Sick sinus syndrome (SSS) occurs from sinoatrial node dysfunction and is the most common indication for permanent pacemaker implantation. This may manifest in multiple different ways, including:

- Tachycardia-bradycardia syndrome (i.e. pauses after converting to sinus rhythm)
- Severe sinus bradycardia
- Sinus pauses/sinus arrest
- Sinoatrial nodal exit block
- Chronotropic incompetence (failure of heart rate to increase during exercise)

The second most common indication for a permanent pacemaker is atrioventricular (AV) nodal disease such as second degree type II AV block or third degree heart block.

The AV blocks occur when there is fibrosis/dysfunction of the atrioventricular node or His-Purkinje system. The AV node itself is subject to autonomic input. If the parasympathetic tone is high of if sympathetic tone is inhibited (beta-blockers), then a 1st degree AV block (prolonged PR interval) or second degree type I AV block may manifest. This is reversible if the autonomic tone is returned to normal.

In contrast, if there is disease of the His-Purkinje system, the rhythm may be second degree type II or third degree heart block, which is not reversible and indicates the need for permanent pacemaker implantation.