Haemodynamic characterisation and heart catheterisation complications in children with pulmonary hypertension: Insights from the Global TOPP Registry (tracking outcomes and practice in paediatric pulmonary hypertension).

BACKGROUND: The TOPP Registry has been designed to provide epidemiologic, diagnostic, clinical, and outcome data on children with pulmonary hypertension (PH) confirmed by heart catheterisation (HC). This study aims to identify important characteristics of the haemodynamic profile at diagnosis and HC complications of paediatric patients presenting with PH. METHODS AND RESULTS: HC data sets underwent a blinded review for confirmation of PH (defined as mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary wedge pressure ≤ 12 mmHg and pulmonary vascular resistance index [PVRI] of >3 WU × m(2)). Of 568 patients enrolled, 472 who fulfilled the inclusion criteria and had sufficient data from HC were analysed. A total of 908 diagnostic and follow-up HCs were performed and complications occurred in 5.9% of all HCs including five (0.6%) deaths. General anaesthesia (GA) was used in 53%, and conscious sedation in 47%. Complications at diagnosis were more likely to occur if GA was used (p=0.04) and with higher functional class (p=0.02). Mean cardiac index (CI) was within normal limits at diagnosis when analysed for the entire group (3.7 L/min/m(2); 95% confidence interval 3.4-4.1), as was right atrial pressure despite a severely increased PVRI (16.6 WU × m(2,) 95% confidence interval 15.6-17.76). However, 24% of the patients had a CI of <2.5L/min/m(2) at diagnosis. A progressive increase in PVRI and decrease in CI was observed with age (p<0.001). CONCLUSION: In TOPP, haemodynamic assessment was remarkable for preserved CI in the majority of patients despite severely elevated PVRI. HC-related complication incidence was 5.9%, and was associated with GA and higher functional class.

Paediatric heart transplantation in Australia comes of age: 21 years of experience in a national centre.

BACKGROUND: Heart transplantation (HT) is established therapy for end-stage heart failure in children with cardiomyopathy or congenital heart disease. AIMS: This review summarises experience at a national referral centre since the first local transplant. METHODS: Medical records of children referred for HT between 1 April 1988 and 1 January 2010 were retrospectively reviewed. All patients listed for HT were included. Survival analysis was used to summarise wait-list time to death/transplant, and separately, time to death in HT patients. RESULTS: One hundred and thirty-nine children were accepted on to the HT waiting list during the study (median age 7.7 (interquartile range (IQR) 2.5, 13.6) years), of whom 93 underwent HT (median age 10.9 (IQR 4.4, 14.6) years). Wait-list mortality was 32% (45 of 139 patients), lowest among children aged >10 years at listing (P < 0.001). Median time to HT was 69 days (range 29-146). Survival post-transplantation was 90% (95% confidence interval 82-95) at 1 year, 82% (72-89%) at 5 years and 68% (50-80%) at 10 years. Increasing case complexity over the study period included pre- and post-transplant circulatory support, management of pulmonary hypertension and introduction of ABO-incompatible HT for infants. Post-transplant survival did not vary according to age, pre-transplant diagnosis or use of pre-transplant circulatory support (all P > 0.05). CONCLUSIONS: Results of paediatric HT in Australia are comparable with international results, despite limitations of geographic isolation, small population and low organ donation rate. Increasing case complexity has not impacted on post-transplant survival.

The Australia and New Zealand Fontan Registry: description and initial results from the first population-based Fontan registry.

BACKGROUND: The Fontan procedure is the final in a series of staged palliations for single-ventricle congenital heart disease, which encompasses rare and heterogeneous cardiac lesions. It represents an unusual and novel physiological state characterised by absence of a subpulmonary ventricle. AIMS: The population is growing steadily, prompting creation of this registry to study their epidemiology, demographic trends, treatment and outcomes. METHODS: This multicentre, binational, prospective and retrospective, web-based registry involving all congenital cardiac centres in the region has identified nearly all Fontan patients in Australia and New Zealand. Patients identified retrospectively were approached for recruitment. New recipients are automatically enrolled prospectively unless they choose to opt-out. Follow-up data are collected yearly. RESULTS: Baseline data were obtained in 1072 patients as at 1 January 2011. Ninety-nine patients died; 64 were lost to follow up. Forty-four per cent of patients lost were between 20 and 30 years of age. The size of the Fontan population is increasing steadily. Among 973 living patients, 541 (56%) gave consent for prospective collection of follow up. Between 1 January 2011 and 1 January 2013, an additional 47 subjects were enrolled prospectively. The current proportion of patients operated with hypoplastic left heart syndrome is currently 29% and is growing rapidly. CONCLUSION: The population surviving after the Fontan procedure has been growing in recent decades, especially since survival with hypoplastic left heart syndrome has improved. The Australia and New Zealand Fontan Registry provides population-based data, and only large databases like this will give opportunities for understanding the population and performing prospective trials.

Congenital heart disease-associated pulmonary arterial hypertension: preliminary results from a novel registry.

BACKGROUND/AIMS: Pulmonary arterial hypertension (PAH) frequently accompanies childhood congenital heart disease (CHD) and may persist into adult life. The advent of specific PAH therapies for PAH prompted formation of a national Australian and New Zealand registry in 2010 to document the incidence, demographics, presentation and outcomes for these patients. METHODS: This multicentre, prospective, web-based registry enrols patients with CHD-associated PAH being followed in a tertiary centre. The inclusion criteria stipulated patient age ≥16 years, a measured mean pulmonary arterial pressure >25 mmHg at rest or echocardiographical evidence of PAH or a diagnosis of Eisenmenger syndrome, and followed since 1 January 2000. A single observer collected standardised data during a series of site visits. RESULTS: Of the first 50 patients enrolled, 30 (60%) were female. The mean age (standard deviation (SD)) at the time of PAH diagnosis or confirmation in an adult centre was 27.23 (10.07) years, and 32 (64%) patients are currently aged >30 years. Fourteen (28%) patients were in World Health Organization Functional Class II and 36 (72%) in Class III at the time of diagnosis. Forty-seven of 50 (94%) had congenital systemic-pulmonary shunts, and 36 (72%) never underwent intervention. Thirteen (26%) had Down syndrome. Confirmation of PAH by recent cardiac catheterisation was available in 30 (60%) subjects. During follow up, a total of 32 (64%) patients received a PAH-specific therapy. CONCLUSIONS: CHD associated with PAH in adult life has resulted in a new population with unique needs. This registry will allow documentation of clinical course and long-term outcomes for these patients.

The Bosentan Patient Registry: long-term survival in pulmonary arterial hypertension.

BACKGROUND/AIMS: The Bosentan Patient Registry (BPR) was a prospective, multicentre, Australian registry funded by Actelion Pharmaceuticals. The primary aim of the registry was to collect survival data in patients with pulmonary arterial hypertension (PAH) treated with bosentan. METHODS: The BPR was initiated in 15 specialized PAH centres. All patients on or starting bosentan were invited to enrol. Treating physicians notified the registry if patients discontinued bosentan, because of either a change in therapy, transplantation, intervention or death. Survival data were validated against the Australian Institute of Health and Welfare National Death Index. RESULTS: Between 2004 and 2007, a total of 528 patients (mean age 59 ± 17 years) were enrolled representing 69% of patients either previously taking or initiated on bosentan during that time. The BPR population was generally older with more advanced functional deficit than patients enrolled in randomized, placebo-controlled trials. Aetiology was idiopathic (iPAH) in 58% and connective tissue disease related (scleroderma (SSc)-PAH) in 42%. For iPAH patients, World Health Organisation functional classes II, III and IV at enrolment was 8.2%, 66.4% and 20.5%, and for the SSc-PAH cohort, 3.2%, 75.8% and 17.9% respectively. The observed annual mortality was 11.8% in patients with iPAH and 16.6% in patients SSc-PAH. CONCLUSION: This large Australian registry provides 'real life' information on the characteristics and management of PAH in clinical practice. Treatment with bosentan improved survival outcomes in both iPAH and SSc-PAH compared with historical controls. Age, disease severity and aetiology were critical factors in determining clinical outcomes.

Long term somatic growth after repair of tetralogy of Fallot: evidence for restoration of genetic growth potential.

OBJECTIVE: To compare actual with predicted long term growth after early repair of tetralogy of Fallot (TOF). DESIGN: Serial preoperative and postoperative anthropometric data were converted with z scores. The presence of restrictive physiology was assessed by echocardiography. PATIENTS: 45 otherwise healthy patients who underwent repair at median age 1.6 years (range 0.2-4.9) were studied. Predicted height was determined from mid-parental height corrected for sex. RESULTS: Mean (SD) weight and height z scores at the time of surgery were significantly depressed (-1.04 (0.82) and -0.93 (0.95), respectively; p < 0.0001 for both). At latest follow up at a median age of 14.2 years (range 11-20.5), mean weight and height z scores were 0.16 (1.1) and -0.05 (0.81) (p = 0.32 and p = 0.41, respectively). The improvement between surgical and late weight and height z scores was significant (p < 0.0001 for each comparison). Catch up growth was largely complete within two years. Age at correction, duration of follow up, and prior surgical procedures were unrelated to growth. Mean current height z scores were similar to those predicted by mid-parental height. Patients with restrictive right ventricular physiology (n = 24) had a significantly greater late z score for weight (0.49 v -0.34; p = 0.01), with a similar trend for height. Low birth weight patients experienced comparable catch up growth but remained shorter than patients with normal birth weight (mean height z score -0.64 v 0.06; p = 0.03). CONCLUSIONS: Early repair of TOF results in significant acceleration of weight and height, with normalisation of long term growth and fulfilment of genetic growth potential.

Mechanisms and management of gingival overgrowth in paediatric transplant recipients: a review.

UNLABELLED: Increasing numbers of children are receiving solid organ transplants namely kidney, liver, heart and lung. Patient survival rates following such transplants are essentially good with much of the success attributable to the development of Cyclosporine A (CyA), an immunosuppressive drug, that minimizes organ rejection. However the gingival overgrowth (GO) associated with the use of CyA is not only disfiguring but in paediatric recipients, may interfere with normal oral development and function. OBJECTIVE: The aim of this review is to summarize current knowledge concerning the aetiology, pathogenesis and management of gingival overgrowth. METHODS: Literature pertaining to gingival overgrowth is reviewed with particular reference to the paediatric population. Emphasis is placed on summarizing the evidence pertaining to the effectiveness of intervention. CONCLUSION: CyA undoubtedly causes gingival overgrowth, the effects and levels of which appears to be more severe in younger patients. There is conflicting evidence as to the effectiveness of oral hygiene regimes, antibiotics and surgery in reducing overgrowth. The introduction of an alternative immunosuppressive agent (Tacrolimus) offers potential as it does not appear to cause overgrowth, although research to date is limited by the small sample size of many of the studies. This is an area in which multicentre studies would be of great value.

Clinical, electrocardiographic, and histologic correlations in children with dilated cardiomyopathy.

OBJECTIVE: To determine whether presenting electrocardiography is related to histologic findings and clinical outcomes in children with dilated cardiomyopathy. BACKGROUND: Lymphocytic myocarditis is an important cause of childhood dilated cardiomyopathy, the outcome of which is unclear. The results of non-invasive investigations are often used to infer the presence or absence of lymphocytic myocarditis. METHODS: Thirty-four children, presenting acutely with dilated cardiomyopathy, underwent both early electrocardiography and endomyocardial biopsy. The parameters examined included heart rate, PR, QRS, and corrected QT intervals, R-wave voltages in Leads V(1) and V(6), S-wave voltages in Leads V(1) and V(6), and sum of SV(1) and RV(6). We expressed measurements as Z scores, based on published normal values for age and gender. RESULTS: A total of 15 patients had lymphocytic myocarditis on endomyocardial biopsy (Group I), and 19 had non-specific histologic findings (Group II). We did not distinguish the 2 groups by age, time to endomyocardial biopsy, or duration of follow-up. Group I patients had significantly smaller R-wave Z scores in Leads V(1) and V(6), and combined S in V(1) and R in V(6) Z scores (p < 0.02 for each). The positive and negative predictive values of an R-wave amplitude in V(6) < 5th percentile were 75% and 65%, respectively, for the diagnosis of lymphocytic myocarditis. An R-wave amplitude in V(6) > 95th percentile had a positive and negative predictive value of 80% and 63%, respectively, for the diagnosis of idiopathic dilated cardiomyopathy. Survival and freedom from late cardiac dysfunction were more common among Group I patients compared with Group II (p

Pulmonary vascular resistance and reactivity in children with end-stage cardiomyopathy.

Pulmonary vascular resistance (PVR) and reactivity were compared in 63 children with end-stage cardiomyopathy (CM) referred for cardiac transplantation. Diagnostic category of CM was the sole determinant of PVR. Compared with other patients, children with restrictive CM were younger at diagnosis and had a significantly higher pulmonary vascular resistance index (PVRI). Children with a baseline PVRI of up to 11.8 units per meter squared (U.m(2)) who showed reactivity underwent successful orthotopic cardiac transplantation.

Relationship of the dimension of cardiac structures to body size: an echocardiographic study in normal infants and children.

Normalization of the dimensions of cardiac structures to the size of the body, using so-called Z scores, is becoming increasingly common in the management of infants and children with congenital heart disease. Current published nomograms for the ascertainment of Z scores for cardiac structures in childhood are based largely on normal data obtained in formalin-fixed hearts. Since decisions concerning management are frequently based on the findings of cross-sectional echocardiograms, the dimensions of 15 cardiac structures were measured using cross-sectional echocardiography in 125 normal infants and children. Regression equations were derived relating cardiac dimensions to the size of the body. The expression of size with the highest correlation to cardiac dimensions was body surface area. Nomograms were then developed from which the Z score of a cardiac structure could be estimated from a knowledge of the body surface area and the echocardiographically derived measurement.

Persistent truncus arteriosus in monozygotic twins: case report and literature review.

We report on a pair of monozygotic twins with persistent truncus arteriosus. They had no evident clinical signs of DiGeorge syndrome. Pathologic examination of the placenta and DNA analysis in chromosomes 7, 8, and 15 was consistent with monozygosity. Fluorescence in situ hybridization test was negative for chromosome 22q11 microdeletion. Family history revealed a female cousin with tetralogy of Fallot. The isolated presence of this conotruncal abnormality in monozygotic twins is extremely rare. The genetic considerations are discussed.

Hypoxic-ischaemic encephalopathy is associated with regional changes in cerebral blood flow velocity and alterations in cardiovascular function.

Doppler-derived indices of cerebral blood flow velocity (CBFV) and echocardiographic parameters of left ventricular function were measured in 18 patients with hypoxic-ischaemic encephalopathy HIE (group I) and in 28 normal controls (group II). Group-I infants had a subnormal distribution of CBFV values increasing over the first 85 h postnatally. CBFV values were constantly higher in the internal carotid than in the anterior cerebral artery. During the first 24 h postnatally, pulsatility and resistance indices of cerebral blood flow were significantly higher in group-I patients. From 30 to 85 h after birth, resistance indices were lower in group-I infants with severe HIE. Depressed left ventricular function and/or hypotension was documented in 50% of group-I patients.

Anatomic features and surgical strategies in double-outlet right ventricle.

BACKGROUND: The objective of this study was to review anatomic features and surgical strategies in children with double-outlet right ventricle (DORV) and to assess risk factors for early mortality. METHODS AND RESULTS: Records were reviewed of all children with DORV undergoing surgery between 1978 and 1993. Noncomplex patients (group 1) had atrioventricular (AV) concordance, a single ventricular septal defect (VSD), balanced ventricles, no straddling AV valves, and no major pulmonary artery anomaly. Group 2 (complex) comprised all remaining patients. Independent risk factors analyzed included location of the main VSD, presence of additional VSDs, coarctation, ventricular outflow obstruction, ventricular hypoplasia, age at operation, operation before 1985, previous palliation, and type of definitive operation. Of 193 patients, 117 were in group 1 and 76 in group 2. In 148 patients, biventricular repair was undertaken, including 111 of 117 group 1 patients and 37 of 76 group 2 patients. Early mortality was higher among group 2 patients undergoing biventricular repair than among group 1 patients (8 of 37 versus 4 of 111, P<.005) and higher than group 2 patients undergoing a Fontan procedure (none of 29, P<.01). Aortic arch obstruction, operation before 1985, and multiple VSDs were significant risk factors for mortality. Age <1 month (P<.05) and multiple VSDs (P<.005) were independent risk factors after definitive repair. Up-to-date follow-up is available on 144 surviving patients, with 127 (88%) in New York Heart Association class I and the remaining 17 in class II. Overall 10-year survival probability was 81%, whereas probability of survival, free from reoperation (after definitive surgery), was 65% at 10 years. CONCLUSIONS: Biventricular repair can be achieved in most patients with DORV with low risk. In complex DORV, a Fontan procedure is associated with a lower surgical mortality.

Senning plus arterial switch operation for discordant (congenitally corrected) transposition.

BACKGROUND: Congenitally corrected transposition of the great arteries is a complex cardiac lesion, usually associated with ventricular septal defect, left ventricular outflow tract obstruction, and tricuspid valve abnormalities. A subset of patients without left ventricular outflow tract obstruction have undergone Senning plus arterial switch operation in an attempt to place the left ventricle in the systemic circuit and the right ventricle in the pulmonary circuit. METHODS: Fourteen patients have had the operation performed since July 1989. Age and weight medians were 12 months (range, 0.5 to 120 months) and 8.2 kg (range, 3.2 to 34 kg). All but 1 patient had a left ventricular to right ventricular pressure ratio greater than 0.7, due to a large ventricular septal defect (with or without a previous pulmonary artery band), severe congestive heart failure caused by right ventricular dysfunction and tricuspid insufficiency, or a pulmonary artery band for left ventricular retraining. At least 10 patients had strong contraindications to "classic" repair, including right ventricular hypoplasia (n = 2), moderate to severe right ventricular dysfunction (n = 5), or moderate to severe tricuspid insufficiency (n = 9). RESULTS: There was one hospital death, occurring in a neonate (7%; 95% confidence interval = 0% to 34%). Actuarial survival beyond 10 months is 81% (95% confidence interval = 42% to 95%), currently with 389 patient-months of total follow-up time. The median grade of tricuspid insufficiency fell from 3/4 preoperatively to 1/4 postoperatively (p = 0.003). Right ventricular function is normal in 11/12 current survivors, all but 1 of whom are in New York Heart Association class I or II. CONCLUSIONS: Senning plus arterial switch operation is a good option for selected patients with congenitally corrected transposition of the great arteries with a similar or lower early risk (as compared with classic repairs). Some of the long-term problems associated with congenitally corrected transposition of the great arteries may be avoided with this strategy.

Gingival overgrowth in pediatric heart and heart-lung transplant recipients.

BACKGROUND: Gingival overgrowth is a recognized side effect of cyclosporine therapy with cosmetic and functional sequelae. This study examines the incidence and severity of gingival overgrowth in pediatric heart and heart-lung transplant recipients. METHODS: Thirty-one pediatric heart and heart-lung transplant recipients underwent a comprehensive dental evaluation. The severity of gingival overgrowth was scored by use of dental plaster casts. Parameters of dental hygiene in each patient included both a plaque index and a gingival inflammation index. The mean cyclosporine level and daily dose (mg/kg/day) at 3 and 12 months after transplantation and at latest follow-up were determined. RESULTS: The mean (+/- SD) patient age at transplantation was 10.5 (+/- 5.5) years, and the mean duration of posttransplantation follow-up was 3.2 (+/- 2.1) years. In all 30/31 (97%) of the cohort had some degree of overgrowth, with children aged less than 10 years at time of transplantation the most severely affected. By univariate analysis gingival overgrowth was inversely related to age at time of transplantation (r = -0.67, p < 0.001). With multiple regression analysis, only age at transplantation was significantly related to gingival overgrowth. CONCLUSIONS: Gingival overgrowth occurs in most pediatric heart and heart-lung transplant recipients treated with cyclosporine and is most severe in the younger patients. Attention to oral hygiene may improve gingival health parameters; however, the daily weight-adjusted dose of cyclosporine is not related to the severity of overgrowth.

Myocarditis in children with dilated cardiomyopathy: incidence and outcome after dual therapy immunosuppression.

BACKGROUND: The true incidence and prognosis of myocarditis in children with acute dilated cardiomyopathy (DCM) at presentation remains uncertain. This study examines the incidence of lymphocytic myocarditis in a consecutive cohort of children with acute DCM at presentation and outcome after dual therapy immunosuppression with cyclosporine and steroids. METHODS: Twenty-nine consecutive children with acute DCM underwent early endomyocardial biopsy. Children with "definite" myocarditis comprised group I (n = 9) and were treated with cyclosporine and prednisolone. Group II (n = 2) had "borderline" myocarditis, and group III (n = 18) nonspecific histologic findings. Outcome was assessed by echocardiographic measurement of left ventricular end-diastolic dimension and fractional shortening, with follow-up endomyocardial biopsy in group I subjects. RESULTS: Myocardial inflammation with or without myocardial necrosis (groups I and II) was present in 38% of all cases. There were no initial clinical, electrocardiographic, or echocardiographic features to distinguish patients in group I from patients in group III. At presentation, the mean +/- SEM left ventricular end-diastolic dimension and fractional score-Z scores of group I patients were 4.6 +/- 1.7 and -5.1 +/- 0.8, respectively, compared with 0.8 +/- 0.3 and -0.9 +/- 0.4, respectively, at withdrawal of immunosuppression (p < 0.001 for both). Both of these parameters did not differ significantly from normal controls at least follow up. Two group I patients had a biopsy-proven relapse after withdrawal of therapy that responded to reinstitution of immunosuppression. At latest follow-up, all nine group I patients had regained normal left ventricular function compared with four of 18 group III patients (p < 0.001). CONCLUSION: Lymphocytic myocarditis is frequent in children with dilated cardiomyopathy and cannot be predicted from noninvasive investigations. The use of cyclosporine and steroids is associated with a favorable outcome, and a controlled trial of dual therapy immunosuppression in children is therefore warranted.

Surgical commissurotomy of the aortic valve: outcome of open valvotomy in neonates with critical aortic stenosis.

Early intervention is necessary in neonates with critical aortic stenosis. The advent of alternate therapy, particularly balloon aortic valvuloplasty, requires a reappraisal of the traditional surgical approach, including the efficacy of initial transvalvar gradient reduction and freedom from recurrence of obstruction in the longer term. This report describes a series of 33 consecutive infants who underwent surgical aortic valvotomy in the first month of life. The hospital mortality was 18 percent with a 5-year probability of survival of 66 percent (90 percent CI, 50 percent to 79 percent). Fourteen reinterventions, nine reoperations and five balloon dilatations, were required at a median age of 0.8 years (range 9 days to 6 years). Three patients died after reintervention (one early and two late). The median follow-up time was 5.8 years (range 0.2 to 14 years). At last follow-up Doppler investigation the average Doppler mean and peak gradients were 34 mm Hg and 18 mm Hg, respectively. Open valvotomy in neonatal aortic valve stenosis allows the use of an appropriate surgical approach with low initial mortality and satisfactory 5-year freedom from reintervention.

Fetal echocardiography.

Fetal echocardiography has provided a means for the detailed assessment of cardiac structure and function from early prenatal life. Indications for a fetal echocardiographic examination and the potential implications for individuals caring for newborns with cardiac malformations are discussed.

Heart transplantation for chyloptysis after Fontan operation.

Chyloptysis is a rare clinical problem, fewer than 10 patients having been reported in the literature. We report a patient with intractable chyloptysis associated with a Fontan procedure, who was palliated by heart transplantation.