Sinus node dysfunction

Sinus node dysfunction (SND), previously called sick sinus syndrome, is an abnormality in sinoatrial (SA) node action potential generation or conduction. It can be caused by factors intrinsic to the SA node (e.g., fibrosis of the SA node, infiltrative diseases) or extrinsic factors (e.g., pharmacotherapy with negative chronotropes, hypothyroidism) and most commonly results in bradycardia. Patients typically present with symptoms of end-organ hypoperfusion due to bradycardia (e.g., fatigue, presyncope, syncope, dyspnea on exertion). Establishing a temporal correlation between symptoms of bradycardia and rhythm abnormalities of SND (e.g., on ECG, stress testing, cardiac monitoring) confirms the diagnosis. Unstable bradycardia requires immediate implementation of advanced cardiac life support (ACLS) measures. Reversible causes of SND should be identified and managed. If reversible causes are not present, permanent pacemaker placement is preferred for long-term management of symptomatic patients. Tachycardia-bradycardia syndrome is a subtype of SND that manifests as alternating episodes of tachycardia and bradycardia and is associated with increased risk of cardiovascular events and mortality.

See also “Management of bradycardia” for related information.

• Incidence: 0.8 per 1000 person-years ^[1]
• Mean age: 68 years (although can occur at any age) ^[1]
• Sex: no specific predilection
• Risk factors ^[1][2]
  • Coronary artery disease
  • Hypertension
  • Diabetes mellitus
  • Obesity
  • Right bundle branch block

Epidemiological data refers to the US, unless otherwise specified.

Intrinsic factors ^[2]

Conditions that alter the structure or function of the SA node

• Degeneration, ischemia, infiltration , or fibrosis of the SA node and surrounding myocardium
• Cardiac intervention (e.g., repair of a septal defect)

Idiopathic degeneration of the SA node is the most common cause of SND. ^[1][2]

Extrinsic factors ^[2][3]

Factors external to the SA node that affect sinoatrial conduction

• Medications such as β-blockers, digoxin, and nondihydropyridine calcium channel blockers (verapamil, diltiazem)
• Excessive vagal tone (e.g., athletes)
• Electrolyte abnormalities
• See “Causes of bradycardia” for details.

Reversible causes of sinus node dysfunction ^[3]

• Symptoms of bradycardia (features of end-organ hypoperfusion) ^[2][3]
  • Fatigue
  • Dizziness or lightheadedness, syncope, presyncope, TIA (seen in ∼ 50% of patients) ^[2]
  • Decreased physical activity tolerance
  • Stokes-Adams attacks
  • Dyspnea on exertion
  • Angina, palpitations
  • Oliguria
• Patients with tachycardia-bradycardia syndrome will also present with symptoms of tachycardia, including palpitations.

The identification of a temporal correlation between symptoms of bradycardia and rhythm abnormalities of SND is considered the gold standard for diagnosing SND. In some individuals, SND may be asymptomatic in the early stages; symptomatic patients have a higher risk of cardiovascular events. ^[2][3]

• Assess patients for clinical features of unstable bradycardia.
  • Hemodynamically unstable patients
    • Initiate immediate treatment for unstable bradycardia (e.g., IV atropine, temporary cardiac pacing).
    • Admit for further management.
  • Hemodynamically stable patients
    • Severe symptoms (e.g., angina, recurrent syncope) OR SBP < 90 mm Hg: Manage as an inpatient with continuous telemetry.
    • No severe symptoms AND SBP ≥ 90 mm Hg: Diagnostic evaluation can be performed on an outpatient basis.
• Identify and treat the underlying cause.
• Consult cardiology.

Approach ^[2][3]

• Correlate symptoms with rhythm abnormalities of SND.
  • Obtain 12-lead ECG.
  • Inconclusive ECG findings: Perform ambulatory cardiac monitoring.
  • Symptoms on exertion: Perform exercise stress test.
• Evaluate for an underlying cause.
  • Evaluate all patients for reversible causes of SND: including medication review, BMP, HbA1c, thyroid function tests
  • Obtain additional studies (e.g., nocturnal polysomnography, TTE) as needed. ^[2][3][4]
• Refer for specialist evaluation for alternative diagnoses or advanced diagnostics if symptoms do not correlate with rhythm abnormalities.

In hemodynamically unstable patients, start immediate treatment for unstable bradycardia without waiting for diagnostic confirmation.

ECG studies ^[2][3]

• Preferred initial diagnostic study: 12-lead ECG
• Second line : ambulatory cardiac monitoring (typically in the following order)
  • Holter monitor or external patch recorder
  • Event monitor or mobile cardiovascular telemetry
  • External patch recorder or implantable loop recorder
• Supportive findings: The presence of any of the following rhythm abnormalities of SND with accompanying symptoms of end-organ hypoperfusion is diagnostic of SND. ^[2][3]

Evaluation for an underlying cause ^[2]

Laboratory studies

Evaluate all patients for common reversible causes of SND as clinically indicated (i.e., based on history and physical examination). ^[3]

• CBC
• BMP with magnesium
• Thyroid function tests
• Hemoglobin A1C
• Consider genetic testing (e.g., for SCN5A, HCN4 mutations) in consultation with a specialist. ^[3]

Additional studies ^[2][3][4]

• Sleep-related symptoms: Consider nocturnal polysomnography.
• Concern for structural heart disease : transthoracic echocardiogram (TTE)
• Suspected structural and/or infiltrative heart disease that cannot be confirmed with other diagnostic techniques: Consider advanced imaging

Advanced diagnostics ^[3][4]

• Indications: diagnostic uncertainty in symptomatic patients
• Modalities
  • Electrophysiology studies: may show prolonged sinus node recovery time in SND
  • Oral theophylline challenge test: Consider prior to pacemaker insertion if a documented bradyarrhythmia and symptoms are both present but the correlation is uncertain

Electrophysiology studies are not recommended in asymptomatic patients, as it is an invasive modality and the risks outweigh the potential benefits. ^[3]

• Atrioventricular block
• See also “Causes of bradycardia.”

Up to 50% of patients with SND eventually develop atrioventricular block, as fibrosis of pacemaker cells often occurs in both nodes. ^[4]

The differential diagnoses listed here are not exhaustive.

The long-term management of SND is detailed here. See “Management of unstable bradycardia” for initial management of SND causing hemodynamic compromise or severe symptoms.

General principles ^[2][3]

• Asymptomatic patients: observation
• Symptomatic patients
  • Manage reversible causes of SND.
  • Severe and/or frequent symptoms of bradycardia due to irreversible causes
    • First-line (after patient stabilization): permanent pacemaker placement
    • Alternative: phosphodiesterase inhibitors
• Tachycardia-bradycardia syndrome: See “Subtypes and variants” for details.

Permanent pacing should not be performed based on ECG findings alone. Permanent pacing is not recommended for asymptomatic patients. ^[3]

Oral anticoagulation is not routinely recommended for patients with SND unless another indication for anticoagulation is present. ^[2]

Management of the underlying cause ^[3]

• Indication: first-line management of patients with reversible causes of SND
• Examples
  • Stop or decrease the dosage of nonessential medications; see “Medication-induced bradycardia” for management of drug toxicity.
  • Management of hypothyroidism
  • Management of obstructive sleep apnea

Permanent pacemaker placement ^[3][4]

Permanent pacing decreases symptom frequency and improves quality of life. ^[2][3]

• Indications
  • First-line management for symptomatic SND caused by intrinsic or irreversible extrinsic factors
  • Symptomatic SND caused by essential medications that cannot be stopped
  • Symptomatic SND with chronotropic incompetence
• Important considerations: Permanent pacing is not routinely recommended in the following circumstances ^[3]
  • Asymptomatic or minimally symptomatic SND
  • Symptoms in the absence of rhythm abnormalities of SND
  • Nocturnal SND

Establishing a temporal correlation between symptoms and rhythm abnormalities aids patient selection for permanent pacing, as permanent pacing is most effective in these patients. ^[3][4]

Rule out reversible causes of SND before considering permanent pacemaker placement. ^[3]

Phosphodiesterase inhibitors ^[2][3]

• Indication: second-line option for patients in whom permanent pacing is indicated but cannot be performed
• Agents: theophylline, cilostazol

Tachycardia-bradycardia syndrome

Definition ^[3]

• A subtype of SND in which there are alternating periods of bradyarrhythmia and atrial tachyarrhythmias (typically atrial fibrillation)
• Present in 40–50% of patients with SND ^[2][8]
• Associated with increased risk of cardiovascular events and mortality. ^[2]

Clinical features ^[2][3]

• Symptoms vary in intensity depending on the extent of bradycardia and tachycardia.
• Symptoms of bradycardia and symptoms of tachycardia, e.g.:
  • Recurrent syncope or presyncope
  • Palpitations
  • Dyspnea
  • Angina pectoris
• Symptoms of atrial tachyarrhythmia-associated thromboembolic complications, e.g., stroke.

Diagnostics

• Diagnostic studies and findings are similar to those for SND.
• Rhythm abnormalities: alternating atrial tachyarrhythmias (e.g., atrial fibrillation , atrial tachycardia , atrial flutter ) and bradycardia (e.g., sinus bradycardia, ectopic atrial bradycardia, sinus pause) ^[3][4][7]

Treatment ^[3]

Arrhythmia control

• Bradycardia not triggered by atrial tachyarrhythmia
  • Permanent pacemaker placement
  • Followed by treatment for tachyarrhythmias
    • e.g., β1-selective beta blockers (cardioselective beta blockers)
    • See “Treatment of atrial fibrillation.”
• Bradycardia triggered by atrial tachyarrhythmia
  • Consider ablation as the sole treatment.
  • If ablation is unsuitable or unsuccessful, treat with a pacemaker and rate control.

Pharmacotherapy for tachyarrhythmia can trigger complete heart block, asystole, and bradyarrhythmias in patients without a pacemaker. ^[3]

Ablation for atrial tachyarrhythmias may be sufficient for the management of both tachycardia and bradycardia in patients with tachycardia-bradycardia syndrome. ^[3]

Thromboembolism prophylaxis

• Patients are at an increased risk of cardiovascular events.
• Assess the need for anticoagulation based on patient risk factors and type of tachyarrhythmia (e.g., see “Anticoagulation in atrial fibrillation.”)