Insights into aortic stenosis progression: factors affecting rate of progression and its impact on survival
Authors: Amanullah M.R , Pio S.M , Sin K.Y , Ajmone Marsan N , Ding Z.P , Delgado V , Ewe S.H , Bax J.J 
Published: November 2020

Abstract

Background
Severe aortic stenosis (AS) is associated with adverse clinical outcomes. Little is known about the rate of progression in patients with moderate AS.

Purpose
Risk factors affecting the rate of progression from moderate to severe AS, and their impact on all-cause mortality were studied in this multicentre registry.

Methods
Based on the echocardiographic diagnosis of moderate AS (valve area &gt;1.0 and ≤1.5 cm2) at the time of first echocardiogram, 962 patients with follow-up were included. Follow-up echocardiograms were reviewed to identify those who developed severe AS (based on the current guidelines). Patients were divided into 2 groups: AS Progressors (progressed to severe AS) and Non-progressors (remained in moderate AS). Among those with AS progression, patients were subdivided into Slow versus Fast Progressors, according to the median time interval between the two echocardiograms. The clinical correlates of fast AS Progressors were analysed using the binary logistic regression. The association between rate of progression (slow versus fast) and all-cause mortality was assessed by the Kaplan-Meier method using log-rank test. A multivariate Cox proportional analysis was used to identify the independent associates of all-cause mortality, with interval of AS progression between the two echocardiograms (in years) included as a continuous variable.

Results
Of the 962 patients with moderate AS, AS progressed to severe in 62% (n=595), while 38% (n=367) remained in moderate AS, over a mean follow-up of 6.8 [IQR 4.2–9.3] years. Older age, renal impairment (eGFR&lt;30ml/min/1.73 m2), hypertension and atrial fibrillation were significantly associated with higher risk of AS progression. Left ventricular (LV) hypertrophy and higher peak aortic velocity were more prevalent in AS Progressors at baseline. Among the AS Progressors (n=595), the median time of AS progression was 2.5 [IQR 1.3–3.9] years. Based on the median time of AS progression, patients were subdivided into: Slow (n=295) versus Fast Progressors (n=300). On multivariate analysis, age, renal impairment (eGFR&lt;30ml/min/1.73 m2), betablocker use, impaired LV ejection fraction and peak aortic velocity were significantly associated with Fast progression of AS. Although the rates of AV intervention were similar between Fast versus Slow Progressors (60% vs. 54%, p=0.137), Fast AS Progressors had worse survival than Slow AS Progressors (Log rank p=0.045, Figure 1), over a mean follow-up of 4.0 [IQR 1.0–6.4] years. Importantly, on multivariable Cox proportional analysis, shorter time of progression from moderate to severe AS was independently associated with increased all-cause mortality (HR=0.92, 95% CI 0.88–0.99, p=0.047).

Conclusion
In a large real-world registry of patients with moderate AS, fast progression to severe AS is associated with worse survival. Close surveillance should be given to those patients who are at higher risk of AS progression.
AS progression and all-cause mortality

Funding Acknowledgement
Type of funding source: None