Abstract Background The recommended standard monitoring of patients with non-severe aortic valve stenosis (AS) involves echocardiography surveillance at 1-2 year intervals. Since many of these costly routine echocardiograms yield no clinical consequences during a prolonged watchful waiting period, we propose to replace them with a risk stratification approach. Purpose The primary aim was to validate the ability of ASGARD risk score to a) identify low-risk AS patients who do not need new echocardiography for safe monitoring, and b) estimate optimal follow-up intervals. Methods We have developed the ASGARD risk score using data from 1196/1739 (69%) asymptomatic AS-patients with mild-to-moderate AS who were enrolled in the randomized, multicentre Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. The primary outcome was a composite of AS-related outcomes, aortic valve replacement, or hospitalization with heart failure during a clinically relevant 2-year follow-up. From multivariable Cox proportional hazards regression analyses, we chose the best prognostic model with the lowest Akaike information criterion (AIC) values and p-values <0.05. The risk score included five predictors: age, sex, systolic blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), and last year's measurement of transaortic maximal velocity (Vmax). Kaplan-Meier plot visualized event rates stratified by quartiles of risk score. We validated the ASGARD risk score in an internal validation cohort of 543 patients (31% hold-out from SEAS-population) and an external validation cohort of 69 asymptomatic out-clinic patients with Vmax ≤4 m/s from six hospitals from capital city. Results Patients from the external validation cohort significantly differed from those in the development cohort in terms of higher age (mean [SD], 71.7 [8.5] vs. 67.4 [9.8] years, p<0.001), less prevalent left ventricular hypertrophy (13.0% vs. 37.5%, p<0.001), and higher event-rates (12.5 [95% CI, 7.6-20.8] vs. 4.5 [3.7-5.4] events per 100 patient-years of follow-up, p<0.001). The ASGARD risk score showed consistent predictive performance across the validation cohorts (external validation: area under the curve: 0.82 [95% CI, 0.73-0.91]; calibration-in-the-large, p=0.24; calibration slope, p=0.15; Brier score, 0.18). The score performed just as well or better than a new Vmax measurement (Figure 1A-1B). In the three upper ASGARD score quartiles, 95% of patients had less than 5% risk of AVR or heart failure until 7.5, 16.5, and 22.5 months, respectively (Figure 1C). Conclusion Without a new echocardiogram, the ASGARD risk score identifies patients at low risk for AS-related events among asymptomatic patients with non-severe AS. The ASGARD risk score also estimates the safe watchful-waiting period of 6, 15, 21, and 24 months for the four ASGARD risk score quartiles in decreasing order.Figure 1

By reading this article, you should be able to: •List the common causative organisms and describe the pathophysiology of endocarditis. •Describe the complications and indications for surgery in patients with endocarditis. •Describe the principles underlying diagnosing endocarditis, the limitations of the associated clinical tests and the role of newer diagnostic tools. •List the important steps in preoperative optimisation, perioperative care, and end-organ monitoring and support for patients undergoing endocarditis surgery. Mike Charlesworth MSci PGCert FRCA MSc FFICM is a consultant in cardiothoracic anaesthesia, intensive care and extracorporeal membrane oxygenation (ECMO). He is an editor of Anaesthesia. He has published more than 90 papers in peer-reviewed journals, and his research interests include cardiac anaesthesia, ECMO, research methods, statistics and sustainable healthcare. Brian Williams FRCA FFICM is a consultant in cardiothoracic anaesthesia, intensive care and ECMO at Wythenshawe Hospital. He is clinical lead for the cardiac catheter laboratories, and his clinical interests include structural heart valve disease, endocarditis and perioperative transoesophageal echocardiography. Simon Ray BSc MD FRCP FACC FESC is honorary professor of cardiology in Manchester. His research interests have focused on valvular heart disease, patent foramen ovale and cardiac involvement in patients with neuromuscular disease. He was president of the British Cardiovascular Society in 2018–21 and is cardiology lead for the NHS ‘Getting It Right First Time’ programme.

Abstract Background Routine echocardiography of asymptomatic patients with non-severe aortic valve stenosis (AS) mainly focuses on the valve condition at 1-2 year intervals but has limited ability to predict the risk of other cardiovascular comorbidities. Thus, there is a compelling need to replace routine echocardiography for low-risk patients with more individualized cardiovascular surveillance for a safe period. Aim First, to develop and validate separate risk stratification models for AS-related events (AVE) and major cardiovascular events (MCE) to identify low-risk AS patients who can safely postpone routine echocardiography replaced by tailored risk stratification and adequate risk factor management. Second, to estimate optimal follow-up intervals according to risk stratification for each outcome. Methods We analyzed serial measurements from 69% of 1579 patients with mild-to-moderate AS who were asymptomatic and event-free one year after inclusion in the randomized, multicenter Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We developed two ASGARD risk scores using multivariable Cox proportional hazard regression analyses, designed as landmark analyses starting at year-1 and with a clinically relevant 2-year follow-up. The ASGARD scores estimated the risk of AVE (composite of aortic valve replacement or hospitalization with heart failure) and MCE (composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, and all-cause mortality). We estimated the prognostic models with backward elimination, selecting the lowest Akaike information criterion values and p<0.05. There were 7 predictors for AVE and 6 for MCE among current demographic, electrocardiograms, laboratory data, and echocardiographic measures one year earlier (baseline) (Figures 1A, 2A). We defined optimal follow-up for risk score quartiles at rates ≤5% visualized on Kaplan-Meier plots. We assessed model performance in 31% of patients held out for internal validation. Results ASGARD development models for both AVE and MCE risk demonstrated overall consistent predictive performance in the internal validation cohort, as evidenced by c-statistics, calibration-in-the-large, calibration slope, Brier score, and goodness-of-fit (all p>0.05) (Figure 1B-C, 2B-C). ASGARD predicted AVE risk similar to a new Vmax measurement (area under the curve [95% CI], 0.82 [0.78-0.87] vs. 0.85 [0.82-0.89) (Figure 1B), and MCE risk better than Framingham cardiovascular risk score (0.76 [0.70-0.82] vs. 0.68 [0.62-0.75]) (Figure 2B). The one-year event rates were ≤5% for the 2 lowest risk score quartiles (Figure 1D, 2D). Conclusion The ASGARD risk scores show promise for long-term, individualized cardiovascular surveillance of low-risk patients with non-severe AS without unnecessary echocardiography. Further studies are warranted for external model validation, continuous optimization, and exploring the potential for implementation in clinical practice.Figure 1Figure 2