New insights into pacemaker activity: promoting understanding of sick sinus syndrome.

Sick sinus syndrome is an abnormality involving the generation of the action potential by the sinus node and is characterized by an atrial rate inappropriate for physiological requirements. Manifestations include severe sinus bradycardia, sinus pauses or arrest, sinus node exit block, chronic atrial tachyarrhythmias, alternating periods of atrial bradyarrhythmias and tachyarrhythmias, and inappropriate responses of heart rate during exercise or stress.1 Although its incidence increases in an exponential-like manner with age,1 it can occur at all ages, including in the newborn.2 The mean age of patients with the syndrome is 68 years, with both genders being affected in approximately equal proportion.2 The syndrome occurs in 1 of every 600 cardiac patients older than 65 years and accounts for approximately half of implantations of pacemakers in the United States.2 The syndrome is a collection of conditions, with a variety of causes intrinsic or extrinsic relative to the node.2 Age-dependent degenerative fibrosis of the tissues of the node has been suggested to be a common cause,2 although this is disputed.1 Clinical aspects of the syndrome have been reviewed many times.1–3 In this review, coinciding with the centenary of the discovery of the node, we offer new insights into intrinsic causes that come from an understanding of the mechanisms underlying pacemaking.