title: Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls.
abstract: OBJECTIVE
  To analyze cases of clozapine-induced myocarditis for clinical and diagnostic trends.
  
  
  METHODS
  A case definition was developed by a multidisciplinary group using reports of myocarditis with clozapine submitted to the Australian Therapeutic Goods Administration. The definition uses for diagnosis either histology or the combination of new signs of cardiac dysfunction combined with a cardiac-specific diagnostic parameter occurring within 45 days of starting clozapine. Potential cases of clozapine-related myocarditis occurring between January 1993 and September 2008 and a comparative group of long-term clozapine users were documented from the patients' medical records.
  
  
  RESULTS
  Thirty-eight of 59 reviewed cases met the case definition. Three patients died, and the diagnosis for these was confirmed on cardiac histology. Nearly all of the remaining patients had persistent tachycardia and elevated troponin level. The time to onset was 14-22 days in all except 2 patients. Of the patients who survived, 66% (23 cases) had eosinophilia occurring 0-7 days (mean, 4.0) after the peak in troponin. C-reactive protein (CRP) level was elevated to above 100 mg/L (952 nmol/L) in 79% (23 cases), and some had elevated levels of CRP when troponin level was still normal. None of the control group (47 patients) met the case definition.
  
  
  CONCLUSIONS
  Eosinophil counts should not be relied on for diagnosis of clozapine-related myocarditis, but elevated CRP may be an early indicator of developing myocarditis. Patients starting clozapine should be actively monitored for myocarditis during the first 4 weeks, with extra care taken during week 3.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Hospital, Melbourne, Victoria 3004, Australia. kathlyn.ronaldson@med.monash.edu.au
authors.forename: Kathlyn J
authors.initials: KJ
authors.lastname: Ronaldson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Taylor
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Topliss
authors.forename: Maros
authors.initials: M
authors.lastname: Elsik
authors.forename: John J
authors.initials: JJ
authors.lastname: McNeil
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001315:Australia; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D004452:Echocardiography / Q000706:statistics & numerical data; D004802:Eosinophilia / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000453:epidemiology; D015637:Gated Blood-Pool Imaging / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000139:chemically induced* / Q000175:diagnosis*; D013610:Tachycardia / Q000175:diagnosis / Q000453:epidemiology; D014336:Troponin / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; D014336:Troponin; D002097:C-Reactive Protein; D003024:Clozapine