Percutaneous Closure of the Patent Ductus Arteriosus in Very Low Weight Infants: Considerations Following US Food and Drug Administration Approval of a Novel Device

Abstract

The Amplatzer Piccolo Occluder (or Amplatzer duct occluder II-additional sizes, ADO-II AS, Abbott, Chicago, Illinois) was approved by the US Food and Drug Administration on January 11, 2019.1US Food and Drug Administration Premarket Approval (PMA) of the AMPLATZER Piccolo Occluder. US Food and Drug Administration, Atlanta2019Google Scholar The class III device is indicated for percutaneous (catheter-based) closure of a patent ductus arteriosus (PDA) in an infant weighing >700 grams and a postnatal age of >3 days. After this regulatory approval, the healthcare community is tasked with answering fundamental questions on the appropriate use of the device in a subgroup of highly vulnerable patients. What is the strength of evidence for the device among very low weight (VLW) infants (<2.5 kg at time of closure)? Is Food and Drug Administration approval sufficient for widespread dissemination of the device or are additional safety and effectiveness data needed? Traditionally, surgical ligation was used to provide definitive ductal closure for symptomatic infants when medical therapy fails or is contraindicated.2Hamrick S.E. Hansmann G. Patent ductus arteriosus of the preterm infant.Pediatrics. 2010; 125: 1020-1030Crossref PubMed Scopus (345) Google Scholar Evidence of adverse outcomes associated with surgical ligation has led to increasing interest in the use of percutaneous techniques as a less invasive alternative for definitive ductal closure.3Weisz D.E. Giesinger R.E. Surgical management of a patent ductus arteriosus: is this still an option?.Semin Fetal Neonatal Med. 2018; 23: 255-266Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 4Bixler G.M. Powers G.C. Clark R.H. Walker M.W. Tolia V.N. Changes in the diagnosis and management of patent ductus arteriosus from 2006 to 2015 in United States neonatal intensive care units.J Pediatr. 2017; 189: 105-112Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 5Hsu K.H. Chiang M.C. Lien R. Chu J.J. Chang Y.S. Chu S.M. et al.Diaphragmatic paralysis among very low birth weight infants following ligation for patent ductus arteriosus.Eur J Pediatr. 2012; 171: 1639-1644Crossref PubMed Scopus (13) Google Scholar, 6Schena F. Francescato G. Cappelleri A. Picciolli I. Mayer A. Mosca F. et al.Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia.J Pediatr. 2015; 166: 1488-1492Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Backes C.H. Rivera B.K. Bridge J.A. Armstrong A.K. Boe B.A. Berman D.P. et al.Percutaneous patent ductus arteriosus (PDA) closure during infancy: a meta-analysis.Pediatrics. 2017; 139 (e20162927)Crossref PubMed Scopus (54) Google Scholar Percutaneous PDA occlusion is considered the procedure of choice for adults, children, and infants ≥5 kg.8Schneider D.J. Moore J.W. Patent ductus arteriosus.Circulation. 2006; 114: 1873-1882Crossref PubMed Scopus (387) Google Scholar Before the Amplatzer Piccolo Occluder, no Food and Drug Administration-approved devices were recommended for percutaneous PDA closure until infants weighed ≥5 kg.7Backes C.H. Rivera B.K. Bridge J.A. Armstrong A.K. Boe B.A. Berman D.P. et al.Percutaneous patent ductus arteriosus (PDA) closure during infancy: a meta-analysis.Pediatrics. 2017; 139 (e20162927)Crossref PubMed Scopus (54) Google Scholar This weight threshold was based on concerns regarding the introduction of large introducer sheaths, stiff delivery systems, and protrusion of the occluder discs into the left pulmonary artery and descending aorta. Despite high rates of technical success with the off-label use of various devices,7Backes C.H. Rivera B.K. Bridge J.A. Armstrong A.K. Boe B.A. Berman D.P. et al.Percutaneous patent ductus arteriosus (PDA) closure during infancy: a meta-analysis.Pediatrics. 2017; 139 (e20162927)Crossref PubMed Scopus (54) Google Scholar healthcare providers called for better devices to address the unique ductal morphology and profile of younger, more immature infants. Consequently, the Amplatzer Piccolo Occluder and its delivery system have a number of modifications (short length, low profile delivery system) that are more suitable for use in VLW infants (Figure).1US Food and Drug Administration Premarket Approval (PMA) of the AMPLATZER Piccolo Occluder. US Food and Drug Administration, Atlanta2019Google Scholar, 9Kenny D. Morgan G.J. Bentham J.R. Wilson N. Martin R. Tometzki A. et al.Early clinical experience with a modified Amplatzer Ductal Occluder for transcatheter arterial duct occlusion in infants and small children.Catheter Cardiovasc Interv. 2013; 82: 534-540PubMed Google Scholar Healthcare professionals are left with an Food and Drug Administration-approved, nonsurgical alternative to achieve definitive ductal closure.1US Food and Drug Administration Premarket Approval (PMA) of the AMPLATZER Piccolo Occluder. US Food and Drug Administration, Atlanta2019Google Scholar However, the clinical benefits of closing a PDA among VLW infants remain unknown.10Benitz W.E. American Academy of Pediatrics Committee on Fetus and NewbornPatent ductus arteriosus in preterm infants.Pediatrics. 2016; 137 (e20153730)Crossref Scopus (79) Google Scholar Not surprisingly, treatment strategies vary markedly among institutions, with some centers aggressively pursuing PDA closure based on evidence that a persistent ductus is associated with greater rates of mortality and linked to harmful longer term outcomes, including chronic lung disease and heart failure.11Brown E.R. Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus.J Pediatr. 1979; 95: 865-866Abstract Full Text PDF PubMed Scopus (149) Google Scholar, 12Elhoff J.J. Ebeling M. Hulsey T.C. Atz A.M. Potential unintended consequences of a conservative management strategy for patent ductus arteriosus.Congenit Heart Dis. 2016; 11: 52-57Crossref PubMed Scopus (10) Google Scholar, 13Noori S. McCoy M. Friedlich P. Bright B. Gottipati V. Seri I. et al.Failure of ductus arteriosus closure is associated with increased mortality in preterm infants.Pediatrics. 2009; 123: e138-e144Crossref PubMed Scopus (253) Google Scholar Alternatively, some centers, based on evidence that all forms of deliberate ductal closure have the potential for adverse side effects and that no studies have shown that treating all preterm infants with a PDA improves outcomes, have adopted a conservative (nonintervention) approach.14Letshwiti J.B. Semberova J. Pichova K. Dempsey E.M. Franklin O.M. Miletin J. A conservative treatment of patent ductus arteriosus in very low birth weight infants.Early Hum Dev. 2017; 104: 45-49Crossref PubMed Scopus (45) Google Scholar, 15Vanhaesebrouck S. Zonnenberg I. Vandervoort P. Bruneel E. Van Hoestenberghe M.R. Theyskens C. Conservative treatment for patent ductus arteriosus in the preterm.Arch Dis Child Fetal Neonatal Ed. 2007; 92: F244-F247Crossref PubMed Scopus (91) Google Scholar These 2 approaches frame the ongoing debate and controversy regarding PDA treatment. A summary of the published evidence on the use of Amplatzer Piccolo Occluder among VLW infants is provided, including a description of feasibility (technical success) and major adverse events (AEs; Table).16Sungur M. Karakurt C. Ozbarlas N. Baspinar O. Closure of patent ductus arteriosus in children, small infants, and premature babies with Amplatzer duct occluder II additional sizes: multicenter study.Catheter Cardiovasc Interv. 2013; 82: 245-252Crossref PubMed Scopus (47) Google Scholar, 17Agnoletti G. Bordese R. Gabbarini F. Closure of a large ductus arteriosus in a preterm infant using the ADO II AS device.Heart. 2012; 98: 1394Crossref PubMed Scopus (5) Google Scholar, 18Narin N. Pamukcu O. Baykan A. Sunkak S. Ulgey A. Uzum K. Percutaneous PDA closure in extremely low birth weight babies.J Interv Cardiol. 2016; 29: 654-660Crossref PubMed Scopus (16) Google Scholar, 19Narin N. Pamukcu O. Baykan A. Argun M. Ozyurt A. Bayram A. et al.Transcatheter closure of PDA in premature babies less than 2 kg.Anatol J Cardiol. 2017; 17: 147-153PubMed Google Scholar, 20Morville P. Akhavi A. Transcatheter closure of hemodynamic significant patent ductus arteriosus in 32 premature infants by Amplatzer Ductal Occluder additional size-ADOIIAS.Catheter Cardiovasc Interv. 2017; 90: 612-617Crossref PubMed Scopus (41) Google Scholar, 21Morville P. Douchin S. Bouvaist H. Dauphin C. Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g.Arch Dis Child Fetal Neonatal Ed. 2018; 103: F198-F201Crossref PubMed Scopus (23) Google Scholar, 22Rodriguez Ogando A. Ballesteros Tejerizo F. Blanco Bravo D. Sanchez Luna M. Zunzunegui Martinez J.L. Transcatheter occlusion of patent ductus arteriosus in preterm infants weighing less than 2 kg with the Amplatzer Duct Occluder II additional sizes device.Rev Esp Cardiol (Engl Ed). 2018; 71: 865-866PubMed Google Scholar, 23Rodriguez Ogando A. Planelles Asensio I. de la Blanca A.R.S. Ballesteros Tejerizo F. Sanchez Luna M. Gil Jaurena J.M. et al.Surgical ligation versus percutaneous closure of patent ductus arteriosus in very low-weight preterm infants: which are the real benefits of the percutaneous approach?.Pediatr Cardiol. 2018; 39: 398-410Crossref PubMed Scopus (42) Google Scholar, 24Berman D. Sathanandam S. Forbes T. Gillespie M. Morray B. Shahanavaz S. Closure of patent ductus arteriosus with the Amplatzer Piccolo Occluder in premature infants.in: Paper presented at the Pediatric Academic Society. April 29-May 6. 2019Google Scholar According to federal regulations, the Food and Drug Administration is tasked with ensuring that “there is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.”26US Food and Drug Administration Electronic Code of Federal Regulations.www.ecfr.gov/cgi-bin/text-idx?SID=97fdb09c5c89bb259b9a960993eb7702&mc=true&node=pt21.8.860&rgn=div5#se21.8.860_17Google Scholar Based on available evidence, the Food and Drug Administration concluded that the device met thresholds for approval. What outcomes are considered “clinically significant”? Would occluding the PDA and eliminating the left-to-right shunt, suffice? Or is evidence that, compared with alternative treatment strategies, percutaneous occlusion improves longer term outcomes, necessary? When healthcare providers offer treatments for the PDA, they do so in anticipation that the potential risks are justified by the potential benefits.27Slaughter J.L. Reagan P.B. Bapat R.V. Newman T.B. Klebanoff M.A. Nonsteroidal anti-inflammatory administration and patent ductus arteriosus ligation, a survey of practice preferences at US children's hospitals.Eur J Pediatr. 2016; 175: 775-783Crossref PubMed Scopus (28) Google Scholar Although the technical feasibility and short-term safety profile of the device are promising,24Berman D. Sathanandam S. Forbes T. Gillespie M. Morray B. Shahanavaz S. Closure of patent ductus arteriosus with the Amplatzer Piccolo Occluder in premature infants.in: Paper presented at the Pediatric Academic Society. April 29-May 6. 2019Google Scholar the lack of comparative studies and longer term efficacy results have left healthcare providers with insufficient evidence to guide the practice of evidence-based medicine. In other words, “just because we can, does not mean we should.”TableAmplatzer Piccolo Occluder use among VLW (<2.5 kg) infantsFirst authors (Publication year)YearType of studySingle or multicenterNo. of successful implants/No. of attempted implantsWeight (kg) at time of procedureNo. of major AEs∗As defined by Bergersen et al.25Sungur et al16Sungur M. Karakurt C. Ozbarlas N. Baspinar O. Closure of patent ductus arteriosus in children, small infants, and premature babies with Amplatzer duct occluder II additional sizes: multicenter study.Catheter Cardiovasc Interv. 2013; 82: 245-252Crossref PubMed Scopus (47) Google Scholar2013RetrospectiveSingle center6/71.8 ± 0.40Agnoletti et al17Agnoletti G. Bordese R. Gabbarini F. Closure of a large ductus arteriosus in a preterm infant using the ADO II AS device.Heart. 2012; 98: 1394Crossref PubMed Scopus (5) Google Scholar2016RetrospectiveSingle center1/12.010Narin et al18Narin N. Pamukcu O. Baykan A. Sunkak S. Ulgey A. Uzum K. Percutaneous PDA closure in extremely low birth weight babies.J Interv Cardiol. 2016; 29: 654-660Crossref PubMed Scopus (16) Google Scholar2016RetrospectiveSingle center10/100.9 ± 0.10Narin et al19Narin N. Pamukcu O. Baykan A. Argun M. Ozyurt A. Bayram A. et al.Transcatheter closure of PDA in premature babies less than 2 kg.Anatol J Cardiol. 2017; 17: 147-153PubMed Google Scholar2017RetrospectiveSingle center12/121.4 ± 0.40Morville et al20Morville P. Akhavi A. Transcatheter closure of hemodynamic significant patent ductus arteriosus in 32 premature infants by Amplatzer Ductal Occluder additional size-ADOIIAS.Catheter Cardiovasc Interv. 2017; 90: 612-617Crossref PubMed Scopus (41) Google Scholar,†Potential overlap between studies.2017ProspectiveSingle center31/321.4 ± 0.57‡Cardiac perforation by catheter wire, death (n = 1); blood loss, transfusion required (n = 1); hypotension, treatment required (n = 5).Morville et al21Morville P. Douchin S. Bouvaist H. Dauphin C. Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g.Arch Dis Child Fetal Neonatal Ed. 2018; 103: F198-F201Crossref PubMed Scopus (23) Google Scholar,†Potential overlap between studies.2018ProspectiveSingle center17/181.0 ± 0.26§Cardiac preformation by catheter wire, death (n = 1); blood loss, transfusion required (n = 1); hypotension, treatment required (n = 4).Rodriguez Ogando et al22Rodriguez Ogando A. Ballesteros Tejerizo F. Blanco Bravo D. Sanchez Luna M. Zunzunegui Martinez J.L. Transcatheter occlusion of patent ductus arteriosus in preterm infants weighing less than 2 kg with the Amplatzer Duct Occluder II additional sizes device.Rev Esp Cardiol (Engl Ed). 2018; 71: 865-866PubMed Google Scholar,¶Potential overlap between studies.2018RetrospectiveSingle center27/271.26 (1.0-1.98)2Embolization (n = 2); “surgical complications” noted in 3 other cases with no further elaboration.Rodriguez Ogando et al23Rodriguez Ogando A. Planelles Asensio I. de la Blanca A.R.S. Ballesteros Tejerizo F. Sanchez Luna M. Gil Jaurena J.M. et al.Surgical ligation versus percutaneous closure of patent ductus arteriosus in very low-weight preterm infants: which are the real benefits of the percutaneous approach?.Pediatr Cardiol. 2018; 39: 398-410Crossref PubMed Scopus (42) Google Scholar,¶Potential overlap between studies.2018RetrospectiveSingle center25/251.33 ± 0.282Embolization (n = 2), percutaneous retrieval.Berman et al24Berman D. Sathanandam S. Forbes T. Gillespie M. Morray B. Shahanavaz S. Closure of patent ductus arteriosus with the Amplatzer Piccolo Occluder in premature infants.in: Paper presented at the Pediatric Academic Society. April 29-May 6. 2019Google Scholar,Abstract only.2019ProspectiveMulticenter71/731.6 ± 0.81Embolization, percutaneous retrieval.Studies were included if the mean or median patient weight was <2.5 kg. Studies that enrolled mixed populations (infants and older children or adults) were included if individual outcomes among infants <2.5 kg could be ascertained. Studies that included various PDA closure devices were included if outcomes among infants <2.5 kg with Amplatzer Piccolo Occluder (or Amplatzer ductal occluder additional sizes, ADO-II AS) could be ascertained.∗ As defined by Bergersen et al.25Bergersen L. Gauvreau K. Marshall A. Kreutzer J. Beekman R. Hirsch R. et al.Procedure-type risk categories for pediatric and congenital cardiac catheterization.Circ Cardiovasc Interv. 2011; 4: 188-194Crossref PubMed Scopus (94) Google Scholar† Potential overlap between studies.‡ Cardiac perforation by catheter wire, death (n = 1); blood loss, transfusion required (n = 1); hypotension, treatment required (n = 5).¶ Potential overlap between studies.§ Cardiac preformation by catheter wire, death (n = 1); blood loss, transfusion required (n = 1); hypotension, treatment required (n = 4).∗∗ Embolization (n = 2); “surgical complications” noted in 3 other cases with no further elaboration.†† Embolization (n = 2), percutaneous retrieval.‡‡ Abstract only.§§ Embolization, percutaneous retrieval. Open table in a new tab Studies were included if the mean or median patient weight was <2.5 kg. Studies that enrolled mixed populations (infants and older children or adults) were included if individual outcomes among infants <2.5 kg could be ascertained. Studies that included various PDA closure devices were included if outcomes among infants <2.5 kg with Amplatzer Piccolo Occluder (or Amplatzer ductal occluder additional sizes, ADO-II AS) could be ascertained. A number of strategies are available to accumulate evidence to better define optimal use of the device. Transparent, publicly reported, postmarketing surveillance is 1 strategy to inform healthcare providers, families, and regulators, particularly regarding device-related AEs.28Resnic F.S. Majithia A. Marinac-Dabic D. Robbins S. Ssemaganda H. Hewitt K. et al.Registry-based prospective, active surveillance of medical-device safety.N Engl J Med. 2017; 376: 526-535Crossref PubMed Scopus (57) Google Scholar Traditionally, the Food and Drug Administration relied on healthcare providers to report AEs attributable to a medical device.29Resnic F.S. Matheny M.E. Medical devices in the real world.N Engl J Med. 2018; 378: 595-597Crossref PubMed Scopus (26) Google Scholar However, healthcare providers may underreport such events, with some studies suggesting that only 1% of all device-related AEs are reported to the Food and Drug Administration, with more serious AEs less likely to be reported.29Resnic F.S. Matheny M.E. Medical devices in the real world.N Engl J Med. 2018; 378: 595-597Crossref PubMed Scopus (26) Google Scholar In response, regulatory agencies and investigators are increasingly turning to active surveillance models.30US Food and Drug Administration FDA facts: postmarket patient registry ensures access to safe and effective devices.www.fda.gov/aboutfda/innovation/ucm484826.htmGoogle Scholar Active surveillance uses either formal registries with ongoing contact with providers to monitor outcomes and side effects over time or a more sophisticated use of electronic health records as a virtual registry. One noteworthy effort that will combine these methods, and is currently being promoted by the Food and Drug Administration, is the National Evaluation System for health Technology (NEST).31US Food and Drug Administration National Evaluation System for Health Technology (NEST).www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhreports/ucm301912.htmGoogle Scholar NEST is a network of data partners, predominantly industry, across the medical device ecosystem. The primary goal of NEST is to generate informative clinical knowledge from diverse data sources (electronic health records, billing data, and clinical registries) in an effort to identify safety problems more quickly and to understand better the benefit–risk profiles of devices as used in clinical care.32Shuren J. Califf R.M. Need for a national evaluation system for health technology.JAMA. 2016; 316: 1153-1154Crossref PubMed Scopus (86) Google Scholar Moreover, NEST is seeking nontraditional partners like PEDSnet, a consortium of the nation's largest children's hospitals engaged in a unified electronic health record system for longitudinal studies, to combine the best methods from registries and records.23Rodriguez Ogando A. Planelles Asensio I. de la Blanca A.R.S. Ballesteros Tejerizo F. Sanchez Luna M. Gil Jaurena J.M. et al.Surgical ligation versus percutaneous closure of patent ductus arteriosus in very low-weight preterm infants: which are the real benefits of the percutaneous approach?.Pediatr Cardiol. 2018; 39: 398-410Crossref PubMed Scopus (42) Google Scholar Because the risk–benefit profiles of percutaneous occlusion are likely to change over time (refinements in clinical technique) and vary according to patient (degree of prematurity, birth weight, severity of respiratory disease, duration of PDA exposure from birth, and PDA size and illness severity), procedural (anesthesia, operator experience), and institutional (site volume) characteristics, the mechanisms for guiding active surveillance of these data as they accumulate are necessary to minimize risk and yield the greatest benefits from this novel device. At present, the optimal use of the Amplatzer Piccolo Occluder is unknown because of the lack of comparative trials with alternative PDA treatments (conservative treatment, surgical ligation). Acknowledging the lack of data, the American Academy of Pediatrics has emphasized the need for equipoise among healthcare providers regarding enrollment of preterm infants into clinical trials designed to assess PDA treatment strategies.10Benitz W.E. American Academy of Pediatrics Committee on Fetus and NewbornPatent ductus arteriosus in preterm infants.Pediatrics. 2016; 137 (e20153730)Crossref Scopus (79) Google Scholar To inform the practice of evidence-based medicine, prospective clinical trials that compares percutaneous closure vs alternative treatment strategies using well-defined inclusion criteria, consistently applied treatment protocols, careful attention to potentially harmful exposures (anesthesia, sedation, radiation), mechanisms for AE surveillance, and longer term follow-up, are needed. This effort will require interdisciplinary (neonatology, pediatric cardiology, congenital cardiac catheterization, anesthesiology), and multi-institutional cooperation. Before the accumulation of sufficient evidence, we suggest a number of potential strategies for the ongoing use of the device in the pediatric community. First, the device should be restricted to healthcare providers with requisite expertise and experience, and institutions with the infrastructure and interdisciplinary collaboration necessary for robust preprocedural and postprocedural evaluation and surveillance. Second, rather than an all-or-none approach, selective use of percutaneous PDA closure in the subgroup of infants beyond the window when drug therapy is most efficacious or spontaneous closure has yet to occur, and who continue to have adverse ductal sequelae, may optimize the risk–benefit profiles. Third, patient selection for device use should be based on clear evidence of a hemodynamically significant PDA that takes into account indicators (clinical, echocardiographic, biomarkers) of adverse ductal consequences. For example, rather than relying on ductal diameter alone as the primary marker of echocardiographic disease severity, additional measurements (eg, left ventricular output, shunt volume) may provide insights regarding the magnitude of the physiologic disturbance.33El-Khuffash A. James A.T. Corcoran J.D. Dicker P. Franklin O. Elsayed Y.N. et al.A patent ductus arteriosus severity score predicts chronic lung disease or death before discharge.J Pediatr. 2015; 167: 1354-1361e2Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar Fourth, to inform the practice of fiscal stewardship, formal economic evaluations alongside clinical trials are necessary. Finally, the unique and complex ductal morphology of VLW infants warrants careful consideration of alternative devices (eg, Medtronic Micro Vascular Plug [Medtronic, Dublin, Ireland], Amplatzer Vascular Plug II) with high rates of technical feasibility and evidence of short-term benefits.34Zahn E.M. Peck D. Phillips A. Nevin P. Basaker K. Simmons C. et al.Transcatheter closure of patent ductus arteriosus in extremely premature newborns: early results and midterm follow-up.JACC Cardiovasc Interv. 2016; 9: 2429-2437Crossref PubMed Scopus (76) Google Scholar, 35Sathanandam S. Justino H. Waller 3rd, B.R. Radtke W. Qureshi A.M. Initial clinical experience with the Medtronic Micro Vascular Plug in transcatheter occlusion of PDAs in extremely premature infants.Catheter Cardiovasc Interv. 2017; 89: 1051-1058Crossref PubMed Scopus (58) Google Scholar Although the Amplatzer Piccolo Occluder provides the healthcare community with a nonsurgical alternative to achieve definitive ductal closure, fundamental questions on the optimal use of the device remain unanswered.36Willis K.A. Weems M.F. Hemodynamically significant patent ductus arteriosus and the development of bronchopulmonary dysplasia.Congenit Heart Dis. 2019; 14: 27-32Crossref PubMed Scopus (16) Google Scholar Active surveillance and routine monitoring of percutaneous PDA closure devices may provide opportunities for earlier identification of adverse safety signals, which can inform healthcare providers, families, and regulators about potential problems or unexpected benefits. In the absence of comparative data, pragmatic, well-designed prospective trials with longer term, clinically meaningful outcomes, are needed.