Patent Ductus Arteriosus Occlusion Device



Patent Ductus Arteriosus Occlusion Device

David Brogan, Darci Phillips and Daniel Schultz

Department of Biomedical Engineering

Vanderbilt University

April 22, 2002

Advisor: Dr. Thomas Doyle

Assistant Professor of Pediatrics, Pediatric Cardiology

Vanderbilt University Medical Center

Instructor: Dr. Paul King

Associate Professor Biomedical and Mechanical Engineering

Vanderbilt University

TABLE OF CONTENTS

1. ABSTRACT 2

2. INTRODUCTION 3

2.1 The Patent Ductus Arteriosus (PDA) 3

2.2 Current Treatments 4

2.3 Design Goals 8

3. METHODOLOGY 9

3.1 Background 9

3.2 Initial Work 10

3.3 Prototype Development 12

4. RESULTS 13

4.1 Preliminary Tests 13

4.2 Safety Analysis 14

4.3 Market Analysis 16

4.4 Device Patenting 16

4.5 Economic Analysis 17

5. CONCLUSIONS 19

6. FUTURE WORK AND RECOMMENDATIONS 20

7. ACKNOWLEDGEMENTS 20

8. REFERENCES 20

Appendices 22

1. ABSTRACT

Patent ductus arteriosus is the persistence after birth of an in-utero shunt from the pulmonary artery to the aorta. To correct this deficiency, an elective procedure is performed at five to ten years of age to close the hole. Current treatment involves catheter insertion of fibrous coils into the duct, relying on endothelialization to completely occlude flow. This project sought to build on two previous groups’ efforts to design an alternative closure device. The final design involves a mushroom shaped foam device held rigid by the insertion of a Nitinol backbone. Biocompatible materials were investigated, specifically a polyurethane foam and resulting prototypes built out of silicone and foam. Both pressure and flow tests were performed on both prototypes to measure their efficacy at occluding flow. The foam device proved to be more compressible and easier to insert, but does not completely stop the flow of water. The silicone completely stopped the flow of water, but did not compress fully into the catheter. A polymer specialty firm (PTG) has been contacted to make a certified prototype out of a custom foam and initial steps have been taken in the application for a patent.

2. INTRODUCTION

2.1 The Patent Ductus Arteriosus (PDA)

The ductus arteriosus is a normal fetal structure, connecting the pulmonary artery and the aorta. Prior to birth the fetus receives oxygen through the mother’s placenta, as his/her lungs are not yet fully developed. Therefore, the ductus arteriosus allows blood to bypass the nonfunctioning pulmonary circulatory system and enters the systemic circulatory system. At birth the placenta is removed when the umbilical cord is cut, the baby begins to breathe on his/her own, and the blood supply to the ductus arteriosus decreases dramatically. As a result the ductus arteriosus closes within 15 hours of delivery [5]. However, if it fails to close within three months of birth, patent (open) ductus arteriosus (PDA) occurs and blood continues to flow from the aorta to the pulmonary artery (Fig. 1).

PDA accounts for 10-12% of all congenital defects and has an estimated incidence of more than 20,000 cases in the United States alone [3]. Additionally, PDA occurs twice as often in girls as in boys. Although the causes of PDA remain unknown, this condition is seen more often in premature infants and infants born to a mother who had rubella (German measles) during the first trimester of pregnancy [11]. Some congenital heart defects may have a genetic link, either occurring due to a gene defect, a chromosome abnormality, or environmental exposure, causing heart problems in certain families to increase [9]. However, PDA typically occurs sporadically, with no clear reason for its development.

Depending on the size and impact of the PDA on the circulatory system, this condition may result in many adverse effects. When the ductus arteriosus remains open, oxygenated blood passes from the aorta to the pulmonary artery, mixing with deoxygenated blood already flowing to the lungs. The effects of this altered circulation may be life-threatening due to pulmonary over-circulation, which may lead to an increased lung workload and fluid in the lungs [11]. Since the PDA creates a hole in the aorta, the pressure in the aorta decreases dramatically. Consequently, there is an increased workload on the heart and an increased risk of congestive heart failure over time [3]. Additionally, the PDA increases the volume load on the left atrium and ventricle of the heart [3]. Furthermore, because the blood is pumped at high pressure through the PDA, the lining of the pulmonary artery becomes irritated and inflamed. Bacteria in the bloodstream can easily infect this injured area, causing a serious illness known as bacterial endocarditis [9].

The size of the PDA (ranges from 2-8 mm, average of 3.1 mm) affects the type of symptoms noted and the severity of the symptoms. A child with a small PDA may reveal a continuous heart murmur, while infants with a larger PDA may exhibit different symptoms; the most common being fatigue, rapid, heavy or congested breathing, a lack of appetite, poor weight gain, and growth retardation [14].

2.2 Current Treatments

Multiple treatments for PDA have been developed, including drug therapy, surgery and implantable devices. Indomethacin is the most commonly used intravenous medication for treating PDA. A relative of aspirin and ibuprofen, indomethacin, works by stimulating the muscles inside the PDA to constrict, thereby closing the connection [6]. This is typically the first method physicians try. It is a safe alternative to the more invasive procedures, such as surgery and the use of implantable devices, especially for premature infants.

Surgical ligation, where the PDA is tied at both ends and cut in the middle, is another available treatment option. Although this method represents the “gold standard,” it is the most invasive option (performed thorascopically) and can therefore be traumatic for small children and infants. The mortality rate for this procedure is negligible; however, the morbidity of anesthesia and thoracotomy, scaring from the surgery and the expense ($20,000) are significant disadvantages [13]. A chest tube is required for at least 24 hours, and causes further discomfort. Additionally, the patient is generally hospitalized for a week, with an expected recovery period of six to eight months.

Non-surgical closure of PDA has become more common, as it is a less invasive intervention and can be done with local anesthetic and sedation. There has been an improvement in implantable devices over the past ten years, with devices now being delivered through catheters as small as 4 French (4F) [5],. As noted the anatomy of PDA varies considerably in size and configuration. Where a diameter is described, it arbitrarily refers to its narrowest segment, which is smaller than 4 mm in 78% of cases [4]. PDA’s have been classified into five types, the most common being Type A, where the ductus arteriosus is funnel shaped with a narrowing at the pulmonary artery junction. Type B is the next common, and is funnel shaped with an aortic ampulla (neck). Type C is tubular, Type D is oval shaped with aortic and pulmonary ampulla, and Type E refers to other rare forms [11]. These different types of PDA’s are identified by a chest x-ray, electrocardiogram or an echocardiogram [11].

Some forms of occlusion devices are more ideal than others for the various types and sizes of PDA. The first device to gain widespread popularity for the occlusion of PDA was developed by Dr. William Rashkind in the 1980s. Though never approved by the FDA for use in the United States, this device is still in use in foreign countries. The Rashkind double umbrella is made up of two tiny sponge umbrellas that are attached to one another. When positioned correctly, the device is astride the PDA, with one umbrella on the aortic side of the PDA and one on the pulmonary artery side. The size of each umbrella is larger than the orifice of the PDA, so the device cannot move. The umbrellas become coated with blood and quickly become non-porous. Eventually natural tissue lining of the blood vessels will grow to cover the device. The standard device size has a diameter of 12 mm. This device was quite successful in closing small PDA's (> 90% success rate), but was limited by the large catheter sizes (8F-11F) required for delivery [8]. This precluded its use in small children, and in 1992 it was removed from trials in the US. Furthermore, since this device is priced at $2500, its application is limited among low income families and less affluent countries.

The Porstmann Plug (or Ivalon plug) is a trans-catheter closure device invented and used around the same time as the Rashkind double umbrella. This device consists of a polyvinyl chloride plug on a stainless steel umbrella fame and is delivered via a catheter. Although clinically effective, an 18F catheter is required for delivery, preventing wide acceptance of the procedure.

Another device used for PDA closure is the Dideris buttoned device. This device consists of a 1-inch square of thin polyurethane foam on a flexible wire that patches holes in children’s hearts. The patch is inserted through the vein in the child’s groin, gently pushed into place by a catheter and secured by tiny buttons. The main advantage of this device is that it can be delivered via a 7F catheter, resulting in minimal vascular damage during delivery [4]. Unfortunately, 29% patients who received this method of treatment experienced a residual shunt [13]. An additional drawback of this device is that it is expensive to manufacture and deliver.

The most common devices used at present are Cook coils and the Amplatzer Duct Occluder. Coils can be delivered through catheters as small as 1.3 mm in diameter (4F) [11]. This allows the procedure to be performed on smaller patients, including premature babies weighing less than 5 kg. Gianturco spring coils were the first coil system to be used. These coils are made of surgical steel that has thrombosing fibers interwoven between them, resulting in quick endotheliazation. Although successful, these coils are difficult to adjust or retrieve, increasing the chance of embolization (loss of coil into bloodstream). Currently controlled release coils—Cook coils—have improved the use of coils to occlude PDA’s. These Cook coils, made from stainless steel with Dacron fibers interwoven throughout, (Fig. 2) allow adjustment and positioning of the coil before release, avoiding protrusion of the coil into the vascular lumen that may otherwise result in turbulent flow of blood or obstruction. As the risk of embolization is lower, smaller coils can be used. Cook coils are manufactured with different diameters to fit different PDA sizes—3 mm, 5 mm, and 8mm diameters [10]. Another advantage of these coils is their cost: $65 per coil. Unfortunately, one coil is often not enough. If the PDA is large or oddly shaped, the patient may require 3 or 4 coils [12]. This can create a twisted knot in the vasculature of the patient. Furthermore, if the coils become dislocated, they must be completely removed and a second attempt can be performed once the patient has recovered.

The Amplatzer Duct Occluder (ADO) is a self-expanding mushroom shaped device made from nitinol wire mesh, with a thin aortic retention disc designed to secure positioning in the aortic ampulla (Fig. 3). Although percutaneous closure of PDA using ADO in pediatric patients appears to be a low risk procedure, it is not recommended for use in infants weighing less than 5kg [11]. This is substantiated by failures in implantation and reversion to surgery, reported by several authors [1, 4, 12]. An infant “normally” reaches 5kg by about two months of age, but an infant with PDA may grow slower, and will be older before use of ADO is recommended. Therefore, this device is not suitable for premature babies. Additionally, the ADO has a projected cost of $2500. Since this device is still in the clinical trial phase, no conclusions about its efficacy and safety can be made.

One major disadvantage of the Porstmann Plug, Cook coils, and Amplatzer Duct Occluder is that they are thick and rigid, forcing the PDA to conform to their shape. This causes undesirable stress and tension on the walls of the PDA. Thus, each device must be individually shaped according to the size and shape of the PDA it is meant to occlude.

Examination of the available PDA occlusion devices has established their disadvantages in terms of size, cost and the inability to conform to the shape of the PDA. Thus, the demand remains for a cost-effective device that can be delivered through a small catheter and successfully occlude the PDA.

2.3 Design Goals

Dr. Thomas Doyle, a pediatric cardiologist at Vanderbilt Medical Center and the advisor for this project, provided our group with specifications for a PDA occlusion device during our first meeting in October 2002. The minimal requirements for the device included the following:

• Made from biocompatible materials

• Conforms to the shape of the PDA and causes occlusion

• Be delivered via a catheter ................
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