Cardiac trabeculae are a network of muscle fibres found in our circulatory system, lying between fast-flowing blood inside the heart and the contracting heart muscle. As long ago as the 16th Century, the artist Leonardo Da Vinci was the first to sketch these muscles, speculating at the time that they warm the blood as it flows through the heart. Yet it is only now that we are beginning to truly understand how important they are to human health. 

The network of fibres is thought to play a role in the efficient pumping and electrical activity of the heart, and they adapt to changes in demand placed on the heart. Increased trabeculation can be seen in healthy people, including pregnant people and those who do extreme sports. The trabeculation pattern can return to normal after the demand on the heart stops. 

Importantly, increased trabeculation is also a feature of diseases, such as cardiomyopathy – heart muscle diseases that are the leading cause for heart transplants and sudden death. The presence of trabeculation on scans has created controversy amongst doctors for many years, leading them to question whether disease causes trabeculation or trabeculation causes disease. The research, published today in Nature Cardiovascular Research and led by Dr Kathryn McGurk working with Professor Declan O’Regan, Head of the Computational Cardiac Imaging group at the LMS, begins to answer this clinical question. 

The interdisciplinary team used sophisticated machine learning to measure and analyse trabeculation on cardiac MRI images from almost 50,000 people’s hearts from UK Biobank – a large-scale biomedical database and research resource. By comparing the MRI imaging data with genetic data for each participant, the team identified a large repertoire of genes responsible for the development and function of trabeculae. Many of these genes overlap with genes that cause cardiomyopathy. The team determined that interactions between both rare and common genetic variants determines how trabeculae in the heart look and how diseases may evolve. 

Taken together, the findings suggest that understanding the genetics of trabeculation adds a missing piece of the puzzle in the drivers of variability in cardiomyopathy and what contributes to the diversity in the appearance of trabeculation in the heart.  

 

“Trabeculae lie in a critical part of the heart and we discovered a repertoire of developmental genes that are associated with their appearance. These genes may also play an important role in explaining the diverse manifestations of inherited heart diseases”

Professor Declan O’Regan 

 

“We’re beginning to understand the genetic, clinical, lifestyle and other factors that influence these structures. They can occur early in the pathogenesis of heart disease and progress with disease, making them useful markers of cardiac remodelling when identified in individuals at particular risk of heart disease.”

Dr Kathryn McGurk 

 

 Dr Kathryn McGurk is a British Heart Foundation Immediate Research Fellow, based at the LMS and the National Heart and Lung Institute, Imperial College London. 

This work was largely funded by the Medical Research Council and British Heart Foundation. 

Published 20 November 2024.  

Read the full article here: McGurk, K.A., Qiao, M., Zheng, S.L. et al. Genetic and phenotypic architecture of human myocardial trabeculation. Nat Cardiovasc Res (2024).