Sinus Node Dysfunction

Robert J. Kim, MD
Staff Cardiac Electrophysiologist
Ashchi Heart & Vascular Center, Jacksonville (FL)
 Disclosures
• None
 Learning Objectives
1. Describe the relevant anatomy of the human sinus node, its normal physiologic
function, and the pathophysiology of its dysfunction.
2. Recognize the signs and symptoms of sinus node dysfunction (SND) and
various electrocardiogram (ECG) features that accompany different clinical
subtypes to facilitate diagnosis and optimize management.
3. Distinguish the two etiologies of SND as either primary or secondary and list
various secondary (or extrinsic) causes that can be reversible in some cases.
4. Describe the available invasive and noninvasive diagnostic modalities for
identifying SND and the indications for their use.
5. Formulate an effective and safe treatment plan for patients with symptomatic
SND to improve their symptoms and quality of life.
 Overview
• SND is a common affliction of older patients.
• ECG typically demonstrates marked sinus bradycardia or asystolic
pauses of varying duration.
• Spectrum of clinical manifestations can range from asymptomatic to
frank syncope.
• SND is thought to be caused by age-related atrophy and fibrosis of the
nodal and peri-nodal cells.
• Significant proportion of patients with SND (~1/3rd) also develop AF.
• PPM is the only definitive therapy to relieve symptoms and improve the
quality of life.
 Anatomy of Sinus Node
• Elongated subepicardial structure located at the posterolateral junction of SVC
and right atrium.
• Blood supply is derived from the sino-atrial branch of right coronary artery (55%
of the time).
• Surrounded by transitional peri-nodal cells that modulate autonomic input and
output.
• Several different types of gap-junction channel proteins (e.g. connexin 45)
expressed on the cell play a crucial role in cell-to-cell communication.
• In patients with SND, there is ample evidence for reduced expression of channel
proteins.
 Normal Physiology of Sinus Node
• SN cells are anatomically arranged by hierarchy such that cells located at the
cephalad region (“leading pacemaker site”) discharge faster than those located
at the more caudal region.
• Normal electrophysiology of the SN is characterized by cyclic spontaneous
diastolic depolarization during phase 4 of the action potential by a unique
interplay of membrane ion channels (“membrane clock”) and intracellular
calcium (Ca2+) handling mechanisms (“Ca2+ clock”)
• Intrinsic automaticity of the sinus node is the consequence of phasic late
diastolic depolarization (net positive charge influx) that brings the membrane
potential to a trigger threshold.
 Many “Displays” of SND
• Severe sinus bradycardia
• Sinus pause
• Sinus arrest
• Sinus node exit block
• Chronotropic incompetence
– Inability to increase HR to satisfy the physiologic demand of activity
• Tachycardia-bradycardia syndrome (i.e. sick sinus syndrome)
– Paroxysmal episodes of atrial tachyarrhythmia (most commonly AF) which alternates
with sinus bradycardia
– Prolonged duration of conversion pause can lead to syncope
Sick Sinus Syndrome

Sinus pauses

Atrial fibrillation
Sinus Arrest/Pause
 Etiology of SND
• Primary cause (intrinsic)
– Age-related atrophy, degeneration and fibrosis of nodal and peri-nodal tissues are the
most common findings.
• Secondary causes (extrinsic)
– Medications
– Acute myocardial infarction
– Obstructive sleep apnea (OSA)
– Metabolic abnormalities
– Infection
– Status post cardiac surgery
– Endocrine disorder (e.g. profound hypothyroidism)
General Principles of Diagnostic Evaluation
• Proper diagnosis of SND is dependent on correlating
suspected symptoms with ECG abnormalities such as
severe sinus bradycardia or sinus pause.
• Ambulatory ECG monitoring modalities such as a Holter and
event monitors can play an important role in diagnosis.
• For symptoms of infrequent nature, a long term monitoring
with an implantable cardiac monitor (ICM)may be
necessary.
 Invasive Diagnostic Evaluation
• Catheter-based electrophysiologic study (EPS) is rarely indicated for the
sole purpose of diagnosing of SND.
• Two basic types of evaluation which have limited sensitivity and
specificity.
1. Sinus node recovery time (SNRT)
 Measures automaticity of the SN by pacing at a constant rate for a set duration of time and observing the
recovery (i.e. return) interval.
 Often performed with pharmacologic blockade to eliminate the sympathetic and parasympathetic
influence on the SN.
2. Sino-atrial conduction time (SACT)
 Assesses conduction time into and out of the SN from pacing site
 Strauss method (uses premature atrial beats), Narula method (uses constant drive train)
 General Principles of Management
• Initial management should be focused on identifying and eliminating
any reversible factors such as metabolic abnormalities, causative
medications, infection, or sleep disorders.
• Pacing therapy can be recommended as a definitive treatment of
symptomatic patients after reversible causative factors have been
addressed.
• Asymptomatic patients with SND do not require treatment.
• Permanent pacing therapy in patients with SND has not been shown to
impact survival, and is recommended only for QOL and symptom
improvement.
 Pharmacologic Intervention
• May be considered when there is evidence for hemodynamic
compromise (uncommon situation) and temporary pacing is not
available
• IV medications should be given under strict hemodynamic monitoring
with continuous telemetry
– IV atropine (0.5mg bolus) repeated every 3-5 minutes up to the maximum dose of
3mg
– Low dose intravenous adrenergic agents (e.g. dopamine, epinephrine)
• Oral theophylline (uncommon use) may boost sinus rate
 Special Topics
• SND and atrial tachyarrhythmia
• SND and endurance athletes
• SND and heart failure
• Familial SND
 SND and atrial tachyarrhythmia
• Atrial tachyarrhythmias (typically AF) and SND frequently coexist; their
clinical association has long been well recognized.
• Incidence of AF in patients with SND is greater than 1 in 3 in a long-
term follow-up study.
• Both entities are associated with progressive atrial structural
remodeling but it is not known precisely how one entity predisposes to
or causes development of the other.
• Remodeling is believed to result from alterations in ion channel
expression and may be reversible in some cases in which duration of
arrhythmia is relatively short.
 SND and endurance athletes
• Resting heart rate of well-trained endurance athletes (e.g. swimmers, marathon
runners) frequently manifest marked bradycardia at rest due to significantly
elevated parasympathetic tone.
• Increase in intrinsic heart rate (IHR) should be demonstrated by full autonomic
pharmacologic blockade but this is typically not observed in vivo.
• Strong evidence suggests that such bradycardia is also mediated by alteration
in expression of ion channel genes (e.g. down-regulation of important
pacemaker channel gene HCN4).
• There are also evidences of progressive atrial fibrosis, atrial dilatation and atrial
arrhythmias in long term endurance athletes.
 SND and heart failure
• Prevalence of SND in patients with HF is higher than in age- and sex-
matched controls without HF.
• EP abnormalities commonly observed include increase in sinus cycle
lengths, prolonged SNRT and SACT, and caudal displacement of sinus
pacemaking activity.
• Patients with HF have significant SN remodeling characterized by
anatomic and structural changes along crista terminalis and reduction
in functional SN reserve.
• Some pharmacologic agents with negative chronotropic effect are in
common use in HF patients and can exacerbate the degree of SND.
 Familial Type of SND
• Inherited causes of SND is rare.
• Various genetic mutations have been identified (e.g. SCN5A, HCN4,
ANK2).
– SCN5A:
• Loss-of-function mutation is the basis of Brugada syndrome.
• This mutation has also been implicated in AF, dilated CMP, long QT syndrome and SND.
– HCN4:
• responsible for coding ion channels for funny current (If), an inward depolarizing current carried by sodium
(Na+) and potassium (K+) ions.
• Mutations are associated with severe sinus bradycardia and AF.
– Mutations of other genes such as ryanodine, calsequestrin and ankyrin are also
associated with severe sinus bradycardia.
 Summary
• The sinus node is a complex anatomic structure composed of several
different cell types with unique electrophysiologic properties that are
modulated by the autonomic nervous system.
• Sinus node rates in general undergo physiologic slowing with age.
However, given significant individual variations, resting sinus rate alone
cannot identify a patient with sinus node dysfunction.
• The clinical manifestations of sinus node dysfunction can include
presyncope or syncope due to intermittent periods of significant
bradycardia, exertional intolerance from chronotropic incompetence,
and palpitations due to paroxysmal episodes of atrial tachyarrhythmia.
 Summary (cont’d)
• Primary sinus node dysfunction is most strongly correlated with advanced age; secondary
causes of sinus node dysfunction include medications, acute myocardial infarction,
obstructive sleep apnea, metabolic abnormalities, certain types of infection, certain
central nervous system pathologies, and sequelae of a cardiac procedure or surgery.
• Proper diagnosis of sinus node dysfunction is predicated on correlating suspected
symptoms with electrocardiogram (ECG) abnormalities such as severe sinus bradycardia,
pause, or sinus arrest. Ambulatory ECG monitoring techniques such as Holter monitoring
and event monitors can play an important role in diagnosis.
• Initial management of sinus node dysfunction should focus on identification and
elimination of any reversible factors such as metabolic abnormalities, causative
medications, infection, or sleep disorders.
• After reversible factors have been addressed or excluded as a possible cause, pacing
therapy is recommended for the treatment of symptomatic patients.