Aortic valve area in aortic stenosis in adults

INTRODUCTION — In adults with normal aortic valves, the valve area is approximately 3.0 to 4.0 cm². As aortic stenosis (AS) develops, minimal pressure gradient is present until the orifice area becomes less than half of normal. The pressure gradient across a stenotic valve is directly related to the valve orifice area and the transvalvular flow [1]. As a result, in the presence of a depressed stroke volume, relatively low pressure gradients can be seen in some patients with severe stenosis (see "Clinical manifestations and diagnosis of low gradient severe aortic stenosis"). On the other hand, during exercise or other high flow states, relatively small systolic impulse-gradients can be measured in patients with minimally stenotic or even normal valves [2].

Complete assessment of the degree of AS requires:

●Measurement of the transvalvular flow

●Determination of the magnitude and duration of the transvalvular pressure gradient

●Calculation of the aortic valve area

There is considerable variability in the relationship between the severity of stenosis and symptom onset. In general, however, symptoms are more common in patients with AS when the valve area is <1.0 cm² (table 1). (See "Natural history, epidemiology, and prognosis of aortic stenosis".)

This topic will review the methods for calculating the aortic valve area, valve resistance, energy loss, and other parameters that reflect severity of stenosis in patients with AS. The 2020 American College of Cardiology/American Heart Association guidelines emphasize transvalvular velocity, pressure gradient, and valve area [3]. A discussion of the use of echocardiography in the evaluation of AS is presented separately. (See "Echocardiographic evaluation of the aortic valve" and "Transesophageal echocardiography in the evaluation of aortic valve disease".)

ECHOCARDIOGRAPHY — Transthoracic echocardiography (TTE) is indicated in patients with signs or symptoms of AS for diagnosis of the cause of AS, assessment of the severity of AS, and evaluation of left ventricular size and function (table 2) [3]. The severity of AS can be adequately assessed by TTE in nearly all patients, though severity of AS may be underestimated if image quality is poor, particularly if Doppler recordings are not well aligned with the aortic valve jet.

Doppler echocardiography

Pressure gradient — The transvalvular pressure gradient and valve area may be derived using Doppler echocardiography (movie 1 and waveform 1 and image 1A-B) (see "Echocardiographic evaluation of the aortic valve" and "Transesophageal echocardiography in the evaluation of aortic valve disease"). Transvalvular pressure gradient estimation utilizing the simplified Bernoulli equation demonstrates a high correlation with direct pressure measurement [4,5]:

where ΔP = maximum pressure gradient between the left ventricle and the aorta (mmHg), V_AV = maximum stenotic jet velocity (m/s), and V_OT = left ventricular outflow tract (ie, subvalvular) velocity. In practice, the minimal contribution of left ventricular outflow tract velocity (V_OT is usually ≤1 m/s) is ignored, and the expression simplifies to:

This is the maximum instantaneous pressure gradient (mmHg) and should not to be confused with the so-called peak-to-peak gradient obtained during cardiac catheterization. The mean Doppler-derived pressure gradient correlates highly with the catheter-derived mean value. (See "Principles of Doppler echocardiography".)

Occasionally, eccentric stenotic jets limit accurate recording despite meticulous technique, possibly leading to underestimation of the true gradient. On the other hand, overestimation of the gradient may result from:

●Mistaken jet (eg, mitral regurgitation).

●Failure to consider subvalvular velocities (eg, in hypertrophic obstructive cardiomyopathy).

●Nonrepresentative jet selection (eg, a postextrasystolic beat).

●Downstream pressure recovery (which is seldom a significant factor with native valves and a normal sized aortic root).

Aortic valve area by continuity principle — Doppler velocities may also be directly applied to an estimation of aortic valve area by the continuity principle. Simply stated, flow volume (Q) measurements at proximate sites in a closed system (such as the heart) should be identical:

where A_OT = area of the left ventricular outflow tract, V_OT = peak velocity in the outflow tract, AVA = area of the stenotic aortic valve, and V_AV = maximum velocity across the aortic valve. The effective orifice area of the stenotic valve can therefore be calculated after simple equation rearrangement:

Some experts prefer use of the left ventricular and aortic time-velocity integrals over that of the peak velocities (TVI_OT = time velocity integral across the outflow tract and TVI_AV = time velocity integral across the aortic valve) [6]:

Doppler-derived effective valve orifice area in AS increases during ejection due to the increase in transvalvular flow, although the valve may remain open for a shorter period compared with that seen in normal individuals [7,8]. Effective orifice area also changes with physiologic changes in transaortic flow rate, as occurs with exercise. Measurement of this change in valve area may be helpful in the assessment of symptom onset and in the evaluation of low output AS [9].

The continuity equation may be expected to be less susceptible to flow variation because the empiric constant of the Gorlin formula is avoided. Similarly, use of Doppler-derived aortic valve resistance should be relatively free of the influence of variations in flow [10]. This hypothesis was confirmed by a study in which Doppler echocardiographic variables were measured at baseline and during an infusion of low dose dobutamine [11]. In another report, it was shown that acute changes in transvalvular flow do not alter the planimetered valve area obtained with transesophageal echocardiography [12].

However, the degree of flow dependence may be related to the structural characteristics of the valve. As an example, one study reported that more flow dependence was associated with tricuspid valves and those with morphologic features of calcific AS while less flow dependence was seen with bicuspid valves and those with features of rheumatic disease [13].

The severity of stenosis may be underestimated in patients with left ventricular dysfunction and low-output states if assessment is based only on the peak velocity and mean gradient; the Doppler-derived valve area must be taken into consideration. (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)

Doppler-derived velocities have been used to evaluate the function of prosthetic heart valves. One study reported that application of the continuity equation and valve resistance provided a reliable method to distinguish whether a high velocity and gradient across a St. Jude aortic valve was secondary to obstruction or increased flow, such as may be seen with paravalvular aortic regurgitation [14]. Parameters that differentiated stenotic from regurgitant and normal valves were the effective orifice area, mean gradient, Doppler velocity index, time to peak velocity, and valve resistance [15]. (See "Overview of the management of patients with prosthetic heart valves" and "Mechanical prosthetic valve thrombosis or obstruction: Clinical manifestations and diagnosis".)

Aortic valve resistance — Aortic valve resistance can be calculated noninvasively using Doppler echocardiography based upon the following equation:

The value of calculating aortic valve resistance was evaluated in a study of 407 patients with AS who underwent Doppler echocardiography prior to valve replacement [16]. Although aortic valve resistance was strongly related to the severity of AS, it did not add any meaningful information once the valve area and gradient were determined [16]. Aortic valve resistance was not related to surgical mortality.

Energy loss index — Patients with AS who have similar aortic valve areas (AVAs) may have different clinical outcomes, suggesting that other factors (eg, pressure recovery) may contribute to outcomes. The energy loss index (ELI) provides an AVA index that is adjusted for pressure recovery. The ELI can be calculated noninvasively using Doppler echocardiography [17]:

where Aa equals the cross-sectional area of the aorta at the sinotubular junction. In a study of 138 patients with moderate to severe AS, the ELI was superior to pressure gradient, AVA, and aortic valve area indexed to body surface area for predicting the combined end point of death or aortic valve replacement; an ELI ≤0.52 cm²/m² was the best predictor of an adverse outcome (positive predictive value 67 percent) [17]. Furthermore, the Doppler calculation of energy loss may correlate better with AVA measured at catheterization than does the Doppler estimate of valve area itself [18]. In another study of 1563 initially asymptomatic patients, the ELI provided independent and additional prognostic information [19].

Planimetry of aortic valve area — Planimetry of the aortic valve orifice with transthoracic or transesophageal echocardiography (TEE) produces a valve area determination that has a positive correlation with the area obtained with the Gorlin equation and the continuity principle described above [20]. To visualize the aortic value with TEE, it is necessary to image the aortic valve in a view orthogonal to the stenotic jet. In one series of 41 patients with calcific AS studied with multiplane TEE, the orifice area was successfully measured in 93 percent; in the remaining patients, the stenosis was obviously very severe ("pinhole stenosis") [21]. The correlation coefficient with valve area determined by catheterization (Gorlin formula) was 0.95, and the sensitivity was 96 percent for predicting severe stenosis (valve area <0.75 cm²).

However, planimetry of valve area has two major limitations: measurement accuracy is limited when valve calcification is present, as occurs in most adults with AS, and it corresponds to the anatomic, not physiologic (ie, effective), valve area [22,23].

OTHER NONINVASIVE IMAGING — There are limited data on two other imaging modalities to estimate aortic valve area: cardiovascular magnetic resonance imaging and computed tomography (CT). In addition, both modalities may be used to evaluate coexisting disease of the aorta.

Cardiovascular magnetic resonance — Using cardiovascular magnetic resonance imaging (CMR), aortic valve area can be derived using the continuity principle [24,25] or planimetry [25-27]. One limitation is that peak transvalvular velocities may be underestimated if phase contrast images are not orthogonal to the stenotic jet. Also, the availability of CMR is limited. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Valvular heart disease'.)

Computed tomography — Cardiac computed tomography (CT) enables quantitation of aortic valve calcification and is used in candidates for transcatheter aortic valve implantation to measure annulus area, leaflet length, and the annular to coronary ostial distance [3]. Cardiac CT may also be used to planimeter aortic valve area but this anatomic measurement does not provide data on transvalvular velocities and gradients. A meta-analysis included 14 studies using multidetector row CT (MDCT) to measure aortic valve area in 509 patients [28]. MDCT overestimated aortic valve area by transthoracic echocardiography with a bias of 0.08 cm². Using transthoracic echocardiography, the pooled estimate of sensitivity of MDCT was 92 percent and the pooled specificity was 94 percent.

CARDIAC CATHETERIZATION — Catheterization is reserved for patients in whom echocardiography is nondiagnostic or when clinical and echocardiographic data are discrepant (table 2) [3]. Given the risk of cerebral embolization associated with crossing the aortic valve in patients with severe calcific AS, left heart catheterization should be avoided in such patients whenever possible. (See "Stroke after cardiac catheterization".)

Simultaneous measurements of cardiac output and the pressure gradient between the left ventricle and the aorta provide the pressure-flow data necessary to calculate the aortic valve area (AVA) and valve resistance [29,30]. Such calculations require painstaking attention to detail in the measurement of pressure and flow. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization".)

Gorlin equation for aortic valve area — Gorlin and Gorlin described the method of evaluating the severity of AS by calculating the AVA based upon invasive measurement of the transvalvular pressure gradient [1]:

where SV = stroke volume (mL per beat), SEP = systolic ejection period (seconds per beat), and ΔP = mean systolic pressure gradient between the left ventricle and aorta (mmHg) (figure 1). The area of the normal adult aortic valve is approximately 3.0 cm². Severe AS is said to be present when the calculated effective valve area is less than 1.0 cm² (table 1). (See 'Critical valve area and severity' below.)

Although the historical standard for determining the transvalvular gradient is the simultaneous measurement of pressures obtained from a catheter in the aorta and one in the left ventricle positioned via a transseptal approach, it is more common for a single left ventricular catheter to be placed retrograde via the aorta. However, the transvalvular gradient may be increased by the presence of a catheter across the stenotic aortic valve, which can reduce the effective orifice area [31]. This effect is proportional to the severity of the underlying AS and is seen only in the most severe AS; this diagnosis should be considered when hypotension develops after the catheter is advanced into the ventricle.

The SEP is usually measured on the simultaneous aortic and left ventricular pressure tracing from the pressure crossover at the beginning of ejection (when left ventricular pressure rises above aortic pressure) to the pressure crossover near the end of systole (when left ventricular pressure drops below aortic pressure) (figure 1). A careful study of left ventricular ejection using an implantable flowmeter suggested that the end of the SEP actually occurs after the second pressure crossover, and corresponds more closely to the timing of the incisura (the notch in the aortic pressure tracing associated with aortic valve closure) [32].

Aortic valve resistance — Pressure and flow data have also been used to calculate aortic valve resistance (R, dyne seconds per cm⁵). Early studies suggested that, compared with valve area calculations, resistance is less sensitive to variations in flow [33,34]:

where ΔP = mean pressure gradient (mmHg), HR = heart rate (beats per min), SEP = systolic ejection period (seconds per beat), and CO = cardiac output (L/min). Valve resistance exceeds 250 dyne seconds per cm⁵ in critical AS.

However, more studies suggest that valve resistance does not describe the fluid dynamics of native valve stenosis because the resistance calculation assumes a linear relationship between pressure and flow, whereas the actual relationship is quadratic [9,22,35]. Aortic valve resistance calculations are rarely used for clinical decision making.

Subvalvular gradients — Patients with AS also have resting subvalvular gradients in the absence of an anatomic basis for subvalvular obstruction; the mechanism may be based upon fluid dynamics, with an inertial effect within a rapidly tapering flow field [36]. These subvalvular gradients can constitute as much as 50 percent of the total measured transvalvular pressure gradient and increase further with exercise. The extent of elevation in cardiac output during exercise is inversely related to the subvalvular gradient.

CRITICAL VALVE AREA AND SEVERITY

Valve area and symptoms — Calculated valve area depicts an effective area that does not always represent the actual anatomic area or clinical-functional impairment. As a result, some patients with severe AS may be asymptomatic, while some symptomatic patients may have only moderate stenosis. Nevertheless, valve area data are an important part of the assessment of patients with AS even though there are limitations inherent in the clinical application of such information.

The term "critical" stenosis was defined based upon theoretical considerations showing that the aortic valve area must be reduced to one-fourth of its natural size before significant changes in circulation occur. As a result, since the triangular orifice area of the normal (adult) aortic valve is approximately 3.0 cm², an area exceeding 0.75 cm² would not be defined as critical [37,38]. The term "critical" is used less frequently, and the preferred terms are "severe" and "nonsevere."

Recognizing these considerations, cardiac symptoms can occur at aortic valve areas that are not "critical." Many of these symptomatic patients have valve areas that are severely stenosed (<1.0 cm² but >0.75 cm²). However, the possibility that valve stenosis is responsible must be considered in symptomatic patients with borderline severe stenosis (eg, valve area of 1.1 cm²), especially if a thorough evaluation reveals no other cause for symptoms.

In some cases, it may be helpful to index valve area for body size to avoid overestimation of stenosis severity in small adults and underestimation of severity in larger adults. Guidelines suggest that an indexed valve area <0.6 cm²/m² represents severe stenosis.

Of note, most prospective studies indicate that aortic velocity or mean gradient is a stronger predictor of clinical outcome than valve area. With very severe AS (velocity over 5 m/s, provided that subvalvular obstruction or severe anemia are not contributing to the high peak velocity), valve area does not provide additional prognostic value [39].

Based upon a variety of hemodynamic and natural history data, clinicians generally grade the severity of stenosis as mild, moderate, severe (table 1) [3,6].

●Mild – Valve area exceeds 1.5 cm²; transvalvular velocity 2.0 to 2.9 m/s; mean gradient <20 mmHg.

●Moderate – Valve area of 1.0 to 1.5 cm²; transvalvular velocity 3.0 to 3.9 m/s; mean gradient 20 to 39 mmHg.

●Severe – Valve area is less than 1.0 cm²; transvalvular velocity ≥4 m/s; mean pressure gradient ≥40 mmHg.

Although such an assessment may be useful in clinical discussions, the absolute valve area is not the primary parameter that defines the optimum timing of valve replacement surgery. As long as there are truly no symptoms, patients with severe AS (those with a critical or near-critical valve area) should be evaluated and followed with special care. Valve replacement is indicated when symptoms develop. (See "Indications for valve replacement for high gradient aortic stenosis in adults".)

One reason for dissociation between aortic valve area and symptoms is concurrent disease. For example, some patients may develop symptoms with moderate stenosis and moderate regurgitation.

Indexing for body size — Severe AS has also been defined as an aortic valve area indexed by body surface area <0.6 cm²/m² [3,6]. Indexing valve area for body surface area is important in children, adolescents, and small adults in whom the valve area may be small but not severely stenotic when adjusted for body size. However, use of body surface area to index aortic valve area in obese individuals may produce misleading results because valve area does not scale with increases in body weight [6].

Another approach to adjust for body size differences is to calculate the velocity ratio, which is the peak left ventricular outflow tract velocity (V_OT) divided by the maximum aortic jet velocity (V_AV). This ratio does not require a consideration of body size because it is dimensionless.

Alternatively, the ratio of the time velocity-integrals for the left ventricular outflow tract and aortic valve can be used.

The double load of aortic stenosis and systemic arterial hypertension — Valvuloarterial impedance (Zi) is an index of left ventricular outflow impedance or resistance developed to account for the double hemodynamic load imposed on the ventricle in patient with concurrent systemic arterial hypertension and valvular AS [40]. Calculations of Zi are based on the arterial systolic pressure and the systolic pressure gradient across the aortic valve. Zi appears to have prognostic value in patients with AS, and it helps explain some of the pathophysiologic features of AS, particularly in patients with hypertension [40,41].

LOW-GRADIENT AORTIC STENOSIS — Patients with severe AS, left ventricular systolic dysfunction, and a low cardiac output often present with only modest transvalvular pressure gradients (less than 30 mmHg). (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)

Such patients can be difficult to distinguish from those with a low cardiac output and mild to moderate AS. In both settings, the low-flow state contributes to a calculated valve area consistent with severe AS. As an example, a cardiac output of 3 L/min and a transvalvular pressure gradient of 16 to 25 mmHg may yield a valve area of 0.6 to 0.7 cm² if the standard hemodynamic formula is used [1]. However, this formula is known to underestimate the valve area and should not be used alone in low flow states. In theory, Doppler-derived valve areas should be less susceptible to low flow states.

It has been suggested that aortic valve resistance might provide a better separation between critical and noncritical AS, particularly in patients with low transvalvular pressure gradients [33,34]. Although valve resistance is less sensitive to flow than valve area, the resistance calculations have not proven to be substantially better than valve area calculations alone.

In patients with low-gradient AS (thought to be related to low flow), it can be useful to determine the transvalvular pressure gradient and calculate the valve area and resistance during a baseline state and again during exercise or other hemodynamic stress (for example, dobutamine infusion). This concept is based upon the observation that the valve area may increase during an increase in the cardiac output in some patients with low-gradient AS [42,43]. If dobutamine produces an increment in cardiac output, an increase in valve area, and a decrease in resistance, it is likely that the baseline calculations produced an overestimation of the severity. (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

SUMMARY

●The severity of aortic stenosis (AS) can usually be accurately assessed with echocardiography. However, the severity of AS may be underestimated if image quality is poor, particularly if Doppler recordings are not well aligned with the aortic valve jet. Also, the severity of AS is difficult to assess when cardiac output is low. (See 'Echocardiography' above and 'Low-gradient aortic stenosis' above.)

●Catheterization to determine the severity of AS is reserved for patients in whom echocardiography is nondiagnostic or when clinical and echocardiographic data are discrepant. (See 'Cardiac catheterization' above.)

●Calculated valve area depicts an effective area that does not always represent the actual anatomic area or functional impairment. This measurement should be considered along with the appearance of the valve, the mean systolic gradient, and peak systolic velocity. (See 'Critical valve area and severity' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William H Gaasch, MD (deceased), who contributed to an earlier version of this topic review.