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Low-Flow, Low-Gradient Aortic Stenosis With Preserved Left Ventricular Ejection Fraction


Low-flow, low-gradient (LF-LG) aortic stenosis (AS) is characterized by a small aortic valve area (AVA<1.0 cm 2 ), a low gradient (mean <40 mm Hg), and a low-flow state (stroke volume index [SVI] <35 mL/m 2 ). The LF-LG AS pattern may occur in the context of either a reduced (i.e., “classical” low-flow; see Chapter 82 ) or preserved (i.e., “paradoxical” low-flow) left ventricular ejection fraction (LVEF). Besides classical and paradoxical LF-LG AS, there is another entity called normal-flow, low-gradient AS that is characterized by a small AVA and low gradient but with a normal SVI and a preserved LVEF ( Fig. 83.1 ). In these patients with normal-flow, low-gradient AS, the SVI is normal, but the mean flow rate (stroke volume [SV]/left ventricular [LV] ejection time) is generally low (<200 mL/s). The purpose of this chapter is to provide an update on the Doppler echocardiographic assessment of paradoxical LF-LG AS.

Figure 83.1
Different patterns of severe aortic stenosis (AS) according to flow, gradient, and left ventricular (LV) geometry in cases of preserved left ventricular ejection fraction (LVEF). The majority of patients with severe AS develop LV hypertrophy with normal LV cavity size ( left ), which allows maintenance of normal LV pump function. These patients with severe AS and normal transvalvular flow generally exhibit a high gradient. In contrast, patients with low LVEF, “classical” low-flow, low-gradient AS ( middle ) are characterized by a dilated left ventricle with markedly decreased LV systolic function most often caused by ischemic heart disease or afterload mismatch. On the other hand, normal LVEF, “paradoxical” low-flow, low-gradient AS ( right ) is characterized by pronounced LV concentric remodeling, leading to impaired filling and reduced pump function. Because of the low flow state, the patients in the two latter categories may present with a low gradient despite presence of severe stenosis. AVA, Aortic valve area; MG, mean transvalvular gradient; SVI, stroke volume index.

Adapted with permission from Pibarot P, Dumesnil JG: Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction, J Am Coll Cardiol 2012;60:1845–1853.

Clinical Presentation and Pathophysiology of Paradoxical Low-Flow, Low-Gradient Aortic Stenosis

Paradoxical LF-LG AS is defined as a small AVA (i.e., AVA<1.0 cm 2 and indexed AVA<0.6 cm 2 /m 2 ), a low gradient (i.e., <40 mm Hg), a low flow (i.e., SVI <35 mL/m 2 ), and a preserved LVEF (i.e., ≥50%). The reported prevalence of this entity includes 5% to 25% of AS patients and has been shown to increase with age, female gender, and concomitant presence of systemic arterial hypertension, metabolic syndrome, or diabetes. The cumulative effect of one or more of these factors contributes to more pronounced or exaggerated LV concentric remodeling, the development of myocardial fibrosis, and, as a result, reduction in the size, compliance, and filling of the LV cavity (see Fig. 83.1 ). , , Moreover, LV systolic function, which is apparently normal when only observing the LVEF, is, in fact, substantially reduced when considering global LV longitudinal strain. Longitudinal strain has been shown to be more sensitive to detect subclinical alterations of intrinsic myocardial systolic function. , Hence, decreased SV in paradoxical LF-LG AS is predominantly caused by impaired LV filling but also in part by abnormal LV emptying. Table 83.1 summarizes the main clinical and Doppler echocardiographic features of paradoxical LF-LG AS, and Fig. 83.2 and , , present an example of a patient with this entity. It is also important to emphasize that several other factors, besides the restrictive LV physiology, may also contribute to the reduction of LV forward SV in patients with AS and preserved LVEF, including reduced arterial compliance, atrial fibrillation, concomitant mitral regurgitation, mitral stenosis, or tricuspid regurgitation. ,

TABLE 83.1
Clinical and Doppler Echocardiographic Features of Paradoxical Low-Flow, Low-Gradient Aortic Stenosis
Clinical Characteristics
Older age
Predominantly women
Frequent comorbidities: systemic hypertension, metabolic syndrome, diabetes
Atrial fibrillation
Doppler Echocardiographic Features
Aortic Valve
Severely thickened and calcified valve with reduced opening
AVA <1.0 cm 2 , AVAi <0.6 cm 2 / m 2 , DVI <0.25
Mean transvalvular gradient <40 mm Hg
Valvuloarterial impedance >4.5 mm Hg.mL –1 .m 2
Left Ventricle
Ejection fraction ≥50%
Small cavity size:

  • End-diastolic diameter <47 mm a

  • End-diastolic volume <55 mL.m –2a

Relative wall thickness ratio >0.5
Impaired LV filling
Impaired GLS: <15% a
SVI <35 mL/m 2
Transvalvular flow rate <200 mL/s a
Other Valves
Mitral regurgitation or stenosis
Tricuspid regurgitation
AVA, Aortic valve area; AVAi, aortic valve area indexed to body surface area; DVI, Doppler velocity index; GLS, global longitudinal strain; LV, left ventricular; SVI, stroke volume index.

a Values based on initial retrospective studies , , , and are given as an indication. Further investigations are needed to determine more precise cut points.

Figure 83.2, Patient with paradoxical low-flow, low-gradient aortic stenosis (AS). This is the case of a 78-year-old woman with a history of calcific AS who is in New York Hear Association functional class III. The parasternal long- and short-axis views show a small left ventricular cavity with pronounced concentric remodeling and preserved left ventricular ejection fraction (LVEF) and a calcified and thickened aortic valve with restricted opening ( A and B ; see Video 83.2A , Video 83.2B , Video 83.2C ). This patient underwent low-dose dobutamine stress echocardiography up to 15 μg/kg/min. The LVEF increased from 60% to 70%, the stroke volume increased from 42 to 52 mL, the peak/mean gradient increased from 51/29 to 94/57 mm Hg ( C and D ), and the aortic valve area increased slightly from 0.70 to 0.77 cm 2 . This is a case of paradoxical low-flow, low-gradient severe AS. This patient underwent a successful aortic valve replacement.

Video 83.2. Patient with paradoxical low-flow, low-gradient aortic stenosis (AS). A–C, This 78-year-old woman has a history of calcific AS and is in New York Heart Association functional class III. The parasternal long- and short-axis views show a small left ventricular cavity with pronounced concentric remodeling and preserved left ventricular ejection fraction and a calcified and thickened aortic valve with restricted opening.

The presence of a low-flow state in the context of preserved LVEF complicates the assessment of stenosis severity and therapeutic decision making. Patients with paradoxical LF-LG severe AS have a 40% to 50% lower referral to surgery compared with patients with the expected normal-flow, high-gradient pattern of AS, likely because of underestimation of stenosis severity consequently to the relatively low gradient. , Yet several studies have demonstrated that these patients have worse prognosis compared with those with normal-flow, high-gradient AS and have much better prognosis when treated surgically than medically. , , , ,

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