Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise.

Although digoxin is often the first choice for control of ventricular response in chronic atrial fibrillation, it fails to slow exercise rates. Diltiazem, a calcium channel antagonist that slows atrioventricular conduction, was administered to 16 patients who failed to achieve adequate rate control on low level exercise testing despite digoxin therapy. Therapeutic response to diltiazem was assessed with submaximal and maximal exercise tests and 24 hour ambulatory electrocardiographic monitoring. During the diltiazem treatment phase, ventricular response at rest diminished (96 +/- 17 versus 69 +/- 10 beats/min, p less than 0.001) as did rate during submaximal exercise (155 +/- 28 versus 116 +/- 26, p less than 0.001), maximal exercise (163 +/- 14 versus 133 +/- 26, p less than 0.001) and average ventricular response during 24 hour monitoring (87 +/- 13 versus 69 +/- 10, p less than 0.001). Rate at rest decreased 26 +/- 15% and submaximal exercise rate diminished 24 +/- 12%. Thirteen (81%) of the 16 patients exhibited at least 15% slowing of rate at rest and during submaximal exercise. Eleven patients (69%) reported alleviation of symptoms. There was no change in serum digoxin levels during diltiazem treatment (1.3 +/- 0.5 versus 1.3 +/- 0.6 ng/ml, p = NS). On withdrawal of diltiazem, ventricular response returned to baseline values. Diltiazem is an effective agent for control of ventricular response, both at rest and during exercise, in digoxin-treated patients with chronic atrial fibrillation.

[1]  C. Kawai,et al.  Comparative Effects of Three Calcium Antagonists, Diltiazem, Verapamil and Nifedipine, on the Sinoatrial and Atrioventricular Nodes: Experimental and Clinical Studies , 1981, Circulation.

[2]  J. Kuhlmann.  Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta‐acetyldigoxin , 1985, Clinical pharmacology and therapeutics.

[3]  E. Kaplinsky,et al.  Inefficacy of digitalis in the control of heart rate in patients with chronic atrial fibrillation: beneficial effect of an added beta adrenergic blocking agent. , 1979, The American journal of cardiology.

[4]  C. Porter,et al.  Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure. , 1984, Journal of the American College of Cardiology.

[5]  B. Chaitman,et al.  Beneficial Effect of Intravenous Diltiazem in the Acute Management of Paroxysmal Supraventricular Tachyarrhythmias , 1983, Circulation.

[6]  D. Hannon,et al.  Comparative electrophysiologic and coronary hemodynamic effects of diltiazem, nisoldipine and verapamil on myocardial tissue. , 1982, The American journal of cardiology.

[7]  J. Mason,et al.  Intracardiac electrophysiologic study of intravenous diltiazem and combined diltiazem-digoxin in patients. , 1982, American heart journal.

[8]  B. Lewis,et al.  Immediate haemodynamic effects of verapamil in man. , 1975, Cardiology.

[9]  D. Harrison,et al.  Acute and Chronic Pharmacodynamic Interaction of Verapamil and Digoxin in Atrial Fibrillation , 1982, Circulation.

[10]  John J. May,et al.  Lack of Effects of Diltiazem on Digoxin Pharmacokinetics , 1985, Journal of clinical pharmacology.

[11]  D. Magometschnigg,et al.  The diltiazem‐digoxin interaction , 1984, Clinical pharmacology and therapeutics.

[12]  J. Griffin,et al.  Concentration-dependent enhancement of junctional pacemaker activity by verapamil in man. , 1985, Circulation.

[13]  E. Kaplinsky,et al.  The Influence of Verapamil on Serum Digoxin Concentration , 1982, Circulation.

[14]  E. Prystowsky,et al.  Effects of Intravenous and Chronic Oral Verapamil Administration in Patients with Supraventricular Tachyarrhythmias , 1980, Circulation.

[15]  U. Elkayam,et al.  Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation. , 1986, Circulation.

[16]  R. Millard,et al.  Reflex Chronotropic and Inotropic Effects of Calcium Channel‐Blocking Agents in Conscious Dogs: Diltiazem, Verapamil, and Nifedipine Compared , 1983, Circulation research.

[17]  A. Yoshida,et al.  Effects of diltiazem on plasma level and urinary excretion of digoxin in healthy subjects , 1984, Clinical pharmacology and therapeutics.

[18]  M. Rosen,et al.  Electrophysiology and pharmacology of cardiac arrhythmias. VI. Cardiac effects of verapamil. , 1975, American heart journal.

[19]  G. Belz,et al.  Interaction between digoxin and calcium antagonists and antiarrhythmic drugs , 1983, Clinical pharmacology and therapeutics.

[20]  R. Sung,et al.  Intravenous verapamil for termination of re-entrant supraventricular tachycardias: intracardiac studies correlated with plasma verapamil concentrations. , 1980, Annals of internal medicine.

[21]  E. Pritchett,et al.  Pharmacokinetic and pharmacodynamic effects of diltiazem. , 1983, The American journal of cardiology.

[22]  A. DeMaria,et al.  Efficacy of diltiazem in angina on effort: a multicenter trial. , 1982, The American journal of cardiology.

[23]  A. L. Wit,et al.  Effect of Verapamil on the Sinoatrial and Atrioventricular Nodes of the Rabbit and the Mechanism by Which it Arrests Reentrant Atrioventricular Nodal Tachycardia , 1974, Circulation research.

[24]  J. Ronan,et al.  Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin. , 1984, American heart journal.

[25]  I. Wiener,et al.  Clinical use of oral verapamil in chronic and paroxysmal atrial fibrillation. , 1982, Chest.

[26]  E. Kaplinsky,et al.  Verapamil and digoxin: their respective effects on atrial fibrillation and their interaction. , 1982, The American journal of cardiology.

[27]  J. Schwartz.  Verapamil in atrial fibrillation: The expected, the unexpected, and the unknown. , 1983, American heart journal.

[28]  K. Theisen,et al.  Effect of the calcium antagonist diltiazem on atrioventricular conduction in chronic atrial fibrillation. , 1985, The American journal of cardiology.

[29]  I. Panidis,et al.  Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis. , 1983, The American journal of cardiology.

[30]  S. Olsson,et al.  Verapamil-induced ventricular regularity in atrial fibrillation. Effects of exercise, isoproterenol, atropine and conversion to sinus rhythm. , 2009, Acta medica Scandinavica.

[31]  D. Harrison,et al.  Prolongation of verapamil elimination kinetics during chronic oral administration , 1982 .

[32]  R. Beasley,et al.  Exercise heart rates at different serum digoxin concentrations in patients with atrial fibrillation. , 1985, British medical journal.

[33]  A. Castellanos,et al.  Electrophysiologic effects of diltiazem hydrochloride on supraventricular tachycardia. , 1982, The American journal of cardiology.

[34]  S. Epstein,et al.  Comparative effects of verapamil, diltiazem, and nifedipine on hemodynamics and left ventricular function during acute myocardial ischemia in dogs. , 1984, Circulation.

[35]  J. Berner.  Comparative clinical electrophysiologic effects of diltiazem, verapamil and nifedipine: A review , 1983 .

[36]  V. Bhargava,et al.  Electrophysiologic and Hemodynamic Effects of Verapamil: Correlation with Plasma Drug Concentrations , 1978, Circulation.

[37]  K. Hossack,et al.  Acute and chronic effects of diltiazem on A-V conduction at rest and during exercise. , 1982, Journal of electrocardiology.

[38]  E. Kaplinsky,et al.  Beta-adrenergic blockade as adjunctive oral therapy in patients with chronic atrial fibrillation. , 1977, Chest.

[39]  E. Kaplinsky,et al.  The beneficial effects of verapamil in chronic atrial fibrillation. , 1979, Archives of internal medicine.

[40]  S. Fujii,et al.  Digoxin-diltiazem interaction. , 1984, The American journal of cardiology.

[41]  U. Elkayam,et al.  Effect of diltiazem on renal clearance and serum concentration of digoxin in patients with cardiac disease. , 1985, The American journal of cardiology.

[42]  J. Hung,et al.  Effects of oral diltiazem in paroxysmal supraventricular tachycardia. , 1983, The American journal of cardiology.

[43]  R. Brown,et al.  Effect of Propranolol on Exercise Tolerance of Patients with Atrial Fibrillation , 1969, British medical journal.

[44]  R. O'rourke,et al.  Differential effects of systemic and intracoronary calcium channel blocking agents on global and regional left ventricular function in conscious dogs. , 1981, American heart journal.

[45]  Calcium channel blocking agents in the treatment of cardiovascular disorders. Part I: Basic and clinical electrophysiologic effects. , 1980 .

[46]  E. Kaplinsky,et al.  Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation. , 1983, Chest.

[47]  E. Kaplinsky,et al.  Verapamil improves exercise capacity in chronic atrial fibrillation: double-blind crossover study. , 1983, American heart journal.