Elucidating the Pathophysiological Link Between Coronary Microvascular Dysfunction and Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is characterised by impaired left ventricular relaxation and increased filling pressure, resulting in reduced exercise tolerance. It is increasing in prevalence, accounts for over half of all heart failure presentations and is associated with similar mortality to heart failure with reduced ejection fraction. Whilst there have been numerous innovations in the management of the latter, few treatments have been shown to be effective in HFpEF, partly because contemporary trials have taken a unified approach to this heterogenous condition. Coronary microvascular dysfunction (CMD) has been frequently documented in HFpEF patients, but it is not clear whether this is a mechanistic determinant or merely an epiphenomenon. The aim of our study is to assess whether patients with HFpEF and CMD differ from those with HFpEF without CMD (and controls without HFpEF) as measured by physiology during exercise, demonstrable inducible ischaemia and objective response to anti-ischaemic therapy. Patients with symptoms suggestive of HFpEF will sequentially undergo dynamic invasive physiology testing, stress perfusion cardiac MRI and be enrolled in a phenotype blinded therapeutic trial. Our findings will help to clarify whether CMD affects pathophysiology and symptoms in HFpEF and whether it represents a potential therapeutic target.