Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.

Congenital heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. To catalog the putative candidate CHD risk genes, we collected 16,349 variants [single-nucleotide variants (SNVs) and Indels] impacting 8,308 genes in 3,166 CHD cases for a comprehensive meta-analysis. Using American College of Medical Genetics (ACMG) guidelines, we excluded the 0.1% of benign/likely benign variants and the resulting dataset consisted of 83% predicted loss of function variants and 17% missense variants. Seventeen percent were de novo variants. A stepwise analysis identified 90 variant-enriched CHD genes, of which six (GPATCH1, NYNRIN, TCLD2, CEP95, MAP3K19, and TTC36) were novel candidate CHD genes. Single-cell transcriptome cluster reconstruction analysis on six CHD tissues and four controls revealed upregulation of the top 10 frequently mutated genes primarily in cardiomyocytes. NOTCH1 (highest number of variants) and MYH6 (highest number of recurrent variants) expression was elevated in endocardial cells and cardiomyocytes, respectively, and 60% of these gene variants were associated with tetralogy of Fallot and coarctation of the aorta, respectively. Pseudobulk analysis using the single-cell transcriptome revealed significant (P < 0.05) upregulation of both NOTCH1 (endocardial cells) and MYH6 (cardiomyocytes) in the control heart data. We observed nine different subpopulations of CHD heart cardiomyocytes of which only four were observed in the control heart. This is the first comprehensive meta-analysis combining genomics and CHD single-cell transcriptomics, identifying the most frequently mutated CHD genes, and demonstrating CHD gene heterogeneity, suggesting that multiple genes contribute to the phenotypic heterogeneity of CHD. Cardiomyocytes and endocardial cells are identified as major CHD-related cell types.NEW & NOTEWORTHY Congential heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. We present a comprehensive analysis combining genomics and CHD single-cell transcriptome. Our study identifies 90 potential candidate CHD risk genes of which 6 are novel. The risk genes have heterogenous expression suggestive of multiple genes contributing to the phenotypic heterogeneity of CHD. Cardiomyocytes and endocardial cells are identified as major CHD-related cell types.

Neonatal sutureless pericardial marsupialization for isolated iatrogenic pulmonary vein stenosis.

A 12-day-old girl underwent extended end-to-end aortic arch reconstruction with proximal pulmonary autograft patch augmentation on moderately hypothermic cardiopulmonary bypass. At the end of the procedure, the right superior pulmonary vein developed a severe stenosis at the insertion site of the left atrial vent, as a consequence of multiple hemostatic sutures. We report the successful intraoperative ad hoc application of the sutureless pericardial marsupialization technique for the herewith described severe, isolated, iatrogenic pulmonary vein stenosis in a neonate.

Implementation of On-table Extubation After Pediatric Cardiac Surgery in the Developing World.

In the recent years there has been increasing trend towards the practice of on-table extubation after pediatric cardiac surgery among practitioner in European and non-European countries. In this article we share our experience with on-table extubation among children after cardiac surgery in the developing world supported with the currently available literature.

Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons Association study.

BACKGROUND: To evaluate indications and results of surgery for primary cardiac tumors in children. METHODS AND RESULTS: Eighty-nine patients aged ≤18 years undergoing surgery for cardiac tumor between 1990 and 2005 from 16 centers were included retrospectively (M/F=41/48; median age 4.3 months, range 1 day to 18 years). Sixty-three patients (68.5%) presented with symptoms. Surgery consisted of complete resection in 62 (69.7%) patients, partial resection in 21 (23.6%), and cardiac transplant in 4 (4.5%). Most frequent histotypes (93.2%) were benign (rhabdomyoma, myxoma, teratoma, fibroma, and hemangioma). Postoperative complications occurred in 29.9%. Early and late mortality were 4.5% each (mean follow-up, 6.3±4.4 years); major adverse events occurred in 28.2% of the patients; 90.7% of patients are in New York Heart Association class I. There were no statistically significant differences in survival, postoperative complications, or adverse events after complete and partial resection in benign tumors other than myxomas. Cardiac transplant was associated significantly with higher mortality rate (P=0.006). Overall mortality was associated to malignancy (P=0.0008), and adverse events during follow-up (P=0.005). CONCLUSIONS: Surgery for primary cardiac tumors in children has good early and long-term outcomes, with low recurrence rate. Rhabdomyomas are the most frequent surgical histotypes. Malignant tumors negatively affect early and late survival. Heart transplant is indicated when conservative surgery is not feasible. Lack of recurrence after partial resection of benign cardiac tumors indicates that a less risky tumor debulking is effective for a subset of histotypes such as rhabdomyomas and fibromas.

Pneumatic pulsatile ventricular assist device as a bridge to heart transplantation in pediatric patients.

Despite the remarkable advances with the use of ventricular assist devices (VAD) in adults, pneumatic pulsatile support in children is still limited. We report on our experience in the pediatric population. A retrospective review of 17 consecutive children offered mechanical support with Berlin Heart as a bridge to heart transplant from February 2002 to April 2010 was conducted. The median patient age was 3.9 years (75 days to 13.3 years). The median patient weight was 14.1 kg (2.9-43kg). Before VAD implantation, all children were managed by multiple intravenous inotropes and mechanical ventilation (14) or extracorporeal membrane oxygenation (3). All patients had right ventricular dysfunction. Nine patients required biventricular mechanical support (BVAD), but in all other cases a single left ventricular assist device proved sufficient (47%). The median duration of VAD support was 47 days (1-168 days). The median pre-VAD pulmonary vascular resistance index (Rpi) was 5.7 WU/m(2) (3.5 to 14.4WU/m(2) ). Eleven patients (65%) were successfully bridged to heart transplantation after a median duration of mechanical support of 68 days (6-168 days). Six deaths occurred (35%), three for neurological complications, one for sepsis, and two others for device malfunctioning. Since 2007, the survival rate of our patients has increased from 43% to 80%, and the need for BVAD has decreased from 86% to 30%. In two patients with Rpi >10WU/m(2) , unresponsive to pulmonary vasodilatator therapy, Rpi dropped to 2.2 and 2WU/m(2) after 40 and 23 days of BVAD support, respectively. Seven patients (41%) required at least one pump change. Of 11 patients undergoing heart transplant, four developed an extremely elevated (>60%) panel reactive antibody by enzyme-linked immunosorbent assay, confirmed by Luminex. All of them experienced at least one acute episode of rejection in the first month after heart transplant, needing plasmapheresis. The survival rate after heart transplantation was 100% with a median follow-up of 25.4 months (6 days to 7.7 years). Mechanical support in children with end-stage heart failure is an effective strategy as a bridge to heart transplantation with a reasonable morbidity and mortality. BVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance.

Extracorporeal membrane oxygenation and high-dose continuous veno-venous hemodiafiltration in a young child as a successful bridge to heart transplant for management of combined heart and kidney failure: a case report.

Combined heart and kidney transplant is an established treatment modality in patients with coexisting end-stage heart and kidney failure. However, there is scarce information on the optimal management of children that are listed for cardiac transplantation with mild to severe renal dysfunction. Herein we report the case of a young child who presented with life-threatening dilative cardiomyopathy and severe renal dysfunction, and who required urgent extracorporeal membrane oxygenation associated with continuous veno-venous hemodiafiltration and eventually underwent successful isolated heart transplantation followed by complete recovery of kidney function.

Power dissipation associated with surgical operations' hemodynamics: critical issues and application to the total cavopulmonary connection.

The issue of the correct determination of the mechanical power dissipated by the blood flow in the circulatory system is very important. This parameter is particularly critical when the patient's circulation has to overcome structural impairments, such as, e.g., in the case of only one functional ventricle. The surgical palliation of such a condition, which is a relatively common form of congenital heart disease, calls for an optimization of the new connection's hydrodynamics. Starting from the general formulation of the energy dissipation rate in a given control volume, this paper discusses the critical assumptions of the formula usually employed to assess the power dissipation in complex connections, such as the total cavopulmonary connection (TCPC). A new formula is derived, in which the mean elevation of the outlet and inlet sections is shown to be relevant, through the use of the piezometric pressure. Moreover, the flow profile at the boundary of the control volume is also important, since the usual approach implicitly assumes that the flow is perfectly flat: this assumption is doubtful, especially in the venous return (as in the TCPC). In the experimental part of the study, the power dissipation was measured in a physical model of the TCPC, and a large difference was found between the usual method and the proposed one, especially at low regime (85% relative difference, at 1.5 l/min total cardiac output). The proposed approach should be adopted in order to improve the accuracy of the hydrodynamical performance's assessment of surgical connections (e.g., TCPC) or implantable devices (e.g., valved conduit).

Unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

AIM: To correlate anatomic and genetic features of paediatric patients with pulmonary atresia, ventricular septal defect (VSD) and multiple aortopulmonary collateral arteries with surgical outcome. METHODS: 44 consecutive patients aged 33 +/- 40 mo underwent either primary one-stage unifocalization (n = 32) or palliative right ventricular outflow tract reconstruction (n = 12) followed by secondary unifocalization and repair (n = 10) based on preoperative morphometric and functional evaluation of pulmonary blood sources. Chromosome 22q11.2 microdeletion occurred in 41% of cases. Combined VSD closure during one-stage procedures was guided by an intraoperative pulmonary flow study. Complete repair was accomplished in 35 cases (83%, 95% CI 72-95%). Variables examined included occurrence of confluent intrapericardial pulmonary arteries, central pulmonary arteries, confluent intraparenchymal pulmonary arteries, dominant collateral or pulmonary arteries, and chromosome 22q11.2 microdeletion. The sensitivity and specificity of the pulmonary flow study in predicting postoperative pulmonary haemodynamics were also tested. RESULTS: Eight-year actuarial survival and freedom from reoperation were 85% and 63%, respectively. Sensitivity and specificity of the pulmonary flow study were 94% and 100%, respectively. None of the anatomical variables examined was significantly related to the outcome of treatment. The only statistically relevant association was detected between survival and occurrence of 22q11.2 microdeletion (p < 0.003). Logistic analysis showed an increased likelihood of positive outcome in relation to first- (p < 0.02) or second-stage (p < 0.04) complete correction. CONCLUSION: Morphology of pulmonary blood supply has no major impact on surgical outcome. Pulmonary flow study is a highly specific and sensitive intraoperative test. Chromosome 22q11.2 microdeletion remains the only variable significantly affecting survival.

Orthotopic heart transplantation for congenital heart disease: an alternative for high-risk fontan candidates?

OBJECTIVE: Evaluation of incremental risk factors for early mortality in children undergoing orthotopic heart transplantation (OHT) for congenital heart disease. METHODS: Between 1988 and 2002, 43 patients (mean age 9.1+/-7.2 years) underwent 44 OHT for complex TGA (6), DORV (4), single ventricle (21), and other end-stage structural heart disease (11). Two discernible ventricular chambers were present in 18 pts (41.8%). Previous reconstructive or palliative procedures had been previously accomplished in 35 pts (83.3%), including atrial switch (5), systemic-to-pulmonary shunts (10), cavopulmonary anastomosis (9), Fontan completion (6), and others (5). RESULTS: 30-day survival for the 2-ventricle subgroup was 94.4+/-5.4% compared with 67.2+/-9.5% for the single ventricle subgroup (P=0.04) (overall 78.6%+/-3.3%). OHT following single ventricle staging to bi-directional cavopulmonary anastomosis exhibited 100% early survival, as opposed to 62.5+/-17.1% for OHT after systemic-to-pulmonary shunts, and 33.3+/-19.2% for OHT following failing Fontan (P=0.010). HLHS diagnosis (0.0085) and failing Fontan (P=0.003) were identified as independent predictors of early mortality by regression logistic modeling, while Fontan stage represented the only predictor of overall mortality by Cox proportional hazard. Overall 10-year survival was 54.3+/-11%. CONCLUSIONS: OHT for structural congenital heart disease with single ventricle physiology entails substantial early mortality and bi-directional cavopulmonary anastomosis enables the best transition to heart transplant. OHT should be considered in the decision making process as an alternative to Fontan completion in high-risk candidates, since rescue-OHT after failing Fontan seems unwarranted.

Inflammatory response to cardiac bypass in ewe fetuses: effects of steroid administration or continuous hemodiafiltration.

OBJECTIVES: We sought to investigate the effectiveness of glucocorticoid administration or continuous venovenous hemodiafiltration on endothelin and corticotropin-releasing factor release or clearance during prolonged fetal cardiac bypass and on the overall performance of fetuses. METHODS: Circulating endothelin 1, 2, and 3 and corticotropin-releasing factor levels were measured in fetal ewes during a 60-minute cardiac bypass period performed with an inline axial flow pump. Blood samples were collected before, during, and 90 minutes after cardiac bypass. Animals were divided into 4 groups. The betamethasone group (n = 6) received maternal treatment with 12 mg of betamethasone 1 and 2 days before the experiment. The methylprednisolone group (n = 5) received fetal treatment with 40 mg/kg intravenous methylprednisolone at the beginning of cardiac bypass. The continuous venovenous hemodiafiltration group (n = 4) underwent continuous venovenous hemodiafiltration with a 0.3-m(2) polysulfone filter during cardiac bypass. The final group was the control group (n = 4). RESULTS: Maternal steroid pretreatment failed to decrease endothelin or corticotropin-releasing factor production when compared with levels in the control animals. Fetal treatment with methylprednisolone produced a significant decrease in endothelin 2 production during cardiac bypass (P <.02) and endothelin 1 production at the end of the experiment (P <.02). Continuous venovenous hemodiafiltration blocked completely the increase of endothelin and corticotropin-releasing factor levels during cardiac bypass (P <.02), which was maintained 90 minutes after cardiac bypass. Acid-base balance was preserved during cardiac bypass by the continuous venovenous hemodiafiltration but worsened after disconnection of the extracorporeal circuit, whereas animals treated with methylprednisolone had better pH, Paco(2), and bicarbonate levels by the end of the experiment. The overall tolerance of the procedure was better in the continuous venovenous hemodiafiltration group during cardiac bypass and in the methylprednisolone group at the end of the experiment. CONCLUSIONS: Continuous venovenous hemodiafiltration provides sustained stability of endothelin levels during fetal cardiac bypass. This technique might help, in association with fetal steroid treatment, to contain the inflammatory response leading to postbypass placental dysfunction.

The beneficial vortex and best spatial arrangement in total extracardiac cavopulmonary connection.

OBJECTIVE: Total extracardiac cavopulmonary connection is an established procedure, but the best spatial arrangement remains controversial. On the basis of our clinical experience with total extracardiac cavopulmonary connection, we performed quantitative and qualitative flow analysis on total extracardiac cavopulmonary connection models simulating the two most frequent arrangements applied to our patients to determine the most favorable hydrodynamic pattern. METHODS: We selected two main groups among 110 patients who underwent total extracardiac cavopulmonary connection, those with left-sided inferior vena cava anastomosis (type 1) and those with facing superior and inferior vena cava anastomoses (type 2). Blown-glass total extracardiac cavopulmonary connection phantom models were constructed on the basis of nuclear magnetic resonance and angiographic images. Flow measurements were performed with a Nd:YAG Q-switched laser and a particle imaging velocimetry system. A power dissipation study and a finite-element numeric simulation were also carried out. RESULTS: When applying superior and inferior vena caval flow proportions of total systemic venous return of 40% and 60%, respectively, a vortex was visualized in the type 1 phantom that rotated counterclockwise at the junction of the caval streams. This apparent vortex was not a true vortex; rather, it represented a weakly dissipative recirculating zone modulating the flow distribution into the pulmonary arteries. The power dissipation and finite-element numeric stimulation confirmed the beneficial nature of the apparent vortex and a more energy-saving pattern in the type 1 phantom than in the type 2 phantom. CONCLUSION: Total extracardiac cavopulmonary connection with left-sided diversion of the inferior vena caval conduit anastomosis is characterized by a central vortex that regulates the caval flow partitioning and provides a more favorable energy-saving pattern than is seen with the total extracardiac cavopulmonary connection with directly opposed cavopulmonary anastomoses.

Treatment of hyperhomocysteinemia in pediatric heart transplant recipients.

BACKGROUND: Graft coronary artery vasculopathy is the main cause of late morbidity and mortality in pediatric cardiac allograft recipients. Growing evidence suggests that elevated plasma homocysteine levels are associated with cardiac allograft vasculopathy following heart transplantation. The purpose of this study was to evaluate the effect of vitamin supplementation as a potential strategy for reducing homocysteine levels in pediatric heart transplant recipients and examine creatinine levels as potential determinants of plasma homocysteine concentration after transplantation. METHODS: We studied 27 pediatric heart transplant patients with homocysteine levels higher than normal. All children received vitamin supplementation (vitamin B(12), vitamin E, vitamin A and folic acid). During treatment, levels of homocysteine, vitamins and creatinine were evaluated after 3, 6, 9 and 12 months. RESULTS: We observed a significant homocysteine concentration decrease after treatment at every determination, whereas no significant change occurred for creatinine. Vitamin B(12) serum level increased markedly, whereas folic acid, vitamin E and vitamin A serum levels showed only minor increases. CONCLUSIONS: We observed a significant increase of mean levels of vitamin B(12) and a moderate increase in the other 3 vitamins. We also observed a significant reduction in homocysteine levels, which returned to normal levels for age. In our patients, there was a correlation, before and after treatment, between homocysteine and creatinine levels, but there was no a direct correlation between creatinine serum levels and homocysteine reduction. We conclude that vitamin supplementation reduces and may normalize homocysteine serum level after pediatric heart transplantation.

Pulmonary atresia with intact ventricular septum and systemic-pulmonary collateral arteries.

Pulmonary atresia with intact ventricular septum and major systemic-pulmonary collateral arteries is a very rare congenital heart lesion with dismal natural history. Herein we report on a case of pulmonary atresia with intact ventricular septum with hypoplastic right ventricle, very small confluent pulmonary arteries, absent arterial duct, and pulmonary blood flow exclusively provided by bronchial-type systemic-pulmonary collateral arteries that was successfully treated at our institution.

Increasing experience with integrated approach to pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

OBJECTIVES: To validate the preliminary surgical results of 'integrated approach' to pulmonary atresia, ventricular septal defect (VSD), and multiple aortopulmonary collateral arteries by retrospective analysis of our center experience. METHODS: Between 01/94 and 03/02, 37 patients aged 22 days to 13 years underwent surgery for pulmonary atresia, VSD, and multiple aortopulmonary collaterals. Case selection was based on preoperative calculation of total neopulmonary arterial index (TNPAI), pulmonary arterial index (PAI), and pulmonary arteries-to-collateral arteries lung segment perfusion ratio (S(pa):S(ca)). The decision for a possible VSD closure during one-stage procedures was based on an intraoperative pulmonary flow study. Twenty-five patients with a TNPAI equal to or greater than 150 mm(2)/m(2) underwent primary unifocalization, irrespective of PAI and S(pa):S(ca). Conversely, 12 patients with a TNPAI less than 150 mm(2)/m(2) and hypoplastic (PAI less than 100 mm(2)/m(2)) dominant (S(pa):S(ca) greater than 1) pulmonary arteries received a first-stage right ventricular outflow tract reconstruction, followed by unifocalization and repair (i.e. VSD closure) in nine cases. RESULTS: Among 34 patients who received total unifocalization, the overall repairability rate was 85% (first instance repairs: n=27; delayed VSD closure: n=2; 95% confidence interval, CI: 73-97%), with a survival rate at 7 years of 81%. Repaired survivors (n=26) are asymptomatic (n=22) or mildly symptomatic (n=4) at a follow-up interval of 43+/-28 months, with a 0.48+/-0.2 mean haemodynamic right ventricular/left ventricular pressure ratio, whereas palliated ones are waiting for either repair (n=3) or catheter study (n=2). Analysis of results has shown the following: (1) 100% (34/34 cases) feasibility of one-stage unifocalization in patients with a preoperative TNPAI equal to or greater than 150 mm(2)/m(2), whereas combined repairability rate was 79% only (95% CI: 65-93%); (2) 100% (12/12 cases) fulfillment of criteria for second-stage repairability (acquired TNPAI greater than 150 mm(2)/m(2)) in all patients treated with right ventricular outflow tract reconstruction; and (3) 93% (95% CI: 83-100%) overall accuracy of intraoperative flow study in predicting either postrepair mean pulmonary arterial pressure (VSD closed: n=23) or balanced pulmonary to systemic blood flow ratio (VSD left open: n=4). CONCLUSIONS: Increasing experience with 'integrated approach' to pulmonary atresia, VSD, and multiple aortopulmonaty collaterals has confirmed the preliminary results of our surgical series. The pulmonary flow study remains the most accurate intraoperative test for successful management of VSD during unifocalization procedures

Orthotopic heart transplantation for failing single ventricle physiology.

OBJECTIVE: Evaluation of incremental risk factors for early mortality in children undergoing orthotopic heart transplantation (OHT) for failing single ventricle physiology. METHODS: Between 1988 and 2002, 25 patients (mean age 9.3+/-7.1 years) underwent OHT for complex congenital heart disease (CHD) with a functional right (15 patients) or left (10 patients) single ventricle. Palliative staging towards Fontan completion had been previously accomplished in 22 patients (88%). Transition to OHT occurred from a shunt stage in 10, a bi-directional cavopulmonary anastomosis (BDG) stage in nine, and after Fontan failure in six patients. RESULTS: Thirty-day survival was 68.0+/-9.3% with no additional mortality up to 14.1 years. OHT following BDG staging exhibited 100% long-term survival, as opposed to 66.7+/-15.7% for OHT after systemic-to-pulmonary shunt, and 33.3+/-19.2% for OHT following failing Fontan (p=0.032). Regression logistic modelling indicated failing Fontan circulation as predictor of higher mortality after OHT (p=0.041). Reintervention was necessary in four patients 40+/-11 months after OHT to address residual superior vena cava (two) and isthmic (two) stenosis. Overall freedom from reintervention was 88.3+/-8.1% at 5 years. CONCLUSIONS: OHT for structural CHD with single ventricle physiology entails substantial early mortality while BDG enables the best transition to heart transplant. OHT should be considered in the decision-making process as an alternative to Fontan completion in high-risk candidates, since rescue-OHT after failing Fontan seems unwarranted.

Total anomalous pulmonary venous connection: long-term appraisal with evolving technical solutions.

OBJECTIVES: To evaluate late outcome of non-isomeric total anomalous pulmonary venous connection (TAPVC) repair, controlling for anatomic subtypes and surgical technique. METHODS: Between 1983 and 2001, 89 patients (median age 54 days) underwent repair for supracardiac (38), cardiac (26), infracardiac (16) or mixed (nine) TAPVC. Ten patients (11.2%) presented associated anomalies other than PDA. Twenty-eight patients (31.5%) were emergencies, due to obstructed drainage. Supracardiac and infracardiac TAPVC repair included the double-patch technique with left atrial enlargement in 29 patients and side-to-side anastomosis between the pulmonary venous (PV) confluence and the left atrium in 29 patients. Coronary sinus unroofing was preferred for cardiac TAPVC repair. Total follow-up was 727.16 patient-years (mean 8.55 years, 98.8% complete). RESULTS: Early mortality was 7.86% (7/89). Ten patients (11.2%) underwent reintervention, including reoperation (eight), balloon dilation (one) and intraoperative stents placement (one), for anastomotic (four) or diffuse PV stenosis (six), with four late deaths. Kaplan-Meier survival is 87.3+/-0.036 SE% at 18.07 years with no difference according to anatomic type or surgical technique. Freedom from PV reintervention for operative survivors is 86.7+/-0.052 SE% at 18.07 years. Cox proportional hazard indicates associated anomalies (P=0.008) and reoperation for intrinsic PV stenosis (P=0.034) as independent predictors of mortality. According to logistic analysis, preoperative obstruction predicts higher risk of reintervention for intrinsic PV stenosis (P=0.022), while the double-patch technique increased the risk of late arrhythmias (P=0.005). CONCLUSIONS: Side-to-side anastomosis provides excellent results for TAPVC repair while left atrial enlargement procedures appear to be associated with higher risk of late arrhythmias. Although early and aggressive reintervention for recurrent PV obstruction is mandatory, intrinsic PV stenosis remains a predictor of adverse outcome.

[Intermediate results of the integrated approach to pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries]. / Risultati a medio termine dell'approccio integrato all'atresia polmonare con difetto interventricolare e collaterali sistemico-polmonari maggiori.

BACKGROUND: The aim of this study was to validate the preliminary surgical results of the integrated approach to pulmonary atresia, ventricular septal defect (VSD), and multiple aortopulmonary collateral arteries by retrospective analysis of our center experience. METHODS: Between January 1994 and January 2003, 40 patients aged 22 days to 13 years underwent surgery for pulmonary atresia, VSD, and multiple aortopulmonary collaterals. Case selection was based on preoperative calculation of total neopulmonary arterial index (TNPAI), pulmonary arterial index (PAI), and pulmonary arteries-to-collateral arteries lung segment perfusion ratio (Spa:Sca). The decision for a possible VSD closure during one-stage procedures was based on an intraoperative pulmonary flow study. Twenty-seven patients with a TNPAI > or = 150 mm2/m2 underwent primary unifocalization, irrespective of PAI and Spa:Sca. Conversely, 13 patients with a TNPAI < 150 mm2/m2 and hypoplastic (PAI < 100 mm2/m2) dominant (Spa:Sca > 1) pulmonary arteries received a first-stage right ventricular outflow tract reconstruction, followed by unifocalization and repair (i.e., VSD closure) in 11 cases. RESULTS: Among 38 patients who received total unifocalization, the overall repairability rate was 84% (first instance repairs: n = 29; delayed VSD closure: n = 3; 95% confidence interval 72-96%), with a survival rate at 7.8 years of 83%. Repaired survivors (n = 29) are asymptomatic (n = 25) or mildly symptomatic (n = 4) at a follow-up interval of 43 +/- 30 months, with a 0.48 +/- 0.2 mean hemodynamic right ventricular/left ventricular pressure ratio. CONCLUSIONS: Increasing experience with the integrated approach to pulmonary atresia, VSD, and multiple aortopulmonaty collaterals has confirmed the preliminary results of our surgical series. The pulmonary flow study remains the most accurate intraoperative test for successful management of VSD during unifocalization procedures.