Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (2024)

The QT interval is the time interval from the beginning of the QRS complex to the end of the T-wave. This interval represents the total time taken to depolarize and repolarize the ventricles (Figure 1). The length of the QTinterval correlates strongly with the risk of potentially life-threatening ventricular arrhythmias. Therefore, the QT interval must always be assessedwhen interpreting the ECG.Long QT syndrome (LQTS)is manifest when a long QT interval induces ventricular arrhythmias.

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Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (1)

The QT intervalis inversely related to heart rate. As the heart rate increases, the QT interval decreases and vice versa. The physiological purpose of this phenomenon is to allow for faster cardiac cycles during tachycardia (e.g during physical exertion). Therefore, to judge whether the QT interval is normal or not, one must adjust for the current heart rate. This is done by adjusting the QT interval for the heart rate, and the resulting QT interval is referred to as corrected QT interval, or simply QTc interval. The primary hazard lies in long QTc intervals, because they induce a very unstablepolymorphic ventricular tachycardia referred to astorsade de pointes. Abnormally short QTc interval is also arrhythmogenic but it is a very rare condition.

Several formulas have been suggested to calculate corrected QT intervals.Some of these formulas follow:

Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (2)

Bazett Formula:QTc = QT interval / √(RR interval)

Fridericia Formula:QTc = QT interval / (RR interval)1/3

Framingham Formula:QTc = QT interval + 154 x (1– RR interval)

Hodges Formula:QTc = QT interval + 1.75 x [(60 / RR interval) − 60]

RR interval = 60 / HR

Calculate corrected QTc interval with traditional formulas

Bazett’s formula is the most commonly used formula. However, all above-listed formulas were developed many decades ago and they have multiple drawbacks. For example, Bazett’s formula is only suitable in adults with a heart rate between 60 and 90 beats per minute. Bazett’s formula over-adjusts at higher heart rates and under-adjusts at lower heart rates.

1 – 15 years, male and femaleAdult, maleAdult, female
Normal<440 ms<430 ms<450 ms
Upper limit440–460 ms430–450 ms450–470 ms
Prolonged>460 ms>450 ms>470 ms

It is recommended that the automatic (machine) calculation of corrected QT interval be used. Such QTc intervals are derived by all modern ECG machines and the formulas used are more precise than those listed above.It is recommended that whenever the QTc interval is prolonged, it should be verified manually.

How to measure the QT interval

Expert opinion suggests that QT intervals should be measured as follows (Anderson et al):

  • The QT interval should be measured manually, from the beginning of the QRS complex to the end of the T wave.
  • The QT interval should be measured in 3 to 5 consecutive beats in leads II, V5 and V6. Leads without U waves are preferred.
  • Calculate the mean QT interval for each lead and use the longest QT interval obtained.
  • Large U waves that are fused with the T wave should be included in the measurement. This may result in an overestimation of the QT interval.
  • If the patient uses QT-prolonging drugs, the QT interval should be measured during peak plasma concentrations of that drug.
  • The QT interval should be adjusted for heart rate.
Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (3)

Long QT interval causes long QT syndrome

An abnormally prolongedQTc interval isreferred to as long QT interval. The upper reference limit for QTc interval is 460 ms in males and 470 ms in females. QTc intervals exceeding these limits may cause torsade de pointes. If this occurs, i.e if a person with a long QT interval experiences such ventricular arrhythmias, the condition is referred to as long QT syndrome (LQTS).

Causes of long QT interval

A long QT interval is either congenital (genetic) or acquired.

Congenital long QT syndromeis caused by mutations in cardiac ion channels. More than 10 types of congenital prolongation of the QT interval have been discovered. Congenital QT prolongation is a very serious condition with high mortality. Among untreated patients who have experienced one episode of syncope, 20% die within 1 year. Fortunately, this mortality figure may be reduced to 1% over 15 years of follow-upwith the use of evidence-based treatments. Three types of LQTS (LQT1, LQT2 and LQT3) represent roughly 90% of all cases of congenital LQTS. It is estimated that the prevalence of congenital QT prolongation is 1 per 2000 individuals in the population (prevalence figures from Italy). Importantly, individuals with congenital QT prolongation frequently report occurrences of unexplained syncope or cardiac arrest in the family. Such hereditary information is a strong predictor of sudden cardiac death.

Acquiredlong QTsyndromeis caused by medications (amiodarone, sotalol, procainamide), hypokalemia, hypomagnesaemiaand pronounced bradycardia. Because each of these factors (medications, electrolyte disorders and bradycardia) are all common, but only appear to cause QT prolongation in some individuals, it is thought that there has to be an underlying genetic susceptibility to develop acquired long QT syndrome.

The risk of developing torsade de pointes (polymorphic ventricular tachycardia) is evident in both congenital and acquired QT prolongation. The longer the QT interval the greater the risk of developing torsade de pointes. In general, torsade de pointes develops at QTc intervals greater than 490 milliseconds.

Torsade de pointes is usually induced by a premature ventricular beat occurring early in the cardiac cycle. The risk of torsade de pointes increases during bradycardia. Torsade de pointes causes syncope (or pre-syncope) but the arrhythmia is usually self-terminating (within 30 seconds). A minority of cases of torsade de pointes progress to ventricular fibrillation, which is fatal unless treatment is given promptly. Figure 2 shows torsade de pointes.

Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (4)

Besides the QT interval itself, the T-wave may provide valuable information regarding the type of long QT syndrome; particularly it may differentiate between type 1LQTS, type 2LQTS and type 3 LQTS. The T-wave should be assessed in the chest leads. Refer to Figure 3. Occasionally persons with LQTS display T-wave alternans, meaning that the amplitude or direction of the T-wave alternates from one beat to the next. T-wave alternans is an indicator of very high risk of torsade de pointes. Sinus pauses may also occur in congenital LQTS.

Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (5)

ECG criteria for torsade de pointes

  • Prolonged QTc interval before the appearance of torsade de pointes.
  • Twisting of the QRS complexes around the isoelectric baseline (polymorphic ventricular tachycardia).

Congenital long QT syndrome (LQTS)

At least 13 variants of congenital LQTS have been described. The mutations haveautosomal inheritance with reducedpenetrance. LQTS type 1, type 2 and type 3 (called LQT1, LQT2 and LQT3) represent 90% of all cases of long QT syndrome. LQT1 and LQT2 each represent roughly 40% of all cases.

LongQT syndrome type 1 (LQT1)is caused by a mutation in the potassium channelKCNQ1 (loss of function mutation). The arrhythmias usually occur during physical activity (for some reason swimming appears to be highly arrhythmogenic) and other situations with high sympathetic activity. LQT1 is characterized by T-wave with a broad base(Figure 3). LQT1 is the most common type of congenital LQTS.

Long QT syndrome type 2 (LQT2)is caused by a mutation in the potassium channelKCNH2 (loss of function mutation). The arrhythmias typically occur at sudden surprises (sudden sounds, fear or other situations with abrupt and sudden stress),stress, physical activity or during sleep. The T-wave has low amplitude with an additional hump or notch (Figure 3).Women with LQT2 who are in the postpartum period have very high risk of developingtorsade de pointes.

Long QT syndrome type 3 (LQT3): is caused by a mutation in the sodium channel SCN5A (leads to increased sodium flows). The risk of arrhythmia is highest during sleep. Bradycardia is also highly arrhytmogenic in these patients. The ST-segment is stretched out, the T-wave occurs late and is pointed (Figure 3).

Long QT syndrome type 4 (LQT4): is rare and represents 1% of all cases. The mutation occurs in theANKB gene which produces a protein that anchors membrane proteins to the cytoskeleton.LQT3 can cause multiple arrhythmias, such as familial catecholamine ventricular tachycardia, atrial fibrillation, conduction defects, sinus node dysfunction and bradycardia.

The other variants of LQTS are extremely rare and usually part of more severe syndromes which engage multiple organ systems. These types are not discussed here.

Schwartz criteria for diagnosis of congenital LQTS

Schwartz criteria are used to diagnose congenital LQTS. These criteria are presented in Table 1.

Table 1. Long QT syndrome diagnostic criteria (Schwartz et al):

QTc interval≥480 ms3
460–479 ms2
450–459 ms (male)1
QTc during 4th minute of recovery from exercise stress test ≥480 ms1
Torsade de pointes2
T-wave alternans1
Low heart rate for age (resting heart rate below the 2nd percentile)0.5
Clinical History
Syncope with stress2
Syncope without stress1
Congenital deafness0.5
Family history
Family members with definite LQTS1
Unexplained sudden cardiac death below age 30 among immediate family members0.5

Evaluation of risk

  • ≤1 point: low probability of LQTS.
  • 1.5 – 3 points: intermediate probability of LQTS.
  • ≥3.5 points: high probability.


  • ECG findings are only valid in the absence of medications or disorders known to affect these electrocardiographic features.
  • QTc is calculated by Bazett’s formula where QTc = QT/√RR.
  • Only one of syncope and torsade de pointes can count.
  • The same family member cannot be counted inboth criteria under Family history.

Long QT syndrome induced by medications and drugs

Long QT syndrome caused by medications is much more common than congenital variants. Medications that may induce or aggravate long QT syndrome include adrenaline, certain antihistamines, erythromycine, trimetoprime, sulfa, pentamidine, kinidine, procainamide, disopyramide, sotalol, probukol, bepridil, difetilid, ibutilid, cisaprid, ketokonazol, itrakonazol, tricyclic antidepressants, fenotiazines, haloperidol, indapimid, certain antiviral drugs, etc (Table 2). The list of drugs that cause LQTS is very long and updated continuously. Thecomplete list is provided by CredibleMeds (www.crediblemeds.com) which is supported by the FDA.

Table 2. Drugs causing or aggravating long QT syndrome.

AnestheticsEnfluraneProbableDrug-drug interactions lead to QT prolongation
HalothaneProbableNonspecific arrhythmias reported in package insert.
AntiarrhythmicsAmiodaroneCertainHighQT interval prolongation, Torsade de pointesi.v. affects QTc less than oral; proarrhythmia infrequent.
DisopyramideCertainQT interval prolongation, Torsade de pointesRate appears lower than that of quinidine
DofetilideCertainHighQT interval prolongation, Torsade de pointesProarrhythmia 0.8%.
FlecainideCertainHighQT interval prolongation, Torsade de pointesProarrhythmia “rare.”
IbutilideCertainHighQT interval prolongation, Torsade de pointesProarrhythmia 1.7%.
ProcainamideCertainHighQT interval prolongation, Torsade de pointesRate appears lower than that of quinidine.
PropafenoneCertainModerateQT interval prolongation, Torsade de pointesProarrhythmia “rare.”
QuinidineCertainHighQT interval prolongation, Torsade de pointes“Quinidine syncope” in 2–6% of patients.
SotalolCertainHighQT interval prolongation, Torsade de pointesProarrhythmia ~2%.
AnticonvulsantsFelbamateProposedTorsade de pointes, according to manufacturer.
FosphenytoinProposedQT interval prolongation according to manufacturer.
AntidepressantsAmitriptylineCertainModerateNonspecific ECG changes reported in package insert.
DesipramineCertainQT interval prolongationVF, sudden death reported by manufacturer.
FluoxetineProbableQT interval prolongation, Torsade de pointes1 in 10,000 ventricular arrhythmias reported by manufacturer.
ImipramineCertainModerateNonspecific arrhythmias reported in package insert.
MaprotilineCertainECG changes; QRS reported in package insert.
NortriptylineCertainNonspecific arrhythmias reported in package insert.
ParoxetineProbableTorsade de pointesLower risk than that of TCAs.
SertralineProbableQT interval prolongation, Torsade de pointesLower risk than that of TCAs.
VenlafaxineProposedQT interval prolongation1:1000 risk of arrhythmia reported in package insert.
AntihistaminesAstemizoleCertainModerateNot applicable
LoratadineProposedUnknownProlongation appears unlikely.
AntiinfectivesClarithromycinProbableModerateQT interval prolongation, Torsade de pointes
ErythromycinCertainMedium highQT interval prolongation, Torsade de pointesKnown drug-drug interactions with other agents (e.g., terfenadine).
FluconazoleProbableRisk may be higher with i.v. dosing.
FoscarnetProposedQT interval prolongation
GatifloxacinProbableQT interval prolongation
KetoconazoleProbableQT interval prolongation, Torsade de pointesKnown drug-drug interactions with other agents (e.g., cisapride).
LevofloxacinProposedTorsade de pointesLower risk than that of similar agents.
MefloquineProposedQT with halofantrine.
MoxifloxacinProbableQT interval prolongationLower risk than that of similar agents.
PentamidineCertainModerateQT interval prolongation, Torsade de pointes
AntipsychoticsChlorpromazineProbableNonspecific ECG changes and sudden death reported by manufacturer.
HaloperidolCertainModerateQT interval prolongation, Torsade de pointes
MesoridazineCertainQT interval prolongation, Torsade de pointes
PimozideCertainQT interval prolongation, Torsade de pointesDrug-drug interactions also lead to QT prolongation.
QuetiapineProposedQT interval prolongation
RisperidoneProposedQT interval prolongationSudden death reported by manufacturer.
ThioridazineCertainModerateQT interval prolongation, Torsade de pointes
ZiprasidoneCertainQT interval prolongation
Cancer drugsArsenictrioxideCertainQT interval prolongation, Torsade de pointes
TamoxifenProbableQT interval prolongationOverdose situations.
Cardiovascular agentsBepridilCertainModerateQT interval prolongation, Torsade de pointesQTc increases by ~8%.
IndapamideProposedQT interval prolongation
IsradipineProposedQT interval prolongation according to manufacturer.QTc increases by ~3%.
Moexipril hydrochlorothiazideProposedQT interval prolongation according to manufacturer.
NicardipineProposedQT interval prolongation according to manufacturer.
Gatrointestinal agentsCisaprideCertainModerateQT interval prolongation, Torsade de pointes
OctreotideProposedQT interval prolongation
DroperidolCertainCertainQT interval prolongation, Torsade de pointes
DolasetronProposedQT interval prolongation according to manufacturer.
Migraine agentsNaratriptanProbableQT interval prolongation
SumatriptanProbableQT interval prolongation
RizatriptanProbable1:1000 risk of arrhythmia.
ZolmitriptanProbableQT interval prolongation
Miscellaneous agentsAmantadineLow
LevomethadylProbableQT interval prolongation, Torsade de pointes
MethadoneProbableSyncope according to manufacturer.
SalmeterolProposedQT interval prolongation according to manufacturer.
TizanidineProbableQT interval prolongation1:1000 risk of arrhythmia.

Management of long QT syndrome (LQTS)

Torsade de pointes with hemodynamic compromise

Torsade de pointes causing syncopeis treated with defibrillation. Start with 150 J (biphasic shock) and increase by 50 J for each shock. Ventricular fibrillation and cardiac arrest is treated with conventional resuscitation.

Hemodynamically stable torsade de pointes

Treatment of torsade de pointes is similar in congenital and acquired LQTS. Torsade de pointes is paroxysmal, which means that the arrhythmia occurs intermittently and self-terminates. It tends to recur, even after successful defibrillation. There is always risk of ventricular fibrillation which is why a defibrillator must be close at hand and readiness to perform resuscitation is necessary.

Treatment algorithm

  1. All medications/drugs that may cause or aggravate the arrhythmia must immediately be stopped.
  2. Magnesium infusion (regardless of blood magnesium levels): 1 gram of magnesium is administered intravenously for 60 seconds. This may be repeated after 5–10 minutes. If a continuous infusion is necessary, the dose is 5–10 mg/min.
  3. Potassium infusion: only necessary ifthe patient has hypokalemia.
  4. Bradycardia must be corrected: bradycardia may induce and aggravate torsade de pointes. To correct bradycardia, the following options are at hand:
    • atropine i.v 1–2 ml 0.5 mg/ml.
    • isoprenaline (isoproterenol) 0.01μg/kg/min, which is titrated up until bradycardia resolves. Note that isoprenaline must be administeredcarefully because it activates beta-adrenergic receptors which is why it may aggravate the arrhythmia. In congenital LQTS isoprenaline is contraindicated becausethe risk of ventricular fibrillation is high. Therefore, isoprenaline may only be used in acquired LQTS and temporarily until a pacemaker can be established.
    • temporary transcutaneous/transvenous pacemaker. The pacemaker electrode should be placed in the atria and the rate should be set to 90 beats per minute. The rate may be increased gradually until the arrhythmia resolves.

The rationale behind atropine, isoprenaline and pacemaker therapy is simple: these three interventions all increase the heart rate, which decreases the QTc interval and thus terminates the torsade de pointes.

Long-term treatment for acquired long QT syndrome

No treatment is necessary after the removal of the medications causing the syndrome.

Long-term treatment for congenitallong QT syndrome

Beta-blockers are very effective in congenital LQTS. Mortality is reduced dramatically if the right drug and right dose is given. Propranolol (usually sufficientwith 3 mg/kg/day) and nadolol (usuallysufficientwith 1 mg/kg/day) are the most effective drugs. Metoprolol has a proven effect but is less effective than propranolol and nadolol. There are no studies available on atenolol, which therefore cannot be recommended. Patients with pronounced bradycardia should not be given beta-blockers due to the risk of provoking torsade de pointes.

Artifical pacemaker may be necessary if the maximal dose of beta-blockers is insufficient. If pacemaker is also insufficient, sympathectomy may be considered. Sympathectomy means that sympathetic nerve ganglia (thoracic) are removed surgically, which leads to the elimination of adrenergic stimulation to the heart. This is an effective method but requires surgery.

ICD (Intracardial Cardiac Defibrillator) is used in the following cases:

  • Patients who have experienced cardiac arrest.
  • Patients who have experienced syncope despite optimal treatment (maximal dose beta blocker, pacemaker and possibly sympathectomy).
  • If the anamnesis is very worrying and the QTc interval is >550 ms. T-wave alternans and sinus pause corroborates this further.

Short QT syndrome (SQTS)

Short QT syndrome is extremely rare but may cause polymorphic ventricular tachycardia. It is defined as QTc interval <0.35 s. Note thathypercalcemia and digoxin which may also shorten the QTc interval.

Additional ECGs of Torsade de Pointes

Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (6)
Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (7)
Long QT (QTc) interval, long QT syndrome (LQTS) & torsades de pointes – Cardiovascular Education (2024)


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