Perspective:

Evaluation for aortic valve replacement (AVR) is indicated among patients with severe aortic stenosis (AS) and symptoms of angina, heart failure, or syncope. The risk of sudden cardiac death is perceived to be low among patients with truly asymptomatic severe AS, leading to a historical recommendation of conservative management. Most studies of the natural history of asymptomatic severe AS suggest a rate of sudden death of 1-3% per year, whereas recent data from the Society of Thoracic Surgeons suggest that the risk of isolated surgical AVR is between 3% and 4%. However, emerging data suggest that certain markers might identify asymptomatic patients at increased risk of cardiac events. This review is an appraisal of the identified prognostic markers that have been identified among asymptomatic patients with severe AS, and attempts to evaluate how these markers might be used to identify patients who might benefit from earlier surgical intervention. Notably, although multiple studies have identified a variety of variables associated with increased risk, data are lacking that a more aggressive approach in those patients results in mitigation of risk.

Ten points to remember are:

1. Calcification. Moderate or heavy calcification of the aortic valve on echocardiography has been associated with increased risk. Aortic valve calcification score on electron beam computed tomography (CT) has been associated with calcification on echocardiography, and with the severity of AS.

2. Jet velocity. A jet velocity >4.0 m/s has been associated with an increased rate of cardiac events. Jet velocities >5.0 and >5.5 m/s have been associated with incrementally higher risk.

3. Left ventricular (LV) architecture and function. Inappropriately high LV mass (>110% of that expected for body size, sex, and wall stress) has been associated with increased risk.

4. LV systolic function. LV ejection fraction is an imperfect marker of LV myocardial systolic function; however, reduced LV ejection fraction is associated with a poor prognosis. Strain and strain rate have been used to assess LV systolic function. Although the techniques are limited by substantial inter-and intra-observer variability, strain and strain rate have been correlated with AS severity, and impaired longitudinal strain has been correlated with worse clinical outcomes.

5. LV diastolic function. Neither transmitral E-wave to A-wave ratio nor tissue Doppler parameters of LV diastolic function has been shown to correlate with symptom onset or with prognosis. However, increased left atrial size has been associated with a worse prognosis.

6. Myocardial fibrosis. The degree of myocardial interstitial fibrosis identified on cardiac magnetic resonance (CMR) imaging has been found to correlate with that found by histopathological examination among patients with severe AS who underwent AVR, and the degree of myocardial fibrosis has been shown to correlate with worsening class and with impaired LV systolic function. However, no studies to date correlate myocardial fibrosis on CMR to the risk of sudden death in asymptomatic patients.

7. Stress testing. Exercise testing is useful to unmask symptoms in patients who might fail to report them spontaneously (due to denial or due to alteration of lifestyle to avoid symptoms). An increase in aortic valve gradient on exercise echocardiography also might have incremental prognostic power for predicting risk.

8. B-type natriuretic peptide (BNP). BNP is higher among symptomatic compared to asymptomatic patients with severe AS, and higher BNP also has been correlated with subsequent development of symptoms. In some patients, elevated BNP can help in ascribing symptoms to AS or to another etiology. A risk score based on a small cohort of patients uses both aortic valve peak velocity and BNP to assess risk:

Risk score = (2 x V_max [m/s]) + (1.5 x ln [BNP]) + 1.5 (if female)

9. Combined valvular and systemic load. Prognosis among patients with AS appears to be affected by both the severity of AS and systemic vascular resistance (which is related to blood pressure). Valvulo-arterial impedance (Z_va, calculated as estimated LV systolic pressure [systemic arterial pressure – mean transvalvular gradient] / stroke volume index) addresses both factors; Z_va ≥4.9 mm Hg/ml/m² has been associated with a worse prognosis among patients with AS.

10. Clinical algorithm. The authors provide an algorithm for the management of asymptomatic patients with severe AS. Patients should undergo valve replacement if there is a low LV ejection fraction (<50%) or other cardiac disease requiring surgical intervention. Among others, exercise testing is advocated, with referral for surgery if symptoms are elicited during testing. Among those who remain asymptomatic during exercise testing, surgical referral could be considered based on perception of high likelihood of rapid progression, change in peak velocity ≥0.3 m/s per year, “very severe” AS (V_max >5 m/s, mean gradient >60 mm Hg, valve area <0.6 cm²), excessive LV hypertrophy (≥15 mm), or either a drop in blood pressure or complex ventricular arrhythmia during exercise testing.