Abstract
Stephen E Kay, James Doery and David Sholl, Departments of Clinical Biochemistry and Adolescent Psychiatry, Monash Medical Centre, Melbourne, Australia:
We refer to the recent correspondence by Reid et al. [1]. They describe a case of myocarditis due to clozapine in a young man who developed electrocardiographic (ECG) changes, but without changes in serum creatine kinase. We report a case of pericarditis associated with clozapine therapy, with ECG changes and serial elevations in serum troponin I, a highly sensitive and specific marker of myocardial injury.
A 16-year-old female with chronic, treatment resistant schizophrenia was seen in the emergency department following a 2-week history of palpitations. One week prior to presentation, she developed central and leftsided chest pain, which was sharp ‘like a knife’, pleuritic in quality, and relieved with paracetamol 1g, orally. The patient also experienced shortness of breath waking her from sleep. Her chest pain worsened 2 days before presentation. She had no history of cardiovascular disease, and was otherwise well. Clozapine, 25 mg daily orally, was commenced 3 weeks prior, and increased to 100 mg daily over 2 weeks. She was also taking benztropine mesylate 2 mg daily orally, and diazepam 2 mg orally, when required for sedation.
On presentation, she had an oral temperature of 37°C; pulse rate of 124 beats/min, respirations of 24/min, and blood pressure of 124/59 mmHg. Physical examination was normal. An ECG showed p-mitrale in lead I, T-wave flattening in lead III, ST-segment elevation concave upward across all leads, and a biphasic P-wave in V1. She was admitted to the adolescent psychiatric unit for monitoring and analgesia, with a diagnosis of pericarditis secondary to clozapine therapy. Her symptoms and ECG changes resolved during admission. Clozapine was continued with the informed consent of the patient, and close consultation with the laboratory and cardiology unit.
Blood tests initially revealed a rise in serum troponin I of 1.89 μg/L (normal, < 0.4), decreasing the following day to 0.29 μg/L (normal, < 0.4). Two weeks later, her troponin I level was < 0.04 μg/L (normal, < 0.4), with complete symptom resolution. On commencement of clozapine, 3 weeks prior to admission, her troponin I was 0.34 μg/L (normal, < 0.4). Patients on clozapine at Monash Medical Centre are routinely monitored with troponin I on commencement of therapy, and at 4-weekly intervals. Significant values in our laboratory for troponin I are acute coronary syndrome < 0.4 μg/L, and acute myocardial infarction > 1.5 μg/L. Serial creatine kinase, urea, creatinine, electrolytes, liver enzymes, and blood films were normal. Viral and bacterial serology was negative. Troponins were assayed on the Dimension RxL clinical chemistry system (Dade Behring Inc., Newark, DE, 19714. U.S.A.), and values were confirmed by re-assay at other Melbourne laboratories.
Clozapine is rarely associated with pericarditis [2], myocarditis and cardiomyopathy [3], or electrocardiograph changes [4], but recent Australian data suggest such cardiac side-effects may be more common than previously thought [1]. Greater monitoring of patients taking clozapine would be expected to detect abnormalities in ECGs, but not necessarily creatine kinase. The most recent and now preferred biological marker is cardiac troponin (I or T) [5, 6]. Troponin I, unlike other cardiac markers, is a highly sensitive and nearly absolutely specific indicator of myocardial damage, reflecting even microscopic areas of myocardial necrosis [5, 6]. Unlike other cardiac markers, troponin I may be elevated for 7–10 days following acute myocardial injury [5, 6]. This is the first reported case of pericarditis due to clozapine, demonstrating elevations in troponin I, which resolved despite continuation of therapy. This report demonstrates the usefulness of troponin I for detecting and monitoring cardiac side-effects in patients taking clozapine, and suggests that troponin I is the preferred marker to monitor cardiac side-effects of clozapine.