Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders.
BACKGROUND
The beneficial effect of immunosuppressive treatment on myocarditis is still controversial, possibly because the immunologic and virological profile of potential candidates is largely unknown.


RESULTS
Out of 652 biopsied patients, 112 had a histological diagnosis of active lymphocytic myocarditis; 41 of these 112 patients were characterized by progressive heart failure despite conventional therapy and were treated with prednisone and azathioprine for 6 months. All were resubmitted to cardiac catheterization, angiography, and endomyocardial biopsy at 1 and 6 months and followed-up for 1 year. A total of 21 patients responded with prompt improvement in left ventricular ejection fraction from 25.7+/-4.1% to 47.1+/-4.4% and showed evidence of healed myocarditis at control biopsy. Conversely, 20 patients failed to respond and showed a histological evolution toward dilated cardiomyopathy: 12 remained stationary, 3 underwent cardiac transplantation, and 5 died. We retrospectively performed a polymerase chain reaction on frozen endomyocardial tissue for the most common cardiotropic viruses and assessed circulating serum cardiac autoantibodies. Viral genomes were present in biopsy specimens of 17 nonresponders (85%), including enterovirus (n=5), Epstein-Barr virus (n=5) adenovirus (n=4), both adenovirus and enterovirus (n=1), influenza A virus (n=1), parvovirus-B19 (n=1), and in 3 responders, who were all positive for hepatitis C virus. Cardiac autoantibodies were present in 19 responders (90%) and in none of the nonresponders.


CONCLUSIONS
In patients with active lymphocytic myocarditis, those with circulating cardiac autoantibodies and no viral genome in the myocardium are the most likely to benefit from immunosuppression. The beneficial effect of immunosuppression in hepatitis C virus myocarditis suggests a relevant immunomediated component of damage.
Frustaci
Andrea
A
Department of Cardiology, Catholic University, Rome, Italy. biocard@rm.unicatt.it
Chimenti
Cristina
C
Calabrese
Fiorella
F
Pieroni
Maurizio
M
Thiene
Gaetano
G
Maseri
Attilio
A
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D001706:Biopsy; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects / Q000821:virology; D006333:Heart Failure / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome
D001323:Autoantibodies; D002316:Cardiotonic Agents; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone