First catheter‐based high‐density endocardial 3D electroanatomical mapping of the right atrium in standing horses

Abstract Background Three‐dimensional electroanatomical mapping is of potential interest in equine cardiology to identify arrhythmia mechanisms, characterise electroanatomical substrates and guide ablation strategies. Objectives To describe three‐dimensional electroanatomical mapping in standing horses. Study design Research methodology, proof of concept study. Methods Four Standardbred horses (2 geldings, 2 mares, median age 4.5 [4‐9] years, mean bodyweight 485 [440‐550] kg) were sedated and placed in stocks. Via the jugular vein, a high‐density multipolar grid catheter (Advisor™ HD Grid Mapping Catheter with EnSite VelocityTM, Abbott Medical) was used for endocardial mapping of the right atrium. The P‐wave on the surface ECG was used as a timing reference for simultaneous local activation time‐ and bipolar voltage‐mapping. For a positional reference a 10‐pole catheter (Abbott Medical) was placed in the caudal vena cava. Results Endocardial right atrial mapping guided by the three‐dimensional mapping system and local electrograms was successfully performed in all four horses. A median of 32719 [25499‐65078] points, covering the entire right atrium, were collected. Three‐dimensional electroanatomical mapping provided detailed information about activation patterns and electrogram‐characteristics of the sinoatrial node, intervenous tubercle and cavotricuspid isthmus. Additionally, transvenous biopsy forceps connected to the mapping system were visualised on screen to guide biopsy collection. Main limitations The feasibility of electroanatomical mapping for the left atrium and in larger breeds requires further study. Conclusions High‐density three‐dimensional electroanatomical mapping of the right atrium is feasible in the standing horse.


| INTRODUC TI ON
Atrial fibrillation (AF) is the most common pathological arrhythmia in both humans and horses. 1,2 In humans, percutaneous catheter-based procedures are used to identify and characterise the underlying mechanisms of the arrhythmia and to guide targeted ablation interventions to treat the arrhythmia. To assist with these procedures, three-dimensional (3D) electroanatomical mapping systems have been developed to create 3D models based on the anatomy of the individual heart. Local bipolar electrograms (EGMs) carrying local activation, bipolar and unipolar voltage (EGM amplitude) information are projected on the 3D model. The amplitude and morphology of EGMs can be used to characterise the extent of the underlying arrhythmogenic structural remodelling, including slowed conduction, low-voltage areas, focal activation and re-entry circuits. Peakto-peak voltage (Vpp) of local bipolar EGMs (voltage mapping) are used to quantify areas of low voltage. In addition to voltage mapping, the activation and propagation of impulses (activation mapping) can help to better understand arrhythmia mechanisms by distinguishing between re-entry mechanisms or local activation by ectopic foci.
For a further in-depth characterisation of the myocardial tissue, the 3D mapping system also enables connection of biopsy forceps to the mapping system to visualise and guide collection of endocardial biopsies from areas of interest, for example low-voltage areas in the 3D electroanatomical map. 3 The use of 3D electroanatomical mapping in horses is sparsely described 4,5 but was recently used to assist in ablation of an anaesthetised horse with atrial tachycardia originating from the right atrium. 6,7 It remains unclear whether sophisticated 3D high-density (HD) mapping techniques can be used in standing horses. This study aimed to test the feasibility of 3D HD endocardial electroanatomical mapping of the right atrium in standing horses. In addition, we aimed to evaluate conduction patterns during intrinsic atrial activation as well as low-voltage areas using a 16 electrode HD electrode grid catheter. Furthermore, we tested whether biopsy forceps could be connected to the mapping system and followed on screen in order to guide transvenous endocardial biopsy collection.

| Study population
In this proof-of-concept study we included four Standardbred horses (2 geldings, 2 mares, median age 4.5 [4][5][6][7][8][9] years, mean bodyweight 485 [440-550] kg). All animals were considered healthy based on clinical and biochemical examinations and no abnormalities were found from electrocardiographic (ECG) or echocardiographic examination. The two mares were teaching horses stabled at the University Hospital, whereas the geldings were recently retired racehorses scheduled for euthanasia for noncardiac-related reasons.

| Preparation of the horses
Electrophysiological studies were performed in standing horses sedated with detomidine (10 µg/kg, Domosedan ® ), butorphanol (10 µg/kg, Torbugesic ® ) and a constant rate infusion of xylazine (1.0 mg/mL, Xysol ® ). An indwelling urinary catheter was placed to reduce movement of the horse during urination. Catheter based electroanatomical mapping of the right atrium (RA) was performed using a 3D electroanatomical cardiac mapping system; EnSite Velocity ™ (Abbott Medical). The EnSite Velocity ™ system uses surface electrodes to create an impedance field around the transthoracic area to locate and visualise intracardiac catheters. An intracardiac catheter was placed in a stable position for an anatomical intracardiac reference. The six surface electrodes and a system reference patch were placed orthogonally around the heart along the X (left-right), Y (neck-leg) and Z (front-back) axis. As the heart of the horse is orientated in an up-right position in the thorax with the right part of the heart rotated cranially, the surface electrodes could be placed on the horse while respecting the X, Y and Z axis of the heart. The adapted sticker location resulted in a change in projection so that the equine anterior-posterior (AP) is comparable to a modified human right anterior oblique (RAO) view. This has to be considered when operating the 3D electroanatomical cardiac mapping system. The surface electrodes were placed as described in Table 1 and shown in Figure 1.
The electrodes were placed on shaved skin and held in place with glue and adhesive foam. Two introducer sheaths (Radiofocus ® Introducer II, 8/10 F, 10 cm, Terumo) were placed in the left jugular vein to give access to the heart.  8 When the reference catheter was placed in the stable position and the mapping catheter was located in the right atrium, the right atrial electroanatomical mapping procedure was guided by the 3D electroanatomical mapping system.

| Electroanatomical mapping protocol
The following catheters were utilised for mapping: (a) 6 F 10 pole cath- EGMs with a peak-to-peak voltage of less than 0.05 mV were classified as scar or electrically silent; between 0.05 and 0.5 mV as low-voltage areas and >0.5 mV considered healthy tissue. 9 To ensure that the complete maps only contained points col-

| Biopsy and further procedures
After the electroanatomical map was created the HD Grid was removed and through an 8 F introducer sheath (Flexor ® check- The two retired racehorses were scheduled for euthanasia (140 mg/ kg pentobarbital [Euthanasol ® ] IV) while the two teaching horses went back to stables to recover. Post-operatively the horses were given 1.1 mg/kg flunixin (Finadyne ® ), and, to avoid intestinal impaction, the horses were treated with 1 L of paraffin oil and 5 L of electrolyte water through nasogastric intubation. No anti-coagulant treatment was given.

| RE SULTS
Although designed for human use, the EnSite Velocity ™ 3D electroanatomical cardiac mapping system in combination with the Advisor ™ HD Grid catheter was feasible for electroanatomical mapping in standing sedated horses. The reference electrodes on the skin had good contact and the size of the horse did not prevent collection of data. A step-wise approach was followed to create the RA electroanatomical map: (a) Guided by echocardiography and bipolar EGMs,

| D ISCUSS I ON
In this proof-of-concept study, we assessed the feasibility of mapping the RA of four standing horses using a 3D electroanatomical (c) Mapping-guided biopsy collection is feasible in standing horses; (d) All horses tolerated the procedure well and the two horses intended for survival recovered with no side effects.
Simple catheter-based atrial electrophysiological procedures, as well as catheter-based transvenous electrical cardioversion of AF, are well described in horses. [12][13][14][15][16] In contrast to humans and small animals, where fluoroscopy is often used to navigate catheters, catheter placement is generally guided by electrical signals and echocardiography in horses, as the width of the thorax makes chest fluoroscopy challenging. 8 In addition, chest fluoroscopy often requires general anaesthesia, while many electrophysiological procedures can be performed in standing horses.
Recently, Van Loon and co-workers described how 3D electroanatomical mapping was used to guide ablation of a right-sided atrial tachycardia in an anaesthetised horse. 6 Activation mapping of right atrial arrhythmias may help to identify arrhythmia mechanisms. In humans, typical atrial flutter is due to re-entry that is dependent on an area of slow conduction through the cavotricuspid isthmus 17 whereas atrial tachycardias often originates from anatomical structures with ectopic activities. 18 The identification of the underlying arrhythmia mechanism is important to guide ablation and treat the arrhythmia.
However, 3D electroanatomical mapping has not yet been described in standing horses, where electrophysiological measurements can be recorded without the periprocedural risks and additional financial costs that comes with general anaesthesia. We report herein on the first electroanatomical mapping procedure in standing sedated horses. Compared to other mapping systems, which require a magnet placed below the body, the EnSite Velocity ™ system used in this study uses patches placed on the body surface,

| Limitations
Despite the difference in size and cardiac anatomy between humans and horses, it was possible to create 3D anatomical maps with the shape of an equine right atrium and follow the activation TA B L E 2 Mapping data for each for the horses included in the study. Included points were defined to be located within 7 mm of geometry surface. Low voltage was defined as <0.

| Conclusions
In summary, 3D electroanatomical mapping of the right atrium is feasible in the standing horse and may be helpful in characterising the underlying mechanisms for right atrial arrhythmias as well as guiding ablation strategies in the future.

CO N FLI C T O F I NTE R E S T S
Rayed Kutieleh is employed by Abbott Medical.

AUTH O R CO NTR I B UTI O N S
E. Hesselkilde, D. Linz and R. Kutieleh contributed to study design, study execution, data analysis and interpretation, and preparation of the manuscript. A. Saljic contributed to study execution, data analysis and interpretation, and preparation of the manuscript. H.
Carstensen, T. Jespersen, P. Sanders and R. Buhl contributed to study design and study execution. All authors gave their final approval of the manuscript.

E TH I C A L A N I M A L R E S E A RCH
Local ethic committee and The Danish Animal Experiments Inspectorate approved the study (license number: 2016-15-0201-01128).

OWN ER I N FO R M ED CO N S ENT
Written owner-informed consent was obtained prior to the study.

DATA ACC E S S I B I L I T Y S TAT E M E N T
The data are available from the corresponding author on reasonable request.