Long QT syndrome, LQTS, is a condition that affects the heart’s electrical activities.

LQTS is largely a genetic disorder: children inherit mutations from their parents that

either cause the disease since birth, or make them more susceptible to develop it later

in life when triggered by certain medications or metabolic imbalances.

LQTS itself is not the problem, many people with the syndrome don't have any symptoms

and may not even be aware of it.

However, it predisposes the patient to a life-threatening type of abnormal heart rhythm, known as torsades

de pointes, which may lead to fainting, seizures, or sudden cardiac arrest.

This complication is usually triggered when heart rate accelerates by adrenergic stimulation,

such as during exercise, stress or strong emotions.

LQTS can cause sudden death in seemingly healthy young people.

On an electrocardiogram that records electrical activities of the heart, P wave represents

atrial depolarization, QRS complex is produced by ventricular depolarization, and T wave

corresponds to ventricular repolarization.

The QT interval, measured from the start of Q wave to the end of T wave, reflects the

time taken for ventricular depolarization and repolarization, which is basically the

duration of action potentials in the cells of the ventricles.

An action potential is essentially a brief reversal of electric polarity of the cell

membrane.

It is made possible by the flow of ions in and out of the cell, through specific ion

channels.

Basically, the depolarizing phase is caused by sodium influx; early re-polarization is

due to initial outflow of potassium; plateau phase occurs when potassium efflux is balanced

by calcium influx, and repolarization is when potassium efflux dominates calcium influx.

The duration of repolarization is determined by the balance of current flow through these

ion channels.

The rate of repolarization is slightly different for the 3 layers of the heart wall: the epicardium,

mid-myocardium or M-cells, and endocardium.

Because M-cells have less potassium channels and more sodium channels, they repolarize

more slowly.

On an ECG, the peak of T wave reflects repolarization of epicardial cells, while the end of T wave

corresponds with repolarization of M-cells.

Long QT syndrome is due to prolongation of underlying action potential durations, and

is most commonly caused by mutations in various ion channels that affect the balance of ion

flow.

Specifically, a reduced outward current caused by loss of function of potassium channels,

or an increased inward current caused by gain of function of sodium or calcium channels,

would increase the duration of repolarization.

If inward currents exceed outward currents during the plateau phase, early after-de-polarizations

and consequently extra heartbeats can be triggered.

Mutations in ion channels also disproportionately lengthen action potentials in M-cells, increasing

the difference in refractoriness of the different layers.

This can cause electrical impulses to travel around in loops, known as re-entrant pathways,

producing the characteristic wave pattern of torsades de pointes.

For diagnosis, patient’s QT interval is measured.

But because QT interval varies with heart rate, a corrected QT interval, QTc, is calculated

after measurement.

Diagnosis, however, cannot rely on QTc values alone.

Asymptomatic patients can have longer than normal QTc and develop no arrhythmias, while

patients with established long QT syndrome may have normal QT intervals at rest.

Diagnosis must therefore also include genetic testing, personal history of fainting, and

family history of sudden death.

Treatment aims to prevent a long QT heart from developing dangerous arrhythmias.

Most patients are treated with beta-blockers, which blunt the heart’s response to adrenaline

produced during exercise and stress, making the heart beat slower, thus reducing the risks

for torsades de pointes.

Medications that shorten QT interval may also be prescribed.

On the other hand, medications that prolong QT interval or precipitate development of

torsades de pointes must be avoided.

Patients are also advised to seek immediate treatments for conditions that may result

in low potassium in the blood.