Dr Arthur M Feldman

A seven-week course of therapy with EECP produced a significant change in exercise time over six months, a primary end point. But the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial disappointed by failing to show any significant EECP effect on the more conclusive alternate primary end point of peak oxygen consumption, according to some observers.

"We think the study demonstrated that, in patients with NYHA class 2-3 symptoms who are optimally medicated with beta blockers and ACE inhibitors, EECP can provide adjunctive therapy. What we see are improvements in exercise duration, quality of life, and NYHA classification," Dr Arthur M Feldman (Jefferson Medical College, Philadelphia, PA) told heartwire.

A more qualified evaluation of the PEECH findings came from the assigned discussant for Feldman's formal presentation of the trial, Dr Andrew D Michaels (University of California, San Francisco). "The PEECH results are mixed, but there is still reason for optimism that EECP may be a positive addition to patients with heart failure treated with optimal medical therapy." However, he observed, "It is somewhat concerning that the end points that were met . . . are subject to the placebo effect."

It is somewhat concerning that the end points that were met . . . are subject to the placebo effect.

In PEECH, 187 patients with stable ischemic or nonischemic NYHA class 2-3 HF and an LVEF <35% despite optimal medical therapy were randomized to continue on medication alone or supplemented by a standard seven-week course of EECP. Medical therapy consisted of beta blockers and either an ACE inhibitor or angiotensin-receptor blocker in the overwhelming majority. Once the EECP treatment course was completed, patients were followed for six months.

Although neither the patients nor the clinical staff supervising the EECP sessions could be blinded to treatment allocation, the investigators who evaluated the patients throughout the follow-up period were blinded to randomization status.

The trial was designed to be "positive" if EECP proved superior to optimal medical therapy for both of the primary end points at a p value of <0.05 or, alternatively, if at least one of the two end points showed a benefit at a p value <0.025, Feldman explained.

Dr Barry Massie

"They met one of their two primary end points at a level that they predetermined would be significant, so in that sense it's a positive trial," Dr Barry Massie (University of California, San Francisco) told heartwire. But of all therapies for cardiovascular disease, perhaps only surgery has a higher potential than EECP for a placebo effect, he observed. In PEECH, "The only measure that one could consider objective, when the patients actually know what therapy they're getting and made a lot of personal effort doing it, was the only one that was negative."

"Whether that invalidates the positive findings is hard to tell. It certainly lessens the enthusiasm," Massie said. The trial was too small to show more reassuring potential benefits in harder end points like death or hospitalization, he observed. On the other hand, advantages with EECP in the softer end points were sustained for six months, which he called "remarkable. . . . Most placebo effects go away over time."

How is EECP supposed to work? Undertaking EECP takes a certain amount of commitment from patients. For each of the standard 35 EECP sessions, typically one hour-long session per day Monday through Friday for seven weeks, they don three sets of inflatable pressure cuffs—one cuff around each calf, one around the lower thigh, and another around the upper thigh and buttock. They lie down and the device is activated. Guided by a computer that takes its cue from the electrocardiogram, the cuffs inflate in sequence at the start of diastole, starting at the calves and progressing toward the heart. According to descriptions in the literature, the resulting retrograde pressure waves increase diastolic filling and intracoronary perfusion pressures. All three pairs of cuffs then deflate simultaneously just at the onset of systole to dramatically reduce systemic vascular resistance—decreasing the heart's workload and oxygen demands and enhancing cardiac output. Plethysmography shows augmentation of diastolic function during EECP counterpulsation (Source: Vasomedical Inc). According to Feldman, the hemodynamic effects are "more robust than what we see with intra-aortic counterpulsation." In the EECP clinical trial and registry experiences, he observed, the resulting functional improvements have persisted for six months to a year. Why that happens isn't exactly known, and that may be part of the reason EECP, which is approved by the US Food and Drug Administration for both angina and HF, has been slow to catch on with mainstream cardiology in the US. "Part of the acceptance problem has been that the mechanism of action hasn't been explained. But I think we're getting much more data now about mechanistic benefits," Feldman told heartwire. Further information about how EECP works should help the technique's image with cardiologists, he said. "Clearly the most exciting is from some very well done trials showing that there's an improvement in vascular reactivity and endothelial function associated with it." Other research supports such a mechanism by showing the hemodynamic effects of EECP increase systemic levels of nitric oxide and suppress endothelin-1 concentrations. The literature points to other physiologic mechanisms that may be contributing, Michaels observed in his presentation. They include increased production of angiogenic growth factors, promotion of collateral flow, improved ventricular contractile function, and peripheral training effects similar to those produced by exercise.