S. Murch

Echocardiographic monitoring for clozapine cardiac toxicity: lessons from real-world experience:

Objective: We aimed to identify the baseline prevalence of cardiac dysfunction in patients commencing clozapine, assess adherence with echocardiographic monitoring recommendations, and evaluate the utility and cost of echocardiographic monitoring for the development of clozapine-associated myocarditis and cardiomyopathy. Methods: A retrospective longitudinal cohort study was undertaken of 159 consecutive patients from a major tertiary centre commencing clozapine in the period January 2002 to July 2009. Results: Some 73% of patients had a baseline study, and 11% had a six-month follow-up study. Nine patients had abnormal left ventricular function at baseline. Myocarditis was identified in three patients, with all cases occurring within the first month of treatment and suspected on clinical grounds before an echocardiogram was performed. One case of possible cardiomyopathy was identified. The cost of echocardiographic screening in the first year of treatment was estimated at

Abnormal right ventricular relaxation in pulmonary hypertension

AUD 209,356 per case of cardiomyopathy detected. Conclusion: The prevalence of cardiac dysfunction in patients commencing clozapine is high, and there are challenges in adhering with the recommended protocol for monitoring. Routine echocardiography is not useful in the detection of clozapine-associated myocarditis. Although cardiomyopathy may be identified, it is rare and associated with significant cost. Recommendations for routine echocardiographic monitoring should be re-examined.

Echocardiographic monitoring for clozapine-associated cardiac toxicity--time for review?

Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure (5.1 ± 6.6 vs. −0.1 ± 3.3 mmHg, P = 0.03) and RV end-diastolic pressure (RVEDP; 11.0 ± 6.3 vs. 3.8 ± 3.7 mmHg, P = 0.004), and RV τ was significantly prolonged (53 ± 32 vs. 31 ± 13 ms, P = 0.04). There were strong correlations between RV τ and RV minimum diastolic pressure (r = 0.93, P < 0.0001) and between RV τ and RVEDP (r = 0.87, P < 0.0001). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group (0.73 ± 0.21 vs. 0.52 ± 0.21 mmHg/mL, P = 0.07) and a correlation between RV systolic pressure and first derivative of maximum pressure change (r = 0.58, P = 0.003). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures.