DNA Damage Following Radiation Exposure in Patients with Congenital Heart Disease Undergoing Cardiac Catheterization: Exposure-Effect Variability and Factors Associated with Impaired DNA Repair

Doctor's Name: 
Doff McElhinney, MD
Hospital/Institution: 
Stanford University

Xvivo Pilot Study of 10 patients

(Funded by Hands for Hearts)

Children with congenital heart disease (CHD) frequently undergo procedures or examinations that use ionizing radiation, including x-rays, computed tomography (CT) scans, and cardiac catheterization procedures. Cardiac catheterization, which is performed both to obtain information about the anatomy and physiology of the heart, and to administer various treatments, is guided by fluoroscopy, which is a form of moving x-rays that can result in relatively high doses of radiation. Although the radiation used in these procedures allows physicians to obtain clinically important images of the heart, blood vessels, and other internal organs and tissues, the radiation can cause damage to cells. One of the potential complications of receiving frequent or high doses of radiation is cancer. This can happen because radiation causes the DNA inside of cells to break, and although the body is very good at repairing broken DNA, errors sometimes occur. The more often the body needs to repair broken DNA, the more likely it is that errors in the repair process will occur. Sometimes, errors in DNA repair can result in a cell becoming cancerous.

Little research has been done and little information is available about how often cancers actually occur in CHD patients. In fact, it is not known whether cancer is actually more common in individuals with CHD who experienced high radiation exposure during childhood than it is in people with lower exposure. However, there is a theoretically increased risk of cancer simply due to the radiation received during catheterization and other examinations. As physicians who take care of young patients, we need to find ways to decrease radiation exposure and the risk of cancer, even if that risk is very small. One way to do that is to reduce radiation exposure, which can be achieved by decreasing the number of radiation-based exams, and through the use of scanners and x-ray machines with features that minimize radiation dose. We can also adopt measures that eliminate unnecessary exposure during catheterization procedures. But the potential impact of such changes will be limited as long as we need to use radiation for these tests.

Another way to reduce the risk of cancer from radiation in children with CHD may be to administer drugs before and during catheterization that reduce DNA damage or help the cells repair broken DNA. To study that type of drug, however, it will be important to understand how many DNA breaks occur in pediatric patients undergoing catheterization and whether there are specific factors that put some patients at higher risk than others. In adults, information about the number of DNA breaks and specific risk factors can be obtained by testing their blood cells before, during, and after catheterization. Unfortunately, little is known about DNA damage and repair in children. If we could measure the damage to cells from radiation during catheterization procedures, we could figure out which patients are at the highest risk and perform trials of drugs designed to prevent or correct the damage. We could also use the same measurements to determine whether the radiation-protection drugs are effective.

Children with congenital heart disease (CHD) frequently undergo procedures or examinations that use ionizing radiation, including x-rays, computed tomography (CT) scans, and cardiac catheterization procedures. Cardiac catheterization, which is performed both to obtain information about the anatomy and physiology of the heart, and to administer various treatments, is guided by fluoroscopy, which is a form of moving x-rays that can result in relatively high doses of radiation. Although the radiation used in these procedures allows physicians to obtain clinically important images of the heart, blood vessels, and other internal organs and tissues, the radiation can cause damage to cells. One of the potential complications of receiving frequent or high doses of radiation is cancer. This can happen because radiation causes the DNA inside of cells to break, and although the body is very good at repairing broken DNA, errors sometimes occur. The more often the body needs to repair broken DNA, the more likely it is that errors in the repair process will occur. Sometimes, errors in DNA repair can result in a cell becoming cancerous.

Little research has been done and little information is available about how often cancers actually occur in CHD patients. In fact, it is not known whether cancer is actually more common in individuals with CHD who experienced high radiation exposure during childhood than it is in people with lower exposure. However, there is a theoretically increased risk of cancer simply due to the radiation received during catheterization and other examinations. As physicians who take care of young patients, we need to find ways to decrease radiation exposure and the risk of cancer, even if that risk is very small. One way to do that is to reduce radiation exposure, which can be achieved by decreasing the number of radiation-based exams, and through the use of scanners and x-ray machines with features that minimize radiation dose. We can also adopt measures that eliminate unnecessary exposure during catheterization procedures. But the potential impact of such changes will be limited as long as we need to use radiation for these tests.

Another way to reduce the risk of cancer from radiation in children with CHD may be to administer drugs before and during catheterization that reduce DNA damage or help the cells repair broken DNA. To study that type of drug, however, it will be important to understand how many DNA breaks occur in pediatric patients undergoing catheterization and whether there are specific factors that put some patients at higher risk than others. In adults, information about the number of DNA breaks and specific risk factors can be obtained by testing their blood cells before, during, and after catheterization. Unfortunately, little is known about DNA damage and repair in children. If we could measure the damage to cells from radiation during catheterization procedures, we could figure out which patients are at the highest risk and perform trials of drugs designed to prevent or correct the damage. We could also use the same measurements to determine whether the radiation-protection drugs are effective.

Award Date 1: 
2015
Award Amount 1: 
$20,000