Etiology of Sick Sinus Syndrome
Sick sinus syndrome (sinus node dysfunction) is most commonly caused by age-dependent, progressive, degenerative fibrosis of the sinus nodal tissue and surrounding atrial myocardium. 1
Primary Intrinsic Causes
Degenerative Fibrosis (Most Common)
- Age-related degenerative fibrosis is the predominant etiology, affecting the sinoatrial node and surrounding atrial tissue, resulting in abnormalities of impulse formation and propagation 1, 2, 3
- This pathological process typically manifests in older adults, predominantly in their 70s or 80s 4
- The fibrotic changes represent idiopathic degeneration of the sinoatrial node that progresses over time 5
Other Intrinsic Structural Causes
- Ion channel dysfunction affecting the sinoatrial node 3, 6
- Cardiac remodeling of the sinoatrial region, particularly in patients with frequent atrial arrhythmias or sustained atrial fibrillation 1, 6
- Infiltrative diseases including sarcoidosis and amyloidosis (though these require prophylactic pacing even when block is transient) 1
- Certain neuromuscular diseases 1
Important Caveat About Coronary Disease
Coronary artery disease is NOT a major cause of sick sinus syndrome, contrary to common misconception 2. While patients may have coexisting coronary disease, the sinus node dysfunction itself stems from degenerative fibrosis rather than ischemic injury.
Extrinsic/Secondary Causes
Medication-Induced (Reversible)
The following medications can exacerbate, unmask, or mimic sinus node dysfunction 1, 5:
- Cardiac glycosides (digoxin) 1
- Beta-adrenergic blockers 1, 5
- Calcium channel blockers (particularly non-dihydropyridines like verapamil and diltiazem) 1, 5
- Membrane-active antiarrhythmic agents, especially sotalol and amiodarone 1
- Class IC antiarrhythmics (flecainide, propafenone) 7
Metabolic and Autonomic Factors
- Electrolyte abnormalities 1
- Autonomic nervous system disturbances, which often contribute to syncope even in patients with intrinsic sinus node disease 1
- Increased vagal tone (physiologic in trained athletes, not pathologic) 1
Pathophysiological Mechanism
The degenerative fibrosis creates a widespread atrial abnormality that serves as substrate for both bradyarrhythmias and tachyarrhythmias 1. This explains why at least 50% of patients develop tachy-brady syndrome, where the same fibrotic process responsible for bradycardia also causes atrial tachyarrhythmias 4, 3.
Clinical Pitfall to Avoid
Always exclude and correct reversible extrinsic causes before attributing symptoms solely to intrinsic sinus node disease 1. Elimination of offending medications is an essential first step, as drug-induced dysfunction may completely resolve with medication adjustment 4, 7. However, when medication substitution is not feasible and symptoms persist, permanent pacing becomes necessary 1.