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

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

Luigi Pannone, Ivan Eltsov, Domenico Laviola, Ioannis Doundoulakis, Domenico Giovanni Della Rocca, Paul-Adrian Calburean, Pasara Vedran, Ludovica Carmagnola, Tommaso Sattin, Antonio Sorgente, Alvise Del Monte, Giacomo Talevi, Gezim Bala, Alexandre Almorad, Ingrid Overeinder, Erwin Ströker, Juan Sieira, Ali Gharaviri, Mark La Meir, Pedro Brugada, Andrea Sarkozy, Gian Battista Chierchia, Carlo de Asmundis

Abstract ■

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. Keywords: Inappropriate sinus tachycardia; Peak frequency map; Preferential conduction pathways; Sick sinus syndrome; Sinoatrial node.