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]])
- Heart Blocks
- 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
- High Dose/Concentration 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
- Hypokalemia (see Hypokalemia, [[Hypokalemia]])
- 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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