New Insights into Molecular Mechanisms for Congestive Heart Failure and Arrhythmias

EHM. What role does genetics research play in understanding the cause and the mechanisms of heart disease?

TO. Genetics plays an important role in the basis of heart disease, and over the past 10 to 20 years we have come to understand just how important heredity factors are.

At the same time, the Human Genome Project has really given us an important tool to be able to investigate genes that might be important in the development of these diseases. In regards to atrial fibrillation, we carried out a research study together with many of our clinical electrophysiology colleagues and identified a subset of patients who have atrial fibrillation with no known risk factors for this common type of arrhythmia, and they tended to be younger individuals.

We looked at these individuals’ family history and determined that a significant number had atrial fibrillation that ran in the family. That really laid the groundwork for our investigations into trying to identify the specific genes that might be responsible for their arrhythmia.

EHM. What is the significance of heredity in susceptibility to atrial fibrillation?

TO. Our understanding is unfolding. We’re relatively early in our investigations. To date, our lab and other laboratories have identified certain genes that are important in regulating the movement of potassium and sodium ions within cells of the heart, but those particular genetic defects probably explain a very small percentage of cases. So really, research is ongoing to try to identify additional genes that might be important in this disease.

EHM. How can research findings help treat patients with a genetic form of atrial fibrillation?

TO. Our long-term objective is to arrive at a better understanding of the genetic and biological underpinnings of the disease, enabling us to develop better ways to treat and prevent the disease. That time has not yet come, so we’re really now in a period of time where we are just beginning to understand the genetic underpinnings, but hopefully, ultimately, this will lead to better treatments.

EHM. How much closer does genetic research bring us to the so-called personalized medicines?

TO. It certainly brings us closer, and time will tell whether we’ll be able to identify, say, a panel of genes that could be tested for in a patient who has atrial fibrillation. The hope would be that with advances in technology, even though there may be many different genes to screen for, it will be feasible from an economic standpoint to be able to test for multiple genes.

EHM. How do you respond to critics of genetic research and those who worry about confidentiality of data?

TO. Certainly, for the research study that we do, we take great care to keep information confidential. So it is only at the point where we have identified a clear-cut genetic basis for disease in a certain family that we would offer to share that information with the participants in the research study.

My hope is that we would have legislation that would prevent, certainly, discrimination of individuals in whom a genetic defect is identified, but it’s an important issue that certainly we need to take great care to ensure that we are promoting health and not doing harm by releasing genetic information.

EHM. How have technological advancements helped support your research efforts?

TO. There’s no question that the advances in technology have been phenomenal. We now have the ability to scan the human genome and interrogate certain genes in a very high-throughput, automated manner. My research over the last 10 or 15 years has really spanned the development of these technologies, and we’ve come a long ways.

EHM. Are we past the infancy stage of working on this with atrial fibrillation?

TO. We’re past the infancy stage, but we’re still just seeing the tip of the iceberg in terms of understanding the genetic basis for atrial fibrillation. But we’re well on the way. We have the tools. We have a comprehensive catalog of the human genome. We have the technology to be able to efficiently analyze DNA. Most importantly, we’ve been able to recruit for our research studies patients and families whose participation is essential for unraveling the genetic basis of atrial fibrillation.

About Timonthy Olsen

Dr. Timothy M. Olson obtained his medical degree in 1987 from the University of Chicago. He is currently Associate Professor of Medicine and Pediatrics at the Mayo Clinic in Rochester, Minnesota, where he practices pediatric cardiology and directs a human genetics research program focused on identifying mutations that cause or confer susceptibility to dilated cardiomyopathy or atrial fibrillation.