The observations that some asymptomatic patients with severe aortic stenosis (AS) may be at higher risk, and that outcomes associated with surgical (SAVR) and transcatheter aortic valve replacement (TAVR) have progressively improved raise the question of whether current indications for AVR that rely on symptoms and/or left ventricular (LV) systolic dysfunction should be reassessed. This review addresses early risk features associated with asymptomatic severe AS in an attempt to help inform management. The following are key points to remember:

1. 1. Echocardiography/Doppler continue to provide important data regarding disease severity and progression.
   • - Peak velocity (<3 m/s, 3-4 m/s, >4 m/s, and >5 m/s [very severe AS]) is a robust prognostic marker in AS.
   • - Rapid progression of AS, defined as an increase in jet velocity >0.3 m/s/year in the setting of moderate or severe aortic valve calcification, is associated with an increased rate of symptom development and mortality.
   • - Valvuloarterial impedance (a measure of combined valvular and vascular afterload) >5 mm Hg/ml/m² also is a marker of poor clinical outcome.
   • - Although current guidelines use a threshold LV ejection fraction (EF) <50% to define LV systolic dysfunction and an indication for intervention, data suggest that patients with LVEF 50-59% experienced less favorable outcomes and more heart failure-related deaths than did patients with LVEF ≥60%.
   • - Reduced LV global longitudinal strain is an early marker of impaired LV contractile function, and in one meta-analysis was associated with increased mortality.
   • - Increased left atrial size, reduced mitral annular systolic (s’) and late diastolic velocities (a’), and the presence of pulmonary hypertension are associated with worse outcomes.
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2. 2. Exercise testing is contraindicated among symptomatic patients with severe AS, but should be considered (after a careful history) among asymptomatic patients to unmask symptoms and evaluate for an abnormal blood pressure response, both indications for AVR. However, the predictive value of the test is lower in older patients.
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4. 3. A recently described staging classification for patients with severe AS based on the involvement of no extravalvular cardiac damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), or right ventricular damage (stage 4) was associated with 1-year all-cause death and cardiac death (Genereux P, et al., Eur Heart J 2017;38:3351-8). However, this requires prospective validation.
   • - Blood biomarkers may be helpful for the assessment of prognosis, but require additional validation.
   • - Elevated natriuretic peptide levels reflect the adaptive versus maladaptive nature of LV hypertrophy, and have been associated with outcomes.
   • - Elevated high-sensitivity troponin I (hs-TnI) allows detection of low-level myocyte death and injury, and may help assess cardiac compensation.
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5. 4. Cardiac magnetic resonance imaging (CMR) can be used to assess LV replacement fibrosis. A pattern of mid-wall late gadolinium enhancement (LGE) has been used as a powerful and “dose-dependent” prognostic marker among patients with AS.
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7. 5. Clinical trials are being used to assess whether clinical outcomes can be improved through earlier intervention among asymptomatic patients with severe AS.
   • - The EARLY TAVR (Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis) trial is a prospective, randomized, multicenter study enrolling 1,109 asymptomatic patients ≥65 years of age with severe AS and LVEF >50%, most of whom will undergo a low-level stress test to confirm the absence of symptoms. Patients will be randomized to TAVR versus active surveillance, with a primary composite endpoint at 2 years (powered for superiority) of all-cause death, all stroke, and unplanned cardiovascular hospitalization.
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   • - A substudy of the EARLY TAVR trial will assess biomarkers in both randomized arms in an attempt to provide insight into a potential utility of biomarker-driven early intervention.
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   • - The EVOLVED (Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients With Severe AS) study is a multicenter, randomized trial investigating whether elevated hs-TnI, ECG strain, and CMR for mid-wall LGE can help predict outcomes among patients randomized to undergo early TAVR or SAVR versus standard watchful waiting, with a primary composite endpoint of all-cause death or unplanned AS-related hospital admission.