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"Broken heart syndrome" protects the heart from adrenaline overload

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27 June 2012

A condition that temporarily causes heart failure in people who experience severe stress might actually protect the heart from very high levels of adrenaline, according to a new study published in the journal Circulation. The research, funded by BBSRC and others, provides the first physiological explanation for Takotsubo cardiomyopathy, also called "broken heart syndrome" because it affects people who suffer severe emotional stress after bereavement, and suggests guidance for treatment.

Around 1-2% of people who are initially suspected of having a heart attack are finally discovered to have this increasingly recognised syndrome.

The Imperial College London study, which simulated the condition in an animal model, suggests that the body changes its response to adrenaline by switching from its usual role in stimulating the heart to reducing its pumping power. Although this results in acute heart failure, most patients make a full recovery within days or weeks.

The researchers propose that the switch in the heart's response to adrenaline might have evolved to protect the heart from being overstimulated by the particularly high doses of adrenaline that the body releases during stress.

Patients with Takotsubo cardiomyopathy, most often older women, experience symptoms that resemble a heart attack, but heart tests reveal no blockage in the coronary arteries; instead the heart has a balloon-like appearance caused by the bottom of the heart not contracting properly. The same condition is sometimes seen in people who are injected with adrenaline to treat severe allergic reactions.

In this new research, the authors simulated the condition by injecting high doses of adrenaline in anaesthetised rats. In these rats, as in Takotsubo patients, heart muscle contraction was suppressed towards the bottom of the heart.

The researchers found that these rats were protected from an otherwise fatal overstimulation of the heart, indicating that adrenaline acts through a different pathway from usual, and that this switch protects the heart from toxic levels of adrenaline.

The study also examined drugs that might be useful for treating Takotsubo cardiomyopathy. Some beta blockers, used to treat high blood pressure, angina and heart failure, reproduced or enhanced the features of Takotsubo, giving new insights into the protective effects of these drugs. Levosimendan, a different type of drug given in heart failure to stimulate the heart without going through the adrenaline receptor pathways, had a beneficial effect.

"Adrenaline's stimulatory effect on the heart is important for helping us get more oxygen around the body in stressful situations, but it can be damaging if it goes on for too long," said Professor Sian Harding, from the National Heart and Lung Institute (NHLI) at Imperial College London, who led the study. "In patients with Takotsubo cardiomyopathy, adrenaline works in a different way and shuts down the heart instead. This seems to protect the heart from being overstimulated."

Study co-author Dr Alexander Lyon, also from the NHLI at Imperial, and consultant cardiologist at Royal Brompton Hospital, set up one of the first specialist services in the UK to look after people who have experienced Takotsubo cardiomyopathy. "Currently it is not fully known how to treat these patients," he said. "Insights from this work show that the illness may be protecting them from more serious harm. We've identified a drug treatment that might be helpful, but the most important thing is to recognise the condition, and not to make it worse by giving patients with Takotsubo cardiomyopathy more adrenaline or adrenaline-like medications.

"At the Royal Brompton Hospital and Imperial College London we are leading a European initiative to bring together experts to understand this recently recognised cardiac syndrome, and we hope the findings from this work will lead to new treatment strategies for these patients during the acute phase of their illness, and to prevent recurrence".

The study was funded by the British Heart Foundation (BHF), the Wellcome Trust, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Academy of Medical Sciences.

Dr Shannon Amoils, Research Advisor at the BHF, said: "This is a fascinating study which presents a possible explanation for the signs of Takotsubo cardiomyopathy, a rare condition that's usually preceded by intense emotional or physical stress. Patients usually have symptoms that resemble those of a heart attack but nearly all fully recover after a short time.

"The study also provides new insights into how the heart may protect itself from stress, which opens up exciting avenues of exploration for research. We must remember though that this is a study in rats, and the findings need to be confirmed in people before we can be sure of their relevance to patients."

ENDS

Notes to editors

Reference: H Paur et al. 'High levels of circulating epinephrine trigger apical cardiodepression in a β2-1 adrenoceptor/Gi-dependent manner: a new model of Takotsubo Cardiomyopathy' Circulation, published online 25 June 2012.

About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible. Website: www.imperial.ac.uk

About the British Heart Foundation

The British Heart Foundation (BHF) is the nation's heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease. For more information visit bhf.org.uk/pressoffice

About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. www.wellcome.ac.uk

About the Royal Brompton & Harefield NHS Foundation Trust

Royal Brompton & Harefield NHS Foundation Trust is a national and international specialist heart and lung centre based in Chelsea, London and Harefield, Middlesex. The Trust helps patients from all age groups who have heart and lung problems and is the country's largest centre for the treatment of adult congenital heart disease. www.rbht.nhs.uk

About the Academy of Medical Sciences

The independent Academy of Medical Sciences promotes medical science and its translation into benefits for society. The Academy's elected Fellows are the United Kingdom's leading medical scientists and scholars from hospitals, academia, industry and the public service. www.acmedsci.ac.uk

The Academy's 'Starter Grants' scheme provides modest funds to enable research active Clinical Lecturers to pursue research work, gather preliminary data and so further strengthen applications for longer-term fellowships and funding.

About BBSRC

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, and with an annual budget of around £445M (2011-2012), we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

For more information about BBSRC, our science and our impact see: www.bbsrc.ac.uk.
For more information about BBSRC strategically funded institutes see: www.bbsrc.ac.uk/institutes.

External contact

Sam Wong, Research Media Officer, Imperial College London

tel: 0207 5942198