The risk for sudden death due to ventricular arrhythmias is increased in individuals who carry mutations in genes that encode cardiac ion channels and associated proteins. Inherited or
de novo mutations in
SCN5A, the gene that encodes the cardiac sodium channel, are linked to Brugada syndrome (BrS), a disease characterised by signs of conduction slowing on the ECG (prolonged PR and QRS intervals), and increased incidence of ventricular arrhythmias that are preceded by coved-type ST-segment elevation in the precordial leads V1 and V2.
1 BrS-linked
SCN5A mutations exert their proarrhythmic effects by causing sodium channel loss-of-function (i.e., reducing cardiac sodium current [I
Na]) by disrupting intracellular trafficking of mutant channel proteins from the endoplasmic reticulum to the sarcolemma, forming channels that conduct no or very small I
Na, or altering the opening and closing (gating) properties of mutant channels in such a manner that the channels are less frequently open.
2,3 Anecdotal reports have suggested that fever may aggravate the typical ECG changes and increase the risk for sudden death in BrS.
4,5 However, the association between fever and the risk for ventricular arrhythmias and preceding ECG changes has not been studied systematically. Recently, we first investigated this association in index patients who were diagnosed with BrS at our institution.
6 In this retrospective study, we assessed the prevalence of fever-triggered ventricular tachycardia, ventricular fibrillation, or sudden death in 111 BrS patients, and compared these data with 41 control participants who were admitted after out-of-hospital cardiac arrest due to ventricular tachycardia or ventricular fibrillation. We found that, compared with control participants, BrS patients experienced cardiac arrest significantly more often during fever. Additionally, we analysed fever-induced ECG changes in 24 BrS patients for whom 12-lead ECGs during both fever and normothermia were available, and compared the data with ECG changes in ten control participants who were admitted for noncardiac reasons. We found that fever, irrespective of the cause, induced additional prolongation of PR and QRS intervals, and aggravated the coved-type ST-segment elevation in leads V1 and V2 in BrS patients. In contrast, the PR interval shortened, and the QRS interval and the ST-segment amplitude in leads V1 and V2 did not change during fever in control participants (figure 1A and B). We also investigated whether the use of antipyretic drugs during fever affected the prevalence of cardiac arrest in BrS patients. Indeed, a larger proportion of patients who had not used paracetamol (acetaminophen) experienced cardiac arrest during fever than those who had used acetaminophen. Thus, this systematic study indicated that fever increases the risk for ventricular arrhythmias and aggravates the typical ECG changes in BrS patients. …
