Pro-BNP as a biomarker of asymptomatic clozapine-related heart dysfunction

Cardiovascular clozapine-related side effects such as tachycardia and orthostatic hypotension are well recognized, but are rarely clinically important. However, the increasing number of life-threatening drug-related complications are giving rise to concerns about cardiac adverse reactions (myocarditis, cardiomyopathy, pericarditis and heart failure). The diagnosis is usually made considering patient's symptoms, such as tachycardia, slightly increased body temperature, subjective chest pain, dyspnea. However, this symptomatology is not always present in a clozapine-related pericarditis. Some authors suggest measuring BNP levels to detect early and asymptomatic cardiac dysfunction. We here report the clinical cases of two women, respectively 22 and 28 years old. They both suffered from an early onset resistant schizophrenia. Clozapine was gradually introduced, at a dose of 200 mg/day, in both patients. After about one month in both cases, while the first patient was nearly asymptomatic, apart from the intermittent fever (only PCR and pro-BNP values were elevated, 16.88 mg/dL and 1004 pg/mL, respectively), the second one showed a classic symptomatology suggestive of pericarditis. Clozapine was discontinued in both patients, resulting in progressive resolution of pericarditis. Interestingly, in the patient in which pro-BNP was elevated, after clozapine cessation, the pro-BNP fell down dramatically. Pro-BNP plasma levels appears to be an interesting test in identifying subjects with asymptomatic cardiac impairment. It would be useful to evaluate if early treatment with beta-blockers and ACE-inhibitors may allow the prosecution of clozapine treatment after developing of mild signs of cardiac toxicity in drug resistant schizophrenic patients responsive to clozapine.