Frank C. Smith

Role of Pulse Oximetry in Examining Newborns for Congenital Heart Disease: A Scientific Statement from the AHA and AAP

BACKGROUND: The purpose of this statement is to address the state of evidence on the routine use of pulse oximetry in newborns to detect critical congenital heart disease (CCHD). METHODS AND RESULTS: A writing group appointed by the American Heart Association and the American Academy of Pediatrics reviewed the available literature addressing current detection methods for CCHD, burden of missed and/or delayed diagnosis of CCHD, rationale of oximetry screening, and clinical studies of oximetry in otherwise asymptomatic newborns. MEDLINE database searches from 1966 to 2008 were done for English-language papers using the following search terms: congenital heart disease, pulse oximetry, physical examination, murmur, echocardiography, fetal echocardiography, and newborn screening. The reference lists of identified papers were also searched. Published abstracts from major pediatric scientific meetings in 2006 to 2008 were also reviewed. The American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. In an analysis of pooled studies of oximetry assessment performed after 24 hours of life, the estimated sensitivity for detecting CCHD was 69.6%, and the positive predictive value was 47.0%; however, sensitivity varied dramatically among studies from 0% to 100%. False-positive screens that required further evaluation occurred in only 0.035% of infants screened after 24 hours. CONCLUSIONS: Currently, CCHD is not detected in some newborns until after their hospital discharge, which results in significant morbidity and occasional mortality. Furthermore, routine pulse oximetry performed on asymptomatic newborns after 24 hours of life, but before hospital discharge, may detect CCHD. Routine pulse oximetry performed after 24 hours in hospitals that have on-site pediatric cardiovascular services incurs very low cost and risk of harm. Future studies in larger populations and across a broad range of newborn delivery systems are needed to determine whether this practice should become standard of care in the routine assessment of the neonate.

Role of Pulse Oximetry in Examining Newborns for Congenital Heart Disease: A Scientific Statement From the American Heart Association and American Academy of Pediatrics

Background— The purpose of this statement is to address the state of evidence on the routine use of pulse oximetry in newborns to detect critical congenital heart disease (CCHD). Methods and Results— A writing group appointed by the American Heart Association and the American Academy of Pediatrics reviewed the available literature addressing current detection methods for CCHD, burden of missed and/or delayed diagnosis of CCHD, rationale of oximetry screening, and clinical studies of oximetry in otherwise asymptomatic newborns. MEDLINE database searches from 1966 to 2008 were done for English-language papers using the following search terms: congenital heart disease, pulse oximetry, physical examination, murmur, echocardiography, fetal echocardiography, and newborn screening. The reference lists of identified papers were also searched. Published abstracts from major pediatric scientific meetings in 2006 to 2008 were also reviewed. The American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. In an analysis of pooled studies of oximetry assessment performed after 24 hours of life, the estimated sensitivity for detecting CCHD was 69.6%, and the positive predictive value was 47.0%; however, sensitivity varied dramatically among studies from 0% to 100%. False-positive screens that required further evaluation occurred in only 0.035% of infants screened after 24 hours. Conclusions— Currently, CCHD is not detected in some newborns until after their hospital discharge, which results in significant morbidity and occasional mortality. Furthermore, routine pulse oximetry performed on asymptomatic newborns after 24 hours of life, but before hospital discharge, may detect CCHD. Routine pulse oximetry performed after 24 hours in hospitals that have on-site pediatric cardiovascular services incurs very low cost and risk of harm. Future studies in larger populations and across a broad range of newborn delivery systems are needed to determine whether this practice should become standard of care in the routine assessment of the neonate.

High Incidence of Cardiac Malformations in Connexin40-Deficient Mice

Abstract— Gap junctions are intercellular channels formed by oligomerization of a protein called connexin (Cx). The heart expresses at least three connexin isotypes: Cx40, Cx43, and Cx45. A possible role for Cx40 in cardiac morphogenesis remains to be determined. We have characterized the anatomy and histology of fetal and newborn hearts obtained from crossing Cx40-deficient mice of mixed genetic background (C57BL/6×129Sv). Hearts were serial-sectioned (5 &mgr;m) along the coronal plane, stained with hematoxylin-eosin, and visualized by conventional light microscopy. Cardiac malformations in mice lacking Cx40 in one allele (Cx40+/−) included bifid atrial appendage, ventricular septal defect, tetralogy of Fallot (TOF), and an aortic arch abnormality. In Cx40−/− mice resulting from crossing of Cx40+/− mice, the most common cardiac malformations were double-outlet right ventricle (DORV), TOF, and endocardial cushion defects. Overall incidence of cardiac malformations was 6/33 (18%) in Cx40+/− mice and 4/12 (33%) in Cx40−/− mice. No cardiac malformations were observed in 15 wild-type mice studied. In addition, we examined 39 hearts from offspring of Cx40−/− matings. Frequency of cardiac malformations was even higher in this group (44%). Over one third of the hearts (14 of 39) showed conotruncal malformations corresponding to either DORV or TOF. Endocardial cushion defects were found in 3 out of 39 hearts. Our results suggest that Cx40 participates in cardiac morphogenesis, likely in association with other (unknown) products whose expression may vary with the genetic background of the mice.

A role for the aryl hydrocarbon receptor in cardiac physiology and function as demonstrated by AhR knockout mice.

The aryl hydrocarbon receptor (AhR), a ligand activated transcription factor, is the receptor for the polycyclic aromatic hydrocarbons found in tobacco smoke, polychlorinated biphenyls, and the environmental pollutant, dioxin. To better understand the role of the AhR in the heart, echocardiography, invasive measurements of aortic and left ventricular pressures, isolated working heart preparations, as well as morphological and molecular analysis were used to investigate the impact of AhR inactivation on the mouse heart using the AhR knockout as a model. Cardiac hypertrophy is an early phenotypic manifestation of the AhR knockout. Although the knockout animals were not hypertensive at the ages examined, cardiomyopathy accompanied by diminished cardiac output developed. Despite the structural left ventricular remodeling, the hearts of these animals exhibit minimal fibrosis and do not have the expected increases in surrogate molecular markers of cardiac hypertrophy. The anatomic remodeling without typical features of molecular remodeling is not consistent with hypertrophic growth secondary to pressure or volume overload, suggesting that increased cardiomyocyte size may be a direct consequence of the absence of the AhR in this cell type.

Procainamide for Rate Control of Postsurgical Junctional Tachycardia

Abstract. This study was conducted to determine the efficacy of procainamide therapy for rapid rate control of postoperative junctional tachycardia (JT). Postoperative JT is one of the most difficult forms of tachycardia to manage. Reported success with a variety of treatments of JT in infants and children has been inconsistent and limited. Rate control using procainamide was achieved in 17 children having rapid JT (heart rate >200 beats/min) between 1986 and 1997. In the first 5 patients (protocol A), following a loading dose of 3 mg/kg over 20 minutes, a continuous procainamide infusion was initiated at a rate of 20 μg/kg/min. The infusion dose was increased in 10 μg/kg steps every 30 minutes to 40–120 μg/kg/min until the heart rate decreased below the target rate of 180 beats/min. In the other 12 patients (protocol B), after a higher loading dose of 10 mg/kg the infusion rate was increased every 10–15 minutes until the heart rate decreased below the target rate of 180 beats/min. Procainamide decreased JT rates in all patients but the response was significantly faster in protocol B. In the patients treated with protocol A, pretreatment JT rates ranged from 203 to 240 (213 ± 17) beats/min and decreased to 195 ± 10 beats/min at 2 hours (p= ns), 186 ± 8.8 at 4 hours (p < 0.02), and 179 ± 8 at 6 hour postinitiation of PA. In protocol B, pretreatment JT rates ranged from 201 to 240 (218 ± 17) beats/min and decreased to 183 ± 20 beats/min at 2 hours (p < 0.001) and 171 ± 12 at 4 hours after starting the procainamide therapy. The mean duration to decrease JT rates below the target rate of 180 beats/min was 3.2 ± 1.1 hours in protocol B compared to 6.4 ± 3.8 hours in protocol A (p < 0.02). Eight of 12 patients in protocol B achieved rate control below the target rate of 180 beats/min within 4 hours despite remaining on significant inotropic support. The procainamide infusion rates to maintain heart rates below 180 beats/min were 40–120 (68.4 ± 22.1) μg/kg/min. No proarrhythmia, bradycardia, or significant hypotension was observed. In this series procainamide provided safe, effective, and rapid rate control of JT occurring in the immediate postoperative period.

Loss of Sinus Rhythm After Total Cavopulmonary Connection

BACKGROUND Total cavopulmonary connection (TCPC) to repair functional single ventricle involves the sinus node area, in contrast to the Fontan procedure. We compared ECG findings after TCPC and Fontan to evaluate the impact of the cavopulmonary connection on sinus rhythm postoperatively. METHODS AND RESULTS The Fontan group consisted of 17 patients repaired at 7.8 +/- 3.1 years of age (mean +/- SD): 11 for tricuspid or pulmonary atresia (TA/PA) and 6 for single ventricle. The TCPC group consisted of 19 patients repaired at 5.1 +/- 3.2 years of age (mean +/- SD) (P < .001): 9 for TA/PA, 4 for single ventricle, and 6 for hypoplastic left heart syndrome. Mean follow-up after Fontan was 7.7 +/- 2.7 years versus 2.8 +/- 1.6 years for TCPC (P < .001). Preoperative ECGs on all TCPC patients showed sinus rhythm (SR), whereas 16 of 17 Fontan patients had SR and one had nonsinus atrial rhythm (NSAR) since birth. On the first postdischarge ECG, 12 of 19 TCPC patients (63%) were in SR, 4 were in junctional rhythm (JR), and 3 were in NSAR. In comparison, 15 of 17 Fontan patients (88%) were in SR with 1 of 17 in NSAR and 1 in supraventricular tachycardia (P < .05 with chi 2 test). By 2 years postoperatively, only 6 of 15 TCPC patients available for follow-up (40%) were in SR, with 7 of 15 in JR and 2 of 15 in NSAR. By contrast, 13 of 17 Fontan patients (76%) remained in SR, with 1 in NSAR and 3 in JR (P < .05 with chi 2 test). TCPC patients with loss of SR did not differ from other patients in the group in age at repair, preoperative diagnosis, or surgeon performing the procedure. CONCLUSIONS This significant incidence of loss of SR temporally related to surgery suggests that operative compromise of the sinus node area is common with TCPC.

Interstitial 6q deletion and Prader-Willi-like phenotype

A third case of an interstitial deletion of the long arm of chromosome 6 with clinical features mimicking Prader‐Willi syndrome (PWS) is presented. Although preliminary clinical evaluation in each case suggested PWS, further review revealed that the features in all three cases are not completely compatible with the characteristic findings in Prader‐Willi syndrome. Furthermore, the deletions in the three cases do not show a consistent region of overlap. Consequently, no particular band or region in 6q can be defined as associated widi obesity. However, our findings confirm the suggestion of Villa et al. in 1995, that individuals with a PWS phenotype who are cytogenetically and molecularly negative for a deletion of 15q11‐q13 should be examined for a deletion of 6q.

New approach to the surgical management of pulmonary arteriovenous malformations after cavopulmonary anastomosis

The development of pulmonary arteriovenous malformations after cavopulmonary bypass in patients with congenital heart disease is well documented. We report successful management of pulmonary arteriovenous malformations after cavopulmonary bypass in a patient with an interrupted inferior vena cava (IVC) and multiple hepatic veins utilizing an extracardiac conduit from the hepatic veins to the hemiazygous continuation of the interrupted IVC. This technique, performed without circulatory arrest or an atriotomy, may limit morbidity associated with intracardiac procedures in patients with single ventricle morphology. Furthermore, this case suggests an alternative technique for completion Fontan in patients with an interrupted IVC and multiple hepatic venous drainage.

A New On-Line Method for Predicting Aortic Root Dilatation During Two-Dimensional Echocardiography in Pediatric Patients with Marfan Syndrome Using the Sinus of Valsalva to Annulus Ratio

The objective of this study was to determine if calculation of the sinus of Valsalva to annulus ratio (SOV/Ann) effectively screens for root dilatation (ARD) during two-dimensional (2D) echocardiography in young patients (1 month–15 years) with suspected or confirmed Marfan syndrome. The aortic root was imaged using 2D echocardiography (parasternal long-axis view) and the SOV/Ann ratio calculated/analyzed in 27 Marfan patients and 45 age-matched controls. All controls had a SOV/Ann ratio <1.45, and 82% of Marfans with ARD had a SOV/Ann ratio 1.45. Five of the Marfan patients with ARD had a SOV/Ann ratio < 1.45 due to normalization of the SOV/Ann ratio because of pathologic annular enlargement. Determination of the SOV/Ann ratio allows rapid on-line screening for aortic root dilatation during 2D echocardiography. A SOV/Ann ratio 1.45 predicted ARD in young Marfan patients with a high degree of accuracy (sensitivity = 0.82, specificity = 1.00). Screening for ARD using the SOV/Ann ratio fails when annular dilatation has progressed to the degree that the SOV/Ann ratio normalizes (SOV/Ann < 1.45). In this subgroup of patients, determination of aortic root dilatation will have to be evaluated by standard methods.

Modified technique for balloon valvuloplasty of critical pulmonary stenosis in the newborn

OBJECTIVES We report our experience in eight consecutive neonates who underwent attempted balloon dilation as an initial therapy for critical valvular pulmonary stenosis, and we review in detail technical modifications that improved the success rate. BACKGROUND Balloon dilation of the pulmonary valve has become the treatment of choice for valvular pulmonary stenosis in children and adults. There are few reports of its effectiveness in critical pulmonary stenosis in the newborn. In this setting, application of the technique of balloon dilation has been limited by the ability to advance the necessary guide wires and catheters across the stenotic, often near-atretic, pulmonary valve. METHODS The pulmonary valve was crossed in all patients. When this could not be accomplished with an end-hole catheter, a soft guide wire was advanced directly across the pulmonary valve through the end-hole catheter positioned in the right ventricular outflow tract below the valve. Initial predilation was achieved in all patients by using a coronary dilation catheter in an effort to facilitate introduction of the definitive balloon dilation catheter. Definitive dilation with a balloon diameter of > or = 110% of the diameter of the pulmonary valve annulus was possible in six patients. RESULTS Right ventricular pressure declined from a mean value of 108 +/- 32 mm Hg to a mean value of 49 +/- 11 mm Hg after balloon dilation, with no change in heart rate or aortic pressure in these six patients after definitive balloon dilation. CONCLUSIONS The results of this small series suggest that critical valvular pulmonary stenosis in the newborn can be successfully treated by transluminal balloon valvuloplasty.