see also:

• bradycardia

• SSS is a syndrome of cardiac rhythm pathologies affecting the sinoatrial node resulting in sinoatrial node pacemaker dysfunction and/or sinoatrial conduction dysfunction
• most cases are due to acquired damage, but some are genetic familial inherited conditions which often present at an early age
• symptomatic SSS generally requires the implantation of permanent pacemaker
• SSS accounts for half of all permanent pacemaker placements
• it was 1st identified in 1967 when noted after DC reversion of arrhythmias ¹⁾
• 1 in 600 patients with heart disease who are over age 65 have SSS, and incidence increases with age

• characterized by persistent inappropriate sinus bradycardia, episodes of sinoatrial block and/or chronotropic incompetence
• episodes of such dysfunction may cause severe reduction in cardiac output resulting in hypotension, light-headedness, syncope or sudden death due to either:
  • severe sinus bradycardia
  • sinus arrest
  • sinoatrial block
  • tachycardia-bradycardia syndrome is common (flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia)

• the pathophysiology is not just related to dysfunction of the sino-atrial node as the name suggests but may be due to impairments within:
  • cardiac neural stimuli system / autonomic influences
  • conducting system
• the sino-atrial node
  • situated in the RA, it is the physiological pacemaker of the human heart and responsible for autonomous heart beat generation
  • the mix of ionic currents allows for the pacemaking function, and in addition its poor electrical coupling protects it from the inhibitory hyperpolarizing influence of the surrounding atrial tissue.
  • the automaticity and thus heart reate is regulated via vagal nerve parasympathetic stimulation which slows it and beta-adrenergic sympathetic stimulation which speeds it - adenosine, adrenergic, and muscarinic receptors are all present in SA nodal tissue.
  • hyperpolarization-activated cyclic nucleotide-gated (HCN) and other types of potassium ion channels are important in the automaticity of the SA node core
  • sodium channels are essential for orderly progression of action potentials from the SA node core, through its periphery, and to the surrounding atrial tissue.
  • calcium has an important role ²⁾

• elderly
• IHD
• rheumatologic
• oncologic
• metabolic
• infectious - myocarditis
• structural
• iatrogenic - radiation Rx;
• amyloidosis
• Lenegre’s disease
• Lev’s disease

• sinus node dysfunction and deafness syndrome (SANDD)
  • bradycardia, profound deafness, and dysfunction of atrioventricular conduction
  • CaV1.3-mediated I-caL dysfunction
• early repolarization (ER) pattern
  • two or more continuous wall or side wall leads with a J point elevation above 0.1 mV
  • ST elevation is above 0.1 mV and exhibits concave upward or oblique type elevation
  • a polygenic inherited disease, similar to hereditary sinus bradycardia, caused by mutations in cardiomyocyte genes encoding ion channels
  • most commonly seen in young men
    • most common pathogenic genes are encoded by cardiac electrical ion channels, including calcium channels (CACNA1C, CACNB2B, and CACNA2D1), ATP-sensitive potassium channels (KCNJ8), sodium channel α subunit 5 (SCN5A) and TTN gene (cardiomyocyte gene)³⁾
• sick sinus syndrome 1 (SSS1)
  • OMIM 608567
  • caused by compound heterozygous mutation in the SCN5A gene (600163) on chromosome 3p22 which is associated with pore-forming α-subunit of the cardiac Na+ channel which is responsible for the generation and rapid propagation of action potentials in the heart.
  • automosomal recessive
• sick sinus syndrome 2 (SSS2)
  • OMIM #163800
  • caused by heterozygous mutation in the cardiac pacemaker channel gene HCN4 (605206) on chromosome 15q24
  • autosomal dominant
• sick sinus syndrome 3 - susceptibility to sick sinus syndrome
  • OMIM 614090
  • influenced by variation in the MYH6 gene
  • allelic frequency of 0.38% in Icelanders
  • lifetime risk of developing SSS is 50% (cf 6% for general population)
• atrial standstill phenotype
  • rare; certain genetic variants of Cx40 with accompanying SCN5A mutations