Mixed Aortic Valve Disease: A Double Trouble

Despite the relatively high prevalence of mixed aortic valve disease, i.e. combined aortic stenosis (AS) and aortic regurgitation (AR), there is very little data on the outcome and management of this entity. Indeed most previous studies that have examined the outcome of patients with AS generally excluded those with concomitant AR, and vice versa. Furthermore, the presence of concomitant AR may interact with the quantitation of AS severity, and vice versa. In a recent nationwide epidemiology study conducted in Sweden, multiple valvular heart diseases represented 10.4% of all valvular disease cases and mixed aortic valve disease accounted for 18.7% of multiple disease cases. In the elegant study published in this issue of Structural Heart, Sorajja et al. retrospectively analyzed the data of 308 asymptomatic patients with moderate or severe AS and compared outcomes according to the presence and severity of concomitant AR. For patients with moderate AS, the 4-year survival free of death, cardiac symptoms, or aortic valve replacement (AVR) was 47.1%, 30.9%, and 29.0% for none, mild, and moderate/severe AR, respectively (p = 0.02) and this association remained significant after adjustment for morbidities in multivariable analyses. Mild AR and moderate/severe AR were, respectively, associated with a 1.8and 2.0-fold increase in the risk of adverse events in asymptomatic patients with moderate AS. On the other hand, concomitant mild or moderate/severe AR was not significantly associated with increased risk of death, symptoms, and AVR in asymptomatic patients with severe AS. This latter finding is consistent with the study by Egbe et al. where asymptomatic patients with moderate/severe mixed aortic valve disease had similar outcomes compared to those with isolated severe AS. Hence the main message of the present article by Sorajja et al. is that the presence of concomitant AR increases the risk of progression to symptoms and need for AVR in patients with moderate AS but not in those with severe AS. That asymptomatic patients with severe AS have comparable long-term outcomes regardless of AR severity may appear, at first glance, counter-intuitive. This intriguing finding may be related to the fact that once AS has reached the severe stage, it becomes the main determinant of outcomes and thereby occults the effect of concomitant AR. In fact, the 4-year event-free survival rate was low (~ 30%) and similar in patients with severe AS and no AR versus those with moderate AS and moderate/severe AR. Hence, the addition of a moderate/severe AR, or even a mild AR, to a moderate AS yields to outcome similar to that of isolated severe AS. On the other, the addition of AR to a severe AS does not appear to change the natural evolution of the disease. Even if not statistically different, the patients with severe AS and moderate/ severe AR, nonetheless, harbored numerically lower event-free survival rates compared to those with severe AS and no AR. The concomitance of severe AS and moderate/severe AR may thus increase the risk of symptoms onset and AVR in some patients. However, in the majority of asymptomatic patients with severe AS, the additional hemodynamic burden related to concomitant AR is likely occulted by the severe AS and does not alter the time to AVR in these patients. Another intriguing finding of this study is that, in patients with asymptomatic moderate AS at baseline, a mild AR has a significant negative impact on outcomes (adjusted hazard ratio for events: 1.8), which is almost as bad as moderate/severe AR (adjusted hazard ratio: 2.2). This may be related to the fact that patients with moderate/severe AS often develop left ventricular (LV) concentric hypertrophy and advanced diastolic dysfunction with reduced LV compliance. In the present study, the vast majority of the patients indeed harbored LV concentric remodeling or hypertrophy with relatively small LV cavities at baseline; LV diastolic function was not reported. Hence, the left ventricle of these patients with AS is primarily adapted to pressure overload and may thus not be able to tolerate an even mild aortic regurgitant volume.