What are the clinical features and management of pacemaker syndrome in patients with single‑chamber ventricular pacing?

Pacemaker Syndrome: Clinical Features and Management

Definition and Pathophysiology

Pacemaker syndrome is the occurrence of overt symptoms—including fatigue, chest discomfort, dyspnea, cough, confusion, presyncope, or syncope—caused by adverse hemodynamics from loss of AV synchrony, ventriculoatrial conduction, or atrial contraction against closed AV valves in patients with an implanted pacemaker. 1

• The syndrome results from suboptimal atrioventricular synchrony or AV dyssynchrony, regardless of pacing mode, though it occurs most commonly with VVI (single-chamber ventricular) pacing in patients who maintain sinus rhythm 1, 2
• Loss of AV synchrony can decrease stroke volume by up to 50% and increase left atrial pressure by up to 25%, particularly affecting patients with diastolic dysfunction or left ventricular hypertrophy 1
• Ventriculoatrial conduction during ventricular pacing produces retrograde atrial activation and "cannon A waves," causing sudden increases in atrial pressure that may trigger systemic hypotensive reflex responses 3

Clinical Features

Symptom Profile

• Twelve of sixteen symptoms were significantly worse in VVI mode compared to DDD mode in blinded randomized trials, with mean symptom scores of 29.0 ± 26.1 in VVI versus significantly lower scores in dual-chamber pacing 1
• Common presentations include syncope, near-syncope, weakness, lightheadedness, fatigue, dyspnea, chest discomfort, cough, and confusion 1, 4
• Symptomatic hypotension with systolic blood pressure drops ≥20 mm Hg during VVI pacing, associated with reproducible symptoms, is characteristic 4, 5

Incidence and Timing

• Severe pacemaker syndrome develops in approximately 18-20% of patients with VVI pacing, with 30-50% of VVI-paced patients experiencing some degree of intolerance driven primarily by pacemaker syndrome 6, 4
• The syndrome occurs early in most patients: 13.8% at 6 months, 16.0% at 1 year, increasing to 19.7% at 4 years 4
• In the PASE trial, 26% of patients randomized to VVIR pacing required crossover to dual-chamber pacing due to severe pacemaker syndrome 1
• In MOST, 38% of patients in the ventricular pacing group had devices reprogrammed to dual-chamber mode for symptoms attributed to pacemaker syndrome 1

Predictive Factors

• No baseline parameter or data obtained at pacemaker implantation can reliably predict the occurrence of clinically significant pacemaker syndrome 1
• A blood pressure drop of 20 mm Hg during ventricular pacing at implantation did not predict development of pacemaker syndrome during follow-up in MOST 1
• Post-implantation predictors include higher percentage of paced beats, higher programmed lower rate, and slower underlying spontaneous sinus rate 4
• Baseline univariate predictors include lower sinus rate and higher programmed pacemaker rate, though these are not reliable for clinical decision-making 4
• Previous heart failure and ejection fraction do not predict pacemaker syndrome development 4

Management Strategy

Definitive Treatment: Mode Conversion

The only definitive treatment for established pacemaker syndrome is conversion from single-chamber ventricular pacing to dual-chamber (DDD/DDDR) pacing to restore AV synchrony. 6, 5

• Dual-chamber pacing resulted in improved symptom scores and less pacemaker syndrome compared with ventricular pacing in multiple randomized controlled trials 1
• Quality of life decreased at the time of pacemaker syndrome diagnosis and improved significantly with reprogramming to atrial-based pacing 4
• In patients who crossed over from VVIR to dual-chamber pacing due to severe pacemaker syndrome, symptoms resolved and dual-chamber pacing abolished pacing hypotension and related symptoms 1, 5
• During mean follow-up of 10 months after conversion to dual-chamber pacing, no patients experienced recurrent syncopal or near-syncopal attacks related to pacemaker function 5

Programming Optimization

• Optimize AV delay settings to prevent pacemaker syndrome even in dual-chamber systems, as excessively prolonged AV delays can cause atrial contraction early in diastole, mimicking pacemaker syndrome 1, 6
• Algorithms that result in excessive prolongation of the AV interval may be detrimental, causing exaggerated AV delays that result in pacemaker syndrome as a consequence of atrial contraction early in diastole 1
• Ventricular-based timing cycles (e.g., MVP mode) can under some circumstances create short-long-short ventricular sequences that have been reported to cause ventricular proarrhythmia 1

Alternative Considerations for Specific Populations

• In younger patients (<70 years) with sinus node disease, normal AV conduction, and no ventricular conduction abnormalities, atrial pacing alone (AAI/AAIR) may be considered, though later development of AV block cannot be predicted 6
• Rate-adaptive pacing alone does not address the fundamental problem of AV dyssynchrony and should not be relied upon as primary management 6

Prevention Strategy

Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients with sinus node dysfunction and intact AV conduction. 4

• Select appropriate pacing mode at initial implantation based on underlying conduction disease, using dual-chamber systems when both atrial sensing and ventricular pacing are needed 6
• Dual-chamber pacemakers were widely adopted in preference to single-chamber pacemakers for treatment of patients with AV conduction disease based on studies showing improved symptom scores and less pacemaker syndrome 1
• Minimize unnecessary ventricular pacing through programming algorithms that favor intrinsic conduction 6

Quality of Life Impact

• In patients with sinus node disease enrolled in PASE, dual-chamber pacing was associated with improved quality of life and cardiovascular functional status compared to ventricular pacing 1
• In MOST, dual-chamber pacing resulted in significant improvement in some subscales of quality of life as assessed by the SF-36 instrument, specifically role physical, role emotional, and vitality 1
• A systematic review by the Cochrane Collaboration reported significant reduction in symptoms of pacemaker syndrome associated with dual-chamber pacing compared to ventricular pacing for both parallel and crossover design studies 1

Critical Pitfalls to Avoid

• Do not attempt to predict which patients will develop pacemaker syndrome based on implantation testing; no reliable predictors exist 1, 4
• Do not implant VVI pacemakers in patients with sinus node dysfunction and intact AV conduction, as this creates the highest risk for pacemaker syndrome 6, 4
• Do not rely on rate-adaptive programming alone to manage symptoms; AV synchrony must be restored 6
• Do not use excessively prolonged AV delays in dual-chamber systems, as this can paradoxically create pacemaker syndrome 1, 6
• Recognize that pacemaker syndrome can occur, though rarely, even with atrial and dual-chamber pacing modes when AV timing is suboptimal 3
• Do not assume that absence of retrograde ventriculoatrial conduction at implantation excludes future pacemaker syndrome risk 1, 3