Translational peak frequency mapping of human sinoatrial node-Bachmann bundle axis: Integrating human in vivo electroanatomic mapping with preclinical microstructural validation.

BACKGROUND

In vivo electroanatomic mapping has enabled functional characterization of the human sinoatrial node (SAN), yet precise localization of SAN exit zones (SAN-EZs) and preferential conduction pathways-particularly along the Bachmann bundle (BB)-remains challenging without direct anatomic validation.

OBJECTIVE

This study aimed to establish a translational framework integrating human in vivo peak frequency (PF) mapping with preclinical anatomic and histologic validation of the SAN-BB conduction axis.

METHODS

High-density endocardial electroanatomic mapping with PF analysis was performed in patients with inappropriate sinus tachycardia, sick sinus syndrome, and normal SAN function. Emphasis maps combining local activation time and PF were used to identify the SAN-EZ and preferential conduction pathways. To address anatomy, complementary preclinical studies were performed using contrast-enhanced micro-computed tomography, 3-dimensional reconstruction, and histology of donor human hearts, focusing on BB microstructure, insertion sites, and myocyte orientation. Frequency analysis was additionally applied to preclinical hearts to compare the BB with the surrounding right atrial myocardium.

RESULTS

In vivo PF mapping reliably identified the SAN-EZ and preferential conduction pathways using a 350-450 Hz frequency band. Patients with sick sinus syndrome exhibited reduced SAN-EZ overlap and fewer superior and septal pathways. Preclinical micro-computed tomography and histology in cadaveric human hearts confirmed the anatomic substrate underlying septal conduction. Frequency analysis of swine hearts revealed higher dominant frequencies within the BB than adjacent right atrial myocardium, supporting in vivo findings.

CONCLUSION

By integrating human functional mapping with preclinical anatomic and histologic validation, this study provides a translational framework for PF-based identification of the SAN-EZ and BB-mediated conduction.