Three-dimensional functional anatomy of the human sinoatrial node for epicardial and endocardial mapping and ablation

Abstract

The sinoatrial node (SAN) is the primary pacemaker of the human heart. It is a single, elongated, 3-dimensional (3D) intramural fibrotic structure located at the junction of the superior vena cava intercaval region bordering the crista terminalis (CT). SAN activation originates in the intranodal pacemakers and is conducted to the atria through 1 or more discrete sinoatrial conduction pathways. The complexity of the 3D SAN pacemaker structure and intramural conduction are underappreciated during clinical multielectrode mapping and ablation procedures of SAN and atrial arrhythmias. In fact, defining and targeting SAN is extremely challenging because, even during sinus rhythm, surface-only multielectrode mapping may not define the leading pacemaker sites in intramural SAN but instead misinterpret them as epicardial or endocardial exit sites through sinoatrial conduction pathways. These SAN exit sites may be distributed up to 50 mm along the CT beyond the ∼20-mm-long anatomic SAN structure. Moreover, because SAN reentrant tachycardia beats may exit through the same sinoatrial conduction pathway as during sinus rhythm, many SAN arrhythmias are underdiagnosed. Misinterpretation of arrhythmia sources and/or mechanisms (eg, enhanced automaticity, intranodal vs CT reentry) limits diagnosis and success of catheter ablation treatments for poorly understood SAN arrhythmias. The aim of this review is to provide a state-of-the-art overview of the 3D structure and function of the human SAN complex, mechanisms of SAN arrhythmias and available approaches for electrophysiological mapping, 3D structural imaging, pharmacologic interventions, and ablation to improve diagnosis and mechanistic treatment of SAN and atrial arrhythmias.

Keywords: Ablation; Adenosine; Crista terminalis; Optical mapping; Reentry; Sinoatrial node; Sinus tachycardia; Three-dimensional electroanatomic mapping.

Figure 1:

A. Anatomical location of human SAN. B. 3D SAN structure superimposed on CE-MRI, located along the crista terminalis (CT). C. Histology section with Masson’s trichrome staining shows the intramural location of the human SAN. D. Left, Masson’s trichrome staining shows human SAN fibrosis (blue). Middle, serial histology of SAN sections representing the transmural thickness of the SAN, stacked to generate computational 3D human SAN (Right). E. 3D computational structural analysis by fiber tracking approach displays microstructure of myofibers, fibrotic tissue, and fat in the human SAN complex (red) and surrounding atrial tissue (green). (Modified from^,,).

Figure 2:

A. Microelectrode recording and surface unipolar multi-electrode mapping of the canine SAN preparation shows that earliest atrial activation (star) occurred more than 100 ms later and 10 mm away from the SAN leading pacemaker. B. 3D human SAN model with SACPs. C. Schematic to show intramural location of the human SAN, and Near-infrared optical mapping (NIOM) SAN and atrial activation maps showing intramural SAN conduction. D. Left, Human SAN and atrial optical action potentials (OAPs) recorded from ex-vivo NIOM experiments. (Modified from^,).

Figure 3.

A. Top left, schematic of human SAN showing SACPs; Middle, near-infrared optical mapping revealed conduction within the SAN complex; Right, histology section of the same lateral region shows the SACP region. Bottom, 3D reconstruction of serial histological sections and computational myofiber tracking of the SACP region containing continuous myofiber tracts between the SAN and atria. B. Top panels, high resolution histological images. Bottom panels, immunostaining images of Cx43 and α-actinin in SACPs. (Modified from^,,).

Figure 4:

Human SAN 3D model showing activation exits either via superior/inferior or both SAN conduction pathways. A-C, Left panels: The ex-vivo human SAN NIOM studies show SAN activation exiting either through superior/inferior or both SACPs rather than two different leading pacemakers. A-C, Middle panels: Human epicardial multi-electrode mapping studies show three examples of superior, inferior and both superior and inferior patterns of earliest atrial activation during sinus rhythm (SR). A-B, Right panels: Two main preferential SAN exits demonstrated with step-wise endocardial high-density catheter mapping in AF patients during stable SR. (Modified from^{, ,}).

Figure 5:

A: Widespread distribution of the earliest atrial activation sites (EAS) recorded with epicardial bipolar electrodes in patients. The EAS formed a widely distributed region along the CT which greatly exceeded dimensions of the human SAN. B. Ex-vivo CE-CMR with human 3D SAN model showing common EAS/Exit sites from SAN via superior, middle and inferior SACPs defined by NIOM in ex-vivo human studies^,,,,. C. Distribution of successful ablation sites of atrial tachycardias on the CT. 3D SAN model showing surface exit sites via the superior and inferior SACPs near the SAN head and tail, respectively. E. Simultaneous endocardial-epicardial mapping of the SAN /CT showing post-pacing caudal shift in activation exits with marked asymmetry in endo–epi exit sites. (Modified from^,,).

Figure 6:

A. Top to bottom, atrial ECG, SAN and atrial OAPs show pause, exit block, and SAN reentrant arrhythmias after 300ms atrial pacing in the ex-vivo human heart; B. SAN 3D model, activation maps and histology sections of microreentry path; C. Macro-reentrant paths within the SAN-SACP-atria structure. (Modified from^,).

Figure 7:

A. Central panel describes challenges in mapping and ablating human SAN arrhythmias. B. DE-MRI can be utilized to visualize SAN and CT. C. Damage to phrenic nerve can be avoided by utilizing an epicardial balloon. D. SAN can be identified with SAN electrogram (EG) recorded from electrodes placed close to the SAN. (Modified from^,,).