Sick Sinus Syndrome

Epidemiology and Etiology

Epidemiology

• More common in the elderly
• Most common reason for placement of an artificial pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias

Etiology

• Degenerative changes Degenerative Changes Spinal Stenosis and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of the sinoatrial (SA) node and surrounding myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy:
  • Age-related tissue change
  • Tissue damage from acquired heart disease (e.g., myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction)
  • Cardiac deposition disease:
    • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
    • Amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis
    • Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis
• Hereditary sick sinus syndrome (SSS) can be due to mutations of the gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics responsible for the formation of the alpha subunit of the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channel (SCN5A).
• Medications:
  • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
• Underlying medical conditions:
  • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
  • Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia

Pathophysiology

Normal physiology

• Sinus or SA node:
  • A cluster of cells near the junction of the right atrium and superior vena cava Superior vena cava The venous trunk which returns blood from the head, neck, upper extremities and chest. Mediastinum and Great Vessels: Anatomy
  • “Natural pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias” that initiates the electrical impulses to stimulate contraction
• Innervation of the heart: 
  • Parasympathetic: reduces sinus node automaticity (↓ heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology)
  • Sympathetic: increases sinus node automaticity (↑ heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology)
• Sequential Sequential Computed Tomography (CT) events of a cardiac cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation:
  1. SA node initiates impulse/ P wave P wave Electrocardiogram (ECG): 
     • Atrial depolarization Depolarization Membrane Potential  
     • Atrial contraction
  2. PR segment:
     • Impulse reaches AV node.
     • Impulse passes to the His bundle.
  3. QRS complex QRS complex Electrocardiogram (ECG): 
     • Atrial repolarization Repolarization Membrane Potential 
     • Depolarization Depolarization Membrane Potential of ventricles
     • Ventricular contraction
  4. ST segment ST segment Isoelectric segment between the s wave and the initial deflection of the t wave. Electrocardiogram (ECG): completion of ventricular depolarization Depolarization Membrane Potential
  5. T wave T wave Electrocardiogram (ECG): repolarization Repolarization Membrane Potential of ventricles
  6. Completion of repolarization Repolarization Membrane Potential

Pathophysiology

Degeneration of the SA node:

• Affects the ability to generate or transmit impulses to the atria → the conduction system as a whole fails to function effectively
• Beats fail to originate in the SA node → may result in tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children– bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias syndrome

Clinical Presentation

Symptoms of bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias or tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children– bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias syndrome include:

• Chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Palpitations Palpitations Ebstein’s Anomaly
• Manifestations of low cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics:
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension 
  • Pallor
  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Confusion
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
• Adams–Stokes attacks: sudden loss of consciousness due to a disorder of the heart rhythm in which there is a slow or absent pulse

The following heart rhythm abnormalities may be seen as a part of SSS:

• Sinus pause: 
  • Temporary failure of the SA node to depolarize
  • Can be seen in a 12-lead ECG as absent P waves
  • Usually, the AV node will take over as a pacemaker (escape rhythm).
  • A sinus pause of < 3 seconds is occasionally found in healthy adults.
  • A pause > 3 seconds may require intervention.
• SA block: 
  • Condition in which the SA node depolarizes but the signal does not progress through the rest of the atria
  • May be viewed as “temporary” SSS; shares many common etiologic factors with SSS
• Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation: 
  • Most common supraventricular arrhythmia
  • Characterized by disorganized atrial contraction and an increased risk of thromboembolic disease
• Atrial flutter Atrial flutter Atrial flutter is a regular supraventricular tachycardia characterized by an atrial heart rate between 240/min and 340/min (typically 300/min), atrioventricular (AV) node conduction block, and a “sawtooth” pattern on an electrocardiogram (ECG). Atrial Flutter: supraventricular tachyarrhythmia Tachyarrhythmia A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Tachyarrhythmias characterized by “sawtooth” flutter waves on ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)

Diagnosis

• Diagnosis is made by ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG).
  • Ambulatory (Holter) monitoring might be needed if the arrhythmia is transient.
  • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) findings can vary widely:
    • Sinus arrhythmia
    • Sinus arrest Sinus arrest The omission of atrial activation that is caused by transient cessation of impulse generation at the sinoatrial node. It is characterized by a prolonged pause without P wave in an electrocardiogram. Sinus arrest has been associated with sleep apnea (rem sleep-related sinus arrest). Bradyarrhythmias
    • Sinus block
    • Asystolic pauses
    • Reentrant tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Cardiac stress test: Exercise or pharmacologic stress test shows an inadequate increase in heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology in relation to stress/physical activity.
• Electrophysiology studies can show prolonged sinus recovery time but are not frequently used for diagnostic purposes owing to low sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests.
• Tilt-table testing can be used to reveal some forms of SSS.

Management

• Treat reversible causes that may be affecting SA function:
  • Electrolyte disturbances
  • Withhold offending medications.
• Stable, asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may not require medical intervention.
• In hemodynamically unstable (systolic BP < 90 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg) or symptomatic ( altered mental status Altered Mental Status Sepsis in Children, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways) patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • Best initial step is atropine Atropine An alkaloid, originally from atropa belladonna, but found in other plants, mainly solanaceae. Hyoscyamine is the 3(s)-endo isomer of atropine. Anticholinergic Drugs and transcutaneous pacing.
  • Sympathomimetics Sympathomimetics Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs can be used if transcutaneous pacing fails:
    • Epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs
    • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS
    • Dobutamine Dobutamine A catecholamine derivative with specificity for beta-1 adrenergic receptors. Sympathomimetic Drugs
  • A temporary external or transvenous pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias may be required.
• The most definitive long-term therapy for refractory disease is pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias placement.
• Concurrent tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children syndromes should be treated accordingly.

Clinical Relevance

The following conditions may predispose to SSS.

• Amyloidosis Amyloidosis Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). Amyloidosis: a disorder caused by extracellular deposition of insoluble abnormal amyloid that alters the function of tissues, especially the cardiac conduction system
• Cardiomyopathies Cardiomyopathies A group of diseases in which the dominant feature is the involvement of the cardiac muscle itself. Cardiomyopathies are classified according to their predominant pathophysiological features (dilated cardiomyopathy; hypertrophic cardiomyopathy; restrictive cardiomyopathy) or their etiological/pathological factors (cardiomyopathy, alcoholic; endocardial fibroelastosis). Cardiomyopathy: Overview and Types: a varied group of myocardial diseases (dilated, restrictive, hypertrophic) associated with impaired systolic and diastolic function
• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism: deficiency of triiodothyronine Triiodothyronine A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones (T₃) and thyroxine Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroid Hormones (T₄): Hashimoto’s disease ( autoimmune thyroiditis Autoimmune thyroiditis Inflammatory disease of the thyroid gland due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-cells and thyroid autoantibodies. The clinical signs can range from hypothyroidism to thyrotoxicosis depending on the type of autoimmune thyroiditis. Thyroiditis) is the leading cause of hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism in non–iodine-deficient regions. Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism may decrease the overall metabolic rate.
• Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis: a genetic autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder caused by mutations in the HFE gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics that results in increased intestinal iron absorption Iron absorption Digestion and Absorption 
• Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis: a multisystem disease Multisystem disease Mitochondrial Myopathies for which the genesis is not yet completely known and which is characterized by noncaseating granulomas Noncaseating granulomas Crohn’s Disease in the affected organs: The main locations for this disease to manifest itself are the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy and the hilar lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy.
• Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia: serum potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia level > 5.5 mEq/L: Severe hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia is rare but can cause respiratory paralysis, generalized muscle paralysis, and cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest.

The following conditions are included in the differential diagnosis for SSS.

• Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope: temporary loss of consciousness caused by a fall in blood pressure: Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope can be due to many causes, ranging from benign Benign Fibroadenoma to life-threatening conditions.
• Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction: ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of myocardial tissue due to obstruction of a coronary artery Coronary Artery Truncus Arteriosus: This is usually accompanied by an increase in cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) abnormalities, and chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.