Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial.

BACKGROUND Pacemakers and theophylline are currently being used to relieve symptoms in patients with sick sinus syndrome (SSS). However, the impact of either therapy on the natural course of the disease is unknown. We conducted a randomized controlled trial to prospectively assess the effects of pacemakers and theophylline in patients with SSS. METHODS AND RESULTS One hundred seven patients with symptomatic SSS (age, 73 +/- 11 years) were randomized to no treatment (control group, n = 35), oral theophylline (n = 36), or dual-chamber rate-responsive pacemaker therapy (n = 36). They were followed for up to 48 months (mean, 19 +/- 14 months). During follow-up, the occurrence of syncope was lower in the pacemaker group than in the control group (P = .02) and tended to be lower than in the theophylline group (P = .07). Heart failure occurred less often in patients assigned to pacemaker therapy and theophylline than in control patients (both, P = .05), whereas the incidence of sustained paroxysmal tachyarrhythmias, permanent atrial fibrillation, and thromboembolic events did not show any apparent difference among the three groups. Heart rate was higher in the theophylline group than in the control group. Both pacemaker therapy and theophylline improved symptom scores after 3 months of treatment; however, a similar improvement was observed in the control group. CONCLUSIONS In patients with symptomatic SSS, therapy with theophylline or dual-chamber pacemaker is associated with a lower incidence of heart failure; pacemaker therapy is also associated with a lower incidence of syncope. The therapeutic benefits of pacemakers and theophylline on symptoms are partly a result of spontaneous improvement of the disease.

[1]  P. Samet,et al.  Electrophysiologic evaluation of elderly patients with sinus bradycardia: a long-term follow-up study. , 2020, Annals of internal medicine.

[2]  O. Ohm,et al.  Sick sinus syndrome treated with permanent pacemaker in 109 patients. A follow-up study. , 2009, Acta medica Scandinavica.

[3]  G. Lamas,et al.  Permanent pacemaker selection and subsequent survival in elderly Medicare pacemaker recipients. , 1995, Circulation.

[4]  L. Thuesen,et al.  Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome , 1994, The Lancet.

[5]  A. Skene,et al.  Treatment of severe heart failure: quantity or quality of life? A trial of enoximone. Enoximone Investigators. , 1994, British heart journal.

[6]  W. Wiersinga,et al.  Two cases of amiodarone-induced thyrotoxicosis successfully treated with a short course of antithyroid drugs while amiodarone was continued. , 1994, British heart journal.

[7]  R. Cappato,et al.  Long-term effects of theophylline in atrial fibrillation with a slow ventricular response. , 1993, The American journal of cardiology.

[8]  M. Brignole,et al.  An abnormal neural reflex plays a role in causing syncope in sinus bradycardia. , 1993, Journal of the American College of Cardiology.

[9]  B. Wilkoff,et al.  Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities. , 1993, Circulation.

[10]  S. Deshpande,et al.  Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. , 1993, The New England journal of medicine.

[11]  K. Maekawa,et al.  Effects of oral theophylline on sick sinus syndrome. , 1993, Journal of the American College of Cardiology.

[12]  F. Jaeger,et al.  Incidence and Predictors of Syncope in Paced Patients with Sick Sinus Syndrome , 1992, Pacing and clinical electrophysiology : PACE.

[13]  A. Bernstein,et al.  Deleterious effects of long-term single-chamber ventricular pacing in patients with sick sinus syndrome: the hidden benefits of dual-chamber pacing. , 1992, Journal of the American College of Cardiology.

[14]  M. Brignole,et al.  Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome. , 1992, The American journal of cardiology.

[15]  D. DeMets,et al.  Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. , 1991, The New England journal of medicine.

[16]  B. Ratto,et al.  Clinical effects of oral theophylline in sick sinus syndrome. , 1991, American heart journal.

[17]  M. Brignole,et al.  Neurally mediated syncope detected by carotid sinus massage and head-up tilt test in sick sinus syndrome. , 1991, The American journal of cardiology.

[18]  B. Ratto,et al.  Electrophysiologic effects of oral theophylline in sinus bradycardia. , 1990, The American journal of cardiology.

[19]  A. Keogh,et al.  Prognostic guides in patients with idiopathic or ischemic dilated cardiomyopathy assessed for cardiac transplantation. , 1990, The American journal of cardiology.

[20]  M. Santini,et al.  Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing. , 1990, The American journal of cardiology.

[21]  S. Kawa,et al.  Long‐Term Follow‐Up of Patients with Sick Sinus Syndrome: A Comparison of Clinical Aspects Among Unpaced, Ventricular Inhibited Paced, and Physiologically Paced Groups , 1988, Pacing and clinical electrophysiology : PACE.

[22]  D. Rubin,et al.  Statistical Analysis with Missing Data. , 1989 .

[23]  K. Ellenbogen,et al.  Reversibility of prolonged chronotropic dysfunction with theophylline following orthotopic cardiac transplantation. , 1988, American heart journal.

[24]  J Brandt,et al.  Long-term pacing in sinus node disease: effects of stimulation mode on cardiovascular morbidity and mortality. , 1988, American heart journal.

[25]  J. Fleiss.  The design and analysis of clinical experiments , 1987 .

[26]  G. Flaker,et al.  Comparative survival following permanent ventricular and dual-chamber pacing for patients with chronic symptomatic sinus node dysfunction with and without congestive heart failure. , 1987, American heart journal.

[27]  K. Ulm,et al.  Survival and Follow‐up After Pacemaker Implantation: A Comparison of Patients With Sick Sinus Syndrome, Complete Heart Block, and Atrial Fibrillation , 1985, Pacing and clinical electrophysiology : PACE.

[28]  A. Watt.  SICK SINUS SYNDROME: AN ADENOSINE- MEDIATED DISEASE , 1985, The Lancet.

[29]  T. D. Sellers,et al.  Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. , 1983, Circulation.

[30]  M. Scheinman,et al.  Electrophysiologic effects of theophylline in young patients with recurrent symptomatic bradyarrhythmias. , 1983, The American journal of cardiology.

[31]  A. Masoni,et al.  Electrophysiology of Normal Sinus Node With and Without Autonomic Blockade , 1982, Circulation.

[32]  J. Gowers,et al.  Survival in sinoatrial disorder (sick-sinus syndrome). , 1980, British medical journal.

[33]  R. Matthay,et al.  Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: noninvasive assessment by radionuclide angiocardiography. , 1978, The American journal of medicine.

[34]  M. C. Rogers,et al.  Prevention of apnea and bradycardia in low-birthweight infants. , 1975, Pediatrics.

[35]  J. Beckwith.  The sudden infant death syndrome: a new theory. , 1975, Pediatrics.

[36]  M. Marcus,et al.  Effects of theophylline on myocardial mechanics. , 1972, The American journal of physiology.

[37]  A. D. Jose,et al.  The normal range and determinants of the intrinsic heart rate in man. , 1970, Cardiovascular research.

[38]  B. Schreiner,et al.  Effects of Aminophylline on the Pulmonary Circulation and Left Ventricular Performance in Patients with Valvular Heart Disease , 1968, Circulation.

[39]  A. Masoni,et al.  Latent abnormalities of sinus node function in patients with organic heart disease and normal sinus node on clinical basis. , 1984, Journal of electrocardiology.

[40]  P. Auld,et al.  Low-dose theophylline therapy in idiopathic apnea of prematurity. , 1980, The Journal of pediatrics.

[41]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1976 .