Natural History of Early Repolarization in the Inferior...

ORIGINAL ARTICLE

Natural History of Early Repolarization in theInferior Leads

Ricardo Stein, M.D.,∗ Karim Sallam, M.D., Chandana Adhikarla, M.D.,†Madhavi Boga, M.D.,† Alexander D. Wood, B.Sc., and Victor F Froelicher, M.D.,†‡From the ∗Exercise Pathophysiology Research Laboratory, Cardiology Division, Hospital de Clınicas de PortoAlegre, Porto Alegre, Brazil; †Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; ‡The Division ofCardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA

Aims: Though early repolarization (ER) in the inferior leads has been associated with increasedcardiovascular risk, its natural history is uncertain. We aimed to study the serial electrocardiographicbehavior of inferior ER and understand factors associated with that behavior.

Methods: We selected electrocardiograms (ECGs) from patients with the greatest amplitude of ERin AVF from ECGs of 29,281 ambulatory patients recorded between 1987 and 1999 at the Palo AltoVeterans Affairs Hospital. Starting from the highest amplitude, we reviewed the ECGs and medicalrecords from the first 85%. From this convenience sample, 36 were excluded for abnormal patternssimilar to ER. The remaining 257 patients were searched for another ECG at least 5 months later,of whom, 136 satisfied this criteria. These ECGs were paired for comparison and coded by fourinterpreters.

Results: The average time between the first and second ECGs was 10 years. Of the 136 subjects,47% retained ER while 53% no longer fulfilled the amplitude criteria. While no significant differenceswere found in initial heart rate (HR) or time interval between ECGs, those who lost the ER pattern hada greater difference in HR between the ECGs. There was no significant difference in the incidence ofcardiovascular events or deaths.

Conclusions: In conclusion, the ECG pattern of ER was lost over 10 years in over half of the cohort.The loss of ER was partially explained by changes in HR, but not higher incidence of cardiovascularevents or death, suggesting the entity is a benign finding.

Ann Noninvasive Electrocardiol 2012;17(4):331–339

electrocardiography; serial ECGs; early repolarization; inferior leads

ST-segment elevation on the resting electrocardio-gram (ECG) in the absence of coronary artery dis-ease or pericarditis was first reported in healthyindividuals in 19471 and titled early repolariza-tion (ER) in 1951.2 In 1976, Kambara and Phillips3

reported that ER often included a distinct notch(J wave) or slur on the down slope of the R wave. ERis a prevalent electrocardiographic finding, affect-ing up to 5% of the population and until recentlythe condition was considered benign. However, ex-

Address for correspondence: Karim Sallam, M.D., Division of Cardiovascular Medicine, Falk CVRC, Stanford University, 300 PasteurDrive, Stanford, CA 94305. Fax: 650-723-8392; E-mail: [email protected]

Disclaimer: The opinions expressed in this article do not necessarily represent the views or policies of the Department of Veterans Affairs.

Conflict of Interest: None

Support: None

perimental, case-control and cohort studies suggestthat this pattern, especially when observed in theinferior leads, is associated with increased risk ofcardiovascular death.4–7

While ER is more common in the young, sug-gesting that it recedes with age, there have beenlimited studies of its prognosis and its naturalhistory is uncertain. Demonstrating that ER candisappear naturally rather than its decreasingprevalence being due to death would supplement

C© 2012, Wiley Periodicals, Inc.DOI:10.1111/j.1542-474X.2012.00537.x

331

332 � A.N.E. � October 2012 � Vol. 17, No. 4 � Stein, et al. � Inferior Early Repolarization

appropriate studies using survival analysis. There-fore, we present a study of the natural history ofinferior ER utilizing serial ECGs in an ambulatoryclinical population.

METHODS

A total of 45,829 unique inpatient and outpa-tient ECGs were recorded for clinical indicationsfrom March 1987 to December 1999 at the VAPalo Alto Health Care System. All patients wereseen at the main Veteran Affairs (VA) facility or itssatellite clinics, and ECGs were ordered by healthcare providers usually to screen for occult diseaseand to obtain a baseline when initiating care. Sinceclinical diagnostic codes were not available, we ex-cluded those with inpatient status (n = 12,319) toeliminate ECGs possibly associated with acutecoronary syndromes and other acute processes.Furthermore, ECGs exhibiting one or more of thefollowing were excluded: atrial fibrillation or flut-ter (n = 1253), ventricular rates > 100 beats perminute (n = 2799), QRS durations > 120 millisec-onds (n = 3141), paced rhythms (n = 290), ventric-ular preexcitation (n = 42), and acute myocardialinfarction (n = 29). This left 29,281 patients forconsideration. Race was determined by self-reportat the time of ECG acquisition.

With the PR interval as the isoelectric line andthe amplitude criteria for visual coding of ER as ≥1.0 mm (1.0 mm when 10 mm = 1 mV) above iso-electric line in inferior lead AVF, ER was identifiedwhen any of the following were seen to fulfill theamplitude criteria: ST elevation at the end of theQRS, J waves as an upward deflection and slurs asa conduction delay on the QRS down stroke. Tosimulate visual reading of the ECG, ≥0.9 mV wasused for computer coding because of the humantendency to round readings to the full millimeterscaling. While our initial reports considered mul-tiple area leads using both a single or contiguouslead criteria, to improve accuracy and reliability ofinterpretation we considered just single leads forER classification. Computer-measured amplitudeof ER in AVF was sorted from greatest to lowestamplitude to identify a convenience sample withthe greatest ER amplitude. Those ECGs underwentvisual confirmation, analysis and coding by threeindependent interpreters with conflicts resolved bythe senior author. Due to the labor-intensive natureof reviewing and coding these ECGs, we decidedto stop when at least 85% of those available with

inferior ER were processed. The ECG database wasthen queried to determine who had a subsequentECG. This ECG was printed for coding by threetrained individuals and visually compared to thefirst ECG. When multiple ECGs were available,the ECG at the longest time interval was chosenfor comparison. Chart review of the patients witha second ECG was performed to determine if anacute medical condition necessitated this ECG. Thepaired ECGs were then compared and coded asto whether they maintained or lost ER. Examplematched ECGs were chosen by sorting the pairs bythe greatest changes in ER amplitude (i.e., lost ER)and the least change (i.e., maintained ER).

NCSS software 2007 (Kayesville, Utah) was usedfor all statistical analyses. Unpaired t-tests wereused for comparisons of continuous variables andchi-square tests were used to compare dichotomousvariables between groups. A significance level of0.01 was used.

RESULTS

Our target population of 136 patients who hada subsequent ECG for studying the natural his-tory of ER was derived at as follows. Of the to-tal 29,281 ambulatory patients with ECGs in ourdatabase, 185 patients were coded as manifestingER solely in the inferior leads and 163 had ER inboth inferior and lateral leads. When this total of348 patients with inferior lead ER with or with-out lateral lead ER were sorted by ER amplitudewith largest first, we chose to evaluate ECGs withER amplitude in the top 85% range. This led to asample of 293 ECGs for visual inspection and cod-ing. When we removed 36 ECGs with pathologi-cal findings that could cause a pattern similar toER (i.e., pericarditis, myocardial injury/infarction),257 ECGs remained. These 257 patients with other-wise normal ECGs were queried for a repeat ECGmore than 5 months later. Of these, 136 (59%) hada subsequent ECGs for comparison and were ourtarget population for studying the natural history ofER. On chart review, 28 patients developed heartdisease over the interval but no acute symptomswere present at the time of the second ECG.

Table 1 provides the demographics and an-nual cardiovascular mortality of the total popula-tion and its subgroups according to selection cri-teria described earlier. Patients with inferior ERwere younger compared to the average population.There were significant differences in demographics

A.N.E. � October 2012 � Vol. 17, No. 4 � Stein, et al. � Inferior Early Repolarization � 333

Table

1.

Dem

ogra

phi

cC

hara

cter

istics

ofth

eTo

talP

opul

atio

nfo

rC

ompar

ison

with

the

Sub

grou

ps

Sho

win

gG

reat

est

Am

ount

ofEa

rly

Rep

olar

izat

ion

(incl

udin

gth

esu

bgr

oup

with

36

pat

ient

sw

ith

ECG

sex

hibitin

gEa

rly

Rep

olar

izat

ion

pat

tern

sdue

topat

holo

gica

lco

nditio

n)

Ear

lyR

epola

riza

tion

Most

Ear

lyR

epola

riza

tion

Most

Ear

lyR

epola

riza

tion

Both

Infe

rior

Both

Infe

rior

Pat

holo

gica

lIn

feri

or

and

Infe

rior

and

EC

Gs

Rem

ove

dC

hara

cter

isti

cA

llSub

ject

sLe

ads

Onl

yLa

tera

lLe

ads

pva

lue

Lead

sO

nly

Late

ralLe

ads

pva

lue

(Tar

get

Popul

atio

n)

N(%

)2

9,2

81

(10

0%

)1

85

(0.6

%)

16

3(0

.6%

)0

.91

37

(0.4

6%

)1

56

(0.5

3%

)0

.32

57

(0.9

%)

Age

(yea

rs)

55

±1

55

2±

16

42

±1

4<

0.0

01

55

±1

44

4±

14

<0

.00

14

7±

14

.15

Mal

es(%

)2

55

44

(87

.2%

)1

82

(98

.5%

)1

58

(96

.9%

)0

.41

25

(91

.2%

)1

52

(97

.4%

)0

.02

24

4(9

4.9

%)

Afr

ican

Am

eric

an(%

)3

88

5(1

3.3

%)

31

(16

.8%

)6

2(3

8.0

%)

<0

.00

11

6(1

1.7

%)

46

(29

.5%

)0

.00

16

1(2

3.7

%)

Bod

ym

ass

index

(kg/

m2

)2

7.3

±5

.52

6.0

±5

.42

4.5

±3

.40

.82

6.0

2±

5.3

25

.4±

5.1

0.4

25

.41

±5

.0H

eart

Rat

e(b

pm

)70.6

±1

2.6

69

.6±

13.1

66.0

±1

2.4

17

1.2

±1

36

9.1

±1

1.3

0.1

69

.8±

11

.69

Infe

rior

Qw

aves

(%)

20

79

(7.1

%)

25

(13

.5%

)4

(2.5

%)

<0

.00

11

7(1

2.4

%)

4(2

.5%

)<

0.0

01

0A

nter

ior

Qw

aves

(%)

59

3(2

.0)

3(1

.6)

4(2

.5%

)0

.61

(0.7

%)

1(0

.6%

)0

.90

CV

Dea

ths

(%)

19

95

(6.8

)1

4(7

.6)

4(2

.5%

)0

.03

sdt1

7(1

2.4

%)

5(3

.2%

)0

.00

21

5(5

.8%

)

ECG

sw

ith

earl

yre

pol

ariz

atio

n—in

feri

orle

ads—

irre

spec

tive

ofth

epre

senc

eof

pat

holo

gica

lEC

Gs:

(137

+1

56

=2

93

).W

hen

36

ECG

sw

ith

abno

rmal

itie

sas

soci

ated

with

earl

yre

pol

ariz

atio

nre

mov

ed:

(293

−3

6=

25

7).


Table

2.

Cha

ract

eris

tics

ofth

eIn

feri

orLe

adEa

rly

Rep

olar

izat

ion

Sub

grou

ps

with

ECG

sEx

hibitin

gP

atho

logi

calC

onditio

nsA

ssoc

iate

dw

ith

EREx

clud

ed

Most

Ear

lyM

ost

Ear

lyR

epola

riza

tion

Rep

ola

riza

tion

Infe

rior

Infe

rior

Gro

upw

ith

Mai

ntai

ned

Lost

Lead

Gro

up2

ndEC

GP

valu

e∗In

feri

or

ER

Infe

rior

ER

Pva

lue∗

Cha

ract

eris

tics

Num

ber

N(%

)2

57

13

66

4(4

7%

)7

2(5

3%

)0

.05

Age

(yea

rs)

47

±1

4.1

54

6.8

±1

2.6

84

7.1

±1

2.5

54

6.4

5±

12

.87

0.8

Age

atse

cond

ECG

(yea

rs)

–5

7.2

3±

12

.25

7.3

±1

2.8

85

7.2

±1

1.7

0.9

6M

en(%

)2

44

(95

%)

13

3(9

8%

)0

.16

2(9

7%

)7

1(9

9%

)0

.6A

fric

anA

mer

ican

(%)

61

(23

.7%

)3

8(2

7.8

%)

0.8

22

(34

.4%

)1

6(3

0.5

%)

0.2

Bod

y-m

ass

index

(kg/

m2

)2

5.4

1±

5.0

26

±5

.00

.04

25

.67

±4

.42

6.4

2±

5.6

0.4

del

taw

eigh

t(L

bs)

–4

±1

9.4

5.7

±2

0.3

2.3

5±

18

.40

.4C

ardio

vasc

ular

Dea

ths

(%)

15

(5.8

%)

5(3

.7%

)0

.11

(1.6

%)

4(5

.5%

)0

.2C

ardio

vasc

ular

even

ts(%

)2

8(2

0.5

%)

8(1

2.5

%)

20

(27

.7%

)0

.04

ECG

Mea

sure

men

tsC

omput

erST

leve

l1st

ECG

(µV)

11

7.8

4±

16

.11

20

.1±

17

.90

.11

21

.79

±1

8.7

11

8.5

±1

7.1

40

.3C

omput

erST

leve

l2nd

ECG

(µV)

–6

5.9

7±

48

.23

91

.76

±3

8.4

54

3±

33

.55

<0

.00

1C

omput

erST

leve

ldiff

eren

ce(µ

V)–

54

.08

±5

2.3

30

.03

±3

7.9

77

5.5

±4

1.6

0H

eart

Rat

eH

eart

Rat

e1

stEC

G(b

pm

)6

9.8

±1

1.6

96

9±

11

.69

0.1

70

.2±

12

.16

7.9

±1

1.2

50

.2H

eart

Rat

e2

ndEC

G(b

pm

)–

74

.7±

18

.57

0.0

4±

16

.77

8.8

8±

19

.30

.00

5D

elta

Hea

rtra

te(b

pm

)–

5.7

±1

8.8

(-)0

.2±

17

.41

1±

18

.60

.00

05

HR

>8

5bpm

1st

ECG

26

(10

.1%

)1

2(8

.8%

)0

.46

(9.3

%)

6(8

.3%

)0

.8H

R>

85

bpm

2nd

ECG

–3

3(2

4.3

%)

11

(17

.1%

)2

2(3

0.5

%)

0.0

6

(Con

tinu

ed)


Table

2.

(Con

tinu

ed)

Most

Ear

lyM

ost

Ear

lyR

epola

riza

tion

Rep

ola

riza

tion

Infe

rior

Infe

rior

Gro

upw

ith

Mai

ntai

ned

Lost

Lead

Gro

up2

ndEC

GP

valu

e∗In

feri

or

ER

Infe

rior

ER

Pva

lue∗

Tim

eFa

ctor

Per

iod

bet

wee

nEC

Gs

(yea

rs)

–1

0.4

6±

6.4

41

0.1

6±

6.9

51

0.7

2±

6.0

40

.6O

ther

ERcr

iter

iaFi

rst

ECG

All

(STE

L,J,

slur

)(%

)2

57

(10

0%

)1

36

(10

0%

)6

4(1

00

%)

72

(10

0%

)J

wav

e(%

)5

2(2

0.2

%)

25

(18

.4%

)0

.71

4(2

1.9

%)

11

(15

.3%

)0

.07

Slu

r(%

)1

81

(70

.5%

)1

00

(75

.3%

)0

.54

7(7

3.4

)5

3(7

3.6

%)

0.3

Jw

ave

orsl

ur(%

)2

33

(91

%)

12

5(9

2%

)0

.76

1(9

5%

)6

4(8

9%

)0

.3ST

elev

atio

non

ly(%

)2

4(9

.3%

)1

1(8

.0%

)0

.73

(4.6

%)

8(1

1.1

%)

0.1

7J

wav

eor

slur

only

(%)

19

6(7

6.3

%)

10

3(7

5.7

%)

0.9

53

(82

.8%

)5

0(6

9.4

%)

0.0

6J

wav

eor

slur

+STE

L(%

)3

7(1

4.4

%)

22

(16

.2%

)0

.68

(12

.5%

)1

4(1

9.4

%)

0.2

Ass

ocia

tion

with

late

ralE

R(%

)1

48

(57

.6%

)8

2(6

0.2

%)

0.6

38

(59

.3%

)4

4(6

1.1

%)

0.8

Sec

ond

ECG

Jw

ave

(%)

–2

0(1

4.7

%)

20

(31

.3%

)0

0Slu

r(%

)–

34

(25

%)

34

(53

.1%

)0

0J

wav

eor

slur

(%)

–5

4(3

9.7

%)

54

(84

.4%

)0

0ST

elev

atio

non

ly(%

)–

10

(7.5

%)

10

(15

.6%

)0

0J

wav

eor

slur

only

(%)

–4

6(3

3.8

%)

46

(71

.8%

)0

0J

wav

eor

slur

+STE

L(%

)–

8(5

.8%

)8

(12

.5%

)0

0A

ssoc

iation

with

late

ralE

R(%

)–

29

(21

.3%

)2

9(4

5.3

%)

15

(20

.8%

)0

.00

1

ER=

earl

yre

pol

ariz

atio

n;H

R=

hear

tra

te;

ECG

=el

ectr

ocar

dio

gram

;STE

L=

ST

elev

atio

n.


A

D

C

B

Figure 1. Four examples of excluded patient’s ECG’s. (A) A 50-year-old Hispanic male; Heart rate of 65 bpm.ECG shows pericarditis. (B) A 69-year-old Caucasian male; Heart rate of 64 bpm. ECG shows hypertrophiccardiomyopathy Q waves. (C) A 69-year-old Caucasian male; Heart rate of 64 bpm. ECG shows inferior myocardialinfarction (old). (D) A 75-year-old Caucasian male; Heart rate 94 bpm. ECG shows inferior myocardial infarction(old).

between patients with ER in the inferior leads onlyversus both inferior and lateral ER. Patients withboth inferior and lateral lead ER were younger andhad a lower heart rate and a higher proportion ofAfrican Americans, a lower prevalence of inferiorq waves and a trend towards increased cardiovas-cular death. The group with ER showed a similardemographic profile as the total population consis-tent with no selection biases.

Table 2 shows the greatest amplitude “normal”ER group (N = 257) divided into those who hada second ECG at least 5 months later (N = 136).The subgroup with a second ECG had no signifi-cant differences from the 257 available for reviewconsistent with an absence of any selection biases.In the greatest amplitude Inferior lead ER and theirsubgroup with a second ECG, slurs or J waves werepresent in 75% as the only manifestation of ER,

while ST elevation alone was present in less than10% of the ECGs. Slurs were nearly four timesmore common than J waves and 15% had bothslurs or J waves and ST elevation. Inferior ER wasassociated with lateral ER in 60% of the cases.

This target group of 136 with inferior lead ERand a subsequent ECG is divided into those whomaintained ER and those who lost it for the majorcomparison in this study. When comparing thosewho maintained inferior ER to those who lost it,47% maintained it while 53% lost it; it is impor-tant to mention that the average time interval be-tween first and second ECG was 10 years. Thosewho maintained inferior ER had no difference inheart rate, while those who lost it averaged 10 beatsper minute higher on the second ECG. There wasno significant difference in male prevalence, bodymass index, cardiovascular events, cardiovascular


Slur Slur J-wave Slur STE

BA C D E

Figure 2. Five examples of paired ECGs with lost early repolarization phenomenon. (A) A 41-year-old AfricanAmerican male; heart rate of 86 bpm. (Top panel). Same male after 3 years; heart rate of 53 bpm. (Bottompanel). (B) A 51-year-old Caucasian male; heart rate of 56 bpm. (Top panel). Same male after 11 years; heartrate of 83 bpm. (Bottom panel). (C) A 20-year-old Caucasian male; heart rate of 75 bpm. (Top panel). Same maleafter 22 years; heart rate of 92 bpm. (Bottom panel). (D) A 32-year-old Caucasian male; heart rate 71 bpm. (Toppanel). Same male after 18 years; heart rate of 110 bpm. (Bottom panel). (E) A 42-year-old Caucasian male;heart rate 85 bpm. (Top panel). Same male after 15 years; heart rate of 82 bpm. (Bottom panel).

deaths, or African Americans in the subgroups. Re-garding other ER criteria, the prevalence of J wavesor slurs, ST elevation or associated lateral ER wasnot statistically different between the maintainedversus lost inferior ER groups.

Figure 1 are examples of ECGs chosen using theamplitude for inferior ER with pathological find-ings associated with conditions that could causeER like patterns and were removed from the study.Figures 2 and 3 are examples of patients who lostinferior ER (greatest change in ER amplitude) andthose who maintained inferior ER (least change inER amplitude), respectively.

DISCUSSION

Our results suggest that in a stable outpatientpopulation, ER in the inferior leads was lost inabout half of the population over an average period

of 10 years. The conditions that could cause thisloss of ER including a higher heart rate, longer timebetween ECGs, ethnicity, gender, cardiac eventsbetween ECGs and death. Within the group thatlost the ER pattern, there was a statistically signif-icant increase in heart rate between the first andsecond ECG. However, there were no significantdifferences between the groups that lost or retainedER as far as age, body mass index, time interval be-tween ECGs, cardiovascular events, cardiovasculardeath, gender, and African American ethnicity. Therelatively small difference in heart rate (11 bpm)could not explain the loss leading us to concludethat our findings represent the natural history ofinferior lead ER.

Our findings are consistent with the concept thatER has a higher prevalence in younger populationsand that the pattern is often lost over time. Howmuch of the loss is due to basal heart rate increases,


J-wave Slur Slur

J-wave Slur J-wave STE

STESlur

BA C D E

J-wave

Figure 3. Five examples of paired electrocardiograms with maintained early repolarization phenomenon. (A) A46-year-old Caucasian male; heart rate of 73 bpm. (Top panel). Same male after 18 years; heart rate of 52 bpm.(Bottom panel). (B) A 37-year-old African American male; heart rate of 47 bpm. (Top panel). Same male after22 years; heart rate of 98 bpm. (Bottom panel). (C) A 41-year-old African American male; heart rate of 74 bpm.(Top panel). Same male after 18 years; heart rate of 74 bpm. (Bottom panel). (D) A 23-year-old Caucasian male;heart rate 63 bpm. (Top panel). Same male after 3 years; heart rate of 61 bpm. (Bottom panel).(E) A 61-year-oldAfrican American male; heart rate 80 bpm. (Top panel). Same male after 17 years; heart rate of 82 bpm. (Bottompanel).

age related myopathic changes and/or death waspoorly defined. Our prior data evaluating thenatural history of ER in lateral leads did not identifythat loss to be associated with changes in heart rate,cardiovascular events, or deaths.8 Similarly, in ourcurrent study we find that the age related attritionof inferior ER is not related to increased cardiovas-cular death. This argues against the hypothesis theECG finding becomes less prevalent as carriers ofthe inferior ER suffer arrhythmic deaths.

ER was long believed to be a benign clinical en-tity until a case cohort study by Haissaguerre etal. identified a higher prevalence of ER in patientswith idiopathic ventricular fibrillation.5 This find-ing was subsequently evaluated on a populationlevel by multiple groups suggesting a small, butstatistically significant, increased risk of arrhyth-mic or cardiovascular mortality associated with

ER.6,7,9–11 We attempted to evaluate the risk in ourown ambulatory population and failed to identifyan increased cardiovascular hazard when control-ling for demographics and concomitant ischemicfindings on ECG.12 We did find a higher preva-lence of other ECG abnormalities with inferior ERcompared to lateral ER. This was again evident inthis study with the high number of ECGs that hadto be excluded due to concomitant ECG findings ofischemia compared to our experience with lateralER.8 This association might explain the increasedcardiovascular risk some groups identified with in-ferior ER.

Study by Tikkanen et al. reported that over 80%of the population with inferior ER retained the phe-nomenon.6 This is divergent from the 53% reten-tion rate we report here and from the 38% reten-tion rate in the lateral leads previously reported.8


The variation in results might be related to severalfactors. The demographics of our populations aredifferent with our population being predominantlymale, more ethnically diverse and older. Further-more, we used a definition of ER that relied mainlyon ST elevation, not limited to J waves or slurs. Inaddition, the average duration of follow up ECGwas longer in our study (10 years vs. 5 years). Thestudy did not stratify risk based on retention or lossof the repolarization pattern.

We acknowledge that prospective populationstudies are the best method to determine prognos-tic significance, but the natural history of a findingcan provide some insight into the behavior of aphenomenon. Our study found that approximatelyhalf of the patients lost ER over time confirmingthe long held classic description that ER decreasesin prevalence with age. If inferior ER carriesan increased risk of cardiovascular deaths thenone would expect to see that the decreasingprevalence of the phenomenon to be associatedat least partially with cardiovascular mortality. Inother words, assuming a sustained risk model, thegroup that retains the ECG phenomenon shouldhave a higher cardiovascular event rate overtime. Our study did not identify this difference,and if anything saw a trend towards decreasedcardiovascular events in the group that retainedinferior ER. This does not provide a prognosticconclusion regarding the phenomenon, whichwas previously reported by our group and others;instead this demonstrates that the loss of ER overtime was not due to cardiovascular deaths.

Main limitations to our study are that it is a retro-spective convenience sample and not a prospectivenatural history study, but our data provides ahypothesis to be tested in prospective fashion. Inaddition, our target population is a selected sam-ple, given that the ECGs were ordered for clinicalindications and not by protocol. Those selectedfor repeat ECGs at a later time could have had anew clinical indication for doing so. However, therepeat ECG did not show diagnostic changes thatcould be associated with pathological conditionscausing the loss of ER nor did chart review revealany acute clinical condition. Also, we chose todefine one lead each for assessing inferior and lat-eral ER. This improves accuracy of identifying ER

and avoids potential discordance between partiallead changes across different ECGs. This increasesthe specificity of identifying ER and decreases theprobability of committing a type 1 error. Lastly,our population was predominantly male, thusrestricting the interpretation of our data to males.

To our knowledge this is the first report describ-ing the natural history of ER in the inferior leads.Our findings suggest that inferior lead ER was lostin over half of the population due to heart ratechanges and other aging related phenomenon, butnot cardiovascular death. This suggests that the agerelated attrition part of the natural history of infe-rior ER is not related to an increased cardiovascularrisk eliminating carriers of the phenomenon.

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3. Kambara H, Phillips J. Long term evaluation of early re-polarization syndrome (normal variant RS-T segment eleva-tion). Am J Cardiol 1976;38:157–161.

4. Gussak I, Antzelevitch C. Early repolarization syndrome:Clinical characteristics and possible cellular and ionic mech-anisms. J Electrocardiol 2000;33:299–309.

5. Haıssaguerre M, Derval N, Sacher F, et al. Sudden cardiacarrest associated with early repolarization. N Engl J Med2008;358:2016–2023.

6. Tikkanen JT, Anttonen O, Junttila MJ, et al. Long-term out-come associated with early repolarization on electrocardio-graphy. N Engl J Med 2009;361:2529–2537.

7. Sinner MF, Reinhard W, Muller M, et al. Association ofearly repolarization pattern on ECG with risk of cardiac andall cause mortality: A population based prospective cohortstudy (MONICA/KORA). PLoS Medicine 2010;7:e1000314.

8. Adhikarla C, Boga Madhavi, Wood AD, et al. Natural his-tory of the electrocardiographic pattern of early repolariza-tion in ambulatory patients. Am J Cardiol 2011;108:1831–1835.

9. Haruta D, Matsuo K, Tsuneto A, et al. Incidence and prog-nostic value of ER pattern in the 12-lead electrocardiogram.Circulation 2011;123:2931–2937.

10. Olson KA, Viera AJ, Soliman EZ, et al. Long term progno-sis associated with J-point elevation in a large middle-agedbiracial cohort: The ARIC study. Eur Heart J 2011;32:3098–3106.

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12. Uberoi M., Jain Nikhil A., Marco Perez, et al. Early repo-larization in an ambulatory clinical population. Circulation2011;124:2208–2214.

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