QT prolongation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Prolonged QT; prolonged QT interval; QT interval prolongation

Overview

QT prolongation refers to a prolongation of the interval on the electrocardiogram during which time the ventricles depolarize and repolarize. QT prolongation is often caused by drugs, genetic abnormalities, and electrolyte disturbances. QT prolongation may predispose the patient to ventricular arrhythmias and sudden cardiac death. Long QT syndrome is one of the many causes of QT prolongation, and is an inherited channelopathy associated with sudden cardiac death.

Causes

Common Causes

Drugs

Drug induced QT prolongation is usually a result of treatment by anti-arrhythmic drugs mainly Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol) or a number of other drugs that have been reported to cause this problem (e.g. Arsenic trioxide, cisapride). Some anti-psychotic drugs, such as Clozapine, Haloperidol, Ziprasidone and Quetiapine have a prolonged QT interval as a rare side effect. Genetic mutations may make one more susceptible to drug induced QT prolongation. Sorafenib, Voriconazole, vandetanib, Eribulin and Ezogabine.

Long QT Syndrome

Genetic abnormalities cause the Long QT Syndrome.

Electrolyte Disturbances

Electrolyte disturbances such as hyperkalaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, and hypomagnesemia can cause QT prolongation.

Neurologic Events

Subarachnoid hemorrhage and other intracranial events can cause QT prolongation. Widely slayed cerebral T waves are often seen as well.

Anorexia Nervosa

Anorexia nervosa and starvation can cause QT prolongation.

Causes by Organ System

Cardiovascular	Ischaemic heart disease, Long QT syndrome, Andersen cardiodysrhythmic periodic paralysis, Jervell and Lange-Nielsen syndrome, Romano-Ward syndrome, Timothy syndrome, Sinus node dysfunction, Second degree AV block, Third degree AV block
Chemical / poisoning	Arsenicals, cesium
Dermatologic	No underlying causes
Drug Side Effect	Alimemazine, Almokalant, Amiodarone, Amitriptyline, Arsenic trioxide, Artemether/lumefantrine, Asenapine, Astemizole, Azimilide, Azithromycin, Bepridil, Bretylium, Budipine, Chloroquine, Cibenzoline, Cisapride, Citalopram, Clomipramine, Clozapine, Crizotinib, Cyclophosphamide,Deferiprone, Degarelix, Desipramine, Diphenhydramine, Disopyramide, Dofetilide, Dolasetron, Doxepin, Dronedarone, Droperidol, Eribulin mesylate, Fesoterodine, Fluconazole, Fluoxetine, Fosphenytoin sodium, Gadofosveset, Granisetron, Grepafloxacin, Halofantrine, Haloperidol, Ibutilide, Iloperidone, Imipramine, Indapamide, Ketanserin, Ketoconazole, Lenvatinib, Lidoflazine, Lubeluzole, Methadone, Methadyl acetate, Midodrine, Mizolastine, Moxifloxacin, Naratriptan, Nicardipine, Nilotinib, Ondansetron, Pasireotide, Pazopanib, Pentamidine, Pimozide, Piperaquine, Prenylamine, Probucol, Procainamide, Propoxyphene, Quinidine, Quinine, Ranolazine, Retigabine, Ritodrine, Ritonavir, Saquinavir, Sertindole, Sotalol, Sparfloxacin, Tedisamil, Telithromycin, Terfenadine, Terodiline, Tetrabenazine, Thioridazine, Vandetanib, Vemurafenib, Venlafaxine, Vernakalant, Voriconazole, Vorinostat, Ziprasidone, Zotepine, Zuclopenthixol, Sematilide, Erythromycin, Azithromycin, Clarithromycin, Posaconazole, Gatifloxacin, Levofloxacin, Spiramycin, Mefloquine, Phenothiazines, Tricyclic antidepressants, Tetracyclic antidepressants, Butyrophenones, Dasatinib, Romidepsin, Sorafenib, Sunitinib, SSRIs, Resperidone, Methadone, Mibefradil, Diuretics, Granisetron, Domperidone, HIV protease inhibitors, Organophosphates, Cocaine, Papaverine, Chloral hydrate, Cesium chloride, Levomethadyl
Ear Nose Throat	No underlying causes
Endocrine	Hypothyroidism
Environmental	Zero gravity, cesium
Gastroenterologic	No underlying causes
Genetic	Andersen cardiodysrhythmic periodic paralysis, Jervell and Lange-Nielsen syndrome, Long QT syndrome, Myotonic dystrophy, Romano-Ward syndrome, Timothy syndrome
Hematologic	No underlying causes
Iatrogenic	Cesium poisoning
Infectious Disease	HIV infection
Musculoskeletal / Ortho	Myotonic dystrophy, Andersen cardiodysrhythmic periodic paralysis, Timothy syndrome
Neurologic	Subarachnoid hemorrhage, Intracranial disease
Nutritional / Metabolic	Acute starvation, Anorexia nervosa, Cesium, Hyperkalaemia, Hypocalcaemia, Hypoglycaemia, Hypokalaemia, Hypomagnesemia
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Ophthalmologic	No underlying causes
Overdose / Toxicity	Alimemazine, Almokalant, Amiodarone, Amitriptyline, Arsenic trioxide, Asenapine, Astemizole, Azimilide, Azithromycin, Bepridil, Bretylium, Budipine, Cesium, Chloroquine, Cibenzoline, Cisapride, Citalopram, Clomipramine, Clozapine, Crizotinib, Desipramine, Diphenhydramine, Disopyramide, Dofetilide, Dolasetron, Doxepin, Dronedarone, Droperidol, Eribulin mesylate, Fluconazole, Grepafloxacin, Halofantrine, Haloperidol, Ibutilide, Imipramine, Indapamide, Ketanserin, Ketoconazole, Lidoflazine, Lubeluzole, Methadone, Methadyl acetate, Midodrine, Mizolastine, Moxifloxacin, Naratriptan, Nicardipine, Nilotinib, Ondansetron, Pasireotide, Pazopanib, Pentamidine, Pimozide, Piperaquine, Prenylamine, Probucol, Procainamide, Propoxyphene, Quinidine, Quinine, Ranolazine, Retigabine, Ritodrine, Ritonavir, Saquinavir, Sertindole, Sotalol, Sparfloxacin, Tedisamil, Telithromycin, Terfenadine, Terodiline, Tetrabenazine, Thioridazine, Vandetanib, Vemurafenib, Venlafaxine, Vernakalant, Voriconazole, Vorinostat, Ziprasidone, Zotepine, Zuclopenthixol, Sematilide, Erythromycin, Azithromycin, Clarithromycin, Posaconazole, Gatifloxacin, Levofloxacin, Spiramycin, Mefloquine, Phenothiazines, Tricyclic antidepressants, Tetracyclic antidepressants, Butyrophenones, Dasatinib, Romidepsin, Sorafenib, Sunitinib, SSRIs, Resperidone, Methadone, Mibefradil, Diuretics, Granisetron, Domperidone, HIV protease inhibitors, Organophosphates, Cocaine, Papaverine, Chloral hydrate, Cesium chloride, Levomethadyl
Psychiatric	Anorexia nervosa, Timothy syndrome
Pulmonary	No underlying causes
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	Connective tissue diseases with anti-Ro/SSA antibodies
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Hypothermia, Acute starvation, Idiopathic

Causes in Alphabetical Order

Acute starvation Alimemazine Almokalant Amiodarone Amitriptyline Andersen cardiodysrhythmic periodic paralysis Anorexia nervosa Arsenic trioxide Arsenicals Artemether/lumefantrine Asenapine Astemizole Azimilide Azithromycin Azithromycin Bepridil Bretylium Budipine Butyrophenones Cesium chloride Chloral hydrate Chloroquine Cibenzoline Cisapride Citalopram Clarithromycin Clomipramine Clozapine Cocaine Connective tissue diseases with anti Ro/SSA antibodies Crizotinib Cyclophosphamide Dasatinib Deferiprone Desipramine Diphenhydramine Disopyramide Diuretics Dofetilide Dolasetron Domperidone Doxepin Dronedarone Droperidol Eribulin mesylate Erythromycin Fluconazole Gatifloxacin Granisetron Grepafloxacin Halofantrine Haloperidol HIV infection HIV protease inhibitors Hyperkalaemia Hypocalcaemia Hypoglycaemia Hypokalaemia Hypomagnesemia Hypothermia Hypothyroidism Ibutilide Idiopathic Imipramine Indapamide Intracranial disease Ischaemic heart disease Jervell and Lange-Nielsen syndrome Ketanserin Ketoconazole Levofloxacin Levomethadyl

Lidoflazine Lubeluzole Mefloquine Methadone Methadone Methadyl acetate Mibefradil Midodrine Mizolastine Moxifloxacin Myotonic dystrophy Naratriptan Nicardipine Nilotinib Ondansetron Organophosphates Papaverine Pasireotide Pazopanib Pentamidine Phenothiazines Pimozide Piperaquine Posaconazole Prenylamine Probucol Procainamide Propoxyphene Quinidine Quinine Ranolazine Resperidone Retigabine Ritodrine Ritonavir Romano-Ward syndrome Romidepsin Saquinavir Second degree AV block Sematilide Sertindole Sinus node dysfunction Sorafenib Sotalol Sparfloxacin Spiramycin SSRIs Sunitinib Tedisamil Telithromycin Terfenadine Terodiline Tetrabenazine Tetracyclic antidepressants Thioridazine Third degree AV block Timothy syndrome Tricyclic antidepressants Vandetanib Vemurafenib Venlafaxine Vernakalant Voriconazole Vorinostat Zero gravity Ziprasidone Zotepine Zuclopenthixol

Diagnosis

Electrocardiogram

How to Measure the QT

The QT interval is often measured incorrectly. It is measured incorrectly by 33% of EP physicians and 75% of general cardiologists. It is measured incorrectly by <5% of Long QT syndrome experts who deal with this on a frequent basis. The presence of a U wave can often lead to a false diagnosis of QT prolongation. In order to avoid this, the "teach the tangent" or "avoid the tail" rule is applied. In this method, a line is drawn on top of the downslope of the T wave as shown below with the dotted green line. The QT interval is measured where this green dotted line intersects with the isoelectric line as shown by the large green arrow. The red arrow is an incorrect assessment of the QT interval at the end of the U wave. Using the red arrow would lead to a misdiagnosis of QT prolongation.

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Examples of QT Prolongation

Shown below is an ECG demonstrating QT prolongation with a duration of 600 ms in lead II:

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Shown below is an EKG demonstrating QT prolongation:

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Shown below is a series of EKG's demonstrating progression of QT prolongation to Torsades de Pointes:

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Shown below is an example of ECG showing Torsades de Pointes with long QT interval.

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Treatment

In general, treatment involves reversing the underlying cause of the QT prolongation.

Replete Potassium and Magnesium

Electrolytes should be repleted or treated.

Withdraw or Reduce the Dose of Offending Drugs

Withdraw or reduce the dose of offending drugs.

Management of Long QT Syndrome

Beta-blockers are first line treatment in LQTs along with electrolyte repletion, and avoidance of triggers (drugs, supplements, loud noises). LQTs is one of the few diseases where genetic testing actually can provide important guidance such as who to put a AICD (defibrillator) in for primary prevention. Left stellectomy) is not a cure, but is second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers or breaks through beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and where the morbidity of an AICD seems excessive. Patients with Long QT syndrome should undergo secondary prevention with AICD implantation for secondary prevention if they sustain an aborted cardiac arrest or sudden cardiac death.

Primary Prevention

Withdrawal of Drugs and Supplements

Certain medications should be avoided in persons with long QT syndrome, to avoid worsening the condition. These medications include certain appetite suppressants, decongestants, and antibiotics such as erythromycin. Illicit drugs such as cocaine and amphetamines can be even more dangerous in persons with long QT syndrome.

Correct Electrolyte Disturbances

Illness that cause hypokalemia due to vomiting and diarrhea can aggravate long QT syndrome. Medications that can lower the levels of potassium in the blood should also be avoided.

Postassium Administration

The use of potassium supplementation is experimental and is not evidence based. The hypothesis is that ff the potassium content in the blood rises, the action potential shortens and it is for this reason that increasing potassium concentration may minimize the occurrence of arrhythmias. It should work best in LQT2 since the HERG channel is especially sensible to potassium concentration, but potassium supplementation is experimental and not evidence based.

Beta Blockers

Beta blockers are first line therapy in the treatment of Long QT syndrome.

Arrhythmia suppression involves the use of medications or surgical procedures that attack the underlying cause of the arrhythmias associated with LQTS. Since the cause of arrhythmias in LQTS is after depolarizations, and these after depolarizations are increased in states of adrenergic stimulation, steps can be taken to blunt adrenergic stimulation in these individuals. beta receptor blocking agents decrease the risk of stress or catecholamine induced arrhythmias.

Mexiletine

Mexiletine is a sodium channel blocker. In LQT3 the problem is that the sodium channel does not close properly. Mexiletine closes these channels and is believed to be potentially of use when other therapies fail. It should be especially effective in LQT3 but there is limited evidence to support this recommendation.

AICD Implantation

Genotype and QT interval duration are independent predictors of recurrence of life-threatening events during beta-blockers therapy. Specifically the presence of QTc >500ms and LQT2 and LQT3 genotype are associated with the highest incidence of recurrence. In these patients primary prevention with ICD (Implantable Cardioverster Defibrilator) implantaion can be considered.

An AICD should be implanted if:

• The QTc is > 550 ms and if it is not LQT1
• LQT2 in women and the QTc is > 500 ms, with or without symptoms
• In infants with 2:1 AV block (controversial)
• In JLNS (LQTS with deafness) given its malignant propensity (controversial)

Sympathetic Denervation

Videoscopic Left Cardiac Sympathetic Denervation Surgery (left stellectomy) is not a cure, but reduces the risk of sudden cardiac death and is indicated if:

• The patient does not tolerate beta blockers or breaks through beta blockers
• The patient faints while on beta blockers
• There is a history of VF terminating AICD shocks
• In young patients under the age of 12 where beta blockers are not deemed protective enough and where the morbidity of an AICD seems excessive.

Secondary Prevention

Patients with Long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.

Contraindicated medications

Congenital QT prolongation is considered an absolute contraindication to the use of the following medications:

• Disopyramide

QTc Bazett interval ≥500 ms is considered an absolute contraindication to the use of the following medications:

• Dronedarone