Introduction

The QT interval is measured from the beginning of the Q wave to the end of the T wave. It reflects the total duration of ventricular depolarization and repolarization, that is, in practice, the electrical systole of the ventricles from isovolumetric contraction to isovolumetric relaxation.

​

The QT interval is inversely proportional to heart rate: it shortens when the heart rate increases and lengthens when the heart rate decreases. An abnormally prolonged QT interval is associated with an increased risk of ventricular arrhythmias, especially torsades de pointes (TdP). An abnormally short QT interval is also a marker of arrhythmic susceptibility; congenital short QT syndrome is associated with an increased risk of atrial fibrillation, ventricular fibrillation, and sudden death.

​

Long QT can be divided into two main groups. Congenital long QT syndrome (LQTS) is an inherited repolarization disorder. Acquired long QT syndrome is most commonly associated with QT-prolonging drugs, electrolyte disturbances, or other secondary factors. Clinically, the most important issue is to distinguish between these, because in the congenital form close relatives may also have the same predisposition, whereas in the acquired form the cornerstone of treatment is removal of the predisposing factors. In addition, the management of patients with congenital and acquired long QT differs.

​

Electrical basis and pathophysiology

The action potential of the cardiac myocyte is generated by sodium, calcium, and potassium currents passing through ion channels in the cell membrane. Phase 0 is formed mainly by rapid sodium influx and corresponds to the QRS complex on the surface ECG. During phases 1–3, repolarization occurs: the sodium current is inactivated, the calcium current maintains the plateau phase, and potassium efflux restores the membrane potential toward the resting level. These depolarization and repolarization events in ventricular cells summate on the surface ECG as the QT interval.

​

QT prolongation usually reflects delayed repolarization, that is, prolongation of action potential duration. This can result from factors that reduce repolarizing potassium currents or increase inward depolarizing currents. Therefore, abnormalities in ion channel structure or function, drugs, electrolyte disturbances, and many cardiac diseases can prolong the QT interval.

​

Long QT: congenital and acquired forms

Acquired long QT

Acquired long QT syndrome is most commonly caused by QT-prolonging drugs and other secondary factors, especially hypokalemia and hypomagnesemia. Hypocalcemia can also prolong the QT interval, although the associated risk of torsades is clearly less common. In addition, for example, malnutrition, vomiting, and diarrhea may predispose to QT prolongation, often through electrolyte and metabolic abnormalities. Ischemia can also prolong the QT/QTc interval, especially in the early phase of acute transmural ischemia, although not always and not in the same way at all stages. In acute coronary syndrome, prolonged QT/QTc is also associated with a worse prognosis. The electrophysiological changes of ischemia are both temporally and regionally variable: in the early phase, repolarization may be prolonged, whereas as ischemia progresses, the action potential often shortens. Mechanistically, this phenomenon is explained by the fact that ischemia increases repolarization heterogeneity and alters ion currents differently in different myocardial regions. The QT/QTc on the surface ECG reflects the net effect of these changes.

​

The likelihood of drug-induced QT prolongation and TdP risk increases especially in situations where drug exposure is increased because of interactions, impaired renal or hepatic function, or rapid intravenous administration. In a small proportion of patients, a QT-prolonging drug may also unmask a latent congenital predisposition to a repolarization disorder.

​

In practice, acquired QT prolongation is often multifactorial: a single QT-prolonging drug often does not explain the situation alone, but concurrent predisposing factors are also present.

​

Congenital long QT

Congenital long QT syndrome is an inherited arrhythmia disorder. The most common form is the autosomal dominant Romano–Ward syndrome. The rarer autosomal recessive form is Jervell and Lange-Nielsen syndrome, which is associated with congenital sensorineural hearing loss.

​

The prevalence of LQTS is approximately 1:2000–2500. The most common genotype is LQT1 (KCNQ1), accounting for about 30–35% of cases. The next most common is LQT2 (KCNH2), about 25–30%, and LQT3 (SCN5A) accounts for about 5–10% of cases. Other subtype forms are clearly rarer.

​

Classical, non-syndromic long QT syndrome is not associated with structural heart disease, but this does not apply to all rare syndromic forms, such as Timothy syndrome.

​

Symptoms and clinical presentation

Manifestations of long QT syndrome include a prolonged QT interval and abnormal T-wave morphology on ECG, as well as syncope caused by episodes of ventricular tachyarrhythmia, cardiac arrest, or sudden death.

​

The typical patient with congenital LQTS is often a child or young person who experiences sudden syncope during physical exertion, intense emotional stress, or sudden fright. However, triggers vary according to the LQTS subtype. Dismissing the symptom, for example as vasovagal fainting, may be fatal. If untreated, the risk of recurrence of arrhythmia episodes and sudden death may be considerable.

​

Episodes of torsades de pointes vary in duration and are often self-terminating. In their mildest form, they may cause only transient blurring of vision or a feeling of weakness, but they usually lead to sudden loss of consciousness without prodromal symptoms. Although syncope is the first symptom in most patients, in some the first manifestation may be cardiac arrest or sudden death.

 

Usually, an ECG recorded already at rest reveals the QT abnormality, but the resting ECG may also be normal even though susceptibility to arrhythmias exists at the cellular level (so-called concealed long QT syndrome).

​

Torsades de pointes

Torsades de pointes is a polymorphic ventricular tachycardia associated with a prolonged QT interval. On ECG, the shape and amplitude of the QRS complexes vary so that they appear to “twist” around the isoelectric line. For a few beats, the QRS deflections may be predominantly upward, then the amplitude decreases, as if crossing the center line, and the following beats become predominantly downward. This distinguishes TdP from the more common monomorphic ventricular tachycardia, in which the QRS remains the same from beat to beat.

​

TdP often begins as short, self-terminating bursts, but if the predisposing electrical disturbance persists uncorrected, episodes may recur increasingly often and become longer. The mechanism involves early afterdepolarizations and repolarization heterogeneity, which facilitate the occurrence of extrasystoles and the reinitiation of ventricular tachycardia.

 

This arrhythmia is life-threatening because the ventricular rate is often very rapid, usually around 200–250/min, making ventricular pumping ineffective. In addition, TdP can degenerate into ventricular fibrillation and lead to cardiac arrest.

 

Measurement of the QT interval

Basic principle

The QT interval is defined as the time from the beginning of the QRS complex to the end of the T wave. Although automated QT measurement is common in practice, manual measurement is preferable because automated algorithms often fail in the presence of abnormal T-wave morphology. This is especially important in patients with LQTS.

​

Measuring QTc is not as simple as it may seem. Even among LQTS experts, variability of up to 70 ms in measurement of the same ECGs has been reported.

​

Defining the end of the T wave

The end of the T wave can be determined by two main methods.

​

In the tangent method, a tangent is drawn to the steepest point of the terminal downslope of the T wave, and the QT ends at the point where this tangent intersects the isoelectric baseline. In practice, the isoelectric baseline is defined as the voltage level at the beginning of the QRS.

 

In the threshold method, QT is measured to the point where the visible terminal portion of the T wave actually meets the isoelectric baseline. It does not use a tangent or extrapolation; rather, the end of the T wave is the visible point at which the wave merges with the baseline. If a U wave is present on the ECG, in this method the T wave ends at the nadir of the T-U complex.

 

The tangent method usually gives a slightly shorter QT/QTc than the threshold method, on average about 10 ms shorter.

 

There is no gold standard between these methods, and there is no full consensus among experts as to which is the “correct” method. The tangent method is often more reproducible, but it may underestimate the final part of repolarization.

​

Biphasic T wave, notched T wave, and U wave

The second component of a biphasic or notched T wave is included in QT measurement (T1 and T2). The U wave is not included in the QT interval.

​

If a U wave follows the T wave such that the end of the T wave no longer clearly meets the baseline, the threshold method no longer defines the end of the T wave literally as the T–baseline intersection. In that case, the practical rule is that QT ends at the nadir of the T-U complex, that is, at the lowest point between the T and U waves, not at the end of the U wave. If T and U are fused and there is no clear nadir, that lead (or the threshold method) is poor for QT measurement. In that case, one should use a lead in which the U wave is not visible, or, if necessary, the tangent method. If it is not clear whether the “second hump” is truly a U wave or still part of the T wave, the terminal portion should not automatically be excluded, because otherwise the QT may be erroneously shortened.

​

In which lead should QT be measured?

QT is preferably measured in lead II or V5, because in these the end of the T wave is most often seen most clearly. In practice, measurement is usually performed over several beats.

​

At the same time, there is also a principle in clinical measurement practice that when measuring from individual leads, one should use the lead in which the QT is longest and at the same time can be reliably delineated.

​

Thus, in practice, measurement is started in lead II or V5, but if another lead reliably shows a longer QT, it should not be ignored. For example, if the QTc measured in lead II or V5 is 485 ms but 510 ms in another lead, the longer value should not automatically be rejected if the measurement was made in a lead in which the beginning of the QRS and the end of the T wave are clearly visible and there is no artifact or U wave present.

​

Repeated 12-lead ECGs

The diagnosis of LQTS should not be based on a single ECG, because QTc varies over time.

​

In practice, this means that one normal ECG does not exclude LQTS, but one prolonged QTc alone is also not sufficient to confirm congenital LQTS. What is essential is serial assessment, careful manual measurement, exclusion of secondary causes, symptoms, and family history.

​

Heart rate correction of QT

Because QT changes with heart rate, it is usually corrected to an estimated value corresponding to a heart rate of 60/min, that is, QTc.

​

The most commonly used formulas are:

• Bazett: QTc = QT / √RR

• Fridericia: QTc = QT / RR^(1/3)

• Framingham: QTc = QT + 0.154 (1 − RR)

• Hodges: QTc = QT + 1.75 (heart rate − 60)

• Rautaharju (for prolonged QRS duration): QT(RR,QRS) = QT − 155 × (60/HR − 1) − 0.93 × (QRS − 139) + k, where k = −22 ms in men and −34 ms in women.
   

Bazett and Fridericia are logarithmic correction formulas, whereas Hodges and Framingham are linear.

​

Bazett’s formula has historically been the most widely used because of its simplicity. It overcorrects (i.e., QTc is falsely long) at high heart rates and undercorrects (QTc falsely short) at low heart rates. Fridericia and Framingham corrections are more accurate in many situations when the heart rate deviates from the usual range.

 

A practical rule of thumb is that a normal QT is less than half of the preceding RR interval, but this is only a rough bedside rule and does not replace actual QTc calculation.

 

Bazett is often described as “adequate” approximately in the heart rate range of 60–100/min, but it is also emphasized that there is no precise universal “reliable heart rate range” and that Bazett is not a mathematically ideal formula.

​

Which formula in which situation?

Although Bazett’s formula is the most popular, for heart rate correction of the QT interval Bazett appears to be the weakest option, especially in tachycardia and during atrial fibrillation. In a large adult dataset analyzing 6609 ECGs from patients in sinus rhythm with narrow QRS complexes, Fridericia and Framingham showed the best rate-correction properties, whereas Bazett performed the worst (Vandenberk et al. 2016). Similar results have also been reported in normal heart rate ranges: Luo et al. (2004) showed in a dataset of 10,303 normal ECGs that in the heart rate range of 60–99/min the reference limits of formulas other than Bazett were fairly similar, whereas Bazett clearly differed from them. In sinus tachycardia, the problems with Bazett are even more pronounced: in a dataset of 6723 patients (HR ≥100/min), it overestimated the prevalence of prolonged QTc and did not predict mortality as well as the other formulas (Patel et al. 2015).

​

In atrial fibrillation as well, the evidence is clinically quite consistent: Bazett should be avoided. In the large Leuven dataset, which included 9167 atrial fibrillation ECGs and in which half of the patients had a heart rate over 100/min, Fridericia was best across the entire heart rate spectrum and significantly better than Bazett, Framingham, and Hodges in tachycardia (Vandenberk et al. 2017). Smaller studies have supported the same practical message: Dash et al. (2019) found that Fridericia correlated best between atrial fibrillation and sinus rhythm, Yu et al. (2022) reported that Framingham was the most stable during atrial fibrillation and that Bazett overestimated QTc, and Luzza et al. (2023) concluded that Bazett was the least accurate in atrial fibrillation, whereas Fridericia, Framingham, and Hodges behaved better.

​

QT correction in screening and diagnosis of congenital LQTS

In screening and diagnosis of congenital LQTS, Bazett’s formula remains established in practice because historical diagnostic cutoffs, scoring systems, and a large part of the validation literature are based on Bazett-corrected QTc.

​

This does not mean that Bazett is physiologically the best formula in all situations, but rather that the diagnostic framework of LQTS has been built around it. Therefore, in LQTS screening and diagnosis, Bazett is usually used, preferably when the heart rate is close to normal (60 bpm) and the measurement is performed manually.

 

The International ECG Recommendations 2018 state that QTc should be measured with Bazett, manually using the tangent method, and ideally in the heart rate range of 60–90/min.

​

QT correction in drug-induced and iatrogenic QT prolongation

In assessment of drug-induced QT in adults, Bazett is generally not considered the best option, because it overcorrects in tachycardia and undercorrects in bradycardia. In such cases, Fridericia is often a more useful default formula, and Framingham is also a reasonable option. This applies particularly to assessment of medication safety and proarrhythmic risk.

​

Practical summary

• LQTS screening/diagnosis: in practice, Bazett

• Adult drug-QT and proarrhythmic risk assessment: often Fridericia, especially at abnormal heart rates
   

In congenital LQTS, the priority is comparability with diagnostic cutoff values, whereas in drug-related QT assessment the priority is the most accurate possible heart rate correction.

​

Example: atrial fibrillation and heart rate 135/min

At a heart rate of 135/min, Bazett is not a good choice because it overcorrects. In such a situation, Fridericia is more practical and preferable.

​

In rapid atrial fibrillation, QT measurement is particularly difficult because of heart rate variability. In that case, the measurement should be performed manually, preferably as the average of several beats. In the setting of a narrow QRS, Fridericia is a practical choice; Framingham may also be useful. However, there is no single formula for atrial fibrillation that is fully established at an authoritative level.

​

Wide QRS, bundle branch block, and pacing

In the presence of a wide QRS, bundle branch block, or paced rhythm, interpretation of QTc becomes more difficult because the QRS itself prolongs QT. In these situations, it may be necessary to consider QRS duration separately, to use the JT interval, or to use special correction methods.

​

ESC mentions that Rautaharju’s formula has been validated in patients with prolonged QRS duration.

​

Diagnosis of congenital LQTS

Normal QTc and diagnostic cutoffs

QTc does not perfectly distinguish the healthy population from congenital long QT syndrome. There is considerable overlap between QTc values in LQTS and in the normal population.

​

According to current thinking, congenital LQTS can be diagnosed if:

• QTc is ≥480 ms on repeated 12-lead ECGs in the absence of QT-prolonging medication, electrolyte disturbance, or another secondary cause. In older HRS/ACC statements, the cutoff is QTc ≥500 ms, or 480–499 ms in the presence of syncope.

• or the Schwartz/LQTS risk score is ≥3.5

• or the patient has a pathogenic LQTS gene variant
   

In a symptomatic patient, even QTc 460 ms or QTc 480–499 ms may strengthen the suspicion, especially in the setting of unexplained syncope.

​

Concealed LQTS

Some patients have a so-called concealed form: in about one quarter of genetically confirmed LQTS carriers, the baseline ECG QTc is normal. Therefore, a QTc below 480 ms—and sometimes even a QTc within the normal range—on a resting ECG does not exclude LQTS. A negative genetic test alone is also not sufficient to exclude the disease. The HRS/EHRA 2011 genetic testing consensus states that the yield of LQTS genetic testing is about 75%, and that a negative genetic test alone cannot exclude the diagnosis of LQTS.

​

The risk of serious events in the normal-QTc group is lower than in the clearly prolonged-QTc group, but still clearly higher than in genotype-negative controls. In this group, genotype and mutation characteristics are more important for risk than resting QTc duration.

 

LQTS patients with normal QTc solely diagnosed on the basis of a positive genetic test are important to identify, as these concealed LQTS patients have an augmented risk of aborted cardiac arrest or sudden cardiac death (4% between birth and age 40) compared to genotype-negative control individuals.

​

Variation of QTc during follow-up

In practice, QTc may sometimes be prolonged and sometimes within normal limits. This is because beyond heart rate and imperfect QT correction formulas many factors such as autonomic tone, fever, and acquired “second hits” affect QT time. Also hormones matter: after puberty, women generally have longer QTc values than men, and in women with LQTS the QT/risk profile can shift across the menstrual cycle, pregnancy, and especially the postpartum period. This is approached such that one normal ECG does not negate the suspicion, but one prolonged QTc also does not by itself confirm LQTS.

 

If QTc is sometimes normal but the history is suspicious, the assessment does not stop there. What is essential is:

• the highest QTc reliably measured on repeated ECGs

• whether unexplained syncope, seizure-like episodes, or cardiac arrest are present

• whether there are young sudden deaths or LQTS in the family

• what the T-wave morphology looks like

• whether there is no secondary explanation for QT prolongation
   

If the resting QTc is borderline or normal but clinical suspicion remains, further investigations are readily pursued.

​

Exercise testing and other provocative tests

In suspected LQTS, the purpose of exercise testing is not primarily to assess ischemia, but to examine the behavior of QT/QTc as the heart rate increases and especially during the recovery phase. In healthy individuals, QT shortens as the heart rate rises, but in LQTS the adaptation of repolarization may be abnormal. QTc may remain disproportionately prolonged or become more pronounced during recovery.

​

In practice, exercise testing usually assesses:

• rest

• peak exercise

• 1-minute recovery

• 4-minute recovery
   

In particular, QTc during the 4-minute recovery phase has been described as useful for revealing concealed QT prolongation in congenital LQTS. Exercise testing is most useful when the resting ECG is not clearly diagnostic.

​

During exercise testing, the absolute QT is first measured manually, but the actual diagnostic interpretation is usually based on QTc. In practice, Bazett’s formula is used in exercise-test diagnosis of LQTS, even though it is known not to be the best formula at high heart rates. This is because the current diagnostic cutoff values are based on it and in practice almost all exercise studies in LQTS have used Bazett. The most important phase of the exercise test is usually not peak exercise but the recovery phase, when the heart rate is more stable and QT is easier to measure.

 

Bazett is not physiologically the best formula at high heart rates, but the exercise-test cutoffs for LQTS have nevertheless been built on Bazett. Accordingly, in exercise testing, a non-Bazett formula should not be directly applied to a Bazett-based cutoff.

 

In the 2023 Canadian update, the measurement method is described such that the average of 3 consecutive absolute QT intervals and the average of the preceding RR intervals are calculated, and these are entered into Bazett’s formula.

 

Brisk standing is a separate provocative test that may also reveal abnormal QT adaptation.

​

Genetic testing

Not all gene defects associated with LQTS are known, and not all can be detected by genetic tests used in clinical practice. Current testing identifies a molecular cause in only some patients (about 75%), so a negative genetic result does not exclude LQTS.

​

Of the previously described “LQTS genes,” only some are now considered well validated as causes of classical LQTS. For several previously reported genes, the evidence has later been judged limited or controversial. The genetic result must always be interpreted in the context of the clinical phenotype.

​

Clinical multigene panels detect most currently recognized panel-included variants, but not all. Some deletions, duplications, and changes not covered by a given laboratory may remain undetected.

​

Risk assessment in congenital long QT syndrome

QTc duration correlates with the risk of arrhythmia and sudden death, but resting ECG QTc alone does not determine risk.

 

Risk is also modified by:

• previous cardiac symptoms

• previous syncope

• cardiac arrest

• genotype

• mutation characteristics

• age

• sex

• treatment

• triggers
   

Previous syncope is an important risk marker. In patients who remain asymptomatic into adulthood, especially if QTc is below 500 ms, the prognosis may be quite good. The effects of age and sex are partly genotype-dependent: in boys, event risk is higher before puberty, but in women risk becomes more pronounced after puberty and remains higher than in men during adulthood.

​

In congenital LQTS, high risk is associated particularly with QTc values >500 ms, and the risk becomes even greater if QTc is >600 ms. At the same time, it must be remembered that in concealed LQTS patients the risk is not zero, even if QTc is normal on the resting ECG.

​

Iatrogenic and drug-induced QT prolongation

In iatrogenic QT prolongation, arrhythmia risk does not begin at one exact number, but increases progressively as QTc lengthens. The most important clinical action thresholds are:

• QTc >500 ms

• QTc increase ≥60 ms from baseline
   

In these situations, the risk of TdP is clearly increased and immediate action is often required. Every additional 10 ms increase in QTc further increases risk. A QTc above 550 ms is already very concerning. Around 600 ms is a severe finding and one of very high concern. There is no single universally applicable absolute percentage risk for arrhythmic susceptibility as QT lengthens.

​

There is no single universal threshold above which “no QT-prolonging drug may ever be given.” However, if QTc is ≥500 ms or QTc has increased by ≥60 ms, new non-essential QT-prolonging drugs should generally not be started, the suspected offending drug should be paused or discontinued if possible, electrolytes should be corrected, and the patient should be monitored.

 

In the ESC cardio-oncology guidelines, if QTc prolongs to >500 ms during treatment, the offending drug should be interrupted, and if QTc is >550 ms, continuous in-hospital monitoring should be considered. The same source recommends maintaining K ≥4.0 mmol/L and Mg ≥1.0 mmol/L. These thresholds apply particularly to oncologic QT-risk drugs and are not a universal general rule for all drugs.

 

If the drug in question is life-saving and there is no alternative, QTc prolongation alone does not automatically make treatment impossible, but the situation requires an explicit benefit-risk assessment and monitoring.

 

QTc prolongation is not always the same as arrhythmogenicity. For example, amiodarone may prolong QT markedly but causes TdP relatively infrequently.

​

Treatment

Treatment of congenital LQTS

In congenital long QT syndrome, the patient should be advised to avoid QT-prolonging drugs and situations that predispose to hypokalemia or hypomagnesemia, such as vomiting, diarrhea, unbalanced weight-loss diets, and other stresses that disturb electrolyte balance. Especially in LQT1 patients, swimming without appropriate supervision and diving into cold water are known risk situations.

​

Beta-blockers are the cornerstone of treatment in congenital LQTS for symptomatic patients and for patients with documented QT prolongation. Treatment is often also indicated in asymptomatic patients with a mild phenotype, but the decision is made on the basis of the overall clinical assessment.

 

The recommended beta-blocker is primarily a non-selective beta-blocker, in practice nadolol or propranolol. Bisoprolol is not the first recommended drug, but may be considered if nadolol or propranolol are not suitable, not available, or not tolerated. However, the evidence for bisoprolol is clearly weaker than for nadolol and propranolol.

 

An implantable cardioverter-defibrillator (ICD) is indicated especially in patients who have survived cardiac arrest, because the risk of recurrence is high even during beta-blocker therapy. In survivors of cardiac arrest, the recurrence risk is significant, and despite beta-blocker therapy recurrence may occur in about 14% over five years. ICD should also be considered if the patient has syncope and/or ventricular arrhythmias despite optimal medical therapy.

 

Left cardiac sympathetic denervation (LCSD) is an important adjunctive therapy if beta-blockers are ineffective, not suitable, or not sufficient alone.

 

Pregnancy does not usually increase arrhythmic events in the same way as the postpartum period. The risk is especially emphasized in the postpartum phase, which is why beta-blocker therapy is continued during pregnancy and during the high-risk period after delivery.

​

Treatment of acquired long QT

The cornerstone of treatment of acquired QT prolongation is removal of the causative factor:

• discontinuation or interruption of the QT-prolonging drug

• correction of electrolyte disturbances

• optimization of potassium

• resolution of drug interactions

• consideration of renal and hepatic function

• assessment and, if necessary, treatment of bradycardia
   

AHA 2020 lists maintenance of potassium >4 mEq/L and magnesium >2 mg/dL (≥1.0 mmol/L) as measures to reduce the risk of drug-induced TdP.

​

However, removal of the causative factor alone is not the only treatment. If the patient has TdP or recurrent pause-dependent polymorphic ventricular tachycardias, pharmacologic treatment has a clear role.

 

The primary acute treatment measures are:

• i.v. magnesium sulfate

• correction of potassium to at least normal, often to the high-normal range

• discontinuation of the offending drug

• rhythm monitoring
   

If TdP recurs or continues, increasing the heart rate with temporary pacing or isoprenaline is an established adjunctive treatment.

​

The basic treatment of acquired/drug-induced long QT is not a beta-blocker. This is an important difference compared with congenital LQTS. In the acquired setting, the arrhythmia is often bradycardia- and pause-dependent, so treatment often involves increasing rather than lowering the heart rate.

​

What is done in the treatment of acquired/drug-induced long QT if potassium correction and magnesium infusion are not sufficient?

At the guideline level, the next treatment is isoprenaline (isoproterenol) infusion to increase the heart rate. In the same situation, an equally recommended option is temporary overdrive pacing; other antiarrhythmic drugs are not as strongly guideline-supported in this indication.

​

Mexiletine may be considered only as a refractory rescue/off-label option in special circumstances, because the support is based on a small single study (N=12), not on a guideline recommendation. In the old ACC/AHA/ESC 2006 guideline, lidocaine was still mentioned as a possible option among other measures in prolonged-QT polymorphic VT/TdP, but this has not been retained in more recent cardiology guidelines. Lidocaine has at most an exceptional salvage role, with mainly case-report-level successes.

​

QT-prolonging antiarrhythmic drugs (e.g., amiodarone) should not be added in this situation.

​

Is isoproterenol used only if the patient’s heart rate is bradycardic?

The guideline-level concept is that isoproterenol is used in recurrent TdP in acquired/drug-induced long QT when the arrhythmia is bradycardia-/pause-dependent and does not settle with magnesium and correction of other triggers. Thus, its use is guided primarily by the mechanism (brady-/pause-dependent TdP) and the need to increase heart rate, not by any single exact lower rate threshold alone.

​

In practice, this means that, for example, a heart rate of 75/min may well still be a situation for isoproterenol use if TdP is still recurrent and clearly pause-dependent, because the aim of treatment is often to raise the heart rate clearly above this to suppress TdP.

​

Isoproterenol infusion is typically titrated to a heart rate of about 90–110/min, higher if necessary if TdP recurs. However, this target of 90–110/min is not a numeric threshold written into the guideline.

​

Congenital vs acquired QT prolongation: difference in risk and treatment

In both situations, a longer QTc is associated with a higher risk of serious ventricular arrhythmia. The practical difference, however, is this:

• in acquired QT prolongation, QTc often functions well as a short-term alarm threshold and treatment trigger

• in congenital LQTS, QTc is an important but imperfect risk marker, because risk is also strongly influenced by genotype, mutation characteristics, prior syncope or cardiac arrest, age, sex, and triggers
   

Therefore, a patient with acquired QT should not be thought of in terms of “500 ms = a certain percentage risk,” but as a whole in which QTc duration, predisposing factors, and the clinical situation together determine risk.

​

The basic treatment of acquired/drug-induced long QT is not a beta-blocker. This is an important difference compared with congenital LQTS. In the acquired setting, the arrhythmia is often bradycardia- and pause-dependent, so treatment often involves increasing rather than lowering the heart rate.

​

Isoprenaline is not routine treatment for congenital LQTS and is generally avoided. Unlike in acquired, pause-dependent drug-induced TdP, the basic treatment of congenital LQTS is a non-selective beta-blocker. Exceptionally, in acute refractory TdP, isoprenaline has been described in case reports; in some genetic LQTS types, isoprenaline is considered arrhythmogenic. If a congenital LQTS patient is in a refractory TdP situation and the TdP is pause-/bradycardia-dependent, the primary treatment is increasing the heart rate with pacing.