[Predictive factors of Doppler echocardiography in persistent pulmonary artery hypertension of the neonate]. / Facteurs prédictifs de l'échocardiographie-doppler dans l'hypertension artérielle pulmonaire persistante du nouveau-né.

INTRODUCTION: echocardiographic evaluation in neonates with persistent pulmonary artery hypertension is often limited to pressure measurements and analysis of pulmonary artery blood flow. The prognostic significance of a more detailed analysis, in particular of the extra-pulmonary shunt, is not known. PATIENTS AND METHOD: we analysed retrospectively the echocardiographs of neonates with persistent pulmonary artery hypertension who were also entered in a randomised therapeutic trial of treatment with inhaled nitric oxide. Our aim was to identify the predictive echographic factors for extra-corporeal circulatory assistance, death and a good response to nitric oxide. RESULTS: out of the 85 neonates studied, an extra-pulmonary right-left shunt across the foramen ovale or the ductus arteriosus was present in 80 patients (94%). Biventricular function was normal in the majority of patients while the cardiac index was reduced (< 2L/min/m2) in 61% of cases. With multivariate analysis, an exclusively right-left ductal shunt was a predictive factor for death (odds ratio 7.8; 95% confidence interval 1.2 to 52.8; p=0.04) while an exclusively left-right ductal shunt was at the limit of significance for circulatory assistance (odds ratio 0.13; 95% confidence interval 0.01 to 1.22; p=0.07). In the 40 patients randomised to receive nitric oxide, 28 responded positively with a reduction of at least 20% in the oxygenation index measured by post-ductal arterial gasometry. The existence of a left-right atrial shunt increased the risk of a poor response to nitric oxide (odds ratio 7.46; 95% confidence interval 1.23 to 45.1; p=0.028). CONCLUSION: precise echocardiographic evaluation of these patients allows identification of prognostic factors and adjustment of vasodilator treatment.

Postoperative ectopic atrial tachycardia in children with congenital heart disease.

The causes and significance of postoperative ectopic atrial tachycardia (EAT) remain unknown. To identify factors associated with postoperative EAT in children after cardiac surgery, we retrospectively studied pre-, intra-, and postoperative variables. The median age for postoperative EAT cases was younger than the general population admitted for cardiac surgical procedures (6 vs 17 months old, p = 0.09). Trends for EAT cases included lower preoperative oxygen saturation (84% vs 99%, p = 0.001), more pre- and postoperative inotropic support, and atrial septostomy (24% vs 6%, p = 0.08). EAT cases had longer cardiopulmonary bypass times and clamp times (115 vs 88 minutes, p = 0.08; 63 vs 46 minutes, p = 0.03, respectively) and had a prolonged intensive care unit stay (10 vs 3 days, p <0.001). Deaths were recorded in 2 of 17 EAT cases versus 0 of 36 randomly selected controls (p = 0.10). EAT resolved before discharge in 10 of 16 surviving patients. The etiology of EAT appears to be multifactorial, and may include disruption of atrial septum, longer pump times, need for inotropic support, and potassium depletion. Thus, young, ill, cyanotic patients were most at risk for postoperative EAT. Although EAT was associated with prolonged intensive care, it resolved in most cases over time.

Mechanical circulatory support for the treatment of children with acute fulminant myocarditis.

BACKGROUND: Viral myocarditis may follow a rapidly progressive and fatal course in children. Mechanical circulatory support may be a life-saving measure by allowing an interval for return of native ventricular function in the majority of these patients or by providing a bridge to transplantation in the remainder. METHODS: A retrospective chart review of 15 children with viral myocarditis supported with extracorporeal membrane oxygenation (12 patients) or ventricular assist devices (3 patients) was performed. RESULTS: All patients had histories and clinical findings consistent with acute myocarditis. The median age was 4.6 years (range 1 day-13.6 years) with a median duration of mechanical circulatory support of 140 hours (range 48-400 hours). Myocardial biopsy tissue demonstrated inflammatory infiltrates or necrosis, or both, in 8 (67%) of the 12 patients who had biopsies. Overall survival was 12 (80%) of 15 patients, with 10 (83%) survivors of extracorporeal membrane oxygenation and 2 (67%) survivors of ventricular assist device support. Nine (60%) of the 15 patients were weaned from support, with 7 (78%) survivors; the remaining 6 patients were successfully bridged to transplantation, with 5 (83%) survivors. All survivors not undergoing transplantation are currently alive with normal ventricular function after a median follow-up of 1.1 years (range 0.9-5.3 years). CONCLUSION: Eighty-percent of the children who required mechanical circulatory support for acute myocarditis survived in this series. Recovery of native ventricular function to allow weaning from support can be anticipated in many of these patients with excellent prospects for eventual recovery of full myocardial function.

Child health status, neurodevelopmental outcome, and parental satisfaction in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn.

OBJECTIVE: To describe health and neurodevelopmental outcomes and parental satisfaction with hospital care among surviving intervention and control enrollees in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn (PPHN). METHODS: All surviving enrollees 1 to 4 years of age were eligible for follow-up. Outcomes were assessed by telephone using a trained interviewer and standardized instruments. Domains assessed included parental report of specific conditions and hospital use, rating of general health, cognitive and motor development, behavior problems, temperament, and satisfaction with the hospital stay. Fisher's exact test and the Wilcoxon rank sum test assessed differences between intervention and control infants. RESULTS: Interviews were completed on 60 of 83 survivors (72%). Eighteen families (22%) could not be located, 2 (2%) were non-English-speaking, and 3 (4%) declined participation. No postdischarge deaths were ascertained. Among those interviewed, race, income, and education of parents of intervention and controls were comparable, as were entry oxygenation index, extracorporeal oxygenation utilization, and days of hospitalization. No differences were found in pulmonary, neurologic, cognitive, behavioral, or neurosensory outcomes; hospital readmission rates; or parental ratings of child's health. The overall neurologic handicap rate was 15%. The rate of hearing deficit was 7%. The rate of significant behavioral problems was 26%. Levels of satisfaction expressed were high for each group. No differences in parental ratings were found between the 2 groups. CONCLUSIONS: No adverse health or neurodevelopmental outcomes have been observed among infants treated with nitric oxide for PPHN. The parents of the critically ill infants enrolled in our clinical trial welcomed their child's inclusion and all expressed satisfaction with the care that their child received while at a tertiary care hospital. Enrollment in either arm of this randomized, controlled trial did not seem to affect parental satisfaction with the hospital care that their child received.

Surgery for coarctation of the aorta in infants weighing less than 2 kg.

BACKGROUND: Low- and very low-birth weight infants are now candidates for reparative cardiac surgery. Outcomes after coarctation repair have not been characterized in this patient population. METHODS: We performed a retrospective review of 18 consecutive neonates less than 2 kg who underwent repair of aortic coarctation between August 1990 and December 1999. RESULTS: Median weight was 1,330 g, and median gestational age was 31 weeks. A ventricular septal defect was present in 5 patients, and Shone's complex in 4. Sixteen patients had resection and end-to-end anastomosis, and 2 had resection and subclavian flap. Median clamp time was 15.5 minutes. One patient died during hospitalization. Two patients died late postoperatively (5-year estimated survival 80%). Mean follow-up was 28.5 months. Eight patients (44%) had a residual or recurrent coarctation, 5 underwent balloon dilation, and 3 underwent reoperation. Freedom from reintervention for recoarctation was 60% at 5 years. Shone's complex or a hypoplastic arch was an independent risk factor for decreased survival (p < 0.001). Very low birth weight was a multivariate predictor for increased risk of recoarctation (p = 0.01). CONCLUSIONS: Coarctation repair in less than 2-kg premature non-Shone's infants can be performed with a low mortality. The rate of recoarctation is higher in the very low-birth weight infants, but can be managed with low risk.

Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn.

OBJECTIVE: We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV). DESIGN: Single-center, prospective, randomized, controlled trial. SETTING: Newborn intensive care unit of a tertiary care teaching hospital. PATIENTS: We studied infants with a gestational age of > or =34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (PaO2 < or =100 mm Hg on FIO2 = 1.0), despite optimal medical management Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded. INTERVENTIONS: The treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted. MEASUREMENTS AND MAIN RESULTS: Primary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively; p = .007). Mortality did not differ with treatment assignment. CONCLUSIONS: Among infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease.

Pulmonary hypertension associated with nonketotic hyperglycinaemia.

Nonketotic hyperglycinaemia (NKH) is an autosomal recessive disorder characterized by defective glycine degradation by the mitochondrial glycine cleavage system. The clinical features include lethargy, hypotonia, apnoea, seizures and severe psychomotor retardation, all attributed to the accumulation of glycine in the nervous system. Pulmonary hypertension (PHN) has not been reported in NKH. We describe four patients with NKH who had PHN in addition to the characteristic manifestations of NKH. This newly recognized association might provide additional insight into the underlying pathophysiology of PHN.

Whole blood ionized magnesium: age-related differences in normal values and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital cardiac disease.

OBJECTIVES: We sought to (1) determine reference values for whole blood ionized magnesium concentrations in newborns, children, and young adults and (2) evaluate the frequency and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital heart disease. METHOD: We prospectively measured ionized magnesium concentrations in 299 subjects (113 control subjects and 186 patients undergoing surgery for congenital heart disease). Subjects were categorized by age. In the surgical group blood samples were obtained before bypass, during bypass (cooling and rewarming), after bypass, and during admission to the intensive care unit. Ionized hypomagnesemia was defined as ionized magnesium level 2 standard deviations below the mean of control subjects in the same age group. Patients were analyzed, controlling for cardiopulmonary bypass time. RESULTS: In the control group ionized magnesium concentrations differed by age. Neonates and adults showed lower ionized magnesium concentrations compared with those of other age groups. Infants exhibited the highest ionized magnesium concentration. In the surgical group patients older than 1 month showed a higher proportion of ionized hypomagnesemia compared with that found in neonates at baseline (P <.001), after bypass (P =. 03), and at admission to the intensive care unit (P =.02). Controlling for cardiopulmonary bypass time, patients older than 1 month who were hypomagnesemic during bypass showed longer intubation time (P =.001) and longer intensive care stay (P =.01) and tended to have a higher pediatric severity of illness score on intensive care admission (P =.14) compared with patients without ionized hypomagnesemia. CONCLUSIONS: There are age-related differences in normal ionized magnesium concentrations. Ionized hypomagnesemia is a common and clinically relevant occurrence among patients older than 1 month of age undergoing surgery for congenital heart disease.

Reconstruction of 3-dimensional right ventricular shape and volume from 3 orthogonal planes.

This study validates a reconstructive technique that describes 3-dimensional right ventricular (RV) shape and volume with the use of 3 standard echocardiographic planes. The volume of 24 cast models of lamb right ventricles (12 normal, 12 hypertensive) was determined by water displacement. Reconstruction of the cast shapes was calculated from 2 sets of digitized data: cast cross-sectional digitized tracings and echocardiographic cross-sectional tracings. Regional volume ratios from both data sets were assessed to quantitatively specify RV regional volume differences between normotensive and hypertensive right ventricles. This method described the 3-dimensional RV shape with no differences between reconstructed volumes and true volumes for either normotensive or hypertensive casts. Between hypertensive and normal groups, regional volume ratios yielded a difference in free wall ratios that was observed to be greater in the hypertensive cast group (P =.007).

A new quantitative method for the diagnosis of right ventricular hypertensive disorders in 3 dimensions.

UNLABELLED: A new 3-dimensional (3D) method is described for the diagnosis of normal and hypertensive right ventricular (RV) conditions on the basis of similarity of RV structure to models of normal average shape or hypertensive average shape. Right ventricular quantification in multiple views (coronal, sagittal, and transverse) was obtained by measuring tangent angle differences (TADs) between RV tracings and average shapes at 128 points around the ventricular contour in each view. The TAD measurements of all views were then combined to quantify the closest 3D fit of the ventricle to a normal or hypertensive model. RESULTS: In 24 lamb casts measured in vitro, an accurate diagnosis was obtained in 11 of 12 normotensive casts (specificity 92%) and 11 of 12 hypertensive casts (sensitivity 92%). CONCLUSION: Accurate 3D diagnosis of in vitro normotensive and hypertensive RV conditions can be realized by measuring the TADs between the ventricle and average-shaped models.

Changes in whole blood lactate levels during cardiopulmonary bypass for surgery for congenital cardiac disease: an early indicator of morbidity and mortality.

OBJECTIVE: Our objective was to evaluate the change in lactate level during cardiopulmonary bypass and the possible predictive value in identifying patients at high risk of morbidity and mortality after surgery for congenital cardiac disease. METHODS: We prospectively studied lactate levels in 174 nonconsecutive patients undergoing cardiopulmonary bypass during operations for congenital cardiac disease. Arterial blood samples were taken before cardiopulmonary bypass, during cardiopulmonary bypass (cooling and rewarming), after cardiopulmonary bypass, and during admission to the cardiac intensive care unit. Complicated outcomes were defined as open sternum as a response to cardiopulmonary instability, renal failure, cardiac arrest and resuscitation, extracorporeal membrane oxygenation, and death. RESULTS: The largest increment in lactate level occurred during cardiopulmonary bypass. Lactate levels decreased between the postbypass period and on admission to the intensive care unit. Patients who had circulatory arrest exhibited higher lactate levels at all time points. Nonsurvivors had higher lactate levels at all time points. A change in lactate level of more than 3 mmol/L during cardiopulmonary bypass had the optimal sensitivity (82%) and specificity (80%) for mortality, although the positive predictive value was low. CONCLUSIONS: Hyperlactatemia occurs during cardiopulmonary bypass in patients undergoing operations for congenital cardiac disease and may be an early indicator for postoperative morbidity and mortality.

Preoperative management of pulmonary venous hypertension in hypoplastic left heart syndrome with restrictive atrial septal defect.

A severely restrictive atrial septal defect (ASD) in neonates with hypoplastic left heart syndrome (HLHS) results in pulmonary venous hypertension, pulmonary edema, and intractable hypoxia. Between January 1983 and June 1998, 21 of 355 neonates presenting with HLHS (5.9%) underwent cardiac catheterization at median age 1 day (range 0 to 25), for creation or enlargement of a restrictive or absent interatrial communication. One patient died during preliminary angiography. Three underwent blade septostomy with 2 procedure-related deaths, and 1 had balloon atrial septostomy (BAS); all 4 died before surgical intervention. Fifteen underwent Brockenbrough atrial septoplasty with transatrial needle puncture and serial balloon dilations of the new ASD, 5 after unsuccessful BAS. The most recent patient had a stent placed across the atrial septum after transatrial needle puncture. In the 16 patients treated with septoplasty or stent, oxygen saturation increased from 50 +/- 4% to 83 +/- 2% (p <0.0001) and transatrial pressure gradient decreased from 16 +/- 1 to 6 +/- 1 mm Hg (p <0.0001). One patient died awaiting transplantation, supportive care only was requested in 1, and 14 underwent stage 1 palliation. Eight of 14 (57%) survived to hospital discharge. Six of 7 (86%) survived bidirectional Glenn and the 3 who have undergone fenestrated Fontan are alive. In neonates with HLHS, a restrictive ASD resulting in profound cyanosis demands urgent intervention. BAS is frequently unsuccessful and blade septostomy has high mortality. Pulmonary venous hypertension can be adequately relieved by Brockenbrough atrial septoplasty or stenting, allowing stabilization before reconstructive surgery or while awaiting transplant.

Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing.

OBJECTIVES: We compared the ability of inhaled nitric oxide (NO), oxygen (O2) and nitric oxide in oxygen (NO+O2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization. BACKGROUND: In patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing. METHODS: In group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O2, return to RA and NO (80 parts per million [ppm] in RA). In group 2, 25 additional patients were studied in RA, 100% O2 and 80 ppm NO in oxygen (NO+O2). RESULTS: In group 1, O2 decreased pulmonary vascular resistance (PVR) (mean+/-SEM) from 17.2+/-2.1 U.m2 to 11.1+/-1.5 U.m2 (p < 0.05). Nitric oxide caused a comparable decrease from 17.8+/-2.2 U.m2 to 11.7+/-1.7 U.m2 (p < 0.05). In group 2, PVR decreased from 20.1+/-2.6 U.m2 to 14.3+/-1.9 U.m2 in O2 (p < 0.05) and further to 10.5+/-1.7 U.m2 in NO+O2 (p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O2 compared with 16/25 in O2 alone (p = 0.01). CONCLUSIONS: Inhaled NO and O2 produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO + O2 provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O2 identifies patients with significant pulmonary vasoreactivity who might not be recognized if O2 or NO were used separately.

Left ventricular assist device improves survival in children with left ventricular dysfunction after repair of anomalous origin of the left coronary artery from the pulmonary artery.

BACKGROUND: Repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in infants carries a high operative risk, particularly in infants with myocardial infarction and poor left ventricular function. The marked recovery of left ventricular function reported late after repair, however, suggests that an aggressive approach to repair should be undertaken. METHODS: Of 31 children undergoing primary repair of ALCAPA at our institution from 1987 to 1996, 26 were infants (6 weeks to 9 months old). All but 2 had severe left ventricular dysfunction, and 8 had moderate to severe mitral regurgitation. Seven children were unable to be weaned from cardiopulmonary bypass because of poor left ventricular function and elevated left atrial pressure. These 7 children were placed on mechanical left ventricular support using a centrifugal pump, with support ranging from 2.2 to 70.6 hours. RESULTS: One child died shortly after the start of left ventricular assist (2.2 hours), and another died of arrhythmia within 24 hours after successful decannulation. All 5 survivors had significant improvement in left ventricular function, with 2 requiring late mitral valve repair. CONCLUSIONS: Infants with ALCAPA who have severe left ventricular dysfunction represent a higher risk group for repair. However, with use of mechanical circulatory support in those unable to be weaned from cardiopulmonary bypass, a high survival rate can be achieved with good long-term recovery. We conclude that an aggressive approach to early repair in all children with ALCAPA is warranted, regardless of the degree of left ventricular dysfunction.

Mechanical circulatory support in children with cardiac disease.

OBJECTIVE: To review the experience from a single center that uses both extracorporeal membrane oxygenation and ventricular assist devices for children with cardiac disease requiring mechanical circulatory support. METHODS: A retrospective chart review was performed for all pediatric patients with cardiac disease who required support with extracorporeal membrane oxygenation or ventricular assist devices. Statistical analysis of the impact of multiple clinical parameters on survival was performed. RESULTS: From 1987 through 1996 we provided mechanical circulatory support for children with a primary cardiac diagnosis using extracorporeal membrane oxygenation (67 patients) and ventricular assist devices (29 patients). Twenty-seven of 67 (40.3%) patients supported with extracorporeal membrane oxygenation and 12 of 29 (41.4%) patients supported with ventricular assist devices survived to hospital discharge. Failure of return of ventricular function within 72 hours of the institution of support was an ominous sign in patients supported with either modality. Univariate analysis revealed the serum pH at 24 hours of support, the serum bicarbonate at 24 hours of support, the urine output over the first 24 hours of support, and the development of renal failure to have a statistically significant association with survival in children supported with extracorporeal membrane oxygenation. None of the clinical parameters evaluated by univariate analysis were significantly associated with survival in the patients supported with ventricular assist devices. CONCLUSIONS: Extracorporeal membrane oxygenation and ventricular assist devices represent complementary modalities of mechanical circulatory support that can both be used effectively in children with cardiac disease.

Inhaled nitric oxide does not affect adenosine 5'-diphosphate-dependent platelet activation in infants with persistent pulmonary hypertension of the newborn.

OBJECTIVE: To investigate the effect of inhaled nitric oxide (NO) treatment in newborns with persistent pulmonary hypertension on adenosine 5'-diphosphate (ADP)-dependent platelet activation. METHODS: After parental informed consent, infants with persistent pulmonary hypertension of the newborn were randomly assigned to receive conventional treatment (control group) or treatment with 40 parts per million of inhaled NO. Platelet activation was measured at time of entry and 30 minutes later by surface expression of P-selectin in response to increasing concentrations of the agonist ADP (0, 2, 5, 10, and 20 microM) using fluorescence-activated flow cytometry. RESULTS: We examined 11 infants in the inhaled NO group and 13 in the control group. P-selectin expression, quantified as mean fluorescence, was not significantly different in the two groups of patients at baseline. Median percent change from baseline fluorescence was assessed using the Wilcoxon matched-pairs signed-rank test. At 30 minutes after enrollment there were no statistically significant changes from baseline fluorescence in either group of patients and at all ADP concentrations. CONCLUSION: Thirty minutes of exposure to 40 ppm of inhaled NO does not inhibit ADP-dependent platelet activation as measured by surface expression of P-selectin in infants with persistent pulmonary hypertension of the newborn.

Duration of complete atrioventricular block after congenital heart disease surgery.

Children with complete heart block following surgery for congenital heart diseases were prospectively followed to assess the timing for recovery of atrioventricular conduction, and to determine if there were clinical variables that reliably predict permanent heart block. Recovery of atrioventricular conduction occurred by postoperative day 9 in 97% of patients with transient heart block.