Determination of left atrial wall thickness and its influence on electroanatomic properties in the human atrium

Atrial fibrillation ('AF') is a common heart condition affecting around 2% of the UK population. When a patient suffers from AF the 'atria' (the upper chambers in their heart) stop pumping. This alters the heart rhythm, and can make the heart beat quickly and erratically. It happens because the electrical signals that normally control the atria are disturbed. AF usually begins as short 'stop - start' episodes lasting minutes to hours. Gradually these episodes become longer and occur more frequently.

AF is a serious condition that can cause stroke and heart failure. Patients with AF are more likely to be admitted to hospital, have a lower life expectancy and can experience severe symptoms. Drugs designed to prevent AF are frequently ineffective and can be dangerous, so procedures that negate or reduce the need for drug treatment are of great importance.

'Catheter ablation' (CA) procedures are 'keyhole' procedures designed to treat AF, which involve cauterisation of parts of the heart responsible for AF. To be effective, the cauterisation must create a scar that crosses the full thickness of the atrial wall. The thickness of the atrial wall varies from under 1mm to over 8mm, so the amount of cauterisation required to form an effective scar varies significantly. CA treatment of the early form of AF ('paroxysmal AF') is effective in up to 90% of patients, while for those with the longer lasting 'persistent' form, the overall success rate is lower (60 - 70%) and up to half of patients require multiple procedures. The most serious complications of CA result from excessive cauterisation that damages the atrial wall, other heart structures or even structures outside the heart. These complications are more likely where the atrial wall is thinnest. Each procedure carries approximately a 5% risk of complication, so there is an urgent need to improve their safety and reduce the number of patients requiring repeat procedures.

Variation in the atrial wall thickness is a significant cause of CA treatment failure. No tool exists to measure wall thickness throughout the atrium. Such a tool would provide the operator with information regarding the necessary - and safe - amount of cauterisation to apply in different areas.

We have developed a technique to measure atrial wall thickness from computed tomography (CT or 'CAT') scans which provides a map of atrial wall thickness in three dimensions. We believe that providing the operator with information regarding wall thickness during procedures would allow safer and more effective treatment of AF.

This tool may also help us to understand the processes that cause AF. Evidence from laboratory experiments suggests that electrical properties of the heart change with atrial wall thickness. We have experience of testing these electrical properties by measuring electrical signals inside the heart. By comparing these measurements with atrial wall thickness we will be able to understand how atrial wall thickness affects the electrical properties of the heart and gain insights into the causes of AF.

We are planning two studies. The first study will include patients with AF who are not planned for CA procedures. We will perform a CT scan of their heart and then collect and monitor clinical information. This will allow us to understand the effect of changes in atrial wall thickness on the clinical features and progression of the condition. The second study will include AF patients who are planned for CA procedures. We will perform a CT scan of the patient's heart. At the time of their CA procedure, we will measure electrical signals in their heart and examine how these measurements are affected by variations in wall thickness.

Our work has the potential to form the basis for a tool to improve the safety and effectiveness of CA procedures for AF. Such a tool could be used around the world. Our work will also address some of the many outstanding questions about the causes of AF.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting approximately 2% of the UK population. It is associated with stroke, heart failure and death. The electrophysiological mechanisms underlying AF remain incompletely understood. Published data suggest left atrial wall thickness (LAWT) affects atrial electrophysiological properties and varies with presence of cardiac pathology. In appropriate patients, AF can be effectively treated by radiofrequency catheter ablation (RFCA). Successful RFCA requires delivery of transmural lesions to the left atrium. A fundamental determinant of transmurality of lesion formation is LAWT, which can vary from <1mm to 8mm. LAWT measurements are not currently available during RFCA.

Hypotheses:
Whole chamber LAWT can be reproducibly assessed using cardiac CT (CCT)
LAWT increases with the presence of AF-associated cardiac conditions and predicts progression of AF
Atrial electrophysiological profile varies with LAWT
Knowledge of LAWT will inform personalised AF management strategies

We have developed a novel method for measuring LAWT throughout the atrium from a CCT dataset. We will recruit to two studies. For the first study we will recruit patients with AF (not planned for RFCA) who will undergo CCT. Clinical parameters will be monitored and correlated with LAWT measurements taken from CCT. For the second study we will recruit patients planned for RFCA who will undergo CCT. At ablation we will assess intracardiac electrophysiological properties which we will correlate with LAWT. In patients undergoing repeat RFCA we will identify LAWT at sites of treatment failure to define the relationship between the two.

LAWT is a critical biophysical parameter on which atrial electrophysiology as well as efficacy and safety of AF treatment is likely to depend. Our results have the potential to impact on treatment outcome while simultaneously illuminating the mechanisms responsible for AF.

The research produced will be of interest to clinicians, researchers and the healthcare industry. Most importantly it will impact on the wellbeing of patients with atrial fibrillation. Clinically the research will be of early, direct relevance to electrophysiologists managing patients with atrial fibrillation and for whom it will offer information regarding disease progression and impact treatment efficacy and safety. In doing so it will directly contribute to their management of patients with heart rhythm disorders for whom they be able to provide more accurate information as well as offering safer and more effective procedures. Our results will be of more general relevance to imaging cardiologists as we define a new indication for cardiac CT imaging and develop the tools to better exploit the potential of this imaging modality. The broadened indication for cardiac CT will facilitate further research into novel ways of deploying this technology in the assessment of the human atrium, likely to be of relevance to cardiologists involved in device implantation and heart failure as well as atrial fibrillation.

Our results will be of direct relevance to researchers investigating the role of structural contributors to electrophysiological mechanisms. Modelling of patterns of propagation is an increasingly important tool for the understanding of electrophysiology. Our results will provide data regarding a basic physical parameter which so far has not been available for incorporation into models of cardiac propagation. As the modelling community develops increasingly realistic representations of the physical environment in which biological phenomena occur, the importance of representative three dimensional surface measurements will become more important. Our technique will provide the first opportunity for the incorporation of accurate clinical information regarding this parameter into models, which is likely to be relevant to areas beyond cardiac electrophysiology.

Our technique has significant commercial potential. It provides the first technique to assess a fundamental physical parameter into the planning of invasive AF treatment and in doing so addresses a currently unmet need for a tool to improve the safety and efficacy of treatment. We anticipate commencing the development of a commercial version of our tool by the end of the proposed fellowship. Through the development of a commercial product with a pre-existing large international market, such a tool would directly benefit the economic competitiveness of the UK.

Up to 2 million patients in the UK suffer with atrial fibrillation and they can experience severe symptoms and are at increased risk of stroke, heart failure and death as a result of their condition. Overall the condition is associated with decreased quality of life. Therefore there is an urgent need to improve the information and treatment available to this population. A tool that allows more accurate provision of information regarding disease progression and increases the safety and effectiveness of currently available treatments for AF would be of significant benefit to patients with heart rhythm disorders. It would facilitate active patient involvement in care and treatment decision making as well as improving outcomes from procedures. In doing so it would directly contribute to the health and wellbeing of patients with heart rhythm disorders, as well as their families and carers. Such a tool would carry a strong incentive for uptake by practitioners and service delivery managers for whom safety and efficacy considerations carry a high priority, in particular in this common condition whose incidence is set to continue increasing as the population ages. The widespread uptake of a technique demonstrating improved safety of AF ablation procedures will positively impact on the financial burden on the NHS who at present provide the care of patients experiencing complications from AF ablation procedures.