Therapy for Sick Sinus Syndrome

ABSTRACT & COMMENTARY

Synopsis: In symptomatic patients with sick sinus syndrome, pacemaker and theophylline therapy reduces the incidence of heart failure, but pacemaker placement also reduces syncope episodes.

Source: Alboni P, et al. Circulation 1997;96:260-266.

Sick sinus syndrome (sss) is a condition of the elderly characterized by bradyarrhythmias, tachyarrhythmias, and various degrees of heart disease. Pacemaker placement has been the bedrock of treatment of this condition, but recent studies suggest that oral theophylline may also be efficacious. Thus, the report of a randomized controlled trial of pacemaker and oral theophylline therapy on the symptoms and complications of SSS is of interest (THEOPACE study). Included patients had to meet all of these criteria: 1) older than 45 years; 2) sinus bradycardia (< 50 bpm) or intermittent sinoatrial block; and 3) symptoms (syncope, dizziness, fatigue). Patients were excluded if their heart rates were less than 30 bpm, if their sinus pauses more than 3 sec, or for a variety of other life-threatening conditions. Of 162 screened patients, 12 were excluded for severe SSS and 43 for other reasons. Thus, 107 patients were randomized to: 1) no treatment; 2) oral theophylline; and 3) permanent pacemaker (DDDR). Primary end points included syncope, heart failure, thromboembolic events, atrial fibrillation, and other symptoms. Appropriate drug treatment was allowed, but patients needing beta or calcium blockers were excluded.

During the 48-month follow-up, syncope occurred less frequently in the pacemaker group than in the theophylline and control groups (6% vs 17% and 23%; P < 0.02). Heart failure was less frequent in both the pacemaker and theophylline groups (3%, 3% vs 17%; P = 0.05). Other end points were not significantly different between the three groups. Theophylline side effects caused the withdrawal of four of the 36 patients in this group (11%). Alboni and colleagues conclude that in symptomatic patients with SSS, pacemaker and theophylline therapy reduce the incidence of heart failure, but pacemaker placement also reduces syncope episodes.

COMMENT BY MICHAEL H. CRAWFORD, MD

The benefits of pacemaker therapy in SSS have always seemed axiomatic. In addition to preventing bradycardia-mediated syncope, a pacemaker permitted using heart rate-lowering drugs for the tachyarrhythmias that some of these patients have. Thus, it is comforting to see this concept proven in a randomized controlled trial. In fact, the results of this controlled trial are quite clear; patients with SSS and syncope benefit from pacing. Noteworthy, however, is the finding that 6% of those paced still had syncope. One explanation is that some of these patients have neurocardiogenic syncope caused by inappropriate vasodilation, which does not respond to pacemaker therapy. Interestingly, most of the patients in this study had carotid sinus massage or head-up tilt testing as part of their workup. In 77% of those with syncope and in 36% of those without syncope, one or both of these tests was positive. Therefore, neural reflex disorders are important even in patients with clear-cut SSS.

There is no question that these were SSS patients; 59% had syncope, 42% had brady-tachycardia syndrome, and 87% had prolonged sinus node recovery times. Most such patients would receive a pacemaker. The uncontrolled reports that theophylline helped SSS patients suggested that pacemaker placement may be avoidable. This study shows that only heart failure incidence was reduced by theophylline, but heart failure was also reduced by pacemaker placement. The reduction in heart failure by pacing is probably related to increased heart rate and possibly preserved atrioventricular synchrony. Theophylline also increased heart rate (range 42-64 vs 38-51 bpm pre; P < 0.001), which may explain its benefit. Also, theophylline is a mild positive inotropic agent, but studies with other positive inotropes have shown increased mortality in heart failure patients. This trial was underpowered to evaluate mortality. Interestingly, atrial arrhythmias were not more frequent on theophylline, but 11% of the patients dropped out of this group due to side effects of theophylline. In my experience, this is low at the doses used (average 550 mg/d in 2 divided doses).

Other findings of interest included the lack of effect of either therapy on preventing atrial tachyarrhythmias and thromboemboli as compared to control. Overall, chronic atrial fibrillation occurred in about 10%, paro- xysmal tachyarrhythmias in 25%, and thromboemboli in 5-10%. Also, minor symptoms improved in all three groups possibly because of a spontaneous increase in heart rate observed in the control group (44-51 bpm; P < 0.002). This finding is unexplained but argues for conservative therapy in those with only minor symptoms and no syncope. The authors’ conclusion that a pacemaker is indicated for SSS patients with syncope is solid, as is conservative therapy for those with minor symptoms. The role of theophylline therapy is less clear. The only role I see for it is the SSS patient with bradycardic symptoms or heart failure unresponsive to standard therapy who does not want a pacemaker. Finally, it should be noted that the results of this study do not apply to patients with severe SSS—a heart rate of less than 30 or more than three-second pauses. Severe SSS patients need a pacemaker. (Dr. Crawford is Chief, Division of Cardiology, University of New Mexico, Albuquerque, NM.)