@phdthesis{01HWD336PQQDHBQPFH4KBT41SY,
  abstract     = {{Dogs that are referred to a veterinary cardiologist will frequently present with a cardiac arrhythmia. Severity of
clinical signs may vary from lethargy and anorexia to more critical signs such as dyspnoea or collapse. If left 
untreated, these arrhythmias can result in serious consequences including tachycardia-induced cardiomyopathy, 
congestive heart failure, and, in the worst-case scenario, sudden cardiac death. Surface electrocardiograms 
(ECGs) are helpful for initial diagnosis and treatment, but often do not reveal the location and mechanism of the 
arrhythmia. To determine this, invasive electrophysiology studies (EPS) involving intracardiac catheterisation are 
typically required. During an EPS, both the mechanism and location of the arrhythmia are examined. Thereafter, 
myocardial ablation lesions are created in an attempt to permanently eliminate the arrhythmia. Over time, the 
basic principles of EPS have undergone significant changes, in particular the way of visualising the catheters 
inside the patient and the way in which the electrophysiological data are presented. Initially, conventional EPS 
relied entirely on fluoroscopic navigation for the above purposes, which involves exposure to ionising radiation. 
This is in contrast to the new three-dimensional electroanatomic mapping (3D EAM) systems, which generate a 
magnetic or impedance field inside the patient, allowing dedicated catheters to navigate in 3D space (the heart) 
without the need for fluoroscopy. This technique can produce an individualised 3D shell of the patient's 
endocardial cavity known as a 3D electroanatomical map. The electroanatomical map is generated from 
individual EAM points that contain electrograms. These maps are processed by a computer to produce colour coded maps that show the localisation and mechanism of the arrhythmia. The use of 3D EAM has expanded 
arrhythmia treatment indications in people and was shown to be safer compared to conventional EPS. Clinical 
research on EPS in dogs has traditionally focused on conventional EPS, predominantly right-sided 
supraventricular tachycardias, and has not thoroughly addressed 3D EAM. This has contributed to the neglect of 
atrial fibrillation (AF) and ventricular tachycardia, despite their high prevalence in the canine population. 
Moreover, there is a paucity of data on the use of unfractionated heparin (UFH) for anticoagulation in dogs during 
EPS. However, left-sided arrhythmias in people are at increased risk of thromboembolism, thus more work is 
needed to identify the ideal method of administering and monitoring UFH.

Chapter 1 presents a prospective canine study aiming at establishing a reference interval (RI) for canine activated 
clotting time (ACT) using a point-of-care (POC) analyser. In addition, we sought to evaluate intra-subject within and between-day variability and analyser reliability. Activated clotting has historically been used primarily as a 
coagulation screening test in dogs but is nowadays mainly used to monitor anticoagulant therapy with UFH during intravascular procedures including EPS. No data on the use of ACT for heparinisation during EPS in dogs  was described. A total of 42 healthy dogs were used in this study. When comparing our results to most other published RIs for ACT in dogs, a higher mean was found. The intrasubject within- and between-day variability 
was low and considered of limited clinical relevance for screening, but it should be taken into account when 
interpreting longitudinal ACT measurements. Combined with the observed analyser reliability, it was concluded 
that the POC analyser is suitable for use in monitoring UFH during EPS.

The study in Chapter 2 was designed to investigate whether UFH administration during interventional procedures 
in dogs could be facilitated by using a UFH dose response test (HDR) or whether taking individual UFH sensitivity 
into account can help predict an appropriate dose of UFH in an individual dog. Individual UFH sensitivity displays 
marked variability between people, and as a result, fixed UFH doses result in a significant proportion of patients 
receiving a suboptimal dose. The study was conducted in eight healthy Beagles undergoing 3D EAM (Chapter 4). 
The ability of the HDR test to calculate the appropriate dose for an in-vivo ACT target ≥300 s was evaluated. 
Furthermore, the in-vitro relationship between ACT and blood UFH concentrations and factor anti-Xa (anti-Xa) 
and plasma UFH concentrations was assessed. Anti-Xa analysis has been shown to have a superior correlation 
with plasma UFH concentrations in humans. The study demonstrated that the HDR test did not accurately 
estimate the required UFH dose in dogs, which might be partially related to a non-linear UFH - ACT relationship 
as observed in-vitro. Anti-Xa showed favourable diagnostic properties, but its use is limited by its unavailability 
as a rapid POC test.

In Chapter 3, we attempted to address the knowledge gap on 3D EAM in dogs and evaluated the feasibility and 
safety of a workflow including 3D EAM of all four heart chambers, 3D EAM-guided biopsies and transseptal 
puncture (TSP) in dogs. The study included a total of eight healthy Beagles. Right atrial and right ventricular 
maps were successfully obtained in all dogs, whilst left atrial and left ventricular maps were successfully 
obtained in six and seven dogs, respectively. The only serious complications encountered included transient 
third-degree atrioventricular block and pericardial effusion following TSP, which arose in one dog and was 
resolved by pericardiocentesis. No major complications were observed in three other dogs that underwent TSP. 
Endomyocardial biopsies could be successfully obtained by 3D EAM-guidance in seven dogs. We conclude that 
3D EAM is feasible, generally safe and allows limited or no use of fluoroscopy.

Chapter 4 presents a case report demonstrating 3D EAM and radiofrequency catheter ablation (RFCA) as a 
successful treatment for persistent AF in a 2-year old German Shepherd dog. In human medicine, 3D EAM-guided 
pulmonary vein isolation (PVI) is the most successful therapy in peoplewith both paroxysmal and also persistent 
AF. However, it has not been previously explored in dogs presenting with spontaneous AF. We were able to show 
that PVI was effective in preventing AF recurrence, maintaining sinus rhythm and reversing signs of exercise intolerance. There were no complications. Our case report shows that 3D EAM has potential as a novel rhythm 
control modality for canine AF and warrants further investigation.

Chapter 5 presents a second case report describing the successful use of 3D EAM and RFCA for the treatment of 
orthodromic atrioventricular reciprocating tachycardia (OAVRT). Currently, OAVRT is the most common indication 
for conventional EPS and RFCA, but the possibility and potential benefits of diagnosing OAVRT with 3D EAM and 
later treating it with RFCA remained unexplored. In Chapter 5, we showed that six RFCA applications were 
sufficient to prevent long-term (1 year) recurrence of OAVRT and achieve resolution of clinical signs.

In conclusion, this work provides new insights in the use of 3D EAM, both in healthy and in diseased dogs. Equally, it raises a number of interesting questions on the topic that merit further study. We first looked for a method to monitor and guide UFH treatment during EPS and provided a RI and instructions for the use of ACT during UFH treatment. 
Unfractionated heparin administration based upon individual UFH sensitivity, proved unreliable. The proposed 
HDR test for individualised UFH dosing inaccurately estimated the required UFH dose for a given target, most 
likely due to a non-linear UFH - ACT relationship as observed in-vitro.Future studies should investigate whether 
dogs have similar UFH requirements, and thus, whether similar anticoagulation targets are justified. The 3D EAM 
protocol allowed high resolution 3D EAM, selective biopsy and safe TSP with no or minimal use of fluoroscopy. 
The same protocol plus RFCA was shown to be effective in the diagnosis and treatment of a dog with persistent 
AF and another with OAVRT. This first description of 3D EAM-guided PVI as an effective treatment for persistent
drug-refractory AF demonstrates the importance of the pulmonary veins in canine AF and should spark a debate 
to rethink rhythm control in symptomatic dogs with (persistent) AF. It also indicates that 3D EAM is a highly 
promising technology that deserves further exploration for other arrhythmias in dogs.}},
  author       = {{Hellemans, Arnaut}},
  language     = {{eng}},
  pages        = {{235}},
  publisher    = {{Ghent University. Faculty of Veterinary Medicine}},
  school       = {{Ghent University}},
  title        = {{High-resolution three-dimensional electroanatomical cardiac mapping : a new era in diagnosis and treatment of canine  arrhythmias with minimal radiation exposure}},
  year         = {{2024}},
}