P&S Journal: Spring 1996, Vol.16, No.2
P&S Research in Cardiology
Several P&S researchers presented findings at the November 1995 scientific sessions of the American Heart Association. Summaries of that research illustrate Columbia's continuing strength in cardiology.
Beta Blocker Reduces Mortality
The addition of carvedilol, an experimental new beta-blocking drug, to conventional therapy for patients with chronic heart failure reduced mortality by 67 percent in a major trial conducted at Columbia-Presbyterian and other medical centers.
"These findings are very exciting because the magnitude of effect is remarkable," said Dr. Milton Packer, director of the Heart Failure Center at CPMC and former Irving Research Scholar. "Most drugs that we have for heart failure do not affect mortality to this degree. Furthermore, this result is even more remarkable since it was observed when added to the best existing therapy."
After 25 months of patient enrollment, the study was terminated early because of the strong evidence signaling the significant favorable effects of carvedilol on survival.
Heart failure, which affects some 3.5 million Americans, is a condition in which a damaged heart doesn't suddenly stop but gradually pumps less and less blood until it ultimately fails to meet the body's minimum needs. It is the only heart disorder that is on the rise and is the most common reason Americans over age 65 are hospitalized.
Although lifestyle changes and medications that reduce the heart's workload can slow the progress of the disease, about 50 percent of heart failure patients die within five years of diagnosis.
The multicenter study was undertaken to assess carvedilol's long-term impact on survival after smaller and shorter pilot studies had demonstrated improvement in both cardiac function and heart failure symptoms, such as shortness of breath.
The study enrolled 1,094 patients with heart failure at 65 clinical centers across the country. All suffered with the type of heart failure in which the left ventricle, a pivotal heart chamber, failed to pump adequately, having an ejection fraction-a measure of the heart's pumping ability-of less than 35 percent. All had mild, moderate, or severe heart failure.
More than 90 percent of the patients enrolled were already taking the three types of drugs considered standard for treating heart failure: digitalis to enhance the pumping power of the heart, diuretics to manage excess fluid, and ACE inhibitors to dilate blood vessels.
New Heart Benefits of ERT
Pivotal findings on how estrogen replacement therapy (ERT) helps protect postmenopausal women from heart disease were reported by Dr. Elsa-Grace Giardina, professor of clinical medicine and director of the Center for Women's Health, and presented at the AHA meeting by Dr. Millie Lee, a research fellow in cardiology at the center.
"Short-term ERT appears to decrease the workload of the heart, which may contribute to its heart-protective effects above and beyond its known benefits in improving the cholesterol profile," Dr. Giardina said. These findings may help explain the 50 percent lower risk of heart disease seen in postmenopausal women who take hormone replacement.
"Our research also suggests that ERT may be of particular benefit to women who are at greatest risk for-or who already have-coronary artery disease," she said.
Improved understanding of how estrogen works can help physicians better select which women should receive ERT after menopause. ERT also can aid in the development of new heart-protective medications for women who can't take estrogen and for men.
While epidemiological studies have shown ERT markedly reduces the risk of heart disease in postmenopausal women, the mechanism of this benefit has been unknown. The Columbia-Presbyterian project was the first crossover study to evaluate the effects of short-term ERT on cardiovascular hemodynamics.
The study enrolled 23 women, whose average age was 57. Seven of these 23 women had coronary artery disease. All were randomized to take a daily dose (for 30 days) of either 0.625 mg. conjugated oral equine estrogen or an inactive treatment. Then, after four weeks of a washout period, all were crossed over to receive the opposite regimen for another 30 days.
All were evaluated before and after each treatment period, both at rest and during exercise echocardiography, which gives a visual picture of how well the heart is working.
"During exercise, women taking ERT had a lower cardiac double product, indicating that their hearts did not have to work as hard to maintain circulation," explained Dr. Giardina. "Furthermore, smaller left ventricular end-systolic diameters in the women on ERT indicated that the heart chamber is contracting more effectively and emptying more blood with each beat." It is not clear whether this improved contractility is a direct effect of ERT or an indirect benefit caused by the lower systolic blood pressure seen in the women on ERT.
Heart Pumps May be Transplant Alternative
Continued improvement in left ventricular assist devices (LVADs) has enabled doctors at CPMC to discharge patients awaiting heart transplantation. "Our early success in sending patients home with these implanted heart assist devices is likely to lead to their use as viable alternatives to heart transplantation," said Dr. Mehmet C. Oz, director of the Mechanical Circulatory Assistance Program and Irving Assistant Professor of Surgery.
Before recent FDA action, LVADs were approved only as a "bridge to transplant"; i.e., they are implanted in people awaiting a donor heart but who suddenly decompensate and cannot survive without extra pumping help. Until recently, LVAD patients had to remain in the hospital, waiting an average of three months for transplantation. However, advances in LVAD technology have enabled physicians at CPMC to discharge seven patients to await transplantation more comfortably-and far less expensively than in an intensive care unit-at home.
"Our work demonstrates that patients can live for prolonged periods at home on artificial circulatory support devices, bringing us closer to the goal of replacing the heart with a mechanical device on a long-term basis," explained Dr. Eric A. Rose, chairman of surgery and originator of the LVAD program.
This is good news for the more than 40,000 Americans who have end-stage heart failure, because only about 2,200 heart transplants are performed annually. In addition to the well-known shortage of donor hearts, many patients are not suitable candidates for transplantation because of their advanced age or other medical problems.
LVADs assist the pumping function of the heart. The earliest models, developed more than 20 years ago, were quite cumbersome, keeping patients tethered to large external pumps and their pneumatic power systems. Recent technology advances have yielded a portable, battery-powered version, its power source worn on a belt or shoulder holster.
The LVAD used at CPMC is the vented electric Thermo Cardiosystems HeartMate. About four inches in diameter, less than two inches thick, and weighing about one and a half pounds, the pump is implanted in the abdomen. It is attached to the heart and receives and pumps blood into the circulation, leaving the natural heart in place to do what little it can offer in maintaining circulation and to continue its role in other important functions.
A cable from the pump extends out of the body and is connected to a battery pack. With proper care, this connection can be maintained for long periods without infection. After discharge, patients and their caregivers must provide simple maintenance for the LVAD, including changing the battery pack every six to eight hours, changing the dressings around the cable exit daily, and keeping it dry.
A major advance of these new LVADs is a textured internal surface that reduces the likelihood of blood clots that can lead to stroke, a serious problem in earlier devices. No anticoagulation medication other than aspirin is needed.
No deaths, serious device malfunctions, or infections have occurred among the discharged patients. All have been able to maintain their LVADs safely.
CPMC pioneered the use of balloon pumps as cardiac assist devices and is now the U.S. leader in clinical application of this technology. Since 1991, 14 patients ranging in age from 16 to 62 have received battery-powered LVAD implants at CPMC, the largest volume of any hospital worldwide. After recuperation, 10 of these patients were considered "dischargeable" before transplantation-that is, physically healthy enough and able to provide appropriate self-care. Of these 10, three were transplanted before they had an opportunity for discharge and seven went home to await a donor heart. So far, the longest time any patient has spent on a battery-powered LVAD has been 503 days.
During their time on the LVAD, most patients have shown marked improvements in blood pressure and cardiac output, as well as in kidney and liver function.
"A major value of LVADs is that they don't just help the heart but also reverse many destructive changes in the body's physiology that arise from heart failure," explained Dr. Oz. Thus, patients are likely to be in better health-and better able to withstand the rigors of major surgery-when transplantation eventually occurs. Indeed, the recovery was so great in two patients that their LVADs were removed and transplants were no longer required.
This success led to a major trial to begin this spring to test LVAD use at home.