Sonia B. Albanese

Pediatric cardiac transplantation for congenital heart defects: surgical considerations and results.

Among 54 children who underwent 55 heart transplantations, 24 (44%) (mean age, 4.9 +/- 4.8 years; range, 9 days to 18 years) had congenital defects with the following diagnoses: single-ventricle variants (6), hypoplastic left heart syndrome variants (5), transposition complex (6), and miscellaneous defects (7). Twenty patients (83%) had undergone 43 prior operations. Additional surgical procedures included repositioning of transposed great arteries (11), reconstruction of the aortic pathway (4), reconstruction of the pulmonary pathway (8), correction of situs inversus (1), and correction of anomalous pulmonary (1) or systemic (1) venous drainage. Reconstructive procedures were performed using donor or recipient tissue or both. There were six early deaths (hyperacute rejection, 1 patient; pulmonary hypertension, 1; graft failure, 2 patients; infection, 2) and six late deaths (sudden death, 2; chronic rejection, 2; nonspecific graft dysfunction, 1; lymphoproliferative disease, 1). The survival rate was 43% +/- 12% at 3 years. No deaths were related to surgical technique. Survival was not significantly different in pediatric recipients with cardiomyopathy (67% +/- 9%; p = 0.22). Accelerated coronary artery disease was noted in 4 operative survivors (22%; 70% confidence limits, 12% to 36%). All late survivors were free from cardiac symptoms after a mean follow-up of 34 +/- 24 months (range, 6 to 71 months). Based on this study, we reached three conclusions. (1) Careful planning of both harvesting and transplantation procedures allows heart transplantation in recipients with congenital heart diseases. (2) The surgical technique may be demanding, but the early risk is not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Early and late failure of tissue-engineered pulmonary valve conduits used for right ventricular outflow tract reconstruction in patients with congenital heart disease

OBJECTIVES To identify factors associated with the surgical outcome in patients undergoing right ventricular outflow tract reconstruction (RVOTR) using decellularized tissue-engineered pulmonary valve conduits (TEPVc) and to study their safety and longevity. METHODS From April 2006 to April 2010, 93 patients underwent either palliative or corrective RVOTR using Matrix P (37) and Matrix P Plus (56) xenogenic decellularized TEPVc (size range 11-27 mm). Median age and weight at operation were 20 (0.16-290) months and 10.15 (2.65-86) kg respectively. Primary and redo surgery occurred in 40 and 60% of cases, respectively. Eighty-eight patients (94.6%) received conduit implantation in the framework of corrective surgery, whereas in 5 (5.4%) a palliative procedure was undertaken. Follow-up was complete in 91% of patients, with a median duration of 12 months (range: 2 days-51 months). Data analysis included diagnosis, type of surgery (palliative vs. corrective) and age at surgery. Predetermined primary outcomes were represented by conduit failure or dysfunction. RESULTS Two patients with Matrix P and two with Matrix P Plus died in the early post-operatively phase (4.3%). None of the deaths were conduit-related. One patient died at conduit replacement. Thirty-three patients (35.5%) experienced conduit failure whereas conduit dysfunction occurred in 27 patients (29%). Two-year freedom from conduit failure and dysfunction was 60.2% (95% CI: 50.1-69.6) and 77.4% (95% CI: 67.9-84.7), respectively. Reasons for failure were conduit stenosis in 20 cases (61%), pseudoaneurysm in 3 (9%), conduit dilatation (>50% of original diameter) in 2 (6%), stenosis of distal anastomosis involving pulmonary bifurcation in 6 (18%) and allograft dissection in 2 (6%). Histological examination showed inflammatory giant-type cells in the presence of a poor autologous cell seeding in all explanted specimens. Univariate and multivariate analyses showed an association between age at surgery ≤1 year and conduit dysfunction (adjusted HR: 2.29; 95% CI: 1.01-5.20, P = 0.04). CONCLUSIONS Compared with the other conduit for RVOTR Matrix conduits showed a high incidence of failure. Our results suggest that the use of Matrix conduits for RVOTR should be considered with caution.

Identification of TBX5 mutations in a series of 94 patients with Tetralogy of Fallot

Tetralogy of Fallot (TOF) (OMIM #187500) is the most frequent conotruncal congenital heart defect (CHD) with a range of intra‐ and extracardiac phenotypes. TBX5 is a transcription factor with well‐defined roles in heart and forelimb development, and mutations in TBX5 are associated with Holt–Oram syndrome (HOS) (OMIM#142900). Here we report on the screening of 94 TOF patients for mutations in TBX5, NKX2.5 and GATA4 genes. We identified two heterozygous mutations in TBX5. One mutation was detected in a Moroccan patient with TOF, a large ostium secundum atrial septal defect and complete atrioventricular block, and features of HOS including bilateral triphalangeal thumbs and fifth finger clinodactyly. This patient carried a previously described de novo, stop codon mutation (p.R279X) located in exon 8 causing a premature truncated protein. In a second patient from Italy with TOF, ostium secundum atrial septal defect and progressive arrhythmic changes on ECG, we identified a maternally inherited novel mutation in exon 9, which caused a substitution of a serine with a leucine at amino acid position 372 (p.S372L, c.1115C>T). The mothers clinical evaluation demonstrated frequent ventricular extrasystoles and an atrial septal aneurysm. Physical examination and radiographs of the hands showed no apparent skeletal defects in either child or mother. Molecular evaluation of the p.S372L mutation demonstrated a gain‐of‐function phenotype. We also review the literature on the co‐occurrence of TOF and HOS, highlighting its relevance. This is the first systematic screening for TBX5 mutations in TOF patients which detected mutations in two of 94 (2.1%) patients.

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.

Imaging modalities in children with vascular ring and pulmonary artery sling

Our aim is to compare new non‐invasive imaging modalities in the evaluation of vascular ring (VR) and pulmonary artery sling (PAS) and to understand the role of bronchoscopy in comparison with them in assessing tracheobronchial tree.

Arterial switch operation: a new technique of coronary transfer

A successful outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) depends in large part on the adequacy of transfer of the coronary arteries to the neoaorta. The present paper describes a new technique of coronary transfer which was used in 43 patients: 28 neonates with TGA and intact septum (with coarctation in one), 10 neonates with TGA and ventricular septal defect (with coarctation in one), 2 children undergoing ASO after failed Senning operation and 3 patients with complex TGA. A standardized uniform technique of coronary transfer was used; this technique involved reimplantation of the two coronary ostia side by side after excision of a single button of neoaortic wall. Most coronary patterns were encountered: the usual pattern in 30, circumflex from right coronary artery in 7, inverted coronary arteries in 3, inverted circumflex and right coronary arteries in 3. There was no early coronary-related mortality or morbidity. One late death (3 months) was probably coronary-related. The overall coronary risk was 2.3% (70% confidence limits = 0.3%-7.5%). The proposed technique of coronary transfer can be used in most patients with TGA (all patients without coronary arteries running between the great arteries) and entails a low coronary risk.

Incidence of Healthcare-Associated Infections in a Pediatric Population With an Extracorporeal Ventricular Assist Device

During the last decade, ventricular assist devices (VADs) have become a precious tool to support children with end-stage heart failure. However, thromboembolic events, bleeding, and infections may have a considerable impact on outcome. We retrospectively analyzed the incidence of healthcare-associated infections (HAIs) in nine patients supported by EXCOR Pediatric (Berlin Heart [BH]) VAD in a pediatric cardiosurgical intensive care unit between January 1, 2009 and March 31, 2011 (27 months). Median age was 8 months (interquartile range [IQR] 6-11), median weight 7.5 kg (IQR 4.5-8.5). Seven patients were supported with a left VAD, two with a biventricular VAD (BiVAD). Six patients with a left VAD underwent heart transplant after 89 days (median, IQR 41-143) of support. One patient is still on the waiting list. All patients with BiVAD died after 12 days of assistance due to VAD malfunction. Sixteen HAIs were reported in five out of nine patients (56%). All infected patients were supported by a left VAD. When compared with noninfected patients, they had a longer mechanical support period (median 131 days, IQR 75-164, vs. 25 days, IQR 11-61, P = 0.03), a longer intensive care unit stay (median 159 days, IQR 85-188, vs. 48 days, IQR 17-87, P = 0.06) and a longer length of hospital stay (median 186 days, IQR 105-222, vs. 64 days, IQR 34-113, P = 0.06). Overall, nine mechanical devices were replaced for thromboembolic issues, most of them (67%) in patients with VAD-related infections. Overall, infection rate was 17.6 per 1000 patients days, 1.3 BH endocarditis per 1000 BH days, 4.0 surgical sites infections per 1000 BH days, 12.5 central line-associated blood stream infections per 1000 central venous catheter days, 5 catheter-associated urinary tract infections per 1000 urinary catheter days, and 13.5 ventilator-associated pneumonia cases per 1000 mechanical ventilation days. Overall, VAD-related infections were 5.4 per 1000 BH days. Of the 17 isolated pathogens, 53% were Gram-negative rods, with a prevalence of Pseudomonas aeruginosa (35.3%). Four bacteria were multidrug resistant (25%), three were carbapenem-resistant P. aeruginosa (50% of all isolated pseudomonads), and one was a methicillin-resistant S. aureus. VADs used as a bridge to cardiac transplantation are associated with a large number of HAIs. Patients with infected VADs were admitted for longer time in intensive care and in hospital with increased healthcare costs but with no impact on survival.

Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic coarctation: Functional characterization of a de novo TBX5 mutation

Holt–Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by upper limb defects and congenital heart defects (CHD), which are often simple septal and conduction defects, less frequently complex CHDs. We report on a 9 year‐old boy with clinical and radiologic features of HOS consisting of bilateral asymmetric hypoplastic thumbs, generalized brachydactyly, limited supination due to radioulnar synostosis, and sloping shoulders, and intermediate atrioventricular canal defect (AVCD) with aortic coarctation. A de novo, previously described mutation, (Arg279ter) was identified in the TBX5 gene. Molecular characterization of this mutation was carried out due to the atypical CHD. In order to investigate whether the mutated transcript of TBX5 was able to escape the post‐transcriptional surveillance mechanism and to produce a truncated TBX5 protein, we analyzed the TBX5 transcript, and protein pattern in HOS, and WT cardiac tissues. Our results demonstrate that the mutant TBX5 transcript is cleared by the cellular mechanism of surveillance. This data provides some support for the hypothesis that a dominant negative mutation, which strongly impairs the WT allele, might be too hazardous to be maintained. The literature suggests that HOS is relatively common among syndromes associated with AVCD.

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.

Airway Complications After Single-Stage Unifocalization for Pulmonary Atresia, Ventricular Septal Defect, and Major Aortopulmonary Collateral Arteries

We analyze the incidence of postoperative severe airflow limitation after single‐stage unifocalization in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries (PA/VSD/MAPCAs) and comment on the treatment performed.