Long QT Syndrome

What Is Long QT Syndrome & What Causes It?

LQTS is a heart disorder where there are changes in the heart’s electrical system but not the heart’s structure. Electrical signals move from the top to the bottom of your heart in a coordinated way and tell your heart to beat in the proper rhythm so that the heart contracts to pump blood around your body. After each beat, the system resets then repeats the cycle.

The electrical signals are the result of many pores on the surface of cells (ion channels) opening and closing rapidly. These pores allow ions like sodium and potassium to move in and out of cells. In LQTS, mutations (also called variants) in the genes responsible for these channels mean that the channels do not work as they are supposed to. This leads to a slow ‘system reset’ after each heartbeat. A cardiologist can often (but not always) detect the issue through the ECG — this delay in the ‘system reset’ is known as a prolonged QT interval on the ECG.

In LQTS, the QT interval can change minute-to-minute — sometimes it is normal whilst at other times it is abnormally prolonged. A patient may experience these prolonged QT intervals as a result of intense emotions, like being excited or angry; being scared or startled; or during or after exercise. The prolongation can also be due to medications and other illnesses. In many people with LQTS, the prolongation is present most of the time, despite no triggers being present. 

The QT prolongation increases the risk of a dangerous heart rhythm called ‘torsades de pointes’ (TdP). TdP can cause serious complications, including fainting and seizures, because the brain is starved of blood when the heart is in TdP. The most feared complication of TdP is sudden death, and this is how LQTS manifests for the first time in some people who were previously well and healthy.

There are different causes of QT prolongation. The two main groups are acquired (occurring later in life because of other factors) and congenital (inherited).

Acquired QT prolongation is a disorder brought about by other medical conditions, medications or mineral (salt) imbalances in the bloodstream (for example low or high potassium in the blood).

Inherited LQTS is a disorder caused by genetic mutations passed on through your family or occurring spontaneously when you were conceived (known as ‘de novo’). Once you have the mutation, you are at risk from birth of developing LQTS and you cannot completely rid yourself of the possibility of doing so. Neither can you reverse the mutation. Instead, an early diagnosis is the best way to improve life expectancy and quality of life.

As a congenital disorder, LQTS is caused by many different genetic mutations in a group of genes that are important for the function of ion channels in the heart. If a parent has a mutation in a gene associated with LQTS, they have a 50% chance of passing it on to their child. This is the more common type of long QT syndrome, previously called Romano-Ward syndrome (one faulty copy of an LQTS gene). There is also a much rarer form of LQTS. This occurs when both parents carry a mutation in only one copy of a LQTS gene, and both parents pass down their faulty copy to a child. The child then has two faulty copies of an LQTS gene. This is Jervell and Lange-Nielsen syndrome, where the full pair of an LQTS gene has the mutation. 

Acquired QT prolongation can be caused by more than 100 different medications, including:

• Antibiotics
• Antifungals
• Heart rhythm drugs (anti-arrhythmics) that lengthen the QT interval
• Antidepressants and antipsychotics
• Anti-nausea medications

QT prolongation can occur in anyone when taking these medications. Therefore, it is important to monitor your health and wellbeing when prescribed new medications, and to let your general practitioner or cardiologist know if you have any concerns.

Similarly, a range of health conditions can lead to dangerous arrhythmias developing in individuals with LQTS, like:

• Hypothermia (body temperature below 37ºC)
• Vomiting, diarrhoea or anorexia leading to low calcium (hypocalcemia), low magnesium (hypomagnesemia) and or low potassium (hypokalemia)
• Strokes or brain bleeds (intracranial)
• Underactive thyroid (hypothyroidism)

Most acquired forms of LQTS can be ‘cured’ by identifying and treating the underlying causes above (for example, stopping the medication that is prolonging the QT interval). However, the congenital form of LQTS remains with you for life. Additionally, the triggers for acquired LQTS can often make congenital LQTS worse, so knowing if an individual has a genetic mutation that causes QT prolongation is very important for their health. Further, it is impossible to know if a person with QT prolongation has the acquired form or the congenital form without specialised genetic testing for long QT syndrome that is then interpreted by a service with expert knowledge of LQTS genetics. Thus, genetic testing is vital in making a clear diagnosis. 

Given that congenital long QT syndrome is inherited, a positive result for LQTS in your genes can indicate that other family members need to be checked also. This can help them get diagnosed sooner and start protecting their health for the best prognosis possible.

Do You Have Long QT Syndrome Symptoms? 

LQTS symptoms can vary in expression and severity between people — even those within the same family. For instance, one person may experience continual development of heart issues, another may remain stable, and another may have minor changes that can only be detected by a cardiologist who is intimately familiar with LQTS.

If you have the disorder, you may experience:

• Sudden fainting (syncope), with or without warning signs like blurred vision, lightheadedness, pounding heartbeats (palpitations) and weakness beforehand.
• Seizures, which can occur at night and be wrongly interpreted by a partner as normal movements in sleep.

Bear in mind, too, that even if you do not have these symptoms, a family history of LQTS and/or unexplained fainting or sudden death should be a warning sign for you to discuss the possibility of LQTS in yourself with your general practitioner or cardiologist. It is possible to have LQTS without any obvious symptoms (or symptoms only occurring during sleep) or for symptoms to only occur at a later stage in life, such as in your 40s. Unfortunately, for a significant proportion of individuals with the condition, sudden death is the first sign of it.

Regardless of whether you have acquired or congenital LQTS, a fast diagnosis and speedy treatment and management of the disorder will help ensure the best possible care. Similarly, if it is an inherited disorder, you can let other family members know to get checked and treat the condition sooner, if required.

How Do You Get a Diagnosis of Long QT Syndrome?

An ECG (electrocardiogram) is typically a key diagnostic test for LQTS. This is because QT prolongation is diagnosed through an ECG. Often, an exercise stress test is also important, as some people only manifest QT prolongation with exercise. However, for a full and accurate diagnosis, your physician will likely take other criteria into account. Physicians must also review a patient’s family health history. Here they will be looking for symptoms like fainting and sudden death. This can even include stranger or unexplained deaths, like a strong swimmer drowning, a road traffic accident without explanation, and sudden infant death syndrome (SIDS). These deaths can be evidence of LQTS, as fainting and sudden death can be caused by the disease.

Additionally, your own history and your family’s history of seizures and epilepsy may also be examined. As LQTS can cause seizures, your physician may ask about when these seizures occurred, such as if they were after exercise or during sleep. This can help distinguish if epilepsy or LQTS is the cause.

In many cases, despite a thorough review, your general practitioner or cardiologist can’t be certain whether you have acquired or congenital LQTS. Then, genetic testing can be crucial to confirm your LQTS diagnosis. This should be conducted by an experienced, specialised service that understands the nuances of cardiac genetics, including how LQTS can vary between people. They will be able to identify the most appropriate test for you and interpret the results for accurate treatment and management.

If you only have the acquired form of LQTS, it will not show up in a genetic test. Therefore, your physician (if they have not already done so) can look for other reasons as to why you have the disorder or symptoms of it.

If you suspect that you may have LQTS, it’s important to work with your general practitioner or cardiologist and other health specialists to determine an accurate diagnosis. Once this has been achieved, treatment can begin immediately. This may be as simple as swapping medications to handle an acquired form of the disorder. Alternatively, if you have inherited long QT syndrome, treatment may involve medications and surgery. 

Regardless, swift treatment is best to help you start recovering or managing the condition for a better life expectancy. In the case of inherited LQTS, it can also be an important sign for other family members to get checked and begin their own treatment.

How Genetic Testing Can Help

Genetic testing can be critical for confirming an inherited LQTS diagnosis. Further, it can also play a significant role in the development of your treatment and management plan with strategies chosen that are most effective for the mutations involved.

Additionally, family members can avoid the need for a complex clinical evaluation by testing themselves. This can speed up their own diagnosis and allow them to also receive swift treatment to best manage the disease and reduce chances of serious complications.

Is Long QT Syndrome in Your Family?

LQTS can be an acquired or inherited disorder, meaning that it is possible for it to be passed through generations of families. Alternatively, you may have a history of other conditions or risk factors for the acquired version.

Therefore, taking the time to review your family’s health history, particularly instances of fainting, seizure or epilepsy, and sudden or unexplained deaths is extremely important. This allows you to approach your general practitioner or cardiologist with compelling evidence suggesting that you may be at risk of having the disorder. 

You can complete this work by yourself or with other family members. Just be sure to note down any instances of:

• Regular fainting.
• Seizures or an epilepsy diagnosis.
• Sudden deaths, including sudden infant death syndrome or the death of an otherwise healthy young person.
• Unexplained deaths that may have been caused by fainting or seizures, like a strong swimmer drowning or an unusual road accident.