The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift

An increasing number of studies clearly demonstrate that coronary microvascular dysfunction (CMD) plays a pivotal role in several cardiovascular diseases.1 In particular, emerging evidence suggests that CMD is the main contributor to myocardial ischaemia in a large subset of patients with chronic stable angina. Indeed, non-obstructive coronary atherosclerosis is observed in up to 50% of patients with angina and positive stress test results undergoing diagnostic coronary angiography.2 Thus, the prevalence of microvascular angina (MVA) is higher than previously thought and associated with worse clinical outcomes than those observed in asymptomatic subjects with similar risk factor burden.3 The diagnosis of MVA is based on the following criteria: (i) symptoms of myocardial ischaemia; (ii) absence of obstructive epicardial coronary artery disease; (iii) evidence of myocardial ischaemia on non-invasive stress testing; and (iv) evidence of impaired coronary microvascular function. The clinical relevance of MVA has historically been overlooked since the diagnostic tools required for the evaluation of the coronary microcirculation are infrequently utilized. A parallel ‘tale’ could be proposed for heart failure (HF) with preserved ejection fraction (HFpEF). Indeed, HFpEF is observed in about 50% of patients presenting with HF symptoms and is characterized by the absence of a relevant reduction of left ventricular ejection fraction (LVEF).4 As with MVA, patients with HFpEF have poorer clinical outcomes compared with asymptomatic subjects exhibiting a similar burden of risk factors. The diagnosis of HFpEF is based on the following: (i) symptoms with or without signs of HF; (ii) normal or only mildy reduced LVEF; (iii) elevated levels of natriuretic peptides; (iv) relevant structural heart disease (i.e. left ventricular hypertrophy, left atrial enlargement) and/or diastolic dysfunction. In both MVA and HFpEF, no therapeutic intervention has hitherto been proven to improve patient outcome; similarly, symptomatic treatment is largely empirical. A key shared characteristic …