GENEtic Predictors of Successful Atrial Fibrillation Treatment (GENE-AF)

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Roberts, Jason (Department of Medicine, Western University)
Mentor: Tang, Anthony S.L.
Network Affiliation: Cardiac Arrhythmia Network of Canada
1. The health problem/issue
Atrial fibrillation is the most common electrical disorder of the heart. At present, 1 in 4 individuals that are 40 years of age and older will develop atrial fibrillation during their lifetime. Patients with atrial fibrillation suffer from palpitations (feeling of pounding in your chest) and have an increased risk of heart failure, stroke, and death. Due to its being so common and its serious health risks, the cost of treating the disorder in the United States alone is estimated to be upwards of $26 billion per year. The current clinical and economic impacts of atrial fibrillation are even more worrisome given that experts anticipate that the number of affected individuals will surge up to 8-fold by 2050. Further exacerbating the burden on both patients and health care systems is a current lack of treatment strategies that are both highly effective and associated with minimal risk. Catheter ablation, a procedure that involves placing flexible tubes into the heart and burning specific areas, is more effective than medication for maintaining normal rhythm (electricity) within the heart, however provides minimal benefit in some patients and has the potential for complications including stroke and death. Blood thinning medications, termed anti-coagulants, are also necessary to prevent strokes, however can also cause serious bleeding in certain individuals.
2. The objectives
The goal of the GENE-AF (GENEtic predictors of successful Atrial Fibrillation therapy) Study is to discover genetic variations (DNA differences between individuals) that better predict how patients will respond to catheter ablation and blood thinning medications. The ability to guide the use of these treatments using a personalized approach that takes into account an individual's genetics has the potential to dramatically improve treatment efficacy, while simultaneously minimizing the risk of complications. In addition to improving the lives of affected patients, this approach should also dramatically reduce costs incurred to health care systems as a result of atrial fibrillation.
3. The approach
In order to identify genetic variations that impact the effectiveness of catheter ablation and blood-thinning medications, we plan to collect blood from patients undergoing the catheter ablation procedure. We will then follow these patients for a period of 1 year to determine how they respond to treatment. We have established partnerships with 2 Canadian clinical trials and two hospitals in order to facilitate enrollment of a large number of patients. The only additional step required from patients to become part of the study is drawing an extra vial of blood. Subseqent DNA isolation and sequencing will be performed at the London Health Sciences Centre and Sick Children’s Hospital in Toronto.
4. The unique factors
The ability to guide medical treatment decisions using genetic information, referred to as personalized medicine, is a new approach to treating patients that carries enormous promise. Development of gene-guided approaches requires in-depth knowledge of both clinical medicine and basic science. Currently, our increasing genetic knowledge of atrial fibrillation has yet to impact the care of affected patients. The proposed study has the potential to allow physicians to selectively utilize catheter ablation in patients that have a high likelihood of success, while sparing patients less likely to respond favorably from the risks of the procedure. Similarly, our results may also allow physicians to tailor dosages of blood-thinning agents to minimize both the risk of stroke
and bleeding complications.
5. How the project is relevant to the objectives of the initiative
Atrial fibrillation is the most common rhythm or electrical disorder of the heart. Affected patients suffer from an impaired quality of life secondary to rapid and irregular heart beats resulting in a sensation that "their heart is beating out of their chest". In addition to an impaired quality of life, atrial fibrillation may also lead to heart failure, stroke, and even death.
6. The impact
The goal of this research is to improve the care of patients with atrial fibrillation allowing them to feel better and prevent complications from the disorder. Effective maintenance of normal heart rhythm will prevent the episodes of "chest thumping", which may result in a dramatic improvement in quality of life in many individuals. Better treatment should also reduce the risk of heart failure, stroke, and death. Finally, a more effective approach to treatment may result in a dramatic reduction in health care costs stemming from atrial fibrillation.