heart disease

Close at Heart

By Kim Kreiger
Illustration by Yesenia Carrero

Radiation treatment for breast cancer can inadvertently graze the heart, leading to damage and disease years later. UConn doctors are working to change that.

closeatheart


Getting radiation treatment for breast cancer can make you feel vulnerable. Sitting in a machine with radiation pointed directly at your chest, you have to trust that the doctor knows what she’s doing, that the X-rays are aimed right, that the machine is properly calibrated … and then you just sit perfectly still.

But what if you could have some control over the process?

Dr. Robert Dowsett, chief of UConn’s Division of Radiation Oncology, and
colleagues in the Carole and Ray Neag Comprehensive Cancer Center are using a new technique to give breast cancer patients agency in their radiation treatments. And they’re taking better care of the patients’ hearts in the process.

A patient can intentionally increase the heart-chest wall distance by more than a centimeter by controlling her breathing using the Deep Inspiration Breath Hold.

Using the technique, called Deep Inspiration Breath Hold, patients can help control the accuracy and timing of their own radiation dose. The patient takes a breath of specific depth before the radiation machine turns on. Doing this correctly can increase the distance between the heart and the breast by a centimeter or two, lowering the amount of radiation hitting the heart by as much as 50 percent.

Jeryl Dickson, 62, of Manchester, Conn., was one of the first patients at UConn Health to use the technique, from late 2015 through Feb. 2. Her doctors, including Dowsett, prescribed a course of radiation therapy to make sure there were no lingering cancer cells remaining after a lumpectomy removed her breast cancer.

“I practiced deep breathing and breath holds prior to radiation treatment with the radiation oncology staff so I could feel what it would be like,” says Dickson.

Radiation treatment of breast cancer can be very effective, eradicating tumor cells hiding in the chest wall. But breast cancer survivors have a heightened risk of heart disease that shows itself years later. Ironically, the heart disease stems from the radiation that originally saved their lives. Radiation is a type of light, and like visible light, it has a tendency to reflect and scatter. Just as even the sharpest spotlight has blurred edges where it blends into shadow, even the best-aimed medical radiation beam occasionally scatters into tissue outside of the tumor it targets. Sometimes it hits the heart.

Dr. Agnes Kim, director of the Cardio-Oncology Program at UConn Health, analyzes echocardiography images as one way to monitor cancer patients’ risk of heart disease.

Dr. Agnes Kim, director of the Cardio-Oncology Program at UConn Health, analyzes echocardiography images as one way to monitor cancer patients’ risk of heart disease.
Tina Encarnacion/UConn Health Photo

“We worry about heart attacks down the road, 10 to 15 years after radiation treatment of cancer in the chest. We also worry about inflammation on the outside of the heart in the short term. We don’t exactly know how the radiation damages the tissue, but it definitely seems to accelerate damage to blood vessels. It can also cause scarring and fibrosis damage,” says Dowsett.

But the distance between the heart and the chest wall varies from person to person. And a patient can intentionally increase the heart-chest wall distance by controlling her breathing using the Deep Inspiration Breath Hold.

To make the best use of the Deep Inspiration Breath Hold technique, Dowsett and his colleagues at UConn Health combine it with an optical scanning system supplied by C-RAD. The scanning system is essentially a computer with a camera that models the surface of the skin on the patient’s chest. It tracks the patient’s breathing, and coaches her to inhale just the right amount. As the patient, you wear virtual-reality goggles in which you see a bar graph showing your inhalation, with a box at the top. Your goal is to hit the box and then hold your breath for the 20 to 30 seconds it takes to complete the radiation treatment. Some patients can hold their breath that long; others can’t. It doesn’t matter, because if you exhale, or giggle, or cough, the system sees your chest move out of the perfect range and stops the radiation. It won’t restart until you get yourself back in position and inhale to just the right spot again.

“The deep breathing technique was not difficult at all,” says Dickson, “Honestly, I was more focused on my cancer, and heart health never entered my mind. But I am glad I put my trust in my doctors, and I never had any doubts.”

UConn Health is the only hospital using this technology in Central Connecticut. It’s a powerful, precise way to make sure the radiation beam gets the cancer, and to minimize the risk to other organs.

Previously, “the area we treated inevitably ended up being bigger than the target (tumor) itself,” Dowsett says. “Now we’ve expanded this to abdominal targets such as the pancreas and adrenal lesions,” while sparing healthy surrounding organs.

Getting to the Heart of the Matter

Why do some patients with high ‘good’ cholesterol also show signs of heart disease? UConn research has found the common gene mutation that may be to blame.

By Kim Krieger

Scientific image of kidney cells dyed colors to show mutated cells

UConn Health endocrinologist Dr. Annabelle Rodriguez-Oquendo’s lab used color stains to figure out where the kidney cells were expressing a mutant gene: those areas glow yellow in this picture. Most of the yellow is in the endoplasmic reticulum, the cell’s transportation network. Photograph provided by Annabelle Rodriquez-Oquendo


Guidelines about cholesterol used to be straightforward: high-density lipoprotein (HDL) cholesterol is healthy, and low-density lipoprotein (LDL) cholesterol is not. Relatively high levels of HDL were no cause for concern, as long as LDL was low.

But recent discoveries show that may be an oversimplification. A common variant in a gene that regulates cholesterol levels may raise the risk of heart disease in carriers with high HDL, according to a new UConn Health study.

Researchers examined a variant called missense rs4238001, which alters the type of protein made by the gene SCARB1. The variant form of SCARB1 changes a liver receptor protein from a glycine to a serine. The change occurs in the liver receptor that grabs HDL out of the blood and breaks it down for disposal. The variant protein makes the receptor more fragile and not as effective at latching onto HDL, leading to higher levels of HDL in the bloodstream.

The study, led by Dr. Annabelle Rodriguez-Oquendo, an endocrinologist at UConn Health, was based on information about more than 5,000 people who participated in the Multi-Ethnic Study of Atherosclerosis in major American cities from 2000 to 2002.

The risk of heart disease among those with the variant was up to 49 percent greater than in the general population.

Rodriguez-Oquendo and her colleagues charted the genotypes of the participants and tracked episodes of heart disease over a period of seven years.

They found that the variant was associated with an increased risk of heart disease, particularly among men and African Americans, findings that were published in the May 20 issue of PLOS ONE.

The risk of heart disease among participants with the rs4238001 variant was up to 49 percent greater than the risk in the general population. Overall, men with the variant had a 29 percent higher risk of heart disease than men without it. African American males with the variant fared the worst, with a 49 percent increased risk. For white males with the variant, the risk was 24 percent higher.

The gene mutation itself is not rare, according to Rodriguez-Oquendo. It occurs in less than 3 percent of Chinese Americans, about 8 percent of African Americans, and 10 to 12 percent of Latinos and Caucasians in the U.S. A genetic test for the rs4238001 variant is already available to help clinicians identify patients who are carriers, so that they can offer counseling about heart risk prevention.

Dr. Annabelle Rodriguez- Oquendo and team

UConn Health endocrinologist Dr. Annabelle Rodriguez-Oquendo looks at DNA data with researchers in her lab. Peter Morenus – UConn Photo

UConn Health endocrinologist Dr. Carl Malchoff uses the test to help patients who aren’t sure whether or how they should treat their high cholesterol. For example, Malchoff had one patient with high HDL and a family history of longevity. But she had suffered a stroke at a young age, and wanted more information before deciding on a treatment.

This particular patient tested negative for the variant. But those who test positive would be advised to use a more aggressive type and dose of cholesterol medication. Patients with the variant could also inform their children that they might also have it.

“Usually if patients don’t have the variant, we assume their high HDL is protective,” Malchoff says.

Sometimes, however, a treatment decision might be more ambiguous, and could require further information before the best therapy is chosen. Another patient of Malchoff’s had high levels of both HDL and LDL cholesterol. She was taking a statin to lower her cholesterol, but was experiencing terrible muscle pain as a side effect. She wondered if there was a way to tell whether her high HDL protected her from the heart disease risk associated with high LDL. If so, could she stop taking the statin?

This patient could be tested for the same variant. If her test was negative, she could assume that her high HDL cholesterol was helping protect her against heart attack, even with high levels of LDL cholesterol. If the test was positive, she would know that her high HDL cholesterol would not protect her. She could then take another type of cholesterol-lowering medication, just not one classified as a statin.

Malchoff and his colleagues at UConn Health are working with Rodriguez-Oquendo to determine when testing for the variant is most helpful.

Read the full research article at the PLOS ONE website.

“My approach to patient care in an academic center is that we should look for things our colleagues in practice can’t do and do those things, so we can help them and be their partners,” Malchoff says of his role in the research.

Now that the UConn study has made the connection between the mutation in SCARB1 and heart disease, the researchers want to figure out a way to fix it.

“We want to go deep in the cell, and figure out how to repair it,” Rodriguez-Oquendo says. The researchers don’t know exactly why changing the protein in a liver receptor from a glycine to a serine makes it more fragile. “We’re really interested in understanding more about how this protein gets chewed up and degraded faster.”

The answers may impact the current standard of care for heart disease prevention and treatment for patients who are carriers of this genetic variant. That could happen through indirect means, such as adjusting hormone levels to alter cholesterol metabolism, or in the future through direct means such as genetic therapy.