Adeno-Associated Virus-mediated Gene Therapy for Cardiac Tachyarrhythmia: A Systematic Review and Meta-analysis.

Cardiac tachyarrhythmia presents a significant healthcare challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential risks, resulting in an elevated disease burden. Adeno-associated virus (AAV)-mediated gene therapy holds promise as a potential future treatment option. Therefore, we aim to provide a measured overview of the latest developments in this rapidly growing field. PubMed and Embase databases were searched up to January 2024. Studies that employed AAV as a vector for delivering therapeutic agents to treat cardiac tachyarrhythmia were included. Twenty-six studies were included with 20 of them published in the last five years. There were 22 novel molecular targets identified. More than 80% of the included studies employed small animal models or utilized AAV9. In atrial fibrillation (AF) pre-clinical studies, AAV-mediated gene therapy reduced AF inducibility by 81% (OR 0.19[0.08,0.45]; p<0.01). Similarly, for acquired and inherited ventricular arrhythmia (VA), gene therapy treated animal models had less inducible VA with OR 0.06[0.03,0.11]; p<0.01. This review highlights the rapid progress of AAV-mediated gene therapy in the treatment of cardiac tachyarrhythmia. While these investigations are currently in the early stages of clinical application, they present promising prospects for gene therapy. (PROSPERO registry: CRD42023479448).