Risk Factors for Peri-Procedural Arterial Ischaemic Stroke in Children with Cardiac Disease.

Improved survival of children with congenital heart disease has led to increasing focus on neurodevelopmental outcome, as close to half of the infants undergoing cardiac surgery are affected by neurodevelopmental disability. Stroke is particularly important as it frequently results in permanent neurologic sequelae. The aim of this study was to investigate risk factors for peri-procedural arterial ischaemic stroke (AIS) in children with cardiac disease. A retrospective case-control analysis of children aged <18 years with radiologically confirmed AIS following a cardiac procedure admitted to the Royal Children's Hospital Melbourne between 1993 and 2010. Each case was matched with two controls with similar cardiac diagnosis, procedure type, age and date of procedure. Demographics and peri-procedural data were collected from medical records and departmental database. Fifty-two cases were identified. Multivariable analysis identified post-procedural infection (OR 6.1, CI 1.3-27, p = 0.017) and length of ICU stay (OR 4.0, CI 1.4-11, p = 0.009) as risk factors for AIS. Although the study is limited to a single-centre cohort, length of ICU stay and post-procedural infection were identified as risk factors for AIS. These findings demonstrate these factors to be important areas to focus attention for stroke prevention in children with cardiac disease.

Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.

BACKGROUND: The life expectancy of patients undergoing a Fontan procedure is unknown. METHODS AND RESULTS: Follow-up of all 1006 survivors of the 1089 patients who underwent a Fontan procedure in Australia and New Zealand was obtained from a binational population-based registry including all pediatric and adult cardiac centers. There were 203 atriopulmonary connections (AP; 1975-1995), 271 lateral tunnels (1988-2006), and 532 extracardiac conduits (1997-2010). The proportion with hypoplastic left heart syndrome increased from 1/173 (1%) before 1990 to 80/500 (16%) after 2000. Survival at 10 years was 89% (84%-93%) for AP and 97% (95% confidence interval [CI], 94%-99%) for lateral tunnels and extracardiac conduits. The longest survival estimate was 76% (95% CI, 67%-82%) at 25 years for AP. AP independently predicted worse survival compared with extracardiac conduits (hazard ratio, 6.2; P<0.001; 95% CI, 2.4-16.0). Freedom from failure (death, transplantation, takedown, conversion to extracardiac conduits, New York Heart Association III/IV, or protein-losing enteropathy/plastic bronchitis) 20 years after Fontan was 70% (95% CI, 63%-76%). Hypoplastic left heart syndrome was the primary predictor of Fontan failure (hazard ratio, 3.8; P<0.001; 95% CI, 2.0-7.1). Ten-year freedom from failure was 79% (95% CI, 61%-89%) for hypoplastic left heart syndrome versus 92% (95% CI, 87%-95%) for other morphologies. CONCLUSIONS: The long-term survival of the Australia and New Zealand Fontan population is excellent. Patients with an AP Fontan experience survival of 76% at 25 years. Technical modifications have further improved survival. Patients with hypoplastic left heart syndrome are at higher risk of failure. Large, comprehensive registries such as this will further improve our understanding of late outcomes after the Fontan procedure.

Favourable anatomy after end-to-side repair of interrupted aortic arch.

OBJECTIVE: To evaluate cardiovascular outcomes in patients with aortic arch repair and their possible correlation with arch geometry. METHODS: Ten patients who underwent end-to-side repair for aortic arch interruption (IAA), older than 10 years were compared to a cohort of 10 post coarctation (CoA) repair patients matched for age, sex and age at repair. Mean age at operation was 9.7±6.5 days. Patients underwent a resting and 24 h blood pressure measurements, exercise study, MRI, transthoracic echocardiography and vascular studies. RESULTS: Seven patients developed hypertension, two from IAA group and five from CoA group. Nine patients (45%) had gothic arch geometry, three from IAA group and six from CoA group. Despite differences in arch geometry, both groups had normal LV mass, LV function and vascular function. CONCLUSION: No differences in functional or morphologic outcomes could be demonstrated between the end-to-side repair of the arch by sternotomy and the conventional coarctation repair by thoracotomy. A favourable arch geometry can be achieved after the end-to-side repair of the aortic arch. In the present study, we could not correlate adverse arch geometry with any adverse cardio-vascular outcomes. After neonatal arch repair, the contributive role of aortic arch geometry to late hypertension remains uncertain.

FXN methylation predicts expression and clinical outcome in Friedreich ataxia.

OBJECTIVE: Friedreich ataxia (FA) is the most common ataxia and results from an expanded GAA repeat in the first intron of FXN. This leads to epigenetic modifications and reduced frataxin. We investigated the relationships between genetic, epigenetic, and clinical parameters in a large case-control study of FA. METHODS: Clinical data and samples were obtained from individuals with FA during annual visits to our dedicated FA clinic. GAA expansions were evaluated by polymerase chain reaction (PCR) and restriction endonuclease digest. DNA methylation was measured using bisulfite-based EpiTYPER MassARRAY (Sequenom, San Diego, CA). FXN expression was determined using real-time reverse transcriptase PCR. Significant correlations between the different parameters were examined using the nonparametric Spearman rank correlation coefficient, as well as univariate and multivariate regression modeling. RESULTS: Characteristic DNA methylation was identified upstream and downstream of the expansion, and validated in an independent FA cohort. Univariate and multivariate analyses showed significant inverse correlations between upstream methylation and FXN expression, and variation in downstream methylation and age of onset. FXN expression also inversely correlated with the Friedreich Ataxia Rating Scale score, an indicator of disease severity. INTERPRETATION: These novel findings provide compelling evidence for the link between the GAA expansion, the DNA methylation profile, FXN expression, and clinical outcome in FA. Epigenetic profiling of FXN could be used to gain greater insight into disease onset and progression, but also as a biomarker to learn more about specific treatment responses and pharmacological mechanism(s). This work also highlights the potential for developing therapies aimed at increasing frataxin levels to treat this debilitating disease.

The Peri/postnatal Epigenetic Twins Study (PETS).

The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the individual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and samples of plasma and serum taken at 28 weeks' gestation. We attended 75% of all births, at which time we collected multiple biological samples including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months; shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD.

Comparison of methods for imputing ordinal data using multivariate normal imputation: a case study of non-linear effects in a large cohort study.

BACKGROUND: Multiple imputation is becoming increasingly popular for handling missing data, with Markov chain Monte Carlo assuming multivariate normality (MVN) a commonly used approach. Imputing categorical variables (which are clearly non-normal) using MVN imputation is challenging, and several approaches have been suggested. However, it remains unclear which approach should be preferred. METHODS: We explore methods for imputing ordinal variables using MVN imputation, including imputing as a continuous variable and as a set of indicators, and various methods for assigning imputed values to the possible categories (rounding), for estimating a non-linear association between an ordinal exposure and binary outcome. We introduce a new approach where we impute as continuous and assign imputed values into categories based on the mean indicators imputed in a separate round of imputation. We compare these approaches in a simple setting where we make 50% of data in an ordinal exposure missing completely at random, within an otherwise complete real dataset. RESULTS: Methods that impute the ordinal exposure as continuous distorted the non-linear exposure-outcome association by biasing the relationship towards linearity irrespective of the rounding method. In contrast, imputing using indicators preserved the non-linear association but not the marginal distribution of the ordinal variable. CONCLUSIONS: Imputing ordinal variables as continuous can bias the estimation of the exposure-outcome association in the presence of non-linear relationships. Further work is needed to develop optimal methods for handling ordinal (and nominal) variables when using MVN imputation.

The burden of rotavirus-related illness among young children on the Australian health care system.

OBJECTIVE: To provide estimates of the annual number and cost of hospital admissions, emergency department (ED) visits and general practitioner (GP) visits for rotavirus (RV) related acute gastroenteritis (AGE) in young children in Australia. METHODS: Numbers of hospitalisations for AGE were determined from national hospital morbidity data from July 1998 to June 2003. The fraction of these hospitalisations that may be attributed to RV was estimated by direct linkage of hospital admissions and pathology data from hospitals in two regions of Australia and by a second indirect method using the seasonal variation of RV infection. Numbers of ED visits were estimated using statewide data from Victoria and New South Wales (NSW), and numbers of GP visits were estimated from representative sample data for GP visits. Costs of RV hospital admissions and ED visits were estimated from national hospital cost data. RESULTS: RV continues to account for around 10,000 hospitalisations annually for children aged less than five in Australia at an average cost of 1890 dollars each. There are an additional 22,000 ED visits a year where the child is not subsequently hospitalised, each at a cost of 320 dollars, and approximately 115,000 visits to GPs by children in this age group for RV-AGE at a cost of 36.60 dollars each. CONCLUSIONS: The annual cost of hospital admissions, ED visits and GP visits associated with RV infection in young children in Australia is approximately 30 million dollars. IMPLICATIONS: Vaccination against RV disease in Australia may provide substantial savings to the health care system, depending on the cost and effectiveness of an immunisation program.

MCAR is not necessary for the complete cases to constitute a simple random subsample of the target sample.

Missing data is the norm rather than the exception in complex epidemiological studies. Complete-case analyses, which discard all subjects with some data values missing, are known to be valid under the very restrictive assumption that the response mechanism is missing completely at random (MCAR). While conditions weaker than MCAR are known under which estimators of regression coefficients are unbiased, one often comes across the view in the literature that MCAR is necessary for the complete cases to form a simple random subsample of the target sample. In this paper, we explain why this is not the case, and we distill an assumption weaker than MCAR under which the simple random subsample condition holds, which we call available at random (AAR). Moreover, we show that, unlike MCAR, AAR response mechanisms can be missing not at random (MNAR). We also suggest how approximate AAR mechanisms might arise in practice through cancellation of selection and drop-out effects, and we conclude that before pooling partially complete and complete cases into an analysis, the investigator should consider how selection might impact on the representativeness of the cases included in the pooled analysis (compared to those comprising the complete cases only).

Ten-year outcomes of Fontan conversion in Australia and New Zealand demonstrate the superiority of a strategy of early conversion.

OBJECTIVE: To investigate the benefits of a strategy of early Fontan conversion. METHODS: Using the Australia and New Zealand Fontan Registry, retrospective analysis of their long-term follow-up data was performed. RESULTS: Between 1990 and 2014, a total of 39 patients underwent surgical conversion in 6 centres at a median age of 23.8 years (IQR: 19.3-28.2), 18.7 ± 5.0 years post-Fontan. One centre tended to perform conversion earlier: interval since first documented arrhythmia 2.9 ± 4.0 vs 4.0 ± 4.2 years, average NYHA Class 2 ± 0.4 vs 3 ± 0.9 (P = 0.008), mean number of preop anti-arrhythmics 1 ± 0.4 vs 2 ± 0.6 (P = 0.05). Two patients underwent conversion to an extracardiac conduit only, while 36 had concomitant right atrial cryoablation, of which 16 also had pacemaker implantation. Nine patients suffered major cardiac-related complications (7 low output syndrome, 3 ECMO, 3 acute renal failure, one stroke) (2/17 from the early conversion centre and 7/22 of the others; P = 0.14). Four patients died in hospital (10.3%) and 4 late after a median of 0.9 years [95% confidence interval (CI): 0.5-1] after conversion. An additional 2 patients needed transplantation at 1 and 8.8 years after conversion, respectively. The 10-year freedom from heart transplantation was 86% (95% CI: 51-97%). Outcomes from the centre with an early conversion strategy were significantly better: 8-year freedom from death or heart transplantation was 86% (95% CI: 53-96) vs 51% (95% CI: 22-74; log-rank P = 0.007). Eight additional patients required pacemaker implantation and 5 had arrhythmia recurrence. CONCLUSIONS: Fontan conversion is associated with lasting survival outcomes up to 10 years after conversion. A strategy of surgical conversion at earlier stage of failure may be associated with better survival free from transplantation.

No difference between aspirin and warfarin after extracardiac Fontan in a propensity score analysis of 475 patients.

OBJECTIVES: The most effective method of long-term thromboprophylaxis after the Fontan procedure is not clear. We compared the rates of thromboembolic events between patients receiving aspirin and warfarin after an extracardiac conduit Fontan procedure in a bi-national registry. METHODS: All patients who underwent an extracardiac conduit Fontan procedure from 1997 to 2010 in Australia and New Zealand were identified. Medication status and routine follow-up and echocardiographic data were obtained from all patients. Survival analysis with propensity score matching and adjustment was performed to determine the treatment effect of warfarin compared with that of aspirin beyond the first year of follow-up, after which time patients had settled on their long-term thromboprophylaxis strategy. RESULTS: Of 570 eligible patients, the data of 475 patients who were regularly followed up without mechanical valve replacement were available for analysis. Long-term thromboprophylaxis consisted of warfarin in 301 patients (63%), aspirin in 157 (33%) and none in 17 (4%). The 10-year rate of freedom from all thromboembolic events was 91% [95% confidence interval (CI) 88-94%]. Thromboembolic events beyond the first year of follow-up occurred in 18 patients (6 on aspirin and 12 on warfarin). After (i) propensity score adjustment and (ii) matching yielding 164 pairs, the hazard rates of thromboembolic events beyond the first year were not statistically different between the warfarin and aspirin groups [(i) hazard ratio (HR) 2.3, 95% CI 0.7-7.4, P = 0.2 and (ii) HR 1.5, 95% CI 0.5-4.7, P = 0.5, respectively]. CONCLUSIONS: No difference in the hazard rates of late thromboembolic events was observed between aspirin and warfarin beyond the first year after the extracardiac conduit Fontan procedure.

Arterial ischemic stroke in children with cardiac disease.

OBJECTIVE: To describe the spectrum of cardiac disorders, timing in relation to interventional procedures, and outcome in children with cardiac disease and arterial ischemic stroke (AIS). METHODS: Children younger than 18 years with cardiac disease and radiologically confirmed AIS admitted to the Royal Children's Hospital Melbourne between 1993 and 2010 were retrospectively identified using ICD-9 and ICD-10 searches. RESULTS: Seventy-six children with cardiac disease and radiologically confirmed AIS were identified with the median age at diagnosis of 5 months (interquartile range 0-58). Cardiac lesions included cyanotic congenital heart disease (CHD) in 42 (55%), acyanotic heart disease in 24 (29%), cardiomyopathies/myocarditis in 6 (8%), infective endocarditis in 3 (4%), and primary arrhythmias in 3 (4%). Stroke occurred following cardiac procedures in 52 patients (68%): 41 post cardiac surgery (4.6 strokes per 1,000 surgical procedures) and 11 post cardiac catheterization (1.7 strokes per 1,000 catheterizations). The median time from procedure to diagnosis of stroke was 3 days (interquartile range 2-7), with 68% (95% confidence interval 58%-79%) of strokes estimated to occur within the periprocedural period. Prevalence of periprocedural stroke varied by diagnostic category, but was most common in patients with cyanotic CHD undergoing palliative surgery (22/2,256, 1%) (p < 0.005). There were 3 AIS-related deaths, and 54 survivors (84%) had persisting neurologic deficits. CONCLUSIONS: Infants with cyanotic CHD were most frequently affected by AIS during the periprocedural period. Prospective cohort studies are required to determine effective primary and secondary prevention strategies.

Medium-term outcomes of bovine jugular vein graft and homograft conduits in children.

BACKGROUND: The bovine jugular vein (Contegra) conduit has been described as an alternative to the homograft for right ventricle (RV) to pulmonary artery (PA) connection. We assessed the outcomes of Contegra conduits and homografts at a single institution. METHODS: We conducted a retrospective review of children (n = 249) who underwent RV-to-PA conduit (Contegra or homograft) implantation from 2001 to 2011. RESULTS: Median operation age was 4.8 years (2 days-18 years). Indications for surgery were as follows: primary conduit insertion (n = 131; 53%), previous conduit failure (n = 57; 23%) or Ross procedure (n = 61; 25%). There were 113 (45%) Contegra conduits and 136 (55%) homografts (92 pulmonary, 44 aortic) inserted. Early mortality was 5% (n = 12). Overall survival was 89% (95% confidence interval (CI): 84-92%) at 5 years and 87% (95% CI: 81-92%) at 10 years. Mortality was associated with smaller conduit size (P = 0.044) and syndrome diagnosis (P = 0.012). Freedom from reoperation was 85% (95% CI: 77-91%) and 75% (95% CI: 59-86%) at 5 years for homografts and Contegra conduits, respectively. Patients required conduit replacement (15%) for endocarditis (n = 4; 11%) or graft failure (n = 34; 89%). Eleven patients developed distal conduit stenosis with the majority occurring in Contegra conduits (n = 7; 64%) (P = 0.004). A larger conduit (P = 0.007) was protective against reoperation. There was no difference in reoperation between conduits (P = 0.41). Mean follow-up was 5 ± 3.2 years (96% complete). Majority of survivors (99%) were in New York Heart Association Class II/I. CONCLUSION: The Contegra conduit and homograft demonstrate similar mid-term outcomes in children. Smaller conduit size is associated with higher graft failure and mortality.

Survival into adulthood of patients with atrial isomerism undergoing cardiac surgery.

OBJECTIVES: To identify determinants of adverse outcomes in patients with atrial isomerism. METHODS: Determinants of survival were analyzed for the group as a whole as well as separately for left and right atrial isomerism. RESULTS: There were 78 cases with right and 104 with left atrial isomerism. Nineteen patients were not offered surgery; 49 (47%) of those with left atrial isomerism and 60 (77%) with right atrial isomerism were directed to single ventricle palliation. A total of 67 patients died. Survival to 25 years was 62% (95% confidence interval [CI], 53%-69%). Independent predictors of mortality were obstructed total anomalous pulmonary venous drainage (P < .001; hazard ratio [HR], 5.2; 95% CI, 2.7-9.7) and asplenia (P = .008; HR, 2; 95% CI, 1.2-3.3). There was no evidence that patients born in the recent era had improved survival (P = .47; HR, 1.1; 95% CI, 0.8-1.5). Survival was better for patients with left than right atrial isomerism: 18 years survival 74% (95% CI, 63%-82%) versus 50% (95% CI, 38%-60%). Independent predictors of mortality for patients with left atrial isomerism were dextrocardia (P = .009; HR, 3.0; 95% CI, 1.3-6.7) and pulmonary stenosis (P = .042; HR, 0.3; 95% CI, 0.1-0.9) and patients with right atrial isomerism, biventricular repair (P < .001; HR, 6.0; 95% CI, 2.8-13), and obstructed total anomalous pulmonary venous drainage (P < .001; HR, 4.2; 95% CI, 2.0-8.6). CONCLUSIONS: A significant proportion of patients with isomerism still die before reaching adulthood. Only a fraction of those with obstructed pulmonary veins survive. Having biventricular repair does not confer a survival advantage to those born with right atrial isomerism.

Repair of partial atrioventricular septal defect: a 37-year experience.

OBJECTIVES: Partial atrioventricular septal defect (pAVSD) is routinely repaired with a low mortality. However, limited data are available on the long-term follow-up of these patients. The current study was designed to determine long-term survival and morbidity of a large cohort of patients operated on at a single institution. METHODS: From 1975 to 2012, 249 consecutive patients underwent pAVSD repair at the Royal Children's Hospital. The follow-up data were obtained from hospital records, correspondence with cardiologists and primary care physicians, patient surveys and the state death registry. RESULTS: The early mortality rate was 1.2% (3/249), while the long-term survival rate was 96% (95% CI: 93-98%) at 10 years and 94% (95% CI: 89-97%) at 30 years. Freedom from reoperation was 84% at 10 years and 75% at 30 years. The most common reoperations were left atrioventricular valve surgery (30/249, 12.1%), resection of left ventricular outflow tract obstruction (12/249, 4.8%) and closure of residual atrial septal defects (5/249, 2.0%). Implantation of a permanent pacemaker was required in 3.2% (8/249) of patients. Despite a substantial reoperation rate, only 43% of patients older than 18 years of age were seen by a cardiologist within the most recent 2 years of the study period, compared with 80% of those younger than 18 years (P < 0.001). CONCLUSIONS: Repair of pAVSD is performed with a low mortality and excellent long-term survival. However, a substantial reoperation rate warrants close follow-up into adulthood.

Intersurgeon variability in long-term outcomes after transatrial repair of tetralogy of Fallot: 25 years' experience with 675 patients.

OBJECTIVE: To compare the long-term reoperation rates among surgeons performing transatrial repair of tetralogy of Fallot. METHODS: The data set of 675 patients undergoing transatrial repair of tetralogy of Fallot at 1 institution from 1980 to 2005 was analyzed for intersurgeon differences in the reoperation rates. RESULTS: A follow-up period >15 years was available for 5 surgeons, allowing for comparison (541 patients; >80 patients/surgeon). The reintervention rate at 10 years varied from 8.8% (95% confidence interval [CI], 5.3%-14.5%) to 26.7% (95% CI, 14.9%-44.9%; hazard ratio, 3.4; P = .001). The procedures of 1 surgeon resulted in a reoperation rate of 10.5% at 20 years (95% CI, 5.4%-25.3%). The type of reoperation required varied among the surgeons. One surgeon had had no reoperations for pulmonary artery stenosis. Of the 5 surgeons, 2 (surgeons 2 and 5) had equivalent overall 10-year reoperation rates (24.1%, 95% CI, 12.9%-42.3%; vs 26.7%, 95% CI, 14.9%-44.9%; P = .32). Surgeon 5 had reoperation almost exclusively for right ventricular outflow tract obstruction (20.6%; 95% CI, 12.4%-33.1%) and surgeon 2 for right ventricular dilation (17.4%; 95% CI, 7.8%-36.3%). None of the patients treated by surgeon 5 required implantation of a valved conduit. CONCLUSIONS: An analysis of the reoperation rate during the long-term follow-up of transatrial repair of tetralogy of Fallot identified variability in the outcomes among 5 surgeons. The analysis of these differences suggested that an optimal amount of opening of the right ventricular outflow tract can lead to a decreased reintervention rate. The analysis of intersurgeon variability in outcomes should be encouraged, because it will lead to improvements in cardiac surgery outcomes.

New engineering treatment of bovine pericardium confers outstanding resistance to calcification in mitral and pulmonary implantations in a juvenile sheep model.

OBJECTIVE: To conduct a test of noninferiority for CardioCel (Admedus, Brisbane, Australia), a chemically engineered bovine pericardium over autologous pericardium treated intraoperatively with glutaraldehyde in a chronic juvenile sheep model of pulmonary valve (PV) and mitral valve (MV) reconstruction. METHODS: We replaced the posterior leaflet of the MV and of 1 PV cusp with patches in ewes aged 10 months. There were 2 groups: CardioCel (n = 6) and control (n = 4). All valves were competent. Echocardiography was performed before euthanasia. The collected data were function, macroscopy, histology, and calcium contents. The primary end points were thickening and calcium content. RESULTS: All animals survived until sacrifice after 7 months. The valves had normal echo. The macroscopic aspect of the valves was excellent. Examination of the slides for both groups revealed a continuous endothelium on both sides of the patch and a layer of new collagen developed on both sides between patch and endothelium and interstitial cells and smooth muscle cell in these layers. The patch had not thickened but the 2 layers of new collagen for the PV showed a median thickening of 37% in the CardioCel group and 111% in the control group (P = .01), and for the MV a thickening of 108% and 251%, respectively, was seen (P = .01). The median calcium content in the PV was 0.24 µg/mg (range, 0.19-0.30) in the CardioCel group versus 0.34 µg/mg (range, 0.24-0.62) in controls (P = .20). In the MV it was 0.46 µg/mg (range, 0.30-1.0) in the CardioCel group and 0.47 µg/mg (range, 0.29-1.9) in controls (P = 1.0). CONCLUSIONS: In this growing lamb model the CardioCel patch allowed accurate valve repair at both systemic and pulmonary pressure. The mechanical properties of CardioCel after 7 months were preserved with a more controlled healing than the treated autologous pericardium and without calcification.

Surgical palliation in patients with a single ventricle and dextrocardia.

BACKGROUND: Dextrocardia is found in a significant proportion of patients undergoing a single-ventricle repair. Surgical outcomes in this cohort are unclear. METHODS: The records of 41 consecutive patients with single-ventricle physiology and dextrocardia presenting in a single institution from 1990 to 2008 were reviewed. Of this cohort, 19 patients had heterotaxy syndrome. Twenty-five of the 41 patients had atrioventricular valve regurgitation (AVVR) on presentation (mild, 13; moderate, 9; severe, 3). RESULTS: One patient died before intervention. Initial surgical palliation was performed in 31 patients. Four patients died postoperatively and 4 interim deaths occurred between initial palliation and bidirectional cavopulmonary shunt (BCPS). Thirty of the surviving 32 patients underwent BCPS, with 2 perioperative deaths. There were 4 additional deaths before Fontan surgery. Twenty-two of the surviving 25 patients underwent a Fontan procedure. There was 1 postoperative mortality. Survival to the age of 15 years was 56% (95% confidence interval [CI], 39%-70%). Patients with moderate or severe regurgitation had higher mortality if they were managed conservatively rather than by surgery (5 of 6 vs 2 of 6; P=.24). Patients with bilateral BCPS had better operative outcomes and survival compared with peers with unilateral anastomosis (odds ratio, 27; P=.005; 95% CI, 2.7-269). The side of the systemic venous pathway did not seem to influence outcomes. CONCLUSIONS: Surgical outcomes of single-ventricle palliation seem poor in patients with dextrocardia. Aggressive management of congenital AVVR might improve the long-term prognosis.

Abnormal left ventricular diastolic function at late follow-up after repair of total anomalous pulmonary venous drainage: the impact of altered ventricular loading in utero.

BACKGROUND: Assessment of diastolic function has not been described after repair of total anomalous pulmonary venous drainage (TAPVD), but studies of exercise capacity demonstrate impaired performance in this population despite normal systolic function. We postulated that diastolic impairment might contribute to this finding. METHODS: We analyzed echocardiographic variables from 28 patients with repaired TAPVD and compared these with data from 32 healthy controls (normals) and 21 subjects with repaired transposition of the great arteries (TGA). RESULTS: Left ventricular (LV) end-diastolic volumes were smaller in the TAPVD group (median, 50 mL/m(2) compared with a median of 64 mL/m(2) in TGA and 67 mL/m(2) in normals; P < .001 in each case). LV diastolic function in the TAPVD group was impaired. Mitral early to late ratio was increased (median, 2.7 in TAPVD compared with a median of 1.9 in TGA [P = .047] and 2.1 in normals [P = .021]). LV isovolumic relaxation time was reduced (median, 50 milliseconds in TAPVD compared with a median of 70 milliseconds in both TGA and normals; P < .001 in each case). Late diastolic and systolic tissue Doppler velocities were lower and the E/e' ratio was higher in the TAPVD group. CONCLUSIONS: Patients with repaired TAPVD are usually regarded as having excellent outcomes, but the finding of LV diastolic dysfunction in this population warrants more careful follow-up. We postulate that the diastolic impairment in these patients is the result of relative unloading of the LV during early cardiac development. These findings may also have implications in considering therapeutic approaches for hypoplastic ventricles in attempting to achieve biventricular repair.

Outcomes of repair of complete atrioventricular septal defect in the current era.

OBJECTIVES: We sought to evaluate the surgical outcomes of the repair of complete atrioventricular septal defects (cAVSDs) in our institution in the current era. METHODS: From 2000 to 2011, 138 patients underwent definitive repair of cAVSD. Repair was performed using a two-patch technique in 92.0% of patients and one-patch technique in 2.2%, and the ventricular septal component was closed directly in 5.8% of patients. RESULTS: Operative mortality was 1.4% (2 of 138). Overall mortality was 5.8% (8 of 138). Follow-up was 96% complete. Freedom from reoperation was 84.3% (95% CI 77.1-91.5%) at 8 years. Age >6 months at repair was associated with higher rates of reoperation (P = 0.001; HR 6.85; 95% CI 2.30-20.44). However, operating at <6 months of age was associated with longer intensive care unit stay (P = 0.019; median 2.7 vs 1.4 days), mechanical ventilation (P = 0.001; median 1.7 vs 0.9 days) and postoperative hospital stay (P = 0.016; median 8 vs 5 days). Moderate or greater left atrioventricular valvular regurgitation (LAVVR) at discharge was a risk factor for reoperation (P < 0.001; HR 10.85; 95% CI 3.75-31.40). CONCLUSIONS: Repair of cAVSD carries low mortality, but a moderate reoperation rate. An optimal time for repair of the cAVSD is between 3 and 6 months of age. Repair prior to 3 months of age and the need for cleft closure were associated with a higher degree of LAVVR at discharge. Greater LAVVR at discharge is a risk factor for reoperation regardless of age at initial repair. In the current era, Down's syndrome is not a risk factor for reoperation.

End-to-side repair for aortic arch lesions offers excellent chances to reach adulthood without reoperation.

BACKGROUND: The purpose of this study was to determine the rate of reinterventions from birth to adulthood after end-to-side anastomosis technique for interrupted and hypoplastic aortic arches. Multicenter data have shown that more than half of patients require arch reintervention in the 2 decades after repair. METHODS: The follow-up of 170 consecutive patients undergoing end-to-side repair through sternotomy for interrupted aortic arch (95) or coarctation (75) in one institution between 1985 and 2012 was reviewed. Associated lesions included ventricular septal defect (143) and bicuspid aortic valve (50). One-stage repair was performed in 158 patients (93%). RESULTS: There were 12 hospital deaths (7%), and 4 early arch reinterventions (2 for bronchial compression). Eleven hospital survivors (7%) were lost to follow-up. After a mean of 10 ± 6 years, there were 9 late deaths. Eighteen-year survival was 93% (95% confidence interval: 87 to 96). Eight patients had bronchial compression, 5 during initial stay and 3 after hospital discharge; 2 of them required surgery. Eighteen-year freedom from arch reoperation was 87% (95% confidence interval: 76 to 93). An additional 10 patients underwent balloon dilation, for an 18-year freedom from reintervention (balloon dilation or surgery) of 77% (95% confidence interval: 65 to 85). At last follow-up, 24 patients (16%) had an echocardiographic gradient greater than 25 mm Hg. Blood pressure was recorded in 105 patients, and only 11 (10%) were hypertensive. CONCLUSIONS: The end-to-side anastomosis technique for repair of aortic arch lesions results in a low rate of mortality, arch reoperation, and late hypertension. The development of arch obstruction requiring balloon dilation warrants continuous follow-up of these patients.