Evaluation of QT Correction Formulas Based on
Electrocardiograms from Population Studies
S. Perz, A. Pfeufer, S. Kääb*, R. Küfner, K.H. Englmeier,
H.E. Wichmann for the KORA Study Group
GSF- Forschungszentrum für Umwelt und Gesundheit, Neuherberg,
Institut für Medizinische Informatik, Institut für Humangenetik
und Institut für Epidemiologie
*LMU/Klinikum-Großhadern, München
QT/QTc Interval
Heidelberg, 17.-18.11.2005
Evaluation of QT Correction Formulas
Background
•
•
•
Cardiac arrhytmias cause up to 50% of sudden cardiac death.
Little knowledge about the specific conditions that trigger the
situation any one individual
Development of severe cardiac rhythm diturbances and cardiac
mortality is associated with a prolonged QT interval
QT/QTc Interval
Heidelberg, 17.-18.11.2005
ECG-Signatures: Definition
Sinus Node
AV-Node
Left
Bundle
His-Bundle
Purkinje-Fibers
Right
Bundle
QRS:
QT:
Excitation
Excitation
+
Repolarization
QT interval and correction for heart rate
QT/QTc Interval
QT Interval Correction for Heart Rate
QT correction according to Bazett
QTc = QT * (60/heart rate) 1/2
[ms]
RR = (60/heart rate) *1000
[ms]
QTc = QT * (RR/1000) 1/2
QT/QTc Interval
[ms]
Heidelberg, 17.-18.11.2005
Towords Optimisation of QT Correction for Heart Rate
QT correction formulae
Bazett:
QTc = QT * RR 1/2
Fridericia:
QTc = QT * RR 1/3
Framingham: QTc = QT + 0.154*(1000 – RR)
Nomogram:
QT/QTc Interval
QTc = QT + 0.116* (1000 - RR)
QTc = QT + 0.156* (1000 - RR)
QTc = QT + 0.384* (1000 - RR)
if
RR > 1000
if 600 < RR <1000
if
RR < 600
Heidelberg, 17.-18.11.2005
Towords Optimisation of QT Correction for Heart Rate
Objective
• To identify the best fit of QT-RR relation considering four
known QT correction formulae using computerized ECG
measurement derived from
- a population-based survey and
- a population-based follow-up
GSF- KORA Study Group
Perz et al.
Population-based studies of the MONICA Project Augsburg
Time table of the Monica Project Augsburg.
Survey and follow-up ECG data used for QT and QTc interval evaluation
GSF – MONICA/KORA Study Group
Population-based studies in Southern Germany
Study region
- City of Augsburg and
two surrounding rural districts
- Population register covers
about 530,000 persons
GSF – MONICA/KORA Study Group
Monica Augsburg Surveys: ECG examination and data collection
• Twelve lead resting ECG
•1 st record: Survey 1984/85
• 2 nd record: Follow-up 1987/88
• N = 3299
Computerized ECG Analysis
MONICA Augsburg Surveys
Perz et al.
Computerized ECG Analysis
Advantages
•
Expert knowledge
•
•
Reproducibility of the analysis
Electronic storage of measurement and
interpretation for
Statistical analysis
•
Valid Phenotyping
GSF Institute of Medical Informatics
KORA Study Group
QT distribution (N=3299)
25
20
15
%
10
5
0
260
300
340
380
420
460
500
540
(ms)
GSF KORA Study Group
Perz et al.
Heart rate distribution (N=3299)
25
20
15
%
10
5
0
30
40
50
60
70
80
90
100
110
120
Heart rate (1/min)
GSF- KORA Study Group
Perz et al.
QT vs. RR (N=3299)
550
500
QT (ms)
450
400
-------------
350
300
BZ
CR
FH
NG
250
400
600
800
1000
1200
1400
1600
RR (ms)
GSF- KORA Study Group
Perz et al.
QT and QTc Distributions
25
QT
QTc (BZ)
20
QTc (CR)
QTc (FH)
15
QTc (NG)
%
10
5
0
260
300
340
380
420
460
500
540
(ms)
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
m (ms)
s (ms)
Rsd 2
QT
383.6
26.5
-
QTc (Bazett)
401.8
21.4
0.35
QTc (Cubic Root)
395.4
18.5
0.49
QTc (Framingham)
395.8
18.2
0.53
QTc (Nomogram)
397.1
17.9
0.54
Variable
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
The benefit of different QT correction
formulae
9 Inter-individual differences
Survey data (1st ECGs)
?
Intra-individual differences of QT intervals
Follow-up data (1st vs. 2nd ECGs)
GSF- KORA Study Group
Perz et al.
Follow-up: QT change s v s. RR change s (N=3)
600
550
500
QT (m s)
cas e 2
450
cas e 3
cas e 1
400
350
300
250
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
RR (ms)
GSF- KORA Study Group
Perz et al.
QT and QTc intervals: 1st vs. 2nd measurement (N=3299)
550
550
QT
Framingham
500
450
(ms)
400
QTc_FH(2)
500
350
450
400
350
300
300
300
350
400
450
500
300
550
500
550
500
550
Nomogram
500
500
(ms)
450
QTc_NG(2)
(m s)
450
(m s)
550
Bazett
Q T c_B Z (2)
400
QTc_FH(1)
Q T 1 ( ms )
550
350
400
350
450
400
350
300
300
350
400
QTc_BZ(1)
450
500
550
300
300
350
400
QTc_NG(1)
(m s)
450
(m s)
550
Cubic root
QTc_CR(2)
(m s)
500
Best fit?
450
400
350
300
300
350
400
QTc_ CR(1)
450
(ms)
500
550
GSF- KORA Study Group: Perz et al.
Distributions of QT and QTc Differences: 2nd - 1st measurement
35
DQT
30
DQTBZ
DQTCR
25
DQTFH
20
DQTNG
%
15
10
5
0
-120
-100
-80
-60
-40
-20
0
20
40
60
80
100
120
ms
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
m (ms)
s (ms)
Ric 2
QT
3.0
21.0
-
QTc (Bazett)
-0.5
16.8
0.36
QTc (Cubic Root)
0.7
13.8
0.57
QTc (Framingham)
0.4
13.9
0.56
QTc (Nomogram)
0.6
13.6
0.58
2 nd – 1 st measurement
of variable
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
Summary and Conclusion
• Correction of the QT- Interval for heart rate reduces the
variance of the QT interval
- cross-sectionally on a population-based scale
- individually (follow-up)
• The QT correction formulas according to the Nomogram
method, according to theFramingham study and also
according to Fridericia are significantly superior to Bazett‘s
formula.
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
References (1)
Bazett HC. An analysis of time relations of the electrocardiogram. Heart 1920;7: 353- 70
Fridericia LS. Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei Herzkranken.
Acta Med Scand 1920,53: 469
Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved method for adjusting the QT
interval for heart rate (the Framingham Heart Study). Am J Cardiol 1992; 70:797-801.
Karjalainen J, Viitasalo M, Mänttäri M, Manninen V. Relation between QT intervals and heart rates from
40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval
values. JACC 1994, 23(7): 1547-53
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
References (2): GSF publications based on investigations of the QT interval (2004-2005)
Perz S, Pfeufer A, Holle R, Hinterseer M, Küfner R, Englmeier K-H, Wichmann H-E, and Kääb S for the KORA Study
Group: Does Computerized ECG Analysis Provide Sufficiently Consistent QT Interval Estimates For Genetic
Research? In: Analysis of Biomedical Signals and Images – Proceedings of the 17th Biennial International
EURASIP Conference Biosignal 2004, Brno, Czech Republic, June 23-25, 2004 (Eds. J. Jan, J.Kozumplik, I.
Provaznik), Vutium Press, 47-49 (2004)
Perz S, Küfner R, Meisinger C, Ziegler D, Englmeier KH and the KORA Study Group: The Effect of Different QT
interval Corrections for Heart Rate on the QT Distributions in Diabetics and Non-Diabetic Subjects. In:
Proceedings der 38. DGBMT-Jahrestagung, Ilmenau, 22.-24.9.2004 (Eds. U. Boenick, A. Bolz, 296-297 (2004)
Pfeufer A, Jalilzadeh S, Perz S, Mueller JC, Hinterseer M, Illig T, Akyol M, Huth C, Schopfer-Wendels A, Kuch B,
Steinbeck G, Holle R, Nabauer M, Wichmann HE, Meitinger T, Kaab S. Common variants in myocardial ion
channel genes modify the QT interval in the general population: results from the KORA study. Circ Res. 2005
Apr 1;96(6):693-701.
GSF- KORA Study Group
Perz et al.
Towords Optimisation of QT Correction for Heart Rate
References (3)
Rautaharju PM, Warren JW,Calhoun HP: Estimation of QT prolongation – a persistent and avoidable
error in computer electrocardiography. J Electrocardiol 1990, 23, 111-117.
de Bruyne MC, Hoes AW, Kors JA, A. Hofman A,. van Bemmel JH, Grobbee E. Prolonged QT interval
predicts cardiac and all-cause mortality in the elderly: The Rotterdam Study. Eur Heart J 1999; 20:
278-84.
Kass RS, Moss AJ. Long QT syndrome: novel insights into the mechanisms of cardiac arrhythmias. J
Clin Invest 2003;112(6):810-5.
Busjahn A, Knoblauch H, Faulhaber HD, Boeckel T, Rosenthal M, Uhlmann R, Hoehe M, Schuster H,
Luft FC. QT interval is linked to 2 long-QT syndrome loci in normal subjects. Circulation 1999;
99(24):3161-4.
GSF
KORA Study Group
Towords
Optimisation
of QT
Correction
for Heart Rate
Evaluation
of QT
Correction
Formulas
Vielen Dank!
QT/QTc Herbstworkshop, Heidelberg, 17.-18.11.2005
Siegfried Perz