Low flow, low gradient aortic stenosis
Synonyms and keywords: Low flow low gradient aortic stenosis, LF-LG aortic stenosis, low flow low gradient aortic stenosis with low ejection fraction, low flow flow gradient aortic stenosis with normal ejection fraction

# Overview
In aortic stenosis, as the aortic orifice area decreases the transvalvular gradient increases; in fact, when the aortic valve effective orifice area decreases below 1 cm2 the mean transvalvular gradient is expected to be greater than 40 mmHg.The transvalvular gradient is highly dependent on the flow of blood through the valve; however, when severe systolic and/or diastolic myocardial dysfunction coexist with the aortic stenosis, there is a decrease in the flow through the valve leading to a prominent decrease in the transvalvular gradient, a condition referred to as low flow, low gradient aortic stenosis (LF-LG AS).  LF-LG AS is a challenging diagnosis that must be done in order to tailor the management plan.  It is important to recognize this entity because it might lead to either underestimation or overestimation of the degree of severity of the aortic stenosis.  Two various scenarios occur in the setting of LF-LG AS depending on the status of the left ventricular ejection fraction (LVEF): LF-LG AS with low LVEF and LF-LG AS with normal LVEF.

# Epidemiology
Low flow low gradient aortic stenosis with low ejection fraction is reported in approximately 5 to 10% of patients with severe aortic stenosis; whereas low flow low gradient aortic stenosis with normal left ventricular ejection fraction is observed in 10 to 25% of patients with severe aortic stenosis.

# Pathophysiology

## Low Flow, Low Gradient Aortic Stenosis with Low Ejection Fraction
- When ventricular systolic dysfunction is present, the myocardium can not contract strongly enough to pump blood with a lot of pressure. In this case, low flow and subsequent low transvalvular gradient are present and this entity is referred to as LF-LG AS with low LVEF.
- LF-LG AS with low LVEF is defined as:
- An aortic valve areas < 1.0 cm2, and
- A left ventricular ejection fraction < 40-50%( 30% in other references), and
- A mean pressure difference or gradient across the aortic valve of < 40 mm Hg
- When low flow low gradient aortic stenosis is present, the challenge is to determine whether the LF-LG AS with low LVEF is a true severe aortic stenosis or a pseudo-severe aortic stenosis.  It is very important to differentiate these two entities as they have different outcomes following aortic valve replacement.
- In true severe aortic stenosis, the aortic stenosis is so severe that it caused secondary left ventricular dysfunction. This systolic dysfunction causes decreased contractility leading to decreased ejection force and low transvalvular flow and gradient.
Following are the features of Pseudo-severe Aortic Stenosis.
- In pseudo-severe aortic stenosis, the aortic stenosis is mild or moderate and it co-exists with another myocardial disease that is independent from the aortic stenosis.  Overestimation of the severity of the aortic stenosis may happen in this context.
- The presence of fibrosis in the left ventricle may cause an incomplete recovery after aortic valve replacement.
- This scenario can also occur among patients in whom there is a history of myocardial infarction and insufficient contractility to mount an aortic gradient.
- It may also occur when myocardial fibrosis develops due to longstanding aortic stenosis.

## Low Flow, Low Gradient Aortic Stenosis with Normal Ejection Fraction
LF-LG AS with normal ejection fraction has been recently described.
- LF-LG aortic stenosis with normal LVEF is usually an advanced stage of valvular and myocardial diseases.  The normal ejection fraction might lead to an underestimation of the severity of the aortic stenosis.
- LF-LG AS with normal ejection fraction has a lot of similarities with normal ejection fraction diastolic heart failure. In fact, it is usually present in older females and in the context of hypertension. The underlying pathophysiology of LF-LG AS with normal ejection fraction is a restrictive myocardium.
- LF-LG AS with normal ejection fraction is characterized by the presence of extensive remodeling due to predominant diastolic dysfunction as well as systolic dysfunction.  However, the decrease in the systolic performance of the left ventricle does not contribute to a decrease in the ejection fraction.

# Diagnosis
- Echocardiography is fairly accurate in the assessment of the severity of aortic stenosis in patients with normal or near normal cardiac output. However, dobutamine stress echocardiography or cardiac catheterization may be required to accurately assess the severity of aortic stenosis in patients with low output aortic stenosis.

## Low Dose Dobutamine Stress Echocardiography
- Low dose (<20 microgram/Kg/min) dobutamine stress echocardiography allows:
The differentiation between severe and pseudo-severe low flow low gradient aortic stenosis through the degree of change of both the effective orifice area and  the transvalvular gradient after dobutamine infusion. Changes following dobutamine infusion are due to the fact that dobutamine causes increase in the flow across the aortic valve.
In pseudosevere aortic stenosis, there is increase in the effective orifice area of the aortic valve, in a way that it is larger than 1.2 cm2, and slight increase in the gradient, in a way that is inferior to 40 mmHg.
In severe aortic stenosis, there is absence or little increase in the effective orifice area of the aortic valve, in a way that is inferior to 1.2 cm2, and increase in the gradient to become greater than 40 mmHg.
The assessment of the presence or absence of left ventricular flow reserve through the degree of change in stroke volume following dobutamine infusion.
Left ventricular flow reserve is an indicator of operative mortality. Left ventricle flow reserve does not predict recovery of left ventricle after aortic valve replacement nor the resolution of symptoms.
The aortic valve area should increase to more than  1-1.2 cm2 with a dobutamine infusion and the mean pressure gradient should rise above 30 mm Hg. While early surgical mortality is 32-33% in patients who fail to to achieve these improvements with dobutamine infusions, it is only 57% in patients who demonstrate an increase in their contractility and gradient. Five years survival after surgery was 88% in patients with improved contractility and only 1025% in patients with unimproved contractility.
- The differentiation between severe and pseudo-severe low flow low gradient aortic stenosis through the degree of change of both the effective orifice area and  the transvalvular gradient after dobutamine infusion. Changes following dobutamine infusion are due to the fact that dobutamine causes increase in the flow across the aortic valve.
In pseudosevere aortic stenosis, there is increase in the effective orifice area of the aortic valve, in a way that it is larger than 1.2 cm2, and slight increase in the gradient, in a way that is inferior to 40 mmHg.
In severe aortic stenosis, there is absence or little increase in the effective orifice area of the aortic valve, in a way that is inferior to 1.2 cm2, and increase in the gradient to become greater than 40 mmHg.
- In pseudosevere aortic stenosis, there is increase in the effective orifice area of the aortic valve, in a way that it is larger than 1.2 cm2, and slight increase in the gradient, in a way that is inferior to 40 mmHg.
- In severe aortic stenosis, there is absence or little increase in the effective orifice area of the aortic valve, in a way that is inferior to 1.2 cm2, and increase in the gradient to become greater than 40 mmHg.
- The assessment of the presence or absence of left ventricular flow reserve through the degree of change in stroke volume following dobutamine infusion.
Left ventricular flow reserve is an indicator of operative mortality. Left ventricle flow reserve does not predict recovery of left ventricle after aortic valve replacement nor the resolution of symptoms.
The aortic valve area should increase to more than  1-1.2 cm2 with a dobutamine infusion and the mean pressure gradient should rise above 30 mm Hg. While early surgical mortality is 32-33% in patients who fail to to achieve these improvements with dobutamine infusions, it is only 57% in patients who demonstrate an increase in their contractility and gradient. Five years survival after surgery was 88% in patients with improved contractility and only 1025% in patients with unimproved contractility.
- Left ventricular flow reserve is an indicator of operative mortality. Left ventricle flow reserve does not predict recovery of left ventricle after aortic valve replacement nor the resolution of symptoms.
- The aortic valve area should increase to more than  1-1.2 cm2 with a dobutamine infusion and the mean pressure gradient should rise above 30 mm Hg. While early surgical mortality is 32-33% in patients who fail to to achieve these improvements with dobutamine infusions, it is only 57% in patients who demonstrate an increase in their contractility and gradient. Five years survival after surgery was 88% in patients with improved contractility and only 1025% in patients with unimproved contractility.
Abbreviations: EOA: Effective orifice area; Pmean: mean pressure gradient

# Treatment

## Surgical and Medical Treatment
Aortic valve replacement is the treatment of choice for aortic stenosis.Given the associated operative risks with aortic valve replacement (AVR), true severe low flow low gradient aortic stenosis must be differentiated from pseudoaortic stenosis as the former benefit from AVR and the latter does not necessarily benefit from AVR. In addition, in case of low flow low gradient aortic stenosis with low ejection fraction, the presence or absence of reserve flow dictates the treatment plan as the operative mortality increases in the absence of reserve flow. As low flow low gradient aortic stenosis with normal ejection fraction is a newly described entity, there is no yet clear recommendations for the management.
Abbreviations: AVR: Aortic valve replacement; EOA: Effective orifice area; Pmean: mean pressure gradient

## Operative Mortality Risk Factors
The risk factors for operative mortality in the case of low flow, low gradient aortic stenosis with low ventricle ejection fraction are:
- Absence of left ventricle flow reserve
- Decreased pre-operative mean transvalvular gradient below 20mmHg at rest
- Coronary artery disease involving several vessels

# ACC/AHA Guidelines

## Dobutamine Stress Echocardiography