Pediatric Long QT Syndrome Workup

Updated: Jun 26, 2014
  • Author: Sreekanth S Raghavan, MBBS, , FACC; Chief Editor: Stuart Berger, MD  more...
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Workup

Approach Considerations

Laboratory studies in patients with suspected long QT syndrome should rule out dyselectrolytemias, especially those involving potassium, ionized calcium, and magnesium.

Epinephrine QT stress testing is an effective diagnostic tool used to unmask concealed long QT syndrome. Two protocols are followed: the Shimizu protocol and the Mayo protocol. These protocols are especially useful in patients with LQT1. Unique responses have also been observed in patients with LQT2 and LQT3, making this test invaluable in the diagnostic workup of long QT syndrome. [8]

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Electrocardiography

The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome. (See the images 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. 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 long QT syndrome. R-R = 1 s; QT interval = 0.56 s; QT interval corrected for heart rate (QTc) = 0.56 s.
Genetically confirmed long QT syndrome with border Genetically confirmed long QT syndrome with borderline values of QT corrected for heart rate (QTc) duration in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4. R-R = 0.68 s; QT interval = 0.36 s; QTc = 0.44 s.

QTc is the best diagnostic and prognostic ECG parameter in families with long QT syndrome (see Table 2, below). A single measurement should be obtained in lead II (if measurable) and then in left precordial leads (preferably V5) as a second choice. (A second opinion is recommended when the QTc is borderline.)

In a study by Mönnig et al, the predictive power for identifying carriers in families with long QT syndrome was found to be highest in leads II and V5. The investigators also found that these ECG leads were optimal for risk stratification. [9]

Table 2. Genetic Basis of Long QT Syndrome (Open Table in a new window)

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

All ECGs in family members of a patient with long QT syndrome need to be reviewed, along with detailed histories and physical examinations. An absence of ECG findings that suggest long QT syndrome in family members must not be construed to exclude long QT syndrome in a patient. More recently, magneto-cartography-derived QT interval has been used along with the heart rate to determine long QT syndrome in fetuses. [10, 11]

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Genetic Testing

Genetic testing for known mutations in DNA samples confirms the diagnosis with high specificity but low sensitivity, because only 50% of patients with long QT syndrome have known mutations. The remaining half of patients with long QT syndrome may have mutations of yet unknown genes.

However, this technology is valuable because it can help in predicting the course of the disease in these patients and aid in risk stratification. A study by Moss et al found that in patients with KCNQ1 mutations, the Cox proportional hazards survivorship model indicated an increased risk for cardiac events in patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06), as well as in patients with mutations resulting in dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26). The investigators found these risks to be independent of traditional clinical risk factors. [12]

Arnestad M et al suggested that 9.5% of the patients with sudden infant death syndrome had relevant LQTS mutations. [13] On the basis of their functional effect, 8 mutations and 7 rare variants were found in 19 of 201 cases; these mutations were likely contributors to sudden death in those patients.

Tester et al sought to determine the spectrum and prevalence of long QT syndrome–associated mutations in a large cohort of autopsy-negative, sudden unexplained death cases. [14] Long QT syndrome–associated mutations (4 novel) were found in 20% of these individuals. Sudden death was the sentinel event in two thirds of the cases. This underscores the importance of postmortem long QT syndrome genetic testing for sudden unexplained death in the pediatric population.

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