Clinical effects syndrome

of oral theophylline

in sick sinus

in 17 patients with symptomatic sinus bradycardia (age: 66 + 11 years), a resting electrocardiogram, a 24-hour Halter recording, and a treadmill test were performed both before and after administration of slow-release theophyiiine (700 mg daily). The drug increased resting heart rate (46 & 7 versus 62 + 16 beats/min, p < O.Ol), mean 24-hour rate (51 & 6 versus 64 + 16 beats/min, p < O.Ol), and minimal 24-hour heart rate (36 k 6 versus 43 k 10 beats/min, p < 0.05). Cardiac pauses >2.5 seconds were present in four patients during control recording, and disappeared after theophyiiine. The daily number of premature supraventricular and ventricular beats increased slightly after the drug. Exercise heart rate was higher after theophylline than during the control test (p < 0.01). Thirteen patients were followed for a period of 17 & 3 months. Suppression of symptoms was achieved in 12 patients. Asthenia and easy fatigue were reduced markedly by the drug. During long-term therapy, the sinus rate was similar to that observed at the steady-state evaluation. in 3 of the 17 patients theophyiline had to be discontinued because of gastric intolerance (in two at the end of the steady-state evaiuatlon and In one during long-term therapy). These data suggest that oral theophylline can represent an effective therapy in some patients with symptomatic sinus bradycardia. (AM HEART J lgg1;122:1361.)

Paolo Alboni, MD, Benedetto Ratto, MD, Riccardo Cappato, MD, Paolo Rossi, MD, Emilio Gatto, MD, and Gian Enrico Antonioli, MD. Cento., Ferrara, and Genoa, Italy

The current therapy for symptomatic sick sinus syndrome (SSS), if there are no removable causes, is based on permanent stimulation. However, though all the aspects of the clinical course of SSS have not been well investigated, some data suggest that implantation of a permanent pacemaker does not represent an ideal therapy: (1) SSSis a relatively benign condition since the overall survival rate of patients with an established sinoatrial disorder is similar to that of the normal population.1-4 (2) The course of symptoms in SSS is very variable from patient to patient. Syncope may not reappear for several years in about 30 % to 407%of the cases;moreover, not uncommonly, syncope represents an isolated manifestation.‘? 2l5For these reasons it is hard to evaluate the actual benefits of either permanent stimulation or pharmacologic therapy. (3) VVI stimulation does not appreciably reduce mortality, even in patients with From the Division of Cardiology, Ospedale Civile, Cento; Division of Cardiology, Arcispedale S. Anna, Ferrara; and Division of Cardiology, Ospedale S. Martino, Geneva. Received for publication Nov. 2, 1990; accepted May 17, 1991. Reprint requests: Dr. Paolo Alboni, Division of Cardiology, Ospedale Civile, 44042 Cento (Fe), Italy. 4/l/32179

symptoms, and AA1 (or DDD) stimulation seems to improve the survival rate in comparison with VVI stimulation only in patients with congestive heart failure.6-8 Controlled studies to compare the survival rate in unpaced patients and in patients with AA1 (or DDD) stimulation have not been carried out up to now. Because of the relatively benign prognosis of SSS and, above all, of the marked variability of the course of symptoms, a pharmacologic therapy appears particularly useful. The drugs used in the past+adrenergic and vagolytic agents-gave disappointing results, both in terms of efficacy and in the high incidence of side effects during long-term treatment. It has been reported that theophylline at therapeutic concentrations induces a modest increase in heart rate in subjects with a normal sinus rate.g*lo During long-term therapy, the drug suppressed symptoms in young patients with paroxysmal bradyarrhythmiasll Moreover, theophylline diminished the frequency and severity of bradycardia in newborn infants with apnea-bradycardia spells.12,l3 Recently, Ellenbogen et a1.14reported two patients with marked sinus bradycardia after orthotopic heart transplantation; oral theophylline increased donor heart rate by about 50%) avoiding pacemaker implantation. Up to now 1361

Alboni et al.




November 1991 Heart Journal

I. Steady-state: Effect of oral theophylline (700 mg daily) on examined parameters Control

RestingHR Mean24-hrHR Minimal 24-hrHR Maximal 24-hrHR No. of pauses>2.5 set (in four pts) LongestR-R interval ExerciseHR

62 i 18beatslmin 63.9+ 16beats/min 42.81?1 10beats/min 114 + 87 beats/min

47.3 rt 59 1962 I 394 msec

1590 I 258 msec

887 rt 1764 168 + 542

No. of VPBs rate; SPB, supraventricular

46 + 7 beats/min 51.2I 6 beatslmin 36 I 6 beats/min 89.6-t 20beats/min

77.4t 17beats/min 85.8+ 14beats/min

1st stage 2nd stage No. of SPBs

HR, Heart



beats; VPB, ventricular


the drug has not been investigated in detail in patients with SSS. We have undertaken a study to assess the effects of oral theophylline in patients with sinus bradycardia not related to drugs. METHODS Patients.

We selected17 patients with symptomatic sinus bradycardia not induced by drugs. We included subjects with: (1) mean resting sinusrate

Clinical effects of oral theophylline in sick sinus syndrome.

In 17 patients with symptomatic sinus bradycardia (age: 66 +/- 11 years), a resting electrocardiogram, a 24-hour Holter recording, and a treadmill tes...
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