A Search for the Hidden Killer - Cardiac Ingerited Diseases

Between 80 and 100 young healthy New Zealanders from 0 to 40 years of age die suddenly and unexpectedly each year. More than one third are due to heart rhythm problems that are likely to run in the family, meaning that half of the other family members are at risk of the same fate. If nothing is found at post mortem, the only chance to find a cause lies in study of the genes. Our research team aims to find these genetic problems, so that effective treatments can be given to other gene carrying family member, to prevent their sudden death. We have found some have long QT syndrome, but the others remain a mystery.

Another potential cause is a disease with the frightening name of catecholaminergic polymorphic ventricular tachycardia (CPVT). Death occurs when adrenaline is released during exercise making the heart suddenly jump into a very fast rhythm, so fast that the heart cannot beat effectively, starving the brain of blood and oxygen. Tests such as the electrocardiogram, or heart ultrasound are completely normal making CPVT is the ‘perfect hidden killer.’ Once detected, death can be prevented by prescribing a simple beta blocker medication or a defibrillator type pacemaker in severe cases. However detection relies on analysis of the genes, in particular a gene known as the heart ryanodine gene.

It is estimated that as many as 12-15 people die from CPTV each year in New Zealand. Half of their family members may also be at risk of dying from the same disease. Until now it has been almost completely undetected.

What are your research objectives?

Ultimately our aim is to reduce sudden death in the young through the discovery of an extremely treatable, potentially lethal condition among the New Zealand population. We want to establish how common this condition is and how many lives can be saved through its detection.

How you will conduct your research?

Blood samples are saved by the forensic pathologists at the autopsy, or by cardiologists looking after patients who have survived cardiac arrest.  DNA is extracted from the samples and the ryanodine gene is sequenced to look formistakes. If one is found, the family is contacted, and family members can be offered testing for that particular mistake to see if they are at risk or not.

Are there others in NZ or globally conducting similar research?

The molecular genetic testing is highly skilled, expensive and time consuming. There is a world-wide effort to find such genetic conditions and new genes are being discovered all the time.

What is innovative about the approach you are taking?

Recent small studies from overseas have highlighted that mutations in theryanoidne gene can occur in about 15% of young sudden death victims with a negative post mortem. We are planning a national study of the incidence of this condition which is a world first. This is made possible by having a       coordinated network of medical and research professionals throughout New Zealand known as the Cardiac Inherited Diseases Group.

In the pilot part of this study, funded by Cure Kids, we will analyse 43 samples from sudden death victims, in whom all other known conditions have been excluded, including long QT syndrome. We will also analyse samples from 17 living patients who presented with a cardiac arrest, but were successfully resuscitated, and for whom no diagnosis has been made.

This will reveal which mutations (mistakes) are prevalent in New Zealand.

If you achieve your objectives what will that mean to those suffering from the disease or to the knowledge advancement of this disease?

The immediate family members will at last have an answer as to why their loved one died so suddenly and unexpectedly. This knowledge will empower the family to take action to prevent further such deaths. The incidence data will be important for future health and Ministry of Justice service planning.

Is there national or international collaboration on your research project?

The Cardiac Inherited Diseases Group has collaborations with the Garvan Institute in Sydney, Vanderbilt University in the USA, and with the University of Wales. These institutions help in the laboratory characterisation of the genetic mistakes that are found. This can be especially important when changes in the genes are found which have never been seen before.

Back to Research Articles