The pathophysiology of ventricular arrhythmia: does inflammation increase the risk of ventricular arrhythmia through hyperthermia and/or inflammatory cytokines?

Sudden cardiac death (SCD) resulting from ventricular tachycardia/fibrillation
(VT/VF) still has a high incidence, because its pathophysiologic basis is not
fully resolved. While the substrate of VT/VF is based on reentrant excitation
due to inherited or acquired ion channel dysfunction and structural
abnormalities, its precipitating factors (triggers) are less clear. The
presence and severity of such factors may explain why some patients with acute
myocardial infarction or inherited arrhythmia syndromes develop VT/VF, while
other patients with the same disorder do not. We recently reported that fever
may provoke ECG changes and VT/VF in patients with inherited arrhythmia
syndromes, i.e., diseases linked to mutant ion channels. Experimental studies
have indicated that these effects are consistent with the effects of
hyperthermia on disrupted ion channels, i.e., ion channels whose function is
modified by a mutation. However, while hyperthermia is linked to clinical and
cellular cardiac electrophysiological changes, it is conceivable that the
inflammatory cytokines, which underlie fever, also modulate cardiac
electrophysiology. Accordingly, although systematic studies are lacking,
anecdotal clinical reports indicate that fever may also be associated with
increased VT/VF risk in common acquired cardiac disease (e.g., myocardial
infarction, heart failure, and drug use). In this study, we aim to explore the
association between inflammation , in particular hyperthermia and inflammatory
cytokines, and the occurence of VT/VF.

The primary objective is to establish whether patients are at increased risk
for VT/VF during inflammation. The secondary objective is to establish whether
increased risk during inflammation is mediated by hyperthermia and inflammatory
cytokines. The third objective is to study whether cytokine gene variants that
are associated with higher serum cytokine levels have an increased prevalence
among patients with VT/VF.

We will conduct an observational study in which we collect data for at least 4
years of all patients with ICD to analyze whether ventricular arrhythmia is
associated with inflammation. Most of the patients with ICD have common
acquired cardiac disease, notably heart failure secondary to ischemic or
non-ischemic cardiomyopathy.

Burden in group 1: blood samples are taken twice prior to and thrice after the
ICD emplacement (every 2 hours 4 tubes of 4.5 ml; total of 5 x 20 = 100 ml
blood). For this, a peripheral venous infusion line is used, which has been
routinely placed for the sake of the ICD emplacement procedure. Thus, no extra
burden of venipuncture is caused in this group of patients.
Burden in group 2: blood samples are taken twice (at presentation and at next
routinely scheduled outpatient clinic visit; each time 20 ml). . Blood samples
are taken through venipuncture. A questionnaire is filled in, which requires
approximately 10 minutes.
Risk: no risks due to the study methods are expected.
Benefit: ICD-related infections might be diagnosed earlier due to frequent ECGs
and body temperature measurements after ICD emplacement.