Clinical Trials
Surgery Projects
Title: Characterization of the Initial Experience with a Miniaturized, Implantable Left Ventricular Assist Device for Children: MicroMed DeBakey VAD® Child
Principal Investigator: Kirk R. Kanter, M.D.
The Food and Drug Administration (FDA) has granted a Humanitarian Device Exemption (HDE) to the MicroMed DeBakey VAD® Child. As a condition of that approval, MicroMed has been required to collect data in a systematic fashion for the first 50 pediatric patients implanted.
For these first 50 patients who are implanted, MicroMed has selected data collection points that coincide with the usual care for these patients.MicroMed and its clinicians believe the appropriateness and the frequency of data collection satisfy the data registry requirement imposed by FDA and provides sufficient supplemental data for evaluation.
Title: Trial of right ventricular vs. modified Blalock-Taussig shunt in infants with single ventricle defect undergoing staged reconstruction.
Principal Investigator: Kirk R. Kanter, M.D.
The normal heart has 4 chambers; the two upper chambers are called atria and the two lower chambers are called ventricles. If a child is born with a missing or a very small ventricle it is referred to as a single ventricle. Children born with a single ventricle in their heart need surgery if they are to survive. Most often they have a series of 3 palliative surgeries. The first of these procedures is putting a shunt in place to deliver blood to the lungs.The shunt is like a man-made blood vessel. There are two possible positions for this shunt. Traditionally, the shunt connects a vessel leading to the body with a vessel leading to the lungs. That shunt is called a modified Blalock-Taussig shunt (MBTS). The other type of shunt is placed from the single ventricle to a vessel leading to the lungs. This shunt is called a RV-to-PA shunt. It is unknown which shunt is better.
Patients who enroll will be randomized to receive one or the other of the two shunts. However, if during the surgery the surgeon realizes the randomized shunt will not work with that patient’s anatomy, whatever is best for the patient will be done.
Information from routine care will be collected to determine the outcomes of surgery. There is one required research visit when the child is 14 months old. That visit will involve questionnaires for the parents to complete an evaluation of the child’s level of development and an echocardiogram if one hasn’t been done recently for routine care.
The second part to this study involves a genetics test. The type of genes (the materials that are needed to construct and operate the human body) that a person carries can change his or her response to a disease or to the medications and procedures used to treat the disease.The gene to be studied for this portion of the study makes a protein called apolipoprotein E or APOE.This sub-study will help to determine whether this gene effects the way the brain develops in infants with single ventricle hearts. The brains of adult patients have been shown to respond differently to disease and injury, depending on the type of APOE that is present. This knowledge will help us understand the genetics of human disease, and may lead to progress in treating children with congenital heart disease. A swab from the inside of the cheek will be used for the genetics test.
Title: Influence of Genetic Polymorphisms on Ventricular Structure and Function in Patients with Single Ventricle Anatomy
Principal Investigator: Paul Kirshbom, M.D.
In the Unites States, approximately 30,000 children are born with congenital heart disease every year. Between 1000 and 2000 of these children have some form of functional single ventricle anatomy, with variants of hypoplastic left heart syndrome (HLHS) comprising about half. Patients with functional single ventricle anatomy are born with a malformation that renders one of their ventricles unusable and surgically unrecoverable. In HLHS, for example, either the mitral or aortic valve can be absent or significantly stenotic, which is generally associated with marked hypoplasia of the left ventricle and the ascending aorta. Other common variants of single ventricle anatomy are tricuspid or pulmonary atresia, often associated with some degree of right ventricular hypoplasia, unbalanced atrioventricular defects, in which either ventricle can be unusable due to malposition of the interventricular septum, and the heterotaxy syndromes. All of these congenital cardiac anomalies, as well as several other less common variants, can be treated with a multi-stage surgical palliation that usually requires three surgical procedures during the first three years of life. At the completion of this series of palliative procedures the children are left with their single functional ventricle driving blood flow to the systemic circulation while their pulmonary circulation is derived from passive drainage of the systemic venous return into and through the pulmonary vasculature. This arrangement, the so-called “Fontan physiology”, can provide an excellent quality of life as these children grow and enter young adulthood; however, it is by no means a normal hemodynamic arrangement and a significant percentage of children with single ventricle anatomy will fail either during the early palliative steps or at some point after they achieve final Fontan palliation.
Failure of single ventricle patients to progress through the multi-stage palliation or late failure of patients after the Fontan procedure can result from a myriad of causes. While ventricular dysfunction is a common finding in failing single ventricle patients, an anatomic reason for their clinical failure, such as myocardial ischemia or ventricular outflow obstruction, often cannot be identified. Many of these patients subsequently die or require cardiac transplantation when their single ventricle fails. Because patient outcomes are highly variable despite similar anatomy and hemodynamics, it has been suggested that genetic variability may play a role in the ability of patients to tolerate long-term single ventricle palliation.
Title: Tricuspid Atresia Study
Principal Investigator: Kirk R. Kanter, M.D.
Tricuspid Atresia (TA) is an abnormality of the heart valve and right side of the heart that occurs to a baby’s heart before birth. The normal opening between the right atrium (upper chamber of the heart) and the right ventricle (lower chamber of the heart) is called the tricuspid valve. When the tricuspid valve does not form during a baby’s development before it is born, blood is unable to flow between the two chambers. With the absence of this blood flow, the right lower chamber does not develop into a normal size. Blood is then forced to travel from the right upper chamber into the left upper chamber through a hole called the patent foramen ovale (PFO) a normal opening between the right and left upper chamber in the baby’s heart before it is born. After birth this hole should close on its own, but does not in this defect since the blood flow keeps it open. This opening allows blood that has been oxygenated by the lungs (red blood) to mix with the unoxygenated blood (blue blood) from the right upper chamber. This mixing causes the blood to have a lower oxygen content overall. This mixed blood is pumped into the left lower chamber. If there is a hole (ventricular septal defect) between the right and left lower chambers, then the mixed blood will travel to the lungs, through the small right lower chamber and the main vessel to the lungs (the Pulmonary Artery) as well as to the body via the left lower chamber and the main blood vessel to the body (the Aorta). Once the baby is born, it has the normal need for oxygen and relies on the lungs to perform the normal exchange of carbon dioxide and oxygen and to give the blood oxygen (red blood). Infants born with Tricuspid Atresia that do not have a hole between the two lower chambers have a small amount of blood flow to the lungs, provided by another small blood vessel called a patent ductus arteriosus (PDA). The PDA normally closes within a few hours up to a few days after the baby is born. This lack of red blood causes the baby to become slightly blue or cyanotic. The baby’s heart will beat faster to pump more blood to the lungs and the baby will begin to breathe faster trying to take in more air. The more work the heart and lungs do to increase the amount of red blood to the body, the more need there is for more red blood. This cycle will cause the baby’s body to release chemicals into the blood that will eventually cause the baby’s heart to stop beating. This could take as long as two weeks to happen if the heart defect is not found.
To fix the heart with this defect usually takes three operations, with the first one as soon as possible after the defect is discovered. If there is a hole between the two lower chambers (ventricular septal defect), but without any narrowing of the pulmonary artery, a small band is placed around the pulmonary artery as a temporary procedure. This temporary procedure prevents too much blood from flowing to the lungs. If there is not enough blood flow to the lungs then a shunt is created, the shunt connects the blood flow from the aorta to the pulmonary artery to supply the lungs with blood. The size of the shunt is based on the infant’s size. The second operation is the Glenn anastomosis and is done when the infant is between four and six months of age. The superior vena cava is sewn to the right pulmonary artery increasing the blue blood flow to the lungs. The shunt is removed at this time. The final operation is the Fontan Procedure. The inferior vena cava is sewn to the junction of the right pulmonary artery and superior vena cava. A special fabric tube (Gore-Tex) is used to create a separation between the inferior vena cava and the heart.
The tissue (atrial septum) between the two upper chambers (right and left atriums) is removed. The heart now has a single atrium and a single ventricle and the blood flow to the lungs bypasses the heart completely.
Long-term outlook for the children will be the basis for this study. Most children have reasonably good exercise tolerance during their daily lives. Currently two areas of concern are serious heart beat irregularity and a break down of the normal protein in the child’s system. After the child is enrolled in the study, he or she will be followed for a period of at least five years with an annual phone survey. The questions included in the survey include the parent/legal guardian’s perception of the child’s health, current medications, level of energy, shortness of breath and a list of any other surgeries or hospitalizations the child has had over the previous year. Patient demographic and physician information will also be kept current to follow the child over this time period.
Title: Proposal for Retrospective Review of Ross Aortic Valve Replacement Patients
Principal Investigator: Kirk R. Kanter, M.D.
The heart consists of four chambers. The top two chambers are called atriums. The bottom two chambers are called ventricles. The top two chambers are separated from the bottom two chambers by valves. Valves are like doors that swing open and shut to allow blood to flow in one direction. On the bottom right chamber (right ventricle) there is a vessel called the pulmonary artery that carries blood to the lungs. This vessel has a valve on the inside of it called the pulmonary valve. On the bottom left chamber (left ventricle) there is a vessel called the aorta and it carries blood to the rest of your body. The aorta has a valve on the inside of it called the aortic valve. Sometimes the valves in the aorta become sick and they must be replaced surgically. One such surgical procedure is known as the Ross procedure. This consists of taking a patient’s own pulmonary valve (the autograft) and replacing the patient’s sick aortic valve with the pulmonary valve. At times, this can involve either enlarging or reducing the diameter of the ring around the aorta to make the valve fit properly. The patient’s own pulmonary valve is then replaced, most typically with a human heart valve (a homograft). There has been some concern in earlier studies that as time goes on, the pulmonary valve that is being used to replace the damaged aortic valve will become wider and over time the patient’s valve may leak.
Contrary to what has been reported, we have not seen this problem. One thing that we have done differently from other centers is that we have modified the insertion technique of the pulmonary valve into the patient’s aorta. This involves a second buttressing or reinforcing suture layer. Suturing is the process of tying or sewing things together. We hypothesize that not only does this have the immediate effect of reducing bleeding problems, but we think that it has the long-term effect of stabilizing the pulmonary valve and preventing the aorta from becoming too large.
In order to show this, we will look at patient’s medical records. The patients will be divided into two groups: treatment groups and control groups. The control group will consists of patients who have had the Ross procedure but they did not get the buttressing or reinforcing suture layer. The treatment group will consists off patients who did receive this reinforcing suture layer. We will collect bleeding incidence information from the patients chart and we will also look at echo data in order to assess the two hypotheses for this study.
Title: Pulmonary Ventricle - Pulmonary Conduits in Infants and Young Children
Principal Investigator: Kirk R. Kanter, M.D.
Children born with the congenital heart disease known as Pulmonary Atresia or Pulmonary Stenosis (an absence of the Pulmonary artery or a severe narrowing of the Pulmonary artery) require intervention at a young age. This procedure involves the insertion of a conduit (or tube) connecting the right ventricle (Pulmonary Ventricle) to the right and left pulmonary arteries to allow blood flow to the lungs. Different types of conduits are available for use, dependant on the size and whether or not a valved conduit will be necessary. These tubes can be made from man-made material, such as Gore-Tex™, or bioprosthetic materials both human and animal. Due to the nature of the immune system and normal growth of these infants and young children these conduits become calcified or too small relatively quickly requiring re-operation. One area of interest involves what the bioprosthetic conduits are treated with to prevent calcification of the conduit and valves. With each subsequent operation the patient is exposed to additional blood products and other normal surgical risks, therefore the impetus to postpone these procedures as long as possible is the common goal.
Title: Pediatric Heart Transplant Study (Registry)
Principal Investigator: Kirk Kanter, M.D.
All children receiving a heart transplant will be entered into a national database. Several times a year, all participating physicians will enter information about follow-up care; therefore, more information can be learned about how children react to transplantation surgery.
Title: Evaluation of a modified perfusion strategy for neonatal aortic arch reconstruction: Does perfusing the lower body during arch repair help?Principal Investigator: Paul Kirshbom, M.D.
Hypoplasia of the aortic arch is a common component of congenital heart disease.In the past, the most common technique utilized for repair of the aortic arch was deep hypothermic circulatory arrest, which involves cooling the child to less than 18°C and then turning off the cardiopulmonary bypass pump. As the aorta is repaired, the child has no circulation to the body or brain. While short periods of circulatory arrest were well tolerated, a modified technique called selective cerebral perfusion was developed to maintain blood flow to the brain during aortic repairs so as to allow for less hurried repairs with less concern over brain ischemia and injury.
Selective cerebral perfusion is designed to provide flow to the brain via the right carotid artery and collateral intracranial vessels while the aortic arch is isolated for repair. It is felt that collateral vessels also allow some perfusion of the lower body, but the adequacy of lower body perfusion during selective cerebral perfusion has not been well documented. While it is clear that some blood reaches the lower body, the incidence of renal and gastrointestinal complications following cardiac repairs involving aortic arch reconstructions remains significant. The goal of this study is to evaluate a simple modification of the standard selective cerebral perfusion protocol designed to increase perfusion to the lower body during aortic arch reconstructions.
Title: SPY imaging system - Its role in pediatric cardiac surgery
Principal Investigator: Brian Kogon, M.D.
In children, complex surgical reconstructions are often required to treat congenital heart defects. As with coronary arerty bypass grafting in adults, vessel and anastomotic site patency is critical to success. Certain congenital heart operations involve complicated blood vessel reconstructions and delicate anastomoses. Thrombosis, narrowing, and occlusion, particularly at suture lines, often contribute to morbidity and mortality. Unfortunately, the current method of evaluating the surgical repair intraoperatively is limited to echocardiography, either trans-esophageal or epicardial. While this modality is excellent for some lesions, there is frequently indirect or poor resolution of anatomy in others. In addition, results are often subject to misinterpretation due to operator dependency. Post-opertaively, vessel and anastomotic sites can be evaluated, not only by echocardiography, but by cardiac catheterization. This additional modality more clearly defines the blood vessel anatomy and can guide catheter-based interventions or operative re-interventions, if needed.
It would be advanatageous to detect potential problems with vessel and anastomotic patency prior to leaving the operating room. The SPY imaging system makes use of the fluorescence properties of Indocyanine Green (ICG) to obtain high quality images of blood vessels. Unlike conventional angiography, indocyanine green fluorescence imaging offers the potential for a reliable, non invasive, inexpensive and rapid method of intraoperative assessment of vessel and anastomotic patency.