Trans catheter closure of Preterm Ductus Arteriosus Dr.Sajit Augustine TnECHO Fellow, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.

Patent ductus arteriosus Persistent patent ductus arteriosus is associated with earlier gestational age and lower birth weight. Rates of patent ductus arteriosus in preterm infants range from 29 to 80%, depending on the population studied. PS Shah et al: Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?

PDA Management: A continuing conundrum

Surgical Ligation Hemodynamically significant PDA + medical Rx failed Unstable babies Contraindications to medical Rx NEC IVH ARF

Surgical Ligation-Complications Little :Texas 212 babies Median GA 26wks, 72 babies ligated Afif 30 babies Mean GA 25.3wks Solid line: Low LVO Dotted line: High LVO

Surgical Ligation-Long term outcomes 500-999g TIPP study (1996-98) Journal of Peds 2007 Post hoc analysis 426 with symptomatic PDA 316 Medical therapy 110 PDA ligation

Surgical Ligation-Long term outcomes Pediatrics 2009 NICHD Neonatal Research Network: 2000-2004, 23-28wks, <1000g N=2838 Supportive: 403 Indo: 1525 Indo+Surgery: 775 Primary surgery: 135 Primary surgery: Increased odds for NDI/BPD Secondary surgery: Increased odds for NDI/BPD

Surgical Ligation-Long term outcomes JAMA Peds Retrospective cohort 2006-2012 N=754, <28wks HSPDA 184 ligations Adjusted for pre ligation morbidities: No difference in the odds of death or NDI, CLD, ROP

Surgical ligation- Variability of Practice Diagnosis rate for each state determined by the number of PDA diagnoses per preterm infant in that state. Ligation rate for each state determined by the number of PDA ligations per preterm infant with a PDA in that state. States of California, Colarado, New Mexico, Nevada, Oklahoma: Highest rate of diagnosis High Ligation rates: Hawaii, Minnesota, Oregon, Oklahoma Weinberg et al, 2016

Surgical Ligation-Summary Surgical ligation is associated with significant procedural morbidity and may or may not be associated with adverse long term outcomes. Is there an alternative?

Transcatheter closure of PDA

Percutaneous Ligation-Proof of Concept Portsmann’s Ivalon plug Rashkind PDA Occluder system Portsmann et al. 1966, 1st transcatheter closure of a PDA without thoracotomy in a 17-year-old boy. The device used was an Ivalon plug, introduced through an 18 F femoral arterial sheath and travelling on a percutaneously laid transductal arteriovenous guide wire. Rashkind: First in Infants (<3500g). Two polyurethane discs mounted on opposing three- or four-arm spines were assembled, resembling two umbrellas. The 146 patients treated in 1987. Success rate: 66% Device embolization:15% Disadvantage: Large & bulky size of the arterial delivery sheath. Portsmann Ivalon plug 13F-28F femoral arterial access Rashkind double disc 8F-11F femoral venous access

Percutaneous Ligation-Proof of Concept Sideris-1993 Clamshell septal umbrella Sideris: Buttoned device. 7F Lock Clamshell device

Premature enthusiasm? High incidence of residual leak Problems Desirable High incidence of residual leak Risk of endarteritis Device instability Major complications Delivery via a small-sized catheter. Repositioning of the device multiple times Easy retrieval of the device. Ability to allow for complete closure without causing any aortic/pulmonary artery obstruction or damage. Gradually abandoned because of a high incidence of residual leak and subsequent persistent risk of endarteritis, device instability or other major complications. Thus, despite initial widespread enthusiasm, reproducible and safe percutaneous PDA closure proved to be more difficult than initially estimated.

Embolization coils Immediate success rate 75-95% Rate of closure inversely related to the size of the ductus. Operator dependent Inexpensive & feasible via small catheter. Unacceptably high rate of coil embolization

Amplatzer Duct Occluder Self expandable repositionable mushroom-shaped device 0.004- inch-thick nitinol wire mesh with Dacron patches within. Masura et al.(1998) reported the initial successful experience with the ADO in 24 patients using an antegrade approach and a transvenous 6F delivery sheath. Masura: Median age of 3.8 years (range 0.4 to 48) and a median weight of 15.5 kg (range 6 to 70). The mean PDA diameter at its narrowest segment was 3.7 +/- 1.5 mm.

The Present: daily practice in the Cath lab Treatment of choice for most PDAs in term infants, children and adults. Timing: Delayed if feasible, until later in the 1st year of life (peripheral vascular injury risk) Pre catheterization care Rule out infection ECHO: Associated lesions, LV volume diameters, Function, PDA size, Pulm art pressure, hemodynamic significance of PDA.

Angiographic classification Krichenko et al described ductal anatomy in lateral projection Type A: Conical ductus Type B: Large and very short ductus Type C: Tubular duct Type D: Multiple constrictions on the ductus. Type E: Elongated ductus. Angiography with 4F/5F pigtail catheter in proximal descending Ao Type A: Well defined Ao ampulla & constriction at pulmonary end. Type B: Mimicks AoPulmonary window. Type C: Varying length, no constriction at pulmonary end.

Coil occlusion Safe & effective for small PDA (<1.5-2mm) 3:1 principle Krichenko type A1 or E Technique: Most common: Arterial retrograde. Indication: 3:1 principle, the coil is the chosen strategy if the total ductal length is more than three times the narrowest diameter of the PDA. Or minimal ductal diameter < 1.5—2 mm as an indication for coil implantation, as device implantation in such small PDAs can be challenging. Shorter ducts/>3mm ducts: Residual shunts or coil embolization. Steps Femoral access 4F/5F pigtail cath in Prox Desc Ao- Angiography PDA is crossed by a 0.035 inch wire and a delivery catheter is then advanced over the wire into the main pulmonary artery (MPA) Rule of thumb, a coil is chosen with a loop diameter that is a minimum of two times the diameter of the narrowest segment of the ductus and the length of coil is suitable to allow for four or five coil loops. Non-ferromagnetic coils (e.g. MREYE) are more commonly used than the prior stainless steel variety.

Device Occlusion ADO most commonly used device worldwide. Approved for >6months & >6kg Antegrade approach PDA >2mm+ sufficient aortic ampulla 0.035-inch wire is passed anterograde from the MPA, across the ductus to the abdominal aorta. Delivery sheath ADO device is positioned Retention skirt deployed first in Desc Ao

Transcatheter-Results and complications Incomplete closure High-velocity residual shunting: Endocarditis, hemolysis. Embolization: Pulmonary arteries, systemic artery. LPA stenosis or coarctation of aorta: LBW, Large PDA with large device. Pass et al: ADO: Successful implantation 99%, Acute angiographic occlusion: 76%, Post cath Day 1: 89%, 1yr: 99.7% Incomplete Closure: Needs Repeated procedures. Embolization: 1% occurrence rate Device closure: Acceptable to leave Cath lab with residual shunting. PDA coil embolization: Leave cath lab only after documentation of angiographical closure.

Post catheterization care Prophylactic antibiotics Post op CXR and ECHO Follow up No residual shunt, normal LV and pulm artery pressure: None after 6 months. LV dysfunction & PAH: q1-3yrs CXR:/ECHO: Confirm position of device/coil, absent of residual shunt.

How rigorous is the evidence regarding technical success and safety?

Search Date Dec 2015 Outcomes: Technical success Safey 38 studies included Significant heterogeneity Publication Bias

Overall adverse Events

Clinically significant adverse events

Transcatheter closure in Preterm & LBW Challenges: Sheath size, stiffness of delivery system, protrusion risk of device in LPA or Ao, technical difficulties for device retrieval. Off-label ADO.

French Muticentre study 58 infants <6kg Success rate 89.7% Procedure related mortality 1.7% Major complication rate: 6.9% Minor complication rate 31% Conclusion: Recommend surgery over percutaneous closure in LBW

62 patients Success rate: 94% No deaths

8 infants <2kg (930-1800g) Coil Case selection: Patient’s weight, PDA size, size of ampulla, and the anticipated coil mass required for complete closure (determined through echocardiography). Success rate: 100% No major procedure or access related complications

The future: new devices and perspectives Growing experience Miniaturization of materials Newer devices: Amplatzer Duct Occluder II

Perspectives Trancatheter closure of PDA remains a challenge in preterm and LBW infants New generation of devices Shorter Large choice of available diameters Suitable for 3F or 4F sheath. Which preterm and how? Fluoroscopic radiation dose or no fluoroscopy (ECHO guided?)

Thank you Questions?