New devices offer options to your advanced CHF patients

Cardiologists guardedly optimistic about pacing and resync gear

(Editor’s note: This is the first of a two-part series on new therapies that offer hope for your end-stage patients. Some are improved bridges to transplant, and some are designed as permanent therapy for patients with no other alternatives. This month, you’ll read about new devices that are gaining on the problem. They take an electrophysiological approach by pacing and resynchronizing the heart. Next month, CHF Disease Management will present other new strategies that promise to improve and extend your patients’ lives.)

According to some cardiologists and cardiac electrophysiologists, there’s new hope for CHF patients in the advanced stages of their disease. Some of those who are most enthusiastic about new technologies are physicians who have been instrumental in testing four new, life-saving devices. But others are guardedly optimistic as well. Technology manufacturers say with half a million new heart failure cases diagnosed each year, and because up to half of those with advanced heart failure develop abnormal rhythms of the heart, it is those patients that the following innovative devices are designed to help.

"For patients with CHF, the heart’s pumping ability is severely impaired, resulting in a poor quality of life and high morbidity," says Richard A. Gray, PhD, in the Cardiac Rhythm Management Laboratory at the University of Alabama at Birmingham. "Improving the function of the heart has the potential to improve their lifestyle and life span. Presumably, increasing the synchrony of the heart’s contraction sequence will help to improve its pumping ability."

He adds new technology may be a reasonable way to improve heart function in CHF patients through ventricular pacing. "The ability to implant leads transvenously provides the opportunity to offer treatment for CHF patients without the difficulties associated with open heart surgery." But he says this treatment path raises some important questions that need to be addressed: How many pacing sites are needed? Where should the leads be placed? What should be the relative timing of the pacing stimuli in relation to the patients’ normal rhythm and among various pacing sites?

"Clearly, the patients we are treating today with advanced heart failure often need something more than medicines to turn off’ all the abnormalities that accompany advanced heart failure," says Marc Silver, MD, who runs the CHF center at Christ Hospital in Chicago, a division of Advocate Healthcare. "Nonpharmacologic therapy, such as multisite pacing, often provides that little bit to get those patients over the hump and allows their hearts to slowly begin to recover and may allow the medications to work. Many patients would prefer a device over still another pill."

Silver says cardiologists think they know some of the ways this process works, but the clinical trials now under way are going to help define who will benefit, for how long, and perhaps why. "This approach of multisite pacing is still another demonstration of the fact that we continue to learn — namely that even the very advanced heart of someone with heart failure may be recoverable if we can support it and get the patient into a more advantaged’ position."

"The theory behind biventricular pacing makes good sense, and the early trial results are encouraging," says Edward F. Philbin, MD, in the Section of Heart Failure and Cardiac Transplantation at Henry Ford Hospital in Detroit. "Appropriately, there is a lot of enthusiasm for biventricular pac-ing among academic heart failure cardiologists. However, we need to see the results of larger trials, and we need mortality data."

Philbin points out that researchers shooting for better CHF treatments have suffered their share of misfires. Therapeutic agents can produce promising results in small, early studies, but then in subsequent definitive studies, they can still fail to show a lower-mortality benefit among patients who receive them.

It’s still not known if promising concepts in electrophysiology will translate into better treatments. "Current implantable defibrillators are not biventricular, and dual chamber pacing must be achieved by another source," says Richard Pozen, MD, national medical director of Vivra Heart Services in Fort Lauderdale, FL. "These new devices offer both a defibrillator and a pacemaker capacity. It has been well known that people who lose synchrony have a reduction in cardiac output. That is the main reason why biventricular pacing developed."

Pozen adds, however, that it is unclear that the improvement in cardiac performance is significant enough and sustained long enough to provide adequate therapy for CHF patients. "These devices have some new twists such as using the coronary sinus [which produces left atrial rather than conventional right atrial pacing] and using right and left ventricular leads instead of traditional right ventricular ones only.

"So far, the number of patients tested seems small compared to the size of the potential population. The bottom line is that physiologically, these devices make sense but the issue is whether the improvements will be substantial enough to improve quality or duration of life and whether results will be sustainable. This may be a unique subset of patients who have both life threatening arrhythmias and CHF, and these devices may offer some advantage over current devices."

Three companies, all located within a short radius of Minneapolis and St. Paul, MN, find themselves revving up at the starting gate. They have products in development, which enable concurrent biventricular pacing and resynchronizing in heart failure patients. Three devices already have been tested in Europe and are being evaluated now in American clinical trails. From Medtronic come the InSync and InSync ICD implantable cardioverter defibrillator (ICD) and the Attain family of leads — Attain LV, Attain SD, and Attain CS; from Guidant come the Contak CD and its Easytrak lead; and from St. Jude Medical come the Frontier system and the Aescula LV lead.

St. Jude’s approach is somewhat different from the other two companies. They are investigating the use of left ventricular pacing for patients with both CHF and atrial fibrillation. According to a financial report, the niche population represents approximately 25% of CHF patients.1

All the systems are anticipated to allow permanent therapy for symptomatic advanced heart failure in patients. And the leads are specifically designed to access the heart through a noninvasive transvenous approach.

Physicians at more than 35 centers in the United States and two in Canada are evaluating the performance of Medtronic’s products on about 300 patients as part of two clinical trials: Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and MIRACLE ICD.

MIRACLE involves Medtronic’s InSync device, and MIRACLE ICD involves Medtronic’s InSync ICD device. Primarily, both studies will measure the effects of cardiac resynchronization therapy on patients’ level of heart failure, on the patients’ ability to perform physical activity, and on their subjective quality of life. In addition, the studies will measure the effects of the treatment on the following factors:

- the timing of the contractions of the heart’s chambers;

- oxygen use during exercise;

- the size and performance of the heart;

- levels of certain hormones associated with heart failure;

- the amount of health care services used by participants;

- length of life.

Angel Leon, MD, of Emory Health Care/ Crawford Long Hospital in Atlanta is a consultant for Medtronic and a trial investigator. Early in November, the cardiac electrophysiologist implanted the InSync ICD with the Attain SD lead into a 70-year-old male who presented with symptomatic advanced heart failure and ventricular conduction abnormalities, and who was at risk for possibly lethal heart rhythm disturbances. The patient was otherwise healthy, but was beyond the age limit when transplant programs would consider him. Leon had been following his case for six years.

"Initially he had coronary artery disease and myocardial infarction. And over the past year and a half, his heart had progressively become weaker and he’d developed symptoms of CHF. His heart had enlarged, it wasn’t pumping efficiently, and he had shortness of breath and was accumulating fluid," says Leon. "On top of that, we’d seen some nonsustained bursts of ventricular tachycardia." So he had a combination of heart failure as well as signs of a potentially dangerous rhythm problem.

"He was maxed out on medical therapy," Leon continues. The patient had been treated with at least two diuretics and the beta-blocker carvedilol. Leon says the patient was an ideal candidate for a device that could both pace the heart in a biventricular mode and protect him against arrhythmia.

The device will stay in the patient’s chest until the batteries weaken, at which time Leon’s team will implant a new power unit under a flap of skin on the chest. "The wires stay in for the rest of his life unless there’s a break that would force us to remove them," he says. "My hope is that it stays in a long time because that will reflect the fact that he’s living a long time."

Leon implanted the InSync device through his patient’s venous system in the pectoral region. "It is a micro-invasive procedure," says the physician, "as all pacemakers are implanted today." Because they didn’t have to open the chest, the patient went home four days after implantation. "The intent of the biventricular pacing was to see if we could help him," says Leon, "but if his meds can be reduced, that would be an extra benefit." As CHF Disease Management was in to press, the patient was doing well.

This was the first time Leon implanted the InSync device with the Attain lead. He’d done a number of similar implants with other devices and with devices that he had modified to accomplish the same result. "Before these devices were available," says Leon, "the only thing we could do if we wanted to achieve the biventricular pacing capability was to modify existing standard defibrillators and adapt them to pace both ventricles."

The device manufactured by Guidant, Contak CD, has similar capabilities for similar situations. It is also in clinical trials at Emory, and while the intended benefits are similar, the studies have somewhat different inclusion criteria. Both trials are focused on the same patient — NYHA III or IV, wide QRS duration, ejection fraction (EF) <35%, and stable drug regime. (See box delineating the two MIRACLE studies’ inclusion and exclusion criteria, p. 3.)

Candidates for Guidant’s study must have symptomatic heart failure despite optimal drug therapy and must have had at least one episode of cardiac arrest manifested by loss of consciousness due to an irregular heart beat, or have ventricular tachyarrhythmias. Some individuals who have pre-existing defibrillators in need of change out may also be eligible. Leon points out that inclusion criteria change continually over time due to U.S. Food and Drug Administration requirements.

Diana Campau of Medtronic explains that the MIRACLE ICD trial is a prospective, multicenter, randomized, parallel controlled study. "Parallel controlled means that all patients will be implanted with the InSync ICD device," she says. "However they will be assisted to one of two active treatment schedules. One group will receive heart resynchronization beginning immediately; the other group will not receive heart resynchronization for the first six months of the study, but will be switched to therapy after six months. Until then, they will receive only drug therapy.

"At the end of the period, results of the two groups will be compared to their status before receiving the implant. They will then be followed in the study for at least six months afterward. The design of this study provides a very high level of scientific validity for the results, so investigators, sponsors, and regulatory authorities can be certain whether this treatment has benefited the participants," Campau explains.

MIRACLE ICD study participants are monitored at one month, three months, and every six months thereafter. The study is expected to last 12 to 24 months.

John Boehmer, MD, medical director of the Heart Failure Center and the heart transplant program at the Hershey (PA) Medical Center, recently implanted Guidant’s Contak in several patients as a part of one of that company’s three ongoing clinical trials. The trials are PATH-CHF (pacing therapy for heart failure), Vigor CHF, and Ventak CHF.

Treatment returned patient to active life

His most recent implant was performed on an 80-year-old male who presented with ventricular tachycardia. "He had a sustained rate of 190," says Boehmer, a Guidant consultant. "He had been out with a pickup truck picking up a load of mulch. On the way to his son’s house, he had a sudden onset, and his son called for an ambulance." Medication failed to cardiovert him, and so, with the patient’s informed consent, Boehmer’s team implanted the device.

"He had a very large heart and an EF of 20%," says Boehmer. "Clinically he was functional Class II prior to this. We first discussed defibrillators, then offered him the Contak." The patient had exertional dyspnea and he fatigued, but he wanted to remain as active as he had been. On advice of his physicians, he thought the device might afford him a better opportunity to maintain his exercise capacity.

"He was implanted successfully," says Boehmer. "He had some nonsustained ventricular tachycardia afterward but is doing well. The tricky part of this procedure had been cannulating and maintaining the coronary sinus, but the Easytrak lead tracks well and goes in nicely. It has not been difficult." Clinically, the patient is back to Class II, and shortly after his surgery, he finished putting out his mulch. "He was in the hospital for three days after implant, five days after presentation, because we had a little trouble with his creatinines."

St. Jude’s new technology for resync-pacing has not yet been approved in Europe, but its FDA-approved Aescula LV lead is stylet-driven and features a tractable S-curve in the distal segment that enhances its maneuverability during implantation in the left ventricle and provides stability after stylet removal. The first implant in this country was performed at the Orlando (FL) Regional Medical Center by principal investigator Aurelio Duran, MD.

Boehmer says St. Jude’s stylet-type lead has characteristics somewhat similar to the Medtronic lead. "Researchers using that lead have been able to gain access to the left heart with the same level of success as ours," he says.

Reference

1. Morgan Stanley Dean Witter. "U.S. and the Americas Investment Research; Medical Technology; Congestive Heart Failure: A major device opportunity?" Financial report. February 8, 1999.

Suggested reading

• Auricchio A, Klein H, Tockman B, et al. Transvenous biventricular pacing for heart failure: Can the obstacles be overcome? Am J Cardiol 1999; 83:136D-142D.

• Stellbrink C, Auricchio A, Diem B, et al. Potential benefits of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia. Am J Cardiol 1999; 83:143D-150D.

• Kass DA, Chen C-H, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999; 99:1,567-1,573.

• Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 1999; 99:2,993-3,001.