Transaortic flow rate to predict short and long term outcomes in individuals with asymptomatic aortic stenosis
Authors: Pallikadavath S , Greenwood J P , Berry C , Dawson D K , Hogrefe K , Kelly D J , Lang C C , Khoo J P , Springings D , Steeds R P , McCann G P , Singh A 
Published: October 2022

Abstract

Background
Echocardiographic derived transaortic flow rate (TFR), defined as stroke volume over left ventricular ejection time, has been shown to be associated with increased mortality in asymptomatic mild to severe aortic stenosis (AS) and superior to stroke volume index (SVi) in individuals with symptomatic discordant AS undergoing aortic valve replacement. However, TFR has not been explored alongside SVi in asymptomatic moderate to severe AS, who are a group of interest in risk stratifying for early intervention. Moreover, there is no data where TFR is indexed to body surface area (TFRi).

Purpose
We explored the prognostic value of TFR, TFRi and SVi in a homogenous cohort of asymptomatic patients with moderate to severe AS.

Methods
Subjects with asymptomatic moderate to severe AS were prospectively recruited to the Prognostic Importance of Microvascular Dysfunction in asymptomatic patients with AS (PRIMID) study, a multi-centre observational study in the UK conducted between April 2012 and November 2014. All subjects underwent extensive phenotyping with transthoracic echocardiography, bicycle exercise testing and cardiovascular magnetic resonance (CMR) imaging, with blinded core-lab analysis. Patients were followed up in person for a minimum of 12 months, and through health records thereafter. The composite outcome of interest was: cardiovascular mortality, AVR for symptoms and major adverse cardiovascular events (hospitalisation with heart failure, myocardial infarction, syncope and arrhythmia) at one-year and at five years. A cox proportional hazards model was used to calculate a hazard ratio (HR) and 95% confidence intervals (95% CI). Known co-variables associated with the composite outcome were added into the multivariable model.

Results
Overall, 173 individuals were included with a mean age of 66.3—-±13.3 years and 76.4% were male. Most individuals had severe AS (71.1%, n=123). There were 47 (64.4%) primary outcome events at one-year and 110 (63.6%) events at five-years. Age, sex, N-terminal pro brain natriuretic peptide (NT-pro-BNP), peak aortic velocity (AV Vmax), a positive exercise tolerance test (ETT), myocardial perfusion reserve and right ventricular ejection fraction measured on cardiac magnetic resonance were included in the multivariable model in addition to TFR or TFRi or SVi. Decreasing TFR and TFRi remained independently associated with one-year and five-year composite outcome (Figure 1). However, SVi was only associated with the composite outcome at five-years. AV Vmax (HR: 4.36, 95% CI: 2.59, 7.34, p&lt;0.01) and a positive ETT (HR: 1.87, 95% CI: 1.03, 3.37, p=0.04) were independently associated with the primary outcome at one-year.

Conclusion
Both TFR and TFRi have a potential role in risk stratifying asymptomatic patients with AS and identifying those for earlier intervention, and may be superior to SVi. However, further prospectively designed studies are needed before this becomes part of the routine clinical practice.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Independent research from a Post-Doctoral Fellowship supported by the National Institute for Health Research (NIHR-PDF 2011-04-51 Geral P McCann).