Coronary dysfunction and heart failure

Angina and non-obstructive coronary artery disease (ANOCA) are still too often interpreted as a reassuring finding, after which patients are sent home without further evaluation. In reality, a large proportion of patients, predominantly women, who undergo coronary angiography for chest pain do not have obstructive disease in the epicardial arteries but continue to have symptoms and a poor outcome. 

In many of these patients, symptoms are driven by coronary dysfunction, including microvascular dysfunction and vasospasm. Patients with microvascular or vasospastic angina frequently experience persistent symptoms, impaired quality of life, and an increased risk of heart failure with preserved ejection fraction (HFpEF), a condition that is particularly prevalent in women and is increasingly recognized because of coronary microvascular dysfunction. 

Both coronary dysfunction and HFpEF are complex and progressive syndromes with a substantial clinical burden, yet therapeutic options remain limited. This largely reflects our incomplete understanding of the underlying biology. Our research focuses on understanding why coronary dysfunction occurs, and how it can be detected and treated more effectively. Within the ENDOTYPE biobank, we collect blood samples from patients with ANOCA undergoing invasive coronary function testing. Uniquely, we also isolate and culture endothelial cells obtained during these procedures. This allows us to directly study the vascular compartment most relevant to disease. We apply advanced molecular approaches, including multi-omics profiling, to define the cellular and molecular mechanisms underlying coronary dysfunction. 

In parallel, we evaluate women with ANOCA for early signs of diastolic dysfunction, the precursor stage of HFpEF, using both resting and exercise echocardiography. Exercise imaging is essential, as abnormalities in relaxation and filling pressures often only become apparent under stress. By identifying these changes early, we aim to define which women are at risk of progression to overt heart failure. 

By integrating imaging with circulating biomarkers, we aim not only to improve early detection, but also to link functional abnormalities to underlying biological pathways, including inflammation, endothelial dysfunction, and microvascular injury. This combined approach is key to moving from symptom-based classification to mechanism-based diagnosis and treatment. 

Funded by the 2020-004 DCVA-IMPRESS consortium, Dutch Heart Foundation Open public private partnership CHARACTERIZE, and Health Holland (PPP Women’s Health)