A large-scale genetic study has shed new light on common heart rhythm disturbances. The study, published today in PLOS Medicine, provides evidence supporting a causal association between electrocardiogram features and irregular heart rhythms, and helps to distinguish the causes and consequences of atrial fibrillation.
Atrial fibrillation, an irregular and often abnormally fast heart rhythm, affects approximately 1 million people in the UK and is associated with an increased risk of stroke, dementia, heart failure and death. Treatment options for atrial fibrillation are limited and show poor long-term success.
Therapeutic developments are reliant on understanding the underlying causes of disease. To elucidate the biological mechanisms for atrial fibrillation and other supraventricular tachycardias (conditions that result in the heart beating faster than normal) University of Oxford researchers used a genetic approach known as Mendelian randomisation. This allowed the use of genetic information to assess whether lifelong differences in features of patients’ electrocardiogram readings are likely to be causal risk factors in the development of these abnormal heart rhythms.
The research was based on almost 300,000 participants in the UK Biobank study, including 19,000 cases of atrial fibrillation. In particular, genetic variants predicting a longer PR interval (the time it takes for the heart pacemaker impulse to go through the top chambers of the heart and reach the ventricles) were associated with lower risk of atrial fibrillation. These effects were not driven by major risk factors for atrial fibrillation, including heart failure, high blood pressure or diabetes, or left atrial size. The results also showed that a longer genetically-predicted PR interval was associated with lower risk of supraventricular tachycardia.
Dr Parag Gajendragadkar, British Heart Foundation Clinical Training Fellow and first author, said ‘It was surprising to see strong associations between electrocardiogram parameters and risks of supraventricular tachycardia as well as atrial fibrillation. This suggests that these arrhythmias may share some common causal features with atrial fibrillation. Additionally, it suggests that atrial fibrillation itself may arise from a variety of different electrical mechanisms in different people.’
Professor Barbara Casadei, British Heart Foundation Professor of Cardiovascular Medicine, in the Radcliffe Department of Medicine and a senior author says: ‘Although we have associated atrial fibrillation with a number of electrical and structural abnormalities of the heart, we can seldom discriminate between those that cause the arrhythmia and those that result from it or are a consequence of coexisting heart conditions. The use of genetic tools helps us identify which comes first and by doing so informs both the search for new treatments and the timing of their administration in individual patients.’
Professor Jemma Hopewell, Professor of Precision Medicine and Epidemiology in the Nuffield Department of Population Health, British Heart Foundation Research Fellow, and senior author of the report says: ‘Our large-scale genetic epidemiological study helps to complete an important piece of the puzzle by supporting a causal relationship between longer atrial conduction times and lower risk of atrial fibrillation, an association that does not appear to be driven by well-known mechanisms such as major cardiovascular co-morbidities. Such insights are central to the development of new therapeutic approaches as well as precision medicine initiatives that can directly impact the lives of patients with atrial fibrillation.’