Long QT syndrome (Clinical)

Definitions

• Long QT syndrome Long QT syndrome Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces QT prolongation on electrocardiogram (ECG). Long QT syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome ( LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome): 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))^[4,6]
• 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome
  • Form of polymorphic ventricular tachycardia Polymorphic ventricular tachycardia Ventricular Tachycardia
  • Caused by early afterdepolarizations
  • Irregular QRS complexes “twisting” around the isoelectric line ( 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 = “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 long QT syndrome Congenital long QT syndrome Long QT Syndrome^[6,13,17]

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 afterdepolarizations →  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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 (K) 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 (Na) 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 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome

Types of congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome:

1. Type 1 Type 1 Spinal Muscular Atrophy is the most common congenital Congenital Chorioretinitis form.
   • Up to 45% of LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 Romano-Ward syndrome A form of long qt syndrome that is without congenital deafness. It is caused by mutation of the kcnq1 gene which encodes a protein in the voltage-gated potassium channel. Long QT Syndrome: 99% of cases; congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome + 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome + periodic paralysis
• Timothy syndrome Timothy syndrome Long QT Syndrome: congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome + 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 Acquired long QT syndrome Long QT Syndrome^[1–3,17]

• 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 ( amiodarone Amiodarone An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting potassium channels and voltage-gated sodium channels. There is a resulting decrease in heart rate and in vascular resistance. Pulmonary Fibrosis, sotalol Sotalol An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers), procainamide Procainamide A class ia antiarrhythmic drug that is structurally-related to procaine. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers), flecainide Flecainide A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers))
    • 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: ketoconazole Ketoconazole Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. Azoles, itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
    • HIV HIV Anti-HIV Drugs antiretroviral drugs (e.g., saquinavir Saquinavir An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits cytochrome p-450 cyp3a. Anti-HIV 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: chloroquine Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Antimalarial Drugs and hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants
    • 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 (e.g., anthracyclines Anthracyclines Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. Antitumor Antibiotics, ivosidenib, lenvatinib, mobocertinib, selpercatinib, vandetanib)
    • Beta-2 agonists
• 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 Presentation

Congenital long QT syndrome Congenital long QT syndrome Long QT Syndrome^[6,7,17]

• 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 Acquired long QT syndrome Long QT Syndrome^[6,7,13]

• 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 Long QT syndrome Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces QT prolongation on electrocardiogram (ECG). Long QT syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. 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^{[4,6,13,14,17]}

• 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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 LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome

Exercise testing^[13,14]

• To assess exercise-associated arrhythmias
• To check QT responses (exercise and recovery) and changes in T wave T wave Electrocardiogram (ECG)
• At 2–5 minutes of recovery:
  • The interval when cardiac events commonly occur during exercise
  • QTc > 470 msec is suggestive of LQTS1
• 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 responses are seen with congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome.

Genetic analysis^[13,14]

• For intermediate and highly suspicious cases of congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome 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

Schwartz score^[13,14]

The Schwartz score is used to estimate the likelihood of congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome.

• ≤ 1: low probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies not recommended
• 1.5‒3: intermediate probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → warrants further testing, including genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies
• ≥ 3.5: high probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability → likelihood of positive genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is approximately 80%

Additional tests

• 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 Vessels)

Management

The following information is based on US and UK recommendations. Management may vary depending on practice location, so care should be taken to follow local clinical guidelines.

Congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome^[5,8,9,13]

Reduce the risk of fatal arrhythmias:

• Avoid QT-prolonging drugs
• Electrolyte repletion (e.g., 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 with vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, or diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication)
• Avoid arrhythmia triggers:
  • Swimming/exercise
  • Emotional distress, noise
  • LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome specialist consultation needed for sports participation 

1st-line medications: beta blockers (BBs)

• 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 with congenital Congenital Chorioretinitis LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome and a history of 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 seizure
• Preferred agents for all 3 genotypes ( patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with LQTS1 have the greatest benefit, but also effective for types 2 and 3)
• Options:
  • 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:
    • Children:  Initial: 0.5–1 mg/kg/day in divided doses every 6–8 hours; titrate dosage Dosage Dosage Calculation upward every 3–5 days; usual dose is 2–4 mg/kg/day; maximum dose, 16 mg/kg/day or 60 mg/day
    • Adults: 10–40 mg orally 3–4 times a day or extended-release form once daily 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):
    • Children: 0.5–1 mg/kg/day orally daily or in 2 divided doses, maximum dose, 2.5 mg/kg/day (based on doses for supraventricular 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, no data available for LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome)
    • Adults: 40–240 mg daily in single dose or 2 divided doses
  • Atenolol Atenolol A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. Class 2 Antiarrhythmic Drugs (Beta Blockers) and metoprolol Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat angina pectoris; hypertension; and cardiac arrhythmias. Antiadrenergic Drugs are not recommended and are associated with increased recurrence rates.

Subsequent therapies (if unable to tolerate BBs or arrhythmias recur despite their use):

• Concomitant drug therapy (consider in consultation with cardiology):
  • Mexiletine Mexiletine Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers): 4–6 mg/kg every 8 hours; protective effect for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with LQTS3
  • Flecainide Flecainide A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers)
  • Ranolazine
  • Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics: not generally indicated, but may be used as a potassium-retention strategy
• Left cardiac sympathetic denervation (LCSD):
  • Effective for persistent arrhythmias on BBs or intolerance to BBs
  • Interrupts the major source of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS released in the heart
  • Reduces the number of subsequent cardiac events overall
  • Similarly effective for all 3 genotypes (excluding infants under 12 months)
  • May be indicated in asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with LQTS2 or LQTS3 and a QTc > 550 msec while on BBs
  • 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 may still need an ICD.
• ICD:
  • Indicated for:
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with LQTS-associated 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) despite adherence to BB therapy
    • Self-limiting Self-Limiting Meningitis in Children 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/ seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures are not equivalent to SCA
    • Recurrent 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 despite BB and LCSD therapy
  • Complications ( incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency, 25% in 5 years):
    • Infection
    • Lead fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures and dislodgment
    • Inappropriate discharges
  • Never indicated based solely on family history Family History Adult Health Maintenance

Physical activity after establishing the correct diagnosis:

• Individuals with LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome can continue to be recreationally active.
• Children and adolescents can resume physical education after diagnosis.
• Athletes with LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome should be evaluated by an LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome specialist; US and European guidelines differ:
  • United States: Based on the 2015 AHA/ACC scientific statement:^[10,11]
    • Asymptomatic individuals who are genotype-positive but have normal QTc at rest can participate in all competitive sports with appropriate safety precautions (e.g., avoid hyperthermia, electrolyte depletion, dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration)
    • AED AED Cardiac electrical stimulators that apply brief high-voltage electroshocks to the heart. These stimulators are used to restore normal rhythm and contractile function in hearts of patients who are experiencing ventricular fibrillation or ventricular tachycardia that is not accompanied by a palpable pulse. Some defibrillators may also be used to correct certain noncritical dysrhythmias (called synchronized defibrillation or cardioversion), using relatively low-level discharges synchronized to the patient’s ECG waveform. Cardiopulmonary Resuscitation (CPR) (automated external defibrillator Defibrillator Cardiac electrical stimulators that apply brief high-voltage electroshocks to the heart. These stimulators are used to restore normal rhythm and contractile function in hearts of patients who are experiencing ventricular fibrillation or ventricular tachycardia that is not accompanied by a palpable pulse. Some defibrillators may also be used to correct certain noncritical dysrhythmias (called synchronized defibrillation or cardioversion), using relatively low-level discharges synchronized to the patient’s ECG waveform. Cardiac Arrest) must be immediately available at sites of training and competing.
    • Symptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may participate in competitive athletics (except for swimming with LQTS1 genotype Genotype The genetic constitution of the individual, comprising the alleles present at each genetic locus. Basic Terms of Genetics) if asymptomatic for 3 months on treatment.
  • Europe: Advise precautionary restriction from all competitive sports.^[12]
• Experts disagree on participation in higher levels of sport for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with an ICD in place.

Acquired LQTS LQTS Long qt syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces qt prolongation on electrocardiogram (ECG). Long qt syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. Long QT Syndrome^[5,15]

Treat causes if known:

• Discontinue QT-prolonging drugs
• Treat 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 and 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

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:

• Hemodynamically unstable patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • CPR CPR The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. Cardiac Arrest/ defibrillation Defibrillation Ventricular Fibrillation (V-fib)
  • 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 IV:
    • Adult dose: 1–2 g over 5–20 minutes 
    • May be repeated if 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 recurs or QT remains prolonged 
• Hemodynamically stable patients Hemodynamically Stable Patients Blunt Chest Trauma:
  • 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 IV:
    • Adult dose: 1–2 g over 5–60 minutes 
    • May be repeated if 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 recurs or QT remains prolonged
    • Continuous infusion may be considered
  • 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

Prevention^[16,17]

• 3 key factors to consider when prescribing drugs associated with QT prolongation:
  • Patient-related risk factors:
    • Female sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria (70% more common than in males)
    • Age > 65 years
    • Uncorrected electrolyte disturbances
  • The potential risk and degree of QT prolongation associated with the proposed drug
  • Co-prescribed medicines that could increase the risk of QT prolongation
• Some websites, such as crediblemeds.org, list medications which have been reported to prolong the QT interval QT interval Electrocardiogram (ECG).

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: 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 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 lab testing showing high TSH and low FT4. It is treated with oral levothyroxine Levothyroxine Thyroid Replacement Therapy (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: 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 < 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 diuretic use, poor dietary intake, and GI 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: diagnosed by 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 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) 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 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.
• Other factors: female sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, low left ventricular ejection fraction Ejection fraction Cardiac Cycle, left ventricular hypertrophy Ventricular Hypertrophy Tetralogy of Fallot, 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, slow heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology

Differential diagnosis

• 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

• 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.