Dallas, TX - The largest-yet analysis of its kind supports the use of cardiac resynchronization therapy (CRT), either with or without defibrillator backup, in patients with NYHA class 4 heart failure, at least in many who are ambulatory and don't require prolonged IV inotropic therapy [1].

The device therapy can help them live and stay out of the hospital longer, and, contrary to some concerns, the implantation procedure doesn't seem to put them at special risk, conclude Dr JoAnn Lindenfeld (University of Colorado Health Science Center, Denver) and associates in a report from the January 16, 2007 issue of Circulation.

The group's retrospective look at the sickest patients in the COMPANION trial, which was instrumental in establishing CRT as a mainstream HF therapy [2], suggests that it can significantly benefit some patients with disease more advanced than NYHA class 3, for whom such evidence has been in short supply.

Although CRT is a recommended option for patients in NYHA class 3 or 4, most CRT studies have had small numbers of class 4 patients and didn't separate them from those in class 3, Lindenfeld told heartwire. No other randomized CRT trial has had even close to COMPANION's >200 patients in NYHA class 4, she observed, adding that the current analysis should give clinicians more confidence in considering such patients for device therapy.

What is reassuring . . . is that appropriately selected ambulatory patients with severe but stable HF and no need for inotropic support can have acceptable risks for procedure-related complications.

"I think what our paper does is give some support to putting these devices in class 4 patients who are like the patients in the study—that is, they were ambulatory and not in the hospital at the time it was decided to do the procedure," Lindenfeld said. "But the mortality in these patients was still high, so I think we still need better ways to pick out who's likely to respond to resynchronization and who is not. That's true of all patients, but it's more of an issue in the class 4 patients, who are so critically ill."

As previously reported by heartwire, the COMPANION trial randomized 1520 patients in the US with NYHA class 3-4 ischemic or nonischemic HF, an LVEF <35%, and QRS-interval prolongation to receive optimal contemporary drug therapy alone or with implantation of a device programmed to either CRT only or with a defibrillator (CRT-D). Patients had to be ambulatory and in sinus rhythm but also must have had "a hospitalization for the treatment of HF or the equivalent" during the preceding year. Exclusion criteria included an HF hospitalization or prolonged IV inotropic or vasodilator therapy within the past month and recent coronary revascularization, "refractory" atrial arrhythmias, or MI.

The device therapies were associated with significant 19% and 20% declines in risk for the primary end point, a composite of death and all-cause hospitalization; CRT-D, but not CRT, also lowered all-cause mortality.

In the current analysis, both CRT and CRT-D, compared with optimal therapy alone, significantly improved the risk of the primary composite end point among the 217 patients who were NYHA class 4 at baseline. In both device groups, risk reductions for all-cause mortality by itself fell short of significance. The median follow-up times were seven months for the control group and 14 months for recipients of either device therapy.

"Improvement in the primary end point was demonstrated for both CRT and CRT-D despite an 18% and 12% rate of failed implantation for CRT and CRT-D, respectively. Although only CRT-D prolonged the time to sudden death, our data do not demonstrate a significant difference between CRT and CRT-D in any of the end points examined," Lindenfeld et al write. "These data represent the first demonstration that NYHA class 4 patients benefit from either CRT or CRT-D."

Device therapy also emerged as relatively safe in the NYHA class 4 cohort, according to Lindenfeld et al. Duration of hospitalization for implantation averaged about four days for both class 3 and class 4 patients; none of the class 4 patients died in the hospital. The one-year risk of adverse events was 40% for the patients who entered the trial in NYHA class 4 and 21% for those initially in class 3 (p<0.0001), but despite the difference, they write, the risk/benefit ratio for device therapy among the NYHA class 4 patients was "excellent."

In an accompanying editorial [3], Drs WH Wilson Tang and Gary S Francis (Cleveland Clinic, OH) write, "What is reassuring from this COMPANION post hoc analysis is that appropriately selected ambulatory patients with severe but stable HF and no need for inotropic support can have acceptable risks for procedure-related complications." Indeed, they write, patient selection is key to the treatment's appropriateness in NYHA class 4 HF. "The goals and potential benefits of CRT/CRT-D therapy can be very different as symptom burden increases, and Lindenfeld and colleagues have presented insightful findings that call for more research in this area."