Long QT Syndrome Workup

Updated: Nov 30, 2017
  • Author: Ali A Sovari, MD, FACP, FACC; Chief Editor: Mikhael F El-Chami, MD  more...
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Workup

Approach Considerations

Routinely check serum levels of potassium (and sometimes magnesium) and thyroid function in patients who present with QT prolongation after arrhythmic events, to eliminate secondary reasons for repolarization abnormalities.

Analysis of repolarization duration (QTc) and morphology on a patient's electrocardiogram (ECG) and on the ECGs of the patient's relatives frequently leads to an accurate diagnosis.

Hinterseer et al found that increased short-term variability of the QT interval—ie, STV(QT)—in symptomatic patients with congenital long QT syndrome (LQTS) could be a useful noninvasive additive marker for diagnostic screening to bridge the gap while waiting for results of genetic testing. [19]  This study is the first in humans to observe this association.

Imaging studies

Imaging studies (eg, echocardiography, magnetic resonance imaging [MRI]) may help only in excluding other potential reasons for arrhythmic events (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) or associated congenital heart diseases in a small subset of patients with LQTS, such as persons with LQT8.

Diagnostic criteria

A presentation with syncope or sudden cardiac death, in combination with a long QT interval on an ECG, typically suggests long QT syndrome (LQTS) and leads to genetic testing to diagnose the disease. In many patients, however, the presentation may not be typical. Therefore, other tests may be indicated.

Schwartz et al suggested diagnostic criteria for LQTS in 1993 that still serve as the best criteria for clinicians. [20] In their model, the criteria are divided to three main categories, as shown in Table 2, below. The maximum score is 9—A score above 3 indicates a high probability of LQTS.

Table 2. Diagnostic Criteria for LQTS (Open Table in a new window)

Criterion Points
Electrocardiogram findings *
QTc, ms >480 3
460-469 2
450-459 in male patient 1
Torsade de pointes 2
T-wave alternans 1
Notched T wave in 3 leads 1
Low heart rate for age§ 0.5
Clinical history
Syncope With stress 2
Without stress 1
Congenital deafness 0.5
Family history   
A. Family members with definite LQTS# 1
B. Unexplained sudden cardiac death at age <30 years in an immediate family member 0.5
LQTS = long QT syndrome.



*In the absence of medications or disorders known to affect these electrocardiographic features.



QTc calculated by Bazett's formula.



Mutually exclusive.



§Resting heart rate below the second percentile for age.



||Mutually exclusive.



The same family member cannot be counted in both A and B.



#Definite LQTS is defined by an LQTS score above 3 (≥4).



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Electrocardiography

As the criteria for long QT syndrome (LQTS) by Schwartz et al suggest, the most helpful electrocardiographic (ECG) findings are prolongation of the QT interval, the presence of torsade de pointes, the presence of T-wave alternans, and the presence of certain morphology of the T waves (wide-based T wave, and notched T wave in three leads).

Correlation between the type of mutation and T-wave morphology has been suggested. Wide-based T waves are most frequently seen in LQT1, whereas notched T waves are most commonly seen in LQT2. In LQT3, T waves may appear normal, with a long, isoelectric ST segment.

T-wave analysis also appears to have the potential to differentiate acquired QT prolongation from congenital LQTS, [21]  as well as help identify on-therapy breakthrough arrhythmic risk in LQT1 and LQT2. [22]  Using an automated T-wave analysis program to retrospectively evaluate 12-lead ECGs of 38 patients with congenital LQTS and 114 patients with drug-induced and/or electrolyte-mediated QT prolongation, Sugrue et al noted the following differences in lead V5 of those with acquired QT prolongation could distinguish these individuals from patients with congenital LQTS in 77% of cases (90% sensitivity, 58% specificity) [21] :

  • Shallower T-wave right slope
  • Larger T-peak to T-end interval
  • Smaller T-wave center of gravity on the x axis

The same investigators used a T-wave analysis program to evaluate ECGs from 407 genetically confirmed patients with LQT1 (n = 246) and LQT2 (n = 161) over a mean follow-up of 6.4 ± 3.9 years and found two independent predictors of future LQTS-associated cardiac events were left slope of T waves in lead V6 and a T-wave center of gravity on the x axis in lead I, particularly in patients with LQTS2. [22]

Prolongation of the QTc interval is defined on the basis of age- and sex-specific criteria (see Table 3, below). QTc is calculated by dividing the measured QT by the square root of the R-R interval, both of which are measured in seconds. QTc prolongation longer than 0.46 seconds indicates an increased likelihood of LQTS. (See the image below.)

Marked prolongation of QT interval in a 15-year-ol Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R = 1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS.

However, approximately 10-15% of gene-positive patients with LQTS present with a QTc duration in the reference range. (See the image below.)

Genetically confirmed long QT syndrome (LQTS) with Genetically confirmed long QT syndrome (LQTS) with borderline values of QT corrected for heart rate (QTc) duration (R-R = 0.68 s, QT interval = 0.36 s, QT interval corrected for heart rate [QTc] = 0.44 s) in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4.

Table 3. Definition of QTc Based on Age- and Sex-Specific Criteria (Open Table in a new window)

Group Prolonged



QTc, sec



Borderline



QTc, sec



Reference Range, sec 
Children and adolescents (<15 years) >0.46 0.44-0.46 <0.44
Men >0.45 0.43-0.45 <0.43
Women >0.46 0.45-0.46 <0.45

In patients with suspected LQTS with borderline QTc values (or even values in the reference range) on standard ECGs or in patients with a score of 2-3 based on the 1993 Schwartz et al diagnostic criteria, an analysis of the dynamic behavior of QTc duration during exercise ECG or long-term Holter monitoring may reveal maladaptation of the QT interval to a changing heart rate. QTc prolongation may be evident at a fast heart rate. Ventricular arrhythmias are rarely observed during exercise testing or Holter recording in patients with LQTS.

No evidence indicates that invasive electrophysiology with attempts to induce ventricular tachycardia facilitates diagnosis.

Bradycardia and tachycardia

Bradycardia and tachycardia each need special attention. Bradycardia is included in the diagnostic criteria and adds 0.5 points to the score. Tachycardia requires special attention, too, because the QTc may be overcorrected in a tachycardic situation (eg, in infants).

T-wave alternans

Visible T-wave alternans in patients with LQTS indicates an increased risk of cardiac arrhythmias (ie, torsade de pointes and ventricular fibrillation).

Detection of microvolt T-wave alternans has low sensitivity and high specificity in diagnosing LQTS. The prognostic value of microvolt T-wave alternans has not been studied systematically.

Pharmacologic provocation

Pharmacologic provocation with epinephrine or isoproterenol helps in diagnosing LQTS in patients with a borderline presentation. It may also provide information regarding the type of mutation present.

Testing family members

It is important to review the ECGs of family members of a patient with LQTS, to obtain detailed histories, and to perform physical examinations. However, an absence of ECG findings of LQTS in family members does not exclude LQTS. In the ideal setting, all family members should be tested for LQTS mutations to help limit the small, but definite, risk of arrhythmia and sudden cardiac death. Testing is especially relevant if the patient was exposed to a drug that prolongs the QT interval.

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Genetic Testing

Patients with a clinical or electrocardiographic (ECG) presentation of long QT syndrome (LQTS) need genetic testing to identify the mutation. Genetic testing for known mutations in deoxyribonucleic acid (DNA) samples from patients is becoming accessible in specialized centers, although such tests can entail considerable expense, and insurance coverage for genetic testing often requires specific physician intervention.

Identification of an LQTS genetic mutation confirms the diagnosis. However, a negative result on genetic testing is of limited diagnostic value, because only approximately 50% of patients with LQTS have known mutations. The remaining half of patients with LQTS may have mutations of yet unknown genes. Therefore, genetic testing has high specificity but low sensitivity.

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Response to Standing

Viskin and colleagues demonstrated that the expected shortening of the QT interval in response to sinus tachycardia induced by standing from a supine position is impaired in patients with long QT syndrome (LQTS). [1] In fact, the QTc interval in patients with LQTS increased with standing position, and more premature ventricular contractions (PVCs) were detected during standing in these patients. Thus, the increased QTc interval in response to standing up, which is associated with increased sympathetic tone, can provide more diagnostic information in patients with LQTS. [1] The increase in QTc in response to standing may persist in patients with LQTS even after heart rate returns to normal. [2]

In addition, this study may reveal that standing up in patients with LQTS may be associated with more focal activities and ventricular arrhythmias. Therefore, syncope while standing up in a patient with LQTS may not be simply a vasovagal syncope but may represent a more dangerous condition.

In a more recent study, investigators evaluating the standing test in 36 congenital LQTS patients (LQT1, LQT2, LQT7, and unidentified genotypes) and 41 control subjects found that the corrected QT interval (QTc) obtained immediately after standing and the QTc change from baseline were significantly higher in the LQTS group than in the control group, and that these QTc evaluations had a high diagnostic value when compared to the baseline QTc. [23] In addition, the use of beta-blocker therapy ameliorated the standing response in the LQTS patients.

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