Development of a successful novel technology for sudden cardiac death risk stratification for clinical use - LifeMap

Sudden Cardiac Death (SCD) is responsible for over 3 million deaths worldwide annually, 100,000 deaths in the UK alone. People die because their heart suddenly develops a lethal heart rhythm that stops it from coordinating and working as a pump. An implantable cardioverter defibrillator (ICD) is a small, £10,000 device, similar to a pacemaker that is placed under the skin, around the shoulder in a small operation. The ICD then sits quietly monitoring the heart; it can detect a lethal heart rhythm in seconds and treat it to restore normal function sometimes without the patient even being aware that their life has been saved.
Unfortunately, we lack an effective means to work out who really needs an ICD. Current guidelines are based on crude clinical information and only 40% of ICD recipients deemed "high-risk" by these guidelines ever make use of them during the first 5 years of follow up. On the other hand, the majority of people who die of SCD may have a risk factor, such as a previous myocardial infarction (heart attack) but the guidelines regard them as "low-risk". For these patients there is currently no way of working out who truly is at low risk and who really needs an ICD to protect them.
We have developed two novel ECG markers based on patented algorithms with supportive clinical scientific evidence in different patient populations. This innovative test is called LifeMap and has been shown to be highly effective for risk assessment of sudden cardiac death. LifeMap analyses the ECG over a spectrum of heart rates and can be performed either in a 10 minute minimally invasive procedure or with exercise. This proposal aims to translate the currently laborious research technique into an effective clinical tool by automating the software, creating a user interface and making it straightforward to acquire clean exercise ECG signals. This grant would bring LifeMap to the next phase of development; ready for a large scale clinical trial following which it could be implemented into daily practice.

Sudden cardiac death (SCD) is responsible for over 3 million deaths worldwide annually. The majority are due to lethal heart rhythm disturbances which could be aborted with implantable cardioverter defibrillators (ICDs). However, selecting appropriate patients for ICDs is extremely difficult. The limiting factor is the poor performance of current SCD risk stratification largely based on the degree of cardiac dysfunction, heart failure status and QRS duration. 60 % of those deemed "high-risk" according to the crude guideline criteria and have ICDs implanted do not ever use them during the 4-5 years device lifespan at a cost of £10,000 per ICD. On the other hand, the majority of SCD occurs in a large population regarded as "low-risk" for which there is no risk assessment available.
We have translated preclinical understanding of electrical restitution in ventricular arrhythmogenesis, into the development of LifeMap. This technology comprises 2 novel ECG markers - Regional Restitution Instability Index (R2I2) and Peak ECG Restitution Slope (PERS), supported by patent applications (R2I2 granted in 4 countries, PERS to be granted in Australia). Using predefined threshold cutoffs, patients positive for both R2I2 and PERS had a relative risk of VA/SCD 21.6 times that of those negative for R2I2 and PERS. The high positive predictive value (80%) of LifeMap markers for SCD/ ventricular arrhythmia (VA) supports that they will be of clinical utility in the large intermediate risk population.
This proposal aims to translate the current, laborious research technique into an effective clinical tool, to be used by medical professionals with minimal training and offer accurate risk assessment for SCD. A novel product will be developed, including automated software with user interface and customised proprietary modules which will produce LifeMap markers acquired during pacing or exercise. This would bring LifeMap to the next phase of development ready for a pivotal trial.

In the UK, 100,000 deaths are caused by sudden cardiac death (SCD). Many of these deaths could be prevented with a device called an implantable cardioverter defibrillator (ICD). Currently, risk stratification for ICD implantation is challenging with crude measures being used in guidelines. This means that a significant proportion of people deemed high risk and who have ICDs implanted do not make use of them. Implanting and ICD carries a substantial morbidity from complications such as infection and inappropriate shocks. Conversely, a large number of people who die from SCD are in populations considered low risk by the guidelines and who at present cannot be further assessed to for potentially life saving ICDs.
Better methods for ICD patient selection are needed. This research creates a "LifeMap": an electrical map of sudden cardiac death risk using the standard ECG measure across a range of heart rates. It has led to the development of 2 clinical markers, which have shown great promise as risk stratification predictors in a series of clinical studies. This research has had a significant impact in the academic arena with output in peer reviewed journals of high impact, recognition with notable awards and international patent granted through peer review. With further development, LifeMap is expected to have transformational impact on the current methods for risk assessment of SCD. Over 40 million cardiac stress tests are being done every year. An effective screening test could benefit a very large number of people, for example, one of the at-risk groups is the 32 million people who have heart attacks annually. The technology being developed would have international potential to improve the allocation of ICDs: saving patients' lives through prevention of SCD and reducing costs through better allocation of resources.
Impact on the scientific community: LifeMap offers new insights into electrical restitution and electrical instability and the mechanisms that link them to ventricular arrhythmia and sudden cardiac death.
Impact on the MedTech industry: we will consider licensing our platform developed in this proposal to ECG manufacturers as addon modules, which would boost their sales significantly. ICD manufacturers will also benefit by the more accurate risk assessment and its potential to increase sales by opening up a new market in patients current inaccurately assessed as being at low risk.
Impact on health professionals: the proposal will provide cutting-edge knowledge to early career professionals; it will facilitate conversations with patients by allowing accurate discussions of the risks and the benefits of ICDs.
Impact on UK economic: this UK based technology and the knowledge brought by the technology to health professionals will advance the UK as a leading country in assessment and management of patients at risk of SCD. The NHS is under considerable cost pressures at present and LifeMap has great potential to improve allocation of resources.