LESS INVASIVE WAY: Dr Ma Dong Rui (left) and Dr Winston Shim in the laboratory where they converted skin cells into heart cells in a petri dish.
BREAKTHROUGH research on a disease that can cause sudden cardiac death may lead to new treatments and better patient survival rates.
Imagine using your own skin to save your heart.
That is what patients with inherited heart diseases may expect in the future, thanks to a medical discovery by a team from the National Heart Centre Singapore (NHCS).
The 10-member team (including two members from the Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore) took skin samples from a 30-year-old Singaporean man and converted them into heartmuscle cells in a petri dish in the lab.
The man was suffering from arrhythmogenic right ventricular cardiomyopathy
(ARVC) – an inherited heartmuscle disease with few symptoms which can cause sudden death.
It remains undiagnosed worldwide, usually only being discovered after autopsies or when the patient has experienced cardiac arrest.
The study was based on earlier research done by Nobel Prize-winning Japanese scientist, Professor Shinya Yamanaka, who turned skin cells into stem cells using induced pluripotent stem cell technology. The NHCS breakthrough means researchers worldwide who have been studying ARVC, now have the world’s first ARVC cellular model to work with.
Dr Winston Shim, Scientific Director, Research and Development Unit (RDU), NHCS, said: “This cellular model means that, for the first time, we can monitor a patient’s heart cells in the lab.
“From there, we can do a battery of tests on these cells to find out what happens to them when they become diseased, without risking the safety of the patient.”
Dr Shim said that, traditionally, scientists do not take cells directly from the heart to study as it is highly invasive and dangerous for patients. Taking skin cells is much easier. They take a tiny piece of skin, the diameter of a straw, from the patient’s inner thigh.
The groundbreaking study, published in the prestigious peer-reviewed European Heart Journal, gives new hope to ARVC sufferers. Dr Ma Dong Rui, the study’s lead author and a research scientist at RDU, NHCS, said: “The study is significant because we now have a model to learn the mechanism of the disease, test drugs and develop new treatment methods.”
The ARVC cellular model also lets doctors better understand the consequences of genetic mutations in the heart. Suspected ARVC cases can be confirmed by DNA tests. But DNA tests cannot explain how the disease manifests itself.
Using the model, the researchers found one possible explanation. The mutated heart cells in the lab had a build-up of “fatty droplets” similar to those found in the heart tissues of ARVC patients during post-mortems.
These fatty changes in the heart can lead to an irregular heartbeat as well as heart arrest.
Dr Shim said: “The heart is an electrical organ. Every beat of the heart requires an electric current generating through the heart cells.
But when heart cells are diseased with fatty droplets, they do not connect well with other heart cells. As a result, the rhythm is disturbed and this can lead to sudden cardiac death.”
It is still too early to say whether ARVC and other inherited heart diseases can be cured, but the scientists say their findings are a good starting point. Associate Professor Philip Wong, Director, RDU, NHCS, said that what’s important is that doctors can now potentially detect patients at risk of this disease even before symptoms appear.
The more doctors learn about ARVC, the more unanswered questions there are; but the cellular model now gives them a platform to ask those questions.
Prof Wong said they are now looking for “family cohorts” of patients with ARVC or similar types of genetic cardiovascular diseases. These include long QT syndrome and Brugada syndrome, which can also lead to sudden cardiac death.
The researchers are also studying the potential of the cellular model in predicting such diseases, or to test potential genetic and drug therapies.
• This story was first published in Singapore Health, Mar/Apr 2013.
What is ARVC?
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, inherited heart-muscle disease. It is linked to life-threatening arrhythmias (irregular heartbeat) and sudden cardiac death. In general, an estimated one in 2,000 to one in 5,000 people are affected by ARVC.
Who are most at risk?
“ARVC is more common in young men in their 20s and 30s. Those who have a family history of sudden cardiac death are at higher risk,” said Associate Professor Philip Wong, Director, Research and Development Unit (RDU), National Heart Centre Singapore (NHCS). Doctors estimate that 90 per cent of ARVC patients have genetic factors such as gene mutations. The rest have unknown factors.
What are the symptoms?
“Symptoms start as abnormal heartbeats, progressing to more dangerous abnormal rhythms,” said Prof Wong. Other symptoms can include palpitations, lightheadedness and fainting spells.
What triggers the condition?
At times, symptoms are triggered by vigorous exercise. But, more often than not, ARVC is difficult to diagnose. In its early stages, there may not even be any symptoms. “Diseases like ARVC may appear without warning and this is one of the reasons some apparently healthy people can suddenly collapse,” said Dr Winston Shim, Scientific Director, RDU, NHCS.
How is it treated?
Currently, doctors can treat only symptoms of the disease. As yet, there is no cure for ARVC. Most symptoms can be controlled with medicines. Doctors may advise those at a high risk of sudden cardiac death to have an implantable cardioverter defibrillator fitted.