Percutaneous Closure of Patent Foramen Ovale Sponsors: Kung Ming Jan, M.D., Ph.D. Judah Weinberger, M.D., Ph.D. Columbia University Medical Center Department of Cardiology Project TA: Jeffrey Garanich, Ph.D. Design Team: Ali Stern Dmitry Oulianov Dolores Miranda Henry Qazi Safiya Arif The City College of New York / Department of Biomedical Engineering

Prenatal oxygenation of blood bypasses lungs. Prenatal oxygenation of blood bypasses lungs. Oxygenated blood passes from right to left atrium through the foramen ovale (FO). Oxygenated blood passes from right to left atrium through the foramen ovale (FO). Fetal circulation Fetal Circulation

Septum primum and secundum overlap. Septa create an opening to allow direct shunting of fetal blood. Prenatal Septal Development

Following birth the P of each chamber changes. Following birth the P of each chamber changes. P changes force septum primum to close over septum secundum. P changes force septum primum to close over septum secundum. In a period of 1-2 weeks 70% of population have fusion of septa primum and secundum. In a period of 1-2 weeks 70% of population have fusion of septa primum and secundum. Neonatal Septal Development

The condition in which the septa fail to seal over and remain patent is known as ASD. The condition in which the septa fail to seal over and remain patent is known as ASD. ASD is an opening (hole) between right and left atria. ASD is an opening (hole) between right and left atria. Atrial Septal Defect

Patent Foramen Ovale PFO, a type of ASD, is a flap- like opening between the atrial septa primum and secundum PFO, a type of ASD, is a flap- like opening between the atrial septa primum and secundum

Clinical Need PFO is present in 20-25% of the population PFO is present in 20-25% of the population PFO has been associated with: PFO has been associated with: Migraines Cryptogenic strokes Systemic embolism

Migraine is a vascular headache Migraine is a vascular headache Over 2,500,000 people in the U.S. have at least one migraine weekly, with a lifetime prevalence of 18% Over 2,500,000 people in the U.S. have at least one migraine weekly, with a lifetime prevalence of 18% PFO are related to Migraines if paradoxic embolism causes headache PFO are related to Migraines if paradoxic embolism causes headache Migraine

Cryptogenic strokes There are 700,000 strokes per year in the U.S. There are 700,000 strokes per year in the U.S % of these are cryptogenic 30-40% of these are cryptogenic 40-70% of cryptogenic strokes are PFO related 40-70% of cryptogenic strokes are PFO related 84, ,000 strokes per year in the United States are by paradoxical embolism due to PFO 84, ,000 strokes per year in the United States are by paradoxical embolism due to PFO

Treatment Options Medical Treatment Medical Treatment Open heart surgery to close the PFO Open heart surgery to close the PFO Percuteneous closure of the PFO Percuteneous closure of the PFO

CardioSeal 2 Double Umbrella implant 2 Double Umbrella implant MP35N Framework MP35N Framework Dacron Dacron Sizes: 17-33mm Sizes: 17-33mm

Amplazter Self expandable Self expandable Short connecting waist Short connecting waist Nitinol Wires Nitinol Wires Sizes: 4-38mm Sizes: 4-38mm

Amplazter Delivery

Disadvantages Designed for ASD Designed for ASD Large surface Area Large surface Area Thrombus formation Thrombus formation Reduced Endothelialization Reduced Endothelialization Poor Apposition Poor Apposition Device Fracture Device Fracture Device Embolization Device Embolization

 Seals PFO only  Consists of two components  Delivery unit  Means of closure  Size requirements  Delivery size: mm diameter  Deployment size: 3.6 x 4.2 cm  Seals area of 8 mm radius around PFO  Biocompatibility  Immunological response  Thrombogenic response  Single use Required Specifications

 Electrical isolation  Isolate main voltage source  Prevent current leakage  Current limits  Direct current < 1 μA  Alternating current < 0.4 μA  Mechanical forces  Structural flexibility Mechanical & Electrical Stability

 Easily operable  Cost efficient  Biodegradable  Degradation time  Particle size  Visible by ultrasound  Non-magnetic Desired Specifications

 In Vitro  Reaction to environment  Fatigue test  Maneuverability  Catheter-device integrity  In Vivo*  Dog testing  Human testing *Evaluation may not be performed in the scope of the project Device Evaluation

Concepts Glue or collagen plugs Glue or collagen plugs Magnetic suturing Magnetic suturing Energy welding devices Energy welding devices Staple pins/sutures Staple pins/sutures Scaffold Scaffold Clipping device Clipping device Intra atrium device Intra atrium device Coiled suturing device Coiled suturing device “Sutura” model “Sutura” model

Hooked Scaffold Implant Polyester scaffold Polyester scaffold Advantages: Advantages: Material Degradation into H2O & CO2 Material Degradation into H2O & CO2 Disadvantages : Disadvantages : Material: too stiff for delivery Material: too stiff for delivery

Intra atrium device (IAD) Advantages: Advantages: Minimal amount of foreign material in the body Minimal amount of foreign material in the body Does not require exact positioning Does not require exact positioning Disadvantages: Disadvantages: Material selection: Complicated knot delivery method

Coiled needle Components: coiled needle, 16mm base unit Components: coiled needle, 16mm base unit Advantages: Advantages: Does not require exact positioning Does not require exact positioning Disadvantages: Disadvantages: Complicated mechanics Complicated mechanics Requires electrical energy Requires electrical energy Complicated knot delivery method Complicated knot delivery method

Sutura Model Suturing device Suturing device Components: 2 retractable arms, thread attached, 2 needles, handle Components: 2 retractable arms, thread attached, 2 needles, handle Advantages: Advantages: Existing device provides successful mechanism Existing device provides successful mechanism Disadvantages: Disadvantages: Complicated manufacturing Complicated manufacturing

Clipping Device Advantages: Advantages: Procedure using the device is reversible in case of failure Simple deployment mechanism Disadvantages: Disadvantages: Requires precision Material properties

Acknowledgements Kung Ming Jan, M.D., Ph.D. Kung Ming Jan, M.D., Ph.D. Judah Weinberger, M.D., Ph.D. Judah Weinberger, M.D., Ph.D. Columbia University Medical Center Columbia University Medical Center Department of Cardiology Department of Cardiology Project TA: Jeffrey Garanich, Ph.D. Project TA: Jeffrey Garanich, Ph.D. Robert Sommer, M.D., Ph.D. Robert Sommer, M.D., Ph.D.