QT correction formulae for LQTS diagnosis

Wojciech Zareba, MD, PhD, and Arthur J. Moss, MD
Heart Research Follow-up Program, Cardiology Unit, University of Rochester
601 Elmwood Ave. Box 653, Rochester, NY 14642, USA

Abstract: The long QT syndrome (LQTS) serves as a paradigm to investigate electrophysiology of ventricular repolarization. The aim of this study was to evaluate the diagnostic usefulness of six different heart rate correction formulae in genetically confirmed LQTS patients. QT interval was measured in lead II, V2 and V5 in ECGs of 569 LQTS carriers and 722-noncarrier family members and corrected for heart rate using six different heart rate correction formulae. The comparison of diagnostic performance of those six QT corrected formulae for identifying patients with genetically confirmed LQTS demonstrated that there are no significant differences between them. In conclusion, regardless of heart rate, different QT interval correction formulae show similar performance when identifying LQTS patients.

Introduction

There is a major unresolved debate regarding optimal correction of QT interval duration for heart rate. The long QT syndrome (LQTS) serves as a paradigm to investigate electrophysiology of ventricular repolarization and was used to identify optimal cut-offs for repolarization duration.^1,2 Since Bazett developed his concept of QTc in 1920s³, there were several attempts to design new formula that could better reflect true repolarization duration over a wide spectrum of heart rates.^4-8 Although some of new formulas (listed below) seem to better adjust for heart rate than Bazett’s formula, clinical practice indicates that the latter is the only standard correction formula used on everyday basis. Bazett’s formula has been criticized as inadequate to reflect true value (prolongation) of repolarization. Nevertheless, no studies addressed the diagnostic usefulness of Bazett’s and other formulae in setting of genetically confirmed long QT syndrome. There is a substantial overlap of QTc values between LQTS carriers and non-carriers and identifying QT correction approach providing more robust distinction between carriers and non-carriers would be of practical value.¹ Simultaneously, there is an increasing demand for repolarization analysis in drug studies, which face the dilemma which heart rate correction formula to use. For the above reasons, we designed a study to compare diagnostic performance of six heart rate correction QT formulae for identifying genetically confirmed LQTS patients.           

Method

In 569 LQTS gene carriers and 722 non-carrier family members QT was measured in baseline ECG in leads II, V2, and V5. Subjects were stratified according to heart rate: ≦60 bpm (177 carrires and and 107 noncarriers), 61-100 bpm (328 carriers  and 472 noncarriers), and >100 bpm (64 carriers  and 143 noncarriers). Six different HR correction formulae were used:

B) BAZETT³  (QTc = QT/RR ^1/2)
 

F) FRIDERICIA⁴  (QTc = QT/RR^1/3)
 

FR) FRAMINGHAM⁵ (QTc = QT+0.154(1-RR))

H) HODGES⁶ (QTc = QT+1.75(HR-60))

R) RAUTAHARJU⁷
for females and males <15 and >50 years:
    (QTI = (QT(HR+100))/656)
for males 15-50 years
    QTI= 100(QT)/((656/(1+0.01HR))+0.4age - 25));

K) KARJALAINEN⁸
for HR<60: QTc = 392(QT)/(0.116(RR)+277);
for HR 60-99: QTc=392(QT)/(0.156(RR)+236);
for HR>100: QTc=392(QT)/(0.384(RR)+99)).

The values of QT intervals analysis in carriers and noncarriers were compared and the magnitude of separation between those two groups was quantified using number of standard deviation units (for noncarriers) differentiating them.

RESULTS

Mean QT corrected values were significantly higher in carries than noncarriers for all heart rate correction formulae. The Table shows difference between carriers and noncarriers expressed as number of standard deviation units of QT values (in lead II) differentiating two groups for three ranges of heart rates. Results were similar for leads V2 and V5. As shown in the table, there was no significant difference in separating carriers from noncarriers among all studied heart rate correction formulae.

Formula	HR (bpm)	Mean QT in NC	Mean QT in C	SD in NC	Delta
B	≦60	399	495	31	3.09
	61-100	423	495	26	2.73
	>100	424	481	26	2.22
F	≦60	406	504	31	3.17
	61-100	406	477	25	2.84
	>100	376	428	25	2.06
FR	≦60	403	505	33	3.12
	61-100	407	474	23	2.81
	>100	375	416	21	1.94
H	≦60	411	514	33	3.12
	61-100	405	472	23	2.89
	>100	410	448	22	1.74
R*	≦60	100	124	7	3.23
	61-100	100	119	6	2.87
	>100	101	114	6	2.16
K	≦60	405	504	31	3.14
	61-100	409	481	25	2.84
	>100	405	458	26	2.07

* Rautaharju formula yields values expressed in percents, not in milliseconds like other formulae
HR - heart rate; C – Carriers; NC – non-carriers; SD – standard deviation of QT measurement in non-carriers
Delta – difference in heart rate corrected QT value between carriers and non-carriers expressed as number of standard deviations for non-carriers.

For heart rates ≦60 bpm, Rautaharju formula was the best one to separate carriers from non-carriers and all other formulae performed somewhat better than Bazett, however, differences were not significant. For heart rates 61-100 bpm, best diagnostic performance was obtained with Hodges formula and all other formulae performed somewhat better than Bazett, however, again no significant difference was observed between them. For heart rates >100 bpm, Bazett formula performed the best and Hodges the worst. Summarizing, despite some trends in different performance of studied QT correction formulae there was no significant difference between them.

CONCLUSIONS

Regardless of heart rate, different QT interval correction formulae show similar performance when identifying LQTS patients

References

1.       Zareba W, Moss AJ, Schwartz PJ et al. Influence of the genotype on the clinical course of the long QT syndrome. N Engl J Med 1998;339:960-5.

2.       Moss AJ, Robinson J. Clinical features of the idiopathic long QT syndrome. Circulation 1992;85(suppl I):I-140-I-144.

3.       Bazett HC: An analysis of time relations of electrocardiograms. Heart 1920;7:353-367.

4.       Federicia LS. Duration of systole in electrocardiogram. Acta Med Scandinav 1920;53:469

5.       Sagie A. Larson MG. Goldberg RJ. Et al. An  improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol 1992;70:797-801.

6.       Hodges, M., Salerno, D., Erlien, D. Bazett's QT correction reviewed: Evidence that a linear QT correction for heart rate is better. JACC 1983;1:694

7.       Rautaharju PM, Zhou SH, Wong S, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992;8:690-5.

8.       Karjalainen J, Viitasalo M, Manttari 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. J Am Coll Cardiol 1994;23:1547-53