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
  • 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
  • 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)
    • 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

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

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
  • 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
  • Human Immunodeficiency Virus (HIV) Medications
  • 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

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


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

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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