Journal of the American College of Cardiology

2009 by the American College of Cardiology Foundation

Published by Elsevier Inc.

EDITORIAL COMMENT

Idiopathic Ventricular
Fibrillation Le Syndrome
dHassaguerre and the
Fear of J Waves*
Sami Viskin, MD
Tel Aviv, Israel

Idiopathic ventricular fibrillation (VF) is a disease of

unknown etiology but with well described clinical (1) and
electrophysiologic (2,3) characteristics. Briefly, young
adults present with syncope or cardiac arrest due to
polymorphic ventricular tachyarrhythmias in the absence
of structural heart disease or identifiable channelopathies
(4). The spontaneous arrhythmias are not related to stress
and are invariably triggered by narrow-complex ventricular extrasystoles with very short coupling intervals (5,6).

Vol. 53, No. 7, 2009

ISSN 0735-1097/09/$36.00
doi:10.1016/j.jacc.2008.11.011

pathic VF patients in this series (8). The VF storms of

Brugada syndrome and idiopathic VF share some characteristics: VF clusters are sometimes triggered by fever,
numerous VF episodes originate from the same myocardial area, and the recurrent arrhythmias are refractory to
conventional antiarrhythmic therapy, including betablockers and intravenous amiodarone (8,10). Both conditions respond to intravenous isoproterenol (79,11),
probably because isoproterenol reduces the dispersion of
repolarization that enables the onset of VF (12). For all
we know, patients with idiopathic VF and early repolarization have a worse (rather than a different) form of
idiopathic VF.
The disappointing response to verapamil reported by
Hassaguerre et al. (8) is noteworthy because verapamil
was the emergency treatment originally proposed for
short-coupled variant of torsade de pointes (an arrhythmia indistinguishable from idiopathic VF) (13). In an
instructive case (14), verapamil abolished the shortcoupled extrasystoles that triggered VF (without prolonging the very short ventricular refractory period), while
nifekalant prolonged the refractory period without suppressing the triggers of arrhythmia (14). Nonetheless,
failure of verapamil has also been the rule in our
experience (3).
The Fall and Rise of Quinidine

See page 612

Hassaguerre et al. (7) recently reported that 1 of 3

patients with idiopathic VF has an intriguing electrocardiogram (ECG) that demonstrates J waves and STsegment elevation in the inferolateral leads (the early
repolarization pattern). In this issue of the Journal,
Hassaguerre et al. (8) report that idiopathic VF patients
with J waves tend to develop arrhythmic storms that
respond solely to isoproterenol and quinidine.
Le Syndrome dHassaguerre

Patients with idiopathic VF and early repolarization

were more often male subjects, had shorter QT intervals,
and had arrhythmias more frequently than idiopathic VF
patients with a normal ECG (7). High-amplitude J waves
conferred a higher risk for arrhythmic storm, and transient augmentation of the J-wave amplitude preceded the
onset of VF (7,8). These observations were confirmed by
Nam et al. (9).
VF storms occur in 18% of patients with symptomatic
Brugada syndrome (10) and occurred in 13% of idio*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv
University, Tel Aviv, Israel.

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The excellent short- and long-term response to quinidine

reported by Hassaguerre et al. (8) should come as no
surprise. Back in 1929, the first published case of idiopathic VF also involved an arrhythmic storm that responded to quinidine (15). For more than 2 decades (2),
Belhassen (2,3,16 18) has led the way of quinidine
therapy for idiopathic VF and Brugada syndrome with
excellent results. Quinidine is also consistently effective
during arrhythmic storms due to Brugada syndrome (11).
In congenital short QT syndrome (a condition similar to
idiopathic VF in many ways) (19), only quinidine (but
not sotalol, flecainide, or ibutilide) normalizes the abnormally short ventricular refractory period and prevents the
induction of VF (20). A prominent transient outward
potassium current (ITo) plays a major role in arrhythmogenesis in these J-wave syndromes (21), and the beneficial effects of quinidine are probably mediated by ITo
blockade (21).
Ironically, the realization that quinidine is often the
only effective drug for VF storms comes at a time when it
is increasingly difficult to obtain quinidine supplies (22).
AstraZeneca, one of its main manufacturers, recently
ceased production (23). As superbly summarized by
Wilde and Langendijk (24), the disappearance of antiarrhythmic drugs like procainamide, mexiletine, and quinidine was driven by revenue issues and though affecting
only a small number of patients, it may have dire
consequences for them. Hopefully, this report by Has-

Viskin
Idiopathic VF

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saguerre et al. (8) will prompt health care systems to

negotiate with the pharmaceutical industry to ensure the
availability of quinidine.

Who Is Afraid of the Big Bad J-Wave?

J waves are commonly observed in healthy individuals,

predominantly in young males (25) and especially among
athletes (26). These age- and sex-related differences
persist during autonomic blockade with atropine and
propranolol (25), suggesting that intrinsic differences in
the contour of the myocardial action potential, secondary
to sex-related diversity in ion-current density mediated
by androgenic receptors (27), affect the size of J waves.
The association between J waves and idiopathic VF
described by Hassaguerre et al. (7) was confirmed by
Nam et al. (9) and our group (26) and is probably here to
stay. In fact, the Haissaguerre et al. study (7) triggered a
fear of J waves. Electrophysiologists may be consulted
about the arrhythmic-death risk after an incidental discovery of J waves. Unfortunately, we do not know how to
distinguish arrhythmogenic from normal J waves.
Hassaguerre et al. (7) observed that patients with VF
have J waves with larger amplitude than matched control
subjects, and we noticed a similar trend (26). Also,
patients with idiopathic VF have QT intervals in the
lower normal range (19) that fail to prolong adequately
during heart rate slowing (28). However, there is too
much overlapping between VF patients and control
subjects in terms of J-wave amplitude (7,26), J-wave
location (26), and QT intervals to permit an accurate
diagnosis. Finally, arrhythmias in idiopathic VF are not
provocable by exercise but may be induced with programmed ventricular stimulation (1). Thus, electrophysiologists may be tempted to recommend electrophysiologic studies for risk stratification of patients with J
waves (like current practices in Brugada syndrome) (29).
That would be unadvisable because the value of VF
induction for predicting spontaneous arrhythmias remains contentious (30). Since idiopathic VF is a rare
disease, and there are no tests for confirming or excluding
it in the asymptomatic patient, asymptomatic patients
with J waves should not undergo further testing. During
the last decade, numerous young and otherwise healthy
individuals worldwide underwent prophylactic implantation of defibrillators because of asymptomatic Brugada
syndrome with inducible VF (31). Yet, the consequences of
that policyin terms of adverse eventsare only now being
appreciated (30). Hopefully, patients with asymptomatic J
waves and inducible VF will not share the same fate.
Reprint requests and correspondence: Dr. Sami Viskin, Department of Cardiology, Tel Aviv Medical Center, Weizman 6, Tel
Aviv 64239, Israel. E-mail: saviskin@tasmc.health.gov.il.

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Key Words: early repolarization y sudden cardiac death y electrical
storm y pacing y antiarrhythmic drugs.