Torsade (Torsade De Pointes)

General Information

History

1966: first described in France by Dessertenne

Definitions

Torsade De Pointes: “twisting of the points”
Torsade is a Type of Polymorphic Ventricular Tachycardia Which Occurs in the Setting of Congenital or Acquired QT Prolongation
- Polymorphic VT: rate >100 bpm with frequent variation of the QRS morphology and/or QRS axis
- Torsade: sinusoidal, cyclical variation of QRS axis, with the peaks of the QRS appearing to turn around the isoelectric line of the waveform (i.e. “twisting of the points”)

Risk Factors for Torsade

Age >65 y/o
Bradycardic States
- Heart Blocks
  - First Degree Atrioventricular Block (see First Degree Atrioventricular Block, [[First Degree Atrioventricular Block]])
  - Incomplete Heart Block with Pauses
  - Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I, [[Second Degree Atrioventricular Block-Mobitz Type I]])
  - Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II, [[Second Degree Atrioventricular Block-Mobitz Type II]])
  - Third Degree Atrioventricular Block/Complete Heart Block (see Third Degree Atrioventricular Block, [[Third Degree Atrioventricular Block]])
- Premature Ventricular Contractions (PVC’s) with Short-Long-Short-Cycles (see Premature Ventricular Contraction, [[Premature Ventricular Contraction]])
- Sinus Bradycardia(see Sinus Bradycardia, [[Sinus Bradycardia]])
Clinically-Silent Risk Factors
- Genetic Polymorphisms Which Result in Reduced Repolarization Reserve
- Occult Congenital Long QT Syndrome
Diuretic Administration: due to direct blockade of potassium current by some diuretics (example: indapamide)
Drug-Related Factors
- High Dose/Concentration of QT Prolonging Medication
  - Exception: quinidine-induced torsade often occurs at low drug concentrations
- Inhibition/Induction of Cytochrome P450 Enzyme
  - Example: erythromycin inhibits cytochrome P450 (and causes direct QT prolongation)
- Multiplicity of Pharmacological Actions
- Narrow Therapeutic Window
- Polypharmacy
- Rapid Intravenous Infusion of QT Prolonging Medication
Female Sex: 2x greater risk than in males
- Sex-Related Differences in Cardiac Ion Channel Densities
- Females
  - Females have longer QT intervals than males and greater response to drugs which block the IKr current
  - Estrogen potentiates the QT prolongation induced by bradycardia
- Males: androgens shorten the QT interval
Grapefruit Juice Ingestion (see Grapefruit, [[Grapefruit]]): flavonoids in juice inhibit CYP3A4 (slowing metabolism of other medications) and directly inhibit the IKr channel -> QT prolongation
Impairment of Drug Metabolism
- Chronic Kidney Disease (CKD) (see Chronic Kidney Disease, [[Chronic Kidney Disease]])
- Cirrhosis/Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
Metabolic Abnormalities
- Hypokalemia (see Hypokalemia, [[Hypokalemia]])
  - Risk of torsade is highest in the setting of antiarrhythmic administration
  - Probably related to enhanced drug-induced blockade of IKr current
- Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]])
- Hypomagnesemia (see Hypomagnesemia, [[Hypomagnesemia]])
  - Risk of torsade is highest in the setting of antiarrhythmic administration
Organic Heart Disease
- Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]]): common risk factor for drug-induced torsade
- Dilated Cardiomyopathy (see Congestive Heart Failure, [[Congestive Heart Failure]])
- Hypertrophic Cardiomyopathy (see Hypertrophic Cardiomyopathy, [[Hypertrophic Cardiomyopathy]])
- Ischemic Heart Disease (see Coronary Artery Disease, [[Coronary Artery Disease]]): torsade is an uncommon myocardial ischemia-associated rhythm (when it occurs, it may be associated with either a normal or prolonged QT interval and recurrent myocardial ischemia)
  - Myocardial Infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]])
  - Myocardial Ischemia (see Coronary Artery Disease, [[Coronary Artery Disease]])
- Kawasaki Disease (see Kawasaki Disease, [[Kawasaki Disease]])
- Left Ventricular Hypertrophy (LVH): common risk factor for drug-induced torsade
- Myocarditis (see Myocarditis, [[Myocarditis]])
- Takotsubo Cardiomyopathy (Stress-Induced Cardiomyopathy) (see Takotsubo Cardiomyopathy, [[Takotsubo Cardiomyopathy]])
QTc >500 msec: especially with long QT syndrome 2-type repolarization pattern (notching, long Tpeak-Tend)
Recent Conversion from Atrial Fibrillation (see Atrial Fibrillation, [[Atrial Fibrillation]])

Etiology

Congenital Long QT Syndrome (see Congenital Long QT Syndrome, [[Congenital Long QT Syndrome]])

Jervell and Lange-Neilsen Syndrome: autosomal recessive
Romano-Ward Syndrome: autosomal dominant
Idiopathic Congenital Long QT Syndrome

Autoimmune Disease with Anti-Ro/SSA Antibodies

General Comments: anti-Ro/SSA antibodies may inhibit IKr current via interaction with the cardiac myocyte “human ether-a-go-go–related gene” (ERG) potassium channel -> this interferes with ventricular repolarization
Mixed Connective Tissue Disease (MCTD) (see Mixed Connective Tissue Disease, [[Mixed Connective Tissue Disease]])
Primary Biliary Cirrhosis (see Primary Biliary Cirrhosis, [[Primary Biliary Cirrhosis]])
Sjogren’s Syndrome (see Sjogren’s Syndrome, [[Sjogrens Syndrome]])
Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])

Endocrine/Metabolic

Anorexia Nervosa (see Anorexia Nervosa, [[Anorexia Nervosa]])
Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]])
Hypokalemia (see Hypokalemia, [[Hypokalemia]])
- Risk of torsade is highest in the setting of antiarrhythmic administration
- Probably related to enhanced drug-induced blockade of IKr current
Hypomagnesemia (see Hypomagnesemia, [[Hypomagnesemia]])
- Risk of torsade is highest in the setting of antiarrhythmic administration
Hypothyroidism (see Hypothyroidism, [[Hypothyroidism]])
Liquid Protein Diets
Starvation

Bradyarrhythmia

Sinus Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]])
Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I, [[Second Degree Atrioventricular Block-Mobitz Type I]])
Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II, [[Second Degree Atrioventricular Block-Mobitz Type II]])
Third Degree Atrioventricular Block/Complete Heart Block (see Third Degree Atrioventricular Block, [[Third Degree Atrioventricular Block]])

Intracranial Disease

Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage, [[Intracerebral Hemorrhage]]): QT prolongation is common in intracerebral hemorrhage (being present in 64% of cases)
Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]]): QT prolongation is common in ischemic CVA (being present in approximately 38% of cases)
Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage, [[Subarachnoid Hemorrhage]]): QT prolongation is common in SAH (being present in 71% of cases)

Organic Heart Disease

Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
Dilated Cardiomyopathy (see Congestive Heart Failure, [[Congestive Heart Failure]])
Hypertrophic Cardiomyopathy (see Hypertrophic Cardiomyopathy, [[Hypertrophic Cardiomyopathy]])
Ischemic Heart Disease (see Coronary Artery Disease, [[Coronary Artery Disease]]): torsade is an uncommon myocardial ischemia-associated rhythm (when it occurs, it may be associated with either a normal or prolonged QT interval and recurrent myocardial ischemia)
- Myocardial Infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]])
- Myocardial Ischemia (see Coronary Artery Disease, [[Coronary Artery Disease]])
Kawasaki Disease (see Kawasaki Disease, [[Kawasaki Disease]])
Left Ventricular Hypertrophy (LVH)
Myocarditis (see Myocarditis, [[Myocarditis]])
Takotsubo Cardiomyopathy (Stress-Induced Cardiomyopathy) (see Takotsubo Cardiomyopathy, [[Takotsubo Cardiomyopathy]])

QT Prolonging Drugs and Toxins (@ = definite association with torsade)

Anorexigens

Fenfluramine (Pondimin, Ponderax, Adifax) (see Fenfluramine, [[Fenfluramine]])
Phentermine (see Phentermine, [[Phentermine]])
Sibutramine (Meridia)

Anti-Arrhythmics

Type 1A Anti-Arrhythmics: Fast Sodium Channel Blockers Which Depress Phase 0, Prolonging Repolarization
- Disopyramide (Norpace) @ (see Disopyramide, [[Disopyramide]])
- Procainamide (Pronestyl) @ (see Procainamide, [[Procainamide]])
- Quinidine (Quinaglute, Quinidex) @ (see Quinidine, [[Quinidine]]): most frequently implicated cause of drug-induced torsade
Type 1B Anti-Arrhythmics: Fast Sodium Channel Blockers Which Depress Phase 0 Selectively in Abnormal/Ischemic Tissue, Shortening Repolarization
- Mexiletine (see Mexiletine, [[Mexiletine]])
Type 1C Anti-Arrhythmics: Fast Sodium Channel Blockers Which Markedly Depress Phase 0 with Minimal Effect on Repolarization/Prolong QRS -> QT Prolongation
- Encainide
- Flecainide (see Flecainide, [[Flecainide]])
- Propafenone (Rythmol, Rytmonorm( (see Propafenone, [[Propafenone]])
Type 3 Anti-Arrhythmics: Potassium Channel Blockers
- Amiodarone (Cordarone) @ (see Amiodarone, [[Amiodarone]]): while chronic amiodarone administration markedly prolongs the QT interval, torsade occurs in <1% of cases
- Bretylium @ (see Bretylium, [[Bretylium]])
- Dofetilide (Tikosyn) @ (see Dofetilide, [[Dofetilide]]): torsade occurs in 0.3-10.5% of cases
- Ibutilide (Corvert) @ (see Ibutilide, [[Ibutilide]]): torsade occurs in 0.9-2.5% of cases
- Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) @ (see Sotalol, [[Sotalol]])
Other: Multichannel Sodium/Potassium/Calcium Channel Blockade with Anti-Adrenergic Activity
- Dronedarone (Multaq) (see Dronedarone, [[Dronedarone]])

Antihistamines (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])

Astemizole (Hismanal) @ (see Astemizole, [[Astemizole]]): withdrawn from US market
Diphenhydramine (Benadryl) @ (see Diphenhydramine, [[Diphenhydramine]])
Ebastine
Hydroxyzine (Atarax, Vistaril) (see Hydroxyzine, [[Hydroxyzine]])
Loratidine (Claritin) @ (see Loratidine, [[Loratidine]])
Mizolastine
Promethazine (Phenergan) (see Promethazine, [[Promethazine]])
Terfenadine (Seldane) @ (see Terfenadine, [[Terfenadine]]): withdrawn from US market

Antimicrobials

Anti-Malarials
- Artemether
- Chloroquine (Aralen) @ (see Chloroquine, [[Chloroquine]]): anti-malarial
- Delamanid: possible risk of prolonged QT
- Halofantrine @: anti-malarial
- Hydroxychloroquine (see Hydroxychloroquine, [[Hydroxychloroquine]]): possible risk of prolonged QT
- Lumefantrine
- Mefloquine (see Mefloquine, [[Mefloquine]]): possible risk of prolonged QT
- Primaquine (see Primaquine, [[Primaquine]]): possible risk of prolonged QT
- Quinine (see Quinine, [[Quinine]])
Azole Anti-Fungals (see Azole Anti-Fungals, [[Azole Anti-Fungals]])
- Fluconazole (Diflucan, Trican) @ (see Fluconazole, [[Fluconazole]])
- Itraconazole (Sporanox) (see Itraconazole, [[Itraconazole]])
- Ketoconazole (Nizoral) (see Ketoconazole, [[Ketoconazole]]): systemic
- Posaconazole (Noxafil, Posanol) (see Posaconazole, [[Posaconazole]])
- Voriconazole (Vfend) (see Voriconazole, [[Voriconazole]])
Fluoroquinolones @ (see Fluoroquinolones, [[Fluoroquinolones]])
- General Comments: the risk of Q-T prolongation with fluoroquinolones is mainly related to additive effects with other Q-T prolonging drugs, as the risk when used alone is small
- High Risk
  - Gatifloxacin (Tequin) (see Gatifloxacin, [[Gatifloxacin]])
  - Grepafloxacin (Raxar) (see Grepafloxacin, [[Grepafloxacin]])
  - Moxifloxacin (Avelox, Avalox, Avelon) (see Moxifloxacin, [[Moxifloxacin]])
  - Sparfloxacin (Spacin, Zagam) (see Sparfloxacin, [[Sparfloxacin]])
- Medium Risk
  - Gemifloxacin (Factive) (see Gemifloxacin, [[Gemifloxacin]])
  - Levofloxacin (Levaquin) (see Levofloxacin, [[Levofloxacin]])
  - Ofloxacin (Floxin, Ocuflox) (see Ofloxacin, [[Ofloxacin]])
  - Sitafloxacin (Gracevit) (see Sitafloxacin, [[Sitafloxacin]])
  - Tosufloxacin (Ozex) (see Tosufloxacin, [[Tosufloxacin]])
- Low Risk
  - Ciprofloxacin (Cipro) (see Ciprofloxacin, [[Ciprofloxacin]])
Human Immunodeficiency Virus (HIV) Medications
- Lopinavir (see Lopinavir + Ritonavir, [[Lopinavir + Ritonavir]])
- Nelfinavir (Viracept) (see Nelfinavir, [[Nelfinavir]])
- Saquinavir (Invirase, Fortovase) (see Saquinavir, [[Saquinavir]])
Macrolides (see Macrolides, [[Macrolides]])
- Azithromycin (Zithromax) @ (see Azithromycin, [[Azithromycin]])
- Clarithromycin (Biaxin) @ (see Clarithromycin, [[Clarithromycin]])
- Erythromycin @ (see Erythromycin, [[Erythromycin]])
- Roxithromycin (Biaxsig, Coroxin, Romac, Roxar, Roximycin, Roxl-150, Roxo, Roxomycin, Rulid, Rulide, Surlid, Tirabicin, Xthrocin) @ (see Roxithromycin, [[Roxithromycin]])
- Telithromycin (Ketek) (see Telithromycin, [[Telithromycin]])
Other Antimicrobials
- Bedaquiline
- Foscarnet (Foscavir) (see Foscarnet, [[Foscarnet]])
- Metronidazole (Flagyl) (see Metronidazole, [[Metronidazole]])
- Pentamidine @ (see Pentamidine, [[Pentamidine]]): intravenous
- Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim, [[Sulfamethoxazole-Trimethoprim]])
- Telavancin (Vibativ) (see Telavancin, [[Telavancin]])

Anti-Muscarinics

Solifenacin (Vesicare) (see Solifenacin, [[Solifenacin]])
Tolterodine (Detrol, Detrusitol) (see Tolterodine, [[Tolterodine]])

Anti-Neoplastic Agents

Arsenic Trioxide (Trisenox) @ (see Arsenic, [[Arsenic]])
Ceritinib (Zykadia) (see Ceritinib, [[Ceritinib]])
Cesium Chloride
Crizotinib (Xalkori) (see Crizotinib, [[Crizotinib]])
Dasatinib (Sprycel) (see Dasatinib, [[Dasatinib]])
Eribulin
Nilotinib (Tasigna) (see Nilotinib, [[Nilotinib]])
Lapatinib (Tykerb, Tyverb) (see Lapatinib, [[Lapatinib]])
Panabinostat
Pazopanib (Votrient) (see Pazopanib, [[Pazopanib]])
Romidepsin
Sorafenib (Nexavar) (see Sorafenib, [[Sorafenib]])
Sunitinib (Sutent) (see Sunitinib, [[Sunitinib]])
Toremifene
Vandetanib
Vemurafenib
Vorinostat

β2 Agonists (see β2-Adrenergic Receptor Agonists, [[β2-Adrenergic Receptor Agonists]])

Short-Acting β2-Adrenergic Receptor Agonists (SABA)
- Albuterol (Salbutamol, Ventolin) (see Albuterol, [[Albuterol]])
- Bitolterol
- Fenoterol
- Isoprenaline
- Levalbuterol (Xopenex) (see Levalbuterol, [[Levalbuterol]])
- Metaproterenol (Alupent) (see Metaproterenol, [[Metaproterenol]])
- Pirbuterol (Maxair)
- Procaterol
- Ritodrine
- Terbutaline (Brethine, Bricanyl, Brethaire, Terbulin) (see Terbutaline, [[Terbutaline]])
Long-Acting β2-Adrenergic Receptor Agonists (LABA)
- Arformoterol (Brovana, Erdotin) (see Arformoterol, [[Arformoterol]])
- Bambuterol (Bambec, Oxeol)
- Clenbuterol (Spiropent, Ventipulmin)
- Formoterol (Foradil, Oxeze, Oxis, Atock, Atimos, Perforomist) (see Formoterol, [[Formoterol]])
- Olodaterol (Striverdi Respimat) (see Olodaterol, [[Olodaterol]])
- Salmeterol (Serevent) (see Salmeterol, [[Salmeterol]])
- Vilanterol (see Vilanterol, [[Vilanterol]])
Ultra Long-Acting Beta Agonists
- Indacaterol (Arcapta) (see Indacaterol, [[Indacaterol]])

Calcium Channel Blockers (see Calcium Channel Blockers, [[Calcium Channel Blockers]])

Bepridil (Vascor) @: withdrawn from US market
Isradipine (DynaCirc, Prescal) (see Isradipine, [[Isradipine]])
Prenylamine @: withdrawn from US market
Terodiline @: withdrawn from US market

Gonadotropin-Releasing Hormone Agonists/Antagonists

Buserelin
Degarelix
Goserelin
Histrelin
Leuprolide (Leuprorelin, Lupron) (see Leuprolide, [[Leuprolide]])
Triptorelin

Neurologic Medications

Apomorphine (see Apomorphine, [[Apomorphine]])
Donepezil (Aricept) (see Donepezil, [[Donepezil]])
Fingolimod
Tetrabenazine

Opiates (see Opiates, [[Opiates]])

Levomethadyl (Orlaam) @: withdrawn from US market
Methadone @ (see Methadone, [[Methadone]])

Psychiatric Drugs

Butryophenones
- Droperidol (Inapsine, Droleptan, Dridol, Xomolix, Innovar) @ (Droperidol, [[Droperidol]]): butyrophenone antipsychotic and antiemetic
- Haloperidol (Haldol) @ (see Haloperidol, [[Haloperidol]]): butyrophenone antipsychotic
Phenothiazines (see Phenothiazines, [[Phenothiazines]])
- Chlorpromazine @ (Thorazine) (see Chlorpromazine, [[Chlorpromazine]])
- Mesoridazine @ (Serentil)
- Prochlorperazine (Compazine) (see Prochlorperazine, [[Prochlorperazine]])
- Thioridazine (Mellaril) @ (see Thioridazine, [[Thioridazine]])
Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) (see Serotonin-Norepinephrine Reuptake Inhibitors, [[Serotonin-Norepinephrine Reuptake Inhibitors]]
- Venlafaxine (Effexor) (see Venlafaxine, [[Venlafaxine]])
- Sibutramine (Meridia)
Selective Serotonin Reuptake Inhibitors (SSRI) (see Selective Serotonin Reuptake Inhibitors, [[Selective Serotonin Reuptake Inhibitors]]
- Citalopram (Celexa) (see Citalopram, [[Citalopram]])
- Fluoxetine (Prozac) @ (see Fluoxetine, [[Fluoxetine]])
- Paroxetine (Paxil) (see Paroxetine, [[Paroxetine]])
- Sertraline (Zoloft) (see Sertraline, [[Sertraline]])
Tricyclic Antidepressants (see Tricyclic Antidepressants, [[Tricyclic Antidepressants]])
- Amitriptyline (Tryptomer, Elavil) (see Amitriptyline, [[Amitriptyline]])
- Clomipramine (Anafranil) (see Clomipramine, [[Clomipramine]])
- Desipramine (Norpramin, Pertofrane) @ (see Desipramine, [[Desipramine]])
- Doxepin (Adapin, Sinequan) @ (see Doxepin, [[Doxepin]])
- Imipramine (Tofranil, Janimine, Praminil) @ (see Imipramine, [[Imipramine]])
- Nortriptyline (Pamelor, Aventyl, Norpress) (see Nortriptyline, [[Nortriptyline]])
- Protriptyline (Vivactil) (see Protriptyline, [[Protriptyline]])
- Trimipramine (Surmontil) (see Trimipramine, [[Trimipramine]])
Other Psychiatric Drugs
- Amoxapine (see Amoxapine, [[Amoxapine]])
- Aripiprazole (Abilify) (see Aripiprazole, [[Aripiprazole]]): possible risk of prolonged QT
- Atomoxetine
- Chloral Hydrate (see Chloral Hydrate, [[Chloral Hydrate]])
- Clozapine (Clozaril) (see Clozapine, [[Clozapine]])
- Lithium @ (see Lithium, [[Lithium]])
- Maprotiline @
- Olanzapine (Zyprexa) (see Olanzapine, [[Olanzapine]]): possible risk of prolonged QT
- Pimozide (Orap) @: diphenylbutylpiperidine antipsychotic
- Quetiapine (Seroquel) (see Quetiapine, [[Quetiapine]])
- Risperidone (Risperdal) (see Risperidone, [[Risperidone]])
- Sertindole @
- Trazodone (see Trazodone, [[Trazodone]])
- Ziprasidone (Geodon, Zeldox) (see Ziprasidone, [[Ziprasidone]])

Serotonin 5-HT3 Receptor Antagonists (see Serotonin 5-HT3 Receptor Antagonists, [[Serotonin 5-HT3 Receptor Antagonists]])

Dolasetron (Anzemet) (see Dolasetron, [[Dolasetron]])
Granisetron (Kytril, Sancuso) (see Granisetron, [[Granisetron]])
Ondansetron (Zofran) (see Ondansetron, [[Ondansetron]])
Tropisetron

Sympathomimetics

Amphetamine (see Amphetamine, [[Amphetamine]]): increases dopamine release
Cocaine (see Cocaine, [[Cocaine]])
Methylphenidate (Ritalin) (see Methylphenidate, [[Methylphenidate]]): norepinephrine and dopamine reuptake inhibitor

Vasoactive Drugs

Dopamine (see Dopamine, [[Dopamine]])
Dobutamine (see Dobutamine, [[Dobutamine]])
Ephedrine (see Ephedrine, [[Ephedrine]])
Epinephrine (see Epinephrine, [[Epinephrine]])
Isoproterenol (see Isoproterenol, [[Isoproterenol]])
Midodrine (see Midodrine, [[Midodrine]])
Nicardipine (see Nicardipine, [[Nicardipine]])
Norepinephrine (see Norepinephrine, [[Norepinephrine]])
Phenylephrine (Neosynephrine) (see Phenylephrine, [[Phenylephrine]])
Vasopressin @ (see Vasopressin, [[Vasopressin]])

Other Medications

Alfuzosin (see Alfuzosin, [[Alfuzosin]])
Adenosine (see Adenosine, [[Adenosine]])
Amantadine (Symmetrel) @ (see Amantadine, [[Amantadine]])
Anagrelide
Atomoxetine (Strattera): selective norepinephrine reuptake inhibitor (NRI)
Bepridil (Vascor)
Cilostazol
Cisapride (Prepulsid, Propulsid) @: withdrawn from US market
Digoxin (Lanoxin) @ (see Digoxin, [[Digoxin]])
Domperidone @ (Motilium, Motillium, Motinorm Costi, Nomit) (see Domperidone, [[Domperidone]]): dopamine antagonist (derived from butyrophenone)
Fosphenytoin (see Fosphenytoin, [[Fosphenytoin]])
Furosemide (Lasix) @ (see Furosemide, [[Furosemide]])
Galantamine (Razadyne)
Indapamide: thiazide-like diuretic
Ivabradine (Corlanor) (see Ivabradine, [[Ivabradine]])
Metoclopramide (Reglan) (see Metoclopramide, [[Metoclopramide]])
Mifepristone
Moexipril (Univasc) (see Moexipril, [[Moexipril]])
Octreotide (see Octreotide, [[Octreotide]])
Papaverine (Pavabid) @: intravenous
Pasireotide
Phenylpropanolamine (see Phenylpropanolamine, [[Phenylpropanolamine]])
Probucol @
Propofol (Diprivan) (see Propofol, [[Propofol]])
Pseudoephedrine (see Pseudoephedrine, [[Pseudoephedrine]])
Ranolazine (Ranexa) (see Ranolazine, [[Ranolazine]])
Tamoxifen (see Tamoxifen, [[Tamoxifen]])
Tacrolimus @ (see Tacrolimus, [[Tacrolimus]])
Terlipressin (see Terlipressin, [[Terlipressin]])
Tizanidine (Zanaflex) (see Tizanidine, [[Tizanidine]])
Vardenafil (Levitra, Staxyn) (see Vardenafil, [[Vardenafil]]): PDE5 inihibitor

Toxins

Cinchona: contains quinine
Organophosphates (see Organophosphates, [[Organophosphates]])

Other QT Prolonging Conditions

Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
Hypothermia (see Hypothermia, [[Hypothermia]])

Physiology

Drug-Induced Blockade of Outward IKr Potassium Current (Mediated by the Potassium Channel Encoded by the KCNH2 Gene)

Almost All QT Prolonging Medications Do So by Blocking the Outward IKr Potassium Current
- The Degree of Drug Blockade of the IKr Current is Inversely Proportional to the Extracellular Potassium Concentration and the Heart Rate
Reverse Use Dependence: defined as the correlation between the heart rate and the QT interval -> this physiologic feature explains why torsade is more commonly observed in bradycardic states
- As Heart Rate Decreases, the QT Interval Prolongs: lower heart rate results in less potassium moving out of the myocardial cell during repolarization -> results in decreased extracellular potassium concentration, enhancing the degree of drug-induced inhibition of IKr -> prolonged QT interval
- As Heart Rate Increases, the QT Interval Shortens

Clinical Precipitants of Torsade in Acquired Long QT States

Short-Long RR Intervals: usually a premature ventricular contraction (PVC) followed by a compensatory pause
Bradycardia or Frequent Pauses: in this respect, torsade in acquired long QT states is sometimes called “pause-dependent”

Clinical Precipitants of Torsade in Some Congenital Long QT Syndromes (Long QT Syndrome Types 1 and 2)

Adrenergic Surge: due to exercise or arousal
However, some congenital long QT syndrome cases demonstrate “pause-dependent” torsade

Diagnosis

Electrocardiogram (EKG) (see Electrocardiogram, [[Electrocardiogram]])

Appearance: cyclical variation of QRS axis, with the peaks of the QRS appearing to turn 180 degrees around the isoelectric line of the waveform approximately every 5-20 beats
Rate: 160-250 bpm
RR Intervals: irregular

Relationship of QT Interval to Risk of Torsade

Normal QTc: 440-460 msec (0.44-0.46 sec)
- Criterion for Prolonged QT in Males (AHA/ACC 2011 Criteria): QTc >470 msec
- Criterion for Prolonged QT in Females (AHA/ACC 2011 Criteria): QTc >480 msec
Risk of Torsade Does Not Correlate Predictably with the QTc: however, the risk of torsade is believed to be highest when the QTc >500 msec

Clinical Manifestations

Cardiovascular Manifestations

Syncope (see Syncope, [[Syncope]])
Cardiovascular Complications
- Degeneration to Ventricular Fibrillation (see Ventricular Fibrillation, [[Ventricular Fibrillation]])
- Degeneration to Sudden Cardiac Death (see Sudden Cardiac Death, [[Sudden Cardiac Death]])

Treatment

Congenital Long QT Syndrome

Beta Blockers (see xxxx, [[xxxx]])

xxx

Mexiletine (Mexitil) (see Mexiletine, [[Mexiletine]])

xxxx

Permanent Dual Chamber Pacemaker

xxx

Left Chamber Sympathetic Denervation (Cardiothoracic Sympathectomy)

xxx

Automatic Implantable Cardioverter-Defibrillator (AICD) (see Automatic Implantable Cardioverter-Defibrillator, [[Automatic Implantable Cardioverter-Defibrillator]])

xxx

Acquired Long QT State

Defibrillation

Indication: hemodynamically-unstable torsade
- Note: arhythmias with a polymorphic QRS appearance (such as torsades) will usually not allow synchronization -> therefore, it is recommended to treat the rhythm similar to VF and deliver high-energy unsynchronized shocks (i.e. defibrillation dose)

Magnesium (see Magnesium Sulfate, [[Magnesium Sulfate]])

Indication: considered first line therapy for torsade
- Benefit Occurs without Shortening of the QT Interval
- Benefit is Observed Even in Patients with Normal Serum Magnesium
Mechanism: unknown
Administration: 2 g IV (in 10 ml D5W) over 1-2 min (in cases of pulseless cardiac arrest) or over 15 min (in cases without cardiac arrest)
Adverse Effects
- Asystole (see Asystole, [[Asystole]]: with rapid infusion
- Hypotension (see Hypotension, [[Hypotension]]): with rapid infusion

Two observational studies showed that IV magnesium sulfate can facilitate termination of torsades de pointes (irregular/polymorphic VT associated with prolonged QT interval)
– Magnesium sulfate is not likely to be effective in terminating irregular/polymorphic VT in patients with a normal QT interval
– A number of doses of magnesium sulfate have been used clinically, and an optimal dosing regimen has not been established
– When VF/pulseless VT cardiac arrest is associated with torsades de pointes, providers may administer an IV/IO bolus of magnesium sulfate at a dose of 1 to 2 g diluted in 10 mL D5W (Class IIb, LOE C).

See Part 8.3: “Management of Symptomatic Bradycardia and Tachycardia” for additional information about management of torsades de pointes not associated with cardiac arrest.
Three RCTs292–294 did not identify a significant benefit from use of magnesium compared with placebo among patients with VF arrest in the prehospital, intensive care unit, and emergency department setting, respectively
- Thus, routine administration of magnesium sulfate in cardiac arrest is not recommended (Class III, LOE A) unless torsades de pointes is present

Temporary Transvenous Overdrive Pacing (Atrial/Ventricular)

Indication: torsade unresponsive to magnesium therapy
Technique: pace at 100 bpm -> this will decrease the dispersion of refractoriness, decrease the development of early after-depolarizations, and may shorten the QT interval (especially in the setting of bradycardia)

Isoproterenol (see Isoproterenol, [[Isoproterenol]])

Indication: may be used as a temporary measure until a temporary pacemaker is available
- Increases the heart rate and decreases the QT interval
Administration: 2 ug/kg/min -> titrate to achieve heart rate of 100 bpm

Lidocaine (see Lidocaine, [[Lidocaine]])

Indication: class 1B antiarrhythmic which shortens the action potential duration -> may be effective
- Less predictable response rate than temporary pacing/isoproterenol

Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]])

Indication: class 1B antiarrhythmic which shortens the action potential duration -> may be effective
- Less predictable response rate than temporary pacing/isoproterenol

Sodium Bicarbonate (see Sodium Bicarbonate, [[Sodium Bicarbonate]])

Indications: quinidine-associated torsade (see Quinidine, [[Quinidine]])
Mechanism: decreases the availability of the active charged form of the drug, decreasing the QT interval

Potassium Chloride (see Potassium Chloride, [[Potassium Chloride]])

Indications: some small studies suggest that this may be beneficial in some cases of torsade related to quinidine or congestive heart failure (even with normal serum potassium concentration)
- Unclear if this therapy is effective in preventing or reversing torsade

References

Drug induced QT prolongation and torsades de pointes. Heart. 2003 November; 89(11): 1363–1372 [MEDLINE]
Arrhythmias associated with fluoroquinolone therapy. International Journal of Antimicrobial Agents 29 (2007) 374–379
Part 8: Adult Advanced Cardiovascular Life Support : 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010, 122:S729-S767
Drug-induced QT interval prolongation: Considerations for clinicians. Pharmacotherapy 2010; 30:684
Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2010 Mar 2;55(9):934-47. doi: 10.1016/j.jacc.2010.01.001.
[MEDLINE]
Assessing QT interval prolongation and its associated risks with antipsychotics. CNS Drugs 2011; 25:473
Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity. Arthritis Care Res (Hoboken). 2011 Oct;63(10):1463-70. doi: 10.1002/acr.20540 [MEDLINE]
CredibleMeds QT drugs list wesbsite sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/
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