Piers E.F. Daubeney

Clinical Features and Outcomes of Childhood Dilated Cardiomyopathy Results From a National Population-Based Study

Background— Despite considerable mortality, population-based prognostic factors for childhood dilated cardiomyopathy are lacking. Methods and Results— A population-based cohort study was undertaken of all children in Australia who presented with cardiomyopathy at age 0 to 10 years between January 1, 1987, and December 31, 1996. A single cardiologist analyzed all cardiac investigations, and a single pathologist analyzed histopathological material. There were 184 subjects with dilated cardiomyopathy. Positive viral identification or lymphocytic myocarditis was found in 30 (68.2%) of 44 cases with available early histology and 8 of 9 cases presenting with sudden death. Freedom from death or transplantation was 72% (95% CI, 65% to 78%) 1 year after presentation and 63% (95% CI, 55% to 70%) at 5 years. By proportional hazards regression analysis, risk factors for death or transplantation comprised age >5 years at presentation (hazard ratio 5.6, 95% CI, 2.6 to 12.0), familial dilated cardiomyopathy (hazard ratio, 2.9; 95% CI, 1.5 to 5.6), lower initial fractional shortening z score (hazard ratio per z-score unit, 0.75; 95% CI, 0.65 to 0.87), and failure to increase fractional shortening z score during follow-up (hazard ratio per unit increase, 0.68; 95% CI, 0.58 to 0.79). At follow-up, 78 (44.6%) of 175 cases diagnosed during life have no symptoms and are not taking any cardiac medication. Conclusions— Early mortality is high in childhood dilated cardiomyopathy, but the clinical status of long-term survivors is good. This population-based study identifies children at risk of adverse events.

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.

Development of Z-scores for fetal cardiac dimensions from echocardiography

Z‐scores for cardiac dimensions are well established in postnatal life, but have yet to be developed for fetal cardiac dimensions. These would be of real advantage to the clinician in accurately quantifying size and growth of cardiac dimensions and to the researcher by allowing mathematical comparison of growth in differing subgroups of a disease. The purpose of this observational study, conducted at tertiary fetal medicine and cardiology units, was to produce formulae and nomograms allowing computation of Z‐scores for fetal cardiac dimensions from knowledge of femur length (FL), biparietal diameter (BPD) or gestational age (GA) using fetal echocardiography.

Cerebral oxygenation measured by near-infrared spectroscopy: Comparison with jugular bulb oximetry

BACKGROUND Near-infrared spectroscopy is a potential tool for measuring adequacy of cerebral oxygenation during cardiac operations. The cerebral microcirculation is predominantly venous (by volume) and therefore regional cerebral oxygenation measured by near-infrared spectroscopy should reflect jugular bulb venous saturations. METHODS We compared simultaneous regional cerebral oxygenation and jugular bulb venous saturation measurements in 40 children (median age, 4.5 years; range 2 weeks to 14.5 years) in the cardiac catheter laboratory (n = 29) and during cardiac operations (n = 11). RESULTS For all patients combined the correlation between regional cerebral oxygenation and jugular bulb venous saturation was 0.69 (p < 0.0001) and was similar for the two groups. For individual children undergoing cardiac operations excellent correlations were obtained (r = 0.78 to 0.96; median, 0.91). However, at low values of jugular bulb venous saturation, regional cerebral oxygenation tended to run high, whereas the converse was true for high values of jugular bulb venous saturation. CONCLUSIONS These findings suggest that near-infrared spectroscopy may be a useful tool for assessing intravascular cerebral oxygenation during pediatric cardiac operations. Prospective studies of neurologic outcome will be required to establish the value of this technique for assessing the adequacy of cerebral protection.

Pulmonary atresia with intact ventricular septum - Impact of fetal echocardiography on incidence at birth and postnatal outcome

Background —Fetal echocardiography is widely established in the United Kingdom for prenatal diagnosis of congenital heart disease. This may result in a substantial reduction in incidence at birth because of selected termination of pregnancy. The objective of this population-based study was to determine the incidence of pulmonary atresia with intact ventricular septum (PAIVS) at birth, the impact of fetal echocardiography on this incidence, and to compare the outcome of cases with and those without prenatal diagnosis. Methods and Results —From 1991 to 1995, all infants born with PAIVS and all fetal diagnoses in the United Kingdom and Eire were studied. There were 183 live births (incidence 4.5/100 000 live births). The incidence was 4.1 cases per 100 000 live births in England and Wales, 4.7 in Scotland, 6.8 in Eire, and 9.6 in Northern Ireland ( P =0.01). There were 86 fetal diagnoses made at a mean of 22.0 weeks of gestation leading to 53 terminations of pregnancy (61%), 4 intrauterine deaths (5%), and 29 live births (34%). The incidence at birth would be 5.6 per 100 000 births in England and Wales, 5.3 in Scotland, and unchanged in Eire and Northern Ireland, if there were no terminations of pregnancy and assuming no further spontaneous fetal deaths ( P =0.28). An initial diagnosis of critical pulmonary stenosis was made in 6 cases, at a mean of 22.3 weeks of gestation with progression to PAIVS by 31.4 weeks. Probability of survival at 1 year was 65% and was the same for live-born infants whether or not a fetal diagnosis had been made. Conclusions —PAIVS is rare, occurring in 1 in 22 000 live births in the United Kingdom and Eire. Termination of pregnancy has resulted in an important reduction in the live-born incidence in mainland Britain.

Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: A three-year prospective study

OBJECTIVES To assess the incidence of microdeletions of chromosomal region 22q11 in a population of infants coming to a regional pediatric cardiac center with selected abnormalities of the ventricular outflow tracts and aortic arch and, further, to provide phenotypic/genetic correlations to determine whether patients with 22q11 deletions can be clinically recognized in infancy. BACKGROUND DiGeorge syndrome and velocardiofacial syndrome are frequently associated with malformations of the ventricular outflow tracts and aortic arch. Both are usually caused by microdeletions of chromosomal region 22q11. The overall importance of such deletions as a cause of these cardiac malformations remains to be established. STUDY DESIGN All infants with the candidate cardiac phenotypes during a 34-month period were studied. Dysmorphic features, type of cardiac defect, serum calcium concentration, and thymic status were recorded. Cytogenetic studies, including high-resolution karyotyping and fluorescence in situ hybridization using cosmids (cEO or cH748) from the DiGeorge critical region, were performed after clinical assessment. RESULTS Fifty infants (including 36 with tetralogy of Fallot with or without pulmonary atresia) were seen during the study period. Twenty-six infants (52%) were dysmorphic, including 19 who were considered to have a phenotypic appearance consistent with 22q11 deletion. Genetic analysis confirmed hemizygosity for 22q11 in 8 of these 19 cases. Results of fluorescence in situ hybridization studies were normal in 22 infants without dysmorphic features and in 5 infants with dysmorphic features not suggestive of a 22q11 deletion. CONCLUSIONS Microdeletions of chromosomal region 22q11 are an important cause of selected malformations of the ventricular outflow tracts and aortic arch and account for about 15% to 20% of cases. These deletions may be clinically recognized in early infancy and can be rapidly confirmed by fluorescence in situ hybridization.

Clinical Features and Outcomes of Childhood Hypertrophic Cardiomyopathy

Background—Population-based studies have provided insight into the natural history of adult hypertrophic cardiomyopathy, but comparable information for affected children is lacking. Methods and Results—All Australian children who presented with primary cardiomyopathy at 0 to 10 years of age between January 1, 1987, and December 31, 1996, were enrolled in a longitudinal cohort study. A single cardiologist reviewed serial cardiac investigations on each subject. A total of 80 subjects with hypertrophic cardiomyopathy were identified. An underlying syndromal, genetic, or metabolic condition was identified in 46 subjects (57.5%). There were no cases of sudden death at presentation. Left ventricular outflow tract obstruction was present in 32 subjects (40%); right ventricular outflow obstruction was present in 10 (12.5%). Freedom from death or transplantation was 83% (95% CI, 73 to 90) 5 years after presentation and 76% (95% CI, 62 to 86) 10 years after presentation. By proportional-hazards regression analysis, risk factors for death or transplantation included concentric left ventricular hypertrophy, age at presentation <1 year, lower initial fractional shortening Z score, and increasing left ventricular posterior wall thickness relative to body surface area. At the latest follow-up, 54 of 65 surviving subjects had no symptoms, and 46 were receiving no regular medication. Conclusions—Syndromal, genetic, and metabolic causes predominate in children with hypertrophic cardiomyopathy. Ventricular outflow tract obstruction is common. The clinical status of long-term survivors is good. This population-based study identifies children with hypertrophic cardiomyopathy who are at risk of adverse events.

Total Anomalous Pulmonary Venous Connection: Morphology and Outcome From an International Population-Based Study

Background— Late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO. Methods and Results— We conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence. Conclusions— Preoperative clinical and morphological features are important risk factors for postoperative PVO and survival.Background— Late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO. Methods and Results— We conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence. Conclusions— Preoperative clinical and morphological features are important risk factors for postoperative PVO and survival. # Clinical Perspective {#article-title-32}

Cerebral oxygenation during paediatric cardiac surgery : identification of vulnerable periods using near infrared spectroscopy

OBJECTIVE Neurologic sequelae remain a well recognised complication of paediatric cardiac surgery. Monitoring of cerebral oxygenation may be a useful technique for identifying vulnerable periods for the development of neurologic injury. We sought to measure regional cerebral oxygenation in children undergoing cardiac surgery using near infrared spectroscopy to ascertain such vulnerable periods. METHODS Observational study of 18 children (median age 1.3 years) undergoing cardiac surgery (17 with cardiopulmonary bypass, 8 with circulatory arrest). Regional cerebral oxygenation was monitored using the INVOS 3100 cerebral oximeter and related to haemodynamic parameters at each stage of the procedure. RESULTS Prior to the onset of bypass, 10 patients had a decrease in regional cerebral oxygenation of > or = 15% points, reaching an absolute haemoglobin saturation less than 35% in 5 cases. The most common cause was handling and dissection around the heart prior to and during caval cannulation. With institution of bypass, regional cerebral oxygenation increased by a mean 18% points to a mean maximum of 75%. During circulatory arrest regional cerebral oxygenation decreased with rate of decay influenced by temperature at onset of arrest (0.25%/min at < 20 degrees C; 2%/min at > 20 degrees C). Reperfusion caused an immediate increase in regional cerebral oxygenation followed by a decrease during rewarming. Discontinuation of bypass caused a precipitous decrease in regional cerebral oxygenation in 5 patients, reaching less than 50% in 3 patients. CONCLUSIONS These observations suggest that the pre- and early post-bypass periods are vulnerable times for provision of adequate cerebral oxygenation. Near infrared spectroscopy is a promising tool for monitoring O2 supply/demand relationships especially during circulatory arrest.

Morphologic and Functional Predictors of Eventual Circulation in the Fetus With Pulmonary Atresia or Critical Pulmonary Stenosis With Intact Septum

OBJECTIVES The purpose of this study was to determine the morphologic and physiological predictors of post-natal surgical pathway in a longitudinal series of fetuses with pulmonary atresia with intact ventricular septum (PAIVS) and/or critical pulmonary stenosis with reversal of ductal flow (CPS) using statistical modeling. BACKGROUND Pulmonary atresia with intact ventricular septum is rarely associated with chromosomal or extra cardiac malformations, so decisions about continuing a pregnancy are strongly influenced by the prediction of univentricular (UV) or biventricular (BV) circulation. METHODS Predictive scores were derived, using a combination of z-scores of fetal cardiac measurements (for femoral length) and tricuspid/mitral valve (TV/MV) ratios, to facilitate early prediction of UV or BV circulation in 21 fetuses with PAIVS (18 fetuses) or CPS (3 fetuses) between 1998 and 2004. We also assessed the predictive value of coronary fistulae and right atrial pressure (RAP) score (comprising the tricuspid valve, foramen ovale, and ductus venosus Doppler). RESULTS One-half of the cohort was first assessed before 23 gestational weeks (range 15.7 to 33.7 weeks). The TV z-score was a good predictor at all gestations, but the best predictive scores for specific gestations were pulmonary valve (PV) z-score (<23 weeks), median TV z-score (<26 weeks), the combination of median PV z-score and the median TV/MV ratio (26 to 31 weeks), and the combination of median TV z-score and median TV/MV ratio (>31 weeks). The RAP score and coronary fistulae were good independent predictors: RAP score >3 predicted BV with area under the curve of 0.833, and detection of fistulae usually predicted a UV route. CONCLUSIONS The best predictive scores for post-natal outcome in fetal PAIVS/CPS are a combination of morphologic and physiological variables, which predict a BV circulation with a sensitivity of 92% and specificity of 100% before 26 weeks.