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Aortic stenosis is the major cause of valve disease in the Western world and a growing healthcare burden. We lack medication capable of slowing disease progression and so rely on aortic valve replacement in patients with severe disease and symptoms. Predicting when this will occur is challenging with the literature suggesting on average slow progression with wide individual variation (rate of change in the mean gradient of ∼3±3 mm Hg/year). Annual or biannual clinical review is therefore required in all patients with serial echocardiography performed in order to track progressive valve narrowing.1 This incurs significant costs and a method capable of predicting the future natural history of aortic stenosis and the likely timing of valve surgery could help streamline patient care.
It is on this background that Nguyen et al2 investigated whether an association exists between baseline aortic stenosis severity and the rate of disease progression. In 149 patients with largely mild and moderate disease, the average rate of haemodynamic progression after a mean follow-up of 2.9±1.0 years was again +3±3 mm Hg/year (mean gradient). As anticipated the fastest rates of progression were observed in those patients with the most advanced aortic stenosis (mild +2±3 mm Hg/year, moderate +4±3 mm Hg/year, severe +5±5 mm Hg/year), indicating that disease progression appears to accelerate with time but that once again this can vary considerably between patients. Although the number of patients in the severe group was small and individual patients were not tracked from mild to moderate to severe disease, the authors do quite reasonably argue that their data support current guidelines recommending serial scanning in all patients and closer follow-up in the latter stages of the disease process.
Perhaps the most interesting aspect of the study is the identification of disease progression using CT calcium scoring. CT calcium scoring has emerged over recent years as an alternative assessment of aortic stenosis severity. While echocardiographic techniques aim to measure the haemodynamic consequence of progressive valve stiffening and narrowing, CT adopts a different approach. Instead it simply measures the burden of calcium within the valve: the aortic valve CT calcium score, expressed in Agatston units (AU), providing a simple anatomical measure of disease severity. This approach has several potential advantages, not least its independence from cardiac loading conditions and the effects of other disease states such as concomitant valve disease, LV dysfunction and hypertension. Until recently we lacked clear thresholds that might differentiate patients with severe and moderate disease. However, following a series of observational studies, we now have sex-specific disease thresholds for men (2065 AU) and women (1275 AU) that appear of potential use in adjudicating disease severity when echocardiographic measures are discordant, and provide powerful prognostic information independent of other standard markers.3–5 The present study builds upon these recent advances, demonstrating that similar to the echocardiographic measures, disease progression as measured by CT calcium scoring increases fastest in those with the most advanced disease (mild +141±113 AU/year, moderate +279±189 AU/year and severe +361±293 AU/year). Moreover compared with the relatively small changes observed with the echocardiographic measures, large increases in the CT calcium score were observed particularly among those with moderate and severe disease. Given the good reproducibility of aortic valve CT calcium scoring,6 this technique might therefore represent a more sensitive means of tracking disease progression than echocardiography. Further work is however required to validate the proposed severity thresholds in independent populations and to explore further the correlations and comparability with haemodynamic measures obtained by echocardiography. It will be particularly important to investigate the haemodynamic effects of the regional distribution of calcium within the valve as topographic differences may have differential consequences for valve mobility and rigidity. Independent of calcification, it will also be important to explore the role of valve fibrosis as this is currently not quantified by either CT or echocardiography.
What then is the explanation for the more rapid rates of disease progression observed with increasing disease severity in this study? One potential explanation is that once established, calcification in the valve proceeds independently from the lipid and inflammatory processes that initiated it. Indeed a self-perpetuating cycle of calcification, altered mechanical stress, valve damage and further calcification may occur in a positive feedback loop (figure 1). In this model, valvular calcium would therefore induce further calcification, ensuring that disease activity and progression increase steadily as aortic stenosis advances. This hypothesis is supported by recent positron emission tomography studies measuring calcification and metabolic activity in the valve7 ,8 and provides an explanation for why even the simplest measures of disease severity and calcium burden offer such powerful prediction of events and progression in aortic stenosis. Regardless of the mechanism, Nguyen et al have provided an important insight into the pathophysiology of this condition: that aortic stenosis begets aortic stenosis and that disease progression will tend to accelerate with time. Our next challenge is to discover how we might break the apparently self-perpetuating cycle driving this phenomenon and develop the medical therapies that are so urgently required for this ubiquitous condition.
Contributors All the authors have helped draft the manuscript and accompanying figure.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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