Image-guided cardiac focused ultrasound neuromodulation regulates heart rate

Symptomatic bradycardia can pose significant health risks, yet available therapies are either transient, invasive, or lack spatial precision. Here, we introduce an image-guided cardiac focused ultrasound (cFUS) neuromodulation approach that noninvasively and selectively engages cardiac sympathetic activity to increase heart rate (HR) while preserving sinus rhythm. Using computed tomography for stereotaxic targeting to the murine right ventricle, cFUS elicited an acoustic dose-dependent chronotropic response with a 17.91 ± 1.11% increase in healthy mice and a 17.41 ± 4.43% increase in propranolol-induced bradycardia mice. It elevated HR through the shortening of PR and QT intervals, and improved cerebral blood flow without affecting oxygen saturation. Mechanistically, cFUS activated sympathetic pathways with mechanical effects and mild focal heating (~1.1 °C). Sympathectomy or drug-induced sympathetic inhibition reduced cFUS efficacy. Safety assessments showed no histological damage, acute inflammation, or behavioral abnormalities. Furthermore, to enhance clinical translatability, we achieved closed-loop HR feedback control for precise HR maintenance with 1% controllability and validated transthoracic cFUS propagation with human ribs via simulation. These findings establish image-guided cFUS under feedback control as a safe, effective, and noninvasive neuromodulation strategy for rapid, precise control of HR, with potential translational relevance for the management of symptomatic bradycardia and other cardiovascular disorders. Xiangkun Piao and colleagues report an image-guided cardiac focused ultrasound neuromodulation approach, enabling rapid and feedback-controlled heart rate regulation in mouse models. This approach offers a potential non-invasive strategy for the management of arrhythmia.