What are the implications of the THEOPACE (Theoretical and Outcome-based Pacing Evaluation in Cardiac Disease) trial on pacing therapy for patients with sick sinus syndrome?

THEOPACE Trial: Key Findings and Clinical Implications

Primary Trial Results

The THEOPACE trial demonstrated that permanent dual-chamber pacemaker therapy reduces syncope recurrence in sick sinus syndrome, while both pacemaker therapy and theophylline reduce heart failure incidence compared to no treatment. 1

The trial randomized 107 symptomatic sick sinus syndrome patients (mean age 73 years) to three groups: no treatment (n=35), oral theophylline (n=36), or dual-chamber rate-responsive pacemaker (n=36), with mean follow-up of 19 months. 1

Impact on Clinical Outcomes

Syncope Prevention

• Pacemaker therapy significantly reduced syncope occurrence compared to no treatment (P=0.02) 1
• Pacemaker therapy showed a trend toward lower syncope rates versus theophylline (P=0.07) 1

Heart Failure Reduction

• Both pacemaker therapy and theophylline reduced heart failure incidence compared to controls (both P=0.05) 1
• This represents a significant morbidity benefit for both interventions 1

Arrhythmia and Thromboembolic Events

• No significant differences were observed among groups for sustained paroxysmal tachyarrhythmias, permanent atrial fibrillation, or thromboembolic events 1
• This finding is notable given that 38% of THEOPACE patients had brady-tachy syndrome 2

Symptom Improvement

• Both pacemaker therapy and theophylline improved symptom scores after 3 months 1
• However, similar improvement occurred in the control group, indicating substantial spontaneous disease improvement 1
• This placebo effect must be considered when interpreting symptomatic benefits 1

Integration into Current Guidelines

ESC Guideline Recommendations Based on THEOPACE and Other Trials

The 2013 ESC Guidelines incorporate THEOPACE data to support Class I, Level B recommendation for dual-chamber pacing in sick sinus syndrome. 2

The guidelines note that syncope was present in 60% of THEOPACE patients, highlighting the severe symptomatic burden in this population. 2

Pacing Mode Selection

• Dual-chamber pacing with preservation of spontaneous AV conduction is indicated (Class I, Level A) for reducing atrial fibrillation risk, stroke risk, avoiding pacemaker syndrome, and improving quality of life 2
• DDDR pacing is preferred over AAIR pacing based on the DANPACE trial, which showed AAIR was associated with higher paroxysmal AF incidence (HR 1.27) and doubled reoperation risk (HR 1.99) 3
• Rate-response features should be adopted (Class IIa, Level C) for patients with chronotropic incompetence, especially if young and physically active 2

Critical Clinical Considerations

Patient Population Characteristics

• THEOPACE enrolled patients with high symptom burden: 60% had syncope and 38% had brady-tachy syndrome 2
• Supraventricular tachyarrhythmias were common in sick sinus syndrome trials (53% in MOST trial) 2

Limitations and Caveats

• Despite adequate pacing, syncope recurs in approximately 20% of patients during long-term follow-up due to associated vasodepressor reflex mechanisms 4, 5, 6
• The therapeutic benefits on symptoms are partly due to spontaneous disease improvement, as demonstrated by control group improvement 1
• No trial has specifically addressed pacing for isolated symptomatic intermittent sinus arrest or prolonged post-tachycardia pauses, though these patients were included in broader sick sinus syndrome populations 2

Survival Impact

• Pacemaker therapy does not prolong survival in sick sinus syndrome, as total survival and sudden cardiac death risk are similar to the general population 2
• Survival is primarily determined by underlying cardiac disease and left ventricular dysfunction, not the sinus node disease itself 4, 6
• Long-term follow-up from the Danish atrial pacing trial showed atrial pacing reduced cardiovascular death (RR 0.52, P=0.022) compared to ventricular pacing 7

Practical Algorithm for Management

Step 1: Confirm Symptomatic Bradycardia

• Document correlation between symptoms (syncope, presyncope, heart failure) and bradyarrhythmia on ECG monitoring 4, 5
• Exclude reversible causes (medications, electrolyte abnormalities) 4, 5

Step 2: Select Pacing Mode

• Implant DDDR pacemaker as first-line therapy 2, 3
• Program to minimize ventricular pacing while avoiding excessively long AV intervals that cause diastolic mitral regurgitation 2
• Activate mode-switch algorithm for atrial fibrillation detection 2

Step 3: Consider Theophylline as Alternative

• Theophylline may be considered in patients who refuse pacing or have contraindications 1
• Provides heart failure reduction benefit similar to pacing 1
• Less effective than pacing for syncope prevention 1

Step 4: Follow-Up Monitoring

• Assess percentage of ventricular pacing at each visit and minimize as much as possible 2
• Monitor for atrial fibrillation development using device diagnostics for anticoagulation decisions 2
• Reassess rate-response programming during follow-up 2
• Recognize that 20% will have recurrent syncope despite adequate pacing due to vasodepressor mechanisms 4, 5, 6