A Genetic Approach to Cardiomyopathy

A Gill Heart & Vascular Institute cardiologist is the first researcher in the world studying how people with a genetic mutation may benefit from a relatively new heart device. The cardiac contractility modulation (CCM) device may reduce the need for other treatments and extend the lives of people with ischemic and nonischemic cardiomyopathy.

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CCM was approved by the FDA in 2019 as a treatment for people with significant heart failure and a weakened heart who are not candidates for biventricular pacing therapy. Before CCM, medication was the only available treatment for these patients. The CCM device is implanted like a pacemaker, but it acts differently by delivering timed electrical pulses to improve the way the heart contracts. This contraction may boost blood flow and help people feel better.

Early research by Dr. Aaron B. Hesselson, M.D., shows cardiomyopathy patients with a mutation in the titin gene may respond better than expected to CCM. The titin gene is the largest protein in the human body and sets the spring tension force of each heart muscle cell. CCM may modify a defective titin protein, which could improve its cellular function and overall cardiac function.

“Could CCM keep these patients from getting transplants and heart pumps? That's what I want to know,” said Dr. Hesselson, Gill’s director of electrophysiologic services. In a recent paper in the journal Heart Rhythm Case Reports, he describes a patient with the titin mutation who regained normal heart function in response to CCM. After getting a CCM device, the patient’s symptoms also improved significantly, and no other treatment was needed.

CCM has been slow to catch on with the electrophysiology community, even though testing for the device started in the early 2000s. Because many patients have a defibrillator or may need one in the future, doctors are reluctant to implant two devices.

It may be possible, though, to eliminate the need for two devices by looking at a patient's genetics. “This device could improve heart strength so you would not need a defibrillator,” said Dr. Hesselson. “Perhaps we could predict before we do the procedure that a specific patient population is much more likely to respond better based upon genetics and potentially even live longer.”

Research on the horizon

Multi-center trials are needed to gather more data and learn more about the possible benefits of CCM for genetic mutations. Dr. Hesselson is talking with at least one other hospital about doing basic science research on the genetics of heart failure and CCM. After the recent journal article, the FDA reached out to him to collaborate on CCM basic research. As a clinical researcher, Dr. Hesselson is less likely to get government funding for his research, so he’s currently seeking other resources to fund his studies.

Currently, patients must have significant symptoms for insurance to pay for CCM. Dr. Hesselson hopes his genetic research could speed up treatment for people with less severe signs of heart muscle weakness. “My hope is that we can change the paradigm on genetic cardiomyopathy management by offering a treatment alternative to patients who are currently relegated to thinking about heart transplant or implantable heart pumps,” said Dr. Hesselson.

Gill researchers will also take part in two upcoming multicenter trials looking at other aspects of CCM. One trial will test a combined CCM–defibrillator device, which could end concerns about implanting two devices. Another will look at whether heart failure patients with minimally weakened or normal heart strength could also benefit from CCM.