Atrial Septal Defect

Atrial Septal Defect

Closure

Thomas Hoy

Department of Biomedical Engineering

VanderbiltUniversitySchool of Engineering

April 27, 2004

Advisor: Dr. Thomas Doyle

Assistant Professor of Pediatrics, VanderbiltUniversityMedicalSchool

Pediatric Cardiology, Vanderbilt University Children’s Hospital

Instructor: Dr. Paul King

Associate Professor of Biomedical Engineering

VanderbiltUniversitySchool of Engineering

I. Abstract

An Atrial Septal Defect (ASD) is a type of congenital heart disease (CHD) that results in an abnormal opening in the atrial septum. The formation of the defect beginsin the early embryonic heart where the atria consist of a common chamber, later in development the atria enlarge and fusion of the septum primum and septum secundum interatrial wall occurs, an ASD forms when this fusion is absent or delinquent. Problemsarise when this type of defect is left until adulthood; the most common life threatening problems associated with this disorder are congestive heart failure, pulmonary hypertension, and atrial arrhythmias occurring mainly in adults.1An ASD is present in 8 out of every 10,000 newborns giving rise to a significant patient base.2 There are two approaches to treating this defect. The surgical approach and the transcatheter approach, both with significant advantages and drawbacks. The goal of this design is to develop a novel device that eliminates the problems associated with the existing transcatheter models. Because every transcatheter device on the market today and many in development consists of a wire framework for structural positioning and support this model is designed to eliminate the wire-related problems arising from this framework and opt for a more biocompatible device. Research and brainstorming of possible solutions to this problem began in December of 2003 with the completion date of the model set for April 27, 2004. The final design, a double balloon detachable device, uses a balloon with a biocompatible support structure surrounding it to occlude the defect. Further progress with this project would depend on finding or developing suitable materials for the construction of a prototype.

II. Introduction

During embryonic heart formation the atria develop a wall or septum dividing a single chamber into two separate partitions. An ASD occurs when this wall does not form completely, resulting in a hole between the right and left atria. Since this defect occurs during embryonic development, it is classified as a type of congenital heart disease that mainly affects the right atrium, right ventricle, and pulmonary arteries.

With a hole between the interatrial septum, a heart with an ASD must work overtime to pump the same amount of blood to the body. In a normally functioning heart the changes in pressure throughout the four chambers allow the valves to open and close with full compliance with each chamber pumping the same amount of blood. A heart with an ASD allows for a pressure sink, called a shunt,across the septum,causing oxygen-rich blood from the higher pressure left atriumto be transmitted to the lower pressure right atrium and back into the lungs; thus, the right atrium is required to continuously pump oxygen-rich blood.1

Overall an ASD occurs in 8 out of every 10,000 newborns and exist in an estimated 4 in every 100,000 adults giving a significant patient base and recurring patient base for the development of new devices.2The majority of children are asymptomatic; however fatigue and shortness of breath are the most common ailments. Because most patients have no symptoms, an ASD is most often discovered during a routine medical examination early in childhood, when aheart murmur heardand investigated.3 Twenty percent of atrial septal defects close spontaneously within the first year of life. One percent becomes symptomatic in the first year, with an associated 0.1% mortality. There is a 25% lifetime risk of mortality in an unrepaired ASD.4 This is why known defects are chosen to be close which has not closed spontaneously by school-age.

There are three types of atrial septal defects. Theostium primum type accounts for 20%, the ostium secundum accounts for 70%, and the sinus venosus accounts for the remaining 10%.1Each is formed in the early embryonic heart as the atrium growsfrom one shared chamber to two separate chambers. As the atriumenlarges the septum primumforms and grows toward the developing atrioventricular (AV)canal area, which is later divided by the atrial and ventricular endocardial cushions. These cushions combinetowards the atria, thereby approaching the septum primum, which is downwardly growing. This process narrows the hole between the atria, called the ostium primum. An ostium primum ASD occurs when there is a deficiency of the endocardial cushions and the AV septum.5 This defect is almost always associated with a cleft in the anterior leaflets of the mitral and tricuspid atrioventricular valves and can result in left-to-right atrial shunting, mitral valve regurgitation, and AV shunting, each of which causes congestion of the right, left, or both sides of the heart, respectively.6

In the ostium secundum ASD,the ostium primum closes completely but not before a central hole appears in the septum primum; thisallows for continuous blood flow from the right atrium to the left atrium, which is essential in embryonic development due to the lack of pulmonary circulation. This hole is the second opening in the septum primum and is called the ostium secundum. As the atria expand to either side of the heart, a fold is produced within the atria near the septum primum. This fold is the septum secundum. The tip of the septum secundum is concave in shape and is called the foramen ovale. It overlays the ostium secundum but does not interfere with blood flow from right to left through the ostium secundum. After birth, as pulmonary circulation begins and the left atrial pressure rises, the septum primum is pushed against the septum secundum, closing the ostium secundum.5An ostium secundum ASD occurs when the septum secundum and foramen ovale do not fuse after birth. This defect is accompanied by a left-to-right shunt across the interatrial septum. This type of defect is more often excessively large because of the increased resorption of tissue of the septum secundum that is to cover the ostium secundum and can result in left-to-right atrial shunting, which causes congestion to the right side of the heart.6

The sinus venosus type is the least prevalent major type of ASD whose embryology is not fully understood. It is usually positioned nearest the top of the atrial septum close to the entrance to the superior vena cava and is formed as a result of the superior vena cava inserting abnormally and thus overriding the atrial septum.7This abnormality generally affects the pulmonary veins, whose purpose is to carry oxygenated blood from the lungs to the left atrium, but with the sinus venosus ASD it causes blood to drain into the right atrium instead.As a result this causes a left-to-right shunt across the atria that result in the enlargement of the right side of the heart as well as the pulmonary artery.6

IIa. Current Treatment Options

There are two methods used for treating atrial septal defects. The first method is a surgical approach.Pioneered in the 1940’s this approach can be used in any situation involving an ASD with treatment options that include direct suture repair, which is reserved for small atrial septal defects, and the more common patch repair. The material utilized for patch closure of ASD’s may be the patient’s own pericardium, commercially available bovine pericardium, or synthetic material.3This type of surgery is “minimally invasive,” where the surgeon gains access to the heart through either the sternum (median sternotomy), between the ribs (right thoracotomy), or under the breast tissue (submammary).8The main drawbacks of surgical closure are costs associated with the procedure, the use of a cardiopulmonary bypass machine, the length of hospital stay, and the overall recovery time of the patient. However, the results of surgical repair of atrial septal defects are excellent. Surgical mortality is less than one percent, and average hospital stay is four days.9 These results indicate that ASD’s of all types may be effectively repaired in infants and children with very low mortality and morbidity.

A more popular method is the transcatheter approachwhich involves the implantation of one of several devices,shown in Table 1, with basically single or double wire frames covered by fabric, using cardiac catheterization, and without the need for cardiopulmonary bypass.This method uses the same technique as a cardiac catheterization with a catheter being introduced into the groin and advanced into the heart. By using a balloon catheter the defect is then sized in comparison so that a device of the appropriate diameter can be chosen. The device is then advanced into the heart, across the ASD, and opened to occlude the defect. The limitations of transcatheter closure include the size and location of the defect. Drawbacks of this procedure include wire related problems such as perforations, wire failure, migration, and clot formation on the device;all of which account for a complication rate of approximately 5% following closure of the defect by a device.10 Other drawbacks include a large septal rim for the device, difficult device retrieval, and problems centering the device. The major advantage of this method is its relatively non-invasive approach. Patients are usually hospitalized and monitored overnight, and many return to work or school within 1-2 days with the ability to resume vigorous exercise within one week. Successful closure of these defects using a device occurs in 80 to 95% of patients with no significant shunting through the occluded defects.9 A comparison of the two methods using a small test group is shown below in Table 2. As you can see the statistical difference between certain sections of the procedure give rise to the advantages and disadvantages of each method.However, certain types of ASD's (sinus venosus and certain primum) have no chance of spontaneous closure, and patients with these types of ASD's are not candidates for transcatheter closure because of the location of the ASD and therefore, open heart surgery is the only alternative for defect closure.8

Table 1. Comparison of Device Characteristics.

Table 2. Comparison of Surgical results to that of a Transcatheter method.

IIb. Design Specificaitons

The objective goal of this design project was to design a device that would better serve the patient and cardiologist. Dr. Doyle described it to me as “a better way of doing the procedure.”Based off the considerations of the drawbacks of the surgical and transcatheter methods it was shown that the development of a new type of transcatheter device would serve the premise of the design project. Listening to the recommendations and design ideas given from my advisor a number of device possibilities arose and through further consultation and research the following parameters for a new device were developed.

The device was to meet the following specifications: to be less costly and more simplistic compared to existing devices, to be easily centered upon the ASD, to have easy use in the medical environment, to be favorable for endotheliazation of the device, to increase the possible success rate of implantation, and to easily conform to this differing size and shapes of defects.

IIc. Timeline

The device designprocess began in December of 2003with research and brainstorming atrial septal defects and possible ways for them to be closed.With the completion date set for April 27, 2004 the four months of time between these dates ensured that a certain amount of work was completed in each month. The first two months were used for research and brainstorming of the device as well as web site development. The next months were used to develop the material and supportive data needed to justify this new device and to design a visual theoretical model. The timeline for the projects development is illustrated on the project website and shows the developmental process throughout the semester.

III. Methods

With so many devices either in market or under development it was difficult to present a novel idea as a solution for this problem. I determined that an improvement upon an existing device would be more fruitful rather than introducing a new design model to the mix. However, when I talked with Dr. Doyle he instructed me on the problems he sees with such existing devices and purposed I try a novel approach that would be more theoretical in nature to solve the problems of today’s devices.

Within the past few years research into novel ways of approach this problem has increased. In the past various solutions have left more questions than answers with the main challenges regarding the fixation of the device to the defect.10Along the lines of developing a novel solution to this problem design development began with an in depth research into existing devices, patents, investigational devices, and a constant redefinition of the design parameters.

After meeting with Dr. Doyle it was determined that the ideal device would relate most closely with the surgical procedure of applying a pericardial patch. This device would exist as a thin membrane-like structure separating the two atriums. Some of the recommendations include thenon-invasive suture of a patch and the occlusion by a detachable balloon device. In the interests of simplicity and cost associated with the device, the detachable balloon approach was chosen as the design option to pursue.

With the detachable balloon device selected as the design questions as to how the balloon would be implanted across the defect needed to be answered. In a study performed in 2001 a group implanted detachable balloons acrossan artificially made ASD in a piglet. This study required that the balloons stay inflated inside the heart for an unlimited amount of time.10 Although the successful in occluding the defect the balloon can not remain inflated after the procedure is completed; therefore, to be practicable in a human the procedure must require that the balloon is deflated during the procedure. This gives rise to the second part of the research into the solution.

There are many ways to adhere one object to another; however, intravenously those options are severely limited. The necessary constraints of the method of adhesion of the balloon to the interatrial septum were that it must be biocompatible, deployable at the will of the cardiologist, and must act as a unit. First, I looked into the possibility of a heat-activated bioadhesive or glue that could be used on the surface of the balloon and activated by heated water passing through the balloon. However, this option was not possible due to the high activation temperatures, toxicity of adhesive, and the inability to bond to both the balloon and the septum effectively. Further investigation revealed another possibility; that of a biodegradable material which offers support to the deflated balloon structure until endothelialization could take over as a support structure. This material is used, like nitinol wire, in coronary stents to brace an ablated artery wall from collapsing; therefore, it has been proven to be safe for use inside various structures of the heart.11Then the final option of using a nitinol wire framework for support of the device was researched and found to be the most practicable solution to this problem being that the material has already proven in the medical environment as a reliable method for device structure.

IV. Results

Upon meeting with Dr. Doyle in early March a final design was chosen and the remaining device constraints were set. The device was to consist of a detachable double balloon catheter that, when advanced into position, would be deflated across the defect and would remain permanently in place. Among the reasons for choosing this manner of occlusion was that the existing and developmental models had either trouble centering upon the defect or required a septal rim 1.5 to 2 times that of the defect10, meaning that they were elaborate and large devices. A study published in Catheterization and Cardiovascular Interventions documented the benefits of such a device in piglets; showing that the use of a balloon catheter to completely occlude a defect required a septal rim only slightly larger than that of the defect as well as being totally devoid of any metallic complications.10This device would be ideal however it is not practicable in the human body because the study require the balloon to remain inflated for an extended period of time following the procedure. This would leave too many variables to account for in the device and pose a significant risk to the patient. However, the results of the experiment showed that implantation of the device was received by the heart tissue with endothelializtion of the device occurring at three weeks after implantation, and with the device being fully covered by tissue at four weeks.10