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Pathophysiological coronary and microcirculatory flow alterations in aortic stenosis

Abstract

Regulation of coronary blood flow is maintained through a delicate balance of ventriculoarterial and neurohumoral mechanisms. The aortic valve is integral to the functions of these systems, and disease states that compromise aortic valve integrity have the potential to seriously disrupt coronary blood flow. Aortic stenosis (AS) is the most common cause of valvular heart disease requiring medical intervention, and the prevalence and associated socio-economic burden of AS are set to increase with population ageing. Valvular stenosis precipitates a cascade of structural, microcirculatory, and neurohumoral changes, which all lead to impairment of coronary flow reserve and myocardial ischaemia even in the absence of notable coronary stenosis. Coronary physiology can potentially be normalized through interventions that relieve severe AS, but normality is often not immediately achievable and probably requires continued adaptation. Finally, the physiological assessment of coronary artery disease in patients with AS represents an ongoing challenge, as the invasive physiological measures used in current cardiology practice are yet to be validated in this population. This Review discusses the key concepts of coronary pathophysiology in patients with AS through presentation of contemporary basic science and data from animal and human studies.

Key points

  • A substantial proportion of patients with aortic stenosis (AS) develop angina pectoris even in the absence of obstructive coronary artery disease.

  • The presence of AS adversely affects coronary blood flow: coronary flow reserve (CFR) becomes markedly impaired when the effective aortic orifice area is <1.0 cm2 and exhausted at <0.5–0.6 cm2.

  • Coronary blood flow at rest is upregulated to meet the increased oxygen demands of a hypertrophied myocardium, preventing further upregulation and impairing CFR.

  • Endothelial dysfunction also occurs in patients with AS, further contributing to a blunted CFR.

  • Relief of AS enables at least partial reversal of these pathophysiological changes; some improvements occur immediately, but others are delayed.

  • Invasive physiological assessment indices (such as fractional flow reserve and instantaneous wave-free ratio) have not been validated in patients with AS, and caution is needed in their interpretation.

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Fig. 1: A representative example of coronary pressure and blood flow velocity traces and separated wave intensity profiles measured over a single cardiac cycle.
Fig. 2: The principal determinants of coronary blood flow.
Fig. 3: Haemodynamic waveforms and associated coronary wave intensity profiles.

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Review criteria

A digital search of the PubMed database was performed to identify articles written in English published between 2000 and 2017 (last update 13 December 2017) using the following search terms: “aortic stenosis”, “coronary physiology”, “wave intensity analysis”, “fractional flow reserve”, “coronary flow reserve”, “instantaneous wave-free ratio”, “endothelial dysfunction”, “left ventricular hypertrophy”, “transcatheter aortic valve implantation”, and “transcatheter aortic valve replacement”. Titles and abstracts were examined, and the full text of all potentially eligible studies was scrutinized. Reference lists of eligible articles were reviewed for further potential citations. Selected papers published before 2000 were also considered.

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M.M. researched the data for the article. M.M. and A.J.B. wrote the manuscript and contributed substantially to discussions of the article content. A.J.B. and J.E.D. contributed to reviewing and/or editing of the manuscript before submission. J.D.C. and K.H.P. contributed substantially to discussions of the article content and review and/or editing of the manuscript before submission.

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Correspondence to Adam J. Brown.

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Competing interests

J.E.D. holds patents pertaining to instantaneous wave-free ratio (iFR) technology. J.E.D. has also served as a consultant for and has received research funding from Volcano Corporation. The other authors declare no competing interests.

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Glossary

Plasma skimming

The separation of red blood cells from plasma at bifurcations in the vascular tree, which divides the blood into relatively more-concentrated and relatively more-dilute streams.

Patient–prosthesis mismatch

A mismatch that occurs when the effective orifice area of an inserted prosthetic valve is too small in relation to body size. Its main haemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves.

SYNTAX score

An angiographic grading system score used to evaluate the complexity of coronary artery disease and prognosis of patients undergoing revascularization.

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Michail, M., Davies, J.E., Cameron, J.D. et al. Pathophysiological coronary and microcirculatory flow alterations in aortic stenosis. Nat Rev Cardiol 15, 420–431 (2018). https://doi.org/10.1038/s41569-018-0011-2

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