B P8 C72 Aortic Valve Stenosis Flashcards
Causes/etiology of AS
1.
2.
3.
A congenital bicuspid valve with superimposed calcification
Calcification of a normal trileaflet valve
Rheumatic disease
The most prevalent anatomy for a bicuspid valve is two cusps with a right-left systolic opening, consistent with congenital fusion of the____________________, seen in 70% to 80% of patients
Right and left coronary cusps
AVA ≤1.0 cm2 with resting aortic Vmax <4 m/s or mean ∆P <40 mm Hg
Dobutamine stress echocardiography shows AVA <1.0 cm2 with V max ≥4 m/s at any flow rate
Stage D2
ACC AHA Class 1 indications for treatment of AS
In adults with severe high-gradient AS (Stage D1) and symptoms of exertional dyspnea, HF, angina, syncope, or presyncope by history or on exercise testing, AVR is indicated
In asymptomatic patients with severe AS and an LVEF <50% (Stage C2), AVR is indicated
In asymptomatic patients with severe AS (Stage C1) who are undergoing cardiac surgery for other indications, AVR is indicated
In symptomatic patients with low-flow, lowgradient severe AS with reduced LVEF (Stage D2), AVR is recommended
In symptomatic patients with low-flow, lowgradient severe AS with normal LVEF (Stage D3), AVR is recommended if AS is the most likely cause of symptoms
Recommendations for Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate
Recommendations for severe AS >80 years old
TAVR is Class 1
The most common clinical presentation in patients with a known diagnosis of AS who are followed prospectively is a _____.
Gradual decrease in exercise tolerance, fatigue,or dyspnea on exertion
The mechanism of exertional dyspnea may be _____, with an excessive rise in end-diastolic pressure leading to pulmonary congestion.
LV diastolic dysfunction
In patients without CAD, angina results from the combination of _____, which reduce the coronary perfusion pressure gradient and impair myocardial flow reserve.
(1) the increased O2 needs of hypertrophied myocardium and reduction of O2 delivery due to decreased myocardial capillary density
(2) endothelial cell loss
(3) increased LVEDP
Syncope most often is caused by the ______ that occurs during exertion when arterial pressure declines because of systemic vasodilation and an inadequate increase in cardiac out- put related to valvular stenosis
Reduced cerebral perfusion
Syncope also has been attributed to malfunction of the baroreceptor mechanism in severe AS, as well as to a _____ to a greatly elevated LV systolic pressure during exercise.
Vasodepressor response
Syncope at rest may be caused by _____ with loss of the atrial contribution to LV filling, which causes a precipitous decline in cardiac output, or to _____ caused by extension of the calcification of the valve into the conduction system.
Transient AF
Transient AV block
The prevalence of _____ without stenosis, defined as irregular thickening or calcification of the aortic valve leaflets, increases with age and ranges from 9% in populations with a mean age of 54 years to 42% in populations with a mean age of 81 years.
Aortic valve sclerosis
In population-based echocardiographic studies, _____% of persons aged 65 or older and _____% of persons 75 or older had calcific aortic stenosis (AS)
> 65 years: 1-2%
> 75 years: 12%
The rate of progression from aortic sclerosis to stenosis is _____% per year.
1.8-1.9%
Valvular AS has three principal causes:
(1) Congenital bicuspid valve with superimposed calcification
(2) Calcification of a normal trileaflet valve
(3) Rheumatic disease
Rarely, AS is caused by severe atherosclerosis of the aorta and aortic valve; this form of AS occurs most frequently in patients with severe hypercholesterolemia and is observed in children with _____.
Homozygous type II hyperlipoproteinemia
Rheumatoid involvement of the valve is a rare cause of AS and results in _____ of the valve leaflets and involvement of the _____.
Nodula thickening
Proximal portion of the aorta
_____ affecting a congenital bicuspid or normal trileaflet valve is now the most common cause of AS in adults
Calcific (formerly “senile” or “degenerative”) aortic valve disease
Aortic sclerosis, identified by either echocardiography or computed tomography (CT), is the initial stage of calcific valve disease and, even in the absence of valve obstruction or known cardiovascular disease, is associated with an increased risk of _____.
Myocardial infarction (MI)
Cardiovascular and all-cause mortality
_____ valves typically produce severe obstruction in infancy and are the most common malformations found in fatal valvular AS in children younger than 1 year but also may be seen in young adults with an anatomy that mimics bicuspid valve disease.
Unicuspid
A congenital bicuspid aortic valve (BAV) is present in approximately 1% to 2% of the population, with a male predominance of approximately _____.
3:1
A BAV may be an isolated abnormality (approximately 50% of the time) or occur in the context of a genetic syndrome (e.g.,Turner syndrome), alongside other congenital heart defects (e.g., hypoplastic left heart, coarctation of the aorta), or with a _____ (most common nonvalvular manifestation).
Thoracic aortic aneurysm
The most prevalent anatomy for a bicuspid valve is two cusps with a right-left systolic opening, consistent with congenital fusion of the _____, seen in 70% to 80% of patients
Right and left coronary cusps
An anterior-posterior orientation, with fusion of the right and noncoronary cusps, is less common, seen in approximately 20% to 30% of patients. Fusion of the left and noncoronary cusps is rarely seen.
A prominent ridge of tissue or raphe may be present in the larger of the two cusps so that the closed valve in diastole may mimic a trileaflet valve.
Unicuspid valves are distinguished from a bicuspid valve by having only ___ aortic commissure.
One
The risk of aortic dissection in patients with BAV is _____ times higher than in the general population
Patients with BAV also are at increased risk for endocarditis (0.4 per 100,000) accounting for approximately 1200 deaths per year, however, the most common cardiac event is need for ______, and most patients with BAV develop calcific valve stenosis later in life, typically presenting with severe AS _______
5-9x
AVR
After the age of 50 years
Although the histopathologic features of calcific stenosis of a BAV are no different from those of a trileaflet valve, the turbulent flow and increased leaflet stress caused by the abnormal architecture are postulated to result in accelerated valve changes,
Rheumatic AS results from _____, leading to retraction and stiffening of the free borders of the cusps
(1) Adhesions and fusions of the commissures and cusps
(2) Vascularization of the leaflets of the valve ring
Normal valve leaflets comprise the fibrosa (facing the aorta), ventricu- laris (facing the ventricle), and spongiosa (located between the fibrosa and ventricularis). _____ are the most predominant cell type; endothelial and smooth muscle cells are also present.
Valve interstitial cells (VICs)
The most consistently observed genetic association is for _____.
Heritable forms of calcific aortic valve disease have been linked to ________
Lipoprotein(a) (Lp(a))
NOTCH1 mutation
Progressive valve obstruction imposes a _____overload state that leads to numerous changes in the structure and function of the left ventricle and accompanying changes in the pulmonary and systemic vasculature.
Chronic pressure overload
LV responses to AS
Hypertrophic myocardial remodeling
Myocardial fibrosis
Myocardial ischemia
Left ventricular diastolic dysfunction
left ventricular systolic dysfunction
The hypertrophied and pressure-overloaded left ventricle transmits increased pressure to the pulmonary vasculature, which leads to pulmonary hypertension in many patients with AS, becoming severe in _____%
15-20%
Maintenance of cardiac output in the face of an obstructed aortic valve imposes a chronic increase in LV pressure. In response, the ventricle typically undergoes hypertrophic remodeling characterized by _______ and ________
Myocyte hypertrophy and increased wall thickness
LV remodeling may manifest as concentric remodeling, ________ or ________
Concentric hypertrophy, or eccentric hypertrophy
LV remodeling reduces wall stress (afterload) and is considered one of the important compensatory mechanisms to maintain LV ejection performance,
In patients with AS, several studies have now documented that increased LV hypertrophic remodeling is associated with more _________ and ________, as well as higher mortality.
Severe ventricular dysfunction and heart failure (HF) symptoms
As a part of the hypertrophic remodeling process, _____ and _______ (not fibrosis from prior MI) may develop, although the incidence and extent of fibrosis are variable and unpredictable and the underlying biologic mechanisms not yet clarified
Diffuse and replacement myocardial fibrosis
What type of fibrosis tend to regress after AVR?
Diffuse fibrosis tends to regress after AVR, whereas replacement fibrosis does not.
In patients with AS, the _____, ______ and _____ all elevate myocardial oxygen (O2) consumption.
Hypertrophied left ventricle, increased systolic pressure, and prolongation of ejection
At the same time, even in the absence of epicardial coronary artery disease (CAD), _______ in the hypertrophied ventricle, ______, _______, ________ all serve to decrease the coronary perfusion pressure gradient and myocardial blood flow
Decreased myocardial capillary density
Endothelial cell loss
Increased LV end-diastolic pressure (LVEDP)
Shortened diastole
_____ underlies symptoms of angina in patients with AS that is often indistinguishable from that caused by epicardial coronary obstruction
Impaired myocardial flow reserve
Myocardial flow reserve is independently associated with aerobic exercise capacity and HF functional class in severe AS and appears to be influenced by the extent of LV hypertrophic remodeling and fibrosis, endothelial cell loss, and severity of valve obstruction.
_________ or ________ may exacerbate this ischemic imbalance and provoke angina that may not be experienced at rest.
Exercise or other states of increased O2 demand
______ each contribute to increased chamber stiffness and higher end diastolic pressures.
Higher cardiomyocyte stiffness, increased myocardial fibrosis, advanced-glycation end products, and metabolic abnormalities
Atrial contraction plays a particularly important role in filling of the left ventricle in AS because it _____ without causing a concomitant elevation of mean left atrial pressure.
Increases LVEDP
This “booster pump” function of the left atrium prevents the pulmonary venous and capillary pressures from rising to levels that would produce pulmonary congestion, while maintaining LVEDP at the elevated level necessary for effective contraction of the hypertrophied left ventricle.
Loss of appropriately timed, vigorous atrial contraction, as occurs in _____ or _____, may result in rapid clinical deterioration in patients with severe AS.
Atrial fibrillation (AF) or atrioventricular (AV) dissociation
Before a reduction in EF occurs, more subtle systolic dysfunction can be detected as _____, which is associated with worse outcomes in patients with severe AS
Reduced longitudinal systolic strain
The development and severity of systolic dysfunction results from a complex interplay of factors, including the
Severity of valve obstruction, metabolic abnormalities, vascular load, maladaptive hypertrophy (resulting in impaired contractility), ischemia, and fibrosis
In these patients, systolic function usually improves after the ventricle is unloaded by ______; the amount of recovery depends on many factors, including the degree to which systolic dysfunction was affected by afterload mismatch versus myocardial fibrosis and altered contractility.
AVR
The hypertrophied and pressure-overloaded left ventricle transmits increased pressure to the pulmonary vasculature, which leads to pulmonary hypertension in many patients with AS, becoming severe in __________.
15% to 20%
Among asymptomatic patients, exercise-induced pulmonary hypertension is associated with decreased event-free survival, and among patients undergoing TAVR or surgical AVR (SAVR), the ________ is associated with increased postoperative mortality.
Presence and severity of pulmonary hypertension
Generally, repeat imaging/monitoring:
Mild AS
Moderate AS
Severe AS
Mild AS - every 3 to 5 years for mild AS, unless a change in signs or symptoms prompts repeat imaging sooner
Moderate AS - every 1 to 2 years
Severe AS - every 6 to 12 months
The cardinal manifestations of acquired AS are
Exertional dyspnea
Angina,
Sncope
Heart Failure
Symptoms can develop at any age but typically begin at _______ with BAV stenosis and in those ______ with calcific stenosis of a trileaflet valve, although even in this age group approximately 40% of patients with AS have a congenital BAV
BAV - 50 to 70 years
Calcific AS - older than 70 years
The most common clinical presentation in patients with a known diagnosis of AS who are followed prospectively is a _________
Gradual decrease in exercise tolerance, fatigue, or dyspnea on exertion
The mechanism of exertional dyspnea may be ______, with an excessive rise in end-diastolic pressure leading to pulmonary congestion. Alternatively, exertional symptoms may be a result of the _____ with exercise
LV diastolic dysfunction
Limited ability to increase cardiac output
The mechanism of exertional dyspnea may be ______, with an excessive rise in end-diastolic pressure leading to pulmonary congestion. Alternatively, exertional symptoms may be a result of the _____ with exercise
LV diastolic dysfunction
Limited ability to increase cardiac output
Angina is a frequent symptom of patients with severe AS, indicates _____
Myocardial ischemia
In patients without CAD, angina results from the combination of the increased O2 needs of hypertrophied myocardium and reduction of O2 delivery due to _______ and ______, and increased LVEDP, which reduce the _____ and impair myocardial flow reserve.
Decreased myocardial capillary density, endothelial cell loss
Coronary perfusion pressure gradient
In patients with CAD, angina is caused by a combination of ____ and ____ characteristic of AS.
Very rarely, angina results from ______ to the coronary vascular bed.
Epicardial coronary artery obstruction and the O2 imbalance
Calcific emboli
Causes of Syncope in AS
Reduced cerebral perfusion that occurs during exertion when arterial pressure declines because of systemic vasodilation
Inadequate increase in cardiac output related to valvular stenosis
Malfunction of the baroreceptor mechanism
Vasodepressor response to a greatly elevated LV systolic pressure during exercise
Syncope at rest may be caused by _____ with loss of the atrial contribution to LV filling, which causes a precipitous decline in cardiac output, or to _____ caused by extension of the calcification of the valve into the conduction system.
Transient AF
Transient AV Block
Gastrointestinal bleeding may develop in patients with severe AS, often associated with ______ (most frequently of the _____) or other vascular malformations.
This complication arises from shear stress–induced platelet aggregation with a reduction in highmolecular-weight multimers of _________ and increases in proteolytic subunit fragments.
These abnormalities correlate with the severity of AS and are correctable by _____.
Angiodysplasia - right colon
von Willebrand factor
AVR
The carotid upstroke directly reflects the arterial pressure waveform.
The expected finding with severe AS is a _________, the parvus and tardus carotid impulse.
Slow-rising, late-peaking, low amplitude carotid pulse
When present, this finding is specific for severe AS.
In addition, with severe AS, radiation of the murmur to the carotid arteries may result in a _____.
Palpable thrill or carotid shudder
The ejection systolic murmur of AS typically is ______ and heard best at the ______ of the heart, with radiation to the carotids.
Late-peaking
Base
Cessation of the murmur _____ is helpful in differentiation from a pansystolic mitral murmur.
Before A2
In patients with calcified aortic valves, the systolic murmur is loudest at the base of the heart, but high-frequency components may radiate to the apex the so-called _________, in which the murmur may be so prominent that it is mistaken for the murmur of mitral regurgitation (MR).
Gallavardin phenomenon
In general, a _____ and _______ murmur indicates more severe stenosis.
Louder and later-peaking
When the _____ and _______, the systolic murmur of AS becomes; rarely, it disappears altogether.
Left ventricle fails and stroke volume falls
________ is helpful in excluding the diagnosis of severe AS, because normal splitting implies the aortic valve leaflets are flexible enough to create an audible closing sound (A2)
Splitting of S2
With severe AS, S2 may be single because
(1) calcification and immobility of the aortic valve make A2 inaudible
(2) closure of the pulmonic valve (P2 ) is buried in the prolonged aortic ejection murmur
(3) prolongation of LV systole makes A2 coincide with P2
The intensity of the systolic murmur varies from beat to beat when the _____ varies, as in AF or after a premature contraction.
This characteristic is helpful in differentiating AS from MR, in which the murmur usually is unaffected.
Duration of diastolic filling
Effects on the murmur of AS:
Squatting
Standing/Strain of Valsalva
The murmur of valvular AS is augmented by squatting which increases stroke volume.
It is reduced in intensity during the strain of the Valsalva maneuver and on standing, both of which reduce transvalvular flow.
This may be helpful in apparently a asymptomatic patients or when symptoms are vague (e.g., fatigue) to unmask symptoms or demonstrate limited exercise capacity or an abnormal blood pressure response.
Exercise testing
Use of Cardiac CT Tomography in AS
Evaluating aortic dilation in patients with evidence or s picion of aortic root disease on echocardiography or chest radiography, particularly those with a bicuspid valve.
Measurement of aortic dimensions at several levels, including the sinuses of Valsalva, sinotubular junction, and ascending aorta,
CT is increasingly used to assess ____ to predict the rate of disease progression or, more often, when the severity of the stenosis is in doubt, particularly in those with ____
Valve calcification
Low-flow, low-gradient AS
It is complementary to e ography in assessing valve morphology and provides valuable information on the location and extent of calcification
CT is also a routine part of the preprocedural evaluation of patients undergoing SAVR or TAVR, principally to look for a _______, as well as determine appropriate _____ and assess _______ and _______ for a potential transcatheter approach
Porcelain aorta
Valve sizing
Aortic and peripheral arterial anatomy
This is recommended only when noninvasive tests are inconclusive, when clinical and echocardiographic findings are discrepant, and for coronary angiography before AVR
Cardiac catheterization
CMR is useful in assessing LV volume, function, and mass, especially in settings in which this information cannot be obtained readily from echocardiograph
CMR is not recommended for assessment of stenosis severity because of ______ of transvalvular velocities
Underestimation
CMR with T1 mapping and late gadolinium enhancement (LGE) may be used to risk stratify patients with AS
This is increasingly recognized as a coexistent disease process in individuals with AS, particularly those with low-flow or low-gradient AS.
Transthyretin cardiac amyloidosis (ATTR-CA)
Markers of more rapid symptom onset in AS include
Greater valve calcification
Higher transvalvular gradient
More rapid increase in transvalvular gradient
Higher B-type natriuretic peptide, among others
Factors associated with more rapid hemodynamic progression include
Older age
More severe leaflet calcification
Renal insufficiency
Hypertension
Obesity
Metabolic syndrome
Smoking
Hyperlipidemia
Eevated circulating levels of Lp(a)
Increased activity of Lp-PLA2
Normal AV area ___
Cut offs?
Severe
Moderate
Mild
Normal AVA - 3-4cm2
Severe AS
Aortic jet velocity of >/= 4.0 m/sec
Mean transvalvular pressure gradient of >/= 40 mm Hg
AVA of < 1.0 cm2
Moderate AS
Aortic jet velocity of 3.0 to 3.9 m/sec
Mean transvalvular pressure gradient of 20 to 39 mm Hg
AVA of 1.0 to 1.5 cm2
Mild AS
Aortic jet velocity of 2.0 to 2.9 m/sec
Mean transvalvular pressure gradient less than 20 mm Hg
Aortic orifice of 1.5 to 2.0 cm2
The most specific definition for severe AS is a peak jet velocity of ___ m/sec or greater or mean gradient of ____ mm Hg or greater, usually accompanied by an AVA of ___
> /= 4 m/sec
/= 40 mm Hg
< 1.0 cm2
This apparent discordance in indices of AS severity occurs because at a normal flow rate, an AVA of 1.0 corresponds to a mean gradient of ______
30 mm Hg
The strongest predictor of AS progression to symptoms is the ______
Doppler aortic jet velocity
This stage is defined as high-gradient severe AS with no symptoms but overt LV systolic dysfunction with an LVEF <50%
Stage C2
This is defined as AVA of 1.0 cm 2or less with an aortic velocity less than 4.0 m/sec or mean gradient less than 40 mm Hg and LVEF less than 50%
Classic low-flow, low-gradient AS
True severe AS based on Dobu echo is defined as
Severe AS is present if there is an increase in aortic velocity to at least 4 m/sec at any flow rate, with AVA that remains less than 1.0 cm2
Dobutamine echocardiography also provides evidence of myocardial contractile reserve (increase in _____ from baseline), which historically has been an important predictor of operative risk and survival after SAVR in these patients.
Increase in stroke volume >20%
This stage in AS can occur with a normal LVEF (≥50%) typically in elderly patients with a small, hypertrophied left ventricle or those with concurrent hypertension.
Low-flow, low-gradient AS also can occur with a normal LVEF (≥50%)
This is often referred to as “paradoxical” low-flow, low-gradient AS because despite a normal EF, transaortic flow is low (_______).
Stroke volume index <35 mL/ m2
________ has been used to augment flow to distinguish truly severe AS from pseudosevere AS, but is less preferred in these patients with a small, hypertrophied ventricle and marked diastolic dysfunction.
Dobutamine
Medical therapy has thus far been shown to have ______ on disease progression in patients with AS
No effect
There is no one class of medicines established as the preferred treatment of hypertension in patients with AS, but because the renin- angiotensin system is upregulated in the valve and ventricle of patients with AS, ______ or ______ may be preferentially considered
Angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)
Concomitant CAD is common in middle-aged and elderly patients with AS. _______, and the decision of whether to prescribe a statin medication should not be influenced by the presence of AS.
Primary and secondary prevention guidelines should be followed
AF or atrial flutter develop in up to one third of older patients with AS, perhaps exacerbated by _____ related to diastolic dysfunction.
Left atrial enlargement
When such an arrhythmia is observed in a patient with AS, the possibility of associated _____ should be considered.
Mitral valvular disease
New-onset AF in a previously asymptomatic patient with severe AS may be a marker of impending symptom onset.
For those with AF and native valve AS, as well as those treated with a bioprosthetic valve more than 3 months ago, anticoagulation with a ______ is an effective alternative to warfarin.
Non–vitamin K oral anticoagulant
This is the procedure of choice for relief of outflow obstruction in adults with valvular AS.
AVR
______ has only a modest hemodynamic effect in patients with calcific AS. It can provide short-term improvement in survival and quality of life, but these benefits are not sustained.
Balloon aortic valvuloplasty
Balloon aortic valvuloplasty is not recommended as an alternative to valve replacement for calcific AS.
In selected cases, it might be reasonable as a bridge to definitive treatment with AVR in unstable patients or as a palliative procedure in patients who are not candidates for AVR.
ACC AHA Class 1 Indications for AVR in AS
In adults with severe high-gradient AS (Stage D1) and symptoms of exertional dyspnea, HF, angina, syncope, or presyncope by history or on exercise testing, AVR is indicated
In asymptomatic patients with severe AS and an LVEF <50% (Stage C2), AVR is indicated
In asymptomatic patients with severe AS (Stage C1) who are undergoing cardiac surgery for other indications, AVR is indicated
In symptomatic patients with low-flow, lowgradient severe AS with reduced LVEF (Stage D2), AVR is recommended
In symptomatic patients with low-flow, lowgradient severe AS with normal LVEF (Stage D3), AVR is recommended if AS is the most likely cause of symptoms
For patients with life expectancy less than 1 year or anticipated poor quality of life not related to their AS, AVR is likely futile and ____ is recommended
Palliative care
_______ leads to an improvement in symptoms, quality of life, and functional capacity and lower rates of hospitalization and death; accompanied by reverse remodeling in the heart and improvements in LV function
AVR
Class 1 indications for TAVR in AS
For symptomatic patients with severe AS who are older than 80 years of age or for younger patients with a life expectancy <10 years and no anatomic contraindication to transfemoral TAVI, transfemoral TAVI is recommended in preference to SAVR.
For symptomatic patients with severe AS who are 65 to 80 years of age and have no anatomic contraindication to transfemoral TAVI, either SAVR or transfemoral TAVI is recommended after shared decision making about the balance between expected patient longevity and valve durability.
For symptomatic patients of any age with severe AS and a high or prohibitive surgical risk, TAVI is recommended if predicted postTAVI survival is >12 months with an acceptable quality of life
Factors to Consider for Patient Selection for Transcatheter Versus Surgical Aortic Valve Replacement
Age
Bicuspid versus tricuspid valve
Valve calcification (amount, location)
Aortic size
Annulus size
Concomitant severe mitral or tricuspid valve disease
Extent, location, and complexity of coronary disease
Severity of left ventricular dysfunction
Transfemoral vascular acces
