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.
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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Bertazzo, S. et al. Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification. Nat. Mater. 12, 576–583 (2013).
Otto, C. M., Kuusisto, J., Reichenbach, D. D., Gown, A. M. & O’Brien, K. D. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 90, 844–853 (1994).
O’Brien, K. D. et al. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of ‘degenerative’ valvular aortic stenosis. Arterioscler. Thromb. Vasc. Biol. 16, 523–532 (1996).
Ramos, J. et al. Large-scale assessment of aortic stenosis: facing the next cardiac epidemic? Eur. Heart J. Cardiovasc. Imag. https://doi.org/10.1093/ehjci/jex223 (2017).
Nkomo, V. T. et al. Burden of valvular heart diseases: a population-based study. Lancet 368, 1005–1011 (2006).
Iung, B. & Vahanian, A. Degenerative calcific aortic stenosis: a natural history. Heart 98 (Suppl. 4), iv7–iv13 (2012).
Ross, J. Jr & Braunwald, E. Aortic stenosis. Circulation 38, 61–67 (1968).
Exadactylos, N., Sugrue, D. D. & Oakley, C. M. Prevalence of coronary artery disease in patients with isolated aortic valve stenosis. Br. Heart J. 51, 121–124 (1984).
Ortlepp, J. R., Schmitz, F., Bozoglu, T., Hanrath, P. & Hoffmann, R. Cardiovascular risk factors in patients with aortic stenosis predict prevalence of coronary artery disease but not of aortic stenosis: an angiographic pair matched case–control study. Heart 89, 1019–1022 (2003).
Rapp, A. H., Hillis, L. D., Lange, R. A. & Cigarroa, J. E. Prevalence of coronary artery disease in patients with aortic stenosis with and without angina pectoris. Am. J. Cardiol. 87, 1216–1217; A1217 (2001).
Vandeplas, A., Willems, J. L., Piessens, J. & De Geest, H. Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis. Am. J. Cardiol. 62, 117–120 (1988).
Lund, O., Nielsen, T. T., Pilegaard, H. K., Magnussen, K. & Knudsen, M. A. The influence of coronary artery disease and bypass grafting on early and late survival after valve replacement for aortic stenosis. J. Thorac. Cardiovasc. Surg. 100, 327–337 (1990).
Baumgartner, H. et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 38, 2739–2791 (2017).
Parker, K. H. & Jones, C. J. Forward and backward running waves in the arteries: analysis using the method of characteristics. J. Biomech. Eng. 112, 322–326 (1990).
Sun, Y. H., Anderson, T. J., Parker, K. H. & Tyberg, J. V. Wave-intensity analysis: a new approach to coronary hemodynamics. J. Appl. Physiol. 89, 1636–1644 (2000).
Davies, J. E. et al. Evidence of a dominant backward-propagating “suction” wave responsible for diastolic coronary filling in humans, attenuated in left ventricular hypertrophy. Circulation 113, 1768–1778 (2006).
Hadjiloizou, N. et al. Differences in cardiac microcirculatory wave patterns between the proximal left mainstem and proximal right coronary artery. Am. J. Physiol. Heart Circ. Physiol. 295, H1198–H1205 (2008).
Komaru, T., Kanatsuka, H. & Shirato, K. Coronary microcirculation: physiology and pharmacology. Pharmacol. Ther. 86, 217–261 (2000).
Brown, A. J. et al. Role of biomechanical forces in the natural history of coronary atherosclerosis. Nat. Rev. Cardiol. 13, 210–220 (2016).
Gould, K. L., Lipscomb, K. & Hamilton, G. W. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am. J. Cardiol. 33, 87–94 (1974).
Vorobtsova, N. et al. Effects of vessel tortuosity on coronary hemodynamics: an idealized and patient-specific computational study. Ann. Biomed. Eng. 44, 2228–2239 (2016).
Tonino, P. A. et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N. Engl. J. Med. 360, 213–224 (2009).
Pijls, N. H. et al. Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow. Circulation 92, 3183–3193 (1995).
van de Hoef, T. P. et al. Fractional flow reserve as a surrogate for inducible myocardial ischaemia. Nat. Rev. Cardiol. 10, 439–452 (2013).
Sen, S. et al. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (Adenosine Vasodilator Independent Stenosis Evaluation) study. J. Am. Coll. Cardiol. 59, 1392–1402 (2012).
Davies, J. E. et al. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI. N. Engl. J. Med. 376, 1824–1834 (2017).
Mandal, A. B. & Gray, I. R. Significance of angina pectoris in aortic valve stenosis. Br. Heart J. 38, 811–815 (1976).
Basta, L. L., Raines, D., Najjar, S. & Kioschos, J. M. Clinical, haemodynamic, and coronary angiographic correlates of angina pectoris in patients with severe aortic valve disease. Br. Heart J. 37, 150–157 (1975).
Hakki, A. H. et al. Angina pectoris and coronary artery disease in patients with severe aortic valvular disease. Am. Heart J. 100, 441–449 (1980).
Alyono, D., Anderson, R. W., Parrish, D. G., Dai, X. Z. & Bache, R. J. Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis. Circ. Res. 58, 47–57 (1986).
Marcus, M. L., Doty, D. B., Hiratzka, L. F., Wright, C. B. & Eastham, C. L. Decreased coronary reserve: a mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries. N. Engl. J. Med. 307, 1362–1366 (1982).
Eberli, F. R. et al. Coronary reserve in patients with aortic valve disease before and after successful aortic valve replacement. Eur. Heart J. 12, 127–138 (1991).
Julius, B. K. et al. Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts. Circulation 95, 892–898 (1997).
Rolandi, M. C. et al. Transcatheter replacement of stenotic aortic valve normalizes cardiac-coronary interaction by restoration of systolic coronary flow dynamics as assessed by wave intensity analysis. Circ. Cardiovasc. Interv. 9, e002356 (2016).
Wiegerinck, E. M. et al. Impact of aortic valve stenosis on coronary hemodynamics and the instantaneous effect of transcatheter aortic valve implantation. Circ. Cardiovasc. Interv. 8, e002443 (2015).
Gutierrez-Barrios, A. et al. Invasive assessment of coronary flow reserve impairment in severe aortic stenosis and echocardiographic correlations. Int. J. Cardiol. 236, 370–374 (2017).
Rajappan, K. et al. Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries. Circulation 105, 470–476 (2002).
Bozbas, H. et al. Coronary flow reserve is impaired in patients with aortic valve calcification. Atherosclerosis 197, 846–852 (2008).
Nemes, A. et al. How can coronary flow reserve be altered by severe aortic stenosis? Echocardiography 19, 655–659 (2002).
Garcia, D. et al. Impairment of coronary flow reserve in aortic stenosis. J. Appl. Physiol. 106, 113–121 (2009) (1985).
Davies, J. E. et al. Arterial pulse wave dynamics after percutaneous aortic valve replacement: fall in coronary diastolic suction with increasing heart rate as a basis for angina symptoms in aortic stenosis. Circulation 124, 1565–1572 (2011).
Seiler, C. & Jenni, R. Severe aortic stenosis without left ventricular hypertrophy: prevalence, predictors, and short-term follow up after aortic valve replacement. Heart 76, 250–255 (1996).
Dellgren, G. et al. Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis. Am. J. Cardiol. 84, 909–913 (1999).
Antonini-Canterin, F. et al. Symptomatic aortic stenosis: does systemic hypertension play an additional role? Hypertension 41, 1268–1272 (2003).
Mureddu, G. F., Cioffi, G., Stefenelli, C., Boccanelli, A. & de Simone, G. Compensatory or inappropriate left ventricular mass in different models of left ventricular pressure overload: comparison between patients with aortic stenosis and arterial hypertension. J. Hypertens. 27, 642–649 (2009).
Holtz, J., Restorff, W. V., Bard, P. & Bassenge, E. Transmural distribution of myocardial blood flow and of coronary reserve in canine left ventricular hypertrophy. Basic Res. Cardiol. 72, 286–292 (1977).
Rembert, J. C., Kleinman, L. H., Fedor, J. M., Wechsler, A. S. & Greenfield, J. C. Jr. Myocardial blood flow distribution in concentric left ventricular hypertrophy. J. Clin. Invest. 62, 379–386 (1978).
Bache, R. J., Vrobel, T. R., Ring, W. S., Emery, R. W. & Andersen, R. W. Regional myocardial blood flow during exercise in dogs with chronic left ventricular hypertrophy. Circ. Res. 48, 76–87 (1981).
Lumley, M. et al. Coronary physiology during exercise and vasodilation in the healthy heart and in severe aortic stenosis. J. Am. Coll. Cardiol. 68, 688–697 (2016).
Panting, J. R. et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N. Engl. J. Med. 346, 1948–1953 (2002).
Lanza, G. A. et al. Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X. J. Am. Coll. Cardiol. 51, 466–472 (2008).
Mahmod, M. et al. Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction. J. Cardiovasc. Magn. Reson. 16, 29 (2014).
Ahn, J. H. et al. Coronary microvascular dysfunction as a mechanism of angina in severe AS: prospective adenosine-stress CMR study. J. Am. Coll. Cardiol. 67, 1412–1422 (2016).
Schwartzkopff, B. et al. Morphometric investigation of human myocardium in arterial hypertension and valvular aortic stenosis. Eur. Heart J. 13 (Suppl. D), 17–23 (1992).
Robicsek, F. Leonardo da Vinci and the sinuses of Valsalva. Ann. Thorac. Surg. 52, 328–335 (1991).
Bellhouse, B. J. & Bellhouse, F. H. Mechanism of closure of the aortic valve. Nature 217, 86–87 (1968).
Bellhouse, B. J., Bellhouse, F. H. & Reid, K. G. Fluid mechanics of the aortic root with application to coronary flow. Nature 219, 1059–1061 (1968).
Kvitting, J. P. et al. Flow patterns in the aortic root and the aorta studied with time-resolved, 3-dimensional, phase-contrast magnetic resonance imaging: implications for aortic valve-sparing surgery. J. Thorac. Cardiovasc. Surg. 127, 1602–1607 (2004).
Heusch, G. Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. Br. J. Pharmacol. 153, 1589–1601 (2008).
Greve, A. M. et al. Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: the SEAS study. Int. J. Cardiol. 180, 122–128 (2015).
Dzau, V. J. & Gibbons, G. H. Autocrine-paracrine mechanisms of vascular myocytes in systemic hypertension. Am. J. Cardiol. 60, 99I–103I (1987).
Joannides, R. et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91, 1314–1319 (1995).
Okahara, K., Sun, B. & Kambayashi, J. Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 18, 1922–1926 (1998).
Ludmer, P. L. et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N. Engl. J. Med. 315, 1046–1051 (1986).
Bonetti, P. O. et al. Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering. J. Am. Coll. Cardiol. 40, 546–554 (2002).
Zeiher, A. M., Krause, T., Schachinger, V., Minners, J. & Moser, E. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 91, 2345–2352 (1995).
Hasdai, D. et al. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation 96, 3390–3395 (1997).
Poggianti, E. et al. Aortic valve sclerosis is associated with systemic endothelial dysfunction. J. Am. Coll. Cardiol. 41, 136–141 (2003).
Diehl, P. et al. Increased levels of circulating microparticles in patients with severe aortic valve stenosis. Thromb. Haemost. 99, 711–719 (2008).
Schumm, J. et al. In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels. Am. Heart J. 161, 893–899 (2011).
Corretti, M. C. et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J. Am. Coll. Cardiol. 39, 257–265 (2002).
McGoldrick, R. B., Kingsbury, M., Turner, M. A., Sheridan, D. J. & Hughes, A. D. Left ventricular hypertrophy induced by aortic banding impairs relaxation of isolated coronary arteries. Clin. Sci. (Lond.) 113, 473–478 (2007).
Pellegrino, T. et al. Relationship between brachial artery flow-mediated dilation and coronary flow reserve in patients with peripheral artery disease. J. Nucl. Med. 46, 1997–2002 (2005).
Oz, F., Elitok, A., Bilge, A. K., Mercanoglu, F. & Oflaz, H. Relationship between brachial artery flow-mediated dilation, carotid artery intima–media thickness and coronary flow reserve in patients with coronary artery disease. Cardiol. Res. 3, 214–221 (2012).
Camuglia, A. C. et al. Invasively assessed coronary flow dynamics improve following relief of aortic stenosis with transcatheter aortic valve implantation. J. Am. Coll. Cardiol. 63, 1808–1809 (2014).
Yotti, R. et al. Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement. J. Am. Coll. Cardiol. 65, 423–433 (2015).
Axell, R. G. et al. Rapid pacing-induced right ventricular dysfunction is evident after balloon-expandable transfemoral aortic valve replacement. J. Am. Coll. Cardiol. 69, 903–904 (2017).
Chenevard, R. et al. Persistent endothelial dysfunction in calcified aortic stenosis beyond valve replacement surgery. Heart 92, 1862–1863 (2006).
Horn, P. et al. Improved endothelial function and decreased levels of endothelium-derived microparticles after transcatheter aortic valve implantation. EuroIntervention 10, 1456–1463 (2015).
Dignat-George, F. & Boulanger, C. M. The many faces of endothelial microparticles. Arterioscler. Thromb. Vasc. Biol. 31, 27–33 (2011).
Rautou, P. E. et al. Microparticles, vascular function, and atherothrombosis. Circ. Res. 109, 593–606 (2011).
Kennedy, J. W., Doces, J. & Stewart, D. K. Left ventricular function before and following aortic valve replacement. Circulation 56, 944–950 (1977).
Ikonomidis, I. et al. Four year follow up of aortic valve replacement for isolated aortic stenosis: a link between reduction in pressure overload, regression of left ventricular hypertrophy, and diastolic function. Heart 86, 309–316 (2001).
Walther, T. et al. Prospectively randomized evaluation of stentless versus conventional biological aortic valves: impact on early regression of left ventricular hypertrophy. Circulation 100 (Suppl.), II6–II10 (1999).
La Manna, A. et al. Left ventricular reverse remodeling after transcatheter aortic valve implantation: a cardiovascular magnetic resonance study. J. Cardiovasc. Magn. Reson. 15, 39 (2013).
Hildick-Smith, D. J. & Shapiro, L. M. Coronary flow reserve improves after aortic valve replacement for aortic stenosis: an adenosine transthoracic echocardiography study. J. Am. Coll. Cardiol. 36, 1889–1896 (2000).
Rajappan, K. et al. Functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis. Circulation 107, 3170–3175 (2003).
Bakhtiary, F. et al. Impact of patient–prosthesis mismatch and aortic valve design on coronary flow reserve after aortic valve replacement. J. Am. Coll. Cardiol. 49, 790–796 (2007).
Akins, C. W. et al. Cardiac operations in patients 80 years old and older. Ann. Thorac. Surg. 64, 606–614 (1997).
Vahanian, A. et al. Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur. J. Cardiothorac. Surg. 42, S1–S44 (2012).
Dewey, T. M. et al. Effect of concomitant coronary artery disease on procedural and late outcomes of transcatheter aortic valve implantation. Ann. Thorac. Surg. 89, 758–767 (2010).
Khawaja, M. Z. et al. The effect of coronary artery disease defined by quantitative coronary angiography and SYNTAX score upon outcome after transcatheter aortic valve implantation (TAVI) using the Edwards bioprosthesis. EuroIntervention 11, 450–455 (2015).
Paradis, J. M. et al. Impact of coronary artery disease severity assessed with the SYNTAX score on outcomes following transcatheter aortic valve replacement. J. Am. Heart Assoc. 6, e005070 (2017).
Masson, J. B. et al. Impact of coronary artery disease on outcomes after transcatheter aortic valve implantation. Catheter. Cardiovasc. Interv. 76, 165–173 (2010).
Iguchi, T. et al. Impact of lesion length on functional significance in intermediate coronary lesions. Clin. Cardiol. 36, 172–177 (2013).
Brosh, D., Higano, S. T., Lennon, R. J., Holmes, D. R. Jr & Lerman, A. Effect of lesion length on fractional flow reserve in intermediate coronary lesions. Am. Heart J. 150, 338–343 (2005).
Gould, K. L. et al. Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making. J. Am. Coll. Cardiol. 62, 1639–1653 (2013).
Pijls, N. H. et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J. Am. Coll. Cardiol. 56, 177–184 (2010).
Tonino, P. A. et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J. Am. Coll. Cardiol. 55, 2816–2821 (2010).
Burgstahler, C. et al. Adenosine stress first pass perfusion for the detection of coronary artery disease in patients with aortic stenosis: a feasibility study. Int. J. Cardiovasc. Imaging 24, 195–200 (2008).
Maffei, S. et al. Preoperative assessment of coronary artery disease in aortic stenosis: a dipyridamole echocardiographic study. Ann. Thorac. Surg. 65, 397–402 (1998).
Patsilinakos, S. P. et al. Adenosine stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis. J. Nucl. Cardiol. 11, 20–25 (2004).
Cremer, P. C. et al. Stress positron emission tomography is safe and can guide coronary revascularization in high-risk patients being considered for transcatheter aortic valve replacement. J. Nucl. Cardiol. 21, 1001–1010 (2014).
Pesarini, G. et al. Functional assessment of coronary artery disease in patients undergoing transcatheter aortic valve implantation: influence of pressure overload on the evaluation of lesion severity. Circ. Cardiovasc. Interv. 9, e004088 (2016).
Scarsini, R. et al. Coronary physiology in patients with severe aortic stenosis: comparison between fractional flow reserve and instantaneous wave-free ratio. Int. J. Cardiol. 243, 40–46 (2017).
Petraco, R. et al. Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry. EuroIntervention 9, 91–101 (2013).
Gotberg, M. et al. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N. Engl. J. Med. 376, 1813–1823 (2017).
Scarsini, R. et al. Physiologic evaluation of coronary lesions using instantaneous wave-free ratio (iFR) in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation. EuroIntervention 13, 1512–1519 (2017).
Gregg, D. E. & Sabiston, D. C. Jr. Effect of cardiac contraction on coronary blood flow. Circulation 15, 14–20 (1957).
Downey, J. M. & Kirk, E. S. Inhibition of coronary blood flow by a vascular waterfall mechanism. Circ. Res. 36, 753–760 (1975).
Spaan, J. A., Breuls, N. P. & Laird, J. D. Diastolic–systolic coronary flow differences are caused by intramyocardial pump action in the anesthetized dog. Circ. Res. 49, 584–593 (1981).
Krams, R., Sipkema, P. & Westerhof, N. Varying elastance concept may explain coronary systolic flow impediment. Am. J. Physiol. 257, H1471–H1479 (1989).
Suga, H., Sagawa, K. & Shoukas, A. A. Load independence of the instantaneous pressure–volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ. Res. 32, 314–322 (1973).
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.
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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- 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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