**5. Hemodynamic classifications of AS**

In patients with AVA < 1 cm<sup>2</sup> , there are six flow-gradient patterns: NF/VHG, NF/HG, LF/HG, LF/LG with reduced LVEF, LF/LG with preserved LVEF, and NF/ LG. VHG is defined as MG ≥ 60 mmHg, and HG is defined as MG ≥ 40 mmHg; stroke volume index (SVI) of normal flow is ≥35 ml/m<sup>2</sup> . Low flow is defined as SVI < 35 ml/m2 . Low gradient is defined as MG < 40 mmHg. LF/LG AS with reduced LVEF is present when the gradient is low, the flow is low, and the LVEF is abnormal (<50%). LF/LG AS with preserved LVEF is present when the gradient is low and the flow is low but the LVEF is normal (>50%) (see **Table 1**).

#### **5.1 High-gradient AS**

*Aortic Stenosis - Current Perspectives*

predictors of patient outcomes [25].

by 0.1 cm2

progression in AS is highly variable. The average rate of progression was reported as increase in *V*max by 0.3 m/s/year and MG by 7 mmHg/year and decrease in AVA

in AS were severity of the aortic valve obstruction. During a follow-up period of 2 years, progression of symptoms requiring AVR was about 80% for patients with *V*max > 4.0 m/s vs. 35% with *V*max of 3.0–4.0 m/s and 15% for patients with *V*max < 3.0 m/s. MG and AVA, other parameters of stenosis severity, were also strong

**4. Discrepancies with echocardiographic criteria for grading AS**

*Comparison of AVA vs. MG in AS patients with preserved LVEF. The predicted values from the Gorlin equation and the fitted curve of the study cohort are shown. The quadrants depict severe AS cutoff points based on the guidelines, and the percentages represent patients per quadrant. Thirty percent of the severe AS patients* 

Echocardiography is the current standard modality for evaluating AS severity. However, challenges due to inconsistencies between measurements of the MG and the calculated AVA in patients with normal systolic function were noted (see **Figure 2**). This finding was attributed primarily to differences in stroke volume and flow across the aortic valve. While it seems possible that discrepancies can occur when the cardiac output is low from reduced LVEF, inconsistent measurements in patients with preserved LVEF were observed. Another potential explanation for the discrepancies was that effective valve area derived by Doppler echocardiography is often smaller than the anatomic valve area measured during cardiac catheterization or by planimetry or at autopsy. So while the initial guidelines for determining AS severity were based on invasive measurements (reflecting the anatomic valve area), echocardiographic Doppler measurements are currently used to make clinical decisions for AS patients still based on the original anatomic valve area criteria. Thus, based on AVA, it is possible that more patients may be categorized as having severe AS

/year [11]. Studies have shown that the strongest predictors of outcomes

**98**

**Figure 2.**

*were diagnosed based on AVA, but not by MG [26].*

Severe VHG AS (*V*max ≥ 5.0 m/s) has significantly worse prognosis than severe HG AS (*V*max ≥ 4.0 m/s) [3], so we acknowledge VHG AS as a separate entity from HG AS. However, most studies assessing AS severity using the new classification system combined NF/VHG and NF/HG as one entity under the subgroup of NF/ HG. Thus, we will characterize these two groups together and highlight some of the relevant findings for VHG AS.

#### *5.1.1 Normal flow/very high gradient or high gradient*

NF/VHG AS pattern is defined as AVA < 1.0 cm2 , MG ≥ 60 mmHg, *V*max ≥ 5.0 m/s, and LVEF ≥ 50% with SVI ≥ 35 ml/m2 . NF/HG AS is defined as MG ≥ 40 mmHg and *V*max ≥ 4 m/s with the same criteria for AVA, LVEF, and SVI as NF/VHG. Patients with these two flow-gradient patterns are the most prevalent (up to 70%) of all the AS groups. These patients tend to have more severe valvular stenosis suggesting more prolonged exposure to the progressive disease process. Compared with the NF/LG group, there is preservation of LV longitudinal function. However, these patients have higher BNP level and lower cardiac-event free survival [27].

When evaluating AS severity, *V*max is an important parameter which closely correlates with outcome. One study assessing the outcome of asymptomatic patients with very severe AS found that the higher the velocity, the lower the event-free survival with most patients experiencing some event within 3 years (see **Figure 3**). Patients with *V*max ≥ 5 m/s were symptomatic at presentation. Furthermore, asymptomatic patients with *V*max ≥ 5.5 m/s were highly likely to develop rapid onset of symptoms [3]. A landmark study evaluating the rate of hemodynamic progression and predictors of outcome in asymptomatic AS patients demonstrated that when *V*max exceeds 4 m/s, virtually all patients become symptomatic in 5 years.

#### **Figure 3.**

*Event-free survival with very severe AS. Kaplan-Meier estimates demonstrate that maximum aortic jet velocity closely correlates with outcome, with higher the velocity, the lower the event-free survival [3].*

The velocity traditionally reflects the chronicity of the degenerative process. *V*max between 3 and 4 m/s were also found to be not benign, and only 20% of patients remained asymptomatic over 5 years. Only when *V*max was <3 m/s, there was an 85% chance that the patient will remain asymptomatic for 5 years [11] (see **Figure 4**).

MG is another well-recognized parameter for defining AS severity. One study assessed the prognostic impact of MG on all-cause mortality in severe AS with preserved LVEF. They found that MG > 60 mmHg at baseline was associated with greater risk of all-cause mortality than lower values, thereby justifying a separate hemodynamic classification. The higher MG also reflected the chronicity of the disease process [28] (see **Figure 5**).

AVA < 1.0 cm<sup>2</sup> also correlated with poor outcome compared to moderate or mild categories. More severe AVAs carried worse prognosis, and like *V*max and MG, they reflected disease chronicity. While the rate of progression is highly variable, the often quoted number is 0.1 cm2 /year [29] (see **Figure 6**). However, when *V*max was high or very high (4–6 m/s), there was no significant difference in the outcome based on the calculated AVA [3].

According to the current ACC/AHA guidelines, symptomatic NF/HG and NF/ VHG severe AS patients have a class I indication for AVR. When asymptomatic, these AS subgroups are recommended to undergo further risk stratification.

#### *5.1.2 Low flow/high gradient*

This pattern of AS is defined as AVA < 1.0 cm<sup>2</sup> , MG ≥ 40 mmHg, and LVEF ≥ 50% with SVI < 35 ml/m<sup>2</sup> . The prevalence of this AS subtype is much less (8%) [30]. These patients have LV remodeling with reduced longitudinal function despite preserved LVEF. As a consequence, LV output is reduced with resultant lower than expected MG. LF/HG AS patients have shown to have high BNP, and their prognosis is similar or worse than those with NL/HG AS. When symptomatic, these patients have better survival with AVR [27, 31].

**101**

**5.2 Low-gradient AS**

**Figure 5.**

**Figure 4.**

normal, ≥35% ml/m2

AVA < 1.0 cm<sup>2</sup>

Three types of low-gradient severe AS have been described based on the LVEF and the flow state. LF/LG AS with reduced LVEF (<50%) is present when there is LV systolic dysfunction with reduced stroke volume in the setting of severe AS which results in decreased transvalvular velocity/gradient. If the LVEF is normal (≥50%), the stroke volume index (SVI) helps determine the presence of LF/LG

*Effect of* V*max on outcomes in asymptomatic AS. Cox regression analysis demonstrating event-free survival in* 

*asymptomatic AS patients categorized by initial peak aortic jet velocity [11].*

) or NF/LG AS (if the SVI is

, and LVEF < 50%. LF/LG AS with

AS with preserved LVEF (if the SVI is low, <35 ml/m2

*5.2.1 Low flow/low gradient with reduced LVEF*

) [32] (see **Table 2**).

, MG < 40 mmHg, SVI < 35 ml/m2

This AS subtype, also known as "classical" LF/LG AS, is defined as

*Impact of MG on outcomes in severe AS. Kaplan-Meier estimates of survival based on MG [28].*

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

*DOI: http://dx.doi.org/10.5772/intechopen.86707*

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis DOI: http://dx.doi.org/10.5772/intechopen.86707*

#### **Figure 4.**

*Aortic Stenosis - Current Perspectives*

disease process [28] (see **Figure 5**).

the often quoted number is 0.1 cm2

based on the calculated AVA [3].

*5.1.2 Low flow/high gradient*

LVEF ≥ 50% with SVI < 35 ml/m<sup>2</sup>

This pattern of AS is defined as AVA < 1.0 cm<sup>2</sup>

these patients have better survival with AVR [27, 31].

AVA < 1.0 cm<sup>2</sup>

**Figure 3.**

The velocity traditionally reflects the chronicity of the degenerative process. *V*max between 3 and 4 m/s were also found to be not benign, and only 20% of patients remained asymptomatic over 5 years. Only when *V*max was <3 m/s, there was an 85% chance that the patient will remain asymptomatic for 5 years [11] (see **Figure 4**). MG is another well-recognized parameter for defining AS severity. One study assessed the prognostic impact of MG on all-cause mortality in severe AS with preserved LVEF. They found that MG > 60 mmHg at baseline was associated with greater risk of all-cause mortality than lower values, thereby justifying a separate hemodynamic classification. The higher MG also reflected the chronicity of the

*closely correlates with outcome, with higher the velocity, the lower the event-free survival [3].*

*Event-free survival with very severe AS. Kaplan-Meier estimates demonstrate that maximum aortic jet velocity* 

mild categories. More severe AVAs carried worse prognosis, and like *V*max and MG, they reflected disease chronicity. While the rate of progression is highly variable,

was high or very high (4–6 m/s), there was no significant difference in the outcome

According to the current ACC/AHA guidelines, symptomatic NF/HG and NF/ VHG severe AS patients have a class I indication for AVR. When asymptomatic, these AS subgroups are recommended to undergo further risk stratification.

(8%) [30]. These patients have LV remodeling with reduced longitudinal function despite preserved LVEF. As a consequence, LV output is reduced with resultant lower than expected MG. LF/HG AS patients have shown to have high BNP, and their prognosis is similar or worse than those with NL/HG AS. When symptomatic,

also correlated with poor outcome compared to moderate or

/year [29] (see **Figure 6**). However, when *V*max

, MG ≥ 40 mmHg, and

. The prevalence of this AS subtype is much less

**100**

*Effect of* V*max on outcomes in asymptomatic AS. Cox regression analysis demonstrating event-free survival in asymptomatic AS patients categorized by initial peak aortic jet velocity [11].*

**Figure 5.**

*Impact of MG on outcomes in severe AS. Kaplan-Meier estimates of survival based on MG [28].*

#### **5.2 Low-gradient AS**

Three types of low-gradient severe AS have been described based on the LVEF and the flow state. LF/LG AS with reduced LVEF (<50%) is present when there is LV systolic dysfunction with reduced stroke volume in the setting of severe AS which results in decreased transvalvular velocity/gradient. If the LVEF is normal (≥50%), the stroke volume index (SVI) helps determine the presence of LF/LG AS with preserved LVEF (if the SVI is low, <35 ml/m2 ) or NF/LG AS (if the SVI is normal, ≥35% ml/m2 ) [32] (see **Table 2**).

#### *5.2.1 Low flow/low gradient with reduced LVEF*

This AS subtype, also known as "classical" LF/LG AS, is defined as AVA < 1.0 cm<sup>2</sup> , MG < 40 mmHg, SVI < 35 ml/m2 , and LVEF < 50%. LF/LG AS with

#### **Figure 6.**

*(A) Adjusted event-free survival based on AVA. (B) Cumulative hazard of death based on AVA [29].*

reduced LVEF accounts for about 5–10% of the AS population [33, 34] and has the worst outcome among all the AS categories [30, 33, 34]. The low flow state is usually associated with LV systolic dysfunction either from pressure overload due to the underlying severe AS or cardiomyopathy of another etiology.

In order to differentiate true-severe AS from pseudo-severe AS, low-dose DSE is the initial recommended study to determine whether there is normal flow reserve (an increase in stroke volume of >20%) or diminished flow reserve (see **Figure 7**). Patients with normal flow reserve may have true-severe AS (MG ≥ 40 mmHg with AVA < 1.0 cm<sup>2</sup> at any stage of DSE) which requires AVR or pseudo-severe AS (MG < 40 mmHg with AVA > 1.0 cm<sup>2</sup> ) where medical therapy is recommended [32, 35]. In patients where the increase in stroke volume with DSE is <20% but >15% and MG is <40 mmHg, the definitive diagnosis of AS severity may remain questionable. In this case, the projected AVA calculation using normal flow rate may be beneficial where a value <1.0 cm<sup>2</sup> is suggestive of true-severe AS [36] (see (Eq. (1)). However, if the stroke volume increase is <15%, further evaluation beyond DSE is often required, and calcium quantification of the aortic valve using MDCT is helpful in confirming the AS severity. The cutoff values for true-severe AS is >1200 AU in women and >2000 AU in men [37, 38].

**103**

**Figure 7.**

*detector computed tomography.*

**Table 2.**

*Subclassification of low gradient AS.*

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

in stroke volume can produce large changes in Zva [39].

Valvuloarterial impedance (Zva) is an index to evaluate global LV hemodynamic

load using Doppler echocardiography (see Eq. (2)). Zva > 5 has been shown to predict adverse outcomes in patients with AS and LV dysfunction. Since AS is a disease of the elderly, in addition to valvular stenosis, vascular stiffness due to various factors including age and hypertension may be present. As a result, the LV may be subject to a double afterload, known as global LV afterload or Zva. In general, higher Zva is associated with worse outcome. However, since Zva is a flow-dependent parameter, this index may be less reliable in low flow states since small changes

*Algorithm for diagnosing LF/LG AS with reduced LVEF. AS, aortic stenosis; AVA, aortic valve area; MG, mean gradient; LVEF, left ventricular ejection fraction; SV, stroke volume; AV, aortic valve; MDCT, multi-*

*DOI: http://dx.doi.org/10.5772/intechopen.86707*

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis DOI: http://dx.doi.org/10.5772/intechopen.86707*

Valvuloarterial impedance (Zva) is an index to evaluate global LV hemodynamic load using Doppler echocardiography (see Eq. (2)). Zva > 5 has been shown to predict adverse outcomes in patients with AS and LV dysfunction. Since AS is a disease of the elderly, in addition to valvular stenosis, vascular stiffness due to various factors including age and hypertension may be present. As a result, the LV may be subject to a double afterload, known as global LV afterload or Zva. In general, higher Zva is associated with worse outcome. However, since Zva is a flow-dependent parameter, this index may be less reliable in low flow states since small changes in stroke volume can produce large changes in Zva [39].

**Table 2.** *Subclassification of low gradient AS.*

*Aortic Stenosis - Current Perspectives*

reduced LVEF accounts for about 5–10% of the AS population [33, 34] and has the worst outcome among all the AS categories [30, 33, 34]. The low flow state is usually associated with LV systolic dysfunction either from pressure overload due to the

*(A) Adjusted event-free survival based on AVA. (B) Cumulative hazard of death based on AVA [29].*

In order to differentiate true-severe AS from pseudo-severe AS, low-dose DSE is the initial recommended study to determine whether there is normal flow reserve (an increase in stroke volume of >20%) or diminished flow reserve (see **Figure 7**). Patients with normal flow reserve may have true-severe AS

apy is recommended [32, 35]. In patients where the increase in stroke volume with DSE is <20% but >15% and MG is <40 mmHg, the definitive diagnosis of AS severity may remain questionable. In this case, the projected AVA calculation

of true-severe AS [36] (see (Eq. (1)). However, if the stroke volume increase is <15%, further evaluation beyond DSE is often required, and calcium quantification of the aortic valve using MDCT is helpful in confirming the AS severity. The cutoff values for true-severe AS is >1200 AU in women and >2000 AU in

at any stage of DSE) which requires AVR

) where medical ther-

is suggestive

underlying severe AS or cardiomyopathy of another etiology.

or pseudo-severe AS (MG < 40 mmHg with AVA > 1.0 cm<sup>2</sup>

using normal flow rate may be beneficial where a value <1.0 cm<sup>2</sup>

(MG ≥ 40 mmHg with AVA < 1.0 cm<sup>2</sup>

**102**

men [37, 38].

**Figure 6.**

#### **Figure 7.**

*Algorithm for diagnosing LF/LG AS with reduced LVEF. AS, aortic stenosis; AVA, aortic valve area; MG, mean gradient; LVEF, left ventricular ejection fraction; SV, stroke volume; AV, aortic valve; MDCT, multidetector computed tomography.*


#### **Table 3.**

*Recommendations for aortic valve replacement in LF/LG AS.*

Two-dimensional and three-dimensional transesophageal echocardiography may also be beneficial for confirming AS severity via direct visualization of the aortic valve anatomy and physiology.

In general, LF/LG AS has the worst prognosis compared to the other categories in part because the severity of AS is often under-recognized and surgical treatment is delayed. Patients with LF/LG AS with reduced LVEF have higher adverse event rates and mortality than LF/LG AS with preserved LVEF. The operative risk is also high in this AS subgroup. However, AVR has shown to have significant survival benefit compared to patients undergoing conservative management [40]. Furthermore, TAVR in LF/LG AS with reduced LVEF has demonstrated to have significant survival benefit compared with standard medical therapy in patients who are not suitable for surgery and similar outcomes compared with SAVR for patients at high surgical risk [41]. According to the ACC/AHA guidelines, true-severe LF/LG AS with reduced LVEF has a class IIa indication for AVR [42] (see **Table 3**).

#### *5.2.2 Low flow/low gradient with preserved LVEF*

LF/LG AS with preserved LVEF, also described as "paradoxical" LF/LG AS, is defined as AVA < 1.0 cm2 , AVA indexed < 0.6 cm2 /m2 , MG < 40 mmHg, SVI < 35 ml/m2 , and LVEF ≥ 50%. This AS pattern has generated much controversy among investigators. Studies have reported that low flow state is present in about 30% of AS patients with normal LVEF [31, 43–46]. This AS subgroup accounts for about 15–35% of the symptomatic and 5–10% of the asymptomatic AS patients [30]. The classic characteristics described with this AS subtype are small LV cavity size with marked concentric hypertrophy, myocardial fibrosis, restrictive diastolic physiology, reduced LV longitudinal systolic function, and increased global LV afterload resulting in reduced SVI and worse outcome [6, 31, 47]. Other factors associated with this pattern include women, older age, systemic and/or pulmonary hypertension, atrial fibrillation, mitral regurgitation, and right ventricular dysfunction [27, 46]. Some studies have shown that these patients have one of the worst prognoses as the disease severity is often underrecognized and surgery is delayed. This pattern has shown to have better outcomes than LF/LG AS with reduced LVEF but worse outcomes than moderate AS, HG AS, and NF/ LG AS [31, 41, 48]. The likelihood of remaining alive in 3 years without AVR has been reported about five fold lower than normal flow state [43].

**105**

**Figure 8.**

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

When evaluating patients with this AS entity, it is essential to first exclude potential technical errors which may affect the gradient, stroke volume, and AVA measurements. Next, an integrated approach assessing the different criteria to support severe AS needs to be evaluated. These parameters include clinical characteristics such as physical examination suggestive of severe AS, patient symptoms, and the presence of hypertension. Potential etiologies of low flow state need to be considered. Qualitative imaging analyses such as the presence of left ventricular hypertrophy and LV strain measurements should also be assessed. Once LF/LG AS with preserved LVEF status is confirmed, quantitation of aortic valve calcification using MDCT may be helpful in differentiating true-severe vs. pseudo-severe AS [35, 49] (see **Figure 8**). One small study showed that low-dose DSE may be useful in

*Algorithm for diagnosing LF/LG AS with preserved LVEF. LF, low flow; LG, low gradient; AS, aortic stenosis; AVA, aortic valve area; MG, mean gradient; LVEF, left ventricular ejection fraction; SVI, stroke volume* 

According to the ACC/AHA guidelines, LF/LG AS with preserved LVEF has a class IIa indication for AVR, if clinical, anatomic, and hemodynamic data support that the patient's symptom is from the obstructive pathophysiology of the aortic valve [42] (see **Table 3**). One randomized trial data showed significant survival benefit after TAVR compared to standard medical treatment or similar clinical outcomes vs. SAVR [41]. In patients with greater degree of LV myocardial fibrosis, more advanced stage of diastolic dysfunction and low SVI demonstrated worse

In contrast to the findings described above, some other investigators have shown differing results for this AS entity. In one prospective study with a large number of patients with asymptomatic AS, there was no difference between the moderate stenosis and the low-gradient "severe" AS groups in terms of valveassociated events, major cardiovascular events, or cardiac death, even when the groups were subcategorized into low flow and normal flow states [53].

confirming the diagnosis with this entity [50].

*index; AV, aortic valve; MDCT, multi-detector computed tomography.*

outcomes after TAVR [51, 52].

*DOI: http://dx.doi.org/10.5772/intechopen.86707*

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis DOI: http://dx.doi.org/10.5772/intechopen.86707*

**Figure 8.**

*Aortic Stenosis - Current Perspectives*

aortic valve anatomy and physiology.

*Recommendations for aortic valve replacement in LF/LG AS.*

**Table 3.**

indication for AVR [42] (see **Table 3**).

defined as AVA < 1.0 cm2

*5.2.2 Low flow/low gradient with preserved LVEF*

reported about five fold lower than normal flow state [43].

Two-dimensional and three-dimensional transesophageal echocardiography may also be beneficial for confirming AS severity via direct visualization of the

In general, LF/LG AS has the worst prognosis compared to the other categories in part because the severity of AS is often under-recognized and surgical treatment is delayed. Patients with LF/LG AS with reduced LVEF have higher adverse event rates and mortality than LF/LG AS with preserved LVEF. The operative risk is also high in this AS subgroup. However, AVR has shown to have significant survival benefit compared to patients undergoing conservative management [40]. Furthermore, TAVR in LF/LG AS with reduced LVEF has demonstrated to have significant survival benefit compared with standard medical therapy in patients who are not suitable for surgery and similar outcomes compared with SAVR for patients at high surgical risk [41]. According to the ACC/AHA guidelines, true-severe LF/LG AS with reduced LVEF has a class IIa

LF/LG AS with preserved LVEF, also described as "paradoxical" LF/LG AS, is

and LVEF ≥ 50%. This AS pattern has generated much controversy among investigators. Studies have reported that low flow state is present in about 30% of AS patients with normal LVEF [31, 43–46]. This AS subgroup accounts for about 15–35% of the symptomatic and 5–10% of the asymptomatic AS patients [30]. The classic characteristics described with this AS subtype are small LV cavity size with marked concentric hypertrophy, myocardial fibrosis, restrictive diastolic physiology, reduced LV longitudinal systolic function, and increased global LV afterload resulting in reduced SVI and worse outcome [6, 31, 47]. Other factors associated with this pattern include women, older age, systemic and/or pulmonary hypertension, atrial fibrillation, mitral regurgitation, and right ventricular dysfunction [27, 46]. Some studies have shown that these patients have one of the worst prognoses as the disease severity is often underrecognized and surgery is delayed. This pattern has shown to have better outcomes than LF/LG AS with reduced LVEF but worse outcomes than moderate AS, HG AS, and NF/ LG AS [31, 41, 48]. The likelihood of remaining alive in 3 years without AVR has been

/m2

, MG < 40 mmHg, SVI < 35 ml/m2

,

, AVA indexed < 0.6 cm2

**104**

*Algorithm for diagnosing LF/LG AS with preserved LVEF. LF, low flow; LG, low gradient; AS, aortic stenosis; AVA, aortic valve area; MG, mean gradient; LVEF, left ventricular ejection fraction; SVI, stroke volume index; AV, aortic valve; MDCT, multi-detector computed tomography.*

When evaluating patients with this AS entity, it is essential to first exclude potential technical errors which may affect the gradient, stroke volume, and AVA measurements. Next, an integrated approach assessing the different criteria to support severe AS needs to be evaluated. These parameters include clinical characteristics such as physical examination suggestive of severe AS, patient symptoms, and the presence of hypertension. Potential etiologies of low flow state need to be considered. Qualitative imaging analyses such as the presence of left ventricular hypertrophy and LV strain measurements should also be assessed. Once LF/LG AS with preserved LVEF status is confirmed, quantitation of aortic valve calcification using MDCT may be helpful in differentiating true-severe vs. pseudo-severe AS [35, 49] (see **Figure 8**). One small study showed that low-dose DSE may be useful in confirming the diagnosis with this entity [50].

According to the ACC/AHA guidelines, LF/LG AS with preserved LVEF has a class IIa indication for AVR, if clinical, anatomic, and hemodynamic data support that the patient's symptom is from the obstructive pathophysiology of the aortic valve [42] (see **Table 3**). One randomized trial data showed significant survival benefit after TAVR compared to standard medical treatment or similar clinical outcomes vs. SAVR [41]. In patients with greater degree of LV myocardial fibrosis, more advanced stage of diastolic dysfunction and low SVI demonstrated worse outcomes after TAVR [51, 52].

In contrast to the findings described above, some other investigators have shown differing results for this AS entity. In one prospective study with a large number of patients with asymptomatic AS, there was no difference between the moderate stenosis and the low-gradient "severe" AS groups in terms of valveassociated events, major cardiovascular events, or cardiac death, even when the groups were subcategorized into low flow and normal flow states [53].

Another large study demonstrated that patients with LF/LG AS with preserved LVEF had better spontaneous survival than the patients with HG severe AS, and the results are unaffected by flow states. Furthermore, the patients with LF/LG AS with preserved LVEF progressed to develop HG AS over time, and in all patients who showed a reduction in transvalvular gradients over time, this decrease was associated with reduction in LVEF [54]. Another study showed that patients with severe LF/LG AS with preserved LVEF had similar outcomes as patients with mild to moderate AS, and there was no significant benefit of AVR in this group [55]. However, a comparison of two studies by Hachicha et al. [31] and Jander et al. [53] showed that there were some differences between the study group findings which may, at least in part, have contributed to the differing outcomes. Some investigators have proposed for reducing the AVA cutoff value for severe AS closer to ≤0.8 cm<sup>2</sup> to avoid overestimation of AS severity [56].

#### *5.2.3 Normal flow/low gradient*

This AS pattern is defined as AVA < 1.0 cm<sup>2</sup> , AVA indexed < 0.6 cm<sup>2</sup> , MG < 40 mmHg, and LVEF ≥ 50% with SVI ≥ 35 ml/m<sup>2</sup> . NF/LG AS has shown to be present in about one third of AS patients [30], and some studies have suggested that this AS pattern may be due to marked reduction in transaortic gradient from systemic hypertension and decreased aortic compliance [57, 58]. Patients with NL/LG AS are reported to have less severe disease than the other AS categories with lower BNP and preserved LV longitudinal function [35]. In terms of diagnosis, technical measurement errors need to be excluded, and aortic valve calcium scoring using MDCT may be beneficial to further determine the AS severity [38]. According to the 2017 European Association of Cardiovascular Imaging and the American Society of Echocardiography Recommendations, however, this entity is considered to be due to measurement errors or the consequence of inconsistent cutoff values for transaortic velocity/ gradient and AVA [35]. Some studies have supported this thought as patients in the NF/LG AS subgroup demonstrated the same outcome as patients with moderate AS [59].

There are no particular recommendations for this subgroup in the current guidelines, and AVR should only be considered in symptomatic patients with confirmed severe AS. One study showed survival benefit in these patients [43], while another study showed no difference in survival in patients who underwent early AVR compared to conservative management [60].

**Projected AVA calculation**

$$\text{Projected AVA} = \text{AVArest} \star \left(\frac{\Delta \text{ AVA}}{\Delta Q}\right) \ast \text{(250 - Qrest)}$$

∆ AVA **=** AVApeak **−** AVArest **=** Change in AVA at rest and at peak DSE

$$
\Delta \text{ Q} = \text{Qpeak} - \text{Qrest} = \text{Change in Q at rest and at peak DSE} \tag{1}
$$

**107**

and clinical outcomes.

**Conflict of interest**

None.

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

Zva **<sup>=</sup>** Systemic Arterial Pressure **<sup>+</sup>** Mean Pressure Gradient \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Stroke Volume Index

although controversy exists about the optimal timing of intervention.

Over the years, the operative risk for SAVR for severe AS has significantly decreased, and TAVR has emerged as a promising alternative treatment for these patients with different operative risk profiles—high, intermediate, and more recently low risk. Recent data have supported that TAVR is superior or noninferior to SAVR in the treatment of severe AS and long-term follow-up assessment will better validate the true comparison between the two approaches and determine the optimal treatment strategy. As the TAVR technology continues to advance, the next generations of bioprostheses will be introduced which may further improve outcomes. Therefore, it is vital to accurately diagnose AS severity and identify those individuals who may benefit from AVR in a timely manner to optimize patient care

Zva **=** Valvuloarterial Impedence (2)

The different hemodynamic categories of severe AS have shown to have varying clinical outcomes. Low flow state has exhibited the worst prognosis due to intrinsic myocardial dysfunction and/or under-recognition of the disease severity resulting in inappropriate delay in AVR. Low-gradient AS with low flow state is of particular challenge for clinical decision-making, especially when differentiating true-severe AS (where AVR may be beneficial) vs. pseudo-severe AS (where conservative medical management is appropriate). In LF/LG AS with reduced LVEF, DSE is beneficial for the confirmation of AS severity and risk stratification. In the setting of partial or no flow reserve, projected AVA and/or calcium scoring with MDCT may be useful to guide management. LF/LG AS with preserved LVEF is an entity where the natural history and the pathophysiology are not well understood. There has been much controversy and differing schools of thought around this AS subgroup. Numerous studies have shown that LF/LG AS with preserved LVEF is associated with poor prognosis, and therefore, careful evaluation and identification of these patients are necessary to ensure proper management. Calcium quantification using MDCT has shown to be the preferred technique for confirming AS severity with this subgroup. However, other investigators have reported that this AS entity represents moderate AS with no significant difference in outcomes between the groups. These discrepant findings may be resolved based on more randomized studies with large cohorts and with the application of more advanced diagnostic imaging techniques capable of overcoming the limitations of the currently available technology to better assess AS severity. In symptomatic high-gradient severe AS, regardless of the flow state, AVR is the only treatment option that has demonstrated to improve symptoms and survival. In asymptomatic high-gradient severe AS, regardless of the flow state, the current guidelines recommend watchful waiting and conservative management,

*DOI: http://dx.doi.org/10.5772/intechopen.86707*

**6. Conclusions**

**Valvuloarterial impedance calculation**

Projected AVA at a normal flow rate (250 ml/s) <1.0 cm<sup>2</sup> suggests severe AS.

AVArest, aortic valve area at rest; DSE, dobutamine stress echocardiography; AVApeak, aortic valve area at peak; *Q*rest, stroke volume at rest; *Q*peak, stroke volume at peak DSE.

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis DOI: http://dx.doi.org/10.5772/intechopen.86707*

#### **Valvuloarterial impedance calculation**

Zva **<sup>=</sup>** Systemic Arterial Pressure **<sup>+</sup>** Mean Pressure Gradient \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Stroke Volume Index

Zva **=** Valvuloarterial Impedence (2)
