CONGENITAL LONG QT SYNDROME (LQTS)

Long QT syndrome remains an underdiagnosed disorder especially because at least 10-15% of LQTS gene carriers have a normal QTc duration. 

Long QT syndrome is a congenital disorder characterized by a prolongation of QT interval on ECG and a propensity to ventricular tachyarrhythmia, which may lead to syncope, cardiac arrest, or sudden death.

The QT interval represent the duration of activation and recovery of the ventricular myocardium. The Bazett formula is the most common form to calculate the QTc, as follows:

            QTc    =   QT/ square root of R-R interval (in seconds)

(QT interval corrected)

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

Prolonged recovery from electrical excitation increases the likelihood of dispersing refractoriness, when some part of myocardium might be refractory to subsequent depolarization.

In LQTS the transmural dispersion of repolarization increases and creates a functional substrate for transmural reentry.

QT prolonged can lead to polymorphic ventricular tachycardia, or torsade de pointes, which itself may lead to ventricular fibrillation and sudden cardiac death. Torsade de pointes is widely thought to be triggered by reactivation of calcium channels, reactivation of delayed sodium current, or a decreased outward potassium current. That result in early afterdepolarization, in a condition with enhanced transmural dispersion of repolarization usually associated with prolonged QT interval.

The transmural dispersion of repolarization also increases the likelihood of early afterdepolarization, the triggering event to torsade de pointes, by prolonging the time window for calcium channels to remain open.

LQTS is caused by mutation of genes encoding for cardiac in channel protein that cause abnormal ion (potassium, sodium, calcium) channel kinetics. At least 10 gene have been identified, 6 types of Roman-Ward syndrome, 1 type of Andersen syndrome, 1 type of Timothy syndrome and 2 types of Jervell and Lang-Nielsen syndrome.

The information about what medication the patient has taken is critical for the differential diagnosis of congenital LQTS and drug-induced QT prolongation; drug-induced LQT also may have a genetic background.

Other causes of LQTS acquired include electrolyte imbalance, marked bradycardia, cocaine, organophosphorus compounds, subarachnoid hemorrhage, myocardial ischemia, protein-sparing fasting, autonomy neuropathy, and human immunodeficiency diseases (HIV).

The Long QT syndrome is usually diagnosed after a person has a cardiac event (the most typical clinical presentation), a family member suddenly dies, or because an ECG shows QT prolongation.

LQTS has been recognized as mainly Romano-Ward syndrome (familial occurrence with autosomal dominant inheritance, QT prolongation and ventricular tachyarrhythmia).

Finding in the physical examination usually do not indicate a diagnosis of LQTS, though some patients may present with excessive bradycardia for their age, hearing loss (congenital deafness), indicating the possibility of autosomal recessive inheritance like the Jervell and Lang-Nielsen syndrome. Skeletal abnormalities, such as short stature and scoliosis are seen in LQT7 (Andersen syndrome), and congenital heart diseases, cognitive and behavioral problems, musculoskeletal diseases, and inmunodysfunction may be see in those with LQT8 (Timothy syndrome).

MEDICAL CARE

All patients with LQTS should avoid drugs that prolong the QT interval or reduce their serum potassium and magnesium levels.

Beta-Blockers are drugs of choice for patient with LQTS.

The implantable cardioverter-defibrillator (ICD) should be implanted for survivor of cardiac arrest and is recommended class IIa for patients with syncope while receiving beta-blockers. ICD can be considered class IIb for primary prevention in patients with high risk (include LQT2, LQT3 and QTc interval greater then 500ms).

Left cervicothoracic stellectomy is another antiadrenergic therapeutic measure used in patients with high risk, especially in those with recurrent cardiac event despite beta-blocker therapy.