Discovery Suggests New Treatment Option for Cardiomyopathy

The failure of dystrophin, one of the building blocks that literally holds heart muscle cells together, can cause dilated cardiomyopathy (DCM), a condition in which the pumping chambers of the heart enlarge and cannot pump adequately, say researchers at Baylor College of Medicine in a report in the March 16 issue of the journal the Lancet.

However, allowing the heart to rest by using a mechanical device called a ventricular assist device, or VAD, allows dystrophin to resume its function and restores the heart to more normal pumping, said Dr. Jeffrey Towbin, professor of pediatrics and cardiology at Baylor and the senior author of the report.

Dystrophin is probably best known for its relationship to Duchenne and Becker muscular dystrophy, diseases in which the muscles in children weaken, wheelchairs become necessary, and dilated cardiomyopathy occurs. A mutation in the dystrophin gene causes these diseases. However, in the case of dilated cardiomyopathy alone, the end portion of the dystrophin protein loses a critical connection between the cell’s contractile apparatus and the cellular membrane. As a result, the heart cannot contract adequately, said Drs. Towbin and Neil Bowles, also a member of the Baylor research team.

Dr. Towbin and his colleagues took samples from 10 patients with ischemic (disease of the coronary artery) and 10 patients with non-ischemic dilated cardiomyopathies resulting from different causes who were awaiting heart transplants. Samples were also obtained from six patients with dilated cardiomyopathy who were being treated with ventricular assist pumps. The researchers compared the patient samples to normal samples taken from transplanted hearts and found the abnormality in the dystrophin of roughly 90 percent of all the patients with cardiomyopathy.

There are two theories about why the protein becomes disconnected. One is mechanical. As the heart pumps harder and harder over a number of years, it weakens the connection to the cell membrane.

"You literally beat your heart to death," Dr. Towbin said." "The harder and faster the heart beats, the more likely it is to destroy the infrastructure of the myocardium (heart muscle). You put the heart to rest and it reconnects the end of the dystrophin molecule to the membrane."

In the studies with patients on the ventricular assist device, the Baylor team found that after four to six weeks on the pump, 90 percent had a reduction in the number of cells with the defective dystrophin-membrane connection.

A second possible cause of the problem is that a chemical produced by the process of heart failure might target that portion of the dystrophin attached to the contractile apparatus and cell membrane, literally severing it at that critical link, suggested Drs. Bowles and Towbin.

Whatever the reason for the dystrophin problem, the finding has important implications for the development of new therapies for cardiomyopathy. The possibility that heart function can be restored in some patients raises the question as to whether some patients would be able to avoid transplantation, they said. Implanting a total artificial heart requires removal of the person’s own heart, eliminating the possibility that it could be restored to near normal function by rest with the support of the pump.

However, Drs. Towbin and Bowles wonder if their finding indicates that the dilated cardiomyopathy will recur.

"If you take patients out of the heart failure state now, will they develop dilated cardiomyopathy again in the future?" asked Dr. Towbin.

Others who participated in the research include Drs. Matteo Vatta (first author), Sonny J. Stetson, Alejandro Perez-Verdia, Mark L. Entman, George P. Noon and Guillermo Torre-Amione.

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©2006 Texas Medical Center

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