Barrow, TGen Find Genes Linked to ‘Broken Heart Syndrome’
Physicians and researchers at Barrow and the Translational Genomics Research Institute (TGen) have identified genetic changes that may predispose people to stress-induced cardiomyopathy (SIC), also known as “broken heart syndrome.”
People with this rare and potentially life-threatening heart disease usually do not show symptoms until they experience some form of intense emotional or physiological stress.
“We studied this disease in the context of aneurysms, but this has been described after the loss of a loved one, after a breakup, and with other states of emotional stress,” said Dr. Yashar Kalani, a chief neurosurgery resident at Barrow. “Any stressor that overwhelms the body can cause this to happen.”
Dr. Kalani and colleagues at Barrow worked with Dr. Matt Huentelman, associate professor of TGen’s neurogenomics division, to conduct the study, which began in 2012 and was published Nov. 24 in the journal Neurosurgery.
To identify the gene variants, Dr. Kalani and Dr. Huentelman used next-generation genome sequencing. They compared thousands of publicly available genetic sequences with those of seven women who developed SIC following ruptured brain aneurysms, looking for common alterations in the genes.
These seven women were among the 21 hemorrhagic stroke patients who were treated at Barrow between 2005 and 2013 and who were also diagnosed with SIC. None of these women had a significant prior history of cardiac problems.
“Any time a disease affects one group of people disproportionately, you start wondering why that certain group is affected,” Dr. Kalani said. “This disease affects almost exclusively women. When you see something like that, you start wondering, does this have something to do with the fact that they have a different genetic makeup than men do? Is there something that predisposes women to this?”
Among the gene variants identified are MYLK2, DSG2, FKTN, and LDB3. These extremely rare variants were previously known to play a role in other cardiac diseases, but not in SIC.
Dr. Kalani and Dr. Huentelman said that knowing which patients have the gene variants associated with SIC could help prevent them from developing symptoms and guide their treatment if a stressor does induce the disease.
“Identification of patients at risk for SIC, based on genetic predispositions, would allow for tailored treatment upon admission of these patients to the intensive care unit, and perhaps prior to a decline of the heart and brain,” Dr. Huentelman said. “The panel of genes identified by our analysis provides a means of identifying patients who may be at risk for developing this heart disorder and may also be useful in helping those at the highest risk to avoid SIC altogether.”
Dr. Kalani said if people with SIC are able to get through the stressful period, they can recover completely—as if there was never any problem with their heart function.
However, he said it has been challenging to treat SIC in critically ill patients, in part because the treatment can exacerbate the sickness.
“We hope to identify patients at risk for SIC and tailor treatment for this cohort,” he said. “That’s the goal of the new, larger project.”
Dr. Kalani and Dr. Huentelman are seeking funding to conduct a larger study on SIC.
“It is possible that other genetic changes can predispose you to this, but we don’t have the full catalog of them yet, which is why we’re going to start a bigger study to investigate this,” Dr. Kalani said. “But this is the first hint into what causes this disease process.”