Long QT syndrome (LQTS) is an ion channelopathy. Ion channelopathies (also sometimes referred to as arrhythmia syndromes or cardiac channelopathies)affect the electrical functioning of the heart without affecting the heart’s structure. They are a group of rare genetic conditions that are caused by abnormalities of the DNA known as mutations. They are usually inherited from parents although they can occur for the first time in a person. (If they occur for the first time they are described as sporadic.)
The mutations affect certain genes – specific segments of the DNA that are responsible for the production of cardiac ion channels. An ion is a chemical substance – such as sodium, potassium or calcium – that carries an electrical charge and forms the basis of the movement of electricity through the heart muscle. Each heart muscle cell is surrounded by a membrane that separates the inside from the outside of the cell . An ion channel is the route (the gate) that the ions take in and out of the heart muscle cells to allow the movement of electricity. The ion channels regulate the flow of electrical charge. If these channels do not behave normally, the electrical function of the heart becomes abnormal. The person can then be prone to arrhythmias (disturbances in the heart’s rhythm) that may cause blackouts or a cardiac arrest.
LQTS is the most common and best understood type of channelopathy.
It occurs in about 1 in 2,000 people. In 70% of people with LQTS, gene testing can identify the ion channels involved. In most cases two of the potassium channels that regulate the movement of potassium ions from the inside to the outside of the cell are affected. In a small proportion of people with LQTS, a sodium channel that regulates the flow of sodium ions from the outside to the inside of cells is affected.
In people with potassium channel associated LQTS, the channels do not behave as efficiently as normal. They let potassium ions into the cell too slowly. If the sodium channel is affected, too many sodium ions are allowed into the cell.
This results in an electrical disturbance in the cells of the heart called prolonged repolarisation. This can be seen on an ECG recording as a lengthening of the time period known as the QT interval.
What are the symptoms?
LQTS varies greatly in severity. Symptoms vary according to the type of channel involved, whether the person is male or female, their age, and the length of the QT interval on the ECG. Males are more likely to have symptoms before puberty, while females are more likely to have them in adolescence and early adulthood. Relatives from the same family who have inherited the same mutation may have very different experiences. For example, some may have a normal QT interval and not have any symptoms; some may have a very abnormal QT interval but no symptoms; and some may have a very abnormal QT interval and have many symptoms that put them at risk.
The most common symptom of LQTS is blackouts. Sometimes palpitations due to extra or ectopic heartbeats can be a problem.
Are there any physical signs?
There are usually no physical signs of LQTS. However, certain rare forms of LQTS may be associated with muscle weakness, minor abnormalities of the skull, chin, fingers and toes or reduced hearing.
How is it diagnosed?
Diagnosis involves having an ECG. Sometimes it is possible to tell which ion channel has been affected just by looking at the ECG recording. Unfortunately, in a proportion of people who might be carriers, the ECG may not show any sign of the condition. Repeated ECGs, exercise tests and 24-48 hour tape monitoring may be needed before the diagnosis is established. More recently some doctors have used slow injections of the hormone adrenaline (epinephrine) via a drip to try and improve the diagnosis of some potassium channel LQTS. There is no evidence however that this is any better than an exercise test.
Genetic testing can identify carriers of the LQTS gene. Unfortunately, this form of testing is limited at the moment, as 3 in every 10 people who are known to have LQTS do not have mutations of the genes known to be associated with LQTS. An additional problem is that many families who do have the mutations appear to have a specific change to the DNA code which is not found in other families (known as a ‘private’ mutation). This sometimes makes it difficult to decide whether a mutation is causing the disease or not. Things are further complicated because people with the same mutation can have effects of varying severity.
Treatment and advice
If you have LQTS, your doctor will advise you to avoid excessive exercise or strenuous athletic activities. He or she will also advise you to avoid certain drugs that can make the condition worse and which could increase the risk of blackouts and cardiac arrest.
Watch CRY’s myheart cardiologist, Dr Michael Papadakis, talk about things to avoid if you have an ion-channel disease below.
Other treatment options will vary depending on the severity of the condition. Those with one or more of the following features will likely need more intervention than those without:
a previous cardiac arrest
a very long QT interval on the ECG
sodium channel mutations
some potassium channel mutations
young, adult women.
The most commonly used drugs for LQTS are beta-blockers. These block the effects of adrenaline and associated natural chemicals in the body that make the heart pump harder and faster. They therefore also block the effects of exercise on the heart. They are effective in the most common forms of LQTS as they reduce symptoms and the risk of cardiac arrest. However, they are less effective in people with the sodium channel form of LQTS.
There are other more recent trends in drug treatment that look promising, but their long-term benefits are unknown. These involve using antiarrhythmic drugs. These drugs block disturbances in the heart rhythm. Potassium supplement pills have also been tried with occasional success.
Pacemaker or implantable cardioverter defibrillator (ICD)
If you are at high risk (for example if you have already had a cardiac arrest), or if drugs have failed to control your symptoms, your doctor may advise you to have a pacemaker or an implantable cardioverter defibrillator (ICD) fitted, as well as taking your medication. A pacemaker and an ICD both consist of an electronic box that is inserted under the skin and attached to the heart by special electrical ‘leads’. A pacemaker controls the heart rate and stops any excessive slowing of the heart that could trigger an arrhythmia. An ICD acts in the same way as a pacemaker but it can also identify any dangerous arrhythmias and deliver an electrical shock to reset the heart.
Another option for high risk patients is to perform surgery to disrupt the nerves that release adrenaline and related chemicals at the heart. This is performed in only a small minority of individuals and is known as cervical sympathectomy and involves operating on the left side of the neck.