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[Dopplersonographic findings in neonates with significant persistent ductus arteriosus].

BACKGROUND: The aim of the study was the description and review of a diagnostic management for treatment of patent ductus arteriosus in preterm neonates. Indomethacin, widely used to effect nonoperative closure of patent ductus arteriosus, has been implicated in vasoactive side effects and requires an accurate diagnosis. PATIENTS AND METHODS: Firstly, the hemodynamic significance of the ductus arteriosus was assessed by clinical signs, such as tachycardia, disturbed microcirculation and a high difference of central and peripheral temperature. The patent ductus arteriosus was confirmed by echocardiography. The left ventricular systolic time intervals and the cerebral perfusion were obtained by pulsed doppler recordings. 48 preterm infants below 1500 g were investigated within the first 12 hours of life and during the first week. RESULTS: In 32 preterm neonates (67 %) a patent ductus arteriosus without hemodynamic significance and in 9 neonates a patent ductus arteriosus with hemodynamic changes was detected. In 9 neonates there were no signs of patent ductus arteriosus. Neonates with typical clinical signs of patent ductus arteriosus exhibited significantly diminished preejection time, prolonged ejection time and a decreased quotient of preejection and ejection time. We found pathologically changed parameters of anterior cerebral artery in neonates with clinical signs of patent ductus arteriosus. To judge the efficiency of the diagnostic management the groups of neonates were compared concerning the evidence of complications. Neonates with ductus arteriosus but without therapy did not reveal more pulmonary problems as well as intracerebral hemorrhages, renal or intestinal disturbances than the group of neonates with treated ductus arteriosus. CONCLUSIONS: Summarizing, we suggest that the described criteria are to be taken into account before treatment of ductus arteriosus in preterm neonates. In this way a wide clinical and echocardiographical investigation will be performed in risk neonates and a useless therapy can be avoided.

Anterior Cerebral Artery↗

Control of the ductus arteriosus.

In the fetus the major function of the ductus arteriosus is to divert flow away from the lungs toward the placenta, therby avoiding unnecessary circulation through the lungs and reducing the work load of the heart. Constriction of the ductus arteriosus is produced by several mechanisms that may interact with one another in producing normal postnatal closure of the ductus arteriosus. The major mechanism is the constrictor effect of an increased O2 environment. This may directly affect the ductus arteriosus muscle or may work through the release of an intermediary substance. Other vasoactive substance circulating in the blood after birth may also play some role in constriction of the ductus arteriosus. There are major species differences in the degree and type of response to the various stimuli and the exact mechanisms ultimately responsible for closure are not yet fully understood.

Acetylcholine↗

Anatomical and sonographic correlation of the fetal ductus arteriosus in first and second trimester pregnancy.

Ultrasonic visualization of the ductus arteriosus in first and second trimester pregnancies was compared with postmortem preparations. Twenty human fetal postmortem specimens from 8 to 19 weeks menstrual age were examined, 11 with microscopic reconstruction, nine with macroscopic dissection. The angle between ductus arteriosus and aortic isthmus (upstream) and ductus arteriosus and descending aorta (downstream) was determined. In 52 normally developing fetuses between 14 and 27 weeks, the angle between the ductus arteriosus and the thoracic spine as visualized in real-time ultrasound was determined. In a further 19 normally developing fetuses between 14 and 25 weeks, ductal blood flow was visualized by colour velocity imaging (CVI). In anatomical preparations, the upstream angle was always less than 90 degrees and the downstream angle was always 80 degrees or more. These angles were unrelated to menstrual age. In both real-time and CVI ultrasound, the angle between ductus arteriosus and thoracic spine remained at approximately 90 degrees. CVI showed highest blood flow velocities at the point of ductal insertion into the aorta. When performing Doppler ultrasound examinations in the fetal ductus arteriosus, no menstrual age dependent angle adjustment appears to be necessary.

Blood Flow Velocity↗

Challenges encountered during closure of patent ductus arteriosus.

Transcatheter closure of patent ductus arteriosus (PDA) was one of the first interventions established in invasive cardiology and is now more than 30 years old. The challenges for successful closure with the first devices in children consisted of handling the rather large introducer sheaths and stiff application systems. Today, interventional closure can be performed with different types of plugs, occluders, and coils. Thus, beyond infancy, transcatheter closure can be successfully performed in almost all cases. Challenging from the technical standpoint can be the closure of window-type ducts, in which excessive protrusion of the device into the descending aorta should be avoided, as well as the closure of tubular ducts, in which secure anchoring of one or more devices in the vessel can be very difficult. For the combination of a coarctation and an open duct, different strategies can be considered. In selected cases, use of a covered stent can be helpful. From the physiological standpoint, open ducts in patients with pulmonary hypertension with or without concomitant congenital heart diseases can be challenging because testing of vasoreactivity with temporarily blocked duct and the option of subsequent treatment with vasodilators may be necessary prior to making the decision whether the patient may benefit from definitive duct occlusion or not. Large ducts in infants less than 8 kg can be difficult to treat due to a relative mismatch of introducers, plugs, or occluders to the small anatomic dimensions. The implantation of multiple coils can be associated with a higher risk of device embolization. Unfortunately, for the large group of preterm infants with very low body weights and large ducts of tubular shape there is currently no standardized interventional therapy available.

Balloon Occlusion↗

Long-term outcome of transcatheter coil closure of small to large patent ductus arteriosus.

Coil closure of patent ductus arteriosus (PDA) has become an accepted alternative to surgical closure in most pediatric cardiac centers. However, little is known about the mid-to long-term outcome of this procedure. Therefore, we evaluated the immediate, short-, and long-term outcome of transcatheter coil closure (TCC) of PDA using single or multiple Gianturco coils or the Gianturco-Grifka Vascular Occlusive Device (GGVOD). One hundred forty-nine patients underwent an attempt at TCC of their PDAs at a median age of 2.4 years (2 weeks to 55 years) and median weight of 13.5 kg (2.3-87 kg). There were 33 patients < 1 year of age. The median PDA minimal diameter was 2 mm (0.4-7 mm) with 26 patients whose PDA minimal diameter was > 4 mm. A 4 Fr catheter was used for coil deployment in 136 patients, a 3 Fr in 4, and an 8 Fr in 4 patients who received the GGVOD. A single coil was used in 77 patients and multiple coils (2-6) were used in 66 patients. One hundred forty-six patients had successful closure (142 had immediate complete closure and 4 had residual shunt), 3 patients failed the initial attempt (2 underwent surgical ligation and 1 had a successful second attempt a year later). Of the four patients with residual shunt, three underwent a second procedure with implantation of 1-3 coils resulting in complete closure in all and one patient had spontaneous resolution of the residual shunt. Complications were encountered in nine patients: six had coil migration with successful retrieval in four; two had left pulmonary artery stenosis (2.4 kg and 6.3 kg infants), and one patient had loss of femoral arterial pulse. The median fluoroscopy time was 16 min (2-152 min). One hundred forty-two patients had the procedure as an outpatient, five patients stayed greater than 24 hr, and two of these patients were in hospital for 1 month for noncardiac reasons. At a median follow-up interval of 3.0 years (1 month to 5.1 years), there were no episodes of delayed coil migration, delayed recanalization, thromboembolic episodes, or bacterial endocarditis. Lung perfusion scans performed at a median follow-up interval of 1.6 years in 31 patients who received multiple coils revealed 45% +/- 5% blood flow to the left lung. Long-term follow-up of coil closure of PDA indicates that the technique is safe and effective for most patients with PDA up to a diameter of 7 mm.

Adolescent↗

Does the risk of infective endarteritis justify routine patent ductus arteriosus closure?

OBJECTIVES: The risk of infective endarteritis in patients with patent ductus arteriosus seems to have declined during the last 30-40 years, and cases of patent ductus arteriosus complicated by infective endarteritis are now very rare. Moreover, with the introduction of antibiotics, there has been a dramatic reduction in mortality from infective endocarditis. Despite these changes, however, the prevention of infective endarteritis has remained the principal indication, apart from haemodynamic reasons, for surgical patent ductus arteriosus closure. The aim of this study was to ascertain whether prevention of infective endarteritis is still a justifiable indication for routine closure in all cases of patient ductus arterious. METHODS: The records of 270 paediatric and adult cases of patent ductus arteriosus was reviewed with respect to infective endarteritis. All Swedish death certificates issued during the period 1960-93 were checked for the occurrence of patent ductus arteriosus in combination with infective endarteritis. RESULTS: There had been no cases of infective endarteritis over an aggregate of 1196 years at risk. Of nearly three million deaths in Sweden during the period 1960-93 two cases were due to infective endarteritis as a complication of patent ductus arteriosus. CONCLUSION: The present findings suggest routine closure of a patent ductus arteriosus, for the sole purpose of eliminating the risk of infective endarteritis, is unnecessary.

Adult↗

Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated?

PURPOSE OF REVIEW: The ductus arteriosus is a vessel that connects the pulmonary artery to the aorta and provides a pulmonary-to-systemic diversion during fetal life. In the vast majority of infants, the ductus arteriosus closes by 3 days of life. In some infants, especially preterm infants with lung disease, there is delayed closure of the ductus arteriosus. There has been controversy as to whether or when the ductus arteriosus should be closed by either pharmacologic or surgical methods. RECENT FINDINGS: There have been several epidemiologic studies describing an association between a patent ductus arteriosus and the development of morbidities, such as chronic lung disease. These associations have suggested to some that a causal relationship exists between patency of the ductus arteriosus and chronic lung disease and other morbidities. However, recent metaanalyses of randomized, controlled trials of the use of indomethacin for the prevention and treatment of the patent ductus arteriosus have not documented a decrease in the incidence of these morbidities after treatment, despite success in closure of the patent ductus arteriosus. SUMMARY: In preterm infants, patency of the ductus arteriosus may represent a normal physiologic adaptation to allow shunting from either systemic-to-pulmonary circulation (eg, in the first day of life) or from pulmonary-to-systemic circulation (eg, in the presence of severe lung disease). Therapies designed to close the ductus arteriosus are contraindicated in some settings and should not be considered a standard of care at any time until these therapies are proven to decrease long-term clinical morbidities in randomized, placebo-controlled trials.

Ductus Arteriosus, Patent↗

Pharmacologic closure of patent ductus arteriosus in the premature infant.

The prostaglandins affect smooth-muscle tone of the ductus arteriosus. Patent ductus often complicates the clinical course of prematurely born infants with respiratory-distress syndrome. In the present study, a single oral or rectal dose of a potent inhibitor of prostaglandin synthesis, indomethacin, was administered to six consecutive premature infants with the syndrome who would otherwise have undergone surgical ligation of the patent ductus. Within 24 hours all the clinical symptoms and physical, echocardiographic and radiographic signs attributable to substantial left-to-right shunting through a patent ductus arteriosus dramatically and permanently disappeared. A transient reduction in renal function was observed in two infants in whom sustained ill-effects did not occur. The observation that constriction and closure of the patent ductus arteriosus may be induced pharmacologically raises important possibilities for the improved treatment of the respiratory-distress syndrome.

Cyclooxygenase Inhibitors↗

Patent Ductus Arteriosus Diagnosed in Old Age.

Patent ductus arteriosus is a relatively common congenital heart disorder occurring in 0.5 percent of births and accounting for up to 10% of all congenital cardiac anomalies. Due to its early closure during infancy, however, patent ductus arteriosus is rare in the adult. A 76 year old woman was previously reported to be the oldest patient with a new diagnosis of patent ductus arteriosus. We present a woman first diagnosed at age 86.

Journal Article↗

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2.

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Animals↗

Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents ductus arteriosus reopening.

Regulation of ductus arteriosus (DA) tension depends on a balance between oxygen-induced constriction and PG and nitric oxide (NO)-mediated relaxation. After birth, increasing Pa(O(2)) produces DA constriction. However, as the full-term ductus constricts, it develops severe tissue hypoxia in its inner vessel wall (oxygen concentration <0.2%). We used isolated rings of fetal lamb DA to determine why the constricted ductus does not relax and reopen as it becomes hypoxic. We used a modification of the 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) technique (Clyman RI, Chan CY, Mauray F, Chen YQ, Cox W, Seidner SR, Lord EM, Weiss H, Wale N, Evan SM, and Koch CJ. Pediatr Res 45: 19-29, 1999) to determine mean tissue oxygen concentration. A decrease in the ductus' mean tissue oxygen concentration from 1.4 to 0.1% lowers the isometric tone of the ductus by 15 +/- 10% of its maximal active tension (the maximal tension that can be produced by the ductus). Although decreases in oxygen concentration diminish ductus tension, most of the vasoconstrictor tone in the ductus is independent of ambient oxygen concentration. This oxygen-independent tone is equivalent to 64 +/- 10% of the maximal active tension. At mean tissue oxygen concentrations >0.2%, endogenous PGs and NO inhibit more than 40% of the active tension developed by the ductus. However, when tissue oxygen concentrations drop below 0.2%, the constitutive relaxation of the ductus by endogenous PGs and NO is lost. In the absence of PG and NO production, tension increases to a level normally observed only after treatment of the ductus with indomethacin and nitro-L-arginine methyl ester (inhibitors of PG and NO production). Therefore, under conditions of severe hypoxia (tissue oxygen concentration <0.2% oxygen), the loss of PG- and NO-mediated relaxation more than compensates for the loss of oxygen-induced tension. We hypothesize that this increased ductus tone enables the vessel to remain closed as it undergoes tissue remodeling.

Animals↗

Chest film diagnosis of patent ductus arteriosus in infants with hyaline membrane disease.

Patent ductus arteriosus in an infant with hyaline membrane disease is usually a serious complication. To evaluate the diagnostic role of chest radiography in these infants, a double-blind study comparing patients with both hyaline membrane disease and patent ductus arteriosus and matched controls was undertaken. Three pediatric radiologists acted as observers. In no instance were they more reliable than chance in predicting the presence of a patent ductus arteriosus. Analysis according to various clinical criteria (e.g., severity of illness, PAO2) also failed to show any subgroup in which the observers were accurate. From these data it is concluded that chest radiography does not play a significant role in the diagnosis of patent ductus arteriosus in infants with hyaline membrane disease.

Clinical Trials as Topic↗

Cost and efficacy of surgical ligation versus transcatheter coil occlusion of patent ductus arteriosus.

OBJECTIVE: The purpose of this study was to compare cost and efficacy of surgical closure of patent ductus arteriosus using new critical pathway methods with outpatient transcatheter coil occlusion of patent ductus arteriosus. METHODS: Surgical techniques included a transaxillary, muscle-sparing thoracotomy, triple ligation of the patent ductus arteriosus, no chest tube, and discharge from the hospital within 24 hours. Transcatheter coil occlusion of patent ductus arteriosus was done as an outpatient procedure. Costs were compared with inclusion of all hospital and professional charges. RESULTS: From July 1994 until March 1996, 20 patients underwent coil occlusion of patent ductus arteriosus and 20 patients underwent surgical closure of patent ductus arteriosus. Duration of hospitalization was significantly less for the patients receiving coil occlusion (11 +/- 6 hours) as compared with that for the patients having surgical ligation (28 +/- 7 hours, p < 0.05). Total charges were similar for surgical ligation ($7101 +/- $408) as compared with those for coil occlusion ($7104 +/- $886, p > 0.05). Morbidity in coil occlusion included inability to occlude the patent ductus arteriosus in two patients (2/20, 10%) and residual patency in two patients (2/18, 11%). Morbidity in the surgical group included nausea and vomiting necessitating hospitalization for more than 36 hours in one patient (1/20, 5%), transient left recurrent laryngeal nerve palsy in one (1/20, 5%), and pneumothorax in two patients (2/20, 10%). There were no instances of residual patency in the surgical group. CONCLUSIONS: Transaxillary thoracotomy without tube thoracostomy and with critical pathway methods allows safe and effective ligation of a patent ductus arteriosus with early hospital discharge. This surgical method has similar cost, higher efficacy rate, and applicability in all patients as compared with newer transcatheter coil occlusion techniques for closure of a patent ductus arteriosus.

Adolescent↗

[Echocardiographic post-neonatal progress of preterm neonates with patent ductus arteriosus].

OBJECTIVE: To identify clinical and echocardiography predictors of the spontaneous closure of patent ductus arteriosus in preterm neonates. METHODS: Sixty-one consecutive preterm neonates (gestational age 30+/-2 weeks, birth weight 1.2+/-0.2 kg) were evaluated by echocardiogram on their third day of life and those with patent ductus arteriosus were selected for a prospective cohort. Echocardiography was repeated weekly until they reached term. Based on their progress, the sample population was divided into two groups, depending on whether spontaneous closure of patent ductus arteriosus took place (Group A) or not (Group B). The prevalence of clinical signs of patent ductus arteriosus and echocardiography findings at baseline were compared between the groups. RESULTS: Patent ductus arteriosus was found in 21 neonates (34%). Spontaneous closure was observed during follow-up of seven patients (Group A, 33% of those with patent ductus arteriosus), in contrast with the remaining 14 patients (Group B, 67%). Clinical signs of patent ductus arteriosus were present in 14% of the patients in Group A, compared with 71% in group B (p = 0.01). At baseline, Group B had a larger ductus diameter in relation to Group A (2.6+/-0.6 mm vs. 1.4+/-0.6 mm; p = 0.003). The area under the ROC curve in relation to ductus diameter was 0.93 (p = 0.003) and 100% sensitivity for identifying cases without spontaneous closure was obtained at the cutoff point of 1.7 mm, while 100% specificity was observed taking 2.2 mm as the cutoff. CONCLUSIONS: In preterm neonates, a patent ductus arteriosus greater than 2.2 mm on the third day of life predicts no spontaneous closure and suggests a need for early treatment, especially when associated with clinical signs.

Birth Weight↗

Pulmonary vasculature changes associated with idiopathic closure of the ductus arteriosus and hydrops fetalis.

Antenatal closure of the ductus arteriosus has been considered as a potential risk factor for the development of hydrops fetalis and persistent fetal circulation of the newborn. We present an infant with antenatal ductal closure who had not received prenatal prostaglandin synthetase inhibitors. The pulmonary vascular morphological findings are described and compared to three additional infants in whom the ductus arteriosus was known to be patent; one with neonatal sepsis and two others with hydrops fetalis. The infants with fetal hydrops, regardless of etiology, had increased muscularization of the acinar pulmonary arteries. In addition, the infant with antenatal closure of the ductus arteriosus also had both a significant decrease in preacinar arterial external diameter and an increase in medial wall thickness. Antenatal closure of the ductus arteriosus appears to enhance in utero pulmonary blood flow and this may be the cause of pulmonary vascular remodeling.

Ductus Arteriosus↗

Evidence for an effector role of endothelin in closure of the ductus arteriosus at birth.

The ductus arteriosus is a special muscular shunt that in the fetus allows blood to bypass the unexpanded lungs. It closes rapidly after birth and this event is initiated by the physiologic rise in blood oxygen tension. Endothelin-1 has been proposed by us as a local mediator for oxygen after demonstrating that it is formed within the ductus and is a potent ductus constrictor. To confirm this possibility, we have now measured the release of endothelin-1 from the isolated ductus of near-term fetal lambs at different oxygen concentrations of the medium. In addition, using the same preparation, we have examined the effect on contractile tone of compounds interfering with the synthesis (phosphoramidon, 50 microM) and action (BQ123, 1 microM) of endothelin-1. We report that release of endothelin-1 from the ductus tends to increase with the oxygen concentration up to a value mimicking the neonatal condition. Phosphoramidon and, to a greater degree, BQ123 inhibit the contraction of the vessel to oxygen. These results implicate endothelin-1 as the effector agent for oxygen in the ductus and, by extension, assign to this peptide a critical role in the closure of the vessel at birth.

Animals↗

Transposition of the great arteries with intact ventricular septum and patent ductus arteriosus.

At the time of initial balloon atrial septostomy a patent ductus arteriosus was found with angiography in 39 of 81 infants with transposition of the great arteries with intact ventricular septum. By angiographic criteria the ductus shunt was considered small in 21 infants and large and significant in 18. In contrast to the usual clinical presentation of neonates with transposition and intact ventricular septum, 12 of these 18 infants with a significant patent ductus arteriosus had only slight cyanosis and 8 presented with tachypnea out of proportion to the degree of cyanosis. Ten of the 18 infants had no continuous murmur, bounding pulses, mid-diastolic rumble or differential cyanosis. Clinically occult narrowing or closure occurred, presumably gradually and relatively late, in six infants. Acute early narrowing or closure, spontaneous (six infants) or surgically produced (three infants), occurred usually within the 1st month of life and was associated with a marked decrease in arterial oxygen saturation in eight infants, often with a rapid clinical deterioration. Persistence of a large patent ductus arteriosus for several months appears to be associated with an increased incidence of early pulmonary vascular disease. Therapeutic considerations for the infant with a large patent ductus arteriosus after initial balloon atrial septostomy include: (1) careful initial follow-up of the infant in clinically stable condition in case the ductus arteriosus should acutely narrow or close and the patient require urgent palliative or corrective surgery; (2) urgent early closure of the ductus in the infant with overt left heart failure with concurrent atrial septectomy or preferably primary corrective surgery; and (3) elective closure of a persistent significant patent ductus arteriosus before age 4 months with concurrent corrective surgery in the infant in clinically stable condition.

Abnormalities, Multiple↗

Cerebral blood flow velocity during occlusive manipulation of patent ductus arteriosus in children.

Patent ductus arteriosus (PDA) with left-to-right shunting modifies the Doppler flow pattern of the intracranial circulation. The ability of increases in cerebral blood flow velocity (CBFV) to predict shunt resolution during PDA occlusion was evaluated. A 2 MHz transcranial Doppler (TCD) monitored diastolic and mean CBFV, plus the systolic/mean CBFV ratio in the middle cerebral artery from before (baseline) to immediately after PDA occlusion. Shunt resolution was verified by echocardiography and/or angiography. A minimum of 40% increase in diastolic-CBFV from baseline was considered successful resolution. Patients were age-stratified into group I (< 15 months; n = 23) and group II (> 15 months; n = 10). Thirty-three children were studied (age, 0.1 to 109 months) during surgical (n = 22) or coil occlusions (n = 11). Transcranial Doppler successfully identified shunt resolution in 78% of cases in group I, as compared to 0% in group II (p < 0.01). Identification rate decreased from 79% in cases of minimum ductal diameter of 3 mm (n = 19) to 21% in smaller ductuses (n = 14) (p < 0.01). Body weight and left-atrium size (p = 0.004) in group I and PDA diameter in group II (p = 0.02), were the only preoperative ductal parameters associated with diastolic-CBFV changes after ductus occlusion. Transcranial Doppler detects shunt resolution in infants with moderate to large PDAs.

Blood Flow Velocity↗