Methods
Study Population
The study population comprises of a total of 10 957 men and women
aged 30 to 59 years, who participated in the Finnish Social Insurance
Institutions Coronary Heart Disease Study (CHD Study) between
1966 and 1972. We excluded 58 subjects with unreadable or missing
ECGs, thus our final study group consisted of 10 899 subjects (52%
of whom were men, mean age 44.08.5 years) from the original
cohort. The CHD Study was a part of the larger prospective Mobile
Clinic Health Survey that was conducted in 35 populations from
different geographical areas in Finland with varying mortality rates
representing the middle-aged Finnish population. The population
groups consisted of either the whole population or a random sample
of the population of a geographical area, and the overall participation
rate of the invited population was 89.6%. A detailed account of the
study rationale and procedures performed at the baseline examination has been described previously.14 In brief, a standard 12-lead
DOI: 10.1161/CIRCULATIONAHA.112.098681
Aro et al
2573
ECG was recorded and blood pressure, body mass index, and serum
cholesterol were measured. Before the examination, the subjects
completed a questionnaire regarding their history of previous diseases, drug therapy, and smoking habits, which was then checked
and completed, if necessary, by a specially trained nurse at the
examination. All symptoms of cardiovascular disease were documented during the examination.
Follow-Up
From the baseline examination between 1966 and 1972, the subjects
were followed for a mean of 3011 years until the end of 2007.
After a median follow-up time of 6 years, a reexamination of most of
the subjects was performed between 1973 and 1976. Less than 2% of
the subjects were lost to follow-up as a result of moving abroad, but,
for the vast majority of even this group, the survival status could be
determined. The mortality data were obtained from the Causes of
Death Register maintained by Statistics Finland, and the death
certificates were obtained for each deceased. Death from cardiac
causes was determined based on the relevant International Classification of Diseases codes. To identify cases of sudden death from
arrhythmia, all deaths from cardiac causes were reviewed by the use
of hospital records and necropsy reports, if available, based on the
definitions presented in the Cardiac Arrhythmic Pilot Study,15 as
described by our group previously.16 All episodes of congestive heart
failure, ventricular arrhythmias, and coronary artery disease serious
enough to require hospitalization were obtained from the Finnish
Hospital Discharge Register, which includes nationwide data on all
inpatient episodes in Finland at an individual level.17
ECG Measurement
A standard 12-lead ECG was recorded with the subject at rest in a
supine position at paper speed of 50 mm/s and calibration of 1
mV/10 mm. The presence or absence of bundle branch block and left
ventricular hypertrophy according to the Sokolow-Lyon criteria was
assessed, and QT-interval (corrected for heart rate according to
Bazett formula) was measured at the time of baseline examinations.
Later, all baseline ECGs were independently reevaluated by 5
physicians for the presence of inverted T waves (T wave negative by
0.1 mV or more in leads other than aVR, aVL, III, and V1). In
addition, QRS duration, ST-segment elevation in leads V1 to V3, and
terminal activation duration (longest value in leads V1 through V3
from the nadir of the S wave to the end of all depolarization) were
measured. All ECGs with inverted T waves in leads V1 through V3
were double checked, and the presence of T-wave inversions and
epsilon waves was established by consensus. Epsilon wave was
defined as a distinct deflection after the end of the QRS complex.18
For the majority of subjects, an additional ECG was taken after a
median of 6 years from the baseline examination, and the persistence
of precordial T-wave inversions was assessed.
Statistical Analysis
All continuous data are presented as meansSD. The general linear
model was used to compare the age- and sex-adjusted mean values
for continuous variables and the prevalence of categorical variables
between the groups. Primary end points were all-cause mortality,
cardiac mortality, and arrhythmic death, and secondary end points
were hospitalization because of congestive heart failure, ventricular
arrhythmias, or coronary artery disease. The hazard ratios and 95%
confidence intervals for death and hospitalization were calculated by
uses of Cox proportional hazards model, with adjustments for age and
sex, subjects without T-wave inversions serving as the reference group.
KaplanMeier survival curves were plotted for T-wave inversions in
leads V1 to V3 and other leads and were compared by means of the
log-rank test. The statistical analyses were performed with SAS software, version 9.1.3 (SAS Institute) and with the Statistical Package for
Social Studies, version 14.0 (SPSS). A probability value of 0.05 was
considered to indicate statistical significance.
Results
ECG Characteristics
Inverted T waves in right precordial leads V1 to V3 were
observed in 54 (0.5%) of the subjects. In 14 (26%) of these
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Circulation
Males, %*
Age, y
Current smoker, %
Cholesterol, mmol/L
BMI, kg/m2
Heart rate, bpm
Systolic blood pressure, mm Hg
Diastolic blood pressure, mm Hg
Chronotropic medication, %
Cardiovascular disease, %
Electrocardiographic LVH, %
QTc duration. ms
QRS duration, ms
History of prior myocardial infarction, %
History of angina pectoris, %
P Value
No TWI
n10 734
TWI V13
n54
TWI Other
n76
TWI V13
TWI Other
52.4
44.08.5
34.0
6.501.31
25.93.8
7615
13821
8212
4.2
7.9
31.4
40827
878
1.1
2.3
12.9
43.68.4
34.1
6.561.78
26.04.4
6913
13522
809
2.3
14.1
23.7
40831
876
0.4
0.0
60.4
49.37.6
39.2
6.641.77
26.74.7
7617
14826
8716
19.3
30.0
39.2
40835
9011
0.0
0.6
0.001
0.77
0.98
0.72
0.94
0.001
0.18
0.18
0.48
0.08
0.22
0.93
0.86
0.63
0.17
0.17
0.001
0.30
0.36
0.08
0.95
0.001
0.001
0.001
0.001
0.13
0.98
0.001
0.19
0.34
Plus-minus values are meansSD. Subjects with no TWI serve as the comparison group for P values. To convert the values of
cholesterol to milligrams per deciliter, divide by 0.02586. TWI indicates T-wave inversion; LVH, electrocardiographic left ventricular
hypertrophy according to the Sokolow-Lyon criteria; QTc, QT corrected for heart rate.
*Adjusted for age.
Adjusted for sex.
Adjusted for age and sex.
Aro et al
Discussion
Inverted T waves in precordial leads beyond V1 are common
in children, but usually these T waves become upright after
pubertal development.19 However, in some healthy individuals, similar juvenile inverted T waves persist into adulthood.4
Therefore, incidentally observed T-wave change in an asymptomatic subject poses a clinical problem, because T-wave
inversions can also be the expression of an underlying cardiac
disease capable of causing sudden cardiac death.5,20 The present
study is the first to directly address the characteristics and
2575
2576
Circulation
the diagnosis was based only on past medical history and clinical
examination. Besides, echocardiography was not generally
available at the time of baseline examination, and therefore some
of the subjects with inverted T waves might have had a structural
cardiac disease not evident during the clinical examination, but
yet caused repolarization abnormalities in their 12-lead ECGs.
Another limitation of the present study is the relatively small
number of subjects with right precordial T-wave inversions,
which precludes definitive conclusions on the prognostic significance of this ECG pattern.
In summary, right precordial T-wave inversion in leads V1
to V3 is a relatively rare finding in the middle-aged general
population, especially in men. Although this electrocardiographic pattern can raise a suspicion of a cardiomyopathy, in
the absence of deeply inverted T waves or other features
suggestive of heart disease, right precordial T-wave inversions appear to carry normal prognosis in the general population. In contrast, inverted T waves in other than right
precordial leads may imply an underlying cardiac pathology
and are associated with increased cardiac mortality.
Sources of Funding
The study was supported by a special federal grant for Paijat-Hame
Central Hospital, and by scholarships from Onni and Hilja Tuovinen
Foundation, the Finnish Medical Foundation, and Sigrid Juselius
Foundation (HVH), Helsinki, Finland.
Disclosures
None.
References
1. Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ,
Gorgels A, Hancock EW, Josephson M, Kligfield P, Kors JA, Macfarlane
P, Mason JW, Mirvis DM, Okin P, Pahlm O, van Herpen G, Wagner GS,
Wellens H, American Heart Association Electrocardiography and
Arrhythmias Committee, Council on Clinical Cardiology, American
College of Cardiology Foundation, Heart Rhythm Society. AHA/
ACCF/HRS recommendations for the standardization and interpretation
of the electrocardiogram: part IV: the ST segment, T and U waves, and
the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on
Clinical Cardiology; the American College of Cardiology Foundation;
and the Heart Rhythm Society. Endorsed by the International Society for
Computerized Electrocardiology. J Am Coll Cardiol. 2009;53:982991.
2. Papadakis M, Basavarajaiah S, Rawlins J, Edwards C, Makan J, Firoozi S,
Carby L, Sharma S. Prevalence and significance of T-wave inversions in
predominantly Caucasian adolescent athletes. Eur Heart J. 2009;30:
7281735.
3. Hiss RG, Averill KH, Lamb LE. Electrocardiographic findings in 67,375
asymptomatic subjects. VIII. Nonspecific T wave changes. Am J Cardiol.
1960;6:178 189.
4. Marcus FI. Prevalence of T-wave inversion beyond V1 in young normal
individuals and usefulness for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. Am J Cardiol. 2005;95:10701071.
5. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular
cardiomyopathy and sudden death in young people. N Engl J Med.
1988;318:129 133.
6. Nasir K, Bomma C, Tandri H, Roguin A, Dalal D, Prakasa K, Tichnell C,
James C, Spevak PJ, Marcus F, Calkins H. Electrocardiographic features
of arrhythmogenic right ventricular dysplasia/cardiomyopathy according
to disease severity: a need to broaden diagnostic criteria. Circulation.
2004;110:15271534.
7. Peters S, Trummel M. Diagnosis of arrhythmogenic right ventricular
dysplasia-cardiomyopathy: value of standard ECG revisited. Ann Noninvasive Electrocardiol. 2003;8:238 245.
8. Peters S, Trummel M, Koehler B, Westermann KU. The value of different
electrocardiographic depolarization criteria in the diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Electrocardiol.
2007;40:34 37.
Aro et al
9. Jain R, Dalal D, Daly A, Tichnell C, James C, Evenson A, Jain R,
Abraham T, Tan BY, Tandri H, Russell SD, Judge D, Calkins H. Electrocardiographic features of arrhythmogenic right ventricular dysplasia.
Circulation. 2009;120:477 487.
10. Marcus FI, Zareba W, Calkins H, Towbin JA, Basso C, Bluemke DA,
Estes NA,III, Picard MH, Sanborn D, Thiene G, Wichter T, Cannom
D, Wilber DJ, Scheinman M, Duff H, Daubert J, Talajic M, Krahn A,
Sweeney M, Garan H, Sakaguchi S, Lerman BB, Kerr C, Kron J,
Steinberg JS, Sherrill D, Gear K, Brown M, Severski P, Polonsky S,
McNitt S. Arrhythmogenic right ventricular cardiomyopathy/dysplasia
clinical presentation and diagnostic evaluation: results from the North
American Multidisciplinary Study. Heart Rhythm. 2009;6:984 992.
11. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA,
Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R,
Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS,
Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W.
Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia:
proposed modification of the task force criteria. Circulation. 2010;121:
15331541.
12. Pelliccia A, Di Paolo FM, Quattrini FM, Basso C, Culasso F, Popoli G, De
Luca R, Spataro A, Biffi A, Thiene G, Maron BJ. Outcomes in athletes with
marked ECG repolarization abnormalities. N Engl J Med. 2008;358:
152161.
13. Pelliccia A, Culasso F, Di Paolo FM, Accettura D, Cantore R, Castagna
W, Ciacciarelli A, Costini G, Cuffari B, Drago E, Federici V, Gribaudo
CG, Iacovelli G, Landolfi L, Menichetti G, Atzeni UO, Parisi A, Pizzi
AR, Rosa M, Santelli F, Santilio F, Vagnini A, Casasco M, Di Luigi L.
Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur
Heart J. 2007;28:2006 2010.
14. Reunanen A, Aromaa A, Pyorala K, Punsar S, Maatela J, Knekt P. The
Social Insurance Institutions coronary heart disease study. Baseline data
and 5-year mortality experience. Acta Med Scand Suppl. 1983;673:1120.
15. Greene HL, Richardson DW, Barker AH, Roden DM, Capone RJ, Echt
DS, Friedman LM, Gillespie MJ, Hallstrom AP, Verter J. Classification
of deaths after myocardial infarction as arrhythmic or nonarrhythmic (the
Cardiac Arrhythmia Pilot Study). Am J Cardiol. 1989;63:1 6.
16. Aro AL, Anttonen O, Tikkanen JT, Junttila MJ, Kerola T, Rissanen HA,
Reunanen A, Huikuri HV. Intraventricular conduction delay in a standard
12-lead electrocardiogram as a predictor of mortality in the general
population. Circ Arrhythm Electrophysiol. 2011;4:704 710.
17. Rapola JM, Virtamo J, Korhonen P, Haapakoski J, Hartman AM,
Edwards BK, Heinonen OP. Validity of diagnoses of major coronary
events in national registers of hospital diagnoses and deaths in Finland.
Eur J Epidemiol. 1997;13:133138.
18. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL,
Malergue C, Grosgogeat Y. Right ventricular dysplasia: a report of 24
adult cases. Circulation. 1982;65:384 398.
19. Suarez RM, Suarez RM Jr. The T-wave of the precordial electrocardiogram at different age levels. Am Heart J. 1946;32:480 493.
20. Okada M, Yotsukura M, Shimada T, Ishikawa K. Clinical implications of
isolated T wave inversion in adults: electrocardiographic differentiation
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
2577
CLINICAL PERSPECTIVE
T-wave inversion in right precordial leads V1 to V3 is a common finding in a 12-lead ECG of children and adolescents,
and is sometimes present in healthy adults, as well. However, right precordial T-wave inversion can also be the first
manifestation of a structural heart disease such as arrhythmogenic right ventricular cardiomyopathy. In the present study,
we assessed the prevalence and prognostic significance of T-wave inversions in a large Finnish middle-aged general
population cohort with a long follow-up. Inverted T waves in right precordial leads V1 to V3 were present in 0.5% of the
subjects, but deeply inverted T waves (5 mm or more) or additional features suggestive of arrhythmogenic right ventricular
cardiomyopathy were extremely rare. The prognosis associated with right precordial T-wave inversion was good and did
not differ from the rest of the population. However, T-wave inversions in leads other than V1 to V3 were associated with
a significantly increased risk of cardiac and arrhythmic death. Thus, although inverted T waves in V1 to V3 can raise a
suspicion of a cardiomyopathy, in the absence of deeply inverted T waves or other features suggestive of a heart disease,
this ECG pattern does not predict adverse outcome. In contrast, T-wave inversions in other than right precordial leads may
reflect the presence of an underlying cardiac pathology and are associated with increased mortality.
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SUPPLEMENTAL MATERIAL
aVR
II
aVL
V3
V4
aVF
III
V1
V5
V2
V6
aVR
II
aVL
III
aVF
V3
V4
V5
V1
V2
V6
aVR
V3
II
aVL
V4
III
aVF
V5
V1
V2
V6
II
aVR
V3
aVL
V4
III
aVF
V1
V2
V5
V6
55ms,
and duration of QRS complex over 110ms in the right precordial leads. The subject died of
cardiac causes at the age of 67 years.