Researchers have developed the first three-dimensional genetic map of the human heart, which has enabled them to discover new genes involved in heart enlargement (hypertrophy) and sudden cardiac death.
One of the most important risk factors for cardiovascular disease is thickening of the heart wall, a condition often caused by high blood pressure, but also by hereditary heart diseases that can lead to life-threatening cardiac arrhythmias. The researchers wanted to understand how genetic variation contributes to changes in the structure and function of the heart, and why some people are more susceptible to these changes than others.
Risk genes for heart disease
By combining genetic data from more than 40,000 people with 3D MRI images of the heart, the scientists were able to identify patterns of genetic influence on the shape and thickness of the heart muscle. Their analysis yielded 42 new genetic locations (loci) that influence the restructuring and thickening of the left ventricle. Of these, 18 genes had never before been linked to heart disease through traditional genetic analyses.
‘This research helps us identify new causes and influencing factors of heart enlargement, which is a major risk factor for serious heart problems,’ says O'Regan. ‘By understanding the genetic mechanisms involved, we will be able to identify patients earlier and treat them more effectively in the future.’
The left ventricle is the heart's main pump and must constantly adapt to changes in blood pressure and physical exertion. According to the researchers, genetic differences can determine how well this adaptive capacity works, which explains why some people develop heart enlargement or heart failure more quickly.
New insights
The study offers new insights not only into the biological processes behind hypertrophy, but also into hypertrophic cardiomyopathy. This is a hereditary condition in which the heart muscle tissue becomes abnormally thick, often without any clear cause.
With this new 3D genetic map, doctors and researchers can establish risk profiles at an early stage, paving the way for personalised prevention and treatment. By linking genetic information to heart structures in imaging, future therapies can be tailored much more accurately to a patient's individual risk profile.
The study, published in Circulation: Genomics and Precision Medicine, was conducted by the Computational Cardiac Imaging Group at the LMS, led by Professor Declan O'Regan. ‘This integration of genetics and advanced MRI imaging marks an important step towards precision medicine in cardiology. Ultimately, this could help prevent sudden cardiac death by identifying risks before symptoms occur.’
Treatment of hereditary heart disease
A few months ago, Australian researchers developed mini-hearts that closely resemble adult heart muscle tissue using stem cell technology. These so-called cardiac organoids offer a promising platform for personalised diagnostics, drug development and therapy research in hereditary heart disease.
Using these models, the team tested new treatment options, including an experimental drug that improved heart function. According to the researchers, this technology significantly accelerates the development of new therapies and represents an important step towards precision medicine, especially for children with hereditary heart diseases.
