Evaluating sex specific differences in dilated cardiomyopathy

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Context Heart failure affects 26 million people globally. It is a leading cause of hospitalisations and early deaths and is a major economic burden, making up 1-2% of the NHS budget. The second commonest cause is dilated cardiomyopathy, a heart muscle condition that affects up to 1 in 250 people, or 240,000 people in the UK. Unfortunately, despite best treatment, mortality for this relatively young population (median age 40) remains high. Approximately half of patients aged 50 with dilated cardiomyopathy and scarring in the heart die or have a heart transplant within 10 years. We urgently need to improve how we care for patients with this condition. Sex (being male or female) may play a critical role in disease progression. My research shows that:(i) Dilated cardiomyopathy affects twice as many men as women. Either men are more at risk or women are protected.(ii) The hearts of men and women with dilated cardiomyopathy differ. Compared to men, women have smaller hearts and better heart function. (iii) Despite this, women have a two-fold increased risk of complications compared to men. Women get twice as many complications after 50 whilst men have the same number of complications regardless of age. This suggests that women are more at risk of complications despite a 'milder' disease and this risk increases after menopause. Despite these observations, we currently treat men and women exactly the same. Aims and objectives In this research programme, I will study how dilated cardiomyopathy affects men and women differently across their lifespan with the aim of improving diagnosis, treatment and prognosis for all patients with dilated cardiomyopathy. I will do three main studies: 1. Women experience a number of unique life events linked to major hormonal changes such as pregnancy and menopause. However, we do not know their impact on dilated cardiomyopathy or its complications. I will study the effect of these on patients in our specialist research centre and in the general population using a large general practice research database. 2. There are no sex specific treatment recommendations in dilated cardiomyopathy. I have developed an international study collating data on ~6500 patients. I will develop a risk prediction model which works well in women. Risk prediction models use patient risk factors to predict prognosis. I will also study whether we should apply different cut offs for risk factors in men and women. 3. Whilst we know there are differences in heart structure between men and women, we do not know why. One reason could be due to differences in how the heart genes are switched on in men versus women. I will look for changes in gene signals in heart tissue from men and women with dilated cardiomyopathy compared to healthy hearts. Who is involved in this research? I will lead this research and collaborate with people with the expertise needed to successfully complete this research. I have a team of collaborators internationally and in the UK from different disciplines including epidemiology, endocrinology, biostatistics, and genetics. Potential impact This study will have immediate impact for patients, clinicians and policy makers. Identifying how and why dilated cardiomyopathy differs in men and women will help us to make sense of the range of health outcomes that patients experience.The results of this study can be applied to diagnosis and risk stratification (i.e. whether patients are at high or low risk of complications) and could lead to sex-specific treatment recommendations. This would lead to realistic improvements in the health of all patients with dilated cardiomyopathy, re-evaluating our current model of treating men and women the same.Patients and national patient groups (Cardiomyopathy UK, Pumping Marvellous) have been engaged in all stages of this study. They say this is an incredibly important patient centred project targeting a major unmet need.