**2.2 Low flow low gradient severe AS with preserved left ventricular ejection fraction (stage D3)**

As opposed to patients with "classic" LFLG AS with reduced LVEF, those with "paradoxical" LFLG AS have preserved LVEF. This entity is defined as an LVEF >50%, the presence of a low flow (stroke volume index <35 ml/m2 ), an AVA <1.0 cm2 , an iAVA <0.6 cm2 /m2 , and a mean aortic valve gradient <40 mmHg [2, 5, 17]. LFLG pattern is seen in 5–15% of patients with severe AS and is more prevalent in women and elderly patients. These patients have excessive LV hypertrophy in response to the hemodynamic stress. As a result they have small LV cavities and hence a low stroke volumes despite the preserved LVEF. Other factors (**Figure 5**) that contribute to low forward flow across the aortic valve include mitral regurgitation/ stenosis, tricuspid regurgitation/stenosis, atrial fibrillation and infiltrative cardiomyopathies like amyloidosis. Paradoxical LFLG AS shares clinical, pathological and hemodynamic similarities with heart failure with preserved ejection fraction. Both conditions are characterized by significant concentric left ventricular hypertrophy

#### **Figure 5.**

*Factors leading to transformation of high gradient severe aortic stenosis to paradoxical low flow low gradient severe aortic stenosis.*

leading to small cavity size and restrictive physiology. In addition there is marked reduction in intrinsic LV systolic function that may not be apparent by routinely used echocardiographic indices. Global longitudinal strain is a more sensitive parameter that helps unmask the apparently normal LVEF in these patients. It is reduced to a larger extent due to fibrosis along the subendocardial layer. These findings suggest that paradoxical LFLG AS is a more advanced stage in the hemodynamic spectrum of severe AS [5, 18, 19] and classified in guidelines as stage D3.

## **2.3 Moderate aortic stenosis with left ventricular dysfunction—"pseudosevere" aortic stenosis**

One of the main challenges in the diagnosis of LFLG severe AS is distinguishing it from pseudo-severe AS, i.e., moderate AS with underlying LV dysfunction, unrelated to aortic stenosis. In this case, the primary culprit is LV dysfunction; typically due to associated cardiomyopathy (ischemic or idiopathic) or myocarditis. The myopathic ventricle fails to generate adequate blood flow to open the aortic valve sufficiently, hence overestimating severity of AS on echocardiography. At the same time, the gradients across the aortic valve are low related to lower transvalvular flow. This produces a hemodynamic picture similar to LFLG severe AS. Studies have shown that in patients with pseudo-severe AS, the 5-year survival with medical therapy is better than in true severe AS and comparable with that of propensity matched patients with heart failure with reduced ejection fraction and no evidence of valve disease (**Figure 6**) [20].

Paradoxically, moderate aortic stenosis for a normal ventricle may be functionally more significant for the myopathic ventricle. Some studies have suggested that moderate AS may have a detrimental effect on outcomes in patients with coexistent LV dysfunction. This concept raises the hypothesis that aortic valve replacement (AVR) may be beneficial in such patients [21, 22]. Trans-catheter Aortic Valve

#### **Figure 6.**

*Kaplan-Meier survival estimates under conservative treatment among 28 patients with pseudo-severe aortic stenosis and 28 propensity-matched patients with systolic heart failure. Reproduced with permission from Fougères et al. [20].*

**13**

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

**3. Diagnosis of low flow low gradient severe aortic stenosis**

Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial is designed to test the above hypothesis. Patients with heart failure with reduced ejection fraction and moderate AS confirmed by resting and/ or dobutamine stress echocardiography are randomized to optimized heart failure therapy alone versus optimized heart failure therapy plus transcatheter AVR.

Transthoracic echocardiogram is the gold standard to detect the "low flow state"

across the aortic valve. Accurate Doppler echocardiographic measurements of stroke volume, AVA, and gradient are important to minimize underestimation of

Typically Doppler echocardiographic assessment is operator dependent. Optimal alignment of the continuous wave Doppler beam with the direction of the aortic flow jet is crucial to accurately quantify aortic valve gradient, aortic valve area and thereby severity of AS. The apical window detects peak velocity in 40% of cases where as the right parasternal window picks up peak velocity in 50% of cases [23]. A multiwindow approach is recommended which includes apical, right

The most common technical pitfall that may lead to an erroneous diagnosis of lowflow state and overestimation of AS severity is underestimation of the left ventricular outflow tract (LVOT) diameter. The effective AVA is determined by the continuity equation method (**Figure 7**), which is based on the principle that the flow across the left ventricular outflow tract should be equal to the flow across the aortic valve. Since the LVOT diameter is squared in the equation, an underestimation of the LVOT diameter may lead to underestimation of valve area and thus the false conclusion that the patient has LFLG severe AS when, in fact, the patient has normal flow and/or moderate AS. The 2009 European Association of Echocardiography/American Society of Echocardiography guidelines suggest measuring the diameter and velocity 5–10 mm below the aortic annulus. However, recent studies suggest measuring the LVOT diameter inner-edge-to-inner-edge from the base of the right coronary cusp anteriorly to the commissure posteriorly [24, 25]. From a practical standpoint, an easy way to measure the LVOT diameter is to assess the pulse wave Doppler signal from the distal to proximal LVOT in the apical view. The LVOT velocity time integral is then measured just below the point where aliasing is seen, when the flow signals are smooth with sharp borders. The LVOT diameter is ideally measured at this point in

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

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

severe AS or an overestimation of moderate AS.

the parasternal long axis view (**Figure 8**).

catheterization laboratory by Nishimura et al. [27].

*3.1.1 Dobutamine stress echocardiography*

**3.1 Echocardiographic caveats in estimating AS severity**

parasternal, suprasternal and right supraclavicular windows.

*Aortic Stenosis - Current Perspectives*

**severe" aortic stenosis**

leading to small cavity size and restrictive physiology. In addition there is marked reduction in intrinsic LV systolic function that may not be apparent by routinely used echocardiographic indices. Global longitudinal strain is a more sensitive parameter that helps unmask the apparently normal LVEF in these patients. It is reduced to a larger extent due to fibrosis along the subendocardial layer. These findings suggest that paradoxical LFLG AS is a more advanced stage in the hemodynamic spectrum of

**2.3 Moderate aortic stenosis with left ventricular dysfunction—"pseudo-**

One of the main challenges in the diagnosis of LFLG severe AS is distinguishing it from pseudo-severe AS, i.e., moderate AS with underlying LV dysfunction, unrelated to aortic stenosis. In this case, the primary culprit is LV dysfunction; typically due to associated cardiomyopathy (ischemic or idiopathic) or myocarditis. The myopathic ventricle fails to generate adequate blood flow to open the aortic valve sufficiently, hence overestimating severity of AS on echocardiography. At the same time, the gradients across the aortic valve are low related to lower transvalvular flow. This produces a hemodynamic picture similar to LFLG severe AS. Studies have shown that in patients with pseudo-severe AS, the 5-year survival with medical therapy is better than in true severe AS and comparable with that of propensity matched patients with heart failure with reduced ejection fraction and no evidence of valve disease (**Figure 6**) [20].

Paradoxically, moderate aortic stenosis for a normal ventricle may be functionally more significant for the myopathic ventricle. Some studies have suggested that moderate AS may have a detrimental effect on outcomes in patients with coexistent LV dysfunction. This concept raises the hypothesis that aortic valve replacement (AVR) may be beneficial in such patients [21, 22]. Trans-catheter Aortic Valve

*Kaplan-Meier survival estimates under conservative treatment among 28 patients with pseudo-severe aortic stenosis and 28 propensity-matched patients with systolic heart failure. Reproduced with permission from* 

severe AS [5, 18, 19] and classified in guidelines as stage D3.

**12**

**Figure 6.**

*Fougères et al. [20].*

Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial is designed to test the above hypothesis. Patients with heart failure with reduced ejection fraction and moderate AS confirmed by resting and/ or dobutamine stress echocardiography are randomized to optimized heart failure therapy alone versus optimized heart failure therapy plus transcatheter AVR.
