Long QT Syndrome

Introduction

Long QT is a rare condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsades de pointes (TdP), a form of irregular heartbeats that originate from the ventricles.  These episodes can lead to palpitations, fainting, and sudden death due to ventricular fibrillation.  Episodes may be provoked by various stimuli, depending on the subtype of long QT. 

Because of the potential severity of symptoms and outcomes, and the potentially treatable nature of the disease, it is important for the pediatrician to be aware of long QT and it's workup.

Pathophysiology

• Congenital or acquired
• Ten genes linked to congenital LQTS, but three genes that encode a cardiac ion channel responsible for ventricular repolarization account for majority of cases (LQT1, LQT2, LQT3)
                 
  • LQT1: most common, triggered by emotional or physical stress (specifically diving and swimming), associated with autosomal recessive Jerrvell and Lange-Nielsen Syndrome (LQTS with congenital sensorneural hearing loss)
  • LQTS2: syncope or sudden death with stress or at rest, events triggered by sudden loud noises (almost diagnostic), normal hearing
  • LQTS3: associated with bradycardia, may be casue of syncope.
• Two clinical phenotypes described in congenital LQTS, based on type of inheritance and resence or absence of sensoineural hearing loss.
             
  • Romano-Ward Syndrome
                          
    • Purely cardiac phenotype
    • Autosomal dominant
    • More common form
  • Jervel and Lange-Nielsen Syndrome
                   
    • More malignant clinical course
    • Associated sensorineural deafness
    • Only been described in LQTS1 abd LQTS5
    • Autosomal recessive

Acquired LQTS usually results from:

• Drugs: antiarrhythmics (class 1A, III), antibiotics (erythromycin, Bactrim), antifungals, TCA antidepressants, antipsychotics (Haldol, resperidone). 
• Electrolyte disturbances: Hypokalemia, Hypomagnesemia, Hypocalcemia.
• Infection: HIV

Clinical Presentation

1. Asymptomatic:  patient may present secondary to a family member with prolonged QT, torsades on EKG.
2. Palpitations: more associated with congenital form. Bradycardia is more associated with the acquired form. 
3. Pre-syncope or syncope: often due to torsades de pointes. In the congenital form, torsades is often secondary to a catecholamine surge. 
4. Seizure
5. Cardiac arrest and death: secondary to ventricular fibrillation

Differential Diagnosis

1. Vasovagal syncope
2. Hypertrophic Cardiomyopathy
3. Brugada syndrome: autosomal dominant disorder characterized by RBBB and ST elevation on anterior leads of EKG
4. Catecholaminergic polymorphic ventricular tachycardia
5. Hypocalcemia
6. Hypothyroidism
7. Medications that prolong QT

Labs/Test

1. Normal physical exam
2. Detailed family history
3. EKG: prolonged QT interval (>460 ms). Often this is measured by QTc (=QT interval / (RR)½), since QT interval can vary with heart rate. QTc is the most useful diagnostic and prognostic parameter for LQTS. - DO  NOT RELY ON THE EKG CALCULATION OF THE QTc - YOU MUST CALCULATE THIS YOURSELF

Schematic representation of normal ECG trace (sinus rhythm) with waves, segments, and intervals labeled. The QT interval is marked by blue stripe at bottom
 http://en.wikipedia.org/wiki/Long_QT_syndrome

Other EKG abnormalities can include:

• polymorphic ventricular tachycardia, i.e. torsades de pointes. Other common forms include multiple PVC or monomorphic VT.

Lead II ECG showing torsades being shocked by an implantable cardioverter-defibrillator back to the patient's baseline cardiac rhythm.
http://en.wikipedia.org/wiki/Long_QT_syndrome

• AV block is also common in the congenital form.
• T-wave abnormalities - notching, alternation in amplitude
• A screening EKG alone is usually insufficient to diagnose at-risk patients. 
• Length of QTc is a predictor of sudden cardiac death
                    

4. Cardiac MRI and Echo: normal, both are used to rule out other diagnoses.
5. Epinephrine challenge or exercise testing: specific to LQT1 mutation
6. Genetic testing: negative test doesn't R/O diagnosis, but positive test can provide prognosis and guide therapeutics, also can help R/O diagnosis in other family members

Treatment may include the following:

1. Beta-blockers: mainstay for congenital form, as they blunt the sympathetic response and are proven to decrease syncopal episodes.
   • Nonselectives - propranolol and nadolol are most effective for LQT1 and LQT2 types. 
   • Propranolol is the first choice for young children.
2. For acquired forms of LQTS; discontinuation of offending drug, correct underlying metabolic or electrolyte disurbance.
3. Cardiac pacing: dual chamber most effective
   • Most useful in patients with bradycardia-induced Torsades
4. Implantable cardioverter-defibrillators (ICDs): considered if the above options don't work, as most children outlive their ICD and require multiple extractions and replacements.
5. Left cardiac sympathetic denervation: resection of the left stellate ganglion and the first four thoracic ganglia.  Usually done as a last resort & results in Horner's syndrome.
6. Avoidance of drugs that can cause QT prolongation (i.e., ondansetron, azithromycin)

Parent Resources

The following may be a helpful resource for families to learn more about Long QT, click on the link below.

References

1. Ackerman, M.J. (1998). Consultation with the specialist: the long QT syndrome. Pediatrics in Review, 19, 232-238.
2. Chockalingam, P. et. al. (2012). Not all beta-blockers are equal in the management of long QT syndromes types 1 and 2. Journal of the American College of Cardiology, 60(20).
3. Miller, M.D. et. al. (1999). Diagnostic accuracy of screening electrocardiograms in long QT syndrome 1. Pediatrics, 108(1), 8-12.
4. Roden, D. (2004). Drug-induced prolongation of the QT interval. NEJM, 350(10): 1013-1022.
5. Roden, D. (2007). Long-QT syndrome. NEJM, 358, 169-176.
6. Rosenthal, G.L. (2008). Identification of genetic abnormalities can aid in development of treatment plan for arrhythmia. AAP News, 29(16).

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