Abstract
We are grateful for the opportunity, presented by the commentary of Ellis and Cameron (2012), to explain in detail our reasons for proposing baseline echocardiography before commencing clozapine as part of the process of monitoring for clozapine-induced myocarditis (Ronaldson et al., 2011a). As these authors rightly point out, there is no evidence that pre-existing cardiac disease is a risk factor for myocarditis associated with clozapine; in fact, to the contrary, there is some indication from fatal cases that coronary artery disease does not change the risk (Ronaldson et al., 2011b). The reasons we have proposed baseline echocardiography do not include risk detection or early diagnosis, which are the criteria Ellis and Cameron (2012) consider would justify baseline investigation.
The detection of left ventricular dysfunction involves considerable subtlety, except when the impairment is gross. While recent expert cardiology opinion recommends a cut-off of 55% for the diagnosis of a normal left ventricular ejection fraction, there is significant overlap of this figure between normal and disease states (Lang et al., 2005); therefore, an assessment of left ventricular systolic function without a baseline echocardiography for serial comparison is problematic. Thus, baseline echocardiography will improve the reliability of diagnosis of myocarditis and reduce unnecessary discontinuation of clozapine, including discontinuation for pre-existing conditions. Unfortunately, as our investigations have shown, myocarditis can develop without troponin being raised above the upper limit of normal, so the diagnosis cannot always be verified by checking troponin (Ronaldson et al., 2011a).
In addition, apart from suicide, occult cardiac disease is the highest cause of sudden or unexpected death in schizophrenia, with an incidence that is significantly higher than that in the general community (Abdelmawla and Mitchell, 2006). The most common causes of sudden cardiac death are coronary artery disease and cardiomyopathy (Kirchhof et al., 2006), both of which would be expected to be identified by baseline echocardiography, but not necessarily from routine clinical evaluation.
Hence, we believe a baseline echocardiography prior to commencing clozapine is clinically warranted, for these two reasons: so that myocarditis, when it is suspected, can be diagnosed with a high degree of specificity, and to detect in the patient with schizophrenia any cardiac disease which would benefit from appropriate treatment.
See Commentary by Ellis and Cameron, 2012, 46(10): 1005–1006