Development and validation of the Aortic valve Stenosis Guarded by Amplified Risk Determination (ASGARD) risk score for safe monitoring in asymptomatic non-severe aortic valve stenosis

Aims Current guidelines recommend serial echocardiography at minimum 1-2-year intervals for monitoring patients with non-severe aortic valve stenosis (AS), which is costly and often clinically inconsequential. We aimed to develop and test whether the biomarker-based ASGARD (Aortic valve Stenosis Guarded by Amplified Risk Determination) risk score can guide the timing of echocardiograms in asymptomatic patients with non-severe AS. Methods and results The development cohort comprised 1093 of 1589 (69%) asymptomatic patients with mild-to-moderate AS who remained event-free one year after inclusion into the SEAS trial. Cox regression landmark analyses with a 2-year follow-up identified the model (ASGARD) with the lowest Akaike information criterion for association to AS-related composite outcome (heart failure hospitalization, aortic valve replacement, or cardiovascular death). Fine-Gray analyses provided cumulative event rates by ASGARD score quartiles. The ASGARD score was internally validated in the remaining 496 patients (31%) from the SEAS cohort and externally in 71 asymptomatic outpatients with non-severe AS from six Copenhagen hospitals. The ASGARD score comprises updated measurements of heart rate and age- and sex-adjusted N-terminal pro-brain natriuretic peptide upon transaortic maximal velocity (Vmax) from the previous year. The ASGARD score had high predictive accuracy across all cohorts (external validation: area under the curve: 0.74 [95% CI, 0.62-0.86]), and similar to an updated Vmax measurement. An ASGARD score <= 50% was associated with AS-related event rates <= 5% for a minimum of 15 months. Conclusion The ASGARD score could provide a personalized and safe surveillance alternative to routinely planned echocardiograms, so physicians can prioritize echocardiograms for high-risk patients.