LQT2

# Overview
LQT2 is the second most common subtype of mutations within long QT syndrome, occurring in 35-45% of LQTS patients. This subtype has been known to come to the attention of the cardiologist as a result of a cardiac event during the post-partum period, or after being triggered by an alarm clock or other auditory stimuli. The LQT2 mutation involves the HERG gene on chromosome 7, which regulates the channel responsible for the  potassium rectifying current, which terminates the cardiac action potential. Most drugs that cause acquired long QT syndrome, do so by blocking the potassium rectifying current via the HERG gene. These drugs include antiarrhythmic drugs, certain non-sedating antihistamines, macrolide antibiotics, certain psychotropic medications, and certain gastric motility agents.

# LQT2 Subtype

## Genetics and Pathophysiology
This form of long QT syndrome most likely involves mutations of the human ether-a-go-go related gene (HERG) on chromosome 7.  The HERG gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (IKr). (The IKr current is mainly responsible for the termination of the cardiac action potential, and therefore the length of the QT interval.)  The normally functioning HERG gene allows protection against early after depolarizations (EADs).
There is a possibility, that like in LQT1 mutations, the location of the mutation may have a differing impact on the individual who is affected. A study of 201 patients showed that persons with mutations in the pore region had a greater risk of cardiac events and sudden cardiac death, and that these manifestations occurred earlier than in persons with mutations in the non-pore regions .

## History and Symptoms
- Seizures - due to oxygen deprivation that occurs during arrhythmia.
- Fainting - fainting or syncope is the most common symptom LQTS.
- A prodrome may occur before losing consciousness, which may consist of lightheadedness, heart palpitations, blurred vision or weakness.
- Sudden death - a fatal arrhythmia that is not quickly intervened on, may cause sudden death.
- In LQT2, syncope, prodrome, or other events may particularly occur in the post-partum period, or in response to auditory stimuli.
- Undiagnosed LQT2 may be present in certain individuals who develop acquired long QT syndrome in response to certain medications.

## Therapy
- Beta-blockers are the first line treatment in LQTS, even in asymptomatic carriers, as they reduce the incidence of syncope and sudden cardiac death.
- Other medications to control non-malignant arrhythmias.
- Electrolytes should be repleted as neccesary.
- Avoidance of triggers (drugs, supplements, loud noises, exercise).
- LQTs is one of the few diseases where genetic testing can provide important guidance, such as in whom to place an AICD (defibrillator) for the primary prevention of cardiac events. 
- Placement of a pacemaker may be indicated.
- Left stellectomy is not a cure, but is a second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and AICD is not appropriate.
- Patients with long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.

# Acquired LQTS with Medications
In some patients, drug associated LQTS appears to be due to a congenital form of LQTS which is clinically latent until until the patient is exposed to a drug, or another factor which may bring forth the manifestations of long QT syndrome. Most drugs that cause long QT syndrome do so by blocking the IKr current via the HERG gene. This causes rapid closure of the potassium channels and an abnormal rise in IKr. Similar to LQT1 this also causes results in a delayed ventricular repolarization and a lengthened QT interval.These include erythromycin, terfenadine, and ketoconazole.  The HERG channel is very sensitive to unintended drug binding due to two aromatic amino acids, the tyrosine at position 652 and the phenylalanine at position 656.  These amino acid residues are poised so drug binding to them will block the channel from conducting current.  Other potassium channels do not have these residues in these positions and are therefore not as prone to blockage. Treatment of drug induced LQTS includes acute therapy for the arrhythmia, discontinuation of the drug that precipitated the long QT syndrome, and the correction of any co-existing metabolic abnormalities such as hypomagnesemia and hypokalemia.