Dr. Lieberman is involved in clinical trials to improve cardiac resynchronization therapy in heart failure patients.

When heart-failure specialists told Randy Lieberman, MD, in 1994 that one of his patients should be released from the hospital and sent home to die, Dr. Lieberman wouldn't accept it. "He wasn't ready to die, and I guess I wasn't ready to let him," recalls this assistant professor of internal medicine/cardiology at Wayne State University and director of cardiac electrophysiology at the Detroit Medical Center.

The patient's heart was failing despite the use of an internal cardiac defibrillator (ICD) that automatically delivered an electrical charge each time his heart began pumping at too high a rate. Called fast heart arrhythmia or ventricular tachycardia, this condition is fatal if prolonged for more than a couple of minutes. "He had progressed to the point where the heart-failure expert doctors called me and told me that they had to turn off the ICD and let him go home, because there was really nothing more we could do for him."

Dr. Lieberman had another idea. He was immersed in a research project on a type of biventricular pacing, which is basically a pacemaker that is specially designed to maintain a regular heartbeat by sending electrical charges to both lower lobes of the heart. Previously, biventricular pacing required open-heart surgery, a taxing procedure even on the healthiest of patients. Lieberman's method involved sliding the wires and leads of the pacemaker into position by following the veins of the heart - a much less-invasive option for patients with advanced heart problems.

"We decided to talk to the patient about the technique to see if he wanted to try this. He said, 'Let's go for it. What do we have to lose?'" During the surgery, Dr. Lieberman remembers trying to direct the leads through the tortuously curving passageways of the veins. After more than six hours, the patient and doctor left the operating room. The leads were in place and the heart was beating, but the patient's heart had been near collapse going into the surgery, and the procedure was long. "I went home that night not sure what I'd find the next morning," Dr. Lieberman said. 

What greeted him the following day nearly took his breath away. "When I arrived, he was sitting up in a chair. I asked him who helped him up out of bed, and he said, 'No one. I just decided to sit up here after coming back from the bathroom.'" Dr. Lieberman was stunned. This was the same patient who 24 hours earlier was unable to walk across a room; the same patient whose life had depended on a drug-infusion pump to flood his heart with special medications. The patient proved his statement by walking around the entire nursing station, Dr. Lieberman recalled.

While that success story is impressive, Dr. Lieberman cautioned that it is just that: one success story. Still, the accomplishment gave the doctor additional confidence that his research was headed in the right direction. Now, nearly six years later, he is working with the company Medtronics to further develop biventricular pacing and is also part of a multicenter research study to determine whether the combination treatment of biventricular pacing plus the use of an internal cardiac defibrillator is effective.

According to Dr. Lieberman, biventricular pacing goes beyond the capabilities of traditional pacemakers. While each sends electrical charges to the heart to speed up the rate to the normal levels necessary to support the body, biventricular pacing is more effective at treating the enlarged heart muscle that is associated with congestive heart failure.

Ordinarily, he described, the brain dispatches an electrical signal to the heart to tell it how fast to beat. That signal spreads almost instantaneously to both the left and right sides of the heart muscle, and it contracts properly. "When the heart becomes very enlarged - what we call dilated cardiomyopathies - the electrical signal doesn't spread as quickly to the right and left sides of the heart," he said, noting that an enlarged heart can be up to three times the normal size. 

Traditional pacemakers are hooked up to one side of the heart, and help the signal travel from top to bottom via the heart's A-V node (atrioventricular node), but not from side to side. In other words, the pacemakers help deliver the electrical impulse from the atrium to the ventricle on one side of the heart, but not from one ventricle to the other.

"One side squeezes earlier than the other. They're out of kilter," he said. The synchronization is crucial, because the blood moves in a perfectly timed loop from the left atrium to the left ventricle and out to the body, then to the right atrium, the right ventricle, and out to the lungs. From the lungs, the blood returns to the left atrium to begin another circuit. When the timing is off, one of the heart's chambers may not have squeezed out its blood before the next supply arrives. Because of this timing problem, each heartbeat in patients with enlarged hearts may only be pumping a sixth of the normal volume.

"We're placing pacemaker leads in a new way into the heart, so we can resynchronize it," Dr. Lieberman said. This technique entails threading the leads through an opening, called the coronary sinus, in the right atrium, then into a tiny blood vessel that travels from the inside to the outside of the heart, and finally down veins on the surface of the heart muscle. "We have a lead going to the left side and a lead going to the right side, we connect them together in our pacemaker, and we cause the left side and the right side of the heart to squeeze better. This allows us to resynchronize the heart."

The most difficult part of the whole procedure is guiding the leads through the veins, he said. "That's been the whole trick. That's why it took us six hours in the initial surgery back in 1994. We had the old types of wires, and we just had to push and shove and try to find the right openings," he described. Now, he is working with Medtronics to develop new techniques, along with wires and leads that are easier to steer, and special catheters and sheathes. He is also one of a four-member team of physicians traveling around the world teaching the surgical procedure to other physicians.

As his work continues, he is participating in a study that is providing solid evidence of the safety and benefits of biventricular pacing, he said. Dr. Lieberman is on the advisory board that designed the MIRACLE trial (Multicenter InSync Randomized Clinical Evaluation). He said the board worked closely with heart-failure-expert doctors to ensure that the data collected in the study is thorough and accurate. 

The MIRACLE trial is looking at several factors, including the distance a patient can walk in six minutes with and without the pacing, which can be turned on and off by the physician. "Without biventricular pacing, most of the patients can walk about 300 meters. With pacing, most of the patients can walk almost 400 meters. That shows a significant improvement," Dr. Lieberman said. The trial will also measure quality-of-life standards and the amount of blood pumped by the heart. With pacing, the average patient pumps 10-15 percent more blood, he said. "Again, that's a significant improvement."

By June 2000, the board expects the trial to be completed and to have data from 30 U.S. centers and more than 200 patients.

Although the MIRACLE trial is still under way, Dr. Lieberman said the encouraging initial results have prompted another clinical trial. "When we started looking at the data and at survival, we noticed that there were patients who were dying suddenly," he said, and often the cause of death was fast-heart-rate arrhythmias. "We need to protect the patients against the life-threatening arrhythmias that cause half of the deaths to heart patients every year. We really wouldn't be doing justice to the patients to just treat them for heart failure, because they might die the next day from an arrhythmia."

He noted, "That's why I started implanting internal cardiac defibrillators when we were doing biventricular pacing." In fact, he believes he was the first surgeon ever to implant a combination biventricular pacing/internal cardiac defibrillator.

The new trial is called the InSync ICD triall. Sponsored by Medtronics, the trial will test the combination treatment. Said Dr. Lieberman, who is one of the researchers involved in the trial, "The question is: Can we reduce the total mortality? Can we make people live longer by treating them with biventricular pacing to improve their heart failure and using an internal cardiac defibrillator to protect them from sudden cardiac death?"

As the population ages, and the number of heart-failure cases rises from the current 400,000-500,000 a year, the advantages will only escalate, he said.

Although the trial results are still pending, Dr. Lieberman hazarded a prediction about the combined treatment of biventricular pacing and internal cardiac defibrillators: "I think that this is going to be one of the greatest benefits ever for the treatment of heart failure."