University of Virginia Health System

Promising Gains in the Fight Against Heart Disease

Gene therapy, internal defibrillators head the list

< March 4, 2003 > Heart disease was the leading killer of Americans every year but one in the 20th century.
But scientists are working on a host of promising new technologies to diagnose and treat the condition.

One development uses gene therapy to create "cellular pacemakers" for the heart. Instead of implanting an electric pacemaker in a patient's weak heart, this technology might one day allow physicians to change the body chemistry so the heart can function despite its weak cells.

The therapy stands atop the American Heart Association's "top 10" list of the most important developments in heart disease and stroke research in 2002.

"There's still a long way to go before the biologic pacemaker is ready for prime time. But 2002 marks the year that researchers showed 'proof of concept,' " says Dr. Robert Bonow, president of the American Heart Association (AHA) and chief of cardiology at Northwestern University in Chicago.

The heart rate is controlled by two sets of "pacing cells" that signal the heart to beat. These timekeepers work by controlling the level of potassium in the heart. But as the pacing cells age, they cannot supply the heart with enough potassium, preventing the heart's cells from firing, the AHA says.

Gene therapy works by disabling the cellular channel that keeps potassium from reaching heart cells. To date, researchers have only tested the therapy on the heart of a guinea pig.

Number two on the "top 10" list is the use of internal defibrillators. Although defibrillators have long been used by physicians and paramedics to stabilize a person in cardiac arrest, physicians have just started implanting them into the heart.

Unlike a pacemaker, which sends a subtle electrical current through the heart when it beats too slowly, a defibrillator shocks the heart with a much larger current when it beats too fast. According to the American College of Cardiology, after the heart is shocked, it often returns to its natural rhythm.

A 20-month study reported last year at the college's scientific sessions showed that the implanted defibrillator was much more effective in saving patients who have abnormal heart rhythms. In a group of more than 1,200 such patients, 14 percent of those with the device died during the trial, compared to 20 percent of those without it.

Another advance—which has implications for all surgeries and implants—involves stents, small tubes that are inserted in an artery or blood vessel to keep it open. Stents are generally used to strengthen a weak section of an artery or relieve a clogged area. But after one is implanted, the body's immune system tries to heal blood vessels damaged by the insertion of the stent, often closing off the artery, Bonow says.

The innovation here is coating the metal or plastic stent with a medicated polymer, which slowly releases a drug directly onto the damaged blood cells, thereby preventing the immune system from responding to the stent. Such coatings could be applied to other implanted devices or transplanted organs to stabilize the immune system, Bonow says.

"I hate to use the word 'revolutionize,' but this has the potential to have a major impact on treatment," Bonow says, adding that he expects the US Food and Drug Administration (FDA) to approve the new stents within a few months.

Other recent advances shift the focus from treatment of cardiovascular disease to prevention. Better medications are now available for cholesterol and high blood pressure for extended periods of time.

And the assessment of heart disease risk now includes subtle relationships between multiple factors, such as weight, diabetes, family history of heart disease, blood pressure, and cholesterol, Bonow says.

Always consult your physician for more information.

Online Resources

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American College of Cardiology

American Heart Association (AHA)

Circulation, Journal of the American Heart Association

US Food and Drug Administration (FDA)

For more information on cardiovascular diseases, please visit the Cardiovascular Disorders information module on this Web site.

In Other Heart Health News:

Gene Therapy Problem Pinpointed

Older cells may be more resistant to viruses carrying help for heart failure

Here is the dream: An older person is dying of heart failure, as his/her aging heart muscles gradually lose the ability to pump blood. Those muscle cells can be reinvigorated by sending in young genes, packed in harmless adenoviruses.

Here is the problem: It is unexpectedly difficult to get those helpful adenoviruses into older cells, much more difficult than getting them into younger cells.

Here is the newly discovered reason, published in a recent issue of Circulation: Older cells have a deficiency of little-known proteins called integrins, which sit just under the cell membrane and facilitate the entry of one substance or another. Now researchers working on gene therapy for heart failure may have a way to make the idea work.

The deficiency of integrins in older cells could be a defense mechanism, says Dr. Roger Hajjar, associate professor of medicine at Harvard Medical School and a researcher at the Massachusetts General Hospital.

"We feel that the aging person has an immune system that is less robust," he says. "A decrease in viral uptake is a way to protect an older person from viral infection."

Hajjar believes it may be possible to boost the activity of integrins, so that fewer adenoviruses can be used when gene therapy becomes a reality. Keeping the viral dose low is desirable because too much could have a toxic effect on patients, particularly older ones, he notes. His adds his group has had some success in animal studies using two molecules, laminin and collagen.

"The idea of replacing genes is a very powerful one," Hajjar says. It offers real hope for "an aging population at a very high risk of heart failure." More than two million Americans are estimated to have heart failure, and it is responsible for almost 40,000 deaths a year.

There will be "a lot of bumps in the road," Hajjar says. But, he adds, "we are on course to start planning for human trials in the next couple of years."

Further down the road, gene therapy that induces new blood vessel growth may be used to treat ischemic heart disease, in which arteries become clogged, he adds.

Always consult your physician for more information.

Personal Programmable Pacemaker

Physicians can tailor device to suit patient's needs

A heart failure pacemaker that can be programmed to suit each patient's needs has been approved by the US Food and Drug Administration (FDA).

Medtronic's InSync III includes a unique feature called sequential bi-ventricular pacing, which allows physicians to control a user's contractions of the left and right sides of the heart.

Heart failure is characterized by impaired pumping ability that causes a lack of oxygen-rich blood to be distributed properly to the body's organs and tissues. Symptoms include extreme fatigue and breathlessness. It is the leading cause of hospitalization among Americans older than age 65, the company says in a press release.

The device uses electrical impulses to coordinate movement of the heart's lower chambers (ventricles), bringing the heart into a more normal pumping rhythm. Research has shown that pacemakers result in 50 percent fewer hospitalizations than among patients on drug therapy alone, Medtronic says.

Always consult your physician for more information.