A simple cheek-swab test can identify children with a potentially deadly heart condition, five years before they would normally be diagnosed, suggests research from scientists in the United Kingdom.
The Guardian reports that arrhythmogenic cardiomyopathy (ACM), which is typically genetic, is responsible for more than 10% of sudden cardiac deaths in children.
The condition is caused by abnormalities in the proteins between heart cells, which lead to problems in the structure and electrical activity of the heart. ACM can often develop and strike without warning.
But research shows abnormalities in the proteins can also be seen in the lining of the cheeks, which can reveal what is happening in the heart. Now doctors have developed a two-minute cheek swab to detect ACM up to half a decade before a child may otherwise be diagnosed.
They revealed details of the test at the European Society of Cardiology congress in Madrid this past weekend.
Experts at Great Ormond Street Hospital and City St George’s, University of London, trialled the test in 51 children between three months and 18-years-old with a known genetic risk of ACM.
They were given cheek swabs every three to six months over a seven-year period. Of the group, 10 went on to develop ACM and eight of the 10 showed abnormalities that were detected by cheek swabs before other tests.
The experts also studied another group of 21 children with no known genetic risk of ACM. Of these, five had abnormalities picked up by cheek swabs.
The research presented in Madrid also found that the swabs revealed changes in the youngsters up to five years before they were diagnosed.
Diagnosis of ACM was confirmed with scans and tests, with researchers suggesting a swab could be an extra step to aid early detection.
Joanna Jager of City St George’s, University of London, said: “There is a real need for a quick and easy test to flag suspected ACM, which can then be confirmed by hospital tests.”
In the UK, it is estimated that about one in 10 000 people have ACM. Symptoms can include heart palpitations, fainting, breathlessness, abnormal heart rhythms and swelling in the stomach, legs or ankles.
Researchers are now developing swab kits that can be used at home and the samples sent away for analysis.
Dr Angeliki Asimaki, a reader in cardiac morphology and sudden death at the school of health and medical sciences at City St George’s, University of London, said: “Our test provides a window into microscopic changes happening in the heart, and it is totally risk-free and non-invasive.
“This has the potential to provide accurate and timely diagnosis of ACM, which could ultimately save lives. Patients, particularly children, have told us they hugely prefer the speed and ease of a cheek swab to alternatives such as blood tests.
“We are currently developing test kits which would allow children to do cheek swabs at home and post them off to researchers for analysis.”
Dr Sonya Babu-Narayan, clinical director of the British Heart Foundation, which funded the research, said: “Arrhythmogenic cardiomyopathy has the potential to develop and strike without warning and sadly can risk sudden death in children, so it’s important that research helps us discover how to diagnose it early.”
Study details
Inflammation in arrhythmogenic cardiomyopathy: the driver or the passenger?
J Jager, C Bueno Beti, S Moscatelli, et al.
Presented at ESC Congress 2025
Background information
Despite decades of research, the diagnosis and management of arrhythmogenic cardiomyopathies (ACM) remain challenging, mostly owing to poor understanding of disease mechanisms. Heretofore, inflammation was regarded as a consequence of myocyte death. However, recent studies suggest that inflammation is in fact driving both the myocardial injury and arrhythmias that characterise ACM through activation of the NFκB pathway. We have previously shown that pathological processes occurring in the hearts of ACM patients are mirrored by equivalent abnormalities in the buccal epithelium. As such, NFκB is activated in both cardiac and buccal cells during periods of unstable disease activity.
Purpose/Aim
We sought to characterise NFκB signalling in buccal mucosa cells from paediatric ACM-patients and silent gene carriers. We aimed to correlate disease status and activation of NFκB signalling with any shifts in key junctional proteins that have been previously shown to occur alongside ACM onset and progression.
Methods
A total of 48 paediatric ACM patients, alongside silent gene carriers for a desmosomal (n=44) or Titin (TTN) variant (n=7), were recruited from a single paediatric referral centre. Buccal swabs were collected every 3-6 months and subjected to immunocytochemistry. Presence of immunoreactive signal for RelA/p65 in nuclei of buccal cells was used as a reliable indicator of aberrantly active NFκB signalling. Distribution of the desmosomal proteins desmoplakin (DSP), plakophilin 1 (PKP1) and plakoglobin (JUP), as well as the gap junction protein connexin43 (Cx43), was also examined.
Results
In 13 individuals (40%), changes in the distribution of junctional proteins in the buccal epithelium coincided with aberrant activation of NFκB. Multiple instances of protein changes alongside positive RelA signal was observed in 2 affected individuals. In 3 patients, RelA signal corresponded with both protein signal depression and clinical deterioration (inc. worsening LVEF, progressive LV/RV dysfunction, syncope, NSVT). Furthermore, DSP variant carriers showed more episodes of positive RelA than PKP2 carriers (DSP n=12, PKP2 n=6), both in single (DSP n=7, PKP2 n=4) and multiple (DSP n=5, PKP2 n=2) instances of immune signalling, agreeing well with the clinical observations that DSP-variant carriers exhibit a more pronounced inflammatory response.
Conclusion
Analysis of serial cheek smears showed that aberrant activation of the NFκB pathway precedes and likely promotes cascade redistribution of junctional proteins both in children diagnosed with ACM as well as silent carriers of ACM-causing variants. Our results add further evidence to the theory that inflammation is not a consequence, but actually a primary driving force, of ACM pathogenesis.
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