What is long QT syndrome?
Long QT syndrome refers to a condition where a person has a particular abnormality of the heart’s electrical system, without any other heart abnormality. The name refers to the way the condition alters the picture of the electrocardiogram (ECG or electrical tracing of the heart). The ECG shows a longer than usual interval between two points on the tracing, which are known as ‘Q’ and ‘T’.

Normally, the muscular contraction of the heart, which allows it to pump blood, is triggered by a tiny electrical current that passes from the top to the bottom of the heart. As this electrical ‘wave’ passes through the walls of the heart they are ‘depolarised’ and during this period the muscle fibres in
them begin to contract. After this has happened the individual heart muscle cells spontaneously ‘repolarise’ or return to their normal resting
electrical state to wait for the next heartbeat. In long QT syndrome, the ‘repolarisation’ or return to normal takes a longer period of time than in a perfectly normal
heart.

There are various causes of a long QT interval on an ECG, such as certain drugs that can interfere temporarily with the QT interval. In most cases it is due to an abnormal gene which can be inherited by other members in the family and is, therefore, termed a genetic condition. Rarely, it may be
associated with deafness in babies.

The hearts of people who have long QT syndrome work perfectly normally most, or all of the time. There is, however, a greater risk than normal that the heart will spontaneously get out of rhythm and stop pumping regularly. In some people this leads to fainting spells or ‘blackouts’. In some people with long QT syndrome, if the rhythm does not recover spontaneously (as it usually does), this can lead to sudden death. The risk of sudden death can be considerably
reduced with simple treatments.

How is the condition inherited within the family?

Long QT syndrome is a genetic condition that is usually inherited in a ‘dominant’ manner. This means that each child of an affected parent has a one in two (50%)
chance of inheriting the syndrome. If a child has not inherited the faulty gene causing long QT syndrome, he or she cannot pass it down to his or her children.
In this sense, it does not ‘skip’ a generation.

In rare cases, it is possible to inherit the gene fault that causes the syndrome, but for some reason the gene fault does not produce an obvious abnormality on the ECG every time it is recorded. This happens in many other genetic conditions; it is not peculiar to long QT syndrome. However, it is very difficult to make a diagnosis in that person, to know if they are at risk of the problems associated with the syndrome, and also to work out the risk of inheritance for that person's children. This is why it is always important for health professionals to take a detailed family history, as this full picture can sometimes help with making a clear diagnosis. Once the specific genetic defect has been found in a family this difficulty can be resolved.

Once a new diagnosis has been made, or if there is a suspected diagnosis of long QT syndrome, it is recommended that all children, brothers and sisters, as well as parents are seen by a cardiologist or a paediatric cardiologist with an interest and expertise in the condition. An ECG will be required to see if the condition has been inherited and other tests, such as an exercise test, may be necessary.

Sometimes it is very difficult to make a firm diagnosis of long QT syndrome on the basis of the ECG recording because some people have a ‘borderline’ lengthening of the QT interval, which may be normal for them, or it may be indicative of the syndrome. At present some people with a borderline QT interval, who are part of a family with definite long QT syndrome, are advised to be treated in the same way as their relatives who have a definite diagnosis.

What are the risks and outcomes of long QT syndrome?

Most people with long QT syndrome survive and live normally, which has enabled the condition to be transmitted from generation to generation through affected families.

Some people with the syndrome have recurrent blackouts. Unfortunately, these are sometimes misdiagnosed as common fainting or dizzy spells, or epilepsy.
These blackouts sometimes, but not always, occur under conditions of exertion, emotion or excitement. Episodes while swimming are common. Less commonly, these can occur during sleep. People who experience blackouts are at risk of sudden death. Fortunately, this risk is considerably reduced with simple modern treatments.

Can one predict who is at highest risk of serious problems?

People who are at highest risk of serious problems associated with long QT syndrome are those who have recurrent blackouts, those with a very long QT interval, and females more than males. Unfortunately, while these features can be used to identify most people who may experience serious problems, there is
still a small risk even for those people who do not have these features.

What can be done about the problems of long QT syndrome?

Beta-blockers, which are medications widely used to treat high blood pressure and other conditions, are also used in long QT syndrome. This is because they
are known to reduce or eliminate blackouts and almost certainly reduce the chances of sudden death in long QT syndrome. Those with slow heart rates may need a permanent pacemaker, to allow treatment with beta-blockers.

For people who continue to have symptoms despite treatment and for those who are unable to take beta-blockers, an operation called ‘stellate ganglionectomy’
may be carried out. This operation decreases the nerve supply to the heart and is usually done only in symptomatic individuals. A few patients who are at very
high risk may receive an implantable defibrillator, which automatically delivers an electrical current to enable the heart to revert to normal should it develop a dangerous abnormal rhythm. As a precaution, it is recommended that everyone in long QT families know the principles of cardiac resuscitation (or CPR as it is sometimes called).

What are the effects of beta-blockers?

Beta-blockers work by dampening the bursts of nerve impulses that go to the heart and excite its electrical system during exercise, or emotion. They slow the heart rate and reduce blood pressure and have been used for many years with no serious long-term effects. In large doses, beta-blockers may cause faintness (especially on standing up suddenly), lethargy and exercise intolerance. Usually these symptoms improve if the dose is reduced slightly. The dose should be just
a little below that which causes these side effects.

Beta-blockers may make asthma worse and this can be a difficult problem for those with long QT syndrome. Certain types of beta-blockers (‘selective
beta-blockers’) are suitable for asthmatics. However, if asthma is already severe, or becomes severe on beta-blockers, it is probably better not to take them unless the person is judged to be at high risk of the serious heart symptoms described.

It is very important that people with long QT syndrome take these drugs if possible, but it is equally important to establish a dose that does not cause major side effects.

Medications and their dosages should only be changed in consultation with the doctor who is treating the condition.

Are there any activities or drugs that should be avoided?

Activities: Most people with long QT syndrome can engage in all normal activities unless they have had symptoms such as dizziness or blackouts during physical exertion. Some restrictions may need to be placed on participation in competitive sport.

Drugs: Some drugs are known to prolong the QT interval in any person who takes them. The drugs come in several categories. Some of the drugs which may prolong the QT interval are listed below:

• Cardiac – Many anti-arrhythmic drugs, such as Quinidine, Sotalol, Amiodarone

• Psychiatric – Phenothiazine drugs, for example Thioridazine (Melleril) and some anti-depressants, e.g. Amitriptyline (Tryptanol)

• Antibiotics – Erythromycin, Ketaconazole and Pentamidine

• Antihistamines – Astemizole (Hismanal), Terfenadine (Teldane)

• Diuretics (fluid tablets) – These may cause a low level of potassium in the blood, which prolongs the QT interval

• Gastrointestinal – Cisapride (Prepulsid)

Other issues:

• Electrolytes: The blood level of potassium may fall as a result of diarrhoea and additional potassium and magnesium supplements may be required.

• Toxins: Liquid protein diets, Chinese herbs and exposure to organophosphates could aggravate long QT syndrome.
  

What does the future hold?

As a result of worldwide genetic research in affected families, a number of different genes, which cause long QT syndrome, have now been identified. This vital research is leading to significant advances with respect to identifying those affected, as well as providing treatment options that aim to treat the cause of the condition, rather than its effects.

Identifying the genetic defects in a particular family will finally assist doctors to make a more accurate diagnosis in other relatives who are at risk of
inheriting the condition. Also, through the identification of particular genes, researchers are beginning to understand what causes the heart condition. That is, more is becoming known about how a particular gene defect alters the gene’s message from one that is designed to make the heart work normally. With such knowledge, eventually it may be possible to ‘neutralise’ or even repair the abnormal gene. In the future, it may be necessary to know the genetic typing of each family in order to select a specific, more effective treatment for that family.

As the result of research and a better understanding of the way abnormal genes change the membranes of heart cells, it is hoped that before too long, beta-blockers, which help prevent the detrimental effects of long QT syndrome, will be replaced by a more specific and effective treatment.

The following organisation can provide further information and support for those affected by long QT syndrome: