Mortality among infants with evolving bronchopulmonary dysplasia increases with major surgery and with pulmonary hypertension.

OBJECTIVE: To assess whether mortality in patients with evolving bronchopulmonary dysplasia (BPD, defined as ⩾28 days of oxygen exposure with lung disease) is independently associated with pulmonary arterial hypertension (PAH) and surgery. STUDY DESIGN: Single institution retrospective birth cohort of preterm infants with gestational age (GA) 230/7 to 366/7 weeks, and evolving BPD delivered between 2001 and 2014. Surgery was classified as minor or major using published criteria. Mortality was analyzed by stepwise logistic regression analysis. RESULTS: Among 577 patients with evolving BPD, 33 (6%) died prior to discharge. Mortality decreased with GA (adjusted odds ratio (aOR): 0.69; 95% confidence interval (CI): 0.55, 0.87), birth weight Z-score (aOR: 0.69, 95% CI: 0.47, 0.996) and increased with PAH (aOR: 30, 95% CI: 2.1, 415), major surgery (aOR; 2.8, 95% CI: 1.3, 6.3), and PAH and surgery (aOR: 10.3, 95% CI: 2.5, 42.1). CONCLUSION: Among preterm patients with evolving BPD, PAH and surgery are independently associated with mortality.

Early echocardiographic prediction of ductal closure in neonates ≤ 30 weeks gestation.

OBJECTIVE: To determine the accuracy of the patent ductus arteriosus:left pulmonary artery ratio (PDA:LPA) on echocardiogram (ECHO) at 3-day postnatal in predicting spontaneous PDA closure in neonates ≤ 30 weeks gestational age (GA). STUDY DESIGN: ECHOs were performed at 72 h to characterize PDA size as closed-to-small (PDA:LPA <0.5) or moderate-to-large (PDA:LPA ≥ 0.5) and at 10 days to determine spontaneous closure (defined as closed-to-small in the absence of medical and/or surgical treatment). Caretakers were blinded to results; treatment was based on standard care. Neonates were prospectively enrolled and stratified: <27 weeks (n=31) and 27 to 30 weeks (n=65). RESULT: Neonates <27 weeks with closed-to-small PDAs had 60% spontaneous closure vs 9% when moderate-to-large (positive predictive value (PPV) 60%, negative predictive value (NPV) 91%). Neonates 27 to 30 weeks had 95% spontaneous closure vs 27%, respectively (PPV 95%, NPV 73%). Inter-observer variability for the initial ECHO was 0.84. CONCLUSION: PDA size defined by PDA:LPA at 3 days postnatal in combination with GA predicts spontaneous PDA closure.

Echocardiographic predictors of symptomatic patent ductus arteriosus in extremely-low-birth-weight preterm neonates.

OBJECTIVE: Identify echocardiographic parameters at or=1 indicated a large PDA, <1 but >or=0.5 moderate, and <0.5 small. Sensitivity, specificity, and positive predictive values (PPV) were determined for ELBW <27 weeks and >or=27 weeks gestational age. RESULT: Neonates with moderate to large PDA at

Myocardial cell damage in Duchenne muscular dystrophy.

We report two cases of Duchenne muscular dystrophy that presented with laboratory evidence of acute transient myocardial cell damage. The mechanism for development of cardiomyopathy associated with Duchenne muscular dystrophy is not well understood, and this report raises the possibility that the progressive deterioration of cardiac function is punctuated by acute episodes of cell damage.

Coarctation index: identification of recurrent coarctation in infants with hypoplastic left heart syndrome after the Norwood procedure.

Assessment of recurrent coarctation after the Norwood procedure by routine measures is complicated by the unusual physiology caused by the presence of a modified Blalock-Tausig shunt with distal aortic arch obstruction. We present a new index that uses 2-dimensional measurement of the reconstructed aortic arch, which is highly sensitive and specific in identifying recurrent coarctation after the Norwood procedure in children with hypoplastic left heart syndrome.

Regional wall motion and strain of transplanted hearts in pediatric patients using magnetic resonance tagging.

Abnormal ventricular systolic torsion is present during histological rejection in adult cardiac transplant patients. Because biomechanical properties of transplanted hearts in the baseline state have not been studied in children, pediatric patients were evaluated to quantify ventricular wall motion and strain. Eight transplant studies and eight normal controls were evaluated. Magnetic resonance tagging was performed to determine radial shortening, twist, and strain in four ventricular anatomic areas at two short-axis levels. Controls had counterclockwise twist. Six transplant studies had clockwise twist, six had akinetic regions, and all had regions of no twist. One demonstrated paradoxical motion of the septum. A comparison between transplant patients and controls revealed strain to be similar in all regions except one (superior wall at the atrioventricular valve level) and strain distribution to be different only in two of eight regions. Pediatric transplant patients demonstrate regional wall motion abnormalities in the absence of rejection. Compared with normal controls, the transplanted left ventricle maintains normal strain in the presence of abnormal twist. This may be a compensatory mechanism and have clinical implications.

The four-chamber view and its sensitivity in detecting congenital heart defects.

We sought to determine the sensitivity of detecting congenital heart defects with routine antenatal ultrasound including the four-chamber view in a population at low risk for cardiac anomalies. Neonatal outcome and anomaly databases were reviewed to identify cases of morphologic cardiac defects from 1988-1992. Of 176 cases identified, 62 (35%) had routine antenatal ultrasound including the four-chamber view. Thirteen of these 62 (21%) were diagnosed by ultrasound and 18 of the 116 (15%) total defects present were seen. Of these, only 16 of 25 (64%) defects reasonably expected to be seen by the four-chamber cardiac view alone were detected. The routine ultrasound four-chamber cardiac evaluation is limited and detection depends on the type of cardiac defect present.

Aortic atresia with interruption of the aortic arch and an aortopulmonary fistulous tract: case report.

We present a case of interruption of the aortic arch (IAA) in association with aortic atresia. A pulmonary artery to ascending aorta fistulous channel at the level of the sinuses of Valsalva of the pulmonary artery was present and supplied the ascending aorta and coronary arteries. The communication had a significant length, so embryologically it is not an aortopulmonary window. There have been only three reported cases in the literature of IAA with aortic atresia; in none was a pulmonary artery to ascending aorta fistulous tract present.

Prevalence, relation to spontaneous closure, and association of muscular ventricular septal defects with other cardiac defects.

Previous studies on muscular ventricular septal defect (VSD) have not taken into account the specific defect location in the septum. We retrospectively reviewed all patients with a muscular VSD, with and without associated malformations, diagnosed over 32 months to determine the prevalence and rate of spontaneous closure of single defects in relation to location in the muscular septum. Defects were classified into 4 groups: midmuscular, apical, anterior, and posterior. Two hundred seven patients were identified, of whom 125 had a single defect. The relative prevalence of single muscular VSD was: midmuscular 55 (44%), apical 31 (25%), anterior 33 (26%), and posterior 6 (5%). Thirty patients had signs of spontaneous closure and only 1 underwent surgery. There was no difference in rate of closure with respect to anatomic locations. Patients with multiple muscular VSD were either referred for surgery in the first year of life or had a course similar to patients with a single VSD. Muscular VSD associated with other cardiac malformations was more often encountered in patients with conoventricular VSD and coarctation of the aorta. The distribution of anatomic groups of muscular VSD in association with malformations was similar to the single VSD.

Magnetic resonance and echocardiographic imaging of pulmonary artery size throughout stages of Fontan reconstruction.

BACKGROUND: Because pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size. METHODS AND RESULTS: This study analyzed the T1-weighted, spin-echo magnetic resonance and echocardiographic images of 36 functional single-ventricle patients throughout stages of Fontan reconstruction (prebidirectional and postbidirectional cavopulmonary anastomosis and after Fontan) and compared them with angiography images at cardiac catheterization. Magnetic resonance imaging had a high degree of agreement with angiography, with the McGoon index agreeing better than the Nakata index and absolute right and left pulmonary diameters. Although echocardiography had fair agreement with angiography, it agreed less well and had a wider standard deviation than magnetic resonance imaging for all indexes and measurements and, based on the prediction interval, would be a poorer prospective measure of pulmonary artery size in this population. In addition, echocardiography was a poorer measure of pulmonary artery size as the size of the vessel increases. Magnetic resonance imaging correctly detected five of five patients with nonconfluent branch pulmonary arteries and six of six patients with stenoses, whereas echocardiography was unable to visualize any of the patients with nonconfluent branch pulmonary arteries with certainty and only two of six (33%) with stenoses. CONCLUSIONS: Magnetic resonance imaging is a useful, noninvasive tool to determine pulmonary artery size in patients undergoing Fontan reconstruction and is superior to echocardiography. Echocardiography was a fair predictor of pulmonary artery size, but magnetic resonance imaging agreed with angiography better than echocardiography and outperformed echocardiography in diagnosing branch pulmonary artery discontinuity and stenoses. Magnetic resonance imaging may avoid unnecessary cardiac catheterization, especially in older patients, and may obviate the need for jugular or subclavian catheterization in those who have undergone bidirectional cavopulmonary anastomosis.

Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow.

The aim of this study was to determine if endothelial cells in the heart release substances into the coronary perfusion medium that modify the contractility of myocardial cells. To assay the effects on the contractility of cardiac muscle of fluid that has passed through the coronary vasculature, a new method has been developed based on the cascade principle used to study vascular smooth muscle function. The coronary venous effluent from an isolated perfused working heart was collected periodically, and after reoxygenation it was used as the bathing medium for trabeculae isolated from the endocardial surface of another heart. The coronary venous effluent changed the contraction of the isolated trabeculae. The amplitude and the direction of the change depended on the degree of oxygen saturation of the coronary effluent before it was reoxygenated and the rate of coronary flow at the time the effluent was collected. The response of the trabecula to the coronary effluent was substantially altered by damaging the endocardial endothelium with a 1-second exposure to 0.5% Triton X-100 in Krebs' solution. It was completely eliminated by damaging endothelial cells in both the perfused heart producing the effluent and the trabecula on which the effluent was assayed. Therefore, endothelial cells are required for the presence of cardioactive substances in the coronary effluent. The production of a labile endothelium-derived upregulating (positively inotropic) factor and a more stable endothelium-derived downregulating (negatively inotropic) factor has been demonstrated and appears to account for all of the changes in myocardial contractility produced by the coronary effluent. Neither of the endothelium-derived substances demonstrated in the isolated perfused heart is nitric oxide or endothelin. The concentration of the endothelium-derived upregulating factor is sensitive to oxygen tension, whereas the concentration of the endothelium-derived downregulating factor is sensitive to the rate of coronary flow but not oxygen tension. The coronary effluent appears to contain substances that stimulate secretion by the endothelial cells (preendothelial factors) as well as substances that have been produced by the endothelial cells (endothelial factors). The results indicate that during the passage of perfusion medium through the coronary vasculature upregulating and downregulating factors are added to the perfusate in relative concentrations that depend at least in part on local tissue PO2 and the rate of coronary flow. In the intact heart, this mechanism could operate to maintain balance between energy supply and work performed.

Endothelial cells are required for the cAMP regulation of cardiac contractile proteins.

The contractile proteins in mammalian cardiac muscle are regulated by a cAMP-dependent reaction that alters the activity of the actomyosin ATPase. The ATPase activity of cardiac actomyosin has also been shown to depend on factors released by small arteries in the myocardial tissue. Endothelial cells have been implicated in the regulation of the contractile force developed by isolated cardiac tissue. To determine whether endothelial cells are required for the cAMP-dependent regulation of the contractile proteins, the effect of cAMP on the actomyosin ATPase activity was measured in cryostatic sections of isolated, quickly frozen rat ventricular trabeculae. In half of the trabeculae, the endocardial endothelial cells had been damaged by a 1-sec exposure to 0.5% Triton X-100. In trabeculae with intact endothelial cells, cAMP increased actomyosin ATPase activity toward an apparently maximum value. In trabeculae with damaged endothelial cells, cAMP did not change actomyosin ATPase activity. The coronary venous effluent from an isolated heart has already been shown to modify the maximum isometric force developed by an isolated trabecula. The extent to which the force of the isolated trabecula is changed by the coronary venous effluent is closely related to the degree to which cAMP has up-regulated the actomyosin ATPase activity in the isolated heart donating the coronary effluent: the greater the degree of up-regulation of ATPase activity, the greater the increase in force produced by the effluent. These results indicate that endothelial cells are required for the cAMP-dependent regulation of cardiac contractile proteins to function, and these results further suggest that the myocardium autoregulates by modulating the cAMP regulation of contractile proteins with endothelial-derived factors.

Noninvasive evaluation of newborns with congenital heart disease.

Over the last decade, diagnosis and management of neonates with congenital heart disease have been greatly influenced by the constant expansion of noninvasive methods. We classify the most common congenital defects presenting in the first 2 weeks of life, based on clinical presentation and hemodynamic characteristics, followed by a discussion of echocardiographic findings in the most common congenital heart lesions and how ultrasound techniques can help solve problems frequently encountered during the early postoperative period.

Noninvasive diagnosis of coarctation of the aorta in the presence of a patent ductus arteriosus.

Although the diagnosis of coarctation of the aorta in the full-term neonate is straightforward when no ductus arteriosus is present, identification of coarctation of the aorta when a ductus arteriosus is patent can be difficult. A patent ductus arteriosus is frequently found in association with coarctation of the aorta, and it may remain open for many days. Thus a reliable method to rapidly identify coarctation of the aorta would obviate the need for cardiac catheterization or an in-hospital observation period until the ductus arteriosus closes spontaneously. Echocardiographic/Doppler examination of 19 consecutive full-term neonates with a birth weight of > 2.9 kg, who subsequently underwent surgical repair of coarctation of the aorta, were reviewed. Fourteen patients with similar weights, a patent ductus arteriosus, and a normal aortic arch were matched for comparison. Based on the findings, the following diagnostic criteria for coarctation of the aorta are suggested: isthmic diameter less than or equal to 3 mm or isthmus equal to 4 mm together with the Doppler finding of continuous antegrade flow in the isthmal segment. Coarctation of the aorta in the full-term neonate can be ruled out when the flow within the ductus arteriosus is exclusively from aorta to pulmonary artery or when the isthmic diameter is equal to or greater than 5 mm.

Endothelial cells regulate cardiac contractility.

Endothelial cells lining the lumen of blood vessels contain the receptors for many substances that alter the contractile tone of smooth muscle in the walls of the blood vessels. In response to their interaction with the signal substances, the endothelial cells release vasoactive factors that modify the contractile state of the vascular smooth muscle. This study was conducted to determine if endothelial cells can also modulate the contraction of cardiac muscle cells and contribute to the physiological regulation of the heart. The venous effluent from the coronary circulation of an isolated perfused working heart was reoxygenated and used to superfuse a trabecula isolated from the right ventricle of another heart. The peak tension and the duration of the contraction of the trabecula were reversibly altered by the effluent fluid. The change in the contraction of the trabecula during its exposure to coronary effluent was inhibited by selectively damaging the endothelial cells in the trabecula before the application of the coronary effluent. The magnitude and direction of the effect of the coronary venous effluent were sensitive to the metabolic and mechanical conditions under which the isolated perfused heart was contracting at the time the effluent was collected. These observations indicate that cardiac tissue can release a substance or substances into the coronary circulation that induce the production of cardioactive factors by endothelial cells.

Contractile proteins in myocardial cells are regulated by factor(s) released by blood vessels.

The importance of perfusion of the coronary vasculature in the regulation of ATPase activity of myosin in rat myocardial cells has been studied. Quantitative histochemistry was used to determine the activity of the enzyme among cells in tissues that had been either perfused through the coronary system or superfused over the surface of the tissue. Enzymatic activity was measured in cryostatic sections from three different preparations: 1) hearts frozen immediately after removal from the animal; 2) isolated hearts frozen after they had been perfused through the coronary circulation; and 3) isolated papillary muscles or trabeculae that had been superfused after dissection and then frozen. ATPase activity was measured in the isolated tissues at different times after dissection. Both calcium- and actin-activated myosin ATPase activities were uniform among cells in both the ventricles of the hearts frozen immediately after dissection and those that had been perfused through the coronary system. In the superfused tissues, although calcium-activated myosin ATPase activity was uniform, actin-activated ATPase activity was not uniform for about 90 minutes after the dissection, the period required for stabilization of the contraction. The pattern of nonuniformity was complex. In all bundles the lowest enzymatic activity was found in the most superficial cells. In very thin bundles, the cells in the center had the highest activity. In the medium and thicker bundles, there were three concentric zones of actin-activated ATPase activity, the superficial zone with the lowest activity, an intermediate zone with high activity, and a central zone with lower activity. Within each zone, the activity was often greatest in myocardial cells immediately next to blood vessels even though the blood vessels had not been perfused. The transverse distribution of ATPase activity of myosin could be explained by a mechanism in which cells in blood vessels (presumably endothelium) release a substance that upregulates myosin ATPase activity, with the rate of release being related to the local oxygen tension. A downregulating substance may also be produced. The period of stabilization of the contraction coincides with the time during which the pattern of actomyosin ATPase activity is nonuniform. These data suggest that the contractile proteins are regulated by a substance produced by blood vessels in proportion to the local PO2, and possibly in relation to shear force on the vascular endothelium.

Importance of (perimembranous) ventricular septal aneurysm in the natural history of isolated perimembranous ventricular septal defect.

Records were reviewed of 247 patients found to have isolated perimembranous ventricular septal defect (VSD) on cross-sectional echocardiography. Patients were separated into 2 groups: those in whom a perimembranous ventricular septal aneurysm (VSA) was associated with the VSD (group A, 77% of patients) and those in whom a VSA was not present (group B, 23%). The VSD was assessed by clinical (125 in group A, 24 in group B) and hemodynamic criteria (65 in group A, 33 in group B). The median follow-up period was 27 months (range 3 months to 25 years). In group A, the VSD closed spontaneously in 11% of the patients, improved clinically in 33% and required surgical closure in 11%. In group B, the VSD closed spontaneously in only 2%, improved clinically in 16% and required surgical closure in 47%. When considering larger VSDs only, 28% required surgery in group A, whereas 84% required surgery in group B (p less than 0.001). The VSA was found at the first echocardiographic examination in 94% of the studies. Thus, VSA is found in a large proportion of patients with perimembranous VSD. It occurs as an early phenomenon and is an important mechanism of closure. The presence of a VSA appears to confer a more favorable prognosis in perimembranous VSD except in patients with Down's syndrome.