Annual Clozapine Echocardiography Surveillance (ACES): A Systematic Review and Retrospective Cohort Analysis

Clozapine-induced cardiomyopathy and myocarditis (CICM) are infrequent but serious complications of clozapine therapy. While early consensus recommended routine echocardiographic surveillance, accumulating evidence suggests limited diagnostic value compared with biomarker-based monitoring. Despite this, surveillance imaging remains embedded in Australian guidelines, raising concerns regarding cost-effectiveness and workforce impact.

A focused systematic review was undertaken across PubMed, EMBASE, Ovid MEDLINE and the Cochrane Library from inception to November 2025 to identify articles reporting CICM incidence in Australian or New Zealand. A single-centre retrospective cohort study was also conducted which examined adults prescribed clozapine at Ipswich Hospital between January 2012 and February 2025. Echocardiograms performed for clozapine-related indications were reviewed. Demographics, echocardiographic findings, biochemical data, and clinical outcomes were extracted. CICM incidence was calculated, and departmental costs per detected case were estimated using local workforce and procedural costs.

Sixteen studies met inclusion criteria, representing 25,894 patients and 42,622 patient-years. The reported incidence of CICM ranged from 0.29% to 9.56%, with a pooled incidence of 0.99% (95% CI 0.86-1.11). In the local cohort (n=200; 904 echocardiograms), only one case of CICM was identified (0.15 per 100 patient-years), it was detected on clinical suspicion rather than routine surveillance imaging. The departmental cost per detected case was AUD $277,335.

CICM is a rare entity with routine echocardiographic surveillance in clozapine-treated patients demonstrating limited diagnostic yield. The workforce and financial costs of surveillance are significant. Our findings reinforce the need for critical review, realignment and national standardisation of current surveillance practices with a more cost-effective and evidence-based strategy for targeted monitoring in clozapine treatment.