A small study in patients with virus-negative inflammatory
cardiomyopathy indicates that six months of immunosuppressive
therapy can improve left ventricular function and results in a
disappearance of inflammatory infiltrates. According to Dr Andrea
Frustaci (La Sapienza University, Rome, Italy), who presented the
results during the final hotline session of the European Society of
Cardiology Congress 2008, the findings justify a strategy of first
testing patients for persistent viral load and, if negative,
proceeding with immunosuppressive therapy.

As he explained in his presentation, the role of immunosuppressive
therapy in inflammatory cardiomyopathy has been debated because of
controversial results in children and adults presenting with either
cardiac arrhythmias or heart failure. Previous studies of
immunosuppression in inflammatory cardiomyopathy have produced mixed
results, but retrospective analyses of these studies have suggested
that the key is to first distinguish between virus-negative patients
and virus-positive patients, in whom antiviral agents may be
effective but immunosuppression may be harmful.

For their study, Frustaci et al randomized 85 patients with active
lymphocytic myocarditis and more than six months worth of LV
dysfunction to immunosuppression (1 mg/kg daily prednisone for four
weeks, followed by a 0.33 mg/kg daily dose for five months) and
azathioprine (2 mg/kg daily for six months) or to placebo. At
baseline, all patients had a mean left ventricular ejection fraction
(LVEF) of 27% and most were in NYHA heart failure class 3 or 4.

At six months, however, 88% of patients in the immunosuppression
group had improved LV diameter and contractility, defined as a >10%
increase in EF and reduction in LV dimension, whereas LV function in
the placebo group actually worsened over the study period. Even in
patients in the immunosuppression group with the most advanced
disease, left ventricular end diastolic dimension (LVEDD) improved
by up to 90 mm.

Lack of a response in 12% of patients in the immunosuppression group
likely points to the presence of viruses that were not picked up in
the initial screening or mechanisms of myocardial damage and
inflammation not susceptible to immunosuppression, Frustaci
concluded.

Dr Andre Keren (Hadassah University Hospital, Jerusalem, Israel),
discussant for the trial, emphasized that Frustaci et al's study
represents the first randomized trial of immunosuppression in
patients with proven chronic myocardial inflammation but with virus-
negative biopsies.

"The remarkable results of this report compare favorably with those
of a previous randomized study of immunosuppression in chronic
myocardial inflammation in which viral status was not evaluated,"
Keren said.

The choice of whether to incorporate immunosuppression into routine
clinical practice will be enhanced, Keren noted, by ongoing
multicenter studies of immunomodulatory therapy.