Noninvasive electrocardiographic imaging for individuals at risk for apparently idiopathic ventricular fibrillation

In the Western world, 20% of all deaths in adulthood is sudden, mostly because
of Sudden Cardiac Death (SCD) caused by VF. VF can be induced by polymorphic
VT. In some cases of VF, after extensive diagnostic workup, no cause can be
found. This is called idiopathic VF. Causes of polymorphic VT can also be
obscure. Current clinical expertise to define which patients are at risk for
(recurrence of) polymorphic VT or idiopathic VF is insufficient with available
diagnostic techniques. This also applies to the general knowledge of
arrhythmogenic mechanisms of VF. This is where a new modality has proven to be
of great potential value: ECG-imaging (ECGI). ECGI combines electrical
body-surface mapping with 256 electrodes placed on the thorax with a CT-scan
obtaining the anatomy of the heart and torso, hereby able to reconstruct local
electrograms, activation and recovery times. In recent research, ECGI provided
numerous extra insights into normal cardiac electrophysiology, but also
electrophysiological disorders and disease. The results strongly suggest that
ECGI can play a pivotal role in further characterizing arrhythmia mechanisms,
therefore could do so for polymorphic VT or idiopathic VF leading to diagnosis
and treatment improvement. Moreover, ECGI seems to have the potential to detect
arrhythmogenic substrate in individuals before their first event, offering the
possibility to diagnose and treat patients before SCA occurs.

By definition, patients with idiopathic ventricular fibrillation do not have
any structural or functional abnormalities as seen with cardiac imaging. A
novel technique named echocardiographic strain imaging allows quantification of
global and regional myocardial mechanics with a high temporal resolution. This
technique has shown to be of added diagnostic and prognostic value in various
cardiac diseases.9,10 Interestingly, this technique can unmask a mechanical
substrate in subjects who for example are at risk of developing arrhythmogenic
cardiomyopathy in which electrical and structural criteria of the disease are
completely absent.11,12 Application of this technique in patients with
idiopathic ventricular fibrillation is not done before, but may unravel a
(subtle) mechanical substrate that is not seen with conventional imaging
modalities.

Primary Objective: To noninvasively obtain arrhythmogenic substrate mapping
using ECGI in patients with polymorphic VT and/or idiopathic VF.

Secondary Objectives:
- To detect similar arrhythmogenic substrates in index patients of family
cohorts with a specific genetic mutation related to arrhythmogenesis, at high
risk for polymorphic VT and/or idiopathic VF
- To evaluate the electrophysiology in this specific patient group and estimate
their possible (increased) risk for polymorphic VT and/or idiopathic VF
- To translate the diagnostic potential of ECGI into an adapted flowchart for
the *general* population of patients at risk for polymorphic VT and/or
idiopathic VF; to apply ECGI in a diverse control group requiring CT as part of
clinical care, as already approved in METC protocol ABR number 32128
- To compare (minimally invasive) electrophysiological (EP) study (in patients
requiring this on medical indication, in Dutch: electrofysiologisch onderzoek:
EFO), with ECGI.
- To noninvasively characterize the mechanical substrate of patients with
unexplained polymorphic VT and VF, family members and control subjects using
echo strain analysis.

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. The optionel strain echocardiography does not contain any risk.

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.