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. 2006 Oct 27;7(4):379–387. doi: 10.1111/j.1542-474X.2002.tb00189.x

Cardiac Effects of Chronic Oral Beta‐Blockade:

Fabrice Extramiana 1,✉, Pierre Maison‐Blanche 1, René Tavernier 2, Luc Jordaens 3, Antoine Leenhardt 1, Philippe Coumel 1
PMCID: PMC7027610  PMID: 12431318

Abstract

Background: Although well established on the sinus node, the effects of beta‐blockade on ventricular repolarization are still conflicting. The aim of the study was to investigate the effects of a chronic beta‐blockade on sinus node and repolarization parameters and their relationship.

Methods: Sixteen healthy volunteers (10 males, mean age: 40 ± 6.7 years) were randomized to placebo or atenolol (100 mg). After 7 days, subjects were crossed over. Heart rate (HR) and HRV indices were calculated from long‐term ECG recordings separately during the day and at night, together with ventricular repolarization parameters (QT interval duration and QT rate‐dependence).

Results: Mean R‐R intervals were significantly and consistently increased after atenolol (Day: 916 ± 103 ms vs. 712 ± 89 ms, and Night: 1149 ± 93 vs. 996 ± 125 ms). HRV changes under atenolol were also consistent, with a significant decrease in sympathovagal ratio. In contrast, atenolol only lowered diurnal QT rate‐dependence (0.123 ± 0.032 vs. 0.190 ± 0.065 on placebo, P < 0.001), but not the nocturnal pattern. After multivariate analysis QT rate‐dependence changes induced by atenolol were correlated with pretreatment QT/RR relation (r = 0.65, P < 0.01) but not with any HR or HRV parameters.

Conclusions: In healthy subjects, repolarization changes following chronic beta‐blockade cannot be predicted by HR or HRV changes, but are dependent on pretreatment rate‐dependence. A.N.E. 2002;7(4):379–388

Keywords: autonomic nervous system, ECG, beta‐blockers, heart rate variability, QT interval

REFERENCES

  • 1. Yusuf S, Peto R, Lewis J, et al. Beta blockade during and after myocardial infarction: An overview of the randomized trials. Prog Cardiovasc Dis 1985;27:335–371. [DOI] [PubMed] [Google Scholar]
  • 2. Lechat P, Packer M, Chalon S, et al. Clinical effects of beta‐adrenergic blockade in chronic heart failure: A meta‐analysis of double‐blind, placebo‐controlled, randomized trials. Circulation 1998;98:1184–1191. [DOI] [PubMed] [Google Scholar]
  • 3. Kjekshus J. Importance of heart rate in determining beta‐blocker efficacy in acute and long‐term acute myocardial infarction intervention trials. Am J Cardiol 1986;57:43F–49G. [DOI] [PubMed] [Google Scholar]
  • 4. The Cardiac Insufficiency Bisoprolol Study II (CIBIS‐II): A randomized trial. Lancet 1999;353: 9–13. [PubMed] [Google Scholar]
  • 5. Cook J, Bigger JT Jr, Kleiger RE, et al. Effect of atenolol and diltiazem on heart period variability in normal persons, J Am Coll Cardiol 1991;17: 480–484. [DOI] [PubMed] [Google Scholar]
  • 6. Gundersen T, Grottum P, Pedersen T, et al. Effect of timo‐lol on mortality and reinfarction after acute myocardial infarction: Prognostic importance of heart rate at rest. Am J Cardiol 1986;58:20–24. [DOI] [PubMed] [Google Scholar]
  • 7. Franz MR, Swerdlow CD, Liem LB, et al. Cycle length dependence of human action potential duration in vivo: Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady state fre quency. J Clin Invest 1988;82:972–979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Martins JB, Zipes DP. Effects of sympathetic and vagal nerves on the recovery properties of the endocardium and epicardium of the canine left ventricle. Circ Res 1980;46: 100–110. [DOI] [PubMed] [Google Scholar]
  • 9. Nattel S, Euler DE, Spear JF. Autonomic control of ventricular refractoriness. Am J Physiol 1981;241:H878. [DOI] [PubMed] [Google Scholar]
  • 10. Duchatelle‐Gourdon I, Hartzell HC, Lagrutta AA. Modulation of the delayed rectifier potassium current in frog car‐diomyocytes by b‐adrenergic agonists and magnesium. J Physiol 1989;415:251–274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Reuter H. Calcium channel modulation by neurotransmit‐ters, enzymes and drugs. Nature 1983;301:569–574. [DOI] [PubMed] [Google Scholar]
  • 12. Nakayama T, Fozzard HA. Adrenergic modulation of the transient outward current in isolated canine Purkinje cells. Circ Res 1988;62:162–172. [DOI] [PubMed] [Google Scholar]
  • 13. Boyett MR, Jewell BR. Analysis of the effects of changes in rate and rhythm upon electrical activity in the heart. Prog Biophys Mol Bio 1980;36:1–52. [DOI] [PubMed] [Google Scholar]
  • 14. Belardinelli L, Isenberg G. Actions of adenosine and isopro‐terenol on isolated mammalian ventricular myocytes. Circ Res 1983;53:287–297. [DOI] [PubMed] [Google Scholar]
  • 15. Litovsky SH, Antzelevitch C. Differences in the electro‐physiological response of canine ventricular subendocar‐dium and subepicardium to acetylcholine and isoprotere‐nol. A direct effect of acetylcholine in ventricular myocardium. Circ Res 1990;67: 615–627. [DOI] [PubMed] [Google Scholar]
  • 16. Charpentier F, Rosen MR. Beta‐adrenergic regulation of action potentials and automaticity in young and adult canine purkinje fibers. Am J Physiol 1994;266:H2310–H2319. [DOI] [PubMed] [Google Scholar]
  • 17. Priori SG, Corr PB. Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines. Am J Physiol 1990;258:H1796–H1805. [DOI] [PubMed] [Google Scholar]
  • 18. Amlie JP, Refsum H, Landmark KH. Prolonged ventricular refractoriness and action potential duration after beta‐adre‐noreceptor blockade in the dog heart in situ. J Cardiovasc Pharmacol 1982;4:157–162. [DOI] [PubMed] [Google Scholar]
  • 19. Euler DE, Scanlon PJ. Effect of propranolol on ventricular repolarization and refractoriness: Role of beta‐blockade versus direct membrane effects. Cardiovasc Drugs Ther 1988;1:605–612. [DOI] [PubMed] [Google Scholar]
  • 20. Gibson JK, Gelband H, Bassett AL. Direct and beta adren‐ergic blocking actions of nadolol (SQ 11725) on electro‐physiologic properties of isolated canine myocardium. J Pharmacol Exp Ther 1977;202:702–710. [PubMed] [Google Scholar]
  • 21. Extramiana F, Maison‐Blanche P, Badilini F, et al. Circa‐dian modulation of QT rate‐dependence in healthy volunteers: Gender and age differences. J Electrocardiol 1999;32: 33–43. [DOI] [PubMed] [Google Scholar]
  • 22. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Circulation 1996;93: 1043–1065. [PubMed] [Google Scholar]
  • 23. Badilini F, Maison‐Blanche P, Coumel P. Heart rate variability in passive tilt test: Comparative evaluation of autoregressive and FFT spectral analyses. Pacing Clin Electro-physiol 1998;21: 1122–1132. [DOI] [PubMed] [Google Scholar]
  • 24. Neyroud N, Maison‐Blanche P, Denjoy I, et al. Diagnostic performance of QT interval variables from 24‐hour electro‐cardiography in the long QT syndrome. Eur Heart J 1998;19:158–165. [DOI] [PubMed] [Google Scholar]
  • 25. Badilini F, Maison‐Blanche P, Childers R, et al. QT interval analysis on ambulatory ECG recordings: a selective beat averaging approach. Med Biol Eng Comp 1999;37:71–79. [DOI] [PubMed] [Google Scholar]
  • 26. Merri M, Moss AJ. Benhorin J, et al. Relation between ventricular repolarization duration and cardiac cycle length during 24‐hour Holler recordings. Circulation 1992;85: 1816–1821. [DOI] [PubMed] [Google Scholar]
  • 27. Oldham P. A note on the analysis of repeated measurements of the same subject. J Chronic Dis 1962;15:969–977. [DOI] [PubMed] [Google Scholar]
  • 28. MacGregor G, Sagnella GA, Macrae KD. Misleading paper about misleading statistics. Lancet 1985;i:926–927. [Google Scholar]
  • 29. Ahnve S, Vallin H. Influence of heart rate and inhibition of autonomic tone on the QT interval. Circulation 1982;65: 435–439. [DOI] [PubMed] [Google Scholar]
  • 30. Ahmed MW, Kadish AH, Goldberg JJ. Autonomic effects on QT interval. Ann Noninvas Electrocardiol 1996;1:44–53. [Google Scholar]
  • 31. Ferraro S, Maddalena G, D'Agosto V, et al. Influence of atenolol on the relationship between heart rate and QT interval in patients with exercise‐induced myocardial ischemia. Clin Cardiol 1992;15:911–915. [DOI] [PubMed] [Google Scholar]
  • 32. Milne JR, Camm AJ, Ward DE, et al. Effect of intravenous propranolol on QT interval. A new method of assessment. Br Heart J 1980;t3:1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Birkhead JS, Vaughan Williams EM, Gwilt DJ, et al. Heart rate and QT interval in subjects adapted to beta‐blockade: Bradycardia and hypotension as uncorrelated adaptations. Cardiovasc Res 1983;17:649–655. [DOI] [PubMed] [Google Scholar]
  • 34. 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. [DOI] [PubMed] [Google Scholar]
  • 35. Singh J. Correcting the QT interval: Is it relevant J Am Coll Cardiol 1995;25:551–552. [DOI] [PubMed] [Google Scholar]
  • 36. Cappato R, Alboni P, Pedroni P, et al. Sympathetic and vagal influences on rate‐dependent changes of QT interval in healthy subjects. Am J Cardiol 1991;68:1188–1193. [DOI] [PubMed] [Google Scholar]
  • 37. Algra A, Roelandt JR, Tijssen JG, et al. Effect of beta‐blockers on the relation between QT‐interval and heart rate in exercise ECG. Eur Heart J. 1987;8: 71–73. [DOI] [PubMed] [Google Scholar]
  • 38. Sarma JS, Venkataraman K, Samant DR, et al. Effect of propranolol on the QT intervals of normal individuals during exercise: A new method for studying interventions. Br Heart J 1988;60:434–439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Lande G, Funck‐Brentano C, Ghadanfar M, et al. Steady‐state versus nonsteady‐state QT‐RR relationship in 24‐hour Holter recordings. PACE 2000;23:293–302. [DOI] [PubMed] [Google Scholar]
  • 40. Viitasalo M, Karjalainen J. QT Intervals at heart rates from 50 to 120 beats per minutes during 24‐hour electrocardio‐graphic recordings in 100 healthy men. Circulation 1992;86:1439–1442. [DOI] [PubMed] [Google Scholar]
  • 41. Browne KF, Prystowsky E, Heger JJ, et al. Prolongation of the QT interval in man during sleep. Am J Cardiol 1983;52: 55–59. [DOI] [PubMed] [Google Scholar]
  • 42. Tavernier R, Jordaens L, Schiettekatte V, et al. Relation of dynamic QT behavior and baseline QT measurements. J Amb Monit 1995;8:207–218. [Google Scholar]
  • 43. Karjalaien J, Viitasalo M, Manttari M, et al. 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: 1547–1553. [DOI] [PubMed] [Google Scholar]
  • 44. Goldberger J. Sympathovagal balance: How should we measure it Am J Physiol 1999;276:H1273–1280. [DOI] [PubMed] [Google Scholar]
  • 45. Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+ current. J Gen Physiol 1990;96: 195–215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Chang MS, Zipes DP. Differential sensitivity of sinus node, atrioventriculaire node, atrium and ventricle to propranolol. Am Heart J 1988;116:371–378. [DOI] [PubMed] [Google Scholar]
  • 47. Extramiana F, Neyroud N, Huikuri HV, et al. QT interval and arrhythmic risk assessment after myocardial infarction. Am J Cardiol 1999;83:266–269. [DOI] [PubMed] [Google Scholar]
  • 48. Pellerin D, Maison‐Blanche P, Extramiana F, et al. Autonomic influences on ventricular repolarization in congestive heart failure. J Electrocardiol 2001;34:35–40. [DOI] [PubMed] [Google Scholar]
  • 49. Boutitie F, Boissel JP, Connolly SJ, et al. Amiodarone interaction with β‐blockers: Analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. Circulation 1999;99:2268–2275. [DOI] [PubMed] [Google Scholar]
  • 50. Arildsen H, Christiansen EH, Pedersen AK, et al. Reproduc‐ibility of QT parameters derived from 24‐hour ambulatory ECG recordings in healthy subjects. Ann Noninvas Electrocardiol 2001;6:24–31. [DOI] [PMC free article] [PubMed] [Google Scholar]

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