PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

Transcatheter Closure of Arterial Duct in Infants < 6 kg: Amplatzer Duct Occluder Type I vs Amplatzer Duct Occluder II Additional Sizes.

Transcatheter closure of arterial duct (AD) remains challenging in low-weight patients and using Amplatzer Duct Occluder devices is still considered off-label in infants < 6 kg. This study aimed to report a large, single-center experience of percutaneous AD closure in infants < 6 kg as well as to compare the most frequently used devices, Amplatzer Duct Occluder type I (ADO I) and Amplatzer Duct Occluder type II Additional Sizes devices (ADO II-AS) (St. Jude Medical Corp, St. Paul, MN, USA). From March 2000 to March 2017, among the 762 patients submitted to percutaneous closure of AD at our Institution, 33 were infants < 6 kg (age 4.8 ± 2.1 months; weight 5.0 ± 0.9 kg). Fourteen patients (45%) underwent ADO I (Group I) and 19 patients ADO II-AS (Group II) device implantation. AD diameter was 2.6 ± 0.8 (range 1.5-4.0) mm resulting in QP/QS of 2.6 ± 0.0.9 (range 1.1-4.5). Successful device deployment was achieved in all patients without procedural morbidity or mortality. Procedural and fluoroscopy times were not significantly different between the groups. However, total X-ray absorbed dose was significantly higher in Group I (121 ± 69 vs 29 ± 16 mGy/cm2, p < 0.01). Immediate, 24 h, and mid-term (46 ± 37 months, median 39) complete occlusion were recorded in 72.7, 90.9, and 97% of patients, respectively without significant difference between the groups. In conclusion, transcatheter closure of AD with Amplatzer Duct Occluder devices is feasible, safe, and effective also in infants less than 6 kg, without significant difference between the most commonly used devices, namely, ADO I and ADO II-AS.

Urinary NT-proBNP levels and echocardiographic parameters for patent ductus arteriosus.

OBJECTIVE: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidities. B type natriuretic peptide (BNP) is synthesized in the ventricles secondary to volume overload and excreted as urinary N-terminal pro-brain natriuretic peptide (NT-proBNP). STUDY DESIGN: We report an observational prospective study of 64 preterm infants with birth weight ⩽1000 g. Echocardiographic parameters were obtained from clinical echocardiograms performed in the first week of life. Urinary NT-proBNP/creatinine ratios (pg mg-1) were measured on the same day of the echocardiograms. RESULTS: Infants with medium to large PDA (n=39) had significantly higher NT-proBNP/creatinine levels compared with infants with small PDA (n=10) (median (IQ range): 2333 (792-6166) vs 714 (271-1632) pg mg-1, P=0.01) and compared with infants with no PDA (n=15) (2333 (792-6166) vs 390 (134-1085) pg mg-1, P=0.0003). Urinary NT-proBNP/creatinine ratios were significantly lower post treatment if PDA closed (n=17), P=0.001 or if PDA became smaller after treatment (n=9), P=0.004. Urinary NT-proBNP/creatinine levels correlated with ductal diameter (P⩽0.0001), but not with LA/Ao ratio (P=0.69) or blood flow velocity through the ductus (P=0.06). CONCLUSION: Our findings indicate that there is a positive correlation between ductal diameter and urinary NT-proBNP in preterm infants.

Morphologic characterization of the patent ductus arteriosus in the premature infant and the choice of transcatheter occlusion device.

OBJECTIVES: The aim of this study was to describe and differentiate the morphology of patent ductus arteriosus (PDA) seen in children born prematurely from other PDA types. BACKGROUND: PDAs are currently classified as types A-E using the Krichenko's classification. Children born prematurely with a PDA morphology that did not fit this classification were described as Type F PDA. METHODS: A review of 100 consecutive children who underwent transcatheter device closure of PDA was performed. The diameter and length (L) of the PDA and the device diameter (D) were indexed to the descending aorta (DA) diameter. RESULTS: Comparison of 26 Type F PDAs was performed against, 29 Type A, 7 Type C and 32 Type E PDAs. Children with Type F PDAs (median 27.5 weeks gestation) were younger during the device occlusion compared with types A, C, and E (median age: 6 vs. 32, 11, and 42 months; P = 0.002). Type F PDAs were longer and larger, requiring a relatively large device for occlusion than types A, C, and E (Mean L/DA: 1.88 vs. 0.9, 1.21, and 0.89, P ≤ 0.01 and Mean D/DA: 1.04 vs. 0.46, 0.87, and 0.34, P ≤0.01). The Amplatzer vascular plug-II (AVP-II) was preferred for occlusion of Type F PDAs (85%; P <0.001). CONCLUSIONS: Children born prematurely have relatively larger and longer PDAs. These "fetal type PDAs" are best classified separately. We propose to classify them as Type F PDAs to add to types A-E currently in use. The AVP-II was effective in occluding Type F PDAs.

The Aristotle score predicts mortality after surgery of patent ductus arteriosus in preterm infants.

BACKGROUND: Outcomes after surgical ligation of patent ductus arteriosus (PDA) in preterm infants are often complicated by prematurity associated comorbidities. The Aristotle comprehensive complexity score (ACCS) has been proposed as a useful tool for complexity adjustment in the analysis of outcome after congenital heart surgery. The aims of this study were to define preoperative risk factors for mortality and to demonstrate the usefulness of ACCS to predict mortality after surgical ligation of PDA in the preterm. METHODS: Included were 49 preterm babies (≤35 weeks of gestation) who had surgical ligation of PDA between May 2009 and July 2012. Median gestational age was 27.6 weeks (range, 23 to 35 weeks) and median birth weight was 1,040 g (range, 520 to 2,280 g). Median age at operation was 15 days (range, 4 to 44 days) and median weight was 1,120 g (range, 400 to 2,880 g). Initial oral ibuprofen was ineffective in 24 patients and contraindicated in 25. All surgical ligations were done at bedside in the neonatal intensive care unit. Preoperative clinical and laboratory profiles were reviewed and ACCS was derived. RESULTS: Eight of 49 patients (16.3%) died at a median of 14 days (range, 2 to 73 days) after PDA ligation. Patients who had contraindications for oral ibuprofen (odds ratio [OR] 8.94; p=0.049), coagulopathy (OR 12.13; p=0.025), renal dysfunction (OR 28.88; p=0.003), intraventricular hemorrhage greater than grade II or seizure (OR 34.00; p=0.002), and ACCS points (OR 29.594; p<0.05) were significantly associated with an increased risk for mortality. Among the risk factors, ACCS showed the largest area under curve (0.991) by receiver-operating characteristic curve analysis. Optimal cutoff value of ACCS for mortality were 15 or greater, with sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.6%. CONCLUSIONS: The ACCS, especially for procedure-independent complexity factors, is a useful tool to predict mortality after ligation of PDA in preterm infants.

Use of diagnostic information submitted to the United Kingdom Central Cardiac Audit Database: development of categorisation and allocation algorithms.

OBJECTIVE: To categorise records according to primary cardiac diagnosis in the United Kingdom Central Cardiac Audit Database in order to add this information to a risk adjustment model for paediatric cardiac surgery. DESIGN: Codes from the International Paediatric Congenital Cardiac Code were mapped to recognisable primary cardiac diagnosis groupings, allocated using a hierarchy and less refined diagnosis groups, based on the number of functional ventricles and presence of aortic obstruction. SETTING: A National Clinical Audit Database. Patients Children undergoing cardiac interventions: the proportions for each diagnosis scheme are presented for 13,551 first patient surgical episodes since 2004. RESULTS: In Scheme 1, the most prevalent diagnoses nationally were ventricular septal defect (13%), patent ductus arteriosus (10.4%), and tetralogy of Fallot (9.5%). In Scheme 2, the prevalence of a biventricular heart without aortic obstruction was 64.2% and with aortic obstruction was 14.1%; the prevalence of a functionally univentricular heart without aortic obstruction was 4.3% and with aortic obstruction was 4.7%; the prevalence of unknown (ambiguous) number of ventricles was 8.4%; and the prevalence of acquired heart disease only was 2.2%. Diagnostic groups added to procedural information: of the 17% of all operations classed as "not a specific procedure", 97.1% had a diagnosis identified in Scheme 1 and 97.2% in Scheme 2. CONCLUSIONS: Diagnostic information adds to surgical procedural data when the complexity of case mix is analysed in a national database. These diagnostic categorisation schemes may be used for future investigation of the frequency of conditions and evaluation of long-term outcome over a series of procedures.

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

Coil occlusion for patent ductus arteriosus larger than 3 mm.

BACKGROUND: Coil occlusion of patent ductus arteriosus (PDA) is now widely accepted as the first-line treatment, but there are few reports of age-dependent differences in the complications associated with this technique. METHODS AND RESULTS: Sixteen patients (11 adults, 5 children) with a PDA larger than 3 mm, who underwent coil occlusion at Sapporo Medical University Hospital between September 1995 and August 2004, were enrolled. Immediate and intermediate outcomes and complications were analyzed. Procedural success rate was 72.7% (8/11) in the children and 100% (5/5) in the adults. Coil migration occurred in 4 children and 1 adult, and 3 adult patients had hemolysis. CONCLUSION: Hemolysis was more frequent in adults than in children even though the residual shunt was trivial.

Indomethacin tocolysis increases postnatal patent ductus arteriosus severity.

UNLABELLED: Postnatally, therapeutic indomethacin administration is usually effective in mediating patent ductus arteriosus (PDA) constriction in premature infants. There are infants, however, who remain resistant to indomethacin and require more aggressive surgical intervention to facilitate ductal closure. Indomethacin tocolysis has been reported to increase the incidence of persistent PDA in premature infants. It was our impression that infants exposed to antenatal indomethacin not only suffered from an increased incidence of PDA, but that they were more symptomatic from PDA and that for them, PDA was more resistant to medical closure. It is this observation that we sought to examine in this study. METHODS: Medical records of all mothers and premature neonates with birth weight

The large window ductus: a surgical trap.

A rare window type of patent ductus arteriosus is reported that was large (15 mm in maximal transverse dimension) but had virtually no length and hence was externally invisible. The smaller aortic isthmus (4 mm in diameter), which was intrapericardial, was mistaken for the ductus and was inadvertently clip-occluded, leading to death. After a specific diagnosis is made, the large window ductus should be patched on cardiopulmonary bypass with a transpulmonary approach.

Reopening after successful coil occlusion for patent ductus arteriosus.

OBJECTIVES: This study was performed to determine the frequency of patent ductus arteriosus (PDA) reopening and the factors that may predict reopening after successful coil occlusion. BACKGROUND: Transcatheter coil occlusion is a widely used and accepted method to close a PDA. After documented successful coil occlusion, we found PDAs that reopened. We hypothesized that specific factors are involved in those that reopened. METHODS: All patients who underwent percutaneous transarterial PDA coil occlusion were studied. Successful coil occlusion was documented. PDA reopening was determined when Doppler-echocardiography (DE) performed after the procedure was negative for PDA flow but at follow-up demonstrated PDA shunting. Patients with a reopened PDA were compared with all other patients in evaluating independent variables. RESULTS: Coil occlusion for PDA was attempted in 22 patients. Clinical success was achieved in 20 patients (91%), and DE was negative for PDA shunting in 19 patients (90%). At follow-up, five patients demonstrated reopening. The PDA minimal diameter was 1.4 +/- 0.5 mm (mean +/- SD) for the reopened group and 1.2 +/- 0.7 mm for the other patients. The PDA length was 2.9 +/- 1.9 mm for the reopened group and 7.1 +/- 3.2 mm for all other patients. All those with type B PDA were in the reopened group. When independent variables were compared between groups, only PDA length and type B PDA predicted reopening (p < 0.05). CONCLUSIONS: PDA reopening may occur after successful coil occlusion. Short PDA length and type B PDA are associated with reopening. The data suggest that in such anatomy, alternative strategies to the current coil occlusion technique should be considered.

[Closure of a persistent ductus arteriosus Botallo without thoracotomy]. / Verschluss des persistierenden Ductus arteriosus Botalli ohne Thorakotomie.

A persisting ductus arteriosus (PDA) was closed with the Rashkind occlusion system in 15 patients (12 children, aged 1.0 to 10.8 years, and three adults, aged 21, 33 and 56 years). The method consists of the implantation of a double umbrella of polyurethane foam mounted on platinum or steel wire introduced into the PDA via a transport catheter, the ductus being closed by thrombosing and epithelialization of the implant. The mean diameter of the PDA (as measured in the lateral aortogram) was 2.4 (1.4-5.3) mm. There were no complications of the procedure, nor any embolization or other serious complications. The PDA was completely occluded in eight patients, while a residual shunt remained in seven. In the oldest patient, aged 56 years, who had a residual shunt, increasing haemolysis required surgical closure of the ductus with a pericardial patch. These results indicate that, for patients weighing over 5 kg and with a ductus diameter of less than 10 mm, the closure method after Rashkind is a sparing and only slightly invasive procedure.

[Electrocardiographic diagnosis of patent ductus atrio-ventricularis]. / Elektrokardiograficheskaia diagnostika otkrytogo atrio-ventrikuliarnogo kanala

The paper deals with the diagnosis of defective development of the patent ductus atrioventricularis. Electrocardiographic changes in 81 patients with firmly established hemodynamic form of the patent ductus atrioventricularis, ascertained during surgery and catheterization, are summarized. Characteristic electrocardiographic signs of the defect distinguishing it from other congenital diseases and differential-diagnostic symptoms of diverse anatomo-hemodynamic forms of the patent ductus atrioventricularis were educed.

Transfemoral plug closure of patent ductus arteriosus. Experiences in 61 consecutive cases treated without thoracotomy.

We successfully closed the isolated patent ductus arteriosus in 58 of 61 consecutive patients using the transfemoral-catheter method originally introduced by Porstmann in 1968. To perform this technique more safely and reliably, some instrumental and technical improvements were made. The indications for this method have been expanded to include the cylindrical or window-type ductus as well as the conical-shaped ductus. Classification into three groups of the configuration of the ductus by angiography has been useful in selecting the shape of the closing plug. Whenever feasible, we consider the catheter technique to be the method of choice to close the ductus.