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Produced by Cardiac Risk in the Young |
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 SADS sudden arrhythmic death syndrome |
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Sudden Arrhythmias - what causes SADS? The conditions responsible for SADS cause a cardiac arrest by bringing on a 'ventricular arrhythmia' (a disturbance in the heart's rhythm), even though the person has no structural heart disease. There is a group of relatively rare diseases called ion channelopathies that affect the electrical functioning of the heart without affecting the heart's structure. This means that they can only be detected in life and not at post-mortem. Ion channelopathies are probably responsible for 4 in every 10 cases of Sudden Arrhythmia Death Syndrome. There are several different types of ion channelopathies including:
Structural heart disease is occasionally found to be a cause of SADS (between 1 and 2 in every 10 cases). Ion channelopathies Ion channelopathies are 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 family. 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 or potassium - that carries an electrical charge and forms the basis of the movement of electricity through the heart muscle. An 'ion channel' is the route 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 can cause blackouts, cardiac arrest and in some cases sudden death. Below we describe the different types of channelopathies, the tests needed to diagnose them and the treatment that may be needed for each one. Long QT Syndrome (LQTS) LQTS is the most
common and best understood type of channelopathy. It occurs in
about 1 in 5,000 people. In 7 in every 10 people with LQTS, the ion
channels involved have been identified.
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 t 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. (See the
LQTS diagram - figure 2B - below.) This results in an electrical disturbance in the
cells of the Rare forms of LQTS known as Andersen's and Timothy Syndromes have been associated with potassium and calcium channel abnormalities respectively. What
are the symptoms? The most common symptom of LQTS is blackouts. Sometimes palpitations due to extra or 'ectopic' heartbeats can be a problem. Potassium channel LQTS is associated with sudden death which is related to exercise or when the person has been startled or awoken suddenly ('sudden arousal'). The sodium channel form is associated with death while asleep. Are
there any physical signs? How is
it diagnosed? Genetic testing can sometimes identify carriers of LQTS. 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 most 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 by the fact that people with the same mutation can have effects that vary greatly in severity. All of this makes it very difficult for doctors to decide on the best way to treat people with this condition. Treatment
and advice
The level of risk of sudden death helps decide on the need for treatment. Those who are statistically at greatest risk of sudden death are people with one or more of the following features:
Children who are most at risk tend to be young boys before puberty, and girls who are passing into puberty. Drugs 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 that can cause sudden death. Potassium supplement pills have also been tried with occasional success. Pacemaker
or ICD Surgery Brugada Syndrome This condition was first identified in the early 1990s. It is an uncommon condition in the western world but seems to be much more common among young men in South East Asia. In the western world it affects mainly young and middle-aged adult men. It has been associated with mutations in the same sodium channel that is affected in LQTS, but this appears to account for only 1 in every 5 people with the condition. The sodium channel behaves abnormally in that movement of sodium ions into the cells is restricted. This results in particular changes on the ECG (as shown below in figure 3C) but no abnormalities in the structure of the heart.
What
are the symptoms? Are
there any physical signs? How
is it diagnosed? Genetic testing is not very useful for diagnosing Brugada Syndrome because mutations have been found in only a small proportion of people known to have the syndrome. Treatment
and advice Unfortunately it can be very difficult for doctors to decide how to treat those people who do not get symptoms but who have an abnormal ECG. An EPS (an electrophysiological study) may help to identify those people who do or do not need an ICD. Research has suggested, however, that people with normal ECGs and no symptoms should be safe without any treatment. It is unusual for children to be at high risk. Carriers are advised to take fever lowering drugs such as paracetamol or ibuprofen due to the potential effect of fever on the ECG. CPVT (Catecholaminergic polymorphic ventricular tachycardia) CPVT is a rare condition found in young people and children. It causes a particular type of arrhythmia. It has been associated with two genes that make proteins found inside the cell - the human ryanodine receptor (a calcium ion channel) and calsequestrin (a protein that interacts with the channel). These regulate the release of calcium ions into the rest of the cell. If these do not function normally, the level of calcium inside the cell becomes too high, resulting in the arrhythmias characteristic of CPVT. What
are the symptoms? The condition can affect children and seems to cause more blackouts in males than in females. Are
there any physical signs? How
is it diagnosed? Treatment
and advice PCCD (Progressive cardiac conduction defect) PCCD is a rare condition. In people with PCCD, the heart's electrical impulses are conducted very slowly and this results in the gradual development over time of 'heart block'. (Heart block is a failure of the heart's electrical impulse to conduct properly from the top chambers [the atria] to the bottom chambers [the ventricles]. The severity of the condition and its associated risk can vary.) PCCD can cause arrhythmias - either because the heart's rhythm is too sluggish (bradycardia and asystole), or because of rapid rhythm disturbances (tachycardia) arising from parts of the heart that have escaped normal regulation. In some people PCCD has been associated with sodium channel mutations that cause changes in channel behaviour similar to those found in people with Brugada Syndrome (see the Brugada Syndrome diagram - figure 2C - above). What
are the symptoms? Are
there any physical signs? How
is the diagnosis made? Treatment
and advice IVF (Idiopathic ventricular fibrillation) This term describes the group of conditions responsible for life-threatening, rapid rhythm disturbances without any signs of heart disease. Brugada Syndrome and CPVT form part of this group but there have been reports of patients with IVF who do not have the ECG changes characteristic of the Brugada Syndrome but who do have sodium channel mutations. Treatment includes having an ICD fitted, and can be successful in protecting the person. Sodium channel disease There are very rare and specific sodium channel mutations that can cause Long QT Syndrome, Brugada Syndrome and/or PCCD in the same family. They can be diagnosed and treated as described above and can be identified by genetic testing. Structural heart disease In some cases, the pathologist cannot confirm a diagnosis of structural heart disease - either because there is no evidence of it, or because there is not enough evidence and the heart is felt to be relatively normal. So the death will be recorded as SADS. This may happen even in cases where evidence of inherited structural heart disease is subsequently detected in other members of the victim's family. The presence of very subtle structural heart disease in the victim may, however, have been enough to cause sudden cardiac death. In these circumstances the most common causes of death are:
We explain each of these in sudden death.
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he flow
of sodium ions from the outside to the inside of cells is affected.
heart called 'prolonged
repolarisation'. This can be seen on an ECG recording as
a lengthening
of the time period known as the 'QT interval'. This is
where the name Long QT Syndrome
comes from.
