Aortic Stenosis

Denisa Hagau, M.D.

Basic Information

Definition

Aortic stenosis (AS) is obstruction to left ventricular systolic outflow across the aortic valve. Symptoms typically appear when the valve orifice decreases to <1 cm² (normal orifice is 3 to 4 cm²). Criteria for severe AS include a valve area <1.0 cm², a mean gradient > 40 mm Hg, or a peak gradient > 4 m/s.

Synonyms

Aortic valvular stenosis
AS

ICD-10CM CODES
I35.0	Nonrheumatic aortic (valve) stenosis
I35.2	Nonrheumatic aortic (valve) stenosis with insufficiency
Q23.0	Congenital stenosis of aortic valve

Epidemiology & Demographics

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Aortic stenosis is the most common valve lesion in adults in Western countries, affecting 3% of persons older than 65 years.
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Calcific stenosis (most common cause in patients >70 yr) occurs in 75% of patients.

Physical Findings & Clinical Presentation

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Harsh midsystolic, crescendo-decrescendo murmur (Fig. 1) best heard at base of heart and radiating into neck vessels; often associated with a thrill or ejection click; may also be heard well at the apex.

FIG.1

Relationship between left ventricle (LV) and aortic (Ao) pressures and the Doppler aortic stenosis velocity curve (in red). The pressure difference between the LV and aorta in systole is four times the velocity squared (the Bernoulli equation). Thus, a maximum velocity (Vmax) of 4.3 m/sec corresponds to a maximum LV to Ao pressure difference of 74 mm Hg and a mean systolic gradient of 44 mm Hg. On physical examination, the slow rate of rise and delayed peak in the carotid pulse (or parvus and tardus) matches the contour of the aortic pressure waveform. The murmur corresponds to the Doppler velocity curve with a harsh crescendo-decrescendo late-peaking systolic murmur, best heard at the aortic region (upper right sternal border). Often, a soft, high-pitched diastolic decrescendo murmur of aortic regurgitation also is appreciated.

From Bonow et al [eds]: Braunwald’s heart disease, ed 9, Philadelphia, 2012, Saunders.
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Signs of severe AS include absent or diminished intensity of the second heart sound and/or late rising carotid upstroke with delayed amplitude (pulsus parvus et tardus), presence of S4, and a reverse splitting of the second heart sound.
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Classic symptoms include angina, syncope, and heart failure.

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Table 1 summarizes the stages of valvular aortic stenosis.

TABLE1 Stages of Valvular Aortic StenosisFrom Nishimura RA, Otto CM, Bonow RO, et al.: 2014 AHA/ACCF guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 63:e57, 2014. In Mann DL, Zipes DP, Libby P, Bonow RO: Braunwald’s Heart Disease, ed 10, Philadelphia, 2015, Elsevier.

Stage	Definition	Valve Anatomy	Valve Hemodynamics	Hemodynamic Consequences	Symptoms
A	At risk of AS	Bicuspid aortic valve (or other congenital valve anomaly) Aortic valve sclerosis	Aortic Vmax <2 m/sec	None	None
B	Progressive AS	Mild to moderate leaflet calcification of a bicuspid or trileaflet valve with some reduction in systolic motion or Rheumatic valve changes with commissural fusion	*Mild AS:* Aortic Vmax 2.0–2.9 m/sec or mean ΔP <20 mm Hg *Moderate AS:* Aortic Vmax 3.0–3.9 m/sec or mean ΔP 20–39 mm Hg	Early LV diastolic dysfunction may be present Normal LVEF	None
C	Asymptomatic severe AS
C1	Asymptomatic severe AS	Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening	*Severe AS:* Aortic Vmax ≥4 m/sec or mean ΔP ≥40 mm Hg AVA typically is ≤1 cm² (or AVAi ≤0.6 cm²/m²) Very severe AS is an aortic Vmax ≥5 m/sec, or mean ΔP ≥ 60 mm Hg	LV diastolic dysfunction Mild LV hypertrophy Normal LVEF	None; exercise testing is reasonable to confirm symptom status
C2	Asymptomatic severe AS with LV dysfunction	Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening	Aortic Vmax ≥4 m/sec or mean ΔP ≥40 mm Hg AVA typically is ≤1 cm² (or AVAi ≤0.6 cm²/m²)	LVEF <50%	None
D	Symptomatic severe AS
D1	Symptomatic severe high-gradient AS	Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening	*Severe AS:* Aortic Vmax ≥4 m/sec, or mean ΔP ≥40 mm Hg AVA typically is ≤1 cm² (or AVAi ≤0.6 cm²/m²), but may be larger with mixed AS/AR	LV diastolic dysfunction LV hypertrophy Pulmonary hypertension may be present	Exertional dyspnea or decreased exercise tolerance Exertional angina Exertional syncope or presyncope
D2	Symptomatic severe low-flow/low-gradient AS with reduced LVEF	Severe leaflet calcification with severely reduced leaflet motion	AVA ≤1 cm² with resting aortic Vmax <4 m/sec, or mean ΔP <40 mm Hg Dobutamine stress echo shows AVA ≤1 cm² with Vmax ≥4 m/sec at any flow rate	LV diastolic dysfunction LV hypertrophy LVEF <50%	HF, angina, syncope or presyncope
D3	Symptomatic severe low-gradient AS with normal LVEF or paradoxical low-flow severe AS	Severe leaflet calcification with severely reduced leaflet motion	AVA ≤1 cm² with aortic Vmax <4 m/sec, or mean ΔP <40 mm Hg AVAi ≤0.6 cm²/m² Stroke volume index <35 ml/m² Measured when the patient is normotensive (systolic BP <140 mm Hg)	Increased LV relative wall thickness Small LV chamber with low-stroke volume. Restrictive diastolic filling LVEF ≥50%	HF, angina, syncope or presyncope
AVA, Aortic valve area; AVAi, aortic valve area indexed to body surface area; BP, blood pressure; HF, heart failure; LVEF, left ventricular ejection fraction; ΔP, pressure gradient; Vmax, maximum aortic velocity.

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Acquired von Willebrand disease is seen in approximately 20% of severe AS, which can lead to GI bleeding from angiodysplasia (Heyde’s syndrome) that resolves after aortic valve replacement.

Etiology

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Idiopathic calcification of the aortic valve (most common cause, presents at ages 60 to 80)
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Progressive stenosis of congenital bicuspid valve (found in 1% to 2% of the population, presents at ages 40 to 60)
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Rheumatic heart disease
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Less common causes include congenital (major cause of AS in patients <30 yr), radiation, and obstructive vegetations (endocarditis)
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Genetic variation in the LPA locus, mediated by Lp(2) levels, is associated with aortic valve calcification across multiple ethnic groups and with incidental clinical aortic stenosis.

Diagnosis

Differential Diagnosis

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Hypertrophic cardiomyopathy
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Mitral regurgitation
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Ventricular septal defect
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Aortic sclerosis. Aortic stenosis is distinguished from aortic sclerosis by the degree of valve impairment. In aortic sclerosis, the valve leaflets are abnormally thickened but obstruction to outflow is absent or minimal.
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Subvalvular membrane or supravalvular AS
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Stages of valvular AS
1. ○
  
  Stage A = at risk of AS
2. ○
  
  Stage B = progressive AS (formerly known as mild and moderate AS)
3. ○
  
  Stage C = asymptomatic severe AS
4. ○
  
  Stage D = symptomatic severe AS

Workup

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ECG: may demonstrate left ventricular hypertrophy and/or left atrial abnormality.
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Chest radiograph: may demonstrate cardiomegaly. Poststenotic dilation of the ascending aorta may also be evident.
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Echocardiography (see “Imaging Studies”)
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Cardiac catheterization in selected patients (see “Imaging Studies”)
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Dobutamine challenge (for low-gradient, low-flow AS)

Imaging Studies

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Chest x-ray:
1. 1.
  
  Poststenotic dilation of the ascending aorta
2. 2.
  
  Calcification of aortic cusps
3. 3.
  
  Rounding of left ventricle (LV) apex
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ECG:
1. 1.
  
  Left ventricular hypertrophy (found in 80% of patients)
2. 2.
  
  Left atrial enlargement
3. 3.
  
  Atrial fibrillation (in late disease)
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Doppler echocardiography: thickening of the left ventricular wall; allows calculation of both aortic valve area and estimation of pressure gradients to determine severity of AS. (Fig. 2).

FIG.2

Echocardiogram recorded in a patient with severe aortic stenosis.

The top panel is a parasternal long-axis view recorded in systole. Left ventricular function is diminished. The aortic valve is markedly thickened and partially calcified. Its motion is markedly reduced, and in systole it appears that the valve occludes the orifice (arrow). The lower panel is a continuous-wave Doppler recorded from the apex of the left ventricle along a line aimed through the stenotic aortic valve. Note the aortic stenosis signal below the zero crossing line. The peak velocity is 430 cm/sec, which corresponds to a maximum gradient of 77 mm Hg and a mean gradient of 49.4 mm Hg. LA, Left atrium; LV, left ventricle; RVOT, right ventricular outflow tract.

From Zipes DP et al, eds: Braunwauld’s heart disease, ed 7, Philadelphia, 2005, Saunders.
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Cardiac catheterization: indicated in symptomatic patients awaiting aortic valve replacement (AVR) in order to detect coexisting coronary artery stenosis that may need bypass at the same time as aortic valve replacement; also indicated in symptomatic patients when noninvasive tests are inconclusive or when there is a discrepancy between noninvasive tests and clinical findings regarding severity of AS because it confirms the diagnosis and the estimates of the severity of the valvular stenosis by directly measuring the gradient across the valve, allowing calculation of the valve area.
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A CT with contrast for imaging the aorta may be needed for annular sizing, aortic measurements, etc., if a transcatheter aortic valve replacement (TAVR) is planned.

Treatment

Nonpharmacologic Therapy

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Strenuous activity should be avoided in patients with moderate to severe AS
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Sodium restriction if CHF is present

General Rx

Medical

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Once symptomatic, AS is a surgical disease. Fig. 3 summarizes a treatment strategy for patients with severe AS.

FIG.3

Management strategy for patients with severe AS. Periodic monitoring is indicated for all patients in whom AVR, by either a surgical or a transcatheter approach, is not yet indicated, including those with asymptomatic AS (stage D or C) and those with low-gradient AS (stage D2 or D3) who do not meet criteria for intervention.∗AVR should be considered with stage D3 AS only if valve obstruction is the most likely cause of symptoms, stroke volume index is <35 ml/m², indexed AVA is ≤0.6 cm²/m², and data are recorded when the patient is normotensive (systolic BP <140 mm Hg). AVA, Aortic valve area; BP, blood pressure; DSE, dobutamine stress echocardiography; ETT, exercise treadmill test; LVEF, left ventricular ejection fraction; ΔP_mean, mean pressure gradient; Vmax, maximum velocity.

From Nishimura RA, Otto CM, Bonow RO, et al.: 2014 AHA/ACCF guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 63:e57, 2014. In Mann DL, Zipes DP, Libby P, Bonow RO: Braunwald’s Heart Disease, ed 10, Philadelphia, 2015, Elsevier.
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Optimize loading conditions by keeping a normal volume status (gentle diuresis for volume overload as preload dependent) and controlling hypertension (HTN) but avoid vasodilators (nitrates); maintain sinus rhythm.
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In 2007, the AHA guidelines for prevention of infectious endocarditis were revised and routine antibiotic prophylaxis to undergo dental or other invasive procedures is no longer recommended, unless the patient has prior endocarditis.

Surgical

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Surgical valve replacement is the treatment of choice in symptomatic patients because there is a 50% mortality rate at 2 years with medical therapy alone. Valve replacement is a Class I indication for patients with (a) symptomatic severe AS, (b) asymptomatic severe AS with LV ejection fraction (EF) <50%, and (c) severe AS undergoing CABG or surgery on the aorta or other heart valves. Valve replacement is a class 2a indication for patients with (a) asymptomatic severe AS and abnormal blood pressure response (decrease in systolic blood pressure) or decreased exercise tolerance during exercise; (b) asymptomatic patients with very severe AS (peak velocity > 5 m/s or mean pressure gradient >60 mm Hg) with low surgical risk; (c) low flow-low gradient (with low ejection fraction <50%) with a positive low-dose dobutamine stress echo; (d) symptomatic patients with low-flow/low gradient severe AS with a normal LVEF ≥50%, a valve area ≤1.0 cm², and a stroke volume index <35 ml/m²; and (e) patients with moderate AS who are undergoing cardiac surgery for other indications. Patients with asymptomatic severe AS with rapid disease progression and low surgical risk are a class 2b indication for valve replacement surgery.
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Percutaneous aortic balloon valvuloplasty serves best as palliative therapy in severely symptomatic patients who are not surgical candidates and as a bridge to surgery in hemodynamically unstable adult patients. It is not an option in patients who are good candidates for surgical valve replacement because restenosis occurs in most adult patients at 6 months.
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For patients in whom transcatheter aortic valve replacement (TAVR) or high-risk surgical AVR is being considered, a heart valve team approach is a class I recommendation.
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TAVR is recommended (class I) in patients who have a prohibitive surgical risk and are predicted to survive >12 months after TAVR.
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Percutaneous heart valve replacement is a catheter-based technology that allows for implantation of a prosthetic valve without open heart surgery. TAVR has been shown to reduce mortality by 20% in patients with severe AS and coexisting conditions that exclude them as candidates for surgical replacement of the aortic valve. In a large meta-analysis of high-risk patients with severe AS who were candidates for surgery, transfemoral TAVR (but not transthoracic TAVR) was associated with lower mortality at 2 years. The surgical group had double the incidence of new-onset atrial fibrillation and major bleeding, but the TAVR group had a higher rate of paravalvular regurgitation, major stroke, and vascular complications. In intermediate-risk patients, transfemoral TAVR was also associated with lower mortality rates, and nontransfemoral TAVR was similar to surgical aortic valve replacement with respect to death or disabling stroke rates, as demonstrated by the same large meta-analysis of four randomized trials. The notable differences were that TAVR resulted in larger aortic valve areas and had a lower rate of acute kidney injury, severe bleeding, and new-onset atrial fibrillation, whereas surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. For low-risk patients, the guidelines still recommend surgical aortic valve replacement. However, the NOTION trial showed that patients randomized to either TAVR or SAVR had similar event rates at 1 year. Limitations of this study included small size and younger patients enrolled subsequently. The trial population was not fully reflective of the population of low-surgical-risk patients with severe symptomatic AS. Other randomized trials are in progress.

Possible predictors of stroke following TAVR were evaluated by a large systematic review and meta-analysis involving 64 studies including 72,318 patients that looked at rates of stroke at 30 days following TAVR. They concluded that female gender, chronic kidney disease, new atrial fibrillation following TAVR, and lower site experience were associated with increased risk of stroke post TAVR.

There also appears to be a risk of early thrombosis after transcatheter aortic valve implantation as demonstrated by a large multicenter study involving 460 patients. There was a 7% incidence of valve thrombosis after Sapien XT or Sapien 3 TAVR, suggesting that warfarin therapy reconsideration may be warranted.

Disposition

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The presence of even mild symptoms is an indicator of poor survival for patients with AS. The average duration of symptoms before death is angina, 5 years; syncope, 3 years; CHF, 2 years.
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Approximately 75% of patients with symptomatic AS will die within 3 yr of symptom onset unless the aortic valve is replaced.

Referral

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Surgical referral for valve replacement in all symptomatic AS patients. There are studies that are examining the presence of moderate or severe valvular calcification, together with a rapid increase in aortic jet velocity and elevated BNP, to identify patients with a very poor prognosis who should be considered for early valve replacement rather than have surgery delayed until symptoms develop. Additionally, patients with severe AS who are asymptomatic should be considered for exercise stress test to see if they are truly without symptoms (low exercise tolerance) or if the BP drops with exercise, both which would be indications for surgical referral. Surgical mortality rate for valve replacement is 3% to 5%; however, it varies with patient’s age (>8% in patients >75 yr).
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In asymptomatic patients, Doppler echocardiography is recommended every 6 to 12 months for severe aortic stenosis, every 1 to 2 years for moderate disease, and every 3 to 5 years for mild disease.
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Referral to cardiology should be considered in patient with low-flow, low-gradient (low ejection fraction) symptomatic aortic stenosis for further work-up (dobutamine stress echo).
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Balloon valvuloplasty is useful in infants and children or poor surgical candidates who do not have calcified valve apparatus; it can be done as an intermediate procedure to stabilize high-risk patients before surgery.
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Patients who are considered high risk for cardiac surgery or have contraindications (porcelain aorta) should be referred to a center with a transcatheter program for TAVR evaluation.
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Role of palliative care
1. ○
  
  If life expectancy with aortic valve replacement (SAVR or TAVR) is <1 year or the patient’s quality of life is unlikely to improve after aortic valve replacement (due to coexisting significant comorbidities), palliative care consultation is extremely valuable as it focuses on shared decision making as well as improving quality of life without interruption of conservative medical therapy.

Ferri – Aortic Stenosis