Non-invasive Risk Stratification for Ventricular Arrhythmias in Ischaemic and non-ischaemic Cardiomyopathy

The number of patients with ischaemic or dilated cardiomyopathy (CMP) is
steadily increasing in western civilized countries, among others due to the
advances in pharmacological and revascularization therapies in coronary artery
disease. Sudden cardiac death due to ventricular arrhythmias is a feared
complication in these patients. The introduction of the implantable
cardioverter defibrillator (ICD) has had a major impact in the treatment of CMP
with a significant reduction in mortality. However, only 35% of treated
patients are faced with an appropriate discharge for the occurrence of
life-threatening ventricular arrhythmias during a follow-up period of three
years. Although the exact characteristics of the myocardial substrate for
ventricular arrhythmias in ischaemic heart disease remains incompletely
understood, several predictors have been identified. Recently, cardiac magnetic
resonance imaging (CMR) with the contrast agent gadolinium has emerged as an
imaging tool that allows accurate quantification of scar tissue. Furthermore,
the MOLLI sequence allows diffuse assesment of fibrosis. It was demonstrated
that size of fibrosis and heterogeneity of scar tissue measured by CMR are
better predictors of inducible ventricular tachycardia (VT) than LVEF in
patients with CMP. Besides the aforementioned, sympathetic activity and cardiac
denervation seem to contribute to the susceptibility of arrhythmias. Animal
experiments have subsequently suggested that the area of viable and perfused
but denervated myocardium is highly sensitive to sympathetic stimuli, which may
trigger ventricular arrhythmias. Furthermore, innervation defects have been
described in patients with dilated cardiomyopathy. Recently, tracers have been
introduced for scintigraphic mapping of presynaptic sympathetic innervation.
Scarce clinical data of several studies using the tracers confirm the
hypothesis that innervation imaging may be useful in the risk stratification
process for ventricular arrhythmias in CMP patients. Given the increasing
importance of this topic in the current era of increasing prevalence of CMP,
ICD implantations, and expanding health care costs, the aforementioned
potential predictors for sudden death due to ventricular arrhythmias in CMP
patients warrant further investigation.

The present study is designed to test the hypothesis that new imaging
modalities like PET with the use of HED and contrast enhanced CMR to quantify
fibrosis size and heterogeneity of scar tissue can give a further risk
stratification for ventricular arrhythmias in patients with ischaemic or
dilated cardiomyopathy and a LVEF < 35%.

BASELINE PARAMETERS:
- Standard physical examination
- ECG
- Minnesota living with heart failure questionnaire
- lab test (among other NT-proBNP and CRP)
- Microvolt T wave alternans testing

Noninvasive imaging protocol:

Echocardiography
- Standard RV and LV evaluation
- Real time 3D echo dataset acquisition

MRI
- RV and LV volumes and function
- Delayed contrast enhancement to detect RV and LV scarring.

PET
- Assessment of myocardial perfusion using H215O
- Assessment of innervation using 11C-HED

Invasive measurements:

Electrophysiological testing during ICD-implantation
- Assessment of excitability of VT/VF

During the same session as the electrophysiological testing the patients will
have implanted an ICD. And after the implantation patients will be subjected to
periodical out-house screening of the device for arrhythmias for a period of at
least three years. Both the electrophysiological data (excitable VT/VF) as well
as the follow-up occurrence of arrhythmias will be related to the baseline
imaging data in an effort to identify the most powerful predictors of
arrhythmias in our study population.

Participants will be exposed to a total of 3.4 mSv for the PET study protocol.
This amount is comparable to less than two times the annually background
radiation.
The adenosine injected during the PET study protocol can induce headache and a
flush. In some cases chestpain can occur. All side-effects disappear quickly
after stopping the adenosine infusion (about one minute).