Nature of electrical abnormalities occurring during the development of heart failure

A Johns Hopkins undergraduate student has contributed to new research showing that electrical changes in the heart leading to heart failure can occur long before a patient exhibits any clinical symptoms. The initial changes can then spur a second, later phase of changes that cause lethal heart rhythm disturbances known as arrhythmias.

The study by Samuel Hahn, 21, a senior biomedical engineering major from Lutherville, Md.; and Fadi G. Akar, Ph.D., a research assistant professor at the Johns Hopkins School of Medicine, was the first to describe the time-course and nature of electrical abnormalities occurring during the development of heart failure. A manuscript of their work has been submitted to a peer-reviewed scientific journal. The two conducted their research in the laboratory of Gordon F. Tomaselli, professor of medicine and vice chair for research in the Department of Medicine.

"By the time most patients are diagnosed with heart failure, it's too late to really improve their condition," Akar said. "By defining the early electrical changes, we hope to identify new targets for therapy that can either reverse or, at the very least, hinder the progression of the vicious cycle of events that ultimately leads to death."

During heart failure, the pumping action of the heart becomes inadequate, resulting in a back pressure of blood along with congestion of the lungs and liver. Nearly 5 million Americans suffer from heart failure and more than 250,000 die annually from the condition, Hahn said. The incidence and prevalence of the disease continue to increase with the aging of the U.S. population.

"Despite remarkable improvements in medical therapy, the prognosis of patients with heart failure remains very poor, with almost 20 percent of patients dying within one year of initial diagnosis, and over 80 percent within eight years," Hahn said. "Of the deaths in patients with heart failure, up to 50 percent are sudden and unexpected, and the result of lethal arrhythmias."

For their study, Hahn and Akar isolated small samples of heart tissue about the size of large postage stamps from dogs in various stages of heart failure. Next, using a technique called optical mapping, they stained the tissue samples with voltage- or calcium-sensitive dyes, and shined a green light on the samples to excite the photosensitive dyes. The excited photosensitive dyes emitted light in different amounts depending upon the cellular voltage or calcium levels in the individual tissue samples. The emitted light was then collected by a sensitive optical detection system, converted to current and stored on a computer for analysis.

Hahn and Akar were able to demonstrate that electrical disturbances occurred in two distinct phases relative to mechanical abnormalities. The early changes involved a delay in the timing of electrical recovery of the heart muscle following each beat, whereas the later changes involved the loss of electrical synchrony among various regions of the heart. The early electrical changes likely contributed to mechanical abnormalities of the heart, and the later changes were a consequence of the compromised mechanical function. The scientists found that both the early and late changes in the electrical properties were required to cause a lethal arrhythmia.

"Sam was instrumental in analyzing the data, and helping perform the experiments," said Akar, noting that their procedure was a two-person job: one to ensure the health of the heart tissue being studied, and a second to ensure the performance of all experimental protocols and the proper acquisition of data by the computer.

"He's been a huge mentor for me," Hahn said of Akar. "Being an undergraduate, you still have to have direction. He's given me guidance, freedom and credit."

Tomaselli also praised Hahn for his persistence and devotion to the project.

"I am often hesitant to take on undergraduate students, particularly during the most rigorous parts of their programs, but I made an exception for Sam, and I am glad that I did," Tomaselli said. "Sam is the type of student who has the attributes to become a leader in biomedical research."

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