This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kong, T. Q. Articles by Kadish, A. H. Search for Related Content PubMed PubMed Citation Articles by Kong, T. Q., Jr Articles by Kadish, A. H.

(Circulation. 1995;92:1507-1516.)
© 1995 American Heart Association, Inc.

Articles

Circadian Variation in Human Ventricular Refractoriness

Thomas Q. Kong, Jr, MD; Jeffrey J. Goldberger, MD; Michele Parker, RN, MS; Ted Wang, MD; Alan H. Kadish, MD

From the Division of Cardiology, Department of Internal Medicine, and the Feinberg Cardiovascular Research Center, Northwestern University Medical School, Chicago, Ill.

Correspondence to Alan H. Kadish, MD, Northwestern Memorial Hospital, 250 E Superior St, Suite 524, Chicago, IL 60611.

Background The incidence of sudden cardiac death is highest in the morning hours. Although a circadian variation in myocardial ischemia may be responsible in part for this observation, other factors also may be contributory. It is not known whether a circadian variation in ventricular refractoriness exists that may be related to the increased morning incidence of sudden cardiac death.

Methods and Results Nine subjects with primary conduction system disease, no evidence of structural heart disease, and permanent pacemakers were studied. Autonomic nervous system function as assessed by tilt table and baroreflex sensitivity testing was normal in all subjects. Using noninvasive programmed stimulation, ventricular effective refractory periods were measured hourly for 24 hours. Potassium, epinephrine, and norepinephrine levels also were measured hourly. In a subset of five subjects, ventricular refractory periods were again measured hourly over 24 hours during ß-blockade. A significant circadian variation in ventricular refractoriness was noted, with a mean difference between the shortest and longest refractory periods in individual subjects of 23 ms and 21 ms at drive cycle lengths of 600 ms and 400 ms, respectively. In eight subjects, the shortest refractory periods observed over 24 hours occurred within 2 hours of waking (random probability <10^-8). Adjustment of refractory period data according to the hour of waking resulted in a better correlation between ventricular refractory periods and time. Although a significant circadian variation was observed in potassium and catecholamine levels, neither was an independent predictor of refractory periods after adjustment for the hour of waking. The adjusted time of day was the only significant (P<.0001) independent predictor of refractory periods. ß-Blockade abolished the circadian variation in ventricular refractory periods.

Conclusions A significant circadian variation in ventricular refractory periods exists. Maximal shortening between hourly refractory periods as well as the shortest refractory periods occur in the early morning hours when the incidence of sudden cardiac death is greatest. Fluctuations in ß-adrenergic tone appear to be largely responsible for this phenomenon.

Key Words: circadian rhythm • refractoriness • death, sudden • electrophysiology

This article has been cited by other articles:

				T. A. Martino and M. J. Sole Molecular Time: An Often Overlooked Dimension to Cardiovascular Disease Circ. Res., November 20, 2009; 105(11): 1047 - 1061. [Abstract] [Full Text] [PDF]

				A. B. Chicos, P. J. Kannankeril, A. H. Kadish, and J. J. Goldberger Parasympathetic effects on cardiac electrophysiology during exercise and recovery in patients with left ventricular dysfunction Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H743 - H749. [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. Behrens and M. R. Franz Circadian variation of arrhythmic events, electrophysiological properties, and the autonomic nervous system Eur. Heart J., December 1, 2001; 22(23): 2144 - 2146. [PDF]

				E.N. Simantirakis, S.I. Chrysostomakis, M.E. Marketou, G.E. Kochiadakis, K.E. Vardakis, H.E. Mavrakis, and P. Vardas Atrial and ventricular refractoriness in paced patients; circadian variation and its relationship to autonomic nervous system activity Eur. Heart J., December 1, 2001; 22(23): 2192 - 2200. [Abstract] [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]

				D. P. Zipes Warning: The Short Days of Winter May Be Hazardous to Your Health Circulation, October 12, 1999; 100(15): 1590 - 1592. [Full Text] [PDF]

				V. Shusterman, B. Aysin, V. Gottipaty, R. Weiss, S. Brode, D. Schwartzman, K. P. Anderson, and for the ESVEM Investigators Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1891 - 1899. [Abstract] [Full Text] [PDF]

				F. J. Venditti, R. M. John, M. Hull, G. H. Tofler, D. M. Shahian, and D. T. Martin Circadian Variation in Defibrillation Energy Requirements Circulation, October 1, 1996; 94(7): 1607 - 1612. [Abstract] [Full Text]