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Purpose: Clozapine is an important atypical antipsychotic agent which is effective in the treatment of refractory schizophrenia. However, its use can be associated with acute myocarditis, tachyarrhythmias and cardiomyopathy. The aim of our study was to investigate left ventricular ejection function (LVEF) in patients who had received Clozapine for at least one year, utilising conventional & two-dimensional (2D) speckle tracking echocardiography & to explore whether a low grade inflammatory state contributes to impaired LVEF.Methods: Echocardiography and biochemical profiles were analysed in 81 consecutive outpatients receiving long-term Clozapine and 20 age-and sex-matched healthy controls. LVEF was assessed by M-mode, fractional shortening (FS), Simpson's biplane and global longitudinal 2D-Strain.Results: Clozapine patients had been treated for 7.0±5.5 (mean±SD) years at the time of review. They had significantly higher resting heart rate (93±12.0 vs 70±7.2, p<0.001), body mass index (BMI- 29.4±6.9 vs 23.5±2.5, p<0.001), history of smoking (p<0.001), illict drug use (p=0.04) and hypercholesterolemia (p=0.006) than controls. Echocardiographic measurements revealed significantly impaired LVEF amongst Clozapine patients as shown in Table 1. All subjects with Simpson's biplane EF<55% were from the Clozapine group (20/81 clozapine vs 0/20 controls, p=0.01). Clozapine patients had significantly higher levels of inflammatory markers: neutrophil count (5.6±2.4 vs 3.6±1.0x10^9/L, p<0.001) and high-sensitivity C-reactive protein (hsCRP-4.3±4.6 vs 0.9±0.8mg/L, p<0.001) but not the eosinophil count (0.13±0.14 vs 0.17±0.12, ns) than controls. Amongst the patients taking Clozapine, there was a significant association between the degree of impairment in 2D-strain and neutrophil count (Beta Coefficient=0.36, p=0.01).Conclusions: There is significant left ventricular dysfunction in schizophrenic patients receiving long term Clozapine, and this is associated with mild systemic inflammation.