Heart rate variability in patients with ventricular arrhythmias: Effect of antiarrhythmic drugs

The purpose of this study was to investigate whether heart rate variability could be reliably assessed in patients with ventricular arrhythmias and to evaluate whether it is affected by antiarrhythmic drugs. The study was based on an analysis of 239 ambulatory electrocardiographic (ECG) recordings obtained from 67 patients with frequent and complex ventricular arrhythmias enrolled in the Antiarrhythmic Drug Evaluation Group (ADEG) study. In each recording, after exclusion of premature ventricular complexes, the number of times during a 24 h period in which two consecutive sinus RR intervals differed by more than 50 ms was calculated. The total 24 h count from each recording was then used as an index of heart rate variability. This method is a reliable marker of cardiac parasympathetic activity. Recordings were analyzed at baseline (n = 56), during longterm treatment with amiodarone (n = 17), flecainide (n = 22) or propafenone (n = 17) and after washout in selected patients (n = 5). Despite the presence of a different number of arrhythmias, total 24 h counts in the same patient appeared reproducible over time (r = 0.83 between two different recordings, n = 49, p Baseline counts (median 1,698, range 26 to 13,648) were not correlated (r = 0.15) with the number of arrhythmias. The three antiarrhythmic drugs had a disparate effect on total 24 h counts: no change was observed in patients treated with amiodarone (median percent change [Δ%]-8, p = NS), whereas a significant (p These results indicate that heart rate variability can reliably be assessed by this total 24 h counts method in patients with frequent ventricular arrhythmias. The presence or suppression of arrhythmias itself did not modify heart rate variability. Class IC antiarrhythmic drugs may significantly affect heart rate variability, and this influence may contribute to the overall effect of these agents on mortality.

[1]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[2]  J. Miller,et al.  The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group. , 1990, The American journal of cardiology.

[3]  P. Schwartz,et al.  Sympathetic nervous system and cardiac arrhythmias , 1990 .

[4]  M. Niemelä,et al.  Impaired vagal heart rate control in coronary artery disease. , 1987, British heart journal.

[5]  H. Huikuri,et al.  Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol. , 1989, Circulation.

[6]  S Cerutti,et al.  Heart rate variability as an index of sympathovagal interaction after acute myocardial infarction. , 1987, The American journal of cardiology.

[7]  D. Wyse,et al.  Right and left ventricular function during chronic amiodarone therapy. , 1988, The American journal of cardiology.

[8]  R. Cappato,et al.  Direct and autonomically mediated effects of oral flecainide. , 1988, The American journal of cardiology.

[9]  H T Davis,et al.  Ventricular Ectopic Beats and Their Relation to Sudden and Nonsudden Cardiac Death After Myocardial Infarction , 1979, Circulation.

[10]  D. Ewing,et al.  Cardiac parasympathetic activity during the early hours of acute myocardial infarction. , 1989, British heart journal.

[11]  G. Schreiber,et al.  Interaction of the antiarrhythmic drug amiodarone with the muscarinic receptor in rat heart and brain. , 1984, Journal of cardiovascular pharmacology.

[12]  A. Camm,et al.  CAST and beyond. Implications of the Cardiac Arrhythmia Suppression Trial. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. , 1990, Circulation.

[13]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[14]  J P Miller,et al.  The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. , 1984, Circulation.

[15]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[16]  F. Witkowski,et al.  Mechanisms controlling cardiac autonomic function and their relation to arrhythmogenesis , 1986 .

[17]  D. Tepper,et al.  Propafenone: a new antiarrhythmic agent. , 1988, American heart journal.

[18]  M D Klein,et al.  Computer detection of ventricular ectopic beats. , 1970, Computers and biomedical research, an international journal.

[19]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[20]  J. Fleiss,et al.  Components of heart rate variability measured during healing of acute myocardial infarction. , 1988, The American journal of cardiology.

[21]  R. Cohen,et al.  An Efficient Algorithm for Spectral Analysis of Heart Rate Variability , 1986, IEEE Transactions on Biomedical Engineering.

[22]  J M Bland,et al.  Statistical methods for assessing agreement between two methods of clinical measurement , 1986 .

[23]  E. Benfenati,et al.  High-performance liquid chromatographic separation and mass spectrometric identification of propafenone, 5-hydroxypropafenone and N-depropylpropafenone. , 1988, Journal of Chromatography A.

[24]  S E Smith,et al.  Beta-adrenoceptor antagonists increase sinus arrhythmia, a vagotonic effect. , 1986, British journal of clinical pharmacology.

[25]  R J Cohen,et al.  Beat to beat variability in cardiovascular variables: noise or music? , 1989, Journal of the American College of Cardiology.

[26]  A. Miller,et al.  Application of a bonded-phase extraction column for rapid sample preparation of flecainide from human plasma for high-performance liquid chromatographic analysis--fluorescence or ultraviolet detection. , 1984, Therapeutic drug monitoring.

[27]  M. Thames,et al.  Responses of sympathetic nerves to programmed ventricular stimulation. , 1987, Journal of the American College of Cardiology.

[28]  J. Paul,et al.  β‐Adrenoceptor Blocking Activity of Diprafenone in Anesthetized Dogs: Comparison with Propafenone and Propranolol , 1989, Journal of Cardiovascular Pharmacology.

[29]  W. Rogers,et al.  Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. , 1989, The New England journal of medicine.

[30]  D. Ewing,et al.  New method for assessing cardiac parasympathetic activity using 24 hour electrocardiograms. , 1984, British heart journal.

[31]  S. Evans,et al.  The end of the p value? , 1988, British heart journal.

[32]  A. Camm,et al.  CAST and beyond. Implications of the cardiac arrhythmia suppression trials. By the Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. , 1990, European heart journal.

[33]  R. Colvin,et al.  Interaction of amiodarone and desethylamiodarone with the cardiac muscarinic receptor in vitro. , 1989, Journal of molecular and cellular cardiology.

[34]  R J Cohen,et al.  Comparison of time- and frequency domain-based measures of cardiac parasympathetic activity in Holter recordings after myocardial infarction. , 1989, The American journal of cardiology.

[35]  R J Cohen,et al.  Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. , 1988, The American journal of cardiology.

[36]  B. Lown,et al.  Sudden cardiac death: the major challenge confronting contemporary cardiology. , 1979, The American journal of cardiology.

[37]  R J Cohen,et al.  Analysis of long term heart rate variability: methods, 1/f scaling and implications. , 1988, Computers in cardiology.

[38]  A. Malliani,et al.  Premature ventricular contractions and reflex sympathetic activation in cats. , 1989, Cardiovascular research.

[39]  S. Connolly,et al.  Myocardial disposition of amiodarone in the dog. , 1983, The Journal of pharmacology and experimental therapeutics.

[40]  H. L. Stone,et al.  Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death. , 1984, Circulation.

[41]  M. Turiel,et al.  Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities as a Marker of Sympatho‐Vagal Interaction in Man and Conscious Dog , 1986, Circulation research.

[42]  M. Weir,et al.  The Cardiac Arrhythmia Suppression Trial Investigators: Preliminary Report: Effect of Encainide and Flecainide on Mortality in a Randomized Trial of Arrhythmia Suppression After Myocardial Infarction. , 1990 .

[43]  L. Horowitz,et al.  Influence of left ventricular dysfunction on flecainide therapy. , 1987, Journal of the American College of Cardiology.

[44]  T. Graboys,et al.  Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs. , 1982, The American journal of cardiology.

[45]  G. Casolo,et al.  Decreased spontaneous heart rate variability in congestive heart failure. , 1989, The American journal of cardiology.

[46]  P. Polster,et al.  The adrenergic antagonism of amiodarone. , 1976, Biochemical pharmacology.