Pierre C. Wong

Cardiovascular Effects of Sildenafil in Neonates and Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension

Background: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. Objective: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. Methods: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 ± 1,019 g; gestational age = 35.6 ± 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. Results: Right cardiac output increased and left cardiac output tended to increase 1.5–4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. Conclusions: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.

Comparison of outcomes between living donor and cadaveric lung transplantation in children.

BACKGROUNDnLong-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL).nnnMETHODSnChildren were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36+/-3.16 years in LL and 12.00+/-4.19 years in CL patients (p = 0.37, ns).nnnRESULTSnThere was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48+/-3.84 months) than LL (13.60+/-10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV1) (p = 0.001) and FEF25-71% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL.nnnCONCLUSIONSnPediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.

Impact of respiratory syncytial virus infection on surgery for congenital heart disease: Postoperative course and outcome

OBJECTIVESna) To describe the postoperative course and outcome of cardiac surgery in children with recent respiratory syncytial virus (RSV) infection; and b) to evaluate whether timing of surgery has any impact on the outcome.nnnDESIGNnRetrospective case series.nnnSETTINGnIntensive care unit and medical and surgical wards of a teaching pediatric hospital.nnnPATIENTSnTwenty-five children (aged 25 days to 3.5 yrs; median, 4 months) with congenital heart disease who had cardiac surgery within 6 months after RSV infection.nnnINTERVENTIONSnNone.nnnMEASUREMENTS AND MAIN RESULTSnWe reviewed the clinical course and outcome of all patients. The cardiac diagnoses included ventricular septal defect (n = 11), tetralogy of Fallot (n = 3), atrioventricular canal (n = 3), and others (n = 8). Thirteen patients had surgery during the same admission as RSV infection (group I), and 12 patients had surgery electively after being discharged to home after RSV infection (group II). Two patients in group I died; both of these patients had undergone total repair of tetralogy of Fallot within 2 wks after admission for RSV infection. Postoperative complications in group I patients included pulmonary hypertension (n = 5), adult respiratory distress syndrome (n = 1), tracheal stenosis (n = 1), left ventricular dysfunction (n = 1), pericardial effusion (n = 1), secondary bacterial or fungal infection (n = 7), and deep venous thrombosis (n = 1). Of all group I patients, the ones who were operated on early appeared to be at higher risk for complications, especially for postoperative pulmonary hypertension. No patient in group II died, and only two patients had minor complications (one had reactive airway disease, and the other had a transient superior vena cava syndrome after a bidirectional Glenn operation).nnnCONCLUSIONSnCardiac surgery performed during the symptomatic period of RSV infection is associated with a high risk of postoperative complications, especially postoperative pulmonary hypertension. These complications appeared to be more frequent and of greater severity in patients who had earlier surgery compared with those who had later surgery. More studies are needed regarding the proper timing of cardiac surgery in patients with congenital heart disease and RSV infection.

Utility of B-Type Natriuretic Peptide in Differentiating Congestive Heart Failure from Lung Disease in Pediatric Patients with Respiratory Distress

Plasma B-type natriuretic peptide (BNP) has been reported to be helpful in differentiating cardiac from pulmonary etiologies of dyspnea in adults. We investigated whether BNP concentration could be applied similarly in children with respiratory distress. BNP levels were measured using a rapid immunoassay in 49 infants and children presenting with acute respiratory distress. The patient’s history, symptoms, physical exam, chest x-ray, and an echocardiogram were used to identify patients with congestive heart failure (CHF) from noncardiac causes of respiratory distress. Results are reported as mean ± SD. Patients with CHF (n = 23) had BNP levels of 693.0 ± 501.6xa0pg/ml, significantly higher than those of the group of patients with lung disease (n = 26), whose BNP was 45.2 ± 64.0xa0pg/ml (p < 0.001). There was no significant difference in age between the two groups (29.7 ± 59.3 vs 13.1 ± 22.6xa0months; p = 0.12). A BNP level of 40xa0pg/ml was 84% accurate in differentiating CHF from pulmonary disease. Fifteen of 23 CHF patients had ventricular volume overload from left-to-right shunting congenital heart defects and 8/23 had left ventricular systolic dysfunction. Age-adjusted comparison of the two subgroups of CHF patients revealed that children with left ventricular systolic dysfunction had significantly higher mean BNP levels than those with left-to-right shunts (1181 ± 487 vs 433 ± 471xa0pg/ml, p = 0.0074). We conclude that BNP level is of value in differentiating cardiac from pulmonary causes of respiratory distress in children.

Hemodynamic Changes After Low-Dosage Hydrocortisone Administration in Vasopressor-Treated Preterm and Term Neonates

OBJECTIVE. We sought to investigate whether the increase in blood pressure and decrease in vasopressor support after hydrocortisone administration are associated with changes in systemic hemodynamics in neonates who receive high-dosage dopamine to maintain blood pressure at the lowest acceptable levels. METHODS. In this prospective, observational study, preterm and term neonates who required dopamine ≥15 μg/kg per minute to maintain minimum acceptable blood pressure received intravenous hydrocortisone 2 mg/kg followed by up to 4 doses of 1 mg/kg every 12 hours. Fifteen preterm and 5 term neonates without a patent ductus arteriosus composed the study population. Echocardiograms and vascular Doppler studies were performed immediately before the first dose of hydrocortisone and at 1, 2, 6 to 12, 24, and 48 hours thereafter. RESULTS. In the 15 preterm infants, during the first 12 hours of hydrocortisone treatment, the 28% increase in blood pressure paralleled that in the systemic vascular resistance without changes in stroke volume or cardiac output, whereas dopamine dosage decreased. By 24 hours, the dosage of dopamine continued to decrease, whereas stroke volume increased without additional changes in systemic vascular resistance. By 48 hours, dopamine dosage decreased by 72%; blood pressure and stroke volume increased by 31% and 33%, respectively; and systemic vascular resistance and cardiac output tended to be higher (14% and 21%, respectively) compared with baseline. Contractility, global myocardial function, and Doppler indices of blood flow in the middle cerebral and renal artery remained normal and unchanged. The findings in the 5 term infants showed a similar pattern for changes in cardiac function, systemic hemodynamics, and organ blood flow after hydrocortisone administration. CONCLUSIONS. In preterm and term neonates who require high-dosage dopamine to maintain blood pressure at the lowest acceptable levels, hydrocortisone improves blood pressure without compromising cardiac function, systemic perfusion, or cerebral and renal blood flow.

Prenatal screening for congenital heart disease using real-time three-dimensional echocardiography and a novel 'sweep volume' acquisition technique

Conventional prenatal screening for congenital heart disease (CHD) involves a time‐consuming and highly operator‐dependent acquisition of the four‐chamber view and outflow tracts. By acquiring the entire fetal heart instantaneously as a single volume, real‐time three‐dimensional echocardiography (RT3DE) may facilitate fetal cardiac screening.

Real-time 3-dimensional fetal echocardiography with an instantaneous volume-rendered display early description and pictorial essay

Objective. Random fetal motion, rapid fetal heart rates, and cumbersome processing algorithms have limited reconstructive approaches to 3‐dimensional fetal cardiac imaging. Given the recent development of real‐time, instantaneous volume‐rendered sonographic displays of volume data, we sought to apply this technology to fetal cardiac imaging. Methods. We obtained 1 to 6 volume data sets on each of 30 fetal hearts referred for formal fetal echocardiography. Each volume data set was acquired over 2 to 8 seconds and stored on the systems hard drive. Rendered images were subsequently processed to optimize translucency, smoothing, and orientation and cropped to reveal “surgeons eye views” of clinically relevant anatomic structures. Qualitative comparison was made with conventional fetal echocardiography for each subject. Results. Volume‐rendered displays identified all major abnormalities but failed to identify small ventricular septal defects in 2 patients. Important planes and views not visualized during the actual scans were generated with minimal processing of rendered image displays. Volume‐rendered displays tended to have slightly inferior image quality compared with conventional 2‐dimensional images. Conclusions. Real‐time 3‐dimensional echocardiography with instantaneous volume‐rendered displays of the fetal heart represents a new approach to fetal cardiac imaging with tremendous clinical potential.

Does Initial Shunt Type for the Norwood Procedure Affect Echocardiographic Measures of Cardiac Size and Function During Infancy? The Single Ventricle Reconstruction Trial

Background— The Pediatric Heart Network trial comparing outcomes in 549 infants with single right ventricle undergoing a Norwood procedure randomized to modified Blalock-Taussig shunt or right ventricle–pulmonary artery shunt (RVPAS) found better 1-year transplant-free survival in those who received RVPAS. We sought to compare the impact of shunt type on echocardiographic indices of cardiac size and function up to 14 months of age. Methods and Results— A core laboratory measured indices of cardiac size and function from protocol exams: early after Norwood procedure (age 22.5±13.4 days), before stage II procedure (age 4.8±1.8 months), and at 14 months (age 14.3±1.2 months). Mean right ventricular ejection fraction was <50% at all intervals for both groups and was higher in the RVPAS group after Norwood procedure (49±7% versus 44±8%; P<0.001) but was similar by 14 months. Tricuspid and neoaortic regurgitation, diastolic function, and pulmonary artery and arch dimensions were similar in the 2 groups at all intervals. Neoaortic annulus area (4.2±1.2 versus 4.9±1.2 cm2/m2), systolic ejection times (214.0±29.4 versus 231.3±28.6 ms), neoaortic flow (6.2±2.4 versus 9.4±3.4 L/min per square meter), and peak arch velocity (1.9±0.7 versus 2.2±0.7 m/s) were lower at both interstage examinations in the RVPAS compared with the modified Blalock-Taussig shunt group (P<0.001 for all), but all were similar at 14 months. Conclusions— Indices of cardiac size and function after the Norwood procedure are similar for modified Blalock-Taussig shunt and RVPAS by 14 months of age. Interstage differences between shunt types can likely be explained by the physiology created when the shunts are in place rather than by intrinsic differences in cardiac function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Predictors of left ventricular outflow obstruction following single-stage repair of interrupted aortic arch and ventricular septal defect

This study looked at echocardiographic predictors of left ventricular outflow obstruction after primary neonatal repair of interrupted aortic arch and ventricular septal defect. Results of this study indicate that the only significant independent predictor of left ventricular outflow obstruction is aortic valve diameter; all patients with an aortic valve diameter <4.5 mm (Z score <-5) subsequently developed obstruction, whereas patients with annuli >4.5 mm (Z score >-5) remained free from obstruction.

Impact of Initial Shunt Type on Cardiac Size and Function in Children With Single Right Ventricle Anomalies Before the Fontan Procedure : The Single Ventricle Reconstruction Extension Trial

BACKGROUNDnIn children with single right ventricular (RV) anomalies, changes in RV size and function may bexa0influenced by shunt type chosen at the time of the Norwood procedure.nnnOBJECTIVESnThe study sought to identify shunt-related differences in echocardiographic findings at 14 months andxa0≤6xa0months pre-Fontan in survivors of the Norwood procedure.nnnMETHODSnWe compared 2-dimensional and Doppler echocardiographic indices of RV size and function, neo-aortic and tricuspid valve annulus dimensions and function, and aortic size and patency at 14.1 ± 1.2 months and 33.6 ± 9.6 months in subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt (MBTS) or right ventricle to pulmonary artery shunt (RVPAS).nnnRESULTSnAcceptable echocardiograms were available at both time points in 240 subjects (114 MBTS, 126 RVPAS). At 14 months, all indices were similar between shunt groups. From the 14-month to pre-Fontan echocardiogram, the MBTS group had stable indexed RV volumes and ejection fraction, while the RVPAS group had increased RV end-systolic volumexa0(pxa0= 0.004) and decreased right ventricular ejection fraction (RVEF) (pxa0= 0.004). From 14 months to pre-Fontan, the treatment groups were similar with respect to decline in indexed neo-aortic valve area, >mild neo-aortic valve regurgitation (<5% at each time), indexed tricuspid valve area, andxa0≥moderate tricuspid valve regurgitation (<20% at each time).nnnCONCLUSIONSnInitial Norwood shunt type influences pre-Fontan RV remodeling during the second and third years of life in survivors with single RV anomalies, with greater RVEF deterioration after RVPAS. Encouragingly, other indices of RV function remain stable before Fontan regardless of shunt type. (Comparison of Two Types of Shunts in Infants with Single Ventricle Defect Undergoing Staged Reconstruction-Pediatric Heart Network; NCT00115934).