Clinical Value of Stress Echocardiography in Moderate Aortic Stenosis
Clinical Value of Stress Echocardiography in Moderate Aortic Stenosis
The management of symptomatic patients with moderate Aortic Stenosis (AS) remains challenging
 and tests that would give more definitive answers are needed. The value of increase in Aortic
 Valve mean Gradient (AVMG), lack of change in Aortic Valve area (AVA) and calculation of
 valve compliance/resistance during stress echo (SE) in the symptomatic moderate AS population
 prognostication has to the investigators knowledge not been examined before. Similarly the
 additive value of myocardial blood flow reserve (MBFR), Computed Tomography (CT) calcium
 score, speckle tracking echocardiography, carotid ultrasonography, and N-Terminal pro B- type
 natriuretic peptide B (NT-proBNP) in the prognostication of this population group especially
 in combination with SE remains unclear.
The prevalence of aortic valve stenosis (AS) has increased over the last few decades due to
 improvement in life expectancy and a growing elderly population. A wealth of data is
 available on patients with severe AS, whereas the risk stratification and management of
 patients with symptomatic moderate AS remains contentious.

 Stress echocardiography (SE) is a recognised tool for the risk stratification of patients
 with asymptomatic severe AS. Exercise is the preferred mode of stress in this group, as it
 provides important prognostic information- such as presence of symptoms, overall exercise
 capacity and precipitation of hypotension. Significant increase in mean gradient (MG) (MG
 >20mmHg) is an independent predictor of valve intervention or cardiovascular death, similar
 to older age, diabetes and high resting gradient and this is recognised in international
 guidelines as a parameter to risk stratify asymptomatic severe AS. The increase in MG in the
 context of increasing transvalvular flow during exercise is usually accompanied by little or
 no change in aortic valve area (AVA). Thus, mechanistically, the increase in MG is associated
 with worse outcome because it reflects the intrinsic non-compliance of the aortic valve and
 hence resistance. A compliant valve will open to accommodate the increased flow during
 stress, whereas a fixed valve orifice will not, resulting in increased gradients. It is
 therefore advised that these patients with asymptomatic severe AS and significant increase in
 MG during exercise may be reasonably considered for aortic valve intervention.

 In moderate AS current guidelines recommend Aortic Valve replacement (AVR) only when other
 cardiac surgery (coronary artery bypass grafting) is planned (class IIa). This is because
 patients with moderate AS are a heterogeneous group with regard to the risk of adverse
 events: some have indeed rapid progression to severe AS, and/or Left Ventricular (LV)
 dysfunction and cardiovascular death, whereas others remain stable for many years. Overall
 moderate AS carries a substantial risk of death or valve intervention, with the estimated
 likelihood of event free survival at 4 years being 55-60%. Furthermore the presence of
 symptoms increases the overall likelihood of risk in moderate AS, as there is a significant
 difference in outcome between minimally symptomatic and symptomatic moderate AS. It maybe
 hypothesised that patients with moderate AS and symptoms in the absence of myocardial
 ischaemia due to flow-limiting coronary artery disease likely has the same valve hemodynamics
 as one with severe AS, particularly decreased valve compliance/increased resistance. These
 characteristics are likely to manifest during exercise when transvalvular flow is increased
 resulting in significant increase in gradient with little change in AVA. Accordingly, resting
 AVA and MG may not be the best parameters for determining suitability for valve intervention,
 particularly as the overall mortality of symptomatic moderate aortic stenosis approaches that
 of symptomatic severe AS. However, clear criteria that risk-stratify patients with
 symptomatic moderate AS and guide timing for intervention do not currently exist.

 Accordingly the role of SE could be expanded beyond assessment of risk in asymptomatic severe
 AS to improve risk stratification in patients with symptomatic moderate AS. This is on the
 assumption that moderate AS associated with symptoms of breathlessness, chest pain or syncope
 is likely to have the same characteristics as severe AS. This means that during SE in
 moderate symptomatic AS one would expect the AVA to remain unchanged, the valve resistance to
 be elevated and the MG to increase.

 Furthermore during SE apart from valve related indices that determine severity (AVA, MG),
 myocardial blood flow reserve (MBFR) has been shown to correlate with severity of AS; reduced
 MBFR is seen in severe AS whereas MBFR<1.8 has an accuracy of 85% for distinguishing severe
 from non-severe AS. It could therefore be that MBFR can also contribute in the risk
 stratification of symptomatic moderate AS.

 It has been suggested that several other tests could contribute to the risk stratification of
 AS i.e. CT calcium score, speckle tracking echocardiography, carotid ultrasonography, and
 N-terminal pro-brain natriuretic peptide (NT-proBNP). Specifically it has been shown that
 aortic valve calcium score correlates with AS severity and that there is moderate agreement
 between AVA as defined by American College of Cardiology (ACC) guidelines and the degree of
 AS determined from AV calcium score. Basal and global longitudinal strain (GLS) have been
 found to be independently associated both with the severity of AS and the presence of
 symptoms. Furthermore GLS can predict all-cause mortality in patients with AS and could
 therefore improve the identification of the optimal timing for AV replacement. The severity
 of AS in general has also been shown to correspond to an increase of carotid plaque and
 intima media thickness (IMT). Finally NT-proBNP values correlate with the severity of AS and
 in moderate AS, NT-proBNP can differentiate between symptomatic and asymptomatic status.
Inclusion Criteria:

 -  Age ≥18 years

 -  Moderate AS with AVA between 1-1.4cm2, and AVMG<40 millimetres of Mercury (mmHg); and

 -  Left Ventricular Ejection Fraction (LVEF) ≥50%; and

 -  Cardiac related symptoms; shortness of breath, chest pain or syncope.

 Exclusion Criteria:

 -  Inability to exercise and undertake pharmacological stress, ie previously known
 intolerance to dobutamine;

 -  Severe aortic or mitral regurgitation or severe mitral stenosis;

 -  Significant pulmonary disease like severe (Chronic Obstructive Pulmonary Disease
 (COPD) or pulmonary fibrosis;

 -  Atrial fibrillation;

 -  Inability to provide informed consent;

 -  Pregnancy;

 -  Other known non-cardiovascular disease associated with poor prognosis like metastatic
 cancer.