Work done at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) has found that scar tissue can build up in some patients with hypertrophic cardiomyopathy, making the heart weak and prone to electrical disturbances.
The study, published in the European Heart Journal - Cardiovascular Imaging, suggests that the timely detection of scar progression on magnetic resonance imaging (MRI) can help clinicians identify those at risk of heart failure and potentially sudden cardiac death in hypertrophic cardiomyopathy.
By detecting scar progression in patients with HCM, we can identify those at risk of heart failure and life threatening arrhythmias. - Dr Betty Raman
Dr Betty Raman, clinical research fellow and first author on the study : “This can help us better target therapy to prevent the onset of heart failure and even improve selection of people for life-saving devices.”
What is HCM?
Hypertrophic Cardiomyopathy (HCM) is the most common inherited cardiomyopathy and the leading cause of sudden cardiac death in young adults and athletes: it is genetically determined and affects more than 1 in 500 people world-wide.
HCM is characterised by abnormal thickening of the heart, and while many people with the condition have no symptoms, others can suffer from chest pain, breathlessness, palpitations and black outs or ‘syncope’. HCM mortality has substantially improved thanks to Implantable Cardioverter Defibrillator (ICD), a life-saving device which can abort sudden cardiac arrest in HCM patients.
But ICD insertion is not without risks, so clinicians need to select the right patients who are most at risk of adverse cardiac events. While we already know that MRI-detected myocardial fibrosis (scarring in the heart) in HCM patients is associated with the risk of sudden death and heart failure, little is known about what happens to scar over time, and whether changes in scar have any implications for patients with HCM. The mechanisms that promote scar growth are also unknown and may help in developing treatments to prevent its progression.
Tracking patients over six years
To address these questions, OCMR researchers tracked 72 patients with HCM with repeated MRI scans over six years. They found that scarring increased in volume within the heart muscle, leading to thinning and weakening of the heart in some patients, and found that inadequate blood supply to the muscle of the heart and low energetic status could increase the risk of scar build-up in HCM. Crucially, people with a higher burden of scar progression had a higher risk of heart failure and electrical disorders.
Professor Stefan Neubauer, lead author and director of the Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford , said: “This study describes the rate of progression of fibrosis in patients with hypertrophic cardiomyopathy, the number one cause of sudden death in younger patients, and some of the mechanisms by which fibrosis progresses.
Our data suggest novel therapeutic strategies to reduce the risk associated with this disease, and also lay the ground for ultimately testing the same concept in the large Hypertrophic Cardiomyopathy Registry, a study of over 2500 patients with this disease, recruitment for which we have recently completed.”
Dr Masliza Mahmod, Head of Clinical Trials at OCMR and one of the study co-authors, said: “Traditionally, the only way one could detect scar in the heart muscle of HCM patients was during open heart surgery or autopsy. Now we can detect this non-invasively on magnetic resonance imaging, even before the onset of symptoms, providing essential information required for making life-saving treatment decisions”
Dr Betty Raman added: “Our findings are important and address a significant gap in our knowledge about the relevance of fibrosis in HCM: Does fibrosis progress in HCM ? How can we detect it ? What does it mean for patients?”
Professor Hugh Watkins, Head of the Radcliffe Department of Medicine and study co-author said: "This work shows that hypertrophic cardiomyopathy is not a static disease; some patients develop progressive scarring and being able to measure and understand the causes of that may help us target preventative treatment”
This work was undertaken in collaboration with researchers from University of London, UK and University of Virginia, USA. The major funders for the study were the National Institute for Health Research, Oxford and Barts Biomedical Research Centres, British Heart foundation, Wellcome Trust, Royal Society and the US National Institute of Health. See the published paper for a full list of funders.