General Information
History
- 1966: torsade was first described in France by Dessertenne (Arch Mal Coeur Vaiss, 1966) [MEDLINE]
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 Ventricular Tachycardia: 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 QT Prolongation
- Systematic Review of the Risk Factors for QT Prolongation (Int J Clin Pharm, 2017) [MEDLINE]: n = 89,532 (10 observational studies)
- Very Strong Evidence was Found for a Risk of QT Prolongation with the Following
- Antiarrhythmic Drugs and QTc-Prolonging Drugs of List 1 of CredibleMeds (see https://crediblemeds.org/)
- Diuretics
- Hypokalemia (see Hypokalemia)
- Little or No Evidence was Found for a Risk of QT Prolongation with the Following
- Alcohol Abuse (see Ethanol)
- Depression (see Depression)
- Diabetes Mellitus (see Diabetes Mellitus)
- Digoxin (see Digoxin)
- Familial History of Cardiovascular Disease
- Heart Rate
- History of a Prolonged QTc Interval/Torsade de Pointes
- Hormone Replacement Therapy
- Hyperlipidemia (see Hyperlipidemia)
- Hypomagnesemia (see Hypomagnesemia)
- Neurological Disorders
- Pulmonary Disorders
- QTc-Prolonging Drugs of List 2 or 3 of CredibleMeds (see https://crediblemeds.org/)
- Renal Failure (see Chronic Kidney Disease)
- HMG-CoA Reductase Inhibitors (Statins) (see HMG-CoA Reductase Inhibitors)
- Very Strong Evidence was Found for a Risk of QT Prolongation with the Following
Risk Factors for Torsade in Hospitalized Patients (J Am Coll Cardiol, 2010) [MEDLINE]
- Advanced Age (>65 y/o)
- Bradycardic States
- Heart Blocks
- First Degree Atrioventricular Block (see 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 II (see Second Degree Atrioventricular Block-Mobitz Type II)
- Third Degree Atrioventricular Block/Complete Heart Block (see Third Degree Atrioventricular Block)
- Premature Ventricular Contractions (PVC’s) with Short-Long-Short-Cycles (see Premature Ventricular Contraction)
- Sinus Bradycardia(see Sinus Bradycardia)
- Heart Blocks
- Diuretic Administration
- Due to Direct Blockade of Potassium Current by Some Diuretics (Example: Indapamide)
- 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)
- Flavonoids in Juice Inhibit CYP3A4 (Slowing Metabolism of Other Medications) and Directly Inhibit the IKr Channel, Resulting in QT Prolongation
- Impairment of Drug Metabolism
- Chronic Kidney Disease (CKD) (see Chronic Kidney Disease)
- Cirrhosis/Liver Disease (see Cirrhosis)
- Metabolic Abnormalities
- Hypokalemia (see Hypokalemia): well documented association with torsade
- Risk of Torsade is Highest in the Setting of Antiarrhythmic Administration
- Probably Related to Enhanced Drug-Induced Blockade of IKr Current
- Hypocalcemia (see Hypocalcemia): rarely associated with torsade
- Hypomagnesemia (see Hypomagnesemia): well-documented association with torsade
- Risk of Torsade is Highest in the Setting of Antiarrhythmic Administration
- Hypokalemia (see Hypokalemia): well documented association with torsade
- Organic Heart Disease
- Congestive Heart Failure (CHF) (see Congestive Heart Failure): common risk factor for drug-induced torsade
- Dilated Cardiomyopathy (see Congestive Heart Failure)
- Hypertrophic Cardiomyopathy (see Hypertrophic Cardiomyopathy)
- Ischemic Heart Disease (see Coronary Artery Disease):
- Epidemiology
- 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
- Clinical
- Myocardial Infarction (MI) (see Coronary Artery Disease)
- Myocardial Ischemia (see Coronary Artery Disease)
- Epidemiology
- Kawasaki Disease (see Kawasaki Disease)
- Left Ventricular Hypertrophy (LVH): common risk factor for drug-induced torsade
- Myocarditis (see Myocarditis)
- Takotsubo Cardiomyopathy (Stress-Induced Cardiomyopathy) (see Takotsubo Cardiomyopathy)
- QTc >500 msec
- Especially with Long QT Syndrome 2-Type Repolarization Pattern (Notching, Long Tpeak-Tend)
- Use of QT-Prolonging Medications: especially with the following 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
- Recent Conversion from Atrial Fibrillation (see Atrial Fibrillation)
- Clinically-Silent Risk Factors
- Genetic Polymorphisms Which Result in Reduced Repolarization Reserve
- Occult Congenital Long QT Syndrome
Etiology
Congenital Long QT Syndrome (see 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)
- Primary Biliary Cirrhosis (see Primary Biliary Cirrhosis)
- Sjogren’s Syndrome (see Sjogren’s Syndrome)
- Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
Endocrine/Metabolic
- Anorexia Nervosa (see Anorexia Nervosa)
- Hypocalcemia (see Hypocalcemia)
- Hypokalemia (see Hypokalemia)
- Epidemiology
- Risk of Torsade is Highest in the Setting of Antiarrhythmic Administration
- Physiology
- Probably Related to Enhanced Drug-Induced Blockade of IKr Current
- Epidemiology
- Hypomagnesemia (see Hypomagnesemia)
- Epidemiology
- Risk of Torsade is Highest in the Setting of Antiarrhythmic Administration
- Epidemiology
- Hypothyroidism (see Hypothyroidism)
- Liquid Protein Diets
- Starvation
Bradyarrhythmia
- Sinus Bradycardia (see Sinus Bradycardia)
- Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I)
- Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II)
- Third Degree Atrioventricular Block/Complete Heart Block (see Third Degree Atrioventricular Block)
Intracranial Disease
- Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage)
- Epidemiology: QT prolongation is common in intracerebral hemorrhage (present in 64% of cases)
- Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)
- Epidemiology: QT prolongation is common in ischemic CVA (present in approximately 38% of cases)
- Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage)
- Epidemiology: QT prolongation is common in SAH (present in 71% of cases)
Organic Heart Disease
- Congestive Heart Failure (CHF) (see Congestive Heart Failure)
- Dilated Cardiomyopathy (see Congestive Heart Failure)
- Hypertrophic Cardiomyopathy (see Hypertrophic Cardiomyopathy)
- Ischemic Heart Disease (see Coronary Artery Disease)
- Epidemiology
- 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
- Torsade is an Uncommon Myocardial Ischemia-Associated Rhythm
- Clinical
- Myocardial Infarction (MI) (see Coronary Artery Disease)
- Myocardial Ischemia (see Coronary Artery Disease)
- Epidemiology
- Kawasaki Disease (see Kawasaki Disease)
- Left Ventricular Hypertrophy (LVH): common risk factor for drug-induced torsade
- Myocarditis (see Myocarditis)
- Takotsubo Cardiomyopathy (Stress-Induced Cardiomyopathy) (see Takotsubo Cardiomyopathy)
QT Prolonging Drugs and Toxins (@ = definite association with torsade)
Anorexigens
- Fenfluramine (Pondimin, Ponderax, Adifax) (see Fenfluramine)
- Phentermine (see Phentermine)
- Sibutramine (Meridia) (see Sibutramine)
Anti-Arrhythmics
- Type 1A Anti-Arrhythmics: Fast Sodium Channel Blockers Which Depress Phase 0, Prolonging Repolarization
- Disopyramide (Norpace) @ (see Disopyramide)
- Procainamide (Pronestyl) @ (see Procainamide)
- Quinidine (Quinaglute, Quinidex) @ (see 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)
- 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)
- Propafenone (Rythmol, Rytmonorm( (see Propafenone)
- Type 3 Anti-Arrhythmics: Potassium Channel Blockers
- Amiodarone (Cordarone) @ (see Amiodarone): while chronic amiodarone administration markedly prolongs the QT interval, torsade occurs in <1% of cases
- Bretylium @ (see Bretylium)
- Dofetilide (Tikosyn) @ (see Dofetilide): torsade occurs in 0.3-10.5% of cases
- Ibutilide (Corvert) @ (see Ibutilide): torsade occurs in 0.9-2.5% of cases
- Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) @ (see Sotalol)
- Other: Multichannel Sodium/Potassium/Calcium Channel Blockade with Anti-Adrenergic Activity
- Dronedarone (Multaq) (see Dronedarone)
Antihistamines (see H1-Histamine Receptor Antagonists)
- Astemizole (Hismanal) @ (see Astemizole): withdrawn from US market
- Diphenhydramine (Benadryl) @ (see Diphenhydramine)
- Ebastine
- Hydroxyzine (Atarax, Vistaril) (see Hydroxyzine)
- Loratidine (Claritin) @ (see Loratidine)
- Mizolastine
- Promethazine (Phenergan) (see Promethazine)
- Terfenadine (Seldane) @ (see Terfenadine): withdrawn from US market
Antimicrobials
- Anti-Malarials
- Artemether
- Chloroquine (Aralen) @ (see Chloroquine): anti-malarial
- Delamanid: possible risk of prolonged QT
- Halofantrine @: anti-malarial
- Hydroxychloroquine (see Hydroxychloroquine
- Lumefantrine
- Mefloquine (see Mefloquine): possible risk of prolonged QT
- Primaquine (see Primaquine): possible risk of prolonged QT
- Quinine (see Quinine)
- Azole Anti-Fungals (see Azole Anti-Fungals)
- Fluconazole (Diflucan, Trican) @ (see Fluconazole)
- Itraconazole (Sporanox) (see Itraconazole)
- Ketoconazole (Nizoral) (see Ketoconazole): systemic
- Posaconazole (Noxafil, Posanol) (see Posaconazole)
- Voriconazole (Vfend) (see Voriconazole)
- Fluoroquinolones @ (see 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)
- Grepafloxacin (Raxar) (see Grepafloxacin
- Moxifloxacin (Avelox, Avalox, Avelon) (see Moxifloxacin)
- Sparfloxacin (Spacin, Zagam) (see Sparfloxacin)
- Medium Risk
- Gemifloxacin (Factive) (see Gemifloxacin)
- Levofloxacin (Levaquin) (see Levofloxacin,)
- Ofloxacin (Floxin, Ocuflox) (see Ofloxacin)
- Sitafloxacin (Gracevit) (see Sitafloxacin)
- Tosufloxacin (Ozex) (see Tosufloxacin)
- Low Risk
- Ciprofloxacin (Cipro) (see Ciprofloxacin)
- Human Immunodeficiency Virus (HIV) Medications
- Lopinavir (see Lopinavir + Ritonavir)
- Nelfinavir (Viracept) (see Nelfinavir,)
- Saquinavir (Invirase, Fortovase) (see Saquinavir)
- Macrolides (see Macrolides)
- Azithromycin (Zithromax) @ (see Azithromycin)
- Clarithromycin (Biaxin) @ (see Clarithromycin)
- Erythromycin @ (see Erythromycin)
- Roxithromycin (Biaxsig, Coroxin, Romac, Roxar, Roximycin, Roxl-150, Roxo, Roxomycin, Rulid, Rulide, Surlid, Tirabicin, Xthrocin) @ (see Roxithromycin)
- Telithromycin (Ketek) (see Telithromycin)
- Other Antimicrobials
- Bedaquiline
- Foscarnet (Foscavir) (see Foscarnet)
- Metronidazole (Flagyl) (see Metronidazole)
- Pentamidine @ (see Pentamidine): intravenous
- Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim)
- Telavancin (Vibativ) (see Telavancin)
Anti-Muscarinics
- Solifenacin (Vesicare) (see Solifenacin)
- Tolterodine (Detrol, Detrusitol) (see Tolterodine)
Anti-Neoplastic Agents
- Arsenic Trioxide (Trisenox) @ (see Arsenic)
- Ceritinib (Zykadia) (see Ceritinib)
- Cesium Chloride
- Crizotinib (Xalkori) (see Crizotinib)
- Dasatinib (Sprycel) (see Dasatinib)
- Eribulin
- Nilotinib (Tasigna) (see Nilotinib)
- Lapatinib (Tykerb, Tyverb) (see Lapatinib
- Panabinostat
- Pazopanib (Votrient) (see Pazopanib)
- Romidepsin
- Sorafenib (Nexavar) (see Sorafenib)
- Sunitinib (Sutent) (see Sunitinib)
- Toremifene
- Vandetanib (Caprelsa) (see Vandetanib)
- Vemurafenib
- Vorinostat
β2-Agonists (see β2-Adrenergic Receptor Agonists)
- Short-Acting β2-Adrenergic Receptor Agonists (SABA)
- Albuterol (Salbutamol, Ventolin) (see Albuterol)
- Bitolterol
- Fenoterol
- Isoprenaline
- Levalbuterol (Xopenex) (see Levalbuterol)
- Metaproterenol (Alupent) (see Metaproterenol)
- Pirbuterol (Maxair)
- Procaterol
- Ritodrine
- Terbutaline (Brethine, Bricanyl, Brethaire, Terbulin) (see Terbutaline)
- Long-Acting β2-Adrenergic Receptor Agonists (LABA)
- Arformoterol (Brovana, Erdotin) (see Arformoterol)
- Bambuterol (Bambec, Oxeol)
- Clenbuterol (Spiropent, Ventipulmin)
- Formoterol (Foradil, Oxeze, Oxis, Atock, Atimos, Perforomist) (see Formoterol)
- Olodaterol (Striverdi Respimat) (see Olodaterol)
- Salmeterol (Serevent) (see Salmeterol)
- Vilanterol (see Vilanterol)
- Ultra Long-Acting Beta Agonists
- Indacaterol (Arcapta) (see Indacaterol)
Calcium Channel Blockers (see Calcium Channel Blockers)
- Bepridil (Vascor) @: withdrawn from US market
- Isradipine (DynaCirc, Prescal) (see 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)
- Triptorelin
Neurologic Medications
- Apomorphine (see Apomorphine)
- Donepezil (Aricept) (see Donepezil)
- Fingolimod (Gilenya) (see Fingolimod
- Tetrabenazine (Nitoman, Xenazine ) (see Tetrabenazine)
Opiates (see Opiates)
- Levomethadyl (Orlaam) @: withdrawn from US market
- Methadone (Dolophine, Methadose ) @ (see Methadone)
- High Methadone Doses or Recent Dose Increases are Often Implicated in Cases Associated with Torsade (Ann Intern Med, 2002) [MEDLINE]
Psychiatric Drugs
- General Comments
- Users of Typical and Atypical Antipsychotics Have Been Demonstrated to Have a Higher Risks of Sudden Cardiac Death as Non-Users of Antipsychotic Medications (Adjusted Incidence-Rate Ratios of 1.99 (95% CI: 1.68-2.34) and 2.26 (95% CI: 1.88-2.72), Respectively) (NEJM, 2009) [MEDLINE]
- Risk Increased with Increasing Dose in Patients on Typical and Atypical Antipsychotics
- Users of Typical and Atypical Antipsychotics Have Been Demonstrated to Have a Higher Risks of Sudden Cardiac Death as Non-Users of Antipsychotic Medications (Adjusted Incidence-Rate Ratios of 1.99 (95% CI: 1.68-2.34) and 2.26 (95% CI: 1.88-2.72), Respectively) (NEJM, 2009) [MEDLINE]
- Bupropion (Wellbutrin) (see Bupropion)
- Epidemiology
- While the Risk of QT/QTc Prolongation with the Majority of Newer Non-SSRI Antidepressants (Bupropion, Desvenlafaxine, Duloxetine, Levomilnacipran, Mirtazapine, Venlafaxine, and Vilazodone) at Therapeutic Doses is Low, the Highest Risk for QT Prolongation Exists with Overdose with Bupropion and Venlafaxine (Ann Pharmacother, 2014) [MEDLINE]
- Epidemiology
- Butryophenones
- Droperidol (Inapsine, Droleptan, Dridol, Xomolix, Innovar) @ (Droperidol): butyrophenone antipsychotic and antiemetic
- Haloperidol (Haldol) @ (see Haloperidol): butyrophenone antipsychotic
- Phenothiazines (see Phenothiazines)
- Chlorpromazine @ (Thorazine) (see Chlorpromazine)
- Mesoridazine (Serentil) @ (see Mesoridazine)
- Prochlorperazine (Compazine) (see Prochlorperazine)
- Thioridazine (Mellaril) @ (see Thioridazine)
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) (see Serotonin-Norepinephrine Reuptake Inhibitors)
- Venlafaxine (Effexor) (see Venlafaxine)
- Epidemiology
- While the Risk of QT/QTc Prolongation with the Majority of Newer Non-SSRI Antidepressants (Bupropion, Desvenlafaxine, Duloxetine, Levomilnacipran, Mirtazapine, Venlafaxine, and Vilazodone) at Therapeutic Doses is Low, the Highest Risk for QT Prolongation Exists with Overdose with Bupropion and Venlafaxine (Ann Pharmacother, 2014) [MEDLINE]
- Epidemiology
- Sibutramine (Meridia)
- Venlafaxine (Effexor) (see Venlafaxine)
- Selective Serotonin Reuptake Inhibitors (SSRI) (see Selective Serotonin Reuptake Inhibitors)
- Citalopram (Celexa) (see Citalopram)
- Escitalopram (Lexapro) (see Escitalopram)
- Fluoxetine (Prozac) @ (see Fluoxetine)
- Paroxetine (Paxil) (see Paroxetine)
- Sertraline (Zoloft) (see Sertraline)
- Tricyclic Antidepressants (see Tricyclic Antidepressants)
- Amitriptyline (Tryptomer, Elavil) (see Amitriptyline)
- Clomipramine (Anafranil) (see Clomipramine)
- Desipramine (Norpramin, Pertofrane) @ (see Desipramine)
- Doxepin (Adapin, Sinequan) @ (see Doxepin)
- Imipramine (Tofranil, Janimine, Praminil) @ (see Imipramine)
- Nortriptyline (Pamelor, Aventyl, Norpress) (see Nortriptyline)
- Protriptyline (Vivactil) (see Protriptyline)
- Trimipramine (Surmontil) (see Trimipramine)
- Other Psychiatric Drugs
- Amoxapine (see Amoxapine)
- Aripiprazole (Abilify) (see Aripiprazole: possible risk of prolonged QT
- Atomoxetine
- Chloral Hydrate (see Chloral Hydrate)
- Clozapine (Clozaril) (see Clozapine)
- Lamotrigine (Lamictal) (see Lamotrigine): prolonged QTc has been reported in the setting of intoxication
- Lithium @ (see Lithium)
- Maprotiline (Ludiomil) @ (see Maprotiline)
- Olanzapine (Zyprexa) (see Olanzapine): possible risk of prolonged QT
- Pimozide (Orap) @: diphenylbutylpiperidine antipsychotic
- Quetiapine (Seroquel) (see Quetiapine)
- Risperidone (Risperdal) (see Risperidone)
- Sertindole (Serdolect) @ (see Serdolect)
- Trazodone (Desyrel, Desyrel Dividose, Oleptro) (see Trazodone)
- Ziprasidone (Geodon, Zeldox) (see Ziprasidone)
Serotonin 5-HT3 Receptor Antagonists (see Serotonin 5-HT3 Receptor Antagonists)
- Dolasetron (Anzemet) (see Dolasetron)
- Granisetron (Kytril, Sancuso) (see Granisetron)
- Ondansetron (Zofran) (see Ondansetron)
- Tropisetron
Sympathomimetics
- Amphetamine (see Amphetamine): increases dopamine release
- Cocaine (see Cocaine)
- Methylphenidate (Ritalin) (see Methylphenidate): norepinephrine and dopamine reuptake inhibitor
Vasoactive Drugs
- Dopamine (see Dopamine)
- Dobutamine (see Dobutamine)
- Ephedrine (see Ephedrine)
- Epinephrine (see Epinephrine)
- Isoproterenol (see Isoproterenol)
- Midodrine (see Midodrine)
- Nicardipine (see Nicardipine,)
- Norepinephrine (see Norepinephrine)
- Phenylephrine (Neosynephrine) (see Phenylephrine,)
- Vasopressin @ (see Vasopressin)
Other Medications
- Alfuzosin (Uroxatral) (see Alfuzosin)
- Adenosine (Adenocard) (see Adenosine)
- Amantadine (Symmetrel) @ (see Amantadine)
- Anagrelide (Agrylin) (see xxxx)
- Atomoxetine (Strattera): selective norepinephrine reuptake inhibitor (NRI)
- Bepridil (Vascor) (see xxxx)
- Cilostazol (Pletal) (see Cilostazol)
- Cisapride (Prepulsid, Propulsid) @: withdrawn from US market
- Digoxin (Lanoxin) @ (see Digoxin
- Domperidone (Motilium, Motillium, Motinorm Costi, Nomit) @ (see Domperidone): dopamine antagonist (derived from butyrophenone)
- Fosphenytoin (see Fosphenytoin)
- Furosemide (Lasix) @ (see Furosemide)
- Galantamine (Razadyne)
- Indapamide (Lozol) (see Indapamide): thiazide-like diuretic
- Ivabradine (Corlanor) (see Ivabradine)
- Metoclopramide (Reglan) (see Metoclopramide)
- Mifepristone (Mifegyne, Mifeprex) (see Mifepristone
- Moexipril (Univasc) (see Moexipril)
- Octreotide (see Octreotide)
- Papaverine (Pavabid) @: intravenous
- Pasireotide
- Phenylpropanolamine (see Phenylpropanolamine,)
- Probucol @
- Propofol (Diprivan) (see Propofol)
- Pseudoephedrine (Afrinol, Sudafed, Sinutab) (see Pseudoephedrine)
- Ranolazine (Ranexa) (see Ranolazine)
- Tamoxifen (Nolvadex, Genox, Tamifen) (see Tamoxifen)
- Tacrolimus (Prograf) @ (see Tacrolimus)
- Terlipressin (Teripress, Glypressin) (see Terlipressin)
- Tizanidine (Zanaflex) (see Tizanidine)
- Vardenafil (Levitra, Staxyn) (see Vardenafil): PDE5 inihibitor
Toxins
- Cinchona (see Quinine): contains quinine
- Hydrocarbon Intoxication (see Hydrocarbons)
- Methanol Intoxication (see Methanol)
- Organophosphates (see Organophosphates/Carbamates)
- Epidemiology
- QT Prolongation May Occur (Cardiovasc Toxicol, 2011) [MEDLINE]
- Epidemiology
Other QT Prolonging Conditions
Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)
- Epidemiology
- XXXX
Hypothermia (see Hypothermia)
- Physiology
Hypoxia (see Hypoxemia)
- Physiology
- Acute Hypoxia Has Been Demonstrated to Prolong the QT Interval in Normal Subjects (Am J Cardiol, 2003) [MEDLINE]
- Nocturnal Hypoxemia Has Been Demonstrated to Prolong the QT Interval in Patients with Chronic Obstructive Pulmonary Disease (COPD) (NEJM, 1982) [MEDLINE]
- Hypoxemia Has Been Demonstrated to Prolong the QT Interval During Sleep in Patients with Coronary Artery Disease (CAD) (Chest, 1982) [MEDLINE]
- Sleep-Disordered Breathing is Associated with an Increased Risk of Nocturnal Ventricular Arrhythmias (Am J Respir Crit Care Med, 2006) [MEDLINE]
- In Patients with Heart Failure and Sleep Apnea, Treatment with CPAP Eliminates Sleep-Disordered Breathing and Decreases Ventricular Irritability (Circulation, 2000) [MEDLINE]
- Severe Obstructive Sleep Apnea Has Been Demonstrated to Prolong the QTc Interval in Patients with Congenital Long QT Syndrome (Independent of Age, Sex, BMI, Use of β-Blockers, and History of Syncope), Which is a Biomarker for Sudden Cardiac Death (Sleep, 2015) [MEDLINE] (see Obstructive Sleep Apnea)
- Severity of Obstructive Sleep Apnea (as Represented by the Apnea-Hypoxia Index and Apnea Index During Sleep) is Directly Related to the Degree of QT Prolongation in This Population
- The Obstructive Sleep Apnea-Related Increase in the QT May Be Mediated by Hypoxic Episodes, Sympathetic Activation, and/or Vagal Bradyarrhythmias
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)
- 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
- Rate is Usually 160-240 bpm (Which is Generally Slower than Ventricular Tachycardia) (J Am Coll Cardiol, 2010) [MEDLINE]
- R-R Intervals
- Irregular R-R Intervals
Clinical Manifestations
Cardiovascular Manifestations
Preceding Prolonged QT Interval
- Background
- Measurement of QT Interval
- Measure from Start of R-Wave to End of the T-Wave (Approximates the Time it Takes the Ventricles to Repolarize)
- While the Best Lead to Measure Varies from Patient to Patient, One Should Choose a Lead with an at Least 2 mm T-Wave with a Defined Ending
- In Situations in Which the End of the T-Wave May Be Difficult to Determine (e.g. Biphasic or Notched T-Waves, T-Waves with Superimposed U-Waves), the End of the T-Wave Can Be Determined by Drawing a Line from the Peak of the T -Wave Following the Steepest T-Wave Downslope (the Intersection of This Line with the Isoelectric Baseline is Considered the End of the T-Wave)
- Calculation of QTc in the Setting of Atrial Fibrillation May Be Challenging, Since the QT Interval Varies from Beat to Beat Depending on the Varying RR Intervals, Requiring a Method to Estimate the QTc
- Method 1: Identify the Shortest and Longest R-R Intervals, Calculate the QTc for Each and Average the 2 QTc Values
- Method 2: Print a Long Rhythm Strip to Determine Whether (on Average) the Interval from R-Wave to the Peak (or Nadir) of the T-Wave is >50% of the R-R Interval: this method does not give an exact QTc value, but provides an indication that it would be longer than the critical threshold of 500 msec if measured
- Wide QRS Complex (e.g. Due to a New Bundle-Branch Block), Will Increase the Total QT Interval (Note that This Does Not Indicate a Prolonged QT), Requiring a Method to Estimate the QTc
- Method 1: Subtract the Difference in QRS Widths Before and After the Block
- Method 2: Measure a J-T Interval from the End of the QRS Complex to the End of the T-Wave, Which Eliminates the QRS in the Measurement Altogether
- Measure from Start of R-Wave to End of the T-Wave (Approximates the Time it Takes the Ventricles to Repolarize)
- Correction of QT for the Heart Rate
- The Bazett Correction is Standardly Used to Adjust the Measured QT for Cycle Length by Dividing the Observed, Uncorrected QT Interval by the Square Root of the R-R Interval (in seconds)
- The Bazett Correction Tends to Produce Overlong QTc Values at Faster Heart Rates, Particularly >85 bpm
- Normal QTc: 440-460 msec (0.44-0.46 sec) (J Am Coll Cardiol, 2010) [MEDLINE]
- Criterion for Prolonged QT (>99% Percentile) in Males (AHA/ACC 2010 Criteria): QTc >470 msec
- Criterion for Prolonged QT (>99% Percentile) in Females (AHA/ACC 2010 Criteria): QTc >480 msec
- Measurement of QT Interval
- Risk of Torsade is Proportional to the Degree of QT Prolongation (J Am Coll Cardiol, 2010) [MEDLINE]
- Each 10 msec Increase in QT Prolongation Contributes Approximately a 5-7% Exponential Risk for Torsade (Circulation, 1991) [MEDLINE] (NEJM, 1998) [MEDLINE]
- Example: a patient with a QTc of 540 msec has a 63-97% higher risk of torsade than a patient with a QTc of 440 msec
- *Data from Patients with Congenital Long QT Indicate that QTc 500 msec is Associated with a 2-3x Higher Risk for Torsade (NEJM, 2003) [MEDLINE] (J Am Coll Cardiol, 2007) [MEDLINE]
- Data from Patients with Drug-Induced QT Prolongation Indicate that QTC 500 msec Imparts an Increased Risk for Torsade (Am Heart J, 1986) [MEDLINE] ( JAMA, 1993) [MEDLINE] (Br J Clin Pharmacol, 2007) [MEDLINE]
- Each 10 msec Increase in QT Prolongation Contributes Approximately a 5-7% Exponential Risk for Torsade (Circulation, 1991) [MEDLINE] (NEJM, 1998) [MEDLINE]
- Problems with Assessing the QT Interval in the Post-Cardiac Arrest Setting
Torsade
- Electrocardiographic (EKG) Features
- Preceding Short-Long-Short Pattern of R-R Cycles
- Short-coupled PVC followed by a compensatory pause and then another PVC that typically falls close to the peak of the T wave
- Believed to Promote the Development of Torsade by Increasing Heterogeneity of Repolarization Across the Myocardial Wall
- However, Because of the Underlying Long QT interval, this R-on-T PVC Does Not Have the Short Coupling Interval Which is Characteristic of Idiopathic Ventricular Fibrillation
- “Warm-Up” Phenomenon (with the Initial R-R Cycles Being Longer than the Subsequent Cycles)
- Cyclical Variation of the 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
- However, the Twisting Morphology May Not Be Evident in All EKG Leads
- Rate is Usually 160-240 bpm (Which is Generally Slower than Ventricular Tachycardia) (J Am Coll Cardiol, 2010) [MEDLINE]
- Irregular R-R Intervals
- Termination
- In Contrast to Ventricular Fibrillation Which Does Not Terminate without Defibrillation, Torsade Frequently Terminates Spontaneously, with the last 2-3 Beats Demonstrating Slowing of the Rate
- Preceding Short-Long-Short Pattern of R-R Cycles
- Syncope (see Syncope)
- Cardiovascular Complications
- Degeneration to Ventricular Fibrillation (see Ventricular Fibrillation)
- Degeneration to Sudden Cardiac Death (see Sudden Cardiac Death)
Prevention
QT Monitoring
General
- QT Monitoring Alone May Be Inadequate to Accurately Predict the Occurrence of Torsade, Since it is Difficult to Accurately Measure the QT Interval in Patients Who Have a Morphologically Distorted QT (Usually Due to T-Wave Changes) (J Am Coll Cardiol, 2010) [MEDLINE]
- The Typical Short-Long-Short Sequence of R-R Intervals Seen Prior to the Start of Torsade is Associated with Marked QT Prolongation and T-U–wave Distortion in the Last Sinus Beat (Terminating the Long Pause) Before the Episode
- Distortion Often Involves Changes in T-Wave Morphology Such as T-Wave Flattening, Bifid T-Waves, Prominent U Waves Which are Fused with T-Waves, and an Extended and Gradual Sloping of the Descending Limb of the T-Wave, Which Makes it Difficult to Determine the End of the T-Wave
- In a Patient with Drug-Induced QT Prolongation, the QT Interval May Be Prolonged During Normal Sinus Rhythm without Adverse Effect, But After a Pause (e.g. After an Ectopic Beat or During Transient Atrioventricular Block), QT Interval Prolongation and T-U Deformity Become Markedly Exaggerated, and Torsade May Be Triggered
- Beat-to-Beat Instability of the QT Interval Not Only Appears Likely to Influence the Accuracy of Measurement, But it May Also Be Related to the Underlying Mechanism of the Arrhythmia
- In Addition to an Ever-Increasing and Distorted QT Interval, Macroscopic T-Wave Alternans is a Rare (But Ominous) Premonitory EKG Sign of Impending Torsade
- In the Future, it May Be Possible to Assess Risk by Using Sophisticated T-U–Wave Morphology Analysis
- However, Until Such Analysis Becomes Available, Exaggerated QT Interval Prolongation with T-U Distortion After a Pause Should Be Considered a Strong Marker for the Risk of Torsade
- The Typical Short-Long-Short Sequence of R-R Intervals Seen Prior to the Start of Torsade is Associated with Marked QT Prolongation and T-U–wave Distortion in the Last Sinus Beat (Terminating the Long Pause) Before the Episode
- American Heart Association Practice Standard for QT Monitoring (J Am Coll Cardiol, 2010) [MEDLINE]
- Initiation of a Drug Known to Cause Torsade
- Because There is Often a Lack of Clarity with Regard to the Types and Amounts of Drugs Taken in an Intentional Overdose Situation, it is Prudent to Monitor QT Intervals in All Overdose Victims
- Until Fully Automated QTc Monitoring is Validated and Widely Clinically Available, a Reasonable Strategy is to Document the QTc Interval Before and at Least Every 8-12 hrs After the Initiation, Increased Dose, or Overdose of a QT-Prolonging Drug
- If QTc Prolongation is Observed, More Frequent QTc Measurement is Recommended
- How long QTc Measurement Should Be Continued Depends on the Drug Half-Life, How Long it Takes for the Drug to Be Eliminated from the Body (Which May Depend on Renal or Hepatic Function), Whether the Drug is Administered Once vs as Ongoing Therapy, How Long it Takes for the QTc to Return to the Predrug Baseline, and Whether the EKG Demonstrates QT-Related Arrhythmias
- Overdose from a Potentially Proarrhythmic Agent
- New-Onset Bradyarrhythmia
- Severe Hypokalemia or Hypomagnesemia
- Initiation of a Drug Known to Cause Torsade
QT Monitoring in Patients Receiving Haloperidol (Haldol)
- Retrospective Belgian Study of EKG Monitoring in Patients Receiving Haloperidol (Int J Clin Pharm, 2016) [MEDLINE]: n = 220
- Study Use the Pro-QTc Score of Haugaa et al (Mayo Clin Proc2013) [MEDLINE]
- Approximately 26.% of Patients Had a Risk Score of C4 (Known to Significantly Increase the Mortality)
- Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes
- Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed
- Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram
- In patients with a risk score C4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020)
Treatment
Congenital Long QT Syndrome
β-Blockers (see β-Adrenergic Receptor Antagonists)
- xxx
Mexiletine (Mexitil) (see Mexiletine)
- xxxx
Permanent Dual Chamber Pacemaker
- xxx
Left Chamber Sympathetic Denervation (Cardiothoracic Sympathectomy)
- xxx
Automatic Implantable Cardioverter-Defibrillator (AICD) (see 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
- Indication
- Magnesium is 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): with rapid infusion
- Hypotension (see 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)
- 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)
- 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)
- 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)
- Indications: quinidine-associated torsade (see Quinidine)
- Mechanism: decreases the availability of the active charged form of the drug, decreasing the QT interval
Potassium Chloride (see 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
Recommendations
- Cardioversion (J Am Coll Cardiol, 2010) [MEDLINE]
- For Torsade Which Does Spontaneously Terminate or Which Degenerates into Ventricular Fibrillation, Immediate Direct-Current Cardioversion Should Be Performed
- Intravenous Magnesium Sulfate (see Magnesium Sulfate) (American College of Cardiology/American Heart Association/European Society of Cardiology 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) (J Am Coll Cardiol, 2006) [MEDLINE]
- *Intravenous Magnesium Sulfate is Recommended For Patients Taking QT-prolonging Drugs Who Present with Torsade and a Prolonged QT-Interval (Class IIa, Level of Evidence: B)
- Intravenous Magnesium Sulfate 2g Can Be Administered as a First-Line Agent to Terminate Torsade, Irrespective of the Serum Magnesium Level
- If Torsade Persists, it May Be Necessary to Repeat Intravenous Magnesium Sulfate 2g Administration
- The Mechanism Underlying the Protective Effect of Magnesium is Unknown
- Increase in Heart Rate (Pacing Clin Electrophysiol, 2002) [MEDLINE]
- An Increase in Heart Rate to Prevent Pauses Which May Trigger Torsade May Be Attempted with Temporary Transvenous Atrial or Ventricular Pacing at Heart Rate >70 bpm
- Potassium Repletion (see Potassium Chloride,) (see Magnesium Sulfate) (American College of Cardiology/American Heart Association/European Society of Cardiology 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) (J Am Coll Cardiol, 2006) [MEDLINE]
- Repletion of Potassium to Supratherapeutic Levels of 4.5-5 mmol/L May Also Be Considered, Although There is Little Evidence to Support this Practice (Class IIb, Level of Evidence: C)
References
General
- 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]
History
- La tachycardie ventriculaire a ́ deux foyers opposes variables. Arch Mal Coeur Vaiss. 1966;59:263–72 [MEDLINE]
Etiology
- Nocturnal hypoxemia and associated electrocardiographic changes in patients with chronic obstructive airways disease. N Engl J Med 1982;306:125–30 [MEDLINE]
- Disordered breathing and hypoxia during sleep in coronary artery disease. Chest 1982;82:548–52 [MEDLINE]
- QT prolongation and the antiarrhythmic efficacy of amiodarone. J Am Coll Cardiol. 1986 Jan;7(1):142-7 [MEDLINE]
- Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. Magnes Trace Elem. 1990;9(3):143-51 [MEDLINE]
- Magnesium deficiency and sudden death. Am Heart J. 1992 Aug;124(2):544-9 [MEDLINE]
- Torsade de pointes associated with the use of intravenous haloperidol. Ann Intern Med. 1993;119:391-4 [MEDLINE]
- Amiodarone and torsades de pointes in patients with advanced heart failure. Am J Cardiol. 1995 Sep 1;76(7):499-502 [MEDLINE]
- Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation 2000;101:392–7 [MEDLINE]
- Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137:501-4 [MEDLINE]
- Drug induced QT prolongation and torsades de pointes. Heart. 2003 November; 89(11): 1363–1372 [MEDLINE]
- Effect of acute hypoxia on QT rate dependence and corrected QT interval in healthy subjects. Am J Cardiol. 2003 Apr 1;91(7):916-9 [MEDLINE]
- Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–22 [MEDLINE]
- Torsade de pointes induced by short-term oral amiodarone therapy. Europace. 2006 Dec;8(12):1051-3 [MEDLINE]
- Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol. 2006 Jan 17;47(2):362-7 [MEDLINE]
- Hypothermia: evaluation, electrocardiographic manifestations, and management. Am J Med. 2006 Apr;119(4):297-301 [MEDLINE]
- ECG changes during induced hypothermia after cardiac arrest. Am J Crit Care. 2006 Nov;15(6):631-2 [MEDLINE]
- Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med 2006;173:910–6 [MEDLINE]
- Long QT syndrome in adults. J Am Coll Cardiol. 2007;49:329–37 [MEDLINE]
- Arrhythmias associated with fluoroquinolone therapy. International Journal of Antimicrobial Agents 29 (2007) 374–379
- Amiodarone–avoid the danger of torsade de pointes. Resuscitation. 2008 Jan;76(1):137-41[MEDLINE]
- Atypical antipsychotic drugs and the risk of sudden cardiac death [published correction appears in N Engl J Med. 2009;361:1814]. N Engl J Med. 2009;360: 225–35 [MEDLINE]
- Drug-induced QT interval prolongation: Considerations for clinicians. Pharmacotherapy 2010; 30:684 [MEDLINE]
- Assessing QT interval prolongation and its associated risks with antipsychotics. CNS Drugs 2011; 25:473 [MEDLINE]
- 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]
- A prospective study on electrocardiographic findings of patients with organophosphorus poisoning. Cardiovasc Toxicol. 2011 Jun;11(2):113-7 [MEDLINE]
- High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in practice (QTIP) study. Crit Care Med. 2012 Feb;40(2):394-9. doi: 10.1097/CCM.0b013e318232db4a [MEDLINE]
- Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clin Proc. 2013;88:315–25 [MEDLINE]
- A comparison of the risk of QT prolongation among SSRIs. Ann Pharmacother. 2013 Oct;47(10):1330-41. doi: 10.1177/1060028013501994. Epub 2013 Oct 21 [MEDLINE]
- QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics. 2013 Jan-Feb;54(1):1-13. doi: 10.1016/j.psym.2012.11.001 [MEDLINE]
- Risk of QT/QTc prolongation among newer non-SSRI antidepressants. Ann Pharmacother. 2014 Dec;48(12):1620-8. doi: 10.1177/1060028014550645 [MEDLINE]
- Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death. Sleep. 2015 Jul 1;38(7):1113-9. doi: 10.5665/sleep.4824 [MEDLINE]
- Risk factors for QTc-prolongation: systematic review of the evidence. Int J Clin Pharm. 2017 Feb;39(1):16-25. doi: 10.1007/s11096-016-0414-2 [MEDLINE]
- The effect of targeted temperature management on QT and corrected QT intervals in patients with cardiac arrest. J Crit Care. 2017 Jun;39:182-184. doi: 10.1016/j.jcrc.2017.02.030 [MEDLINE]
- CredibleMeds QT drugs list wesbsite sponsored by Science Foundation of the University of Arizona. Available at https://crediblemeds.org/ Lexicomp Online. Copyright ©1978-2016 Lexicomp, Inc. All Rights Reserved
Clinical
- The long QT syndrome: prospective longitudinal study of 328 families. Circulation. 1991;84: 1136-44 [MEDLINE]
- Influence of genotype on the clinical course of the long-QT syndrome: International Long-QT Syndrome Registry Research Group. N Engl J Med. 1998;339:960–5 [MEDLINE]
- Risk stratification in the long-QT syndrome. N Engl J Med. 2003;348:1866–74 [MEDLINE]
- Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care. Am Heart J. 1986;111:1088–93 [MEDLINE]
- Mechanism of the cardiotoxic actions of terfenadine. JAMA. 1993;269:1532-6 [MEDLINE]
- In-hospital cardiac arrest is associated with use of non-antiarrhythmic QTc-prolonging drugs. Br J Clin Pharmacol. 2007;63:216 –23 [MEDLINE]
Prevention
- Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium. Int J Clin Pharm. 2016 Apr;38(2):310-20. doi: 10.1007/s11096-015-0242-9 [MEDLINE]
Treatment
- What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers. Pacing Clin Electrophysiol. 2002;25:1612-5 [MEDLINE]
- ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol. 2006;48:e247–346 [MEDLINE]
- Part 8: Adult Advanced Cardiovascular Life Support : 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010, 122:S729-S767