A cardiology case (VIDEO) A male patient 82 years old with a systolic heart murmur of Aortic Stenosis.
The patient has a systolic murmur of aortic stenosis. The second heart sound is not audible which is an indication of severe aortic stenosis. The ECG shows signs of left ventricular hypertrophy: increased Sokolow index and ST- T wave abnormalities with typical morphology of left ventricular strain. Echo shows concentric left ventricular hypertrophy with moderate left ventricular systolic dysfunction: here ejection fraction EF is about 40%. There is severe stenosis of the aortic valve: here peak velocity is 5 m/s, and mean pressure gradient is 75 mm Hg- A peak velocity at least 4 m/s and a mean gradient at least 40 mmHg are considered as accurate indications of severe aortic stenosis. There is also moderate mitral regurgitation, and a dilated left atrium. In transmitral flow: E wave> A wave, but this cannot be a normal pattern, because of the following reasons: The patient obviously has diastolic dysfunction, since there is systolic dysfunction: because diastolic dysfunction generally precedes systolic dysfunction. Left ventricular hypertrophy and a dilated left atrium, are other factors favoring diastolic dysfunction in this patient. So the pattern of transmitral flow is pseudonormal, also named "grade II systolic dysfunction". A pseudonormal pattern is accompanied by an elevated left ventricular diastolic pressure. The patient has an indication for intervention. Main, class I, indications for intervention in severe aortic stenosis, AS, are the following: 1. Severe AS and any symptoms related to AS. 2. Severe AS in patients undergoing CABG, surgery of the ascending aorta or another valve. 3. In asymptomatic patients with severe AS and systolic left ventricular dysfunction: EF <50%, not due to another cause. 4. In asymptomatic patients with severe AS and abnormal exercise test showing symptoms on exercise clearly related to AS. Our patient is asymptomatic but has left ventricular dysfunction probably caused by the severe AS. So there is an indication for intervention, valve replacement, but because of his age and risk factors, any such intervention must be preceded by coronary angiography. The STS mortality risk score, Society of Thoracic Surgeons mortality risk score for cardiac operation, for this patient favors surgery. So surgery seems to be a better choice according to the current guidelines, over transcatheter aortic valve implantation,TAVI for the given patient : TAVI is generally preferred for patients with especially high surgical risk: STS mortality risk score of at least 10 %, or when using another mortality scoring system: A logistic EuroSCORE ≥20%. This patient has a calculated STS mortality risk score of about 3 % The decision has to be made by a heart team, cardiologists and cardiac surgeons, and there are also other factors taken into account. The heart team may decide that TAVI is a better option for a given patient, even if the risk score shows intermediate surgical risk, with STS mortality score 4-10%, if there are other concerns, based on the results of the patient's clinical findings and workup.
Aortic stenosis is a disease in which progressive obstruction to
left ventricular outflow results in the following: 1) concentric hypertrophy of the left ventricle, due to pressure overload, 2) symptoms of angina, dyspnea, and syncope; and 3) if severe and untreated, it can lead to sudden cardiac death.
Etiology of aortic stenosisAnatomically it can be divided into supravalvular aortic stenosis, fixed subvalvular aortic stenosis, and valvular aortic stenosis, which is the most common form.
Valvular aortic stenosis has many causes, including senile degenerative disease (which is the most common cause and occurs in elderly individuals), congenital bicuspid (one of the common causes especially in young people and in middle-aged people due to progressive degeneration of the valve), congenital unicuspid aortic valve (rare) and rheumatic heart disease (common in developing countries). Bicuspid aortic valves occur in 1-2% of the population and are often associated with dilation of the ascending aorta.
Echocardiography (two-dimensional and Doppler) can be used to determine the level of obstruction and to assess its severity.The pathophysiologic processes of aortic stenosis result from:
1) An increase in afterload, which causes increased cardiac work, progressive left ventricular hypertrophy, and increased myocardial oxygen demand.
2) A decrease in systemic and coronary blood flow from obstruction.
Myocardial ischemia occurs in patients with aortic stenosis, even if epicardial coronary arteries are normal, because of a mismatch in myocardial oxygen supply and demand.
These are the causes of the classic symptom triad of dyspnea (commonly exertional dyspnea even in patients with a normal systolic function), angina, and syncope, that can develop in severe aortic stenosis. Abnormalities of diastolic function (due to left ventricular hypertrophy and ischemia) are common in patients with aortic stenosis and cause increased left ventricular filling pressures that can be reflected onto the pulmonary circulation.
The clinical presentation of aortic stenosisThe clinical presentation of patients with aortic stenosis can be variable. Some patients are asymptomatic, and the diagnosis is suspected because of a systolic heart murmur, detected on physical examination. Others have one or more symptoms from the aforementioned classic triad. Sudden death may be the initial manifestation of aortic stenosis, although this is rare.
On physical examination, the characteristics of the murmur of aortic valvular stenosis are the following: Timing: Mid-systolic, Shape: crescendo-decrescendo (intensity rises and falls during systole). Location of maximal intensity: Right 2nd intercostal space, at the base of the heart. Radiation: Upward to the carotid arteries. Pitch: Low, Quality: Rough.
Is it possible to differentiate between the systolic murmur of valvular aortic stenosis (AS) and the systolic murmur of hypertrophic obstructive cardiomyopathy (HOCM) with maneuvers affecting cardiac preload?
Yes. Preload is the quantity of blood returning to the heart through the veins. Maneuvers that decrease preload, such as taking the standing position, or the straining phase of the Valsalva maneuver decrease the volume of blood ejected through the stenotic valve and so they decrease the intensity of the murmur of AS.
In HOCM, a decreased preload (venous return) causes a decrease in cardiac filling and left ventricular volume and so it results in a transient increase in the severity of the dynamic obstruction in the left ventricular outflow tract. This increases the intensity of the murmur in HOCM. The opposite effects are observed with maneuvers that increase preload, such as squatting and the release phase (the termination) of the Valsalva maneuver. Then in AS the murmur increases in intensity and in HOCM the murmur intensity decreases.
Severe aortic stenosis is characterized by a dampened (slow and of reduced magnitude) upstroke of the carotid artery pulse, a late-peaking systolic ejection murmur of large duration, an aortic component of the second heart sound (A2) which is absent or reduced and a sustained left ventricular impulse. The duration of the murmur and the timing of its peak correspond better to the stenosis severity than its intensity.
Echocardiography in aortic stenosisTwo-dimensional echocardiography can show the location (valvular, subvalvular, or supravalvular) and the cause of the obstruction. Doppler echocardiography is efficient for assessing the severity of aortic stenosis, which cannot be judged on the basis of the 2-dimensional image alone. Echocardiographic criteria for the determination of the severity of aortic stenosis: Moderate aortic valvular stenosis is characterized by a mean gradient of 25-40 mmHg and a valve area (calculated with the continuity equation) of 1-1.5 cm2
Severe aortic valvular stenosis is diagnosed when the mean gradient is >40, but ≤80 mmHg and valve area ≥0.7 but <1 cm2
(or valve area indexed to body surface area <0.6 cm2 /m2 but this calculation is only used for individuals with a small body size).
Critical (=very severe) aortic stenosis: mean gradient >80 and valve area <0.7 cm2. It is important to calculate the aortic valve area and the method to perform this calculation is discussed below:
How to calculate the aortic valve areaThe aortic valve area (AVA) is calculated by applying the continuity equation. According to this principle, since blood flow is continuous, the volume of blood ejected through the left ventricular outflow tract (LVOT) equals the volume of blood that crosses the aortic valve: AVA x VTIAoV = CSALVOT x VTILVOT
Solving for AVA, yields: AVA = CSALVOT x VTI LVOT/VTIAoV.
CSALVOT is the cross-sectional area of the LVOT. The LVOT is considered as having a circular cross-section, and so if r is the radius of the LVOT and D= the diameter of the LVOT=2r,
the CSALVOT is calculated:
CSALVOT= πr2 =3,14r2 =3,14(D/2)2 =3,14 D2/4= 0,785D2
The diameter D is measured from the parasternal long axis view immediately proximal to the leaflets of the aortic valve, or 0.5 cm proximal to the valve. VTI is the time velocity integral (calculated by the machine as the area under the curve of the Doppler velocity signal). VTI LVOT is the time velocity integral of the flow through the LVOT during systole. (The pulse wave Doppler signal of the flow through the LVOT, 0.5-1cm proximal to the orifice of the aortic valve is used for this measurement). VTIAoV is the time velocity integral of the flow through the aortic valve (AoV) during systole (the continuous wave Doppler signal of the flow through the AoV is used for this measurement). Thus, if D is the diameter of the LVOT,
AVA = 0,785D2 x VTI LVOT/VTIAoV.
You should index AVA to body surface area (BSA) if the patient is at extremes of body habitus (very small, or very large body weight).
As mentioned above, severe aortic stenosis is characterized by:
AVA <1 cm2, AVA/BSA <0.6 cm2/m2
The dimensionless indexThe dimensionless index is a ratio of velocities or VTIs of the LVOT and the aortic valve, that does not require measurement of the diameter of the LVOT (which is a frequent source of error):
LVOT peak velocity or VTI divided by the AoV peak velocity or VTI.
In severe AS this ratio is <0.25 whereas in mild AS >0.5.
Low flow- low gradient (LF-LG) aortic stenosis (AS) with a low left ventricular ejection fraction (LVEF)
Low flow-low gradient (LF-LG) aortic stenosis (AS) with a reduced left ventricular ejection fraction (EF) is observed in approximately 5% -10% of patients with aortic stenosis. The diagnosis and treatment of these patients is challenging. This condition is characterized by the combination of an aortic valve area compatible with severe aortic stenosis (AS) <1.0 cm2 , or < 0.6 cm2 /m2, but a relatively low mean transvalvular gradient (i.e., <40 mm Hg), and a low left ventricular ejection fraction ( LVEF) <50 % and a low flow state (i.e., stroke volume index <35 ml/m2 and/or cardiac index <3.0 L/min/m2). The stroke volume index is the stroke volume divided by the body surface area. The stroke volume is the volume of blood ejected by the left ventricle through the LVOT and the aortic valve in systole and is calculated as CSALVOT x VTI LVOT.
The low flow state is the result of the left ventricular (LV) systolic dysfunction. The LV systolic dysfunction can be the result of an increased afterload due to the aortic stenosis (AS) itself, or it can be the consequence of another myocardial disease (e.g. ischemic cardiomyopathy, dilated cardiomyopathy) with a coexisting AS.
The diagnostic problem in low flow-low gradient AS with a low LVEF is to distinguish true severe AS from pseudo-severe AS. In pseudo-severe aortic stenosis, there is a moderate or mild stenosis of the valve, but the low flow state causes incomplete opening of the aortic valve and thus the calculated valve area appears to be significantly reduced.
The distinction between true severe AS from pseudo-severe AS is required for therapeutic decision-making. Patients with true severe aortic stenosis (AS) generally benefit from aortic valve replacement, but in those with pseudo-severe AS, aortic valve replacement is not indicated.
Low-dose (5-20 μg/kg/min) dobutamine stress echocardiography (stress echo) is helpful in distinguishing true severe AS from pseudo-severe AS and for the assessment of the left ventricular contractile reserve (also called "LV flow reserve").
For this purpose, longer stress-echo stages (5-8 min) should be used. This enables measurements to be acquired once the heart rate and hemodynamics have reached a steady state.
During dobutamine stress echo in patients with true severe aortic stenosis (AS) there is no marked increase in the calculated aortic valve area, which remains <1 cm2, but the mean transvalvular gradient increases and reaches a level of ≥40 mmHg or the peak velocity reaches a level > 4 m/s.
In patients with pseudo-severe AS, in dobutamine stress echo there is a mean gradient < 40 mm Hg (at peak stress), a peak stress aortic valve area >1 cm2, and/or an increase in valve area of ≥0.3 cm2. The prevalence of pseudo-severe AS is 20%-35%.
In cases of indeterminate AS severity (when there is a discordance between aortic valve area and mean gradient measurements during stress echo) the MDCT AoV Ca score is assessed. This is a score showing the severity of aortic valve calcification obtained by multidetector computed tomography (MDCT). The presence of an MDCT AoV Ca score >1200 in women and >2000 in men indicates true severe aortic stenosis, whereas with lower scores the stenosis is characterized as pseudo-severe.
The importance of left ventricular flow reserve (contractile reserve)The assessment of the left ventricular flow reserve (also known as "contractile reserve") by stress echocardiography, provides information about operative risk. LV flow reserve is present when there is an increase in stroke volume of ≥ 20% during dobutamine stress echo. In cases of LF-LG aortic stenosis with a reduced EF, if there is an inadequate contractile reserve in dobutamine stress echo, then the severity of aortic stenosis cannot be determined with this test. In this setting, a useful test for the determination of AS severity is the calcium score of the aortic valve assessed with a computer tomography.
An inadequate LV flow reserve predicts a high operative risk but does not predict a lack of recovery of the left ventricular (LV) function, or a lack of improvement in symptomatic status, and late
survival after the operation. The absence of LV flow reserve should not preclude consideration of aortic valve replacement in patients with low flow-low gradient AS, if the valvular stenosis is true-severe, but it is a predictor of an increased operative risk. Patients with no LV flow reserve who survive the operation, demonstrate a postoperative improvement in LVEF, symptoms, and the late survival rate, which is comparable to those in patients with flow reserve. Thus patients with no flow reserve (no contractile reserve), but true severe AS, who survive after aortic valve replacement have a much better course than patients with severe AS and no flow reserve receiving only medical (drug) treatment.
Patients with true-severe AS, if flow reserve is present (a rise in stroke volume ≥ 20% in stress echo) are usually managed with surgical aortic valve replacement.
Patients with true-severe AS, if flow reserve is not present also need aortic valve replacement, but they have a high operative mortality. Thus, in these patients, usually transcatheter aortic valve replacement (TAVR, or TAVI) should be considered, although some can also be managed surgically.
Patients with pseudo-severe AS are managed medically (medical treatment for heart failure with reduced |EF).
Paradoxical low flow-low gradient aortic stenosis, with preserved LVEFThe assessment of patients with aortic stenosis (AS), sometimes becomes complicated by discordant echocardiographic findings, such as the combination of a small aortic valve area <1.0 cm2 consistent with severe AS and a low mean gradient (<40 mm Hg) indicative of non-severe AS. Such findings
raise uncertainty about the actual severity of the aortic stenosis (AS) and the potential indication of aortic valve replacement if the patient has symptoms. Discordance between the calculated aortic valve area (small) and the gradient (low) is often the result of low left ventricular outflow because even a modest decrease in flow can produce a significant reduction in the gradient. This may lead to an underestimation of stenosis severity.
Patients with true severe aortic stenosis (AS) may demonstrate a low gradient if there is a reduced flow through the aortic valve. This low-flow, low-gradient (LF-LG) aortic stenosis may occur in the context of either a reduced or preserved left ventricular ejection fraction (LVEF). A LF-LG aortic stenosis with a preserved (normal) LVEF, is called "paradoxical low flow-low gradient aortic stenosis".
Paradoxical low flow-low gradient (LF-LG) aortic stenosis is characterized by:
A small aortic valve area <1.0 cm2 or <0.6 cm2/m2 of body surface area
A low mean gradient ( <40 mmHg),
A low flow (stroke volume index <35 ml/m2), and
A preserved LVEF (≥ 50%).
The aortic valve is thickened and calcified, with reduced opening.
Doppler velocity index DVI is <0.25
There is a small left ventricular (LV) cavity size:
End diastolic diameter <47 mm/ end diastolic volume <55 mL/m2
Impaired LV filling (mitral inflow velocities and the diastolic mitral annular velocites show indications of significant diastolic dysfunction)
Global LV longitudinal strain is reduced, usually <15%
Paradoxical LF-LG aortic stenosis tends to occur more often in patients of older age, female gender, and with concomitant hypertension, diabetes, or metabolic syndrome. In paradoxical LF-LG aortic stenosis, the decrease in flow (stroke volume) is predominantly due to an impaired diastolic function (impaired LV filling), occurring in a ventricle of small internal dimensions and with concentric hypertrophy. A concomitant intrinsic systolic dysfunction is also present when more sensitive indices are examined, such as the peak mitral annular S velocity measured with tissue Doppler, or peak left ventricular systolic longitudinal strain (percentage of LV shortening). This kind of "subclinical" systolic dysfunction also seems to contribute (to a lesser extent than the impaired LV filling) to a reduced stroke volume.
In patients with LF-LG aortic stenosis with preserved LVEF, besides significant LV diastolic dysfunction with reduced left ventricular compliance, several other factors may also contribute to the reduction of the flow rate through the aortic valve (low flow). Such factors are atrial fibrillation, reduced arterial compliance (arterial "stiffness" is common in older individuals), and concomitant dysfunction of other valves (mitral regurgitation or stenosis, or tricuspid regurgitation).
The assessment of the patient with paradoxical LF-LG aortic stenosis with preserved LVEF, includes several steps:
At first, one must carefully repeat the measurements, to exclude possible errors. A usual source of errors is at the measurement of the area of the left ventricular outflow tract (LVOT), which is multiplied by the TVI (time velocity integral) of the LVOT, in order to calculate stroke volume. The accuracy of the measurement of the LVOT diameter is very important. Moreover, a good practice is to measure the LVOT diameter at the base of the cusps of the aortic valve, where the LVOT has a more circular shape, instead of making the measurement below the aortic annulus, where the LVOT cross-section is often elliptical. If no measurement error is identified and the echocardiographic examination is also concordant with the other features of this entity (e.g. concentric hypertrophy, a small LV, diastolic dysfunction, preserved EF, etc), then one must check if there is hypertension (which may have an effect on afterload and flow). The presence or absence of symptoms related to AS also plays an important role in the therapeutic decisions. If there are no symptoms the patient remains under frequent follow-up, but aortic valve replacement is not indicated. If there is hypertension, antihypertensive treatment is given and the patient is reassessed with echocardiography. If measurements still indicate paradoxical LF-LG aortic stenosis, after hypertension has been corrected, or in a patient with normal arterial blood pressure and the patient also has symptoms that can be attributed to AS, it is important to evaluate the true severity of the aortic stenosis (AS). This will guide further treatment. Thus, a normotensive patient with symptoms of AS and echocardiographic features of LF-LG aortic stenosis with preserved LVEF, will be tested with dobutamine or exercise stress echocardiography. This will distinguish pseudo-severe from severe AS. As in classical LF-LG aortic stenosis with a reduced LVEF, also in paradoxical LF-LG aortic stenosis with a preserved LVEF the stroke volume and the transvalvular flow rate is low. Thus, the flow may not be high enough to fully open the aortic valve and this may result in a lower calculated aortic valve area, in a valve which may be only moderately stenotic.
Exercise stress echocardiography can confirm the presence of symptoms and assess the response of the aortic valve area and the gradient to an increased flow rate (as a result of the exercise ).
The projected aortic valve area at a normal flow rate can also be calculated.
The MDCT AoV Ca score can be helpful in cases of paradoxic LF-LG aortic stenosis with preserved EF. This is a score showing the severity of aortic valve calcification obtained by multidetector computed tomography (MDCT). The presence of an MDCT AoV Ca score >1200 in women and >2000 in men indicates true severe aortic stenosis, whereas lower scores are an indication of a pseudo-severe (not really severe) aortic stenosis.
If the patient is symptomatic and the AS is severe, then aortic valve replacement is indicated, either via a surgical or transcatheter procedure. If a low MDCT aortic valvular calcium score indicates that AS is pseudo-severe (not true-severe) then aortic valve replacement is not indicated, but the patient will need a regular follow-up.
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Useful links and bibliography
2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease
ESC Guidelines on the management of valvular heart disease (version 2012)
LINK2017 AHA/ACC Focused Update- Valvular Heart Disease