This cohort study investigates if contrast-enhanced cardiac computed tomography can localize the atrioventricular conduction system through the identification of the insular fat of the conductive myocardium.
Key Points
Question
Can contrast-enhanced cardiac computed tomography accurately localize the atrioventricular conduction system by identification of the fat that insulates the conductive myocardium?
Findings
In a cohort of 20 patients referred for atrial fibrillation ablation, myocardial low attenuation on contrast-enhanced computed tomography (CECT) indicating fat deposition at the top of the triangle of Koch was within the registration error range of the intracardiac His signal in all cases.
Meaning
The atrioventricular conduction system is insulated from surrounding atrial and ventricular myocardium by fat, and results suggest that the fat can be accurately localized using CECT.
Abstract
Importance
Noninvasive localization of the compact atrioventricular node and the proximal specialized conduction system (AVCS) would enhance planning for transcatheter aortic valve and complex or congenital heart disease surgical procedures.
Objective
To test the hypothesis that preprocedure contrast-enhanced cardiac computed tomography (CECT) can accurately localize the AVCS by identification of the fat that insulates the conductive myocardium.
Design, Setting, and Participants
This was a prospective cohort study that took place at an academic tertiary care center. Included in the study were patients with CECT acquired less than 1 month before atrial fibrillation ablation and electroanatomic localization of the His electrogram signal on electroanatomic mapping (EAM) between January 2022 and January 2023.
Exposures
Preprocedure CECT.
Main Outcomes and Measures
The distance from the His electrogram signal to the fat segmentation encompassing the AVCS on CECT, after registration of the images to EAM.
Results
Among 20 patients (mean [SD] age, 66 [10] years; 15 male [75%]) in the cohort, the mean (SD) attenuation of the AVCS fat segmentation was 2.9 (21.5) Hounsfield units. The mean (SD) distance from the His electrogram to the closest AVCS fat voxel was 3.3 (1.6) mm.
Conclusions and Relevance
Results of this cohort study suggest that CECT could accurately localize the fatty tissue that insulates the AVCS from surrounding atrial and ventricular myocardium and may enhance the efficacy and safety of procedures targeting the conduction system and structures in its proximity.
Introduction
The atrioventricular cardiac conduction system (AVCS) contains myocytes responsible for transmitting excitatory impulses from the atria to the ventricles.1 The AVCS is histologically recognized as myocytes insulated from adjacent myocardium by fibrofatty tissue,2 with fat deposition demonstrated along the compact atrioventricular node and His bundle,3 once it becomes insulated from the atrial myocardium, within the septum.4 The superior extension of the inferior atrioventricular groove is sandwiched between the right atrial wall of the triangle of Koch and the crest of the muscular ventricular septum and can be visualized on contrast enhanced cardiac computed tomography (CECT),5 a technique that also identifies myocardial fat with high specificity.6 The AVCS penetrates the atrioventricular myocardial discontinuity either at the apex of the inferior pyramidal space or lower within the inferoseptal recess of the left ventricular outflow tract.7 We sought to test the hypothesis that CECT can accurately localize the penetrating portion of the AVCS, ie, the His bundle, in a cohort of patients undergoing atrial fibrillation (AF) ablation.
Methods
Study Population
Between January 2022 and January 2023, we prospectively identified patients with CECT acquired less than 1 month before AF ablation at the Hospital of the University of Pennsylvania. To enhance clarity regarding data generalizability, patient race (African American, White, or undeclared) was included in study data. The Hospital of the University of Pennsylvania atrial fibrillation (HUP-AF) ablation registry is a prospectively collected and abstracted database that enrolls all patients undergoing AF ablation at HUP. Collection of consent-exempt registry data was approved by the HUP institutional review board. The research adhered to Helsinki Declaration guidelines.
CECT
CECT was performed with a 2 × 192-detector scanner (Somatom Force [Siemens]; collimation = 512 × 0.6 mm, gantry rotation time = 610 milliseconds, in-plane resolution, 0.45 × 0.45 × 0.45 mm, prospectively or retrospectively triggered at 70% of the RR interval [ie, the time elapsed between 2 successive R waves of the QRS signal], 120-kV tube voltage). Heart rate was maintained at less than 70 beats per minute by intravenous metoprolol. Iodinated intravenous contrast (100 mL, rate of 4-5 mL per second, Isovue-370 [Bracco Diagnostics]) was injected and timed to optimize myocardial perfusion. Image reconstruction was performed at 70% of the RR using soft-tissue convolution kernel.
Image Analysis
Fat density, ie, very low attenuation (<30 Hounsfield units [HU]), in the inferior pyramidal space on axial images was identified (Figure 1). Adjacent musculature of the right atrium, left atrium, right ventricle, and left ventricle were identified and contoured. The top of the triangle of Koch, bounded posteriorly by the tendon of Todaro (ie, line connecting the anterior inferior vena cava ostium to the superior septal aspect of the tricuspid valve), anteriorly by the septal leaflet of the tricuspid valve, and inferiorly by the coronary sinus, was interrogated for low attenuation representing AVCS fibrofatty deposition connecting the atrial and myocardial contours. The search area within the triangle of Koch was focused on the tissue near the apex of the inferior pyramidal space and/or the region beneath the right coronary cusp of the aorta. Image analyses were performed by ADAS 3D (ADAS 3D Medical SL).
Figure 1. Process for Identification of the Atrioventricular Node and the Proximal Specialized Conduction System (AVCS) and Validation on Mapping.
The top of the triangle of Koch, bounded posteriorly by the tendon of Todaro (line connecting the anterior inferior vena cava ostium to the superior septal aspect of the tricuspid valve), anteriorly by the septal leaflet of the tricuspid valve, and inferiorly by the coronary sinus, was interrogated for low attenuation (<30 Hounsfield units [HU]) representing AVCS fibrofatty deposition connecting the atrial and myocardial contours. The search area within the triangle of Koch was focused on the tissue near the apex of the inferior pyramidal space and/or the region beneath the right cusp of the aorta. Images in the left panels highlight the low attenuation region with a purple contour and the electroanatomic map registration of the His location with yellow tag contour. The right panels show the same images without contours. The 3-dimensional segmentation is shown in the middle panel. The yellow arrowhead represents the His electrogram signal, and the red arrowhead represents the low attenuation region (<30 HU). RIPV indicates right inferior pulmonary vein; RSPV, right superior pulmonary vein.
Electroanatomic Mapping and AF Ablation
Our mapping and AF ablation techniques have been previously described.8 Electroanatomic maps were created with the Carto 3 system (Biosense Webster) using multipolar PentaRay (20 electrodes with 2-6-2–mm spacing) catheters during distal CS pacing. The location of the His electrogram was marked on the EAM using Thermocool Smarttouch SF (Biosense Webster) catheter with 5g or greater force to confirm a contact signal. Pulmonary vein (PV) isolation was performed with confirmation of bidirectional PV entrance and exit block. Non-PV triggers were targeted when identified.
Statistical Analyses
The cardiac anatomy CECT image segmentation was registered to the EAM generated from the clinical procedure using the PV ostia as landmarks. After the procedure, the Euclidean distance, ie, the length of the line segment between the His electrogram signal and the closest AVCS fat segmentation voxel in 3-dimensional space, was measured using ADAS 3D software. If more than 1 His electrogram signal location was tagged, the mean distance for all His locations in that patient was used. Continuous variables are expressed as mean and SD and categorical variables as count and percentage. The independent-samples t test, Fisher exact test, or χ2 test was used to compare differences across groups, as appropriate. All P values were 2-sided, and a P value <.05 was considered statistically significant. Statistical analyses were performed using Stata, version 18 SE (StataCorp).
Results
Study Cohort
The cohort included 20 patients (mean [SD] age, 66 [10] years; 5 female [25%]; 15 male [75%]; 3 African American [15%]; 15 White [75%]; 2 undeclared [10%]). Of all patients, 17 (85%) had hypertension, and 6 (30%) had persistent AF. At baseline, the mean (SD) PR interval during sinus rhythm was 160 (24) milliseconds. Coronary artery disease was prevalent in 8 patients (40%), and history of first- or second-degree AV block was noted among 5 patients (25%). Patient characteristics are summarized in the Table.
Table. Patient Characteristics.
| Clinical variable | Participant group (N = 20) |
|---|---|
| Age, mean (SD) y | 66 (9.7) |
| Body mass index, mean (SD)a | 28.6 (3.6) |
| Sex, No. (%) | |
| Female | 5 (25) |
| Male | 15 (75) |
| Persistent atrial fibrillation, No. (%) | 6 (30) |
| Hypertension, No. (%) | 17 (85.0) |
| Systolic blood pressure, mean (SD), mm Hg | 126 (16) |
| Diastolic blood pressure, mean (SD), mm Hg | 75 (11) |
| Diabetes, No. (%) | 2 (10) |
| Coronary artery disease, No. (%) | 8 (40) |
| Obstructive sleep apnea, No. (%) | 6 (30) |
| Aortic stenosis, No. (%) | 2 (10) |
| Aortic regurgitation, No. (%) | 4 (20) |
| Stroke or transient ischemic attack, No. (%) | 0 |
| History of first- or second-degree atrioventricular block, No. (%) | 5 (26.5) |
| PR interval, mean (SD), millisecond | 160 (24) |
| CECT image finding, mean (SD) | |
| Intensity of AVCS segmentation, HU | 2.9 (21.5) |
| Volume of AVCS segmentation, mL | 0.4 (0.3) |
| Left atrial volume index, mL/m2 | 32.7 (8.0) |
| Left ventricular ejection fraction, % | 54.0 (9.9) |
Abbreviations: AVCS, atrioventricular node and the proximal specialized conduction system; CECT, contrast-enhanced computed tomography; HU, Hounsfield unit.
Calculated as weight in kilograms divided by height in meters squared.
CECT Image Findings
On preprocedural CECT, the mean (SD) left atrial volume index was 32.7 (8.0) mL/m2, and the mean (SD) echocardiographic left ventricular ejection fraction was 54.0% (9.9%).
Low attenuation was noted at the apex of the triangle of Koch in all patients (Figure 2 and eFigure 1 in Supplement 1). The mean (SD) attenuation of the AVCS fat segmentation was 2.9 (21.5) HU. On EAM, the mean (SD) distance from the His electrogram to the closest AVCS fat voxel was 3.3 (1.6) mm (eFigure 2 in Supplement 1). There was no association between the HU intensity or volume of the AVCS-fat on CT and the PR interval.
Figure 2. Anatomic Relationship of the Aortic Root, Triangle of Koch, and Low Attenuation Atrioventricular Node and the Proximal Specialized Conduction System (AVCS) Fat in 2 Patients.
The figure illustrates the low attenuation region at the apex of the triangle of Koch. Each column represents a different patient. The top panels highlight the region of the triangle of Koch. As described by Koch in 1909, the triangle is an anatomical area in the right atrium, with the coronary sinus orifice, tendon of Todaro, and septal leaflet of the right atrioventricular valve as its boundaries. It is difficult to show all anatomic landmarks in a single image plane; however, the corresponding boundaries are highlighted in the top panels with the insertion region of the septal leaflet of the tricuspid valve highlighted as a white dashed line; the inferior isthmus, leading to the orifice of the coronary sinus, as the red dashed line; and the imaginary tendon of Todaro (a line connecting the triangle apex to the Eustachian ridge) as the yellow dashed line. The middle panels highlight the proximity of the apex of the triangle of Koch to the right cusp of the aorta and the membranous septum. The attenuation density of the region at the tip of yellow arrows is noted. The bottom panels show 3-dimensional reconstructions of the left atrium and the aortic root with the low attenuation region at the top of the triangle of Koch segmented (red arrowhead: <30 Hounsfield units [HU]) and registered to the intracardiac His electrogram signal (yellow arrowhead). RIPV indicates right inferior pulmonary vein; RSPV, right superior pulmonary vein.
Discussion
This cohort study demonstrates the ability of widely available conventional CECT to accurately localize the AVCS validated by invasive electroanatomic mapping.
Shinohara et al9 previously demonstrated the feasibility of AVCS (including the compact node, His bundle, and both left and right bundle branches) visualization as a low-density structure on phase-contrast CT in ex vivo whole-heart human specimens, validated against histological analysis. Micro-CECT has also been used to visualize the AVCS in nonhuman mammalian hearts.10 Our study builds on these findings by demonstrating the ability of CECT to accurately delineate the AVCS, with simple image processing techniques that are easy to replicate, and does not necessitate specialized image acquisition protocols or contrast agents.
Limitations
This study has some limitations. This was a single-center study with a small sample size and a homogeneous population of patients with AF without congenital heart disease, which reduces the generalizability of our results. Although attenuation less than 30 HU is specific for fat on CECT, the AVCS segmentation, intended to identify the fat surrounding the conduction system, is expected to contain not only the specialized conducting myocardium but also some fibrous tissue due to spatiotemporal resolution limitations and volume averaging. Future studies are needed to validate our findings, particularly when the expected AVCS anatomy is congenitally altered. A prior study has implicated excessive fatty infiltration in the compact AV node transitional area in conduction disturbances.11 In this study with a small sample size, we did not find an association between HU intensity or fat volume and PR interval or first- or second-degree AV block.
Conclusions
In conclusion, results of this cohort study suggest that CECT accurately localized the AVCS compared with invasive electroanatomic mapping. Noninvasive visualization of the AVCS may provide utility in planning for electrophysiologic, interventional, and surgical procedures by providing an anatomic roadmap. This may be potentially useful in ablation of para-Hisian atrial and ventricular arrhythmias or anterior and midseptal accessory pathways and transcatheter valve replacements. If the findings can be validated in patients with congenital heart disease, CECT may lower the incidence of iatrogenic conduction system injury during congenital heart surgery.
eFigure 1. Anatomic Relationship of the Aortic Root, Triangle of Koch, and Low Attenuation AVCS Fat in All 20 Patients
eFigure 2. Three Dimensional (3D) Reconstructions of the Aortic Root, Left Atrium, and Low Attenuation AVCS Fat in All 20 Patients
Data Sharing Statement.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure 1. Anatomic Relationship of the Aortic Root, Triangle of Koch, and Low Attenuation AVCS Fat in All 20 Patients
eFigure 2. Three Dimensional (3D) Reconstructions of the Aortic Root, Left Atrium, and Low Attenuation AVCS Fat in All 20 Patients
Data Sharing Statement.
