Scientists at the Victor Chang Cardiac Research Institute (VCCRI) in New South Wales, Australia, have discovered a method of using computer gaming technology as a tool for better diagnosis of patients suffering from a life threatening, cardiac electrical disorder called long QT syndrome (LQTS) that can disrupt heart rhythm and stop the heart from pumping blood effectively, resulting in sudden death. Heartbeat rhythm is controlled by a high-fidelity electrical communication system, and heartbeat rhythm disturbances can result in unexpected sudden cardiac arrest.
Harnessing the same technology used to power video games, the VCCRI researchers succeeded in building a “virtual heart” that can simulate hundreds of thousands of heartbeats. Scientists then screen the heartbeats, searching for abnormalities.
The research findings are reported in a paper published in the journal Nature Communications entitled “Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2” (NATURE COMMUNICATIONS | 5:5069 | DOI: 10.1038/ncomms6069 | www.nature.com/naturecommunications 1) coauthored by Adam P. Hill (corresponding author), Arash Sadrieh, Stefan A. Mann, Emily C. Hodkinson, Chai-Ann Ng, Matthew D. Perry, and Jamie I. Vandenberg of the Division of Molecular Cardiology and Biophysics at the Victor Chang Cardiac Research Institute at Darlinghurst, New South Wales, Australia and St Vincent’s Clinical School at the University of New South Wales in Sydney, Australia; Luke Domanski of the CSIRO eResearch and Computational and Simulation Sciences at Canberra, Australia; and Joe Pitt-Francis of the University of Oxford Department of Computer Science,Oxford, UK.
The scientists note that LQTS2 represents one of the simplest arrhythmia syndromes with a well-described ECG phenotype, but despite this, predicting who is most at risk of lethal cardiac events is difficult, in part because of the great variability in presentation in relation to QT interval — the primary diagnostic criterion. Features of surface electrocardiograms (ECG) that measure electrical activity of the heart can be equally variable in LQTS patients, posing an obvious and well-documented diagnostic dilemma. The coauthors note that due to these diagnostic shortcomings, LQTS can variously result in sudden death of young persons or remain asymptomatic into adulthood.
In this paper, the researchers report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and employ a novel computational framework in order to to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Additionally, they show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20 percent variation in levels of ionic conductance that contribute to repolarization reserve, which they note has significant implications for interpreting whole-genome sequencing data, and underscores the importance of interpreting the entire molecular signature of disease in any given individual.
A VCCRI release notes that analysis on this scale has never been possible before, since running the data on a standard desktop PC would have taken 21 years to get the job done. However, in this instance, the simulation took just ten days, thanks to Australia’s national science agency the Commonwealth Scientific and Industrial Research Organisation (CSIRO)’s multimillion dollar Bragg supercomputer that’s been ranked the most energy efficient supercomputer in Australia and number 10 in the world on the Green500 list. The cluster improves scientific computing by multi-tasking and increasing processing speeds, allowing CSIRO scientists to take on much more complex and challenging research problems. Over 100 CSIRO scientists have been trained to use the cluster and some are already using it for their research, reporting 6-200 times speedups The CPU-GPU supercomputer combines traditional CPUs with the more powerful, Graphics Processing Units (GPUs), and is one of the world’s fastest computers — able to process data at Teraflop speeds.
While graphics processing units (GPUs) have typically been used to render complex graphics in computer games, they can also be used to accelerate scientific computing by multi-tasking on hundreds of computing cores. A video demo can be accessed here:
The Nature Communications paper coauthors explain that heartbeat simulations were performed on the Bragg Accelerator Cluster, which consists of 128 Dual Xeon 8-core E5-2650 Compute Nodes each with 128 GB of RAM and FDR10 InfiniBand interconnect. GPU resources on the Bragg cluster comprise 132 Fermi Tesla M2050 GPUs (a total of 59,136 CUDA cores) and 254 Kepler Tesla K20 GPUs (a total of 633,984 CUDA cores). To confirm the accuracy of the researchers GPU-based implementation of Chaste, the wild-type model was simulated for 2 s of output, with results compared with the same simulation scenario implemented on the standard CPU-based version of Chaste. They found that the two simulations were identical, and say their GPU implementation of Chaste will be available in future software versions. Virtual principle simulations together with a Matlab workspace containing all data and simulation
outcomes used in this study are available at the VCCRI Hill lab site:
These findings take scientists a step closer to understanding cardiac rhythm disturbances observes Dr. Adam Hill, a Computational Cardiologist at the VCCRI, and a co-senior author of the study and the Nature Communications paper. Dr.Hill is a member of the Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, and established the Computational Cardiology group at the VVCRI in 2011.
“This research is hugely exciting!” says Dr. Hill in the VCCRI release. “We were able to identify why some patients have abnormal ECG signals, and how a person’s genetic background can affect the severity of their disease. In the past we were limited because we didn’t have enough computational grunt to do an effective job.”
Dr. Hill and his research colleagues hope their discovery will open the door to better and more timely LQTS diagnosis, and much better treatment.“We hope this will help doctors read ECGs more accurately, which will mean faster, more accurate diagnosis,” says Dr. Hill. “By understanding why the same disease affects people differently, the right treatment can be given to the right patients.”
Another of the paper’s coauthors is Dr. Jamie Vandenberg, a co-deputy director of the Victor Chang Cardiac Research Institute and Head of the VCCRI Cardiac Electrophysiology Laboratory who also holds an NHMRC Senior Research Fellowship and is a conjoint Professor at the University of New South Wales. Dr. Vandenberg Jamie is recognized internationally as an expert in cardiac electrophysiology, particularly for his research on hERG K+ channels and the molecular basis of inherited cardiac arrhythmia syndromes, and is an editorial board member of the Journal of Physiology, the most highly ranked primary research journal in the Physiological Sciences.
Scientists at the Victor Chang Institute are currently using the researchers discoveries to develop automatic computerized tools for diagnosing heart rhythm disorders.
The Victor Chang Cardiac Research Institute
The late Dr. Victor Chang was a pioneer of the modern era of heart transplantation whose achievements include developing Australia’s National Heart Transplant Program at St Vincent’s hospital, which has since performed more than 1200 successful heart, heart-lung, and single lung transplants since 1984. Dr. Chang also recognized the value of research — playing a key role in development of an artificial heart valve and, in later years, an artificial heart.
In 1986 Victor Chang was awarded a Companion of the Order of Australia and the University of New South Wales awarded him its highest degree of M.D. Honoris Causa for “scholarly achievement and humanitarian endeavour.”
Victor Chang died in tragic circumstances in Sydney on 4 July 1991. In 2000, he was named Australian of the Century by the people of Australia.
The Victor Chang Cardiac Research Institute, initially under the auspices of St Vincent’s Hospital Sydney, opened on 14th February 1994, thanks to generous donations from the late Kerry Packer, AC; Australia’s Federal Government; and the Australian public. A year later, the Institute was incorporated as an independent research facility on 27th February 1995.
The Victor Chang Cardiac Research Institute Limited is a Research Ministry within Mary Aikenhead Ministries, which operates in accordance with the Canonical Statutes approved by the Holy See. Mary Aikenhead Ministries also assumes an Australian civil identity under Australian law as the Trustees of Mary Aikenhead Ministries. The Trustees operate pursuant to the Constitution of Trustees of Mary Aikenhead Ministries.
Mary Aikenhead Ministries was established by the Holy See as a Public Juridical Person at the request of the Congregation of the Religious Sisters of Charity of Australia to succeed to, and to carry on and expand, various health and aged care, education and welfare ministries conducted by the Sisters of Charity.
The Victor Chang Cardiac Research Institute
The Victor Chang Cardiac Research Institute
VCCI Vandenberg Lab