Wellcome Leap: VISIBLE – Women’s Heart Disease Revealed

Funding programme to support research projects that address heart disease in women by developing implementation strategies that expand effective care for coronary microvascular disease.

The Wellcome Leap Programme, established by Wellcome, aims to deliver breakthroughs in human health by providing funding at scale and within short timeframes. 

As part of the Leap Programme, Wellcome is launching the call ‘VISIBLE: Women’s Heart Disease Revealed’. The call is jointly funded by Wellcome and Pivotal with support from the British Heart Foundation.

The call addresses the topic of coronary microvascular dysfunction – the underlying cause in many cases of angina with no obstructive coronary arteries (ANOCA) – which is frequently left undiagnosed because standard tests fail to detect it. With cardiovascular disease the leading cause of death in women, the funding scheme aims to address this diagnostic gap which leaves women facing elevated cardiovascular risk, significant impacts on work, wellbeing and quality of life, as well as  high lifetime healthcare costs.

The goal of VISIBLE is to increase the proportion of women presenting with stable angina who receive effective diagnosis and treatment for coronary microvascular disease from less than 1% to more than 80%, without increasing the risk of missed diagnosis or treatment of obstructive coronary artery disease. In so doing, the programme aims to demonstrate advances capable of reducing the burden of cardiovascular disease for millions of women worldwide.

Central to the programme is the recognition that coronary microvascular disease encompasses multiple endotypes with distinct, yet overlapping, pathophysiological mechanisms, including functional and structural abnormalities. By refining and validating these endotypes, the programme aims to move beyond empiric care toward mechanism-informed diagnosis and treatment.

The programme is divided into four ‘thrusts’ which set out thematic focus areas as follows:

• Thrust 1: Develop scalable approaches for diagnosis and monitoring of coronary microvascular disease.
  
  This part of the programme aims to develop scalable diagnostics to detect coronary microvascular disease with >80% sensitivity and >80% specificity. The focus is on diagnostic approaches that are deployable early in the diagnostic workup, at a scale and comparable to current non-invasive testing for obstructive coronary artery disease. This may include strategies using artificial intelligence or machine learning to identify signatures of coronary microvascular disease from data already acquired in routine care, or those accessing microvascular beds outside of the heart to obtain markers of the disease. Biomarkers and other patient characteristics (eg, symptom patterns) linked to coronary microvascular disease may also be used to support risk stratification, diagnosis, or monitoring of disease activity and treatment response.
• Thrust 2: Identify risk factors and evaluate prognosis of coronary microvascular disease endotypes. 
  
  This part of the programme seeks to:
  • 2A: Identify upstream risk factors for coronary microvascular disease (effect sizes ≥1.5) to define treatment targets.
  • 2B: Define prognosis of coronary microvascular disease endotypes.
• Thrust 3: Build and validate multiscale human-relevant models of the coronary microvasculature to interrogate causal mechanisms of coronary microvascular disease.
  
  This part of the programme seeks to develop and apply integrated, multiscale models, coupling human cell-based systems with computational frameworks, to establish causal relationships between upstream drivers, proposed disease mechanisms, and resulting changes in coronary microvascular function.
• Thrust 4:  Develop treatment strategies that improve both coronary microvascular function and patient-centred outcomes.
  
  This part of the programme focuses on proof-of-concept studies testing existing interventions in well-characterised patient populations that most likely will benefit. Successful interventions are expected to demonstrate statistically significant improvement (p < 0.05) in prespecified coronary microvascular function domains, with effect sizes appropriate to the targeted mechanism, and specific treatment goals for coronary flow reserve and angina burden defined by the programme.