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Retrievable patent ductus arteriosus plug for interventional, transvenous occlusion of the patent ductus arteriosus. Evaluation in lambs and preliminary clinical results.

RATIONALE AND OBJECTIVES: The clinically most widely used devices (Porstmann-plug, Rashkind-umbrella, Botallooccluder) have inherent specific limitations (eg, transarterial approach, residual shunts, limited retrieval). The authors assess practicability, efficacy, and tissue reaction of the new retrievable transvenous plug device for the occlusion of the persistent patent ductus arteriosus (PDA). METHODS: A foam plug (polyvinyl alcohol) is mounted on a titanium core pin where, at both ends, small legs (titanium nickel alloy) with titanium heads are anchored, to ensure safe fixation in the ductus. The device is introduced transvenously through a long sheath (Mullins sheath) and held by a modified biopsy forceps allowing complete retrieval until final release. A common lamb model of large PDAs (n = 11) was used to test for practicability and the histomorphologic outcome. Clinical results were obtained from a consecutive series of 16 patients (aged 13 to 71 years). RESULTS: In all lambs, placement of the plug within the PDA was possible. Histopathology (follow-up 10 to 215 days; mean 112 days) revealed an adequate ingrowing of the device and no pathologic foreign body reaction. The diameter of the human PDAs ranged from 3 to 7 mm (mean 5 mm). The size of the sheath used for introducing the plug (diameter 8 to 16 mm) ranged from 8 to 16 French. Fourteen of 16 PDAs were closed immediately after or on day 1 after implantation, 1 was closed after the 12-month follow-up, and 1 needed an additional plug after 30 months for definitive closure. CONCLUSIONS: The device demonstrated practicability and biocompatibility in our experimental lamb model and effectively closed the PDA in a consecutive series of 16 patients. A greater number of patients and a longer follow-up period are necessary for the definitive clinical assessment of the new device.

Adolescent↗

Furosemide for symptomatic patent ductus arteriosus in indomethacin-treated infants.

BACKGROUND: Inhibition of prostaglandin synthesis mediates closure of the ductus arteriosus and renal side effects after indomethacin administration. Because furosemide increases prostaglandin production, it could potentially help prevent indomethacin-related toxicity but also decrease ductal response to indomethacin. OBJECTIVES: The primary objectives of this review were to assess (1) whether furosemide affects the incidence of failure of ductal closure after indomethacin and that of indomethacin-related toxicity and (2) the effect of furosemide on mid-term and long-term outcome. The secondary objective was to determine whether the effect of furosemide on renal function and water balance depends on prior extracellular volume (assessed by blood urea nitrogen [BUN]/creatinine ratio). SEARCH STRATEGY: We searched electronic databases (Medline, Embase and Cochrane) and selected abstract books, without language restriction. SELECTION CRITERIA: We selected studies with (1) random allocation to either indomethacin alone or indomethacin and furosemide and (2) analysis of either short-term risk-benefit ratio of furosemide, mid- or long-term outcome, or the relationship between extracellular volume at study entry and changes in renal function. DATA COLLECTION AND ANALYSIS: We assessed studies for possible bias and for quality of assessment of ductal patency. We assessed categorical variables using relative risk and absolute risk reduction. We assessed the effects of furosemide on renal function and fluid balance by comparing changes from baseline in the treatment group with those in controls. Subsets were determined a priori based on BUN/creatinine ratio at study entry. MAIN RESULTS: All 3 studies fulfilling the entry criteria had limitations, including possible or definite bias. There was substantial heterogeneity among studies. Furosemide administration did not significantly increase the risk of failure of ductal closure; however, sample size was insufficient to rule out even a 31% increase. In the subset with initial BUN/creatinine ratio > 20 mg/mg, 2 of 18 patients receiving furosemide could not complete a 3-dose course of indomethacin because of toxicity. Minimal or no information was available about any of the other main outcome variables. Furosemide increased urine output regardless of the initial BUN/creatinine ratio, leading to a 5% weight loss during a 3-dose course, an undesired effect in patients with initial BUN/creatinine ratio > 20 mg/mg. Furosemide increased creatinine clearance only in patients with initial BUN/creatinine ratio <20 mg/mg. REVIEWER'S CONCLUSIONS: There is not enough evidence to support the administration of furosemide to premature infants treated with indomethacin for symptomatic patent ductus arteriosus. Furosemide appears to be contraindicated in the presence of dehydration in those infants.

Cyclooxygenase Inhibitors↗

Etiology of patent ductus arteriosus in dogs.

Patent ductus arteriosus (PDA) is the most common congenital heart disease in dogs and usually causes heart failure and death unless corrected at a young age. Previous histologic studies in a line of dogs derived from Miniature Poodles with hereditary PDA identified varying degrees of hypoplasia and asymmetry of ductus-specific smooth muscle and the presence of aortalike elastic tissue in the ductus wall sufficient to cause patency. To determine if similar structural abnormalities cause PDA in other dogs, serial-section, 3-dimensional histology of ductal architecture was studied in 8 non-Poodle purebred dogs with PDA with no immediate family history of PDA. Morphologic abnormalities were observed in 7 of 8 dogs with PDA and essentially were the same as those in dogs known to have a hereditary form of PDA. These findings suggest that apparently sporadic PDA in these breeds is caused by a genetic defect in the structure of the ductus arteriosus that is similar or identical to that in the Poodle. The relatives of dogs with PDA, particularly parents, offspring, and siblings, should be screened for evidence of PDA. Dogs with PDA should not be used for breeding, regardless of breed.

Animals↗

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↗

Transfemoral closure of patent ductus arteriosus in adult patients.

Patent ductus arteriosus is an uncommon anomaly in adult patients. Surgical closure of patent ductus arteriosus in this age group presents difficult problems to the surgeon. We report our experience of 21 adult patients (19-62 years of age, mean 40 years) who underwent closure of the ductus by transfemoral implantation of a Rashkind double umbrella device. The patients came to light because of atrial fibrillation, congestive heart failure, residual flow after surgical ligation of the duct or because of incidental diagnosis made during physical examination or chest X-ray. In ten patients the pulmonary arterial pressure was normal (systolic pressure < 30 mmHg), in eleven it was elevated (systolic pressure from 30 to 100 mmHg, mean 50 mmHg). In seven patients the duct was clearly calcified and the size of the duct varied from 3 to 9 mm (mean 4.3 mm). In 16 patients the ductus resulted perfectly closed after implantation of the first double umbrella device, two patients had minimal residual aortopulmonary flow, whereas in three patients the residual shunt was significant; two of these also developed haemolysis and went to surgery, in the latter the shunt was completely abolished after implantation of a second 17-mm device 16 months later. In conclusion transcatheter closure of patent ductus arteriosus in adults is feasible, even in the presence of calcifications and/or pulmonary hypertension; taking into account the significant surgical risk, PDA umbrella closure should be considered the first choice procedure in this group of patients.

Adult↗

Patent ductus arteriosus in the elderly.

Patent ductus arteriosus presenting in an elderly patient is unusual. This report describes the oldest patient (72 years) to undergo successful surgical interruption of a patent ductus arteriosus with a unique clinical presentation of typical angina pectoris with normal coronary anatomy. A possible pathophysiologic mechanism for this previously unreported presenting symptom is proposed. The natural history of patent ductus arteriosus and the role of surgery in the elderly patient are discussed.

Aged↗

Thoracoscopic clipping and ligation of a patent ductus arteriosus.

Several techniques of patent ductus arteriosus occlusion primarily by thoracotomy have been practiced. They have shown to be more reliable than nonsurgical procedures. Videothoracoscopy has been useful in several intrathoracic surgical procedures with faster recovery and minimal mortality and morbidity. We report 2 patients with clipping and ligation of a patent ductus arteriosus by a thoracoscopic approach. This technique may be useful in children with a noncomplicated patent ductus arteriosus. It allows an easier recovery and causes less pain.

Child↗

Molecular determinants of atrial and ventricular septal defects and patent ductus arteriosus.

Septation defects and patent ductus arteriosus are the most common human cardiovascular malformations (CVMs). Genetic factors play a major part in the origin of these malformations. Recent molecular analyses have shed light on several mendelian forms. In the autosomal dominant Holt-Oram syndrome, both atrial and ventricular septal defects are inherited in association with limb deformity as a result of mutations in the gene encoding the TBX5 transcription factor. Mutations in the NKX2.5 transcription factor gene cause autosomal dominant familial atrial septal defects in association with progressive atrioventricular block as well as complex congenital heart disease. Common atrial syndromes in autosomal dominant Ellis-van Creveld syndrome arise in the context of axial skeletal and limb malformation as a result of mutations in the EVC gene, whose function is unknown. Patent ductus arteriosus occurs in several syndromic forms of congenital heart disease, including Holt-Oram syndrome. Recent analyses of autosomal dominant Char syndrome, which includes, with variable penetrance, patent ductus arteriosus as well as craniofacial and hand malformations, have shown that the syndrome is caused by mutations in the TFAP2B transcription factor gene. Ongoing analyses are poised to determine the contribution of these genes as well as others yet to be identified to common, sporadic forms of congenital heart disease.

Abnormalities, Multiple↗

Effectiveness of five-loop coils to occlude patent ductus arteriosus.

Coil occlusion of patent ductus arteriosus with 5-loop coils was undertaken in 10 patients without coil embolizations, and with 90% immediate occlusion and 100% occlusion at follow-up. We conclude that 5-loop coil occlusion of patent ductus arteriosus is safe and effective.

Adult↗

Thoracoscopic clipping of patent ductus arteriosus in premature infants.

Patent ductus arteriosus is a frequent indication for surgical intervention in preterm infants. Commonly this operation is performed through a dorsolateral thoracotomy. In an animal trial (piglets smaller than 1,400 g) instruments and technique for thoracoscopic clipping of patent ductus arteriosus were developed. Since January 1993, 3 premature infants have been treated with this new minimally invasive procedure. The instruments and the surgical technique are demonstrated.

Ductus Arteriosus, Patent↗

Safety and efficacy of using 0.052-inch Gianturco coil for closure of large ( > or = 4mm) patent ductus arteriosus.

Transcatheter closure of patent ductus arteriosus (PDA) is now a well-established treatment alternative to surgery in many cardiology centers. Of all the methods used, transcatheter coil occlusion is the preferred therapy. For small PDA, the method using 0.038" Gianturco coils has proven safe and effective. However, this therapeutic strategy has encountered some difficulties with large PDA. This study provides an alternative strategy, using 0.052" Gianturco coil and complete closure of residual shunt with multiple coils to close large PDA. Fifteen patients underwent transcatheter coil occlusion of large ( > or = 4mm) patent ductus arteriosus. The intermediate success rate was 86.7%. There were four complications and only two patients had to be referred for surgery.

Adolescent↗

Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus.

BACKGROUND: Oxygen (O2)-sensitive K+ channels mediate acute O2 sensing in many tissues. At birth, initial functional closure of the ductus arteriosus (DA) results from O2-induced vasoconstriction. This mechanism often fails in premature infants, resulting in persistent DA, a common form of congenital heart disease. We hypothesized that the basis for impaired O2 constriction in preterm DA is reduced expression and function of O2-sensitive, voltage-gated (Kv) channels. METHODS AND RESULTS: Preterm rabbit DA rings have reduced O2 constriction (even after inhibition of prostaglandin and nitric oxide synthases), and preterm DA smooth muscle cells (DASMCs) display reduced O2-sensitive K+ current. This is associated with decreased mRNA and protein expression of certain O2-sensitive Kv channels (Kv1.5 and Kv2.1) but equivalent expression of the L-type calcium channel. Transmural Kv1.5 or Kv2.1 gene transfer "rescues" the developmental deficiency, conferring O2 responsiveness to preterm rabbit DAs. Targeted SMC Kv1.5 gene transfer also enhances O2 constriction in human DAs. CONCLUSIONS: These data demonstrate a central role for developmentally regulated DASMC O2-sensitive Kv channels in the functional closure of the DA. Modulation of Kv channels may have therapeutic potential in diseases associated with impaired O2 responsiveness, including persistent DA.

4-Aminopyridine↗

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.

Aorta, Thoracic↗