Long QT Syndrome – Overview, Types, Causes and Risk Factors

Overview of Long QT Syndrome

Long QT syndrome (LQTS) is a disease that can cause a dangerous rapid heart rate and irregular rhythm involving the bottom pumping chambers of the heart (ventricles). The heart has both muscular and electrical components. Electricity flowing through the heart muscle triggers the muscle to squeeze (contract) or beat. Heart muscle cells use highly coordinated ion channels to keep the flow of electricity moving to generate normal heartbeats.

Ion channels are what the electrolytes potassium, sodium, and calcium flow through within the heart’s cells. In LQTS, a problem in the ion channels leads to an upset in the flow of electricity that causes a prolonged “repolarizing” of the heart cells. This delay means the heart isn’t ready for the next beat. This can create a set-up for a very rapid and dangerous heart rhythm (arrhythmia) that may cause fainting or sudden death. These arrhythmias are called ventricular tachycardia, ventricular fibrillation, or Torsades de pointes.

The name, long QT, stems from a reading on the electrocardiogram (ECG) machine. Healthcare providers use the ECG to evaluate your heartbeat and rhythm. The ECG machine records and measures each of your heartbeats as 5 “waves.” Each wave has a different letter designation: P, Q, R, S, and T. The relationship between the Q and T waves is important and is known as the QT interval. During this interval, the lower chambers (ventricles) are “repolarizing” or preparing for the next wave of electricity that will elicit a heartbeat. When the interval lasts longer than it normally should, it disrupts the timing of your heartbeat and can cause dangerous arrhythmias, or irregular heart rates.

Common Types of Inherited LQTS

Most people with long QT syndrome (LQTS) have the inherited form, which means that you are born with the condition. Of the known types of inherited LQTS, the most common are types 1, 2, and 3.

Long QT syndrome type 1 (LQT1)

In LQT1, the potassium ion channels in the heart do not work properly, disrupting the heart’s electrical activity. Emotional stress or physical exercise, particularly swimming, can trigger arrhythmias (abnormal heartbeat) in people with LQT1.

Torsades de pointes (French for ‘twisting of the points), the most dangerous type of ventricular tachycardia, occurs more often in people with LQT1. Although people with this condition may have more episodes of arrhythmia, the episodes usually stop on their own, without treatment. That means the episodes are less likely to be fatal.

Long QT syndrome type 2 (LQT2)

LQT2 results from insufficient potassium ion activity in the heart. This deficiency prevents proper electrical function in the heart and leads to arrhythmia (abnormal heart rhythm).

Emotional stress, surprise, and startling can cause arrhythmias in people with LQT2. A common trigger is sudden, loud noises such as alarm clocks or car horns.

Long QT syndrome type 3 (LQT3)

LQT3 occurs when too little sodium flows through the heart’s ion channels. Because this sodium flow is essential to proper electrical activity in the heart, a lack of sodium flow can trigger an arrhythmia (abnormal heart rhythm).

People with LQT3 often develop arrhythmias during sleep or rest, caused by a slow heart rate. Although people with LQT3 have fewer episodes of arrhythmia, these episodes are more likely to be fatal.

Epidemiology

The prevalence of congenital causes, also known as Long QT syndrome (LQTS), is difficult to estimate but may be expected in 1 in 2,500 to 1 in 10,000 individuals. It is more common in females and usually presents with cardiac events in childhood, adolescence, or early adulthood. There are, however, case reports of it manifesting in the fifth decade of life. Family history is positive for Long QT syndrome in 40%, and for sudden cardiac death in 30% of patients. Acquired causes are relatively more common than congenital causes. Some studies report the prevalence of QT prolongation to be as many as 30% of patients in the intensive care unit.

Long QT Syndrome Pathophysiology

Depolarization of cardiac cells involves a rapid influx of the positive ion’s sodium and calcium. Repolarization begins with the rapid transient outflow of potassium (Kþ). This is followed by the flow of outward current through the slowly activating (iKs) and rapidly activating (iKr) delayed rectifier Kþ channels. Inward current through Ca2þ channels and the influx of sodium ions through late activating iNa channels partially counter the outward flow of current. The duration of repolarization is determined by the balance of current flow through these channels.

The rate of repolarization recorded from epicardial (Epi), mid-myocardial (M cells), and endocardial (Endo) sites in the heart is not homogeneous. Because M cells are less dense in iKs channels and denser in iNa channels than surrounding regions, the rate of repolarization is slower than that of the epicardium or endocardium. This results in asynchronous repolarization of the myocardium, causing a physiological transmural dispersion of repolarization (TDR). The morphology of the T wave is dependent on the time course of repolarization across the myocardium.

The peak of the T wave coincides with the repolarization of the shortest epicardial action potential, whereas the end of the T wave corresponds with repolarization of the M cells which have a longer action potential. Therefore, the TDR is the difference in repolarization time between the M and epicardial cells, and is represented on the ECG by the interval from the peak to the end of the T wave (Tp-e).

The action potential and hence the QT interval is prolonged by a reduction in iK channel function or an increase in iNa channel conductance. When this ion channel dysfunction involves M cells, there is a disproportionate lengthening of the action potential causing a prolongation of the TDR. This may result in late calcium inflow, with the development of early afterdepolarizations (EADs). If these EADs reach a threshold amplitude, torsade de pointes can be triggered.

Causes

LQTS can be categorized as congenital (inherited, genetic) or acquired (triggered by some condition, medication or event).

Congenital (Inherited) LQTS

People with congenital LQTS have a genetic mutation that affects sodium or potassium channels in the heart. Sodium and potassium help generate electricity inside the cells.

Children may be diagnosed in infancy or later, either because they go through an episode of seizures or cardiac arrest, or because of family members known to have the mutation. Babies have even been diagnosed in utero. Boys are more likely than girls to have a dangerous cardiac episode from LQTS by age 15.

On the other hand, there are people whose family members have LQTS and who share the genetic mutation, but never have symptoms themselves. This may be because their LQTS is very mild or because they have not been exposed to the “right” combination of triggering conditions or medications. Anyone diagnosed with congenital LQTS should inform family members so they can be tested.

Acquired LQTS

Acquired long QT syndrome is the result of conditions, medications or events that prolong the QT interval. It is more common in women than men. Stopping the medication and/or correcting the condition causing LQTS often resolves the issue. Sometimes the symptoms are caused by not one but several triggers — for example, a genetic mutation combined with a medication that prolongs the QT interval.

Triggering Conditions

Electrolyte Imbalances

• Potassium deficiency (hypokalemia)
• Magnesium deficiency (hypomagnesemia)
• Blood calcium deficiency (hypocalcemia)

Other Conditions

• Malnutrition
• Hypothyroidism
• A history of heart disease, including heart failure, heart attack, left ventricular hypertrophy or bradycardia
• A history of stroke

Triggering Medications

A wide variety of drugs may lengthen the QT interval. If you have been diagnosed with LQTS, consult your physician about which drugs put you at risk. The most common types of drugs are:

• Antibiotics
• Antifungals
• Antiarrhythmics

Rarely, grapefruit juice may increase the risk of a dangerous cardiac event when combined with a triggering drug.

Important clinical traits of the inherited long QT syndrome (LQTS)

Symptoms of Long QT Syndrome

Many people with long QT syndrome do not experience any symptoms.

If you do experience symptoms, they usually occur before the age of 40 years. Symptoms occur when your heart suddenly starts beating erratically due to a dangerous arrhythmia, which can result in the brain being deprived of oxygen.

Possible symptoms of long QT syndrome include:

• Fainting, which can be triggered by exercise (especially swimming) and emotions (such as surprise from a loud noise, excitement, anger or fear);
• Making loud gasping noises during sleep or when waking from sleep (sleep can trigger abnormal heart rhythms in some forms of long QT syndrome); and
• Seizures.

Unfortunately, sometimes the first symptom of long QT syndrome is sudden, unexplained death.

Long QT syndrome may be suspected after events such as an unexplained drowning or near drowning in a strong swimmer (which may be due to fainting while swimming) or a car accident on a straight road.

Long QT Syndrome Risk factors

QT prolongation increases the risk of developing abnormal heart rhythms, including the life-threatening arrhythmia torsades de pointes (TDP). This type of arrhythmia can lead to sudden cardiac death.

The likelihood of QT prolongation resulting in TDP increases with the following risk factors:

• Having a family history of TDP
• Being female
• Being older
• Taking certain medications

The following conditions can also increase the likelihood of QT prolongation causing TDP:

• Dehydration
• Conditions that cause electrolyte imbalances
• Raised blood cholesterol
• Diabetes
• Thyroid disorders
• Left ventricular hypertrophy
• Heart disease

Also, certain external triggers such as exercise, noise, and stressful events may trigger arrhythmias in congenital long QT syndrome.

Complications of Long QT Syndrome

Proper medical treatment and lifestyle changes can help prevent complications related to long QT syndrome.

Potential complications of long QT syndrome include:

• Torsades de pointes (“twisting of the points”). This is a life-threatening irregular heartbeat (arrhythmia). The heart’s two lower chambers (ventricles) beat fast and chaotically, making the waves on an ECG monitor look twisted. The heart pumps out less blood. The lack of blood to the brain causes sudden fainting, often without warning.

If the episode lasts for a long time, fainting can be followed by a full-body seizure. If the dangerous rhythm does not correct itself, then a life-threatening arrhythmia called ventricular fibrillation follows.

• Ventricular fibrillation. This condition causes the lower heart chambers to beat so fast that the heart quivers and stops pumping blood. Unless a defibrillator is used to reset the heart’s rhythm, ventricular fibrillation can lead to brain damage and sudden death.
• Sudden death. Long QT syndrome has been linked to sudden death in young people who otherwise appear healthy. The condition might be responsible for some unexplained events in children and young adults, such as unexplained fainting, drownings or seizures.

Diagnosis of Long QT Syndrome

If you have symptoms or a family history that indicates long QT syndrome, you will have tests including:

• Physical exam
• Electrocardiogram (ECG): This test records the electrical impulses in the heart and can detect any abnormal patterns, such as a long QT interval.
• Holter monitor: This is a wearable device that monitors the heart’s electrical activity as you go about your daily activities.
• Genetic testing: Blood tests can identify gene mutations that cause long QT syndrome.

The picture illustrates an ECG typical set up

Treatment

The treatment for Long QT Syndrome is aimed at reducing the risk of the arrhythmia from occurring. Lifestyle changes and medication are very effective and will be tailored to the individual.

Medications

The first treatment is usually a beta-blocker medication such as propranolol, atenolol or nadolol. This group of medications helps control irregular heartbeats and can slow the heart rate.

Lifestyle modifications

Your Cardiologist will provide information specific to your child regarding what lifestyle changes or modifications you may need to adhere to. For most, this will mean avoiding strenuous activity, especially competitive sports and swimming, and for some they will need to avoid loud noises that may startle them or awake them when sleeping.

Implantable cardioverter defibrillator

If beta-blockers are not effective in managing your child’s heart rhythm, your child may need to have an operation to implant an implantable cardioverter defibrillator (ICD). This device is similar to a pacemaker but is also able to deliver an electrical shock if it senses that the heart is beating in a potentially dangerous rhythm. This can help return the heart to normal rhythm and get it pumping again.

Automatic External Defibrillator

An Automated External Defibrillator (AED) is a portable device that is used to deliver an electric shock in order to make the heart rhythm normal again. In this way it is similar to an ICD, however the AED is an external machine that has adhesive pads that need to be applied to the chest in order for the shock to be delivered. The current devices are all preprogramed to analyse the rhythm once the pads are applied and will audibly instruct the user what action is required. It is best to speak to your Cardiologist about whether this device is recommended for your child.

Surgery

You may need surgery to cut the nerves that cause dangerous heart rhythms. This keeps your heart beating at a steady pace and lowers the risk of arrhythmias caused by stress or exercise.

How to prevent Long QT Syndrome?

You can’t prevent inherited LQTS. But you can do things to reduce your risk for things that can trigger arrhythmias and sudden death:

• See your healthcare provider regularly.
• Take your medicines as prescribed. Don’t take medicines that prolong the QT.
• Follow limits on certain activities such as strenuous exercise and driving.
• Stay away from high-stress situations that may trigger LQTS.
• Ask your healthcare provider if you need a potassium supplement.
• Wear a medical alert bracelet.

Lifestyle and home remedies

Lifestyle changes may be recommended to reduce the chances of a long QT syndrome-related fainting spell or sudden cardiac death.

Know which sports are safe: It may be possible to stay fully active in sports, including competitive sports, after carefully reviewing the risks and benefits with your health care provider. In general, people with long QT syndrome should never swim alone. Recreational activities are likely to be OK if you take a buddy along in case you have a fainting episode.

Check for startling sounds: Turn down the volume on doorbells and other devices (such as telephones) that may startle you, especially during sleep.

Manage emotions: Being very excited, angry or surprised can trigger heartbeat changes in some people with long QT syndrome.

Check your medicines: Avoid drugs that could cause prolonged QT intervals. If you’re not sure, ask your health care provider. It’s a good idea to let your provider know about all the medications and supplements you take, even those you buy without a prescription.

Get regular health checkups: If you have changes in your symptoms or condition, your health care provider may update your treatment plan or suggest additional treatments.