Long QT Syndrome

Clinical Presentation

1.         Palpitations

2.         Pre-syncope or syncopeö often due to torsades de pointes

3.         Cardiac arrest and deathö secondary to ventricular fibrillation

Differential Diagnosis

1.         Vasovagal syncope

2.         Hypertrophic Cardiomyopathy

3.         Brugada syndrome

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: abnormal, prolonged QT interval

4.         ECHOö  normal (only helps to R/O other causes)

5.         Cardiac MRIö normal

6.         Epinephrine challengeö specific to LQT1 mutation

7.         Genetic testingö 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

Pathophysiology

     1. Congenital or acquired

     2. 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)

            a. LQT1: most common, triggered by emotional or physical stress (specifically diving and swimming), associated with autosomal recessive Jerrvell and Lange-Nielseen Syndrome (LQTS with congenital sensorneural hearing loss)

            b. LQTS2: syncope or sudden death with stress or at rest, events triggered by sudden loud noises (almost diagnostic), normal hearing

            c. LQTS3: associataed with bradycardia, may be casue of syncope.

   3. Two clinical phenotypes described in congenital LQTS, based on type of inheritance and resence or absence of sensoineural hearing loss

            a. Romano-Ward Syndrome

i More common form

ii Autosomal dominant

iii Purely cardiac phenotype

           b. Jervel and Lange-Nielsen Syndrome

i Autosomal recessive

ii Only been describe in LQTS1 abd LQTS5

iii Associated with LQTS and sensorineural deafness

iv More malignant clinical course

    4. Acquired LQTS usually results from drugs that prolong the QT interval, electrolyte disturbances, or metabolic abnormalities.

Risk Stratification

1.         Length of QTc at resentation is a predictor of sudden cardiac death.

Treatment

1.         Beta-blockers

a.         Long acting: nadolol and atenolol

2.         Implantable cardioverter-defibrillators (ICDs)

a.         Considered for patients with high risk for cardiac death

2.         Left cardiac sympathetic denervation (i.e. left stellate cardiac ganglionectomy)

1.         Main indications are failure of medical therapy, frequent shocks with an IC despite medicataions.

2.         Cardiac pacing

1.         Used in patients with congenital LQTS who remain symptomatic despite beta blockers, particularly thosie in whom bradycardia facilitates torsades de pointes (paatients with LQTS3, which is associated with bradycardia)

2.         For acquired forms of LQTS; discontinuation of offending drug, correct underlying metabolic or electrolyte disurbance.

References

1.         Roden, D. Long QT Syndrome. NEJM 2008;358:169-76.

2.         Chiang,CE, Roden, DM The long QT syndrome: genetic basis and clinical implications. J AM Coll Cardiol 2000;36 1-12

3.         Haverkamp,W et al. The potential for QT prolongations and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications.  Report on a policy conference of the European Society of Cardiology.  Eur Heart J 2000;21 1216-1231

4.         Schwartz,PJ et al. Left cardiac sympathitic denervation in the management of high-risk patients affected by the long QT syndrome.  Circulaation 2004;109;1826-1833

5.         Viskin,S Cardiac pacing in the long QT syndrome: review of available data and practical recommendations. J Cardiovasc Electrophysiol 2000;11:593-600

6.         Zipes,DP et al. ACC/AHA/ESC 2006 Guideline for Management of Patient with Ventricular Arryhthmias and the Prevention of Sudden Cardiac Death.  J Am Coll Cardiology 2006;48:1064-1108