Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events

Reingold ECG Center, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.

OBJECTIVES. This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability. BACKGROUND. Recent Holter monitoring data have revealed a high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized. METHODS. We developed and validated a new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of data from 21 healthy subjects. RESULTS. Measurement of 6,048 segments showed mean (+/- SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms, respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels. CONCLUSIONS. The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach a peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardia and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.

This article has been cited by other articles:

				T. Krasemann, C. Strompen, J. Blumenberg, J. Gehrmann, G. Burkhardtsmaier, and J. Vogt Changes of the corrected QT interval in healthy boys and girls over day and night Eur. Heart J., October 2, 2008; (2008) ehn452v1. [Abstract] [Full Text] [PDF]

				S. A. Shah, L. Schlesselman, D. Cios, J. Lipeika, A. A. Patel, J. Kluger, and C. M. White Effects of echinacea on electrocardiographic and blood pressure measurements Am. J. Health Syst. Pharm., August 1, 2007; 64(15): 1615 - 1618. [Abstract] [Full Text] [PDF]

				S. A Shah, S. Sander, D. Cios, J. Lipeika, J. Kluger, and C M. White Electrocardiographic and Hemodynamic Effects of Coenzyme Q10 in Healthy Individuals: A Double-Blind, Randomized Controlled Trial Ann. Pharmacother., March 1, 2007; 41(3): 420 - 425. [Abstract] [Full Text] [PDF]

				K. Zerumsky and B. F. McBride Ranolazine in the management of chronic stable angina Am. J. Health Syst. Pharm., December 1, 2006; 63(23): 2331 - 2338. [Abstract] [Full Text] [PDF]

				G. Nilsson, P. Hedberg, T. Jonasson, I. Lonnberg, and J. Ohrvik QTc interval and survival in 75-year-old men and women from the general population. Europace, April 1, 2006; 8(4): 233 - 240. [Abstract] [Full Text] [PDF]

				S. M.J.M. Straus, J. A. Kors, M. L. De Bruin, C. S. van der Hooft, A. Hofman, J. Heeringa, J. W. Deckers, J. H. Kingma, M. C.J.M. Sturkenboom, B. H. Ch. Stricker, et al. Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults J. Am. Coll. Cardiol., January 17, 2006; 47(2): 362 - 367. [Abstract] [Full Text] [PDF]

				P. Korantzopoulos, K. Siogas, S. Viskin, D. Justo, D. Zeltser, G. Curigliano, C. Cipolla, F. de Braud, R. A. Cruciani, R. K. Portenoy, et al. Drug-Induced Prolongation of the QT Interval N. Engl. J. Med., June 17, 2004; 350(25): 2618 - 2621. [Full Text] [PDF]

				B. F. McBride, A. K. Karapanos, A. Krudysz, J. Kluger, C. I. Coleman, and C. M. White Electrocardiographic and Hemodynamic Effects of a Multicomponent Dietary Supplement Containing Ephedra and Caffeine: A Randomized Controlled Trial JAMA, January 14, 2004; 291(2): 216 - 221. [Abstract] [Full Text] [PDF]

				S. M. Al-Khatib, N. M. A. LaPointe, J. M. Kramer, and R. M. Califf What Clinicians Should Know About the QT Interval JAMA, April 23, 2003; 289(16): 2120 - 2127. [Abstract] [Full Text] [PDF]

				T. Yamashita, A. Sekiguchi, Y.-k. Iwasaki, K. Sagara, H. Iinuma, S. Hatano, L.-T. Fu, and H. Watanabe Circadian Variation of Cardiac K+ Channel Gene Expression Circulation, April 15, 2003; 107(14): 1917 - 1922. [Abstract] [Full Text] [PDF]

				S. S. Baker, N. S. Talner, A. S. Milazzo Jr, S. P. Sanders, A. M. Valente, R. J. Kanter, I. M. Paul, and J. S. Li Measures of Cardiac Repolarization and Body Position in Infants Clinical Pediatrics, January 1, 2003; 42(1): 67 - 70. [Abstract] [PDF]

				X. H.T. Wehrens, M. A. Vos, P. A. Doevendans, and H. J.J. Wellens Novel Insights in the Congenital Long QT Syndrome Ann Intern Med, December 17, 2002; 137(12): 981 - 992. [Abstract] [Full Text] [PDF]

				P. A. Lanfranchi, A. S.M. Shamsuzzaman, M. J. Ackerman, T. Kara, P. Jurak, R. Wolk, and V. K. Somers Sex-Selective QT Prolongation During Rapid Eye Movement Sleep Circulation, September 17, 2002; 106(12): 1488 - 1492. [Abstract] [Full Text] [PDF]

				G. Kabakci, O. Onalan, M. Kemal Batur, A. Yildirir, R. Cagrikul, T. Acil, L. Tokgozoglu, A. Oto, F. Ozmen, and S. Kes What is the Optimal Evaluation Time of the QT Dispersion After Acute Myocardial Infarction for the Risk Stratification? Angiology, July 1, 2001; 52(7): 463 - 468. [Abstract] [PDF]

				E. Yetkin, K. Senen, M. Ileri, R. Atak, S. Topaloglu, K. Ergun, A. Yanik, I. Tandogan, S. Cehreli, E. Duru, et al. Diurnal Variation of QT Dispersion in Patients With and Without Coronary Artery Disease Angiology, May 1, 2001; 52(5): 311 - 316. [Abstract] [PDF]

				W. J. Kostis and J. C. Belina Differences in Beat-to-Beat Variability of the QT Interval Between Day and Night Angiology, November 1, 2000; 51(11): 905 - 911. [Abstract] [PDF]

				F. E. S. Cruz Filho, I. G. Maia, M.a. L. A. Fagundes, R. C. P. Barbosa, P. A. G. Alves, R. M. S. Sa, S. H. Boghossian, and J. C. Ribeiro Electrical behavior of T-Wave polarity alternans in patients with congenital long QT syndrome J. Am. Coll. Cardiol., July 1, 2000; 36(1): 167 - 173. [Abstract] [Full Text] [PDF]

				A. Englund, S. Behrens, K. Wegscheider, E. Rowland, and for the European 7219 Jewel Investigators Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1560 - 1568. [Abstract] [Full Text] [PDF]

				H. Swan, M. Viitasalo, K. Piippo, P.a. Laitinen, K. Kontula, and L. Toivonen Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects J. Am. Coll. Cardiol., September 1, 1999; 34(3): 823 - 829. [Abstract] [Full Text] [PDF]

				P. Smetana, V. N. Batchvarov, K. Hnatkova, A. J. Camm, and M. Malik Sex differences in repolarization homogeneity and its circadian pattern Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1889 - H1897. [Abstract] [Full Text] [PDF]