eMedicine Specialties > Cardiology > Arrhythmias
Long QT Syndrome: Differential Diagnoses & Workup
Updated: Jun 18, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Drug-induced QT prolongation
QT prolongation in the course of other diseases (eg, myocardial infarction, cerebral hemorrhage)
Vasovagal syncope
Seizures
Workup
Laboratory Studies
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.
Genetic testing for known mutations in DNA samples from patients is becoming accessible in specialized centers. Identification of an long QT syndrome (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 a low sensitivity.
Imaging Studies
Imaging studies (eg, echocardiography, 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 small subset of patients with long QT syndrome, such as those with LQT8.
Other Tests
- A presentation with syncope or sudden cardiac death and a long QT on ECG typically suggests long QT syndrome (LQTS) and leads to genetic testing to diagnose the disease. However, in many patients, the presentation may not be typical. Therefore, other tests may be indicated.
- In 1993, Schwartz et al suggested diagnostic criteria that still serve as the best criteria for clinicians.5 In their model, the criteria are divided to 3 main categories, as shown in Table 2. The maximum score is 9, and a score of >3 indicates a high probability of LQTS.
Table 2. Diagnostic Criteria for LQTSOpen table in new window
[ CLOSE WINDOW ]Table
Criterion Points ECG 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 <30 y in an immediate family member 0.5 Criterion Points ECG 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 <30 y in an immediate family member 0.5
*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 the age.
||Mutually exclusive
¶The same family member cannot be counted in A and B.
#Definite LQTS is defined by an LQTS score of more than 3 (>4). - As criteria above suggest, the most helpful ECG findings are prolongation of the QT interval, torsade de pointes, T-wave alternans, and certain morphology of the T waves (wide-based T wave, and notched T wave in 3 leads). Correlation between the type of mutation and T-wave morphology has been suggested. Wide-based T waves are most frequently seen in LQT1, and notched T waves are most commonly seen in LQT2. In LQT3, T waves may appear normal with a long, isoelectric ST segment.
- Prolongation of the QTc interval is defined on the basis of age- and sex-specific criteria (see Table 3). 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 >0.46 seconds indicates an increased likelihood of LQTS (see Media file 1).
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 Media file 2).
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 new window
Table
Group | Prolonged QTc, s | Borderline QTc, s | Reference Range, s |
| Children and adolescents (<15 y) | >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 |
Group | Prolonged QTc, s | Borderline QTc, s | Reference Range, s |
| Children and adolescents (<15 y) | >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 |
- Both bradycardia and tachycardia need special attention. Bradycardia is among diagnostic criteria and adds 0.5 point to the score. Tachycardia needs special attention, too, because the QTc may be overcorrected in tachycardic situation (eg, in infants).
- In patients with suspected LQTS with borderline QTc values (or even values in the reference range) on standard ECGs or patients with a score of 2-3 based on the 1993 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 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.
- Visible T wave alternans in patients with LQTS indicate 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 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.
- The patients with a clinical or ECG presentation of LQTS need genetic testing to identify the mutation. At present, these genetic tests are not widely available. In a patient with a high probability of LQTS, an absence of any mutation on genetic testing based on diagnostic criteria does not rule out the possibility of LQTS. The patient might have an as-yet unidentified mutation.
- 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 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.
More on Long QT Syndrome |
| Overview: Long QT Syndrome |
 Differential Diagnoses & Workup: Long QT Syndrome |
| Treatment & Medication: Long QT Syndrome |
| Follow-up: Long QT Syndrome |
| Multimedia: Long QT Syndrome |
| References |
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Further Reading
Keywords
long QT syndrome, LQTS, congenital long QT syndrome, Romano-Ward syndrome, Jervell and Lange-Nielsen syndrome, JLN syndrome, ventricular tachyarrhythmias, syncope, cardiac arrest, sudden death, Anderson syndrome, Timothy syndrome
