Better mechanistic understanding and risk stratification of ventricular arrhythmias through ECGI

Cardiovascular diseases are responsible for approximately 17 million deaths
every year in the world, approximately 25% of which are sudden cardiac death
(SCD). The annual incidence of out-of-hospital cardiac arrests (OHCAs) in
Europe is 636,000 . Both are caused by ventricular tachyarrhythmias (VTAs), of
which the incidence can be assumed to be significantly higher. Premature
ventricular complexes (PVCs) can be the trigger to induce these VTAs and can be
closely related to them. However, arrhythmogenic mechanisms of the PVCs and
arrhythmia on a whole-heart level can be obscure.

The variety of patients that have or have a higher risk for VTAs and SCD is
large, varying from patients with ischemic or non-ischemic cardiomyopathies,
patients with non-structural heart disease, but also specific groups of
patients with congenital heart disease are mentioned in literature to have a
higher risk of VTAs and SCD. Moreover, even if the arrhythmogenic mechanisms
precipitating to VTA are known for a specific patient, it remains a major
challenge to predict the risk of recurrent episodes. This is clearly
demonstrated by the fact that the implantation of an ICD is recommended for
primary prevention of SCD (class I, level A) based on ejection fraction during
rest, which is an inaccurate and hemodynamic parameter, unrelated to the
electrophysiology of the patient.

For these reasons, an increased mechanistic understanding of VTAs and improved
risk stratification for both VTAs and SCD are needed 8. Although still very
important, the use of the 12-lead electrocardiogram is not sufficient, because
of its low resolution, particularly regarding regional de- and repolarization
characteristics. Catheter-based high-density electro-anatomical mapping during
an electrophysiological study is of value, but time- consuming, costly and may
lead to complications. This is where a new modality has proven to be of
potential value: ECG-imaging (ECGI). ECGI combines electrical body-surface
mapping with 256 electrodes placed on the thorax with a CT or MRI scan
obtaining the anatomy of the heart and torso. By combining these techniques, a
high-resolution three-dimensional epicardial electrophysiological map can be
reconstructed using mathematical formulations, showing local electrograms and
activation and recovery times. Within our team, Cluitmans et al. validated this
method in-vivo in dogs, proving it gives a correct reconstruction of epicardial
electrophysiology.

Other research groups also showed (epicardial) ECGI to be a non-invasive
high-resolution alternative/addition that provides numerous extra insights into
normal cardiac electrophysiology, but also electrophysiological disorders and
disease, not (easily) detectable with current clinical techniques. ECGI
highlighted the role of increased dispersion in several arrhythmogenic
diseases. Furthermore, ECGI is able to show conduction block, areas of early
repolarization, and steep electrical gradients, unidirectional conduction
block, focal ectopy, and excitation in relation to a history of reentrant
tachyarrhythmias. Several studies have highlighted to role of ECGI in detecting
arrhythmogenic substrate that could not be detected with routine clinical
tools. The results strongly suggest that ECGI can play a pivotal role in
further characterizing arrhythmia mechanisms, and therefore could do so for
ventricular arrhythmia diagnosis and treatment improvement. Moreover, this
novel tool seems to have the potential to detect arrhythmogenic substrate in
individuals at risk for (recurrent) VTAs, allowing preventive measures and
possibly reducing morbidity and cardiac death. Lastly, better mechanistic
understanding of VTAs through ECGI could aid in diagnosis and treatment, by
i.e. guiding ablations.

Main objective
To identify and describe the electrophysiological substrate and triggers in
patients with (an increased risk of) VTAs using ECGI, in order to improve
understanding of arrhythmic mechanisms and use these for arrhythmia risk
stratification and management.

Secondary objectives
- To identify and describe the cardiac electropathology using ECGI in control
subjects.
- To integrate information obtained by ECGI with other imaging modalities of
the heart, (for example CT, CMR, electro-anatomical mapping) for improved
understanding of disease pathology. By combining the results, a more personal
approach can be made in the future, which can potentially lead to better risk
stratification and better guidance for treatment options.
- To identify and describe the cardiac electrophysiology using ECGI in patients
who require an electrophysiological study (EP), to obtain knowledge about the
comparison between endo- and epicardial activation and repolarization, learn
about transmurality of the electrophysiological substrate, and potentially
develop integrative modalities which in the future may guide such procedures.

Prospective (cohort) study

For the BSP procedure there is no substantial risk of physical or mental harm.
The electrode system is passive and is electrically
isolated from the recording components. Some skin irritation to the electrode
attachment could occur in a small minority of patients.
Application of the electrode strips is mildly uncomfortable, as the attached
strips slightly reduce movement freedom and the patient
is asked to move as little as possible. Furthermore, the patient*s torso is
undressed during the whole procedure, but will be covered
with blankets.

For the CT procedure , in which case an extended cardiac CT scan is performed,
the radiation dose should be taken into
consideration. Importantly, control patients selected for the procedure would
already receive a cardiac CT for medical reasons. The
CT procedure for these patients is extended with a low-dose thoracic scan, to
obtain the electrode positions. The radiation dose of
the CT procedure consists of the cardiac CT (~5mSv) and the low-dose thoracic
scan (~1mSv). We consider the radiation burden to
be in balance with the major benefits that non-invasive reconstruction methods
for electrical heart activity will bring to the patients. In
comparison: the average yearly ionizing radiation background exposure is 2,6
mSv per person in the Netherlands.

To perform the cardiac CT scan, an iodine-contrast agent is given
intravenously. The patient could develop a mild allergic reaction to
the contrast agent used during cardiac CT (incidence 1/20, only causing mild
discomfort), with as very rare complication
anaphylactic shock (incidence 1/3000-14.000) 15. Because the contrast is given
intravenously, subjects could develop phlebitis at
injection site.