By THOMAS M. BURTON Staff Reporter of THE WALL STREET JOURNAL March 20, 2001

• Skyaid comment: It has been very difficult to determine who needs an ICD implanted before heart failure.
  The total costs if all candidates got implants were in the range of $100,000 per life saved.
  This may be cost effective for those who have already have heart disease.

ORLANDO, Fla. -- The startling idea that electrical devices can treat millions of desperately ill patients with congestive heart failure has just passed a pivotal test.

A surgically implanted electrical device called the InSync, from pacemaker giant Medtronic Inc., dramatically improved the condition of clinical-study patients whose hearts have weakened pumping capacity. These results, to be made public Tuesday at the American College of Cardiology meeting here, are from the first major study in which this electrical "resynchronization" of the heart was pitted against a placebo. (Placebo-group patients had the devices installed but not switched on for six months.)

"The results were markedly positive," says William T. Abraham, the University of Kentucky's chief of cardiovascular medicine, who headed the clinical study. "I think this will be a rapidly adopted therapy that will have substantial impact on heart-failure patients' lives."

Nearly five million Americans suffer from what is called chronic or congestive heart failure, and their numbers are growing at 10% a year, a rate so high that some researchers describe the problem as an epidemic. About one million patients a year are admitted to hospitals with acute heart failure, an advanced stage of the condition in which their lungs and lower extremities are typically laden with fluid and they are gasping for breath.

Dr. Abraham estimates that 750,000 to 1.3 million of the five million Americans suffering from heart failure have a cardiac electrical malfunction and are potential candidates for Medtronic's InSync device. A similar fraction of the approximately 15 million heart-failure patients overseas also would be candidates.

Thus the stakes are huge for Minneapolis-based Medtronic, and for Guidant Corp. of Indianapolis, which makes a competing device. Collectively, these represent potentially the largest advance in the treatment of heart-failure patients in several years. While Guidant isn't presenting research results at this meeting, people familiar with a Guidant study of its Contak CD device say patients with it also fared considerably better than those in a placebo group. Both companies have applied for possible Food and Drug Administration approval. A third company, St. Jude Medical Inc. in St. Paul, Minn., estimates it is about a year behind its competitors in testing such a device.

Both the InSync and the Contak are based on the idea that heart failure, in about one-quarter to one-half of the affected patients, is in large part an electrical malfunction. This typically means there is a problem in the network of nerves that send signals to the heart telling it to pump.

The InSync device is a silver box slightly bigger than a quarter that is implanted in the shoulder area, and has electrical leads running through blood vessels to the heart. The device, which works off a battery, sends signals to help better synchronize the heart's pumping. In the study being presented Tuesday, the InSync was tested in 134 people who are in the most-advanced stages of heart failure. Whether the device will help less-advanced cases remains to be proven.

"Heart failure" is something of a misnomer. It doesn't mean that the heart has completely failed, but that its pumping ability is compromised. Most often, this is due to coronary artery disease and heart attacks, although in some rare instances viruses can cause heart inflammation that leads to heart failure. Other causes can include high blood pressure and heart valve disease. Patients' bodies compensate by building up more fluid: If there is a greater volume of blood to circulate, a weakened heart can propel it through the body more easily. In time, though, that fluid can wreak havoc. It accumulates in places like the lungs, and causes patients to gasp desperately for breath even when resting. Hence, the name "congestive heart failure."

These patients frequently come into emergency rooms unable to breathe after slight dietary changes such as eating a salty pizza. They often need to stay for days in the hospital, and such visits cost about $40 billion annually in the U.S. alone.

Because many such patients suffer from faulty cardiac wiring, their hearts' ventricles beat out of sync instead of working in tandem. So blood sloshes back and forth uselessly inside the heart, rather than carrying oxygen to vital organs. Morton Mower, a Baltimore cardiologist who later became a Guidant researcher, first discovered more than 20 years ago that electricity from a pacemaker-like device could help heart-failure patients. But Guidant and Medtronic, intent on first delivering products like new-generation cardiac defibrillators, have only in the past decade cast their gaze on heart failure.

In the past few years, however, there have been very compelling success stories with individual patients using early prototypes of InSync and Contak. Many skeptics until now have argued this could simply be a powerful "placebo effect" at work. One such skeptic has been Milton Packer, Columbia University's chief of circulatory physiology. Dr. Packer has pointed out that patients really want to respond when doctors try therapies, especially dramatic and invasive ones like a surgically installed device.

That is why it is so important that this latest clinical trial has a very large placebo group for comparison. Patients were randomly assigned to it or the treatment group, in which 134 patients got their devices turned on. The placebo, or control, group included 132 patients.

All patients continued to receive standard drugs like ACE inhibitors to dilate arteries and veins, and diuretics to reduce fluids. Then the patients were measured on three scales: their degree of impairment when they are at rest compared with when they are active, the distance they could walk in six minutes, and their "quality of life" according to certain objective measures. The research involved 44 medical centers in the U.S. and Canada. "All three of the measurements were markedly positive" compared with the control group, says Dr. Abraham. He points out that, as expected, patients in the placebo group improved -- but not as much as those with InSync turned on.

Now, having seen the data from the Medtronic trial, Dr. Packer takes a more upbeat stance. "There's no doubt that this is a positive trial and met its objective in a convincing manner," he says. "One would imagine that this type of approach does make a meaningful impact on patients."

Chevelle Hayes, a 33-year-old mother of three from Trotwood, Ohio, illustrates the long-term improvements produced by the device, as well as the power of the placebo effect. Apparently because of a case of meningitis, Ms. Hayes's heart was failing by age 31, and she was on the list for a heart transplant. At one point, she literally couldn't breathe and had to be rushed to the hospital two years ago. While drugs helped, she began deteriorating.

She had the InSync installed, but was initially in the placebo group. Even so, she says, "I was able to convince myself I felt somewhat better." Now that the device has been on for about 18 months, she has improved greatly. "I can stay up all day now," she says. "I'm able to cook dinner, and take care of my children."

Write to Thomas M. Burton at tom.burton@wsj.com

see also ICD saves 100,000 lives a year.