The study showed that IFNB-1b treatment led to a significant reduction of viral load, with some evidence of clinical improvement in those with CVC, and indicates for the first time that a biopsy-based specific and causal therapy is possible for this condition, Schultheiss noted. But he stressed that a phase 3 trial is needed for definitive proof of concept and that he is currently in discussions about this with Bayer. A final decision has not yet been made on the phase 3 study, he told heartwire, but added that the company "is much more positive than we thought."

This is provocative but not definitive.

Discussant of the study, Dr Michael Felker (Duke University, Durham, NC), said that although this was only a phase 2 study, it is nevertheless the largest randomized controlled trial conducted to date in CVC. "Now, instead of just treating these patients with heart-failure therapies," there may be the option of a specific treatment, he said. However, he also stressed that a phase 3 trial is needed to help understand the relative benefits and risks of IFNB-1b in this patient population.

And Dr Clyde Yancy (Baylor University Medical Center, Dallas, TX) told heartwire he has some concerns about this study: "This is provocative but not definitive."

Idiopathic, or unexplained, dilated cardiomyopathy (IDCM) is a common cause of heart failure that disproportionately affects younger patients and is the most frequent indication for heart transplantation. Findings of viral persistence in the myocardium have been found in around 50% of IDCM patients, leading to the concept of a new clinical entity of CVC. Such patients have a poor prognosis, Schultheiss noted.

In their placebo-controlled, randomized, double-blind, Europe-wide multicenter study, 143 patients with CVC were randomized to one of two doses of IFNB-1—4 MIU per injection or 8 MIU per injection—or placebo every other day. This is a much lower dose than is used in MS, Schultheiss said, "because we expected cardiovascular side effects, but we didn't get them." Patients were treated for 24 weeks followed by a 24-week follow-up phase and had to undergo serial endomyocardial biopsies, as this is the only way to make a clear diagnosis of CVC, the German doctor explained.

The primary end point was virus load reduction/elimination, which was reduced overall in both groups taking IFNB-1b compared with those on placebo (p=0.048). There was a significant effect of the treatment on quality of life in the interferon group compared with placebo (p=0.032), and there was also some indication of reduction in NYHA class in those taking the interferon, he noted. However, this lost significance by the end of the study due to an improvement in this parameter in the control group.

There also appeared to be a differential effect of the therapy on viral load reduction, depending on the type of virus causing the CVC, Schultheiss noted, with the effect being greater in those with CVC caused by enteroviruses or adenoviruses and less in those in whom the CVC is caused by a parvovirus.

Discussant Felker told a press conference that the aim of this phase 2 trial "was not to prove definitively that something has a clinical effect, but to look for a signal worth pursuing in phase 3." Although this was a positive trial in many regards, there were a variety of clinical events that did not reach significance with the treatment, such as the six-minute walk, he noted.

And there remain many unanswered questions, he said, noting, "What is the optimal timing in the disease course for interferon therapy? Is interferon more effective against some viruses than others?

"IFNB-1b is an expensive therapy—around $10 000 a year, requiring every-other-day injections," he pointed out. "A phase 3 trial will help us better understand the benefits and risks."

Although biopsying the heart sounds barbaric, in the right hands it is safe, but it's not something your average cardiologist is accustomed to doing.

Another important point, he stressed, is whether the low complication rate of endomyocardial biopsy seen in expert centers in this study can be replicated in broader clinical practice. "Although biopsying the heart sounds barbaric, in the right hands it is safe, but it's not something your average cardiologist is accustomed to doing," he commented

One doctor on the press conference panel said the risks of endomyocardial biopsy are similar to that of coronary procedures, but Yancy told heartwire this is only true of patients who have already had a heart transplant. In patients who have not had a transplant—which was the patient population in this study—the risk is higher, he explained.

"We need to pause for long enough to look for biomarkers so we can forgo the issue of having to specify biopsy," Yancy said.

"I would have hesitancy moving ahead with this: it's costly, the study has demonstrated only a reduction in viral load, and it's not clear that this would improve clinical outcomes. The risks are unrealized, and the patient cohort has not been defined in a precise way," Yancy concluded.