Immune-mediated myocarditis following adeno-associated virus (AAV) gene therapy was observed at a rate of fewer than 10 cases per 100 patient-years, with events occurring predominantly within the first few weeks after treatment, according to a systematic review and meta-analysis published in Circulation: Heart Failure. The analysis included 80 studies comprising 1939 patients and evaluated cardiac adverse events reported after AAV-based gene-replacement therapy.

Literature searches across MEDLINE, Embase, and PubMed (2005–2025) identified eligible studies reporting vector characteristics, dosing, timing, and clinical features of adverse events. A random-effects model was applied, and additional myocarditis cases were identified through VigiBase and the US Food and Drug Administration Adverse Event Reporting System.

Across 2122 patient-years of follow-up, 734 adverse events were reported, including 71 myocarditis cases. The pooled incidence was 8.6 per 100 patient-years (95% confidence interval [CI] 5.8–10.7; I²=63.2%). Events were observed in neuromuscular conditions including Duchenne muscular dystrophy, spinal muscular atrophy, and X-linked myotubular myopathy, and were associated with recombinant AAV vectors, particularly serotype 8.

All myocarditis cases followed intravenous doses exceeding 1×10¹³ vector genomes/kg. Myocardial injury was most frequent in the first week after administration (90%), while myocarditis occurred more commonly after the second week (55%), with no reported cases beyond one month. Most events were mild, with 12% showing transient left ventricular dysfunction that resolved during follow-up.

Overall, myocarditis and myocardial injury occurred infrequently and were generally mild, with events clustering early after therapy and following higher-dose intravenous administration.