New serial contrast technique for assessment of left to right shunting patent ductus arteriosus in the neonate

A new serial echocardiographic contrast technique for detection of patent ductus arteriosus has been developed and validated by clinical course (33 infants), surgical observations (13 infants) and autopsy observations (4 infants). A left to right shunting patent ductus arteriosus was demonstrated in 30 of 33 prospectively studied premature infants (mean weight 1,371 g) using this new contrast method. The demonstration of left to right ductal shunting was accomplished by hand injection of a nonviscous material (saline solution, 5 percent dextrose in water or the patient's own blood) through an umbilical arterial catheter placed with its tip located above the diaphragm during recording of a suprasternal notch echocardiogram. In positive studies, both the transverse aortic arch and right pulmonary artery were opacified. If no left to right shunt existed, only the transverse aortic arch was opacified.This serial study helped elucidate the natural history of patent ductus arteriosus. Twenty-four of the 30 patients with a positive study initially had a left to right shunting patent ductus arteriosus without an audible murmur. Three of these patients with silent patent ductus arteriosus later had congestive heart failure and two required operative ligation of the patent ductus. The high rate of detection of silent patent ductus arteriosus and its bedside confirmation when suspected are important in the serial management of critically ill newborns with this condition. The test is safe and sensitive and it is useful for early demonstration of silent patent ductus arteriosus, for clarifying the origin of murmurs and for confirming spontaneous, operative or pharmacologie closure of a patent ductus arteriosus.     

Patency of the ductus arteriosus in normal neonates: two-dimensional echocardiography versus Doppler assessment

Two-dimensional echocardiography using a high resolution, 7.5 ,Jsz transduce was compared with Doppler echocardiography for the assessment of patency of the ductus arteriosus in normal newborn infants. Twenty-eight neonates were studied between 1 and 10 hours (mean 5.5) after birth and both examinations were possible in 27 (96%). Doppler echocardiography under two-dimensional direction indicated ductal patency in all 27 neonates. Doppler sampling in the pulmonary end of the ductus rather than the main pulmonary artery was more sensitive for detecting patency. When two-dimensional echocardiography only was used to predict patency, there was 85% sensitivity. Two-dimensional echocardiography showed no evidence of ductus arteriosus narrowing ion four neonates studied shortly after birth. In 18, the pulmonary portion of the ductus arteriosus appeared narrowed and in 8 of these, the narrowing extended toward the mid-portion of the ductus. In five others, there was only mid-ductus arteriosus narrowing. It is concluded that high resolution two-dimensional echocardiography can be used to assess ductus arteriosus morphology, but is limited in predicting ductal patency near the time of normal physiologic closure. Combined two-dimensional and Doppler echocardiography is a highly sensitive technique for detection of ductal patency when sampling is performed in the pulmonary end of the ductus arteriosus.     

Closure of the ductus arteriosus with indomethacin in ventilated neonates with respiratory distress syndrome. Effects of pulmonary compliance and ventilation

The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.     

PDA: To treat or not to treat

Management of patent ductus arteriosus in extremely preterm infants remains a topic of debate. Treatment to produce ductal closure was widely practiced until the past decade, despite lack of evidence that it decreases morbidities or mortality. Meta‐analyses of trials using nonsteroidal anti‐inflammatory drugs have shown effectiveness in accelerating ductal closure, but no reduction in neonatal morbidities, regardless of agent used, indication, timing, gestational age, or route of administration. Surgical ligation closes the ductus but is associated with adverse effects. Recent experience with conservative approaches to treatment suggest improved neonatal outcomes and a high rate of spontaneous ductal closure after discharge. Careful postdischarge follow‐up is important, however, because potential adverse effects of long‐standing aortopulmonary shunts may be an indication for catheter‐based ductal closure. Identification of extremely preterm infants at greatest risk of potential harm from a persistently patent ductus, who may benefit most from treatment are urgently needed.     

Idiopathic occlusion of the fetal ductus arteriosus without lumen narrowing

Constriction of the fetal ductus arteriosus in utero can be caused by pharmacological agents or can occur spontaneously. The spontaneous constriction and closure of the ductus arteriosus have been reported sporadically in the previous literature, either completely obliterated or constricted ductus arteriosus causing narrowing. This cardiac defect was characterized by no blood flow through the ductus arteriosus without lumen narrowing. The fetal echocardiography revealed the features of premature closure of the ductus arteriosus. We report a case of occlusion of the ductus arteriosus at 38 weeks of gestation that had a favorable postnatal outcome after immediate cesarean section.     

Follow-up of coil occlusion of patent ductus arteriosus

Objective. We sought to determine the prevalence and fate of residual ductal shunting following coil occlusion of patent ductus arteriosus.Background. Although transcatheter coil occlusion of patent ductus arteriosus has gained popularity, few follow-up data have been reported.Methods. A review of 75 patients who underwent coil occlusion was performed. Residual shunting was investigated by Doppler echocardiography in follow-up. Angiograms were reviewed to obtain minimal ductal diameter and ductal angiographic type.Results. Residual shunts were found in 31 patients (41%) on the day of the procedure, and of these, spontaneous closure was noted in 17 (55%) at 2 weeks to 20 months of follow-up. Of the 75 patients studied, 5 (7%) required a second coil procedure, and 10 (13%) remained with persistent residual shunts at most recent follow-up. Actuarial analysis estimated a 6 ± 5% prevalence of residual shunts 20 months after a single coil procedure and 3 ± 3% after all coil procedures. Minimal ductal diameter was associated with immediate complete ductal occlusion by a single coil. These patients had significantly smaller (p = 0.003) minimal ductal diameters (1.2 ± 0.7 mm) than those who required two coils during their initial procedure to achieve immediate occlusion (1.9 ± 0.7 mm), those who required a second coil procedure (2.0 ± 0.9 mm), those who had spontaneous closure of residual shunts (1.9 ± 0.7 mm) and those with persistent residual shunts (2.0 ± 0.9 mm). No association was identified between ductal angiographic type and outcome of coil occlusion. No late adverse clinical events of coil occlusion or evidence of recanalization was found.Conclusions. Small residual shunts are common after coil embolization of patent ductus arteriosus, but most close spontaneously. Actuarial analysis estimates complete closure in 94% at 20 months, and reintervention was required in only 7% of patients.     

Clinical Features of the Complete Closure of the Ductus Arteriosus Prenatally

Objective. Prenatal constriction of the ductus arteriosus associated with maternal drug ingestion was reported several decades ago. There are fewer reports of the complete closure of the ductus arteriosus; therefore, the clinical features of the latter are poorly understood. The aim of this study is to clarify the clinical features of complete ductal closure and postnatal pulmonary hypertension by performing echocardiography of the fetus. Patients. We diagnosed four fetuses with complete ductal closure by performing fetal echocardiography and reviewed the prenatal and postnatal medical records of the mother and fetus. Results. One mother each had bronchial asthma, ulcerative colitis, and idiopathic thrombocytopenic purpura, and they had received nonsteroidal anti‐inflammatory drugs and/or corticosteroids during pregnancy. The fourth mother did not have basal disease and had not ingested any drugs. Fetal diagnosis was performed at 32–38 weeks of gestation. All fetuses had right heart dilatation with tricuspid regurgitation in the absence of any cardiac defects, and Doppler echocardiography indicated that the right ventricular pressure was elevated. Two of the fetuses had fetal hydrops, which suggested severe right heart dysfunction. All fetuses were delivered by emergent cesarean delivery. After birth, all the infants developed persistent pulmonary hypertension and required oxygen inhalation. Of these, three required mechanical ventilation, and two, nitric oxide inhalation. All infants improved within 2 weeks, and they had no neurological and cardiac complications after discharge. Conclusion. Right heart dilatation and severe tricuspid regurgitation in the absence of a cardiac defect in the fetus strongly suggested ductal dysfunction. Careful evaluation of ductal patency and right ventricular function can lead to precise early diagnosis and good prognosis.     

Two-dimensional echocardiographic and color flow Doppler evaluation of ductal occlusion with the Rashkind prosthesis

To evaluate the results of ductal occlusion with the Rashkind prosthesis, 78 children (group 1, 19 boys and 59 girls; mean age at occlusion, 4.5 +/- 4.0 years) with isolated patent ductus arteriosus (n = 73) or in association with other lesions (n = 5) were evaluated by pulsed and color flow Doppler 9 +/- 7 months (range, 2-26 months) after occlusion. Thirty children who had undergone patent ductus arteriosus ligation (group 2, 9 boys and 21 girls; mean age at study, 5.7 +/- 4.9 years; mean follow-up after ligation, 44 +/- 58 months) were evaluated in the same way. The prevalence of residual ductal shunting and the main pulmonary arterial flow patterns were recorded. Residual ductal shunting in group 1 was 38% on day 1, decreasing slowly to 31% at 3 months, 27% at 6 months, and 19.7% at 1 year or more due to further spontaneous shunt resolution. The residual shunting rate in group 2 (6%) was significantly lower than that at 1 year or more in group 1 (p less than 0.001). Successful reocclusion in 5 of 6 in a subset of patients in group 1 followed for 1 year or less reduced further the prevalence of residual shunting. Residual shunting after patent ductus arteriosus occlusion is more common than after ligation, but continues to decrease during follow-up.     

Esophageal stethoscope in thoracoscopic interruption of patent ductus arteriosus

There is a significant rate of residual or recurrent ductal patency after video-assisted thoracoscopic closure of patent ductus arteriosus. Between February 2000 and October 2004, this procedure was carried out on 145 consecutive patients in whom heart sounds were monitored intraoperatively with an esophageal stethoscope. Changes in continuous cardiac murmurs were recorded after placing the 1(st) and 2(nd) vascular clips. There was no ductal flow after clipping twice in 138 (95%) patients; in the other 7, residual flow was abolished at the 3(rd) attempt. All patients left the operating room with no residual ductal patency on echocardiography. After 6 months, there was no incidence of residual patency. Intraoperative esophageal stethoscopy provides remarkably loud and clear heart sounds for direct monitoring and reliable evaluation of the entire course of thoracoscopic patent ductus arteriosus closure, without interrupting the surgical procedure, thus avoiding re-intervention and complications associated with residual ductal flow.     

Suprasternal cross-sectional echocardiography in assessment of patient ducts arteriosus.

Ninety-four patients with patent ductus arteriosus, whose ages ranged from 28 weeks gestation to 8 years, were assessed by suprasternal cross-sectional echocardiography. A further group of 37 cases without a patent ductus arteriosus were assessed by the same technique. The appearances of the ductus via this approach varied according to the ventriculoarterial connections. Reliable assessment of patency was possibly in 87 cases. In seven cases where the ductal lumen was less than 2 mm in size, a false negative diagnosis was made. In the 37 patients without a patent ductus arteriosus, no false positive diagnoses were made. Suprasternal cross-sectional echocardiography enables a reliable assessment of ductal patency, provided the lumen falls within the range of lateral resolution of the equipment being used.     

Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial.

OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).     

A rational approach to ligation of patent ductus arteriosus in the neonate.

During a 23-month period, 25 premature infants underwent ligation of a patent ductus arteriosus performed in the neonatal intensive care unit utilizing a limited posterolateral muscle-retracting incision. This approach afforded adequate exposure with minimal surgical time and trauma. All infants manifested severe respiratory distress and congestive heart failure. Both standard and contrast echocardiographic studies were used for noninvasive preoperative evaluation. Echocardiographic study proved to be a highly reliable and sensitive indicator of ductal patency. Eight infants (32 percent) died at 8 to 225 days of age. The primary cause of death was progressive pulmonary disease with subsequent failure of multiple organ systems. Seventeen (68 percent) of the 25 infants survived to leave the hospital. Advantages of ligation of a patent ductus arteriosus in the neonatal intensive care unit include the elimination of problems of transportation (thermoregulation, ventilation, and loss of lines) and continuity of ongoing care and monitoring. The standard facilities of the neonatal intensive care unit proved completely satisfactory for ligation of a patent ductus arteriosus. Ligation in the neonatal intensive care unit is suggested to minimize potential complications of care in the operating room and transport of these critically ill infants.     

Real-time Doppler color flow mapping for detection of patent ductus arteriosus

In this study, ultrasound Doppler color flow mapping systems were utilized to examine flow in the pulmonary artery in 31 premature and term infants (aged 4 hours to 9 months) with patent ductus arteriosus accompanying respiratory distress syndrome, as an isolated lesion, or with patent ductus in association with other cyanotic or acyanotic congenital heart disorders. The flow mapping patterns were compared with those of a control population of 15 infants who did not have patent ductus arteriosus. In unconstricted ductus arteriosus, the flow from the aorta into the pulmonary artery was detected in late systole and early diastole and was distributed along the superior leftward lateral wall of the main pulmonary artery from the origin of the left pulmonary artery back in a proximal direction toward the pulmonary valve. In constricted patent ductus arteriosus, or especially in a ductus in association with cyanotic heart disease, the position of the ductal shunt in the pulmonary artery was more variable, often directed centrally or medially. Waveform spectral Doppler sampling could be performed in specific positions guided by the Doppler flow map to verify the phasic characteristics of the ductal shunt on spectral and audio outputs. Shunts through a very small patent ductus arteriosus were routinely detected in this group of infants, and right to left ductal shunts could also be verified by the Doppler flow mapping technique. This study suggests substantial promise for real-time two-dimensional Doppler echocardiographic flow mapping for evaluation of patent ductus arteriosus in infants.     

Reversed shunting across the ductus arteriosus or atrial septum in utero heralds severe congenital heart disease

Objectives. This study was performed to define the significance of Doppler color flow mapping in demonstrating reversal of the direction of the normal physiologic flow across the atrial septum and ductus arteriosus in the human fetus.Background. Reversal of the physiologic shunting across the ductus arteriosus or atrial septum in utero (i.e., left to right) can be readily identified by Doppler color flow mapping, complemented by pulsed and continuous wave Doppler information.Methods. We reviewed echocardiograms recorded at our three institutions from 1988 to 1993, which displayed reversal of flow by Doppler color flow in 53 fetuses of gestational age 18 weeks to term. The diagnoses were confirmed by postnatal echocardiography, operation or autopsy. Reversal of shunting was consistently associated with severe heart disease.Results. Reversed atrial shunting was found with severe left heart obstructive lesions, including 19 with hypoplastic left heart syndrome, 3 with critical aortic stenosis, 2 with double-outlet right ventricle and 1 each with an interrupted aortic arch, atrioventricular septal defect and severe left ventricular dysfunction due to dilated cardiomyopathy. Reversed ductus arteriosus shunting was found with severe right heart obstructive lesions, including nine fetuses with pulmonary atresia, six with severe obstructive tricuspid valve abnormalities, five with severe tetralogy of Fallot, four with Ebstein's anomaly and two with single ventricle and pulmonary stenosis. Associated cardiac lesions were common in both groups. Only 3 of the 15 infants who were delivered alive from the reverse ductus arteriosus shunt group and 4 of 12 from the reverse atrial shunt group still survive.Conclusions. The finding of reversed flow by Doppler color flow mapping during fetal life provides a key to subsequent accurate diagnosis and denotes a spectrum of diseases with a very poor prognosis.     

Management of patent ductus arteriosus in preterm infants.

OBJECTIVE: To evaluate the incidence of symptomatic patent ductus arteriosus (PDA) in preterm infants, and the results of the intravenous indomethacine treatment and surgery. METHODS: Among 394 preterm infants (<37 weeks), symptomatic PDA was diagnosed by echocardiography in 51 babies and they were examined retrospectively. All infants were managed conservatively and then IV indomethacine was given to non-responders (n=30). Surgical closure was performed in 12 babies. RESULTS: The incidence of symptomatic PDA in preterm infants was 12.9%: median age: 3 days, mean birth weight: 1434+/-540 g (540-2900g) and mean gestational age (GA) 30.9+/-3.3 weeks (23-37 weeks). With indomethacine, ductal closure was achieved in 70% infants. Early clinical improvement was observed in all cases that underwent surgery and most of them had a low birth weight (<1500 g) and an early gestational age (<32 weeks). None of them died due to operation. CONCLUSION: The incidence of symptomatic PDA is high in preterm infants. Treatment with indomethacine improves ductal closure and is associated with few reversible adverse effects. In the other hand, early clinical improvement and high success rate were achieved after surgery. If indomethacine fails to achieve ductal closure, decision of surgery must be made immediately.     

Late follow-up after thoracoscopic ductal ligation

Interventional catheterization and minimally invasive surgical techniques offer the real possibility of a reduction in cost and morbidity when compared with the traditional surgical approach to patent ductus arteriosus. Video-assisted thoracoscopic surgery may prove to be a superior technique because of its application to a wider range of patients needing ductal closure, a lower incidence of residual shunting, no evidence for recurrent shunting, and the absence of intravascular foreign bodies.     

Relation of limiting ductal patency to survival in neonatal Ebstein's anomaly

Fetal and neonatal Ebstein's anomaly has a poor prognosis, and there are few contemporary reviews of management and outcomes. This study retrospectively reviewed a management algorithm promoting early ductal closure after anatomic pulmonary obstruction had been excluded or relieved in neonatal Ebstein's anomaly from 1995 to 2004. Twenty-eight patients with Ebstein's anomaly were identified, 9 prenatally (8 with hydrops) and 19 postnatally, at a median age of <24 hours. Celermajer index scores predicted a mortality rate of 35%. Prostaglandins were administered to 24 of 28 patients. Prostaglandins were continued for obstructive lesions in 9 until the relief of pulmonary outflow obstructions or aortic coarctation repair. In 8 of 9 patients, prostaglandins were discontinued after intervention. One patient continued receiving prostaglandins until a Blalock-Taussig shunt was performed 3 weeks after surgical valvotomy. Prostaglandins were discontinued in 17 of 24 patients with uneventful ductal constrictions. The ductus arteriosus persisted in 5 patients with hemodynamic instability, of whom 4 underwent ductal ligation, with immediate improvement. In 1 of 24 patients, unrecognized right ventricular outflow tract obstructions became apparent when prostaglandins were discontinued. Prostaglandins were restarted until a primary superior cavopulmonary anastomosis was performed at 7 weeks. The median follow-up period of 26 survivors was 34 months (range 3 to 106), 4 after bidirectional superior cavopulmonary anastomoses and 1 after a Fontan procedure. In conclusion, in neonatal Ebstein's anomaly of the tricuspid valve, prolonged patency of the ductus arteriosus in patients without anatomic outflow tract obstructions is deleterious. "Circular shunts" may develop in patients with pulmonary and tricuspid insufficiency. The ligation or spontaneous constriction of the ductus arteriosus may result in hemodynamic improvement. This approach to neonatal Ebstein's anomaly of the tricuspid valve has yielded a substantial reduction in mortality to 7% in a high-risk cohort.     

The newborn transitional circulation: a two-dimensional Doppler echocardiographic study

To characterize changes in circulation after birth, 11 normal full-term infants were examined with two-dimensional and pulsed Doppler echocardiography. The initial examination was performed within 10 hours after delivery and serially for 3 days. Retrograde diastolic pulmonary artery velocities, which are evidence for a patent ductus arteriosus, were detected in 10 infants (91%) on day 1, in 2 (18%) on day 2 and in none on day 3. Retrograde systolic descending aortic velocities, which are evidence of flow from the aorta into the ductus arteriosus, were observed in 10 infants (91%) on day 1, 9 (81%) on day 2 and 7 (64%) on day 3. Persistence of the retrograde systolic velocity in the descending aorta in the absence of retrograde diastolic velocity in the pulmonary artery is consistent with physiologic ductal closure beginning near the pulmonary artery end of the ductus arteriosus. Localized turbulent retrograde systolic flow, proximal to the septal leaflet of the tricuspid valve and consistent with tricuspid insufficiency, was detected in six patients (55%) on day 1, in eight (73%) on day 2 and in seven (64%) on day 3. Thus, tricuspid insufficiency appears to be a frequent observation in healthy newborns. Normal Doppler velocities in the great arteries and across the tricuspid and mitral valves of newborns up to 3 days of age are presented. These normal measures of intracardiac flow velocities may be used for comparison to identify abnormal flow profiles in newborns with congenital heart defects.     

Predictive Value of Blood N-Terminal Pro-Brain Natriuretic Peptide Concentrations for Early Patent Ductus Closure in Very Preterm Infants

ObjectivesIt has been shown that blood concentrations of NT-proBNP may be useful in identifying preterm infants at risk of hemodynamically significant patent ductus arteriosus and its complications. The aim of the study was to assess predictive value of serum NT-proBNP levels for early ductus arteriosus (DA) closure in very preterm newborns.MethodsFifty-two infants <32 weeks’ gestation aged <72 hours with patent ductus arteriosus (PDA) diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent planned echocardiographic (daily) and two serum NT-proBNP measurements within the first 10 days after birth. Depending on the DA closure within the first 10 days of life, 2 groups of patients were formed retrospectively, with closed (n = 30) or patent (n = 22) DA by this age.ResultsIn the first 10 days of life, DA closure occurred in 19 (70%) treated infants and in 11 (44%) infants managed expectantly (p > 0,05). Initial concentrations of NT-proBNP were significantly higher in infants that had patent ductus arteriosus (PDA) at 10 days of life. By the eighth day, median NT-proBNP values in both groups significantly decreased but remained considerably higher in newborns with PDA. NT-proBNP serum concentrations on the second day of life could reliably predict DA closure within the first 10 days after birth in treated babies (the AUC was significant 0.81 [95% CI: 0.58–1.03], p < 0.05) but not in infants who were managed expectantly.ConclusionsSerum NT-proBNP concentrations on the second day of life could reliably predict early PDA closure in treated but not in expectantly managed very preterm infants.