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Understanding the inner workings of the human heart

image of Leonardo da Vinci hearts
Five hundred years ago, Leonardo da Vinci studied the human heart, observing its connections, blood supply, valves, and musculature. In this interpretation of da Vinci’s drawings, arteries (in gray) snake and branch around the outside of the heart. Image: Leonardo da Vinci / Public domain / Illustration, Ben Wigler

image of the Harbor Transcript logo Summer 2021 edition

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Researchers have investigated the function of a complex mesh of muscle fibers that line the inner surface of the heart. The study, published in the journal Nature, sheds light on questions asked by Leonardo da Vinci 500 years ago, and shows how the shape of these muscles impacts heart performance and heart failure.

In humans, the heart is the first functional organ to develop and starts beating spontaneously only four weeks after conception. Early in development, the heart grows an intricate network of muscle fibers—called trabeculae—that form geometric patterns on the heart’s inner surface. These are thought to help oxygenate the developing heart, but their function in adults has remained an unsolved puzzle since the 16th century.

etching of heart
An illustration of a heart’s interior. Highlighted in purple, the trabeculae line the inside of the ventricles, the heart’s large pumping chambers. The image is based on a 1908 engraving from Brockhaus Konversations-Lexikon. Image: ©Basicmoments – / Illustration, Ben Wigler.
“Our work significantly advanced our understanding of the importance of myocardial trabeculae,” explains CSHL Fellow Hannah Meyer at Cold Spring Harbor Laboratory. “Perhaps even more importantly, we also showed the value of a truly multidisciplinary team of researchers. Only the combination of genetics, clinical research, and bioengineering led us to discover the unexpected role of myocardial trabeculae in the function of the adult heart.”

To understand the roles and development of trabeculae, an international team of researchers used artificial intelligence to analyse 25,000 magnetic resonance imaging (MRI) scans of the heart, along with associated heart morphology and genetic data. The study reveals how trabeculae work and develop, and how their shape can influence heart disease. UK Biobank has made the study data openly available.

Leonardo da Vinci was the first to sketch trabeculae and their snowflake-like fractal patterns in the 16th century. He speculated that they warm the blood as it flows through the heart, but their true importance has not been recognized until now.

“Our findings answer very old questions in basic human biology. As large-scale genetic analyses and artificial intelligence progress, we’re rebooting our understanding of physiology to an unprecedented scale,” says Ewan Birney, deputy director general of EMBL.

photo of a golf ball closeup
The dimples on a golf ball reduce air resistance so the ball can fly further. Stock Media provided by AngeloDeVal / Pond5
The research suggests that the rough surface of the heart ventricles allows blood to flow more efficiently during each heartbeat, just like the dimples on a golf ball reduce air resistance and help the ball travel farther.

The study also highlights six regions in human DNA that affect how the fractal patterns in these muscle fibers develop. Intriguingly, the researchers found that two of these regions also regulate branching of nerve cells, suggesting a similar mechanism may be at work in the developing brain.

The researchers discovered that the shape of trabeculae affects the performance of the heart, suggesting a potential link to heart disease. To confirm this, they analyzed genetic data from 50,000 patients and found that different fractal patterns in these muscle fibers affected the risk of developing heart failure. Nearly 5 million Americans suffer from congestive heart failure.

Further research on trabeculae may help scientists better understand how common heart diseases develop and explore new approaches to treatment.

“Leonardo da Vinci sketched these intricate muscles inside the heart 500 years ago, and it’s only now that we’re beginning to understand how important they are to human health. This work offers an exciting new direction for research into heart failure,” says Declan O’Regan, clinical scientist and consultant radiologist at the MRC London Institute of Medical Sciences. This project included collaborators at Cold Spring Harbor Laboratory, EMBL’s European Bioinformatics Institute (EMBL-EBI), the MRC London Institute of Medical Sciences, Heidelberg University, and the Politecnico di Milano.

This story originally appeared in the Winter 2020 edition of the Harbor Transcript magazine.


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RCUK/Medical Research Council (MRC); British Heart Foundation (BHF); Wellcome Trust; National Institute of Environmental Health Sciences; Heidelberg University; Simons Center for Quantitative Biology at Cold Spring Harbor Laboratory; National Institute for Health Research Biomedical Research Centre; Edmond J. Safra Foundation and Lily Safra; National Institute for Health Research; UK Dementia Research Institute, UK Research and Innovation Health; Research Center for Molecular Medicine (HRCMM); Deutsche Herzstiftung e.V.; and Joachim Herz Stiftung.


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Meyer, H. et. al., “Genetic and functional insights into the fractal structure of the heart”, Nature, August 19, 2020. DOI: 10.1038/s41586-020-2635-8

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