows. The same boundary conditions were applied on each model, in order to simplify the analysis of the influence of configurations on the flow characteristics. Control volume power losses and energy efficiency in different models were calculated and compared. Flow patterns in the models were demonstrated by streamlines corresponding to the venae cavae. RESULTS When the flow rate of the right pulmonary artery (RPA) was 40-60% of the total pulmonary flow, control volume power loss was lower than the other three models in the model of TCPC 2 and was higher than the other three models in the model of TCPC 4. CONCLUSIONS For this patient, anastomosing the left superior vena cava (LSVC) and right superior vena cava (RSVC) on the PAs close together will cause higher power loss and lower energy efficiency in the TCPC connection. If the LSVC and RSVC had been connected to the PAs as near as possible to stimulate growth of the central PAs when performing I-stage BBDG procedure, the extracardiac conduit from IVC would be better connected just under the anastomotic site in the following TCPC procedure to avoid high power loss.

Extracardiac Fontan with direct cavopulmonary connections: midterm results

OBJECTIVES The aim of this study was to analyse the midterm results following superior and inferior direct cavopulmonary connections (DCPC) to create a Fontan circulation in patients with functionally univentricular hearts. METHODS A retrospective review of patients operated on between January 2005 and December 2011 was carried out. RESULTS Thirty consecutive patients who underwent this type of operation were retrospectively reviewed. There were 18 (60%) males and 12 (40%) females, with a median age of 69 months (range 16-150 months) and median weight of 23 kg (range 11-46 kg). Aortic cross-clamping was used in 10 patients, with a median cross-clamp time of 40 min (range 23-99) and a median cardiopulmonary bypass (CPB) time of 135 min (range 76-179 min). The remaining 20 patients were operated on without aortic cross-clamping. Their median CPB time was 104 min (range 78-139 min). Fenestration was performed in 16 patients. The associated intracardiac procedures were performed in 10 patients. The follow-up period ranged from 2 months to 6 years. Operative mortality and late mortality after discharge was zero. The major postoperative complications included supraventricular tachycardia in one patient, oliguria and peritoneal dialysis in one and chest drainage (>30 ml/day) persisting >7 days in five (20%). One patient developed sinus bradycardia in association with sinus pauses 2 months after discharge. One patient developed pericardial effusion 1 month after discharge. A computational fluid dynamic study was performed in one patient. The computational fluid dynamic study showed that DCPC may have a better power efficiency. CONCLUSIONS Superior and inferior DCPCs to create a Fontan circulation in appropriately selected patients with functionally univentricular hearts can be performed with a low risk and a low rate of reinterventions. The midterm results are favourable.

Late complete atrioventricular block and tricuspid regurgitation after percutaneous closure of a perimembranous ventricular septal defect

Percutaneous closure of a perimembranous ventricular septal defect (VSD) is nowadays a valuable alternative to surgical closure. Preliminary results regarding the safety of this device and the low incidence of aortic and tricuspid regurgitation are encouraging. However, owing to the close proximity of the perimembranous VSD to the conduction system, concern about atrioventricular block has been raised. The published reports on this complication describe the latest onset of complete atrioventricular block (CAVB), presenting at 37.8 months after implantation. We report here 1 case of delayed CAVB with severe tricuspid regurgitation occurring 5 years after implantation of an eccentric Amplatzer perimembranous VSD occluder (APmVSDO; AGA Medical, Golden Valley, Minn).

Decreased Yes-Associated Protein-1 (YAP1) Expression in Pediatric Hearts with Ventricular Septal Defects

Background Ventricular septal defects (VSDs) are the most common and simplest type of congenital heart diseases (CHDs). Animal studies have suggested that the downregulation of Yes-associated protein 1 (YAP1) during embryonic development causes VSD-associated CHDs. However, how YAP1 contributes to isolated VSD (iVSD) is unclear. Methods and Results Twenty right atrial specimens were obtained from iVSD patients during routine congenital cardiac surgery and we assessed YAP1 expression in these specimens. For controls, six right atrial specimens were obtained from normal hearts of children without heart disease, three of whom died from cerebral palsy, and three who underwent heart transplants. YAP1 mRNA and protein levels and nuclear localization were significantly reduced in iVSD specimens compared to normal heart specimens. Concomitantly, mRNA levels of YAP1 downstream targets CTGF and AXL were also significantly decreased in iVSD specimens. Although Ki67-positive cardiomyocytes in iVSD specimens were comparable to normal heart specimens, Ki67-positive non-cardiomyocytes were significantly decreased. Conclusions YAP1 expression was markedly decreased in hearts of iVSD children. Given the important role of YAP1 during heart development, downregulation of YAP1 expression may contribute to iVSD and affect the proliferation of non-cardiomyocytes.

Treatment Strategies for Primary Tumors of the Heart in Children: A 10-Year Experience

BACKGROUND The goal of this study was to determine the optimal treatment strategy for children with primary tumors of the heart. METHODS We reviewed 88 children with primary heart tumors in our center from January 2004 to December 2013. Operative patients were followed every 6 months in the first postoperative year and then regularly every 12 months; nonoperative patients were followed once a year after diagnosis. Demographic information of imaging, operative details, and postoperative data were obtained from medical records. Statistical analyses were carried out by means of Fishers exact tests and Students t test. RESULTS Of the 23 patients who underwent surgical removal of the tumors (range, 12 days to 14.4 years; median, 1.3 years), 19 patients had stable postoperative hemodynamics, 4 had low cardiac output, and 2 patients died (mortality, 9%). The follow-up ranged from 6 months to 9 years; 2 patients had tumor recurrence, and 1 patient was lost to follow-up. The rest of the operative patients remained in normal sinus rhythm and had normal cardiac function. The 65 patients treated nonoperatively (range, 1 day to 14.4 years; median, 0.4 years) were followed closely for 1 month to 9.8 years; only 1 patient died (of unknown reasons), 1 patient received a cardiac transplant, and 9 patients were lost to follow-up. CONCLUSIONS Operative resection is optimal for primary tumors of the heart in patients with obvious symptoms or hemodynamic changes. Rhabdomyomas have the potential for spontaneous regression, and nonoperative follow-up therefore is acceptable even if symptoms appear. Operative risk is greater in younger patients and in patients with cardiac valvular dysfunction.