**2. Natural history of AS**

AS is a progressive valvular heart disease with gradual valvular narrowing resulting in LV outflow tract (LVOT) obstruction over time. Degenerative calcific AS is the most common type of this disease process and predominantly affects the elderly. With this condition, there is a long latent period during which the patient is asymptomatic although there is progression of obstructive physiology at the aortic valve and LV pressure overload. Survival in asymptomatic patients undergoing conservative management with watchful waiting is not statistically different from ageand gender-matched controls [7]. However, once symptoms of angina, syncope, or heart failure develop, there is a very rapid decline. Patients with AS who develop angina have a 5-year survival, syncope 3-year survival, and heart failure, the most ominous of all, 2-year survival (see **Figure 1**) [8, 9]. Thus, when symptoms are corroborated by established echocardiographic criteria for severe AS, some form of intervention is required because these individuals only have a 3-year survival of about 25%. In severe asymptomatic AS, the rate of symptom onset is higher when significant calcification of the aortic valve is present and in older patients [7]. Other factors demonstrated to predict symptom onset and surgical outcome include brain natriuretic peptide (BNP) [10]. While the risk of sudden death is a major concern in patients with asymptomatic AS undergoing conservative management, numerous studies have shown that the risk is very low, <1% per year [7, 11, 12].

Over the years, there has been marked decrease in the operative risk of AS. Furthermore, while prior studies have shown rather benign prognosis of asymptomatic severe AS patients, suggesting that delay in surgery can be safe until the development of symptoms, there is controversy as to the optimal timing of AVR

**97**

**Figure 1.**

*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

and whether elective or early intervention during the asymptomatic stage might be better long term. At present, the surgical mortality for AVR is <2% for severe AS in patients with New York Heart Association (NYHA) functional class I or II heart failure, whereas this risk is significantly higher with class III or IV [13]. Thus, even though the patient may be asymptomatic, AS severity can progress and cause LV dysfunction during the conservative management period and significantly increase the surgical risk [14]. Furthermore, there is concern regarding the development of significant LV myocardial hypertrophy and irreversible myocardial fibrosis due to pressure overload which may result in persistent postoperative diastolic dysfunction and heart failure, even if AVR is successful [15, 16]. However, a general recommendation cannot be made at this time due to insufficient evidence to justify the benefit of AVR in asymptomatic patients to outweigh the risks of surgery and complications related to prosthesis long-term. However, those patients who may benefit from early surgical intervention should be identified through risk stratification [17]. Over the past decade, transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment strategy for symptomatic severe AS patients who are not suitable or prohibitive for surgical AVR (SAVR) [18, 19] or at high risk for surgery [20, 21]. This technology then expanded to benefit patients with intermediate operative risk, where TAVR using a self-expanding prosthesis was noninferior to SAVR at 24 months follow-up [22]. More recently, TAVR using a balloon-expandable SAPIEN 3 system in low-risk patients was shown to be superior to SAVR based on a composite of death, stroke, and rehospitalization at 1-year follow-up, despite excellent surgical results [23]. Long-term follow-up studies are underway to help

*Natural history of aortic stenosis. A long, latent, asymptomatic period is present followed by a very rapid decline in survival with the onset of symptoms of angina, syncope, and/or heart failure in severe AS patients [8].*

determine the true therapeutic impact of TAVR vs. SAVR.

*V*max ≥ 4.0 m/s, MG ≥ 40 mmHg, and AVA < 1.0 cm<sup>2</sup>

**3. Severe AS: definition and rate of hemodynamic progression**

AS severity quantitation is based on the degree of LVOT obstruction caused by progressive narrowing of the aortic valve orifice. Echocardiography with Doppler evaluation is the main modality for diagnosing AS. Traditionally, hemodynamic severity of AS has been described based on peak aortic jet velocity (*V*max), MG, and AVA. According to the 2014 ACC/AHA guidelines, severe AS is defined as

[24]. The rate of hemodynamic

*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 1.**

*Aortic Stenosis - Current Perspectives*

**2. Natural history of AS**

**Table 1.**

AS severity and the necessity of integrating the valve gradient with flow patterns were recognized when a significant subset of patients were found to have small AVAs suggestive of severe AS with lower gradients despite preserved LVEF [6]. As a result,

*).*

classification of AS was proposed which can be categorized into six subgroups based on LV flow state [normal flow (NF) vs. low flow (LF)] and pressure gradient [very high gradient (VHG) vs. high gradient (HG) vs. low gradient (LG)]. These six flowgradient patterns (NF/VHG, NF/HG, LF/HG, LF/LG with reduced LVEF, LF/LG with preserved LVEF, and normal NF/LG) have shown to represent distinct pathophysi-

AS is a progressive valvular heart disease with gradual valvular narrowing resulting in LV outflow tract (LVOT) obstruction over time. Degenerative calcific AS is the most common type of this disease process and predominantly affects the elderly. With this condition, there is a long latent period during which the patient is asymptomatic although there is progression of obstructive physiology at the aortic valve and LV pressure overload. Survival in asymptomatic patients undergoing conservative management with watchful waiting is not statistically different from ageand gender-matched controls [7]. However, once symptoms of angina, syncope, or heart failure develop, there is a very rapid decline. Patients with AS who develop angina have a 5-year survival, syncope 3-year survival, and heart failure, the most ominous of all, 2-year survival (see **Figure 1**) [8, 9]. Thus, when symptoms are corroborated by established echocardiographic criteria for severe AS, some form of intervention is required because these individuals only have a 3-year survival of about 25%. In severe asymptomatic AS, the rate of symptom onset is higher when significant calcification of the aortic valve is present and in older patients [7]. Other factors demonstrated to predict symptom onset and surgical outcome include brain natriuretic peptide (BNP) [10]. While the risk of sudden death is a major concern in patients with asymptomatic AS undergoing conservative management, numerous

ologic types of severe AS with different clinical outcomes (see **Table 1**).

studies have shown that the risk is very low, <1% per year [7, 11, 12].

Over the years, there has been marked decrease in the operative risk of AS. Furthermore, while prior studies have shown rather benign prognosis of asymptomatic severe AS patients, suggesting that delay in surgery can be safe until the development of symptoms, there is controversy as to the optimal timing of AVR

), a new hemodynamic

under the umbrella of severe AS (based on AVA < 1.0 cm2

*Hemodynamic classification of severe aortic stenosis (AVA < 1.0 cm2*

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*Natural history of aortic stenosis. A long, latent, asymptomatic period is present followed by a very rapid decline in survival with the onset of symptoms of angina, syncope, and/or heart failure in severe AS patients [8].*

and whether elective or early intervention during the asymptomatic stage might be better long term. At present, the surgical mortality for AVR is <2% for severe AS in patients with New York Heart Association (NYHA) functional class I or II heart failure, whereas this risk is significantly higher with class III or IV [13]. Thus, even though the patient may be asymptomatic, AS severity can progress and cause LV dysfunction during the conservative management period and significantly increase the surgical risk [14]. Furthermore, there is concern regarding the development of significant LV myocardial hypertrophy and irreversible myocardial fibrosis due to pressure overload which may result in persistent postoperative diastolic dysfunction and heart failure, even if AVR is successful [15, 16]. However, a general recommendation cannot be made at this time due to insufficient evidence to justify the benefit of AVR in asymptomatic patients to outweigh the risks of surgery and complications related to prosthesis long-term. However, those patients who may benefit from early surgical intervention should be identified through risk stratification [17]. Over the past decade, transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment strategy for symptomatic severe AS patients who are not suitable or prohibitive for surgical AVR (SAVR) [18, 19] or at high risk for surgery [20, 21]. This technology then expanded to benefit patients with intermediate operative risk, where TAVR using a self-expanding prosthesis was noninferior to SAVR at 24 months follow-up [22]. More recently, TAVR using a balloon-expandable SAPIEN 3 system in low-risk patients was shown to be superior to SAVR based on a composite of death, stroke, and rehospitalization at 1-year follow-up, despite excellent surgical results [23]. Long-term follow-up studies are underway to help determine the true therapeutic impact of TAVR vs. SAVR.

#### **3. Severe AS: definition and rate of hemodynamic progression**

AS severity quantitation is based on the degree of LVOT obstruction caused by progressive narrowing of the aortic valve orifice. Echocardiography with Doppler evaluation is the main modality for diagnosing AS. Traditionally, hemodynamic severity of AS has been described based on peak aortic jet velocity (*V*max), MG, and AVA. According to the 2014 ACC/AHA guidelines, severe AS is defined as *V*max ≥ 4.0 m/s, MG ≥ 40 mmHg, and AVA < 1.0 cm<sup>2</sup> [24]. The rate of hemodynamic 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 by 0.1 cm2 /year [11]. Studies have shown that the strongest predictors of outcomes 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 predictors of patient outcomes [25].

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

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

#### **Figure 2.**

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

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*Hemodynamic Classifications of Aortic Stenosis and Relevance to Prognosis*

that AVA cutoff value for severe AS be changed to 0.8 cm<sup>2</sup>

relative to the peak flow velocity and MG. Therefore, some authors have suggested

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;

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

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

*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

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.

low and the flow is low but the LVEF is normal (>50%) (see **Table 1**).

. Low gradient is defined as MG < 40 mmHg. LF/LG AS with

There are other potential etiologies of discrepant AVA and MG measurements in the setting of preserved LVEF which also need to be taken into consideration. First, technical errors need to be excluded. For example, LVOT diameter measurement may be inaccurate, and/or LVOT velocity time integral may be underestimated due to misplacement of the pulsed wave Doppler sample in the LVOT, leading to the underestimation of the stroke volume and the AVA. Second, patients with small body habitus and small LV dimensions could have lower stroke volume and lower transaortic gradient. Therefore, additional diagnostic studies such as dobutamine stress echocardiography (DSE), calcium scoring using multi-detector computed tomography (MDCT), and/or BNP may be necessary to corroborate AS severity and guide management strategy.

[26].

, there are six flow-gradient patterns: NF/VHG,

. Low flow is defined

, MG ≥ 60 mmHg, *V*max ≥ 5.0 m/s,

. NF/HG AS is defined as MG ≥ 40 mmHg and

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

**5. Hemodynamic classifications of AS**

stroke volume index (SVI) of normal flow is ≥35 ml/m<sup>2</sup>

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

NF/VHG AS pattern is defined as AVA < 1.0 cm2

higher BNP level and lower cardiac-event free survival [27].

In patients with AVA < 1 cm<sup>2</sup>

as SVI < 35 ml/m2

**5.1 High-gradient AS**

relevant findings for VHG AS.

and LVEF ≥ 50% with SVI ≥ 35 ml/m2

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

relative to the peak flow velocity and MG. Therefore, some authors have suggested that AVA cutoff value for severe AS be changed to 0.8 cm<sup>2</sup> [26].

There are other potential etiologies of discrepant AVA and MG measurements in the setting of preserved LVEF which also need to be taken into consideration. First, technical errors need to be excluded. For example, LVOT diameter measurement may be inaccurate, and/or LVOT velocity time integral may be underestimated due to misplacement of the pulsed wave Doppler sample in the LVOT, leading to the underestimation of the stroke volume and the AVA. Second, patients with small body habitus and small LV dimensions could have lower stroke volume and lower transaortic gradient. Therefore, additional diagnostic studies such as dobutamine stress echocardiography (DSE), calcium scoring using multi-detector computed tomography (MDCT), and/or BNP may be necessary to corroborate AS severity and guide management strategy.
