Long QT Syndrome

Definitions

• Long QT syndrome (LQTS): a ventricular electrical disorder characterized by delayed myocardial repolarization Repolarization Membrane Potential and demonstrated as prolonged QT interval QT interval Electrocardiogram (ECG) on electrocardiogram Electrocardiogram 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) ( 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))
• QT interval QT interval Electrocardiogram (ECG):
  • The measurement from the start of the Q wave to the end of the T wave T wave Electrocardiogram (ECG) on an 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)
  • Represents ventricular depolarization Depolarization Membrane Potential and repolarization Repolarization Membrane Potential
• QTc: the corrected QT interval QT interval Electrocardiogram (ECG), which accounts for varying heart rates
• Normal QT interval QT interval Electrocardiogram (ECG):
  • On average: 400–440 milliseconds
  • After puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty, women tend to have a longer QT interval QT interval Electrocardiogram (ECG) than men.
• Prolonged QT interval QT interval Electrocardiogram (ECG):
  • Males:
    • Normal: ≤ 430 milliseconds
    • Borderline prolonged QT interval QT interval Electrocardiogram (ECG): 431–450 milliseconds
    • Prolonged QT interval QT interval Electrocardiogram (ECG): > 450 milliseconds
  • Females:
    • Normal: ≤ 450 milliseconds
    • Borderline prolonged QT interval QT interval Electrocardiogram (ECG): 451–470 milliseconds
    • Prolonged QT interval QT interval Electrocardiogram (ECG): > 470 milliseconds
• Torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia:
  • A life-threatening arrhythmia associated with LQTS
  • Form of polymorphic ventricular tachycardia Polymorphic ventricular tachycardia Ventricular Tachycardia
  • Caused by early afterdepolarizations
  • Irregular QRS complexes “twisting” around the isoelectric line (torsade de pointes = “twisting of points”)
  • Rate of 160–250/min
  • Often terminates spontaneously, but can lead to sudden cardiac death Sudden cardiac death 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

Etiology

Congenital Congenital Chorioretinitis long QT syndrome

Pathophysiology:

• Defects in genes Genes 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. DNA Types and Structure coding for ion channels Channels The Cell: Cell Membrane (i.e., cardiac channelopathies)
  • Change in flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of positive ions affects repolarizing current in cardiomyocytes → prolongs the action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential (QT prolongation) → leads to early afterdepolarization →  increased risk of torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia 
  • These genetic mutations Genetic Mutations Carcinogenesis account for 80% of LQTS cases:
    • Loss-of-function mutations in KCNQ1-encoded and KCNH2-encoded  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 channels Channels The Cell: Cell Membrane: prolong action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential duration by reducing K efflux
    • Gain-of-function mutations in the SCN5A-encoded sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane: prolong action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential duration by the contribution of increased late sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia currents (which raises Na [ sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia] influx)
• Sympathetic innervation of the heart:
  • A trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation for torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia is a surge in sympathetic tone (such as an extreme emotional event).
  • Stimulation of left stellate ganglion prolongs the QT interval QT interval Electrocardiogram (ECG) 
  • Not found in acquired LQTS

Types of congenital Congenital Chorioretinitis LQTS:

1. Type 1 Type 1 Spinal Muscular Atrophy is the most common congenital Congenital Chorioretinitis form.
   • Up to 45% of LQTS cases
   • Defect in KCNQ1 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
2. Type 2 Type 2 Spinal Muscular Atrophy
   • Up to 40% of LQTS cases
   • Defect in KCNH2 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
3. Type 3 Type 3 Spinal Muscular Atrophy
   • Up to 10% of LQTS cases
   • Defect in SCN5A 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

Variety of associated conditions:

• Romano-Ward syndrome: 99% of cases; congenital Congenital Chorioretinitis LQTS without extracardiac manifestations ( autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance)
• Jervell and Lange-Nielsen syndrome: congenital Congenital Chorioretinitis LQTS + sensorineural hearing loss Sensorineural hearing loss Hearing loss resulting from damage to the cochlea and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the auditory nerve and its connections in the brainstem. Hearing Loss ( 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)
• Anderson-Tawil syndrome: congenital Congenital Chorioretinitis LQTS + periodic paralysis
• Timothy syndrome: congenital Congenital Chorioretinitis LQTS + cutaneous syndactyly Syndactyly A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements. Development of the Limbs + autism

Acquired long QT syndrome

• Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome/pharmacologic:
  • Most common cause
  • LQTS caused by blocking 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 outflow during the rapid repolarization Repolarization Membrane Potential phase:
    • Antiarrhythmic drugs
    • Antibiotics ( macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides, fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones, antifungals, HIV HIV Anti-HIV Drugs antiretroviral drugs, antimalarial drugs Antimalarial drugs Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person’s bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. Antimalarial Drugs)
    • Antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines (older nonsedating antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines, e.g., terfenadine)
    • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics ( methadone Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. Opioid Analgesics, fentanyl Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. Opioid Analgesics)
    • Psychotropic agents (antidepressants, antipsychotics)
    • Gastric motility Gastric motility Gastrointestinal Motility drugs (cisapride), antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics ( ondansetron Ondansetron A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. Antiemetics)
    • Antineoplastics
    • Beta-2 agonists
    • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication (due to resultant electrolyte abnormalities)
• Metabolic disorders:
  • Electrolyte disturbances: hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia, hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes
  • 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
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa nervosa, starvation (due to resultant electrolyte abnormalities)
• Bradyarrhythmias Bradyarrhythmias 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:
  • Sinus node dysfunction Sinus node dysfunction A condition caused by dysfunctions related to the sinoatrial node including impulse generation (cardiac sinus arrest) and impulse conduction (sinoatrial exit block). It is characterized by persistent bradycardia, chronic atrial fibrillation, and failure to resume sinus rhythm following cardioversion. This syndrome can be congenital or acquired, particularly after surgical correction for heart defects. Bradyarrhythmias
  • Atrioventricular (AV) block (2nd or 3rd degree)
• Other:
  • 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 ( MI MI 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)
  • Intracranial disease 
  • HIV HIV Anti-HIV Drugs infection 
  • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia
  • Toxic exposure (e.g., organophosphates)

Clinical Manifestations

Congenital Congenital Chorioretinitis long QT syndrome

• Often diagnosed in the first 3 decades of life
• Most commonly asymptomatic
  Diagnosis may be made:
  • When a patient seeks medical attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment after a cardiac event in a family member
  • As an incidental finding in an 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) done for another indication
• Those with symptoms present with:
  • 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
  • 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 followed by seizure (may be misdiagnosed as primary seizure disorder)
  • Sudden 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 (SCA)
  • In rare cases, the sentinel event is sudden cardiac death Sudden cardiac death 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 ( SCD SCD Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease).
• LQTS type 1 Type 1 Spinal Muscular Atrophy:
  • Cardiac events preceded by exercise (62% of events) or stress
  • Swimming is a highly specific trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation!
  • Risk during sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep is low.
• LQTS type 2 Type 2 Spinal Muscular Atrophy:
  • Arrhythmia after an extreme emotional event, exercise, or auditory stimuli (sudden noise or alarm/telephone ringing)
  • Postpartum cardiac event: almost exclusively in LQTS 2
  • Cardiac events can also occur at rest or during sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep.
• LQTS type 3 Type 3 Spinal Muscular Atrophy
  • Highest risk of cardiac events while at rest or asleep
  • Fewer events with exercise or stress because the QTc shortens with 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

Acquired long QT syndrome

• Symptoms are only present with an episode of arrhythmia.
• Symptoms vary with the rate and duration of torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia as well as with comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:
  • Palpitations Palpitations Ebstein’s Anomaly
  • Light-headedness or presyncope Presyncope Syncope
  • 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 
  • Sudden 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

Diagnosis

The diagnosis of long QT syndrome can be made via an 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) of the patient and/or 1st-degree relatives.  A careful medication review is indicated for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

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

• Prolonged QTc (corrected QT interval QT interval Electrocardiogram (ECG))
  • The QT interval QT interval Electrocardiogram (ECG) needs to be “corrected” to account for varying heart rates and is often automatically reported as the QTc.
  • Correction formula: QTc = QT interval QT interval Electrocardiogram (ECG) ÷ √ RR interval RR interval Electrocardiogram (ECG) (in sec)
  • QTc interval > 450 ms MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis in males
  • QTc interval > 470 ms MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis in females
• LQTS can degenerate into fatal arrhythmias, especially torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia:
  • Short-lived but can have multiple successive episodes
  • Can progress to ventricular fibrillation Ventricular fibrillation Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular Fibrillation (V-fib)
  • 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 include:
    • Prolonged QTc in last sinus beat preceding onset of arrhythmia
    • 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 of 160–250/min
    • Wide QRS complexes (> 120 ms MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis) with QRS axis QRS axis Electrocardiogram (ECG) rotating over a sequence of 5–20 beats
    • Irregular RR interval RR interval Electrocardiogram (ECG)
• Ambulatory 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) monitoring: may provide corroborative information for suspected cases of congenital Congenital Chorioretinitis LQTS

Exercise testing

• To assess exercise-associated arrhythmias
• Check QT responses (exercise and recovery) and changes in T wave T wave Electrocardiogram (ECG)
• Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables response with type of congenital Congenital Chorioretinitis LQTS
• QTc > 470 ms MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis at 2–5 minute recovery is suggestive of LQTS 1 (where cardiac events commonly occur during exercise)

Genetic analysis

• For intermediate and highly suspicious cases of congenital Congenital Chorioretinitis LQTS based on clinical presentation, family history Family History Adult Health Maintenance, and 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)
• For asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with serial ECGs showing QTc > 460 ms MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis

Additional tests

• Medication review
• Laboratory tests (metabolic panel, thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones [TSH])
• Other cardiac workup based on probable cause (myocardial perfusion, echocardiogram Echocardiogram Transposition of the Great Arteries)

Management

Congenital Congenital Chorioretinitis LQTS

• Reduce the risk of fatal arrhythmias:
  • Avoid QT-prolonging drugs
  • Electrolyte repletion
  • Avoid triggers of arrhythmia (swimming/exercise, emotional distress, noise; LQTS specialist consult for sports participation recommended)
• First-line 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) ( propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs or nadolol Nadolol A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine disorders and for tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers))
• Left cardiac sympathetic denervation:
  • Rarely performed
  • May work in some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who do not respond to or cannot tolerate 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)
  • Not curative; high-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will still need an implantable cardioverter-defibrillator (ICD)
• Recurrent symptoms despite medical therapy warrant placement of an ICD.

Acquired LQTS

• Correct treatable medical causes quickly (e.g., electrolyte abnormalities and metabolic disturbances)!
• Remove the offending drug.

In the setting of torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia

• Hemodynamically stable patients Hemodynamically Stable Patients Blunt Chest Trauma:
  •  IV magnesium sulfate Magnesium Sulfate A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Laxatives, cardiac monitoring
  • Overdrive pacing: for those not responsive to IV magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes
• Hemodynamically unstable patients Hemodynamically Unstable Patients Blunt Chest Trauma:
  • Defibrillation Defibrillation Ventricular Fibrillation (V-fib)
  • IV magnesium sulfate Magnesium Sulfate A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Laxatives

Clinical Relevance

Predisposing factors

The following medical conditions may predispose individuals to QT prolongation:

• 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: the deficiency of T3 T3 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 and T4 T4 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. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones. 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 is diagnosed by the estimation of TSH and free T4 T4 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. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones. It is treated by the administration of synthetic T4 T4 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. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones.
• Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia: plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products 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 < 3.5 mEq/L. Risk factors for hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia include aging, poor dietary intake, diuretic use, and gastrointestinal losses. 
• Hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia: low serum ionized calcium Ionized Calcium Hypocalcemia levels. 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 levels are regulated by the parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone (PTH), which is secreted by the parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy gland. The presentation of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia can range from asymptomatic to life-threatening dysrhythmias.

Differential diagnosis

The following conditions may be included in a differential diagnosis for prolonged QT interval QT interval Electrocardiogram (ECG):

• Vasovagal syncope Vasovagal syncope Loss of consciousness due to a reduction in blood pressure that is associated with an increase in vagal tone and peripheral vasodilation. Syncope: a drop in blood pressure resulting in poor blood and oxygen flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification that results in temporary loss of consciousness. 
• 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: obstruction of coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology resulting in decreased blood supply to the 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. The typical presentation of MI MI 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 is chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, shortness of breath Shortness of breath 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, and diaphoresis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have 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 or sudden death.

Complications

Untreated QT prolongation may evolve into the following complications:

• Torsades de pointes Torsades de pointes A malignant form of polymorphic ventricular tachycardia that is characterized by heart rate between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long qt intervals exceeding 500 milliseconds or bradycardia. Torsades de pointes may be self-limited or may progress to ventricular fibrillation. Ventricular Tachycardia: a specific form of polymorphic ventricular tachycardia Polymorphic ventricular tachycardia Ventricular Tachycardia in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a long QT interval QT interval Electrocardiogram (ECG). It is characterized by rapid and irregular QRS complexes, which appear to be twisting around the baseline.
• Ventricular 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: a group of arrhythmias with heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology > 100/min that originates from within the ventricle. There are 3 main types of ventricular tachyarrhythmias: ventricular fibrillation Ventricular fibrillation Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular Fibrillation (V-fib), monomorphic ventricular tachycardia Monomorphic ventricular tachycardia Ventricular Tachycardia, and polymorphic ventricular tachycardia Polymorphic ventricular tachycardia Ventricular Tachycardia. 
• 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 sudden complete cessation of cardiac activity with hemodynamic collapse. Cardiac rhythms known to produce a pulseless 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 are shockable rhythms Shockable Rhythms Cardiac Arrest ( ventricular fibrillation Ventricular fibrillation Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular Fibrillation (V-fib), pulseless ventricular 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) and non-shockable rhythms ( pulseless electrical activity Pulseless electrical activity Electrocardiogram (ECG) shows a cardiac rhythm without a palpable pulse. May be organized (with normal-appearing ECG complexes) or unorganized (no discernible complexes on ecg). From electromechanical dissociation, or no cardiac filling (“empty heart”). Cardiac Arrest, asystole Asystole No discernible electrical activity, flatline on electrocardiogram (P waves and QRS complexes are not present). Cardiac Arrest). Rapid identification Identification Defense Mechanisms and intervention are critical to saving a patient’s life.