Right ventricular function during exercise in children after heart transplantation.

Aims: Right ventricular (RV) dysfunction is a common problem after heart transplant (HTx). In this study, we used semi-supine bicycle ergometry (SSBE) stress echocardiography to evaluate RV systolic and diastolic reserve in paediatric HTx recipients. Methods and results: Thirty-nine pediatric HTx recipients and 23 controls underwent stepwise SSBE stress echocardiography. Colour tissue doppler imaging (TDI) peak systolic (s') and peak diastolic (e') velocities, myocardial acceleration during isovolumic contraction (IVA), and RV free wall longitudinal strain were measured at incremental heart rates (HR). The relationship with increasing HR was evaluated for each parameter by plotting values at each stage of exercise versus HR using linear and non-linear regression models. At rest, HTx recipients had higher HR with lower TDI velocities (s': 5.4 ± 1.7 vs. 10.4 ± 1.8 cm/s, P < 0.001; e': 6.4 ± 2.2 vs.12 ± 2.4 cm/s, P < 0.001) and RV IVA values (IVA: 1.2 ± 0.4 vs. 1.6 ± 0.8 m/s2, P = 0.04), while RV free wall longitudinal strain was similar between groups. At peak exercise, HR was higher in controls and all measurements of RV function were significantly lower in HTx recipients, except for RV free wall longitudinal strain. When assessing the increase in each parameter vs. HR, the slopes were not significantly different between patients and controls except for IVA, which was lower in HTx recipients. Conclusion: In pediatric HTx recipients RV systolic and diastolic functional response to exercise is preserved with a normal increase in TDI velocities and strain values with increasing HR. The blunted IVA response possibly indicates a mildly decreased RV contractile response but it requires further investigation.

Magnetic resonance imaging reveals elevated aortic pulse wave velocity in obese and overweight adolescents.

The aortic pulse wave velocity (PWV) measured via cardiac magnetic resonance (CMR) can be used to non-invasively assess changes in arterial stiffness and potential underlying vascular dysfunction. This technique could unmask early arterial dysfunction in overweight and obese youth at risk for cardiovascular disease. We sought to determine the association between vascular stiffness, percentage body fat, body mass index (BMI), and cardiac function in adolescents across the weight spectrum through both CMR and standard applanation tonometry (AT)-based PWV measurements. PWV and left-ventricular cardiac function were assessed using 3.0 T CMR in obese and overweight (OB/OW) participants (n = 12) and controls (n = 7). PWV was also estimated via carotid-femoral AT. OB/OW participants did not differ from healthy-weight controls regarding cardiometabolic risk factors or physical activity levels, but there was a trend towards higher levels of triglycerides in obese/overweight participants (P = 0.07). Mean PWV was higher in obese participants when corrected for age and sex (P = 0.01), and was positively associated with BMI (ß = 0.51, P = 0.02). PWV estimated through AT was not significantly different between groups. Cardiac function measured by left-ventricular ejection fraction z-score was inversely associated with mean PWV (ß = -0.57, P = 0.026). Increasing arterial stiffness and decreasing cardiac function were evident among our overweight and obese cohort. PWV estimated by CMR could detect early increases in arterial stiffness vs. traditional AT measurements of PWV.

Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention after Kawasaki Disease: The Pediatric Canadian Series.

Coronary artery (CA) aneurysms are serious complications of Kawasaki disease (KD) responsible for ischemic events. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are reported with limited data on indications and comparative efficacy. Retrospective multicenter comparison of CA intervention following KD is performed in this study. Twenty two cases were available from 5 centers, of whom 11 underwent CABG, 10 PCI and 1 systemic thrombolysis. Age at intervention (8.3 ± 3.9 vs 11.3 ± 4.9 years, p = 0.14) and interval from diagnosis (5.6 ± 4.1 vs 6.5 ± 4.7 years, p = 0.64) were similar between CABG and PCI. Interventions were based on angiography in 15 patients or cardiac event in 7, with no difference between CABG and PCI (p = 0.24). Patients with CABG were more likely to undergo multivessel intervention (73 vs 10 %, p = 0.006). None of the patients needed reintervention after CABG, compared to 6 after PCI and 1 after systemic thrombolysis (p = 0.004). Signs of ischemia on stress testing or MIBI were present in 15 patients before intervention and persisted in 9 patients following last intervention, in a significantly higher proportion after CABG than PCI (80 vs 17 %, p = 0.01). In this series, CABG, which mostly involved multivessel intervention, was superior to PCI. Nevertheless, larger-scale studies may help define patient selection criteria for a beneficial PCI approach.

Risk factors for specific causes of death following pediatric heart transplant: An analysis of the registry of the International Society of Heart and Lung Transplantation.

We sought to determine temporal changes in COD and identify COD-specific risk factors in pediatric primary HTx recipients. Using the ISHLT registry, time-dependent hazard of death after pediatric HTx, stratified by COD, was analyzed by multiphasic parametric hazard modeling with multivariable regression models for risk factor analysis. The proportion of pediatric HTx deaths from each of cardiovascular cause, allograft vasculopathy, and malignancy increased over time, while all other COD decreased post-HTx. Pre-HTx ECMO was associated with increased risk of death from graft failure (HR 2.43; p < 0.001), infection (HR 2.85; p < 0.001), and MOF (HR 2.22; p = 0.001), while post-HTx ECMO was associated with death from cerebrovascular events/bleed (HR 2.55; p = 0.001). CHD was associated with deaths due to pulmonary causes (HR 1.78; p = 0.007) or infection (HR 1.72; p < 0.001). Non-adherence was a significant risk factor for all cardiac COD, notably graft failure (HR 1.66; p = 0.001) and rejection (HR 1.89; p < 0.001). Risk factors related to specific COD are varied across different temporal phases post-HTx. Increased understanding of these factors will assist in risk stratification, guide anticipatory clinical decisions, and potentially improve patient survival.

Development and Impact of De Novo Anti-HLA Antibodies in Pediatric Heart Transplant Recipients.

There is increasing evidence that de novo anti-HLA antibodies, more specifically de novo donor-specific antibodies (DSA) following solid organ transplantation may be associated with negative outcomes including rejection in the first year and graft loss. Limited data are available in pediatric heart transplant recipients. We sought to prospectively determine the incidence, class and early impact of de novo anti-HLA antibodies in a cohort of pediatric heart transplant recipients. Serial panel reactive antibody testing posttransplant was performed in 25 patients (14 males) transplanted between January 2008 and June 2010. Five patients were sensitized pretransplant; all patients had negative direct crossmatch. Seventy-two percent developed de novo anti-HLA antibodies at a median of 2.6 weeks (IQR 1.2 weeks to 6.2 months) posttransplant; 67% of these were DSA. The majority of recipients in our cohort developed de novo anti-HLA antibodies within the first year posttransplant, with two-thirds being donor-specific. Acute cellular rejection, though frequent, was not different in patients with antibody development regardless of class or specificity, and there was no antibody-mediated rejection, graft loss or early cardiac allograft vasculopathy.

Adolescents with severe obesity: outcomes of participation in an intensive obesity management programme.

BACKGROUND: Most interventions for childhood obesity are randomized controlled studies. Less is known about the effectiveness of clinical obesity programmes. OBJECTIVE: To assess outcomes in adolescents participating in the SickKids Team Obesity Management Program (STOMP) vs. a comparison group of obese adolescents. METHODS: Severely obese adolescents (n = 75) in STOMP (15.1 ± 1.8 years, body mass index [BMI] 44.8 ± 7.8 kg m(-2) ) were compared with adolescents (n = 41) not in the programme (14.9 ± 2.0 years, BMI 34.5 ± 8.0 kg m(-2) ). Outcomes were change in BMI, cardiometabolic, psychological and health behaviour measures. RESULTS: At 6 months, STOMP patients' BMI was unchanged (0.08 ± 0.3; P = 0.79) and they reported improvements in quality of life and depression (-3.6 ± 1.4; P = 0.009), and increases in measures of readiness to change (RTC). Between-group differences in change between 0 and 6 months, in favour of STOMP patients, were observed for homeostatic measurement assessment-insulin resistance (HOMA-IR; -2.7 ± 1.0; P = 0.007), depression scores (-3.5 ± 1.7; P = 0.04), diet-RTC (0.6 ± 0.2; P < 0.001) and physical activity (1.7 ± 0.9; P = 0.05). At 12 months, STOMP patients increased BMI (0.8 ± 0.5; P = 0.07), but they exhibited decreased waist circumference (-7.4 ± 2.1 cm; P = 0.001) and HOMA-IR (-1.9 ± 0.6; P = 0.002). Between-group differences in change between 0 and 12 months, in favour of STOMP patients, were observed for waist circumference (-5.9 ± 2.4 cm; P = 0.01), HOMA-IR (-2.9 ± 0.7; P < 0.001) and diet-RTC (0.9 ± 0.2; P < 0.001). CONCLUSIONS: STOMP participants did not experience a significant reduction in BMI but did have improvements in cardiometabolic, psychological and health behaviour outcomes. Evaluation of paediatric clinical obesity programmes using multiple measures is essential to understanding real-world outcomes.

Children after fontan have strength and body composition similar to healthy peers and can successfully participate in daily moderate-to-vigorous physical activity.

The objective of this study was to evaluate the active lifestyle capacity (daily physical activity, strength, flexibility, body composition) of children after the Fontan procedure; hypothesized to be lower than healthy peers. Participants (n = 64, 25 females) were 9.0 ± 1.7 years of age (range 6.0-11.7 years). Fontan completion occurred at 3.3 ± 1.4 years of age (5.7 ± 2.0 years prior). Canadian Health Measures Survey protocols assessed aerobic endurance (paced walking up/down steps), strength (handgrip), flexibility (sit and reach), body composition (body mass index), and daily moderate-to-vigorous physical activity (7-day accelerometry). Difference scores compared participant data to published norms (t tests). Linear regression evaluated age/gender/demographic factor associations. Children after Fontan had strength scores similar (mean difference 1.1 kg) to their peers were less likely to be obese (mean difference of body mass index = 1.1 ± 2.5, p = 0.001) and performed 50 min of moderate-to-vigorous activity (MVPA) per day (12 ± 17 min/day below healthy peers, p < 0.001). Estimated peak endurance (61 % of expected) and flexibility (64 % of expected) were lower than peers (p < 0.001). Almost all (60/63) participants demonstrated the capacity to perform at least 20 min of MVPA per day. Difference from norms was smaller among children younger at Fontan completion (4 ± 2 min/year) and taking antithrombotic medication (7 ± 18 and 22 ± 17 min/day for taking/not taking, respectively). Children after Fontan demonstrate the capacity for the daily physical activity associated with optimal health. They have similar strength and good body composition. We recommend that children after Fontan be counselled that they can successfully participate in healthy, active lifestyles and physically active peer play.

The effect of puberty on fat oxidation rates during exercise in overweight and normal-weight girls.

Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre-early pubertal girls had higher max FOR [6.9 ± 1.4 mg·kg fat free mass (FFM)(-1)·min(-1)] than NW mid-late pubertal girls (2.2 ± 0.9 mg·kg FFM(-1)·min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 ± 2.1 mg·kg FFM(-1)·min(-1)), and OW mid-late pubertal girls (3.3 ± 0.9 mg·kg FFM(-1)·min(-1)) (P < 0.05). Bivariable analyses showed positive associations between FOR with homeostatic model assessment of IR (P = 0.001), leptin (P < 0.001), and leptin-to-adiponectin ratio (P = 0.001), independent of percent body fat. Max FOR decreased in NW girls during mid-late puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls.

Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic & Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology.

All children have a natural need to move, play, and perform activities. Physical activity is necessary for optimal physical, emotional, and psychosocial development for healthy children as well as children with congenital heart disease (CHD). In this paper we provide recommendations for physical activity, recreational sport, and exercise training in children and adolescents with CHD. In general, children with CHD should be advised to comply with public health recommendations of daily participation in 60 min or more of moderate-to-vigorous physical activity that is developmentally appropriate and enjoyable and involves a variety of activities. While all patients with CHD can participate and benefit from physical activity and exercise, those with specific lesions or complications may require counselling regarding precautions and recommendations.

Effects of an acute, outpatient physiotherapy exercise program following pediatric heart or lung transplantation.

This prospective interventional study investigated the impact of a three-month, ambulatory HA or HB, semi-individualized, PT-prescribed exercise program following pediatric HTx or LTx. SMW distance, strength, and flexibility were assessed at start and completion of the program and one yr after enrollment. Subjects received either an HB or HA exercise program three times per week. The cohort demonstrated clinically and statistically significant improvements in SMW distances at three months (425.7 ± 109.4-500.6 ± 93.6 m, p < 0.001) and at one yr (528.5 ± 66.6 m, p = 0.001), although there was no difference between the two groups at any time. Similar improvements were also observed in strength and flexibility measures. Correlates with higher SMW distance at three months and one yr included older age, male gender, and underlying diagnosis other than CHD. Male gender and diagnosis other than CHD were associated with a slower improvement in the SMW distance. This is the first report of institutionally based, outpatient exercise rehabilitation in the recovery following pediatric thoracic transplantation. We found similar improvements to HB interventions up to one yr after surgery. Further study of the role of exercise rehabilitation and long-term fitness outcomes is needed.

Predictive value of bronchoscopy after infant cardiac surgery: a prospective study.

BACKGROUND AND AIMS: Airway evaluation following infant cardiac surgery often reveals evidence of tracheobronchial narrowing. We studied the association between airway narrowing and extubation failure (EF) in this population. METHODS: Prospective cohort study of infants (age ≤6 months) from March-September 2009. Flexible bronchoscopy (FB) evaluations were obtained using a standardised protocol after operative intervention. The primary endpoint was the development of extubation failure (EF; defined as the need for invasive mechanical ventilation ≤48 h after primary extubation) and several secondary endpoints. RESULTS: Fifty-three patients were evaluated at a median age of 81 [interquartile range (IQR) 13-164] days and weight of 4.2 (IQR 3.2-6.0) kg; 13 (25 %) of the patients had single ventricle palliations and two subsequently underwent heart transplantation. Significant airway narrowing was noted in 15 of 30 [50 %, 95 % confidence interval (CI) 31-69 %] patients who underwent FB; ten of the 53 patients (19 %, 95 %CI 10-32 %) subsequently developed EF. Narrowed airway calibre on bronchoscopy had a sensitivity and specificity of 50 % (95 %CI 28-71 %) and 50 % (95 %CI 28-71 %), respectively, for EF. The single greatest predictor of EF by univariate analysis was the need for preoperative ventilation [odds ratio (OR) 6.5, 95 %CI 1.3-33.2, p = 0.03]. Patients with EF had a greater likelihood of intensive care readmission (OR 4.8, 95 %CI 1.1-21, p < 0.04) during the same hospital admission. CONCLUSIONS: Airway narrowing on FB is noted frequently after infant cardiac surgery. Overall assessment and presence of narrowing on bronchoscopy had poor sensitivity and specificity for EF in our cohort. Expert assessment of tracheobronchial narrowing on FB has poor to moderate inter-rater reliability.

Enhanced exercise performance and survival associated with evidence of autonomic reinnervation in pediatric heart transplant recipients.

Following heart transplantation (HTx), loss of autonomic input to the allograft results in elevated resting heart rate (HR) and decreased chronotropic reserve. As enhanced exercise capacity and HR recovery post exercise are suggestive of reinnervation in pediatric cohorts, we used heart rate variability (HRV) analysis to assess autonomic reinnervation in pediatric HTx recipients. Pediatric patients transplanted between 1996 and 2010 and with serial 24-hour Holter recordings post-HTx were analyzed for HRV using time and frequency domain measures. Of 112 patients, 68 (57%) showed evidence of autonomic reinnervation that was not associated with age at HTx. Evidence of reinnervation was associated with a significant increase in low-frequency power spectrum (p<0.001), suggesting sympathetic reinnervation. Patients with evidence of reinnervation showed higher percent-predicted maxVO(2) on performing an exercise test (+10.2 ± 3.6%, p = 0.006) and improved HR recovery at 3 minutes (-11.4 ± 3.9 bpm, p = 0.004), but no difference in percent-predicted maximal HR. Cox hazards modeling using presumed sinus reinnervation criteria at last Holter recording as a time-dependent covariate was associated with decreased hazard of mortality and/or retransplantation (HR: 0.2, 95% CI 0.04-1.0, p = 0.05). In conclusion, a majority of pediatric HTx recipients demonstrate evidence of reinnervation that is associated with functional outcomes. Studies to assess graft reinnervation as a marker of long-term prognosis are warranted.

Development of donor-specific isohemagglutinins following pediatric ABO-incompatible heart transplantation.

Graft acceptance following pediatric ABO-incompatible heart transplantation has been associated with a deficiency of donor-specific isohemagglutinins (DSI) due to B-cell elimination. Recent observations suggest that some of these patients do produce DSI. The purpose of this study was to examine the pattern of, risk factors for development and clinical impact of DSI. All children who underwent an ABO-incompatible heart transplant (1996-2009) were included. Serial postheart transplantation DSI titers and clinical outcomes were reviewed. DSI were produced in 27% of the patients (n = 11/41). Anti-A production was significantly greater in "at risk" patients than Anti-B (39% vs. 8%; p = 0.04). Risk factors associated with the development of DSI included: older age at transplantation (HR: 1.15/month, p = 0.04), pretransplant Anti-B level ≥ 1:8 (HR: 9.61, p = 0.004) and HLA sensitization (HR: 2.80, p = 0.11). The presence of DSI did increase the risk of cellular rejection but not antibody-mediated rejection, allograft vasculopathy, graft loss or death. Although these antibodies do not result in any significant clinical consequences, their presence suggests that B-cell tolerance is not the sole mechanism of graft acceptance.

Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

OBJECTIVES: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE). METHODS: Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies. RESULTS: The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001). CONCLUSIONS: An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.

The role of atorvastatin in regulating the immune response leading to vascular damage in a model of Kawasaki disease.

Superantigens have been implicated in a number of diseases including Kawasaki disease (KD), a multi-system vasculitis resulting in coronary artery aneurysms. We have characterized a murine disease model in which coronary arteritis is induced by a novel superantigen found in Lactobacillus casei cell wall extract (LCWE). Using this animal model of KD, we have identified three pathogenic steps leading to coronary artery aneurysm formation. These steps include T cell activation and proliferation, production of the proinflammatory cytokine tumour necrosis factor (TNF)-α and up-regulation of matrix metalloproteinase 9 (MMP-9), an elastolytic protease. In addition to their cholesterol-lowering effects, 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors (statins) have pleotropic immunomodulatory properties. Thus, we examined the effect of atorvastatin in modulating each of these three critical pathogenic processes leading to aneurysm formation in the disease model. Atorvastatin inhibited lymphocyte proliferation in response to superantigen stimulation in a dose-dependent manner. This inhibition was also observed for production of soluble mediators of inflammation including interleukin (IL)-2 and TNF-α. The inhibitory effect on proliferation was rescued completely by mevalonic acid, confirming that the mechanism responsible for this inhibitory activity on immune activation was inhibition of HMG-CoA reductase. Similarly, TNF-α-induced MMP-9 production was reduced in a dose-dependent manner in response to atorvastatin. Inhibition of extracellular-regulated kinase (ERK) phosphorylation appears to be the mechanism responsible for inhibition of MMP-9 production. In conclusion, atorvastatin is able to inhibit critical steps known to be important in the development of coronary aneurysms, suggesting that statins may have therapeutic benefit in patients with KD.

Outcomes of prenatally diagnosed tetralogy of Fallot: Implications for valve-sparing repair versus transannular patch.

OBJECTIVES: To assess outcomes of prenatally diagnosed tetralogy of Fallot and determine factors associated with the choice to undergo a valvesparing repair versus transannular patch, and the use of prostaglandins at birth. METHODS: All cases at The Hospital for Sick Children (Toronto, Ontario) with a fetal diagnosis of tetralogy of Fallot from 1998 to 2006, were reviewed for demographic and fetal echocardiographic data to determine factors associated with the valve-sparing repair and need for perinatal support. RESULTS: Sixty-four fetuses met inclusion criteria (median gestational age 22 weeks) with 47 live births. Twenty-six underwent valve-sparing repair (median age 5.7 months) and 14 underwent transannular patch repair (median age 4.5 months). There were seven deaths before surgery and one post-transannular patch repair. One patient required a transannular patch repair after the initial valve-sparing repair. Twelve of 29 (41%) patients received prostaglandins at birth. Type of surgical repair, use of prostaglandins and postnatal death were among the outcomes investigated. The mean pulmonary valve (PV) z-score was -3.0+/-2.0 and the mean PV/aortic valve (AoV) ratio was 0.65+/-0.10. Lower PV z-score (P=0.04), smaller PV/AoV ratio (P=0.04) and the presence of nonantegrade arterial duct flow (P=0.02) were associated with prostaglandin use. A higher PV/AoV ratio was associated with valvesparing repair (P=0.04). Fetal z-scores of the PV, AoV and right pulmonary artery at 29 to 32 weeks gestational age correlated with respective postnatal z-scores (P=0.01). CONCLUSION: Fetal echocardiographic variables were associated with the use of prostaglandins and valve-sparing repair in fetuses with tetralogy of Fallot, and at 29 weeks, correlated with postnatal valve diameters.

Equivalent outcomes for pediatric heart transplantation recipients: ABO-blood group incompatible versus ABO-compatible.

ABO-blood group incompatible infant heart transplantation has had excellent short-term outcomes. Uncertainties about long-term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO-incompatible recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart transplantation recipients (< or =14 months old, 1996-2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor-specific antibodies against blood group antigens, in only two ABO-incompatible patients were these antibodies implicated in antibody-mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow-up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO-blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO-compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor-specific isohemagglutinins and the implications for graft accommodation are warranted.

Left ventricular morphology influences mortality after the Norwood operation.

BACKGROUND: Within the spectrum of congenital heart disease referred to as hypoplastic left heart syndrome (HLHS), there is variation in the morphology and function of the left ventricle which could influence outcomes after stage I Norwood palliation. OBJECTIVE: To determine if left ventricular (LV) morphology is associated with outcome after stage I Norwood palliation for HLHS. METHODS: Echocardiograms were reviewed from 108 patients who had undergone Norwood palliation at our institution over the past 11 years. Total cardiac diameter, thickness of the interventricular septum (IVS), LV area and LV myocardial area were calculated. Competing risk analysis was performed for survival to a stage II operation and to determine potential predictors. RESULTS: From the Norwood operation up to stage II operation, mortality was predicted by IVS thickness, while the absence of right ventricular (RV) dysfunction was predictive of survival to stage II operation. For the complete pathway, from Norwood to the Fontan operation, mortality was predicted by IVS, a lower RV fractional area change and the presence of significant tricuspid regurgitation. Cardiac transplantation during this period was predicted by a lower RV fractional area change (p = 0.02) and a larger LV area in diastole. CONCLUSIONS: These results indicate that LV hypertrophy and decreased RV function adversely effect survival after the Norwood operation. They suggest that LV morphology, especially septal hypertrophy, can influence outcomes in HLHS and should be considered when evaluating treatment options.

Anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course: clinical profile and approach to management in the pediatric population.

An anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course (interarterial coronary artery [IACA]) is a rare congenital anomaly associated with sudden cardiac death. The cardiac and surgical databases at a single pediatric institution were reviewed for a description of the clinical profiles and associated risk factors of this coronary anomaly. From 1994 to 2006, IACA was diagnosed for 31 patients with a median age of 6.2 years (range, birth to 16 years). The symptoms for 6 (19%) of the 10 patients (32%) presenting with symptoms were deemed to be cardiac in origin. The symptoms for the remaining 21 patients (68%) were incidental findings. Of the 31 patients, 29 (94%) had normal resting electrocardiograms (ECG). A total of 17 patients underwent dobutamine stress echo. None had wall motion abnormalities, but two had ECG changes indicating ischemia, and 4 had abnormal coronary flow, as detected by Doppler echocardiography. Seven patients, with either acute symptoms or testing suggestive of ischemia, underwent surgery. All seven had an interarterial left main coronary artery. There was one cardiac-related death. No sudden death was found in either the surgery or nonsurgery group during the mean follow-up period of 23 and 58 months, respectively. Whether surgical intervention modifies the natural history of the anomaly or not remains to be determined.

Waiting before birth: outcomes after fetal listing for heart transplantation.

Following fetal diagnosis of a profound heart defect, transplantation (HTx) is an alternative to pregnancy termination or neonatal surgical palliation. Retrospective review of the cardiac and transplant databases of fetal listings for HTx between 1990 and July 2006 was undertaken to describe outcomes after listing. We identified 26 fetal listings (of 269 total listings). Diagnoses included congenital heart disease (n = 24) and cardiomyopathy (n = 2). Seven patients were delisted after birth: in five cases parents opted for surgical palliation, two clinically improved. One patient died wait-listed (stillborn). Time wait-listed as a fetus ranged from 1-41 days (median 19 days). Eighteen patients underwent HTx (median weight 2.8 kg, range 2.1-10.9 kg); median days wait-listed after birth was 22 (4 h-123 days). Two fetuses were surgically delivered at 36 weeks gestation when a donor organ became available; 11 were transplanted as neonates (<30 days). The median age at HTx was 1 month (4 h-2.6 months). Fetal listing for HTx increases the potential window of opportunity for a donor organ to become available; patients had low wait-list mortality and a fair intermediate-term outcome. Well-defined criteria for eligibility for fetal listing and priority allocation to infants over fetuses seem rational approaches for centers that offer fetal listing.