*3.1.1 Dobutamine stress echocardiography*

Once technical errors in measurement are ruled out, it is essential to distinguish LFLG true severe AS from pseudo-severe AS. deFilippi et al. [26] were the first to demonstrate that low dose (up to 20 μg/kg/min) dobutamine stress echocardiography (DSE) may be used in these patients to distinguish true versus pseudo-severe stenosis. The use of DSE for this purpose has received a class IIa (level of evidence: B) recommendation in the American College of Cardiology/American Heart Association-European Society of Cardiology (ACC/AHA-ESC/EACTS) guidelines [1–3], and a similar protocol has also been used for invasive assessment in cardiac catheterization laboratory by Nishimura et al. [27].

**Figure 7.** *Continuity equation, formula to calculate aortic valve area. The LVOT is assumed to be cross sectional in area.*

Dobutamine recruits myocardial contractility in normal and hibernating myocardium, thus enhancing stroke volume and transvalvular flow. This is referred to as "stroke volume reserve." Patients with more than 20% rise in stroke volume at peak dobutamine levels are referred to as having stroke volume reserve. When the flow across the valve increases, depending on the underlying condition, one of two possibilities occurs. If the patient has true severe AS, the valve being intrinsically restricted cannot open up further. In this case the transaortic gradients will increase with little or no change in aortic valve area. On the other hand in patients with pseudo-severe AS, aortic valve area increases significantly (>0.6 cm2 /m2 ) with little or no change in trans-aortic gradients (**Figure 9**).

Though not incorporated into guidelines, in our experience, DSE can also be used in patients with LFLG severe AS with preserved LVEF. Dobutamine is able to recruit the subendocardial longitudinally oriented myocardial fibers and further increase transvalvular flow. Studies have estimated that about 30–40% of patients with LFLG severe AS may not have adequate stroke volume reserve (<20% rise in stroke volume with peak dobutamine stress) [9, 21, 26–28]. They have higher operative mortality (22–33%) than those with flow reserve (5–8%) [9]. However the presence or absence of flow reserve cannot be used to predict recovery of LV function after valve replacement

**15**

**Figure 9.**

**Figure 8.**

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment*

and cannot be used to determine long term prognosis. The French Multicenter Study of LFLG AS reported that, in patients with no LV flow reserve who survived surgical aortic valve replacement (SAVR) had similar improvement in post-operative LVEF and late survival rate compared to patients with preserved LV flow reserve [29] (**Figure 10**). These findings suggest that DSE is useful to distinguish true severe from pseudosevere AS and estimate operative risk. However, DES does not predict recovery of

*In the presence of stroke volume reserve, if the valve area remains more or less constant with increase in gradient >40 mmHg, it is suggestive of true severe AS. On the other hand, if the valve area increases with no* 

*The pulse wave Doppler is walked from the distal to proximal LVOT. At point 3, aliasing is noted suggesting that the Doppler signal is within the turbulent aortic jet. The pulse wave Doppler is moved just distal to point 3 (at point 2) where laminar LVOT velocities are seen. The LVOT VTI is measured at this point and the LVOT* 

*diameter at this corresponding point in the parasternal long axis view.*

*significant change in gradients, it is suggestive of pseudo severe AS.*

*DOI: http://dx.doi.org/10.5772/intechopen.84435*

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.84435*

#### **Figure 8.**

*Aortic Stenosis - Current Perspectives*

Dobutamine recruits myocardial contractility in normal and hibernating myocardium, thus enhancing stroke volume and transvalvular flow. This is referred to as "stroke volume reserve." Patients with more than 20% rise in stroke volume at peak dobutamine levels are referred to as having stroke volume reserve. When the flow across the valve increases, depending on the underlying condition, one of two possibilities occurs. If the patient has true severe AS, the valve being intrinsically restricted cannot open up further. In this case the transaortic gradients will increase with little or no change in aortic valve area. On the other hand in patients with

*Continuity equation, formula to calculate aortic valve area. The LVOT is assumed to be cross sectional in area.*

Though not incorporated into guidelines, in our experience, DSE can also be used in patients with LFLG severe AS with preserved LVEF. Dobutamine is able to recruit the subendocardial longitudinally oriented myocardial fibers and further increase transvalvular flow. Studies have estimated that about 30–40% of patients with LFLG severe AS may not have adequate stroke volume reserve (<20% rise in stroke volume with peak dobutamine stress) [9, 21, 26–28]. They have higher operative mortality (22–33%) than those with flow reserve (5–8%) [9]. However the presence or absence of flow reserve cannot be used to predict recovery of LV function after valve replacement

/m2

) with little

pseudo-severe AS, aortic valve area increases significantly (>0.6 cm2

or no change in trans-aortic gradients (**Figure 9**).

**14**

**Figure 7.**

*The pulse wave Doppler is walked from the distal to proximal LVOT. At point 3, aliasing is noted suggesting that the Doppler signal is within the turbulent aortic jet. The pulse wave Doppler is moved just distal to point 3 (at point 2) where laminar LVOT velocities are seen. The LVOT VTI is measured at this point and the LVOT diameter at this corresponding point in the parasternal long axis view.*


#### **Figure 9.**

*In the presence of stroke volume reserve, if the valve area remains more or less constant with increase in gradient >40 mmHg, it is suggestive of true severe AS. On the other hand, if the valve area increases with no significant change in gradients, it is suggestive of pseudo severe AS.*

and cannot be used to determine long term prognosis. The French Multicenter Study of LFLG AS reported that, in patients with no LV flow reserve who survived surgical aortic valve replacement (SAVR) had similar improvement in post-operative LVEF and late survival rate compared to patients with preserved LV flow reserve [29] (**Figure 10**).

These findings suggest that DSE is useful to distinguish true severe from pseudosevere AS and estimate operative risk. However, DES does not predict recovery of

#### **Figure 10.**

*Patients with no LV flow (contractile) reserve (Group II) defined as 20% increase in stroke volume during DSE have markedly reduced survival compared with those with LV flow reserve (Group I), regardless of the type of treatment. Aortic valve replacement is associated with dramatic improvement in survival in patients with LV flow reserve and a trend for better survival in those with no flow reserve. \* p 0.001 versus medical; § p 0.07 versus medical. Adapted with permission from Monin et al. [9].*

LV function, improvement in symptom status, and late survival after SAVR [9, 13, 30]. Though the absence of flow reserve portends higher perioperative mortality, DSE should only be used as a diagnostic modality. The absence of LV flow reserve should not exclude patients for AVR [9, 12].

#### *3.1.2 Projected effective orifice area*

DSE results maybe inconclusive in 30–40% due to inadequate stroke volume reserve [9, 13]. In this patient subset, the investigators of the TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study proposed to calculate the projected effective orifice area (EOA) that would have occurred at a standardized flow rate of 250 ml/s (EOAProj) [21, 31] (**Figure 11**). This parameter, standardized for flow, has been shown to better predict the actual hemodynamic severity of the valve stenosis and the clinical outcome of patients with classical or paradoxical LFLG AS, as compared with standard stress echocardiography parameters [8, 21, 33]. A projected AVA <1.0 cm2 confirms the presence of true severe AS (**Figure 11**). Some patients may not have an adequate increase in stroke volume but nevertheless will have an increase in transvalvular flow rate due to shortening of ejection time. The phase III of the TOPAS study is currently underway and is expected to be completed by 2022.

#### *3.1.3 CT calcium score of the aortic valve*

About 15–20% of patients may have inconclusive results from DSE and may not have adequate transvalvular flow rate to calculate projected effective orifice area. DSE can be used in patients with paradoxical LFLG AS; however, some patients with very small LV cavities can develop dynamic LVOT obstruction and hypotension. For such patients, an alternative method to assess aortic stenosis severity is proposed.

Multi detector computerized tomography (MDCT) scan without contrast can accurately quantify calcium distribution along the AV leaflets. Calcium burden along the AV leaflets has been shown to correlate with severity of aortic stenosis [34]. It is an anatomical test independent of hemodynamics, blood flow and does not require administration of contrast or any stress agents. For the quantitation of calcification, a non-contrast MDCT scan during trained end-inspiration breathhold is performed. Radiation exposure for such an examination is <3 mSV. The amount of calcification in the region of the aortic valve is quantitated using the

**17**

>500 AU/cm2

**Figure 11.**

*is 0.81 cm<sup>2</sup>*

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment*

modified Agatston method, in which calcification is defined as four adjacent pixels with a density >130 Hounsfield Units [35]. The aortic valve calcium score measured by MDCT strongly correlates with hemodynamic severity, the progression rate, and the clinical outcomes of AS patients [34, 36, 37]. Women tend to develop less calcification for the same degree of severity of stenosis. Cut off values for valve calcification to differentiate severe versus non-severe AS in men is >2000 AU and in women >1200 AU [34, 38]. The same approach should be applied when using cutoff point for aortic valve calcium density (i.e., calcium score indexed to LVOT area):

*DSE in a patient with low flow low gradient state across the aortic valve. Even with dobutamine the valve area* 

 *and the mean gradient is still <40 mmHg. Due to inconclusive results, the projected effective orifice* 

It is important to note that MDCT grossly underestimates valve fibrosis and hence significantly underestimates severe AS in younger patients [39]. Hence this technique may be used in older patients where the degenerative aortic valve pathol-

The advent of echocardiography revolutionized the field of cardiology providing hemodynamic data that could only be previously obtained by invasive cardiac catheterization. However echocardiographic derivations are based on some basic assumptions, which might not be reliable for all patient anatomy. Furthermore, there are limitations on subjective assessment by personnel with varying experience. Doppler measurements are dependent on the angle of insinuation of the sound waves against the jet of blood flow across the aortic valve (**Figure 13**). Depending on the restriction along the leaflet coaptation edges, the jet of blood through the stenosed AV, can be eccentric. This makes it almost impossible to align the continuous wave Doppler perpendicular to the jet. The peak velocity is inversely proportional to the cosine of the angle of insinuation. Even a 1° off axis tilt may reduce the peak velocity by 0.04 m/s representing an error of 1%, considering a cut off value of 4 m/s for severe aortic stenosis. When the estimated velocity is squared to calculate pressure gradient

*3.1.4 Invasive assessment of aortic stenosis in the catheterization laboratory*

in women [34–38] (**Figure 12**).

 *suggesting the presence of true severe* 

in men versus >300 AU/cm2

*area is calculated at a normalized flow rate of 250 ml/s which is 0.84 cm2*

*AS. Adapted with permission from Clavel et al. [32].*

*3.1.4.1 Pitfalls of echocardiography in diagnosis of AS*

across the aortic valve, any error is exponentially increased.

ogy is driven by valve calcification.

*DOI: http://dx.doi.org/10.5772/intechopen.84435*

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.84435*

#### **Figure 11.**

*Aortic Stenosis - Current Perspectives*

not exclude patients for AVR [9, 12].

*flow reserve and a trend for better survival in those with no flow reserve. \**

*medical. Adapted with permission from Monin et al. [9].*

*3.1.3 CT calcium score of the aortic valve*

*3.1.2 Projected effective orifice area*

AVA <1.0 cm2

**Figure 10.**

LV function, improvement in symptom status, and late survival after SAVR [9, 13, 30]. Though the absence of flow reserve portends higher perioperative mortality, DSE should only be used as a diagnostic modality. The absence of LV flow reserve should

*Patients with no LV flow (contractile) reserve (Group II) defined as 20% increase in stroke volume during DSE have markedly reduced survival compared with those with LV flow reserve (Group I), regardless of the type of treatment. Aortic valve replacement is associated with dramatic improvement in survival in patients with LV* 

*p 0.001 versus medical; §*

*p 0.07 versus* 

DSE results maybe inconclusive in 30–40% due to inadequate stroke volume reserve [9, 13]. In this patient subset, the investigators of the TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study proposed to calculate the projected effective orifice area (EOA) that would have occurred at a standardized flow rate of 250 ml/s (EOAProj) [21, 31] (**Figure 11**). This parameter, standardized for flow, has been shown to better predict the actual hemodynamic severity of the valve stenosis and the clinical outcome of patients with classical or paradoxical LFLG AS, as compared with standard stress echocardiography parameters [8, 21, 33]. A projected

may not have an adequate increase in stroke volume but nevertheless will have an increase in transvalvular flow rate due to shortening of ejection time. The phase III of the TOPAS study is currently underway and is expected to be completed by 2022.

About 15–20% of patients may have inconclusive results from DSE and may not have adequate transvalvular flow rate to calculate projected effective orifice area. DSE can be used in patients with paradoxical LFLG AS; however, some patients with very small LV cavities can develop dynamic LVOT obstruction and hypotension. For such patients, an alternative method to assess aortic stenosis severity is proposed. Multi detector computerized tomography (MDCT) scan without contrast can accurately quantify calcium distribution along the AV leaflets. Calcium burden along the AV leaflets has been shown to correlate with severity of aortic stenosis [34]. It is an anatomical test independent of hemodynamics, blood flow and does not require administration of contrast or any stress agents. For the quantitation of calcification, a non-contrast MDCT scan during trained end-inspiration breathhold is performed. Radiation exposure for such an examination is <3 mSV. The amount of calcification in the region of the aortic valve is quantitated using the

confirms the presence of true severe AS (**Figure 11**). Some patients

**16**

*DSE in a patient with low flow low gradient state across the aortic valve. Even with dobutamine the valve area is 0.81 cm<sup>2</sup> and the mean gradient is still <40 mmHg. Due to inconclusive results, the projected effective orifice area is calculated at a normalized flow rate of 250 ml/s which is 0.84 cm2 suggesting the presence of true severe AS. Adapted with permission from Clavel et al. [32].*

modified Agatston method, in which calcification is defined as four adjacent pixels with a density >130 Hounsfield Units [35]. The aortic valve calcium score measured by MDCT strongly correlates with hemodynamic severity, the progression rate, and the clinical outcomes of AS patients [34, 36, 37]. Women tend to develop less calcification for the same degree of severity of stenosis. Cut off values for valve calcification to differentiate severe versus non-severe AS in men is >2000 AU and in women >1200 AU [34, 38]. The same approach should be applied when using cutoff point for aortic valve calcium density (i.e., calcium score indexed to LVOT area): >500 AU/cm2 in men versus >300 AU/cm2 in women [34–38] (**Figure 12**).

It is important to note that MDCT grossly underestimates valve fibrosis and hence significantly underestimates severe AS in younger patients [39]. Hence this technique may be used in older patients where the degenerative aortic valve pathology is driven by valve calcification.

#### *3.1.4 Invasive assessment of aortic stenosis in the catheterization laboratory*

#### *3.1.4.1 Pitfalls of echocardiography in diagnosis of AS*

The advent of echocardiography revolutionized the field of cardiology providing hemodynamic data that could only be previously obtained by invasive cardiac catheterization. However echocardiographic derivations are based on some basic assumptions, which might not be reliable for all patient anatomy. Furthermore, there are limitations on subjective assessment by personnel with varying experience. Doppler measurements are dependent on the angle of insinuation of the sound waves against the jet of blood flow across the aortic valve (**Figure 13**). Depending on the restriction along the leaflet coaptation edges, the jet of blood through the stenosed AV, can be eccentric. This makes it almost impossible to align the continuous wave Doppler perpendicular to the jet. The peak velocity is inversely proportional to the cosine of the angle of insinuation. Even a 1° off axis tilt may reduce the peak velocity by 0.04 m/s representing an error of 1%, considering a cut off value of 4 m/s for severe aortic stenosis. When the estimated velocity is squared to calculate pressure gradient across the aortic valve, any error is exponentially increased.

#### **Figure 12.**

*Quantitation of aortic valve calcium by multi-detector computed tomography for the assessment of stenosis severity in low-gradient aortic stenosis. (A) Multi-detector computed tomography can be used to quantitate aortic valve calcification by the modified Agatston method. With this method, calcification is defined as four adjacent pixels with density 0.130 Hounsfield units. Different cut-point values of valve calcium score should be used in women (0.1200 AU) versus men (0.2000 AU) to differentiate true-severe versus pseudo-severe stenosis in low-flow, lowgradient aortic stenosis. (B) Serial multi-detector computed tomography slices at the level of the aortic valve showing a severely calcified valve with a calcium score of 5040 AU consistent with true-severe aortic stenosis. Calcified areas are displayed in yellow in the bottom images. (C) Mild calcification (score 271 AU) consistent with pseudo-severe aortic stenosis. (D) Pitfalls in the assessment of aortic valve calcification by multi-detector computed tomography. For the calculation of calcium score, it is important to only include aortic valve calcification and exclude calcification of aorta, coronary arteries, LVOT, and mitral annulus. Adapted with permission from Clavel et al. [32].*

Another common limitation of echocardiography is the assumption that LVOT is circular in cross section, when in fact it is circular in only 1–2% of cases (**Figure 14**). The LVOT is a three-dimensional (3D) dynamic structure that is often elliptical, with the antero-posterior dimension representing the smaller minor axis diameter, as compared with the generally larger diameter in the sagittal plane. Hence, 2D echocardiography may underestimate the LVOT area compared with 3D imaging modalities such as 3D echocardiography, MDCT, or cardiac magnetic resonance [40–43]. To overcome the potential underestimation of the LVOT diameter and stroke volume and AVA by 2D echocardiography, the use of a hybrid approach has been suggested, where the LVOT area is measured by MDCT or 3D echocardiography and the LVOT and aortic flow velocities are measured by Doppler echocardiography [43, 44]. However, it is also important to note, the AVA value generally used to define severe AS <1.0 cm2 , has been established and validated by outcome studies, where AVA was measured by standard 2D Doppler-echocardiography [2, 4]. A recent study demonstrated that the hybrid approach systematically overestimates the LVOT area and thus AVA. The best discriminative hybrid AVA to predict mortality in patients with AS under medical treatment was larger (1.2 cm2 ) versus the Doppler-echocardiographic AVA (1.0 cm2 ) [43].

Finally, it becomes difficult to obtain LVOT velocity time integral when there is associated subaortic fixed or dynamic obstruction contributing to transvalvular gradients.

**19**

**Figure 13.**

**Figure 14.**

*thus underestimating velocities.*

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment*

*DOI: http://dx.doi.org/10.5772/intechopen.84435*

*3.1.4.2 Invasive assessment of severe AS*

*CT showing elliptical shape of the LVOT.*

Currently invasive measurement is recommended only when non-invasive tests are inconclusive, the patient has poor echo windows or when there is significant discrepancy between the patient's clinical symptoms and echocardiographic data. **Figure 15** shows the steps of invasive assessment of aortic stenosis in the catheterization lab. Ideally simultaneous pressure gradients are measured by obtaining dual arterial access. Single arterial puncture may also be used for diagnosis by inserting a 7F long sheath reaching the ascending aorta from where pressure can be transduced from the side port of the long sheath. The pressure from the left ventricle should be transduced through a 5F pigtail catheter inserted into the left ventricle through the long sheath. The cardiac output is measured either by thermodilution using a Swan Ganz catheter or by Fick's principle. Dobutamine stress can be achieved using incremental doses, infused through a venous sheath. Cardiac output, mean gradient

*Doppler measurements are angle dependent. For optimal values the angle of insinuation should be parallel/ antiparallel (0 or 180°) to the flow of blood. As the Doppler angle increases, the measured velocities decrease,* 

across the aortic valve, aortic valve area and iAVA is calculated after at least

2 minutes of incremental dobutamine infusion [27].

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.84435*

#### **Figure 13.**

*Aortic Stenosis - Current Perspectives*

Another common limitation of echocardiography is the assumption that LVOT is circular in cross section, when in fact it is circular in only 1–2% of cases (**Figure 14**). The LVOT is a three-dimensional (3D) dynamic structure that is often elliptical, with the antero-posterior dimension representing the smaller minor axis diameter, as compared with the generally larger diameter in the sagittal plane. Hence, 2D echocardiography may underestimate the LVOT area compared with 3D imaging modalities such as 3D echocardiography, MDCT, or cardiac magnetic resonance [40–43]. To overcome the potential underestimation of the LVOT diameter and stroke volume and AVA by 2D echocardiography, the use of a hybrid approach has been suggested, where the LVOT area is measured by MDCT or 3D echocardiography and the LVOT and aortic flow velocities are measured by Doppler echocardiography [43, 44]. However, it is also important to note, the AVA value generally

*of aorta, coronary arteries, LVOT, and mitral annulus. Adapted with permission from Clavel et al. [32].*

*Quantitation of aortic valve calcium by multi-detector computed tomography for the assessment of stenosis severity in low-gradient aortic stenosis. (A) Multi-detector computed tomography can be used to quantitate aortic valve calcification by the modified Agatston method. With this method, calcification is defined as four adjacent pixels with density 0.130 Hounsfield units. Different cut-point values of valve calcium score should be used in women (0.1200 AU) versus men (0.2000 AU) to differentiate true-severe versus pseudo-severe stenosis in low-flow, lowgradient aortic stenosis. (B) Serial multi-detector computed tomography slices at the level of the aortic valve showing a severely calcified valve with a calcium score of 5040 AU consistent with true-severe aortic stenosis. Calcified areas are displayed in yellow in the bottom images. (C) Mild calcification (score 271 AU) consistent with pseudo-severe aortic stenosis. (D) Pitfalls in the assessment of aortic valve calcification by multi-detector computed tomography. For the calculation of calcium score, it is important to only include aortic valve calcification and exclude calcification* 

studies, where AVA was measured by standard 2D Doppler-echocardiography [2, 4]. A recent study demonstrated that the hybrid approach systematically overestimates the LVOT area and thus AVA. The best discriminative hybrid AVA to predict

Finally, it becomes difficult to obtain LVOT velocity time integral when there is associated subaortic fixed or dynamic obstruction contributing to transvalvular

) [43].

mortality in patients with AS under medical treatment was larger (1.2 cm2

, has been established and validated by outcome

) versus

**18**

gradients.

**Figure 12.**

used to define severe AS <1.0 cm2

the Doppler-echocardiographic AVA (1.0 cm2

*Doppler measurements are angle dependent. For optimal values the angle of insinuation should be parallel/ antiparallel (0 or 180°) to the flow of blood. As the Doppler angle increases, the measured velocities decrease, thus underestimating velocities.*

**Figure 14.** *CT showing elliptical shape of the LVOT.*

#### *3.1.4.2 Invasive assessment of severe AS*

Currently invasive measurement is recommended only when non-invasive tests are inconclusive, the patient has poor echo windows or when there is significant discrepancy between the patient's clinical symptoms and echocardiographic data. **Figure 15** shows the steps of invasive assessment of aortic stenosis in the catheterization lab. Ideally simultaneous pressure gradients are measured by obtaining dual arterial access. Single arterial puncture may also be used for diagnosis by inserting a 7F long sheath reaching the ascending aorta from where pressure can be transduced from the side port of the long sheath. The pressure from the left ventricle should be transduced through a 5F pigtail catheter inserted into the left ventricle through the long sheath. The cardiac output is measured either by thermodilution using a Swan Ganz catheter or by Fick's principle. Dobutamine stress can be achieved using incremental doses, infused through a venous sheath. Cardiac output, mean gradient across the aortic valve, aortic valve area and iAVA is calculated after at least 2 minutes of incremental dobutamine infusion [27].

#### **Figure 15.**

*Invasive assessment of low flow gradient AS in the Cathlab. Panel A shows the initial setup of the catheters. A 7F long sheath is positioned with its tip in the ascending aorta from where aortic pressures are transduced. A 5F pigtail is positioned in the LV through the long sheath to measure LV pressures. A Swan Ganz catheter is positioned in the pulmonary artery to measure cardiac output at each stage. Panel B—at baseline the patient is shown to have an indexed valve area of 0.5 cm2 , with a mean gradient of 34 mmHg across the aortic valve. Panel C—with 10 μg/min of dobutamine, the trans-aortic gradients increase from 34 to 57 mmHg with no significant change in indexed valve area suggesting the presence of true severe AS.*

#### **Figure 16.**

*Four-step algorithm for the diagnostic and therapeutic management of low-gradient AS. AVC ¼ aortic valve calcification; AVCd ¼ aortic valve calcification density; AVR ¼ aortic valve replacement; CMR ¼ cardiac magnetic resonance; MDCT ¼ multi-detector computed tomography; RCT ¼ randomized controlled trial; TEE ¼ transesophageal echocardiography; TTE ¼ transthoracic echocardiography. Reproduced with permission from Clavel et al. [1].*

**21**

*Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment*

down in the LVOT, thus facilitating accurate diagnosis.

estimating transvalvular pressure gradients.

gradient aortic stenosis.

**4. Prognosis and management**

outcomes following intervention.

**ventricular ejection fraction: (stage D2)**

Invasive assessment is not limited by the factors that confound echocardiographic measurement mentioned above. In the presence of serial obstruction, an end hole catheter can be positioned above and below the point of interest and pressure gradients can be reassessed. In this scenario, it is possible to determine the site that contributes maximally to gradients—either the valve or the obstruction further

Another advantage of invasive assessment is that the operators often perform coronary angiography prior to potentially inducing dobutamine stress. When there is no flow limiting coronary artery disease, higher doses of dobutamine (up to 40 μg/ kg body weight) can be used to obtain a conclusive result. When there is associated significant coronary artery disease, high dose dobutamine (>30 μg/kg body weight) can result in a "biphasic response," further reducing blood flow across the aortic valve, thus confounding results. This is one of the main reasons why a low dose dobutamine is recommended when doing a DSE. In the cardiac catherization laboratory however, any significant coronary artery disease can be treated percutaneously before escalating to higher doses of dobutamine to diagnose LFLG severe AS.

The disadvantage of invasive assessment is the potential complications of cardiac catheterization, especially when crossing the heavily calcified aortic valve; in particular stroke. In the presence of a small aortic root, the phenomenon of "pressure recovery" may confound gradients by increasing aortic pressure and under

The diagnosis of LFLG severe aortic stenosis requires a systematic approach with a series of tests. **Figure 16** summarizes an algorithm for assessment of low flow low

The importance of establishing the diagnosis of LFLG severe AS is reflected in its differing prognosis to high gradient severe AS. Not only are the outcomes with conservative management worse in LFLG AS, studies have also suggested poorer

Among the subgroups of severe AS, classical LFLG AS has the worst clinical outcome. With medical management the 2-year survival is approximately 40–60%. Thirty-day mortality of SAVR is high depending on the presence or absence of flow reserve (8–33%) [8, 9, 12, 13, 29]. However, if patients survive SAVR, there is a prognostic benefit compared to medical therapy. There is limited head to head randomized data comparing SAVR and TAVR in patients with LFLG severe AS. There are few studies that suggest that TAVR leads to better and faster LV function recovery compared to SAVR [45, 46]. It is well known that TAVR, especially with supraannular valves leads to less patient prosthesis mismatch, which is an independent predictor of worse outcomes [46], especially in patients with reduced LV ejection fraction. In patients with no flow reserve who represent the highest risk subgroup, TAVR may have a definite survival benefit over SAVR. Thought the PARTNER I trial conclusively proved the superiority of TAVR to medical management and similar outcomes to SAVR [47], patients with no LV flow reserve as well as those with very low LVEF were excluded. More randomized studies are needed to confirm the superiority of TAVR over SAVR in patients with classical LFLG severe AS (stage D2). The heart team plays the central role in selecting the most appropriate modality of treatment, i.e., TAVR versus SAVR versus medical management (**Figure 17**).

**4.1 "Classical" low flow low gradient severe AS with reduced left** 

*DOI: http://dx.doi.org/10.5772/intechopen.84435*

#### *Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.84435*

*Aortic Stenosis - Current Perspectives*

*is shown to have an indexed valve area of 0.5 cm2*

*Invasive assessment of low flow gradient AS in the Cathlab. Panel A shows the initial setup of the catheters. A 7F long sheath is positioned with its tip in the ascending aorta from where aortic pressures are transduced. A 5F pigtail is positioned in the LV through the long sheath to measure LV pressures. A Swan Ganz catheter is positioned in the pulmonary artery to measure cardiac output at each stage. Panel B—at baseline the patient* 

*Panel C—with 10 μg/min of dobutamine, the trans-aortic gradients increase from 34 to 57 mmHg with no* 

*Four-step algorithm for the diagnostic and therapeutic management of low-gradient AS. AVC ¼ aortic valve calcification; AVCd ¼ aortic valve calcification density; AVR ¼ aortic valve replacement; CMR ¼ cardiac magnetic resonance; MDCT ¼ multi-detector computed tomography; RCT ¼ randomized controlled trial; TEE ¼ transesophageal echocardiography; TTE ¼ transthoracic echocardiography. Reproduced with* 

*significant change in indexed valve area suggesting the presence of true severe AS.*

*, with a mean gradient of 34 mmHg across the aortic valve.* 

**Figure 15.**

**20**

**Figure 16.**

*permission from Clavel et al. [1].*

Invasive assessment is not limited by the factors that confound echocardiographic measurement mentioned above. In the presence of serial obstruction, an end hole catheter can be positioned above and below the point of interest and pressure gradients can be reassessed. In this scenario, it is possible to determine the site that contributes maximally to gradients—either the valve or the obstruction further down in the LVOT, thus facilitating accurate diagnosis.

Another advantage of invasive assessment is that the operators often perform coronary angiography prior to potentially inducing dobutamine stress. When there is no flow limiting coronary artery disease, higher doses of dobutamine (up to 40 μg/ kg body weight) can be used to obtain a conclusive result. When there is associated significant coronary artery disease, high dose dobutamine (>30 μg/kg body weight) can result in a "biphasic response," further reducing blood flow across the aortic valve, thus confounding results. This is one of the main reasons why a low dose dobutamine is recommended when doing a DSE. In the cardiac catherization laboratory however, any significant coronary artery disease can be treated percutaneously before escalating to higher doses of dobutamine to diagnose LFLG severe AS.

The disadvantage of invasive assessment is the potential complications of cardiac catheterization, especially when crossing the heavily calcified aortic valve; in particular stroke. In the presence of a small aortic root, the phenomenon of "pressure recovery" may confound gradients by increasing aortic pressure and under estimating transvalvular pressure gradients.

The diagnosis of LFLG severe aortic stenosis requires a systematic approach with a series of tests. **Figure 16** summarizes an algorithm for assessment of low flow low gradient aortic stenosis.

## **4. Prognosis and management**

The importance of establishing the diagnosis of LFLG severe AS is reflected in its differing prognosis to high gradient severe AS. Not only are the outcomes with conservative management worse in LFLG AS, studies have also suggested poorer outcomes following intervention.

#### **4.1 "Classical" low flow low gradient severe AS with reduced left ventricular ejection fraction: (stage D2)**

Among the subgroups of severe AS, classical LFLG AS has the worst clinical outcome. With medical management the 2-year survival is approximately 40–60%. Thirty-day mortality of SAVR is high depending on the presence or absence of flow reserve (8–33%) [8, 9, 12, 13, 29]. However, if patients survive SAVR, there is a prognostic benefit compared to medical therapy. There is limited head to head randomized data comparing SAVR and TAVR in patients with LFLG severe AS. There are few studies that suggest that TAVR leads to better and faster LV function recovery compared to SAVR [45, 46]. It is well known that TAVR, especially with supraannular valves leads to less patient prosthesis mismatch, which is an independent predictor of worse outcomes [46], especially in patients with reduced LV ejection fraction. In patients with no flow reserve who represent the highest risk subgroup, TAVR may have a definite survival benefit over SAVR. Thought the PARTNER I trial conclusively proved the superiority of TAVR to medical management and similar outcomes to SAVR [47], patients with no LV flow reserve as well as those with very low LVEF were excluded. More randomized studies are needed to confirm the superiority of TAVR over SAVR in patients with classical LFLG severe AS (stage D2).

The heart team plays the central role in selecting the most appropriate modality of treatment, i.e., TAVR versus SAVR versus medical management (**Figure 17**).

A comprehensive risk stratification algorithm that takes into consideration risk scores (STS), frailty indices, major organ compromise and procedure specific impediments is used by the heart team to risk stratify the patient. Ideally the risk stratification process may also take into consideration specific factors that are not mentioned in the guidelines. These include preoperative NHYA class >III, low trans-aortic gradient (<20 mmHg), absence of flow reserve and reduced global longitudinal strain. A reduced global longitudinal strain, by itself suggests high risk, independent of risk scores (STS/Euroscore) [8, 9, 12].

Palliative balloon aortic valvuloplasty and medical management should be considered in patients with an expected life expectancy <1 year (**Figure 17**). In patients with classical LFLG severe AS with prohibitive and high surgical risk TAVR is recommended. In patients with intermediate surgical risk, SAVR or TAVR may be considered depending heart team evaluation; depending on other factors such as frailty, major organ compromise and procedure specific impediments (hostile chest in case of SAVR or vascular access route for TAVR).
