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In developed countries, the etiology of aortic stenosis (AS) is a process akin to atherosclerosis (Fig. 47–1), wherein the initial lesion is plaque-like with a central core of lipids and macrophages.1 Over time the plaque becomes calcified and in 15% of cases actually contains lamellar bone. The process holds in common many of the risk factors for atherosclerotic coronary disease, including hyperlipidemia, hypertension, and the metabolic syndrome. Approximately 1% to 2% of the population is born with a bicuspid aortic valve (BAV) instead of a tricuspid aortic valve. About one-third of such valves become stenotic, with significant stenosis occurring about one to two decades sooner in bicuspid than in tricuspid valves. Why there is earlier progression in bicuspid valves is uncertain but may be in part genetic in origin and in part as a result of the flow characteristics of bicuspid valves. Because of the resemblance of the AS lesion to that of coronary atherosclerosis, it was postulated that statins, so effective in treating coronary disease, might retard the progression of AS. Unfortunately, three randomized trials failed to show any benefit of statin use in AS when applied to patients with a range of disease severity.2,3,4 On one hand it could be argued that even earlier application of statins would be required to show benefit, or on the other hand, statin failure could be because of the tendency for statins to promote plaque calcification.5 This tendency helps stabilize the coronary plaque, avoiding rupture and subsequent coronary events; conversely this tendency in the aortic plaque might cause decreased leaflet mobility, worsening rather than retarding progression.6 Although statins failed to alter the progression of AS, it is clear that AS is an active disease in which inflammation is involved. As such, many potential therapeutic targets exist. One promising target is lipoprotein(a) (LP(a)), which seems more tightly associated with AS than is low-density lipoprotein (LDL) and which can be dramatically reduced by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. These agents reduce both lipid moieties but are not known to be pro-calcific.7
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In the developing world, rheumatic heart disease is still the most common cause of AS. Other causes include congenital AS and unicuspid and quadricuspid aortic valve.
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Pathophysiology and Its Relationship to Symptoms
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As shown in Fig. 47-2A, depicting the natural history of AS in 1968 and modified by changes in that history over time (Fig. 47-2B), the presence or absence of the classic ...