Looking beyond the calcium on the aortic valve in aortic stenosis

This editorial refers to the article ‘Mitral annular calcification in severe aortic stenosis: prognostic value of calcification severity and mitral valve dysfunction’, by P. Vanhaecke et al.,1 https://doi.org/10.1093/ehjci/jeaf214. Mitral annular calcification (MAC) has long been established as a prevalent phenomenon in the ageing population, especially in patients with pressure overload conditions as aortic stenosis (AS) with a prevalence up to 65%,2–7 and with a three-fold increase in severe mitral stenosis compared with patients with isolated MAC.8 While several studies have focused on the prognostic importance of MAC and MAC-related mitral valve disease (MVD) in general,3,4,7,9–11 the potential implications of MAC in the management of patients with severe AS is still debatable. In to a paucity in data, this partly reflects the lack of consensus as how to diagnose and grade MAC, resulting in multiple definitions of MAC severity.5,6,9,10 In this issue of European Journal of Cardiovascular imaging, Vanhaecke et al. present the results from a single-centre observational retrospective study assessing the prevalence and prognostic impact of the presence and severity of MAC and MAC-related MVD assessed by echocardiography in 613 patients with severe AS. During the 6 years follow up period, 37.2% underwent aortic valve replacement (AVR) [11.7% surgical and 25.4% transcatheter AVR (TAVR)]. The authors should be congratulated conducting this important study and providing data on a not very well elucidated subject. The high prevalence of MAC in this study is not surprising as it aligns with existing data from AS patients referred for TAVR.2–7 Despite defining severe AS as aortic valve area (AVA) < 1.0 cm2 or indexed AVA < 0.6 cm2/m2 regardless of transvalvular gradients, and thus including 22% patients with potentially moderate AS, the rate of MAC was 50%, delineating the importance of understanding the coexistence of these two conditions in depth. Patients with severe MAC had lower aortic mean gradient and higher Doppler velocities indexes suggesting a bias in the severity of AS in MAC subgroups. Still, the presence of MAC associated with a higher cardiovascular comorbidity burden and emerged as an important predictor of all-cause mortality, even after adjustment for well-known cardiovascular risk factors (hazard ratio = 1.23 [1.02–1.66]). Interestingly, mild and moderate MAC, in contrast to severe, shared similar outcomes, probably reflecting the difficulties in graduating MAC. The current paper utilized the method suggested in a recent position paper,10 in which mild MAC is defined as 270° of the mitral annulus. While it is reassuring that the reproducibility of this method is excellent with a Kappa statistics of 0.93, assessment of calcium by echocardiography can be difficult as it may be unable to reliably differentiate calcium from fibrosis with the possibility of echocardiography overestimating the degree of MAC. In this regard, computed tomography is considered to be the gold standard with lower inter-observer variability,2,6–8 and multimodal imaging may thus be essential when graduating MAC. Still, echocardiography provides essential measures of the impact of MAC on valvular function, that not only is dependent on the percentage of calcified annulus,6 and which seems to be the most important prognostic factor in patients with MAC, as a transmitral mean gradient ≥ 5 mmHg associated with a poor prognosis in patients regardless of MAC. This finding is in line with several retrospective cohort studies were even lower cut-off of mean transmitral gradient ≥ 3 mmHg have been demonstrated to be strongly associated with all-cause mortality.11,12 However, the proportion of significant MVD was relative high (20.7%) taking the prevalence of severe MAC (8.2%) in to consideration, suggesting that non-MAC-related MVD patients also were included, potentially overestimating the prognostic impact of MAC-related MVD. Furthermore, patients referred to AVR had a better prognosis than those treated conservatively, emphasizing that AVR may be beneficial in the setting of MAC, in particular when MAC is mild or moderate as suggested by others.13 However, it is well established that patients with AS not referred for AVR have a worse prognosis; reflecting frailty, patient and physician choices etc. It is thus possible that the better outcome in patients referred for AVR reflects referral bias, and immortal time bias rather than a true effect. Subsequently, with the study not able to provide information on how many patients developed symptoms without being referred for AVR, or if symptoms improved after AVR among those with MAC, the paper is not able to provide a clear response as to how much patients with concomitant MAC and MAC-related MVD benefit from AVR. Despite of the inherent limitations due to study design including the formally heterogeneous group of patients with severe AS, the paper of Vanhaecke et al. provides important information on the prognostic value of MAC and MAC-related MVD and adds yet another piece to the puzzle of how to treat patients with AS and MAC. Jordi Sanchez Dahl (Conceptualization [lead]; Methodology [lead]; Writing—original draft [lead]; Writing—review & editing [lead]), and Camilla Engelsgaard (Conceptualization [equal]; Writing—original draft [equal]; Writing—review & editing [equal]) Data sharing is not applicable to this article as no new data were created or analysed in this study.