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STATE-OF-THE-ART PAPER
From the Research Center and Department of Medicine, Montreal Heart Institute
and Universit de Montral, Montreal, Quebec, Canada. Supported by Canadian
Institutes of Health Research (MOP 68929), Leducq Foundation (07/CVD/03), Plan
Nacional de Investigacion Cientfica, Desarrollo e Innovacion Tecnologica, Instituto
de Salud Carlos III/FIS (CM06/00189 and CM08/00201), and Fundacion Alfonso
Martn Escudero. The authors have reported that they have no other individual
relationships to disclose. Drs. Benito and Guasch contributed equally to this paper.
Manuscript received February 26, 2010; revised manuscript received May 20, 2010,
accepted May 25, 2010.
Historical Background
The ER pattern is defined by ST-segment elevation, often
accompanied by slurring or notching on the terminal QRS,
called a J-wave (Figs. 1A and 1B). This pattern was first
described as a normal variant by Shipley and Hallaran in
1936 (19). Reports in the 1950s and 1960s confirmed with
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Epidemiological Aspects
Early repolarization occurs in 1% to 9% of the general
population (10,16,18), and in 15% to 70% of IVF cases
(16,17,2325). Based on such series, ER is considered to
convey a 4- to 10-fold SCD risk increase (16,25). In the
35 to 45 year age range of maximal ER-related SCD
incidence (16,24,26), a J-wave is estimated to increase
IVF risk from 3.4 per 100,000 to 11 per 100,000 (25).
However, estimates based on index series of IVF cases
may not be applicable to asymptomatic individuals with
ER. In a longitudinal survey of 10,864 asymptomatic
individuals (age at recruitment 44 8 years, follow-up
30 11 years), arrhythmic death risk increased 1.4-fold
with 0.1-mV and 2.9-fold with 0.2-mV J-point
elevation in the inferior leads (18).
Male sex is strongly associated with ER: over 75% of
individuals with ER are men. Men present greater J-point
elevation than women do (18,25) and represent 75% of
malignant cases (16,17). Male predominance may result
from larger epicardial transient outward current (Ito) density
versus Ito in women (27), although the detailed sex-related
ion-channel expression profile remains to be established.
The ER pattern is more common in younger physically
active individuals (10,18) and may regress with aging
(20,28). Estimates of the prevalence in trained individuals
range from 20% in noncompetitive athletes to 90% in elite
athletes. In this population, ER often appears in mid
Figure 1
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Pharmacological Responses
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Benito et al.
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Early repolarization
Normal
Repolarization
0 mV
0 mV
0.3 s
-80 mV
-80 mV
T-wave
T-wave
ST-segment
ST-segment
Region B
Region A
ECG
Figure 2
LV
RV
Action potentials recorded from regions A (red) and B (blue) are shown (top), together with electrocardiogram (ECG) from region A (middle).
See text for discussion. AP action potential; LV left ventricle; RV right ventricle.
Benito et al.
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Epi
Endo
INa
ICaL
Ito
IKr
IKs
IKI
INa/Ca
J-wave
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Figure 3
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Transmural
voltage
gradient
Epi2
Endo
Epi1
B
Endo
Epi1
Epi2
Figure 4
(A) With enhanced repolarization in regions with prominent Ito, all-or-none repolarization can occur, creating a substrate for arrhythmias. (B) Simultaneous action potentials from 2 epicardial (Epi1 and Epi2) and 1 endocardial site (Endo), and surface ECG. A loss of the action potential dome in Epi1, but not in Epi2, leads to apparent
propagation of the dome from Epi2 to Epi1, inducing re-entry. Adapted, with permission, from Yan et al. (44). Abbreviation as in Figure 2.
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Inherited
Syndromes
ER Involving ER
Table 1 SCD
Inherited
SCDInvolving
Syndromes
Brugada Syndrome
Short-QT Syndrome
KCNJ8/IKATP (35)
CACNA1C, CACNB2B/ICaL (43)
ER Syndrome
KCNH2/IKr (59)
KCNQ1/IKs (60)
KCNJ2/IK1 (61)
CACNA1C, CACNB2B/ICaL (53)
ECG
Drug therapy
Quinidine (16)
Isoproterenol (15)
Quinidine (48)
Isoproterenol (49)
Quinidine (50)
Transmural
voltage
gradients
Epi2
Endo
Epi2
Epi1
Endo
Epi1
C
B
Endo
Epi2
Endo
J-wave
Epi1
ST-segment
T-wave
J-wave
ST-segment
Figure 5
T-wave
ST-segment
T-wave
ER Effects on Action Potentials and ECG, Illustrating the Potential Role of J-Wave as a Marker of ER Risk
(A) Early repolarization (ER) can enhance phase 1 notch (Epi2) or cause all-or-none repolarization from phase 1 (Epi1). (B) Enhanced phase 1 notch causes prominent
J-wave. (C) All-or-none repolarization does not cause J-wave but produces large transmural repolarization gradients that persist when Epi1 APs have regained excitability,
potentially causing ectopic activity (dashed lines). (D) Variable AP repolarization responses to ER generates both prominent J waves and ectopic activity. Abbreviations
as in Figures 2 and 3.
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REFERENCES
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43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
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58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
References
Citations
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