Heart failure with preserved ejection fraction (HFpEF) is characterised by symptoms and/or signs of heart failure, normal or mildly reduced left ventricular ejection fraction (LVEF), elevated natriuretic peptides and relevant structural heart disease (left ventricular hypertrophy, left atrial enlargement or diastolic dysfunction). It is found in up to 50% of patients presenting with heart failure symptoms. Microvascular angina (MVA) is characterised by symptoms of microvascular ischaemia, absence of obstructive epicardial coronary artery disease (CAD), evidence of myocardial ischaemia on non-invasive stress testing and coronary microvascular dysfunction (CMD). Non-obstructive CAD is observed in up to 50% of patients with angina and positive stress tests undergoing coronary angiography.
In an opinion piece published by the European Heart Journal, Crea et al. draw parallels between HFpEF and MVA.(1) These conditions are both more prevalent in post-menopausal women and associated with poorer outcomes than in asymptomatic patients with similar risk factor profiles. For both HFpEF and MVA, symptomatic treatment is largely empirical and no therapeutic intervention has been proven to improve patient outcomes.
But do MVA and HFpEF represent two clinical presentations of a disease continuum? Indeed, CMD can be demonstrated in both conditions. In addition, breathlessness is a common finding in MVA and angina is reported frequently in HFpEF. If the common soil hypothesis of MVA and HFpEF is correct, then a paradigm shift is required to incorporate CMD as both a common diagnostic and therapeutic target for these disease entities. The prevailing underlying mechanisms may have different contributions across the spectrum of disease. These may include smooth muscle hyper-reactivity, vascular remodelling, myocardial fibrosis and advanced coronary rarefaction.
Potential strategies for early diagnosis of CMD include non-invasive assessment of coronary flow reserve (using echocardiography, cardiac magnetic resonance or positron emission tomography), invasive assessment of coronary microvascular spasm (using intracoronary acetylcholine during coronary angiography) and identification of new biomarkers. Standardisation of diagnostic criteria will be required. In terms of treatment, the authors suggest that the underlying mechanisms of CMD, rather than the phenotype of MVA and/or HFpEF, should be targeted. This may explain why currently available pharmacological agents have failed to improve symptoms and outcomes in patients with either condition. Therapeutic strategies to treat the structural and functional abnormalities in CMD will probably need to be patient specific and tailored to the prevailing underlying mechanism across the disease continuum.
- Crea et al. The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. European Heart Journal 2016 (Epub ahead of print).