MRI scans could help detect life-threatening heart disease, suggests study

Magnetic resonance imaging (MRI) scans of the heart could help to detect a life-threatening heart disease and enable clinicians to better predict which patients are most at risk, according to a new study led by UCL (University College London) researchers.

Lamin heart disease is a genetic condition that affects the heart’s ability to pump blood and can cause life-threatening abnormal heart rhythms. It is caused by a mutation in the LMNA gene, which is responsible for producing proteins used in heart cells. It often affects people in their 30s and 40s.

Lamin disease is rare but also often undiagnosed. About one in 5,000 people in the general population carry a potentially harmful LMNA mutation and up to one in 10 with a family history of heart failure will have lamin heart disease.

The new study, published in the journal JACC: Cardiovascular Imaging, found that MRI detected heart inflammation, scarring, and impaired function among carriers of a mutated LMNA gene whose hearts would have been classed as healthy according to more standard tests.

The team argued that this information from MRI – the gold standard of heart imaging – should be included in how disease risk is estimated and inform decisions about which patients should receive a heart transplant or an implantable defibrillator (a device that monitors the heartbeat and can deliver an electrical shock if a dangerous rhythm is detected).

Currently, risk estimates are based on data from electrocardiograms (ECGs), which only track the heart’s electrical activity, as well as patient sex, genetics, symptoms and a basic measure of heart function by ultrasound (echocardiogram).

Senior author Dr Gaby Captur (UCL Institute of Cardiovascular Science and the Royal Free Hospital, London) said: “Genetics alone cannot predict how this disease will progress. Two people with the same variant can have completely different outcomes.

“The current tool to predict risk is not brilliant and underperforms for women in particular. Predicting risk is important because it determines which patients are recommended to have a defibrillator. These devices are for life and the decision to have one is major and life-changing. Currently, seven out of 10 people who receive one don’t end up benefiting from it.

“Our study needs to be repeated in a larger group of patients, but our findings show the potential of cardiac MRI to improve disease risk predictions and to become a standard part of how we manage lamin heart disease.”

Lead author Dr Cristian Topriceanu (UCL Institute of Cardiovascular Science) said: “Cardiac MRI picks up scarring of the heart tissue, inflammation and signs the heart muscle is not working as well as it should among carriers of an LMNA mutation who do not have more overt signs of disease and whose heart is pumping blood normally. These are signals that other tests such as an ECG or an echocardiogram would have missed.

“Gene therapies that could tackle the cause of lamin heart disease are currently being trialled. Our findings suggest a potential role for MRI in tracking disease progression and response to treatment. MRI can also identify people with the earliest-stage disease, who display subtle abnormalities suggesting that their disease is progressing, and hence may benefit the most from new therapies.”

The LMNA gene instructs the body to make proteins lamin A and C, which are critical to the structure and stability of the nuclei (command centres) of heart cells. Mutations to the LMNA gene can lead to problems including dilated cardiomyopathy (where the heart muscle wall becomes enlarged and weaker), life-threatening heart rhythms and disruption to the electrical signals regulating the heartbeat. Lamin disease affects people at younger ages and has higher rates of sudden cardiac death than other, similar forms of heart muscle disease.

Currently, close family members of individuals with lamin disease are screened for an LMNA mutation. Carriers of a mutated gene are usually followed up with electrocardiograms and echocardiograms to detect conduction disease (a disorder of the heart's electrical system), arrythmias, and early heart dysfunction. The frequency of follow-up depends on symptoms and abnormalities detected (if any).

For the new study, researchers analysed MRI data from 187 people. Sixty-seven of these had lamin heart disease, 73 had dilated cardiomyopathy without a known genetic cause, and 47 were healthy volunteers.

The research team found that heart damage, inflammation, and scarrings were central features of lamin heart disease, but not of non-genetic dilated cardiomyopathy.

The team also found that participants with a specific LMNA mutation – a shortened, or truncated gene – had worse heart functioning. A truncated LMNA gene has previously been linked to more aggressive disease than other LMNA mutations, but the cardiac MRIs showed why this might be in terms of the mechanics of the heart.

Reference:

Constantin-Cristian Topriceanu, Mashael Al-Farih, George Joy, Fiona Chan, Matt Webber, Denis C. Ilie-Ablachim, Hunain Shiwani, Mansoon Tamang, Catherine Banks, Stephen Pettit, Steffen E. Petersen, Ben O’Brien, Alun D. Hughes, Iain Pierce, William E. Moody, Richard P. Steeds, Paolo E. Puddu, Peter Kellman, Konstantinos Savvatis, Saidi Mohiddin, James C. Moon, Andrea Barison, Paolo Piras, Gabriella Captur, The Cardiovascular Magnetic Resonance Phenotype of Lamin Heart Disease, JACC: Cardiovascular Imaging, 2025, https://doi.org/10.1016/j.jcmg.2025.01.004.