Long QT Syndrome (LQTS) can affect anyone, even the young who are in the pink of health.

Long QT Syndrome (LQTS) is dangerous because it can strike without warning and cause sudden death.

Long QT Syndrome (LQTS): A patient story

Mr Wong (not his real name) was in the pink of health and an all-round athlete who regularly ran marathons. So, when the 27-year-old suddenly slumped over at his desk one morning, his colleagues thought he was simply fooling around.

When he failed to respond to their nudges and calls after several minutes, they realised that he had stopped breathing. A colleague called for an ambulance while another started emergency cardiopulmonary resuscitation (CPR) on him.

When paramedics arrived, they tried to revive him. An electrocardiogram (ECG) done at the emergency department showed the presence of Long QT Syndrome (LQTS) – a disorder of the electrical activity that controls the heartbeat, and a known cause of sudden cardiac death in young, otherwise healthy people. Despite aggressive intervention by the medical team, Mr Wong unfortunately passed away.

Long QT Syndrome (LQTS): How it occurs

Victims of LQTS develop sudden, uncontrollable and chaotic heart rhythms during exercise, when feeling strong emotions, or for no apparent reason. It is a known cause of collapse and sudden death in young athletes running marathons. If not corrected within a couple of minutes, these erratic heart rhythms can cause death.

Some people with LQTS experience symptoms such as palpitations, fainting spells or seizures, but many do not, and remain unaware they have the condition. Even if LQTS is diagnosed – often through ECG results during a routine check-up – there is currently no known cure for it.

The Department of Cardiology from the National Heart Centre Singapore (NHCS), a member of the SingHealth group, shared, “These dangerous heart rhythms can occur at any time and there need not be any specific trigger. Prolonged QT is a well-known cause of sudden cardiac death.”

Long QT Syndrome (LQTS) in Singapore

In Singapore, about 1 in 5,000 people have Long QT Syndrome (LQTS). The incidence for LQTS is not as high as that of diabetes, which is one in five for those above the age of 50. But the difference is that diabetes is a chronic disease and doesn’t kill people suddenly, unlike LQTS which may affect the young in the prime of their lives.

Long QT Syndrome (LQTS): How to prevent

The only way to prevent deaths in LQTS patients is for them to get an automated implantable cardioverter defibrillator (ICD) implanted in their bodies.

The device monitors heart rhythms, and when it detects a dangerous one, delivers electrical shocks to reset the heart rate. However, this does not cure or correct the underlying cause of the condition.

Long QT syndrome (LQTS): Causes and risk factors

LQTS is usually inherited and can affect young victims. In the patient story mentioned above, a check with the family revealed that the patient's father too had also died of sudden cardiac death some years back.

Long QT syndrome (LQTS) symptoms: How to know if you have it

Since LQTS has no signs or symptoms, many people are unaware they have it. Do consult a doctor if:

  1. Your parent, sibling or child has been diagnosed with LQTS. The condition may be inherited.

  2. You suddenly faint during physical exertion or when you experience intense emotions.

  3. You have seizures. A continually erratic heartbeat deprives the brain of oxygen – this condition is what causes seizures.

Long QT syndrome (LQTS): Treatment

Studies have shown that if left untreated, more than 50 per cent of people with inherited Long QT Syndrome (LQTS) die within 10 years.

To manage LQTS, patients are advised to avoid competitive sports. Treatment includes the following:

  • Medication: Drugs like beta blockers slow the heart rate by blunting the heart’s reaction to adrenaline in times of stress, fear or exertion, making dangerous rhythms in a patient with LQTS less likely. 

  • Medical procedures: An Implantable Cardioverter Defibrillator (ICD) is implanted under the skin of the patient’s chest, where it continuously monitors his heartbeat. It will deliver electrical shocks to restore a normal heart rhythm when necessary.

A potent​ial cure for long QT syndrome (LQTS) discovered

Researchers at National Heart Centre Singapore (NHCS) have made a breakthrough – they discovered a potential cure for long QT syndrome (LQTS), in a petri dish.

The 10-member team from NHCS’ Research and Development Unit was working on Long QT Syndrome 2 (LQTS 2), one of 13 types of LQTS, when they made the discovery.

All 13 types of LQTS look the same on echocardiogram (ECG) readings. Types 1, 2 and 3 are the most common. LQTS 2 is caused by mutation in the hERG (human ether-a-go-go related gene), which affects the electrical system that controls heartbeats.

The team used existing stem cell research to identify a drug compound that could reverse the effects of this mutation. The drug compound allows the faulty proteins to bypass the cell’s ‘quality control check’, which then results in an increase in the inflow and outflow of potassium and corrects the effects of LQTS 2.

How was this breakthrough achieved

The breakthrough occurred when the team used stem cells from a young patient with LQTS to mimic the disease in a petri dish. In two to three weeks, they generated human-induced pluripotent stem cells. 

They spent six weeks maturing the cells, then reprogrammed them into beating heart cells (real heart cells beating in a petri dish). ECG readings of these cells mirrored the patient’s heart condition, giving researchers a cellular model with which to understand how LQTS 2 develops in the human body.

The team then tested various drugs on the cellular model. Doing this in the petri dish allowed them to test without any risk to the patient, and to continuously monitor how the cells were reacting to the drugs. After a year of rigorous testing, they saw on ECG readings that a compound known as ALLN could correct the heart cells’ prolonged QT.

Next steps: Clinical trials ahead

The team’s task now is to test for toxicity and safety in similar conditions before finding partners to bring these drugs to clinical trials. Conventional drug testing can be a long and laborious process; it can take about 15 years to progress from a discovery to a commercially available drug.

The breakthrough is expected to quicken the quest for a cure. Using this platform the team can potentially halve the time required for drug testing by doing away with multiple drug screenings. The team were able to focus our search for drugs that only affect the hERG mechanism instead of testing multiple drugs. Previously, the team used computer simulations, but now we can show what happens during drug testing on actual live cells that mimic the disease. Results can be seen right there in the petri dish.

There are other advantages. Making such drugs commercially available will involve partnering with pharmaceutical companies,drug discovery incubators and others, to test the compounds. The likelihood of these partnerships forming is high, as the team’s research in proving the efficacy of the drug has lowered the risks of testing, which can be very expensive.

“With our current knowledge of the drug and LQTS 2 manifestation, we were able to cherry-pick drugs likely to be out on the market for testing. Selecting these drugs means we know where to look for side effects,” the team said.

People with LQTS 2 will have to be on the drug for life, to manage the effects of the disease and reduce the risk of sudden cardiac death.

How did Long QT syndrome (LQTS) get its name?

The QT interval on an ECG indicates the time the heart takes to recharge before beginning its next contraction. In LQTS, the QT interval is prolonged as the electrical system controlling the heart’s rhythms takes longer to recharge. The delay may result in dangerous heart rhythms.

*The patient's description in the patient story is based on the typical profile of a patient with long QT syndrome (LQTS).

Ref: I23 (ed)