INTRODUCTION — The long QT syndrome (LQTS) is a disorder of myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram (ECG) (waveform 1). This syndrome is associated with an increased risk of polymorphic ventricular tachycardia, a characteristic life-threatening cardiac arrhythmia also known as torsades de pointes (waveform 2A-B). The primary symptoms in patients with LQTS include palpitations, syncope, seizures, and sudden cardiac death.

LQTS may be either congenital or acquired. These two primary syndromes (congenital and acquired LQTS) may be related, as some patients who develop acquired LQTS may have an inherited predisposition with abnormalities in repolarization that represent the forme fruste of LQTS. Acquired LQTS usually results from drug therapy (table 1), although hypokalemia, hypomagnesemia, and bradycardia can increase the risk of drug-induced LQTS. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Mutations in LQTS genes'.)

The clinical manifestations, diagnosis, and management of acquired LQTS will be reviewed here. The causes and pathophysiology of acquired LQTS, as well as the clinical manifestations, diagnosis, and management of congenital LQTS, are discussed elsewhere. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology" and "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Congenital long QT syndrome: Diagnosis" and "Congenital long QT syndrome: Treatment".)

CLINICAL PRESENTATION AND EVALUATION — The clinical presentation of acquired LQTS is variable; many patients are asymptomatic and identified solely by QT prolongation on the ECG, while a minority are symptomatic and present with palpitations, syncope, or sudden cardiac arrest. The evaluation of all patients with suspected acquired LQTS includes a thorough history, including medications and recent changes in medications, along with a 12-lead ECG and bloodwork (which includes serum electrolytes, particularly potassium and magnesium, as well as a toxicology screen).

Symptoms — In the absence of arrhythmias, patients with acquired LQTS will be asymptomatic. When an arrhythmia develops, the type and intensity of symptoms, if present, will vary depending upon the rate and duration of the torsades de pointes (TdP) along with the presence or absence of significant comorbid conditions. Patients with acquired LQTS who notice symptoms typically present with one or more of the following symptoms:

●Palpitations

●Syncope or presyncope

●Sudden cardiac arrest

Most commonly, symptomatic patients will be lightheaded or presyncopal and may or may not report palpitations. If the ventricular tachyarrhythmia rate is fast and/or the duration of the episode is sustained, this can lead to hypotension and associated hemodynamic compromise, and patients may experience syncope. While TdP is frequently self-terminating, if the arrhythmia persists, patients may present with sudden cardiac arrest.

ECG findings — All patients with suspected acquired LQTS should have a 12-lead ECG performed. The QT interval should be measured manually on all available ECGs (including old ECGs for comparison, when available) using multiple leads (preferably leads II and V5) and then corrected for heart rate. The 2011 American Heart Association/American College of Cardiology (AHA/ACC) scientific statement on prevention of TdP in hospital settings recommended that a QTc over the 99th percentile should be considered abnormally prolonged [1]. This corresponds to a QTc of >470 milliseconds for men and pre-pubertal females, and >480 milliseconds for post-pubertal women. A QTc >500 milliseconds is considered highly abnormal for both men and women.

Normal QTc ranges and general ECG principles — Overall, the average QTc in healthy persons after puberty is 420±20 milliseconds. In general, the 99th percentile QTc values are 470 milliseconds in postpubertal males and 480 milliseconds in postpubertal females. The QT interval varies inversely with the heart rate; therefore, the QT measurement is adjusted for the heart rate, resulting in the corrected QT interval, or QTc. (See "Congenital long QT syndrome: Diagnosis", section on 'QT rate correction'.)

●Measuring the QT interval – The computer-derived QTc should always be confirmed or corrected manually. The QT interval is measured from the onset of the QRS complex to the point at which the T wave ends or the tangent reaches the baseline if the end of T wave cannot be precisely determined (waveform 1). Accurate measurements can be technically challenging, largely due to difficulties in clearly identifying the end of the T wave. The QT interval should be measured in multiple beats and in several leads. The technique of measuring the QT interval is discussed separately. (See "ECG tutorial: ST and T wave changes", section on 'Prolonged QT interval'.)

●Impact of U waves – Identifying the termination of the T wave can be particularly difficult when a prominent U wave is present. The U wave should not be included if it is distinct from and smaller than 50 percent of the T wave. Erroneous inclusion of the U wave in the QT interval measurement can lead to overdiagnosis of LQTS [2]. Sometimes, a prominent U wave may exaggerate the appearance of a prolonged QTU.

●Impact of bundle branch block or other intraventricular conduction delay – A variety of methods have been proposed for assessment of the duration of repolarization in patients with native or paced right or left bundle branch block or other wide QRS [3-8]. The rate-corrected JT interval can be utilized as a surrogate for QT and can distinguish those with repolarization abnormalities such as LQTS from depolarization delay [3].

●Which lead should be used? – QT intervals vary significantly among leads [9]. Most normal reference ranges are based upon measurements from lead II, and lead V5 is often favored because of the clarity of T wave termination [10,11].

QT rate correction — Under normal circumstances, the duration of repolarization depends upon the heart rate. The QT interval is longer at slower rates and shorter at faster rates. For this reason, formulas have been developed to "correct" the QT interval for heart rate (or the duration of the RR interval), although none are ideal (calculator 1) [12-15]. The most commonly used rate correction formula was developed by Bazett [16]:

Although this approach is simple and generally accurate, it is less accurate at heart rate extremes and results in overcorrecting at high heart rates and undercorrecting at low heart rates [12]. Normative values are available for newborns and older children, which are standardized by age [17]. (See "ECG tutorial: Basic principles of ECG analysis", section on 'QT interval'.)

QT nomogram — A QT interval nomogram based upon QT interval and heart rate is an alternative method for assessing arrhythmia risk. The nomogram was developed based upon a literature review of TdP cases and compared with Bazett QT rate correction [18]. The sensitivity and specificity of the QT nomogram were 96.9 (95% CI 93.9-99.9) and 98.7 percent (95% CI 96.8-100), respectively. The nomogram performed similarly to Bazett QTc = 500 ms with sensitivity and specificity of 93.8 (95% CI 89.6-98.0) and 97.2 percent (95% CI 94.3-100) and with higher specificity than Bazett QTc = 440 ms with sensitivity and specificity of 98.5 (95% CI 96.3-100) and 66.7 percent (95% CI 58.6-74.7). However, this nomogram has not been prospectively validated.

DIAGNOSIS — The diagnosis of acquired LQTS can be made in a patient with sufficient QT prolongation on the surface ECG in association with a medication or other clinical scenario (ie, hypokalemia or hypomagnesemia) associated with QT prolongation. Ideally, the diagnosis is made following review of a full 12-lead ECG, but sometimes a single-lead rhythm strip is adequate if a full 12-lead ECG cannot be obtained. The acquired QT prolongation is typically reversible upon removal of the underlying etiology, such as discontinuation of an offending medication or correction of electrolyte derangements.

MANAGEMENT — The initial management of patients with torsades de pointes (TdP) varies depending on the hemodynamic stability of the patient. Emergency management is required in unstable patients (algorithm 1), while additional time may be spent determining the etiology and treating any underlying precipitating factors in patients who are hemodynamically stable (although treatment for such patients should usually be promptly administered). Following initial management and stabilization of the patient, subsequent management of the patient will be guided by the initial presentation (ie, hemodynamically stable or unstable) and the initial approach to treatment.

The cornerstone of the management of patients with acquired LQTS is addressing the underlying cause by identifying and stopping any precipitating drug(s) and aggressive correction of any metabolic abnormalities, such as hypokalemia or hypomagnesemia [19]. All drugs that prolong the QT interval (table 1) (see also www.crediblemeds.org/) should be avoided because they predominantly act by a common mechanism, inhibition of IKr current [20-33]. Correcting hypokalemia may be particularly important because a low serum potassium concentration enhances the degree of drug-induced inhibition of IKr, increasing the QT interval [22]. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment'.)

Acute management of TdP — All patients with TdP should have an immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamically stable or unstable. While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should:

●Attach the patient to a continuous cardiac monitor

●Establish intravenous (IV) access

●Obtain a 12-lead ECG

●Administer supplemental oxygen

●Send blood for appropriate initial studies

Differentiation between a hemodynamically stable versus unstable patient is as follows (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'):

●An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure (HF), but generally remains awake with a discernible pulse. Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms (algorithm 1).

●A stable patient shows no evidence of hemodynamic compromise despite a sustained rapid heart rate, but should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as the TdP persists.

Patients with TdP who are initially stable may rapidly become unstable, particularly in the setting of extremely rapid heart rates (greater than 200 beats per minute) or significant underlying cardiac comorbidities.

Unstable patients — Patients with TdP who are felt to be hemodynamically unstable, severely symptomatic, or become pulseless require prompt treatment with electrical cardioversion/defibrillation. Initial treatment with antiarrhythmic medications, with the exception of IV magnesium, is not indicated for hemodynamically unstable or pulseless patients.

Stable patients — Patients with TdP who are hemodynamically stable on presentation may remain stable or may become unstable rapidly and without warning. As such, therapy should be promptly provided to most patients.

●For patients with a single episode of TdP, treatment with IV magnesium along with correction of metabolic/electrolyte derangements and/or removal of any inciting medications may be sufficient. The patient should be carefully monitored until electrolytes are normalized and the QT interval nearly normalizes.

●For patients with multiple self-terminating episodes of TdP, the same therapies are utilized as for patients with a single episode (ie, IV magnesium, correction of metabolic/electrolyte derangements, and/or removal of any inciting medications), along with additional interventions to regularize the heart rate, which include overdrive atrial pacing and/or IV isoproterenol infusion.

Therapies with proven benefit — Specific therapy of TdP, the usual ventricular arrhythmia in acquired LQTS, differs from that in congenital LQTS due in part to pathophysiologic differences between the two forms (table 2). As an example, a bradycardia usually is associated with TdP in acquired LQTS, whereas catecholamine surges trigger TdP in some types of congenital LQTS (figure 1).

●Magnesium – IV magnesium sulfate is first-line therapy, being highly effective for both the treatment and prevention of recurrence of long QT-related ventricular ectopic beats or TdP [34-36]. The benefit occurs without shortening of the QT interval and is seen even in patients with normal serum magnesium concentrations at baseline. The rate of magnesium infusion is slower when a pulse is present, as rapid magnesium infusion may be associated with hypotension and asystole.

•Adults with TdP and pulse – The standard regimen for an adult is a 1 to 2 gram IV bolus of magnesium sulfate (2 to 4 mL of 50% solution [500 mg/mL]) mixed with D5W to a total volume of 10 mL or more (eg, 50 to 100 mL over 15 minutes) [36,37]. If no response is seen or TdP recurs, the magnesium sulfate dose may be repeated immediately to a total of 4 grams in one hour. Use of continuous infusion (as an adjunct to bolus dosing) varies among clinicians. Some clinicians administer a continuous infusion of 0.5 to 1 g/hour (8 to 16 mg/min) if TdP persists after one or more bolus doses.

•Adults with TdP and no pulse – Magnesium is administered in conjunction with electrical cardioversion/defibrillation. 1 to 2 g magnesium sulfate (2 to 4 mL of 50% solution [500 mg/mL]) is diluted in 10 mL D5W and administered as a bolus over 1 to 2 minutes; the intraosseous route is used if IV not available. If Td recurs or the QTc remains prolonged, some experts administer up to 2 additional 2 g bolus doses as needed (total maximum dose of 6 g).

•Children – The bolus dose in children is 25 to 50 mg/kg; there are no published data on IV maintenance dosing in children.

●Overdrive pacing – Temporary transvenous overdrive pacing (atrial or ventricular) generally is reserved for patients with long QT-related TdP who do not respond to IV magnesium [34,35]. Additionally, patients with a pre-existing permanent pacemaker may have the device reprogrammed to increase the pacing rate, while patients with a pre-existing implantable cardioverter-defibrillator (ICD) may additionally have the ICD reprogrammed to a prolonged detection time, thereby delaying ICD shock for episodes of TdP that may self-terminate.

Pacing at rates of approximately 100 beats per minute will decrease the dispersion of refractoriness and the development of early afterdepolarizations, and may shorten the surface QT interval, especially if there is an associated bradycardia. Many of the class IA and class III antiarrhythmic drugs that cause TdP have a property of "reverse use dependency," in which the QT interval decreases as the heart rate increases and lengthens as the heart rate slows [38] (see "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Torsades de pointes'). These changes may be mediated in part by changes in the extracellular potassium concentration [22].

The efficacy of overdrive pacing was illustrated in a report of nine patients with life-threatening ventricular arrhythmias and drug-induced LQTS [39]. Acceleration of the heart rate produced immediate suppression of all arrhythmias, with a reduction in the QT interval from 0.65 to 0.50 seconds. Similar findings were noted in another small series [40].

●Isoproterenol – Isoproterenol (initial dose 0.05 to 0.1 mcg/kg per min in children and 2 mcg/min in adults, then titrated to achieve a heart rate of 100 beats per minute) also can be used to increase the sinus rate and decrease the QT interval [34,35,41]. We favor placement of a temporary pacemaker in the treatment of most cases of TdP that do not respond to magnesium. However, isoproterenol can be used as a temporizing measure prior to pacing.

●Alkalinization of the plasma, via the administration of sodium bicarbonate, is useful when TdP is due to quinidine [42]. (See "Enhanced elimination of poisons", section on 'Urinary alkalinization'.)

Therapies with unproven benefit

●Potassium – An IV infusion of potassium may be beneficial in patients with a normal baseline serum potassium concentration. The potential benefit of IV potassium was illustrated in a report of 20 normokalemic patients with QT prolongation due to quinidine or HF [43]. The administration of IV potassium (0.5 meq/kg to a maximum of 40 meq) raised the plasma potassium concentration by 0.7 meq/L, reversed QT prolongation and QT morphologic changes (U waves and bifid T waves), and decreased QT dispersion. It is uncertain, however, if this therapy is effective for preventing or reversing TdP.

●Class IB antiarrhythmic drugs – Medications such as lidocaine and phenytoin shorten the action potential duration and, based upon small case series, may be effective in the acute management of TdP and ventricular fibrillation [44-48]. They appear to be less predictably effective than pacing or isoproterenol [35,44].

Initial management of QT prolongation without symptoms — Patients with prolonged QT with syncope (without documented TdP) or ECG signs of instability (ventricular ectopy, T wave alternans, atrioventricular [AV] block, or QRS widening) should be admitted for telemetry observation during withdrawal of the toxic agent (with immediate availability of an external defibrillator) and treatment of arrhythmias if indicated. In addition, admission and monitoring during drug withdrawal is suggested for patients with markedly prolonged QTc (>500 milliseconds) or an increase in QTc of at least 60 milliseconds compared with the predrug baseline value [1].

Mild QT prolongation (QTc <500 milliseconds and <60 milliseconds increase from baseline) without TdP or syncope may be tolerated and monitored as an outpatient when it is associated with needed therapy with a drug known to cause it. Specific protocols for such management have not been established, but we suggest intermittent monitoring with ECGs and Holter recordings particularly at times of dose changes.

Precautions when using QT-prolonging drugs — For patients who are treated with drugs that have been associated with LQTS (table 1) (see also www.crediblemeds.org/), the following recommendations have been made [49]:

●Caution should be used when prescribing a drug that prolongs the QT interval in patients with one or more risk factors (see "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Risk factors'). Decisions regarding use of a QT-prolonging drug should be based upon an individualized risk-benefit analysis. Alternative agents should be considered. Use of more than one QT-prolonging drug should be avoided whenever possible.

●A baseline ECG should be obtained prior to the administration of the drug. ECGs should also be obtained during the course of treatment to detect prolongation of the QT interval. The 2011 AHA/ACC scientific statement on prevention of TdP suggests a strategy of documenting the QTc interval before and at least every 8 to 12 hours after the initiation, increased dose, or overdose of QT-prolonging drugs [1]. If QTc prolongation is observed, documentation of more frequent measurements is recommended.

●Patients being treated with QT-prolonging drugs should be instructed to report promptly any new symptoms including palpitations, syncope, or near-syncope. They should also report clinical changes that could lead to hypokalemia, such as gastroenteritis or the initiation of diuretic therapy. Any identified electrolyte abnormalities should be promptly corrected to minimize the risk of arrhythmias.

●The duration of QTc monitoring depends upon the duration of treatment with the QT-prolonging drug and the drug half-life. ECG monitoring, once on steady-state of new drug regimen, should be performed to measure QTc.

Long-term management — Patients with acquired LQTS should be educated about the culprit drugs and other QT-prolonging drugs (including being provided with a list as available at www.crediblemeds.org/) and potential drug-drug interactions [1]. Additional information can also be found using the Lexicomp drug interactions tool. In some patients, drug-associated acquired LQTS represents a "forme fruste" of congenital LQTS in which a mutation or polymorphism in one of the known LQTS genes is clinically concealed; therefore, it is diagnostically inapparent until the patient is exposed to the inciting drug or other predisposing factor.

In patients with eating disorders, nutritional rehabilitation will correct the QT prolongation over the longer term (3 to 18 months) [50,51]. These patients have long-term risks of recurrent electrolyte derangements and arrhythmias. (See "Eating disorders: Overview of prevention and treatment".)

A permanent pacemaker may be required in the occasional patient with a chronic bradyarrhythmia (due to sinus node dysfunction or AV block) who has bradycardia- or pause-dependent TdP (table 3). (See "Permanent cardiac pacing: Overview of devices and indications".)

SCREENING OF FAMILY MEMBERS — In addition to treating the underlying cause, a thorough history and ECG screening of immediate family members is recommended because of the potential for unmasking an inherited form and, therefore, potential for other family members to harbor mutations causing congenital LQTS. (See "Acquired long QT syndrome: Definitions, causes, and pathophysiology", section on 'Mutations in LQTS genes' and "Congenital long QT syndrome: Diagnosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Long QT syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Acquired long QT syndrome (LQTS) usually results from drug therapy, hypokalemia, and/or hypomagnesemia (table 1). Some patients with acquired LQTS have an underlying "forme fruste" of congenital LQTS. (See 'Introduction' above.)

●The clinical presentation of acquired LQTS is variable; many patients are asymptomatic and identified solely by QT prolongation on the electrocardiogram (ECG), while a minority are symptomatic and present with palpitations, syncope, or sudden cardiac arrest. The evaluation of all patients with suspected acquired LQTS includes a thorough history, including medications and recent changes in medications, along with a 12-lead ECG and bloodwork (which includes serum electrolytes, particularly potassium and magnesium, as well as a toxicology screen). (See 'Clinical presentation and evaluation' above.)

●The diagnosis of acquired LQTS can be made in a patient with sufficient QT prolongation on the surface ECG in association with a medication or other clinical scenario (ie, hypokalemia or hypomagnesemia) associated with QT prolongation. (See 'Diagnosis' above.)

●The initial management of patients with torsades de pointes (TdP) varies depending on the hemodynamic stability of the patient. Emergency management is required in unstable patients (algorithm 1), while additional time may be spent determining the etiology and treating any underlying precipitating factors in patients who are hemodynamically stable (although treatment for such patients should usually be promptly administered). (See 'Acute management of TdP' above.)

•Patients with TdP who are felt to be hemodynamically unstable, severely symptomatic, or become pulseless require prompt treatment with electrical cardioversion/defibrillation. Initial treatment with antiarrhythmic medications, with the exception of intravenous (IV) magnesium, is not indicated for hemodynamically unstable or pulseless patients.

•Patients with TdP who are hemodynamically stable on presentation may remain stable or may become unstable rapidly and without warning. As such, therapy should be promptly provided to most patients. For patients with a single episode of TdP, treatment with IV magnesium along with correction of metabolic/electrolyte derangements and/or removal of any inciting medications may be sufficient. For patients with multiple self-terminating episodes of TdP, we use the same therapies as for patients with a single episode, along with additional interventions to regularize the heart rate, which include overdrive atrial pacing and/or IV isoproterenol infusion.

●Patients with prolonged QT with syncope (without documented TdP) or ECG signs of instability (ventricular ectopy, T wave alternans, atrioventricular block, or QRS widening) should be admitted for telemetry observation during withdrawal of the toxic agent (with immediate availability of an external defibrillator) and treatment of arrhythmias if indicated. In addition, admission and monitoring during drug withdrawal is suggested for patients with markedly prolonged QTc (>500 milliseconds) or an increase in QTc of at least 60 milliseconds compared with the predrug baseline value. (See 'Initial management of QT prolongation without symptoms' above.)

●Patients with acquired LQTS should be educated about the culprit drugs and other QT-prolonging drugs (including being provided with a list as available at www.crediblemeds.org/) and potential drug-drug interactions. (See 'Long-term management' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Stephen Seslar MD, PhD, and the late Mark E. Josephson, MD, who contributed to an earlier version of this topic review.