Moderate aortic stenosis: a new actor has come into stage

J Thorac Dis 2020;12(11):7064-7068 | http://dx.doi. org/10.21037/jtd-2020-48 It is well established that patients with severe aortic stenosis (AS) have a poor prognosis once symptoms develop. European and American guidelines both recommend surgical (SAVR) or transcatheter (TAVR) aortic valve replacement in severe AS in the presence of symptoms or left ventricular systolic dysfunction, defined as a left ventricular ejection fraction (LVEF) <50% (1,2). However, controversy still exists regarding the optimal timing of intervention in asymptomatic patients with severe AS, as several studies have shown that even truly asymptomatic patients based on an exercise test can have an increased risk of adverse events. Significant advances in SAVR and TAVR made in recent years have paved the way for large randomized trials that are currently evaluating the potential benefits of an early intervention in asymptomatic patients with severe AS (AVATAR, EvolVeD, ESTIMATE, EARLY-TAVR). Pending the results of these trials, staging the AS based on the evaluation of cardiac structural and hemodynamic changes as a whole, integrating information from rest and exercise echocardiography, cardiac magnetic resonance imaging (CMR) and biomarkers profile, can provide additional clues to the better understanding of the severity of the disease (3-5). In recent years, several small studies have shown that mild and moderate AS was not a benign disease, as initially envisioned, being associated with an increased incidence of cardiovascular events (6). As an example, Delesalle et al. reported an increased mortality rate (47%±3%) at 6 years of follow-up in patients with moderate AS and preserved LVEF (7). Patients with moderate AS and LV dysfunction appeared to have an even worse prognosis, with a 61% risk of adverse events (death, aortic valve replacement and heart failure hospitalization) at 6 years (8). In the HAVEC registry, concerning a larger cohort of patients with moderate AS, Lancellotti et al. reported a 2-, 4-, and 8-year survival rate of 94%±1%, 89%±2%, and 78%±4%, respectively. Independent determinants of cardiovascular mortality were body surface area, dyslipidemia, peak aortic jet velocity, LVEF and aortic valve intervention. A peak aortic jet velocity >3.5 m/s and a LVEF <60% were the predicting cut-off points associated with a worse outcome (9). A recent study by Strange et al. appraised the shortand long-term outcome of more than 240,000 patients with mild, moderate and severe AS form the National Echocardiography Data of Australia (NEDA) registry (10). In this study, there was a significant and gradual increase in the risk of long-term mortality from mild to severe AS (adjusted hazard ratio from 1.44 to 2.09), supporting the consideration of AS as a disease continuum. But perhaps the most important observation from this trial was that, while the risk of long-term death in patients with mild AS was close to the risk observed in patients without AS, the risk of death in patients with moderate AS was close to that seen in patients with severe AS (5-year mortality of 56% and 67%, respectively). In addition, the authors observed a marked increase in the risk of death from all causes and cardiovascular disease once the mean AV gradient was >20 mmHg, even after adjustment for age, sex, LV systolic or diastolic dysfunction, and aortic regurgitation (10). The question that comes to our mind is why these Editorial Commentary