6.3: Aortic valve Stenosis

Obstruction of the left ventricle outflow can occur at subvalvular level (eg hypertrophic cardiomyopathy), supravalvular level or valvular level. Aortic valve stenosis is left ventricle outflow obstruction at valvular level.

In industrialized countries, aortic stenosis is the most common lesion among patients referred for treatment of valvular disease.[11] Age-related degenerative calcified aortic stenosis is the most common cause of aortic stenosis in adults in North America and Western Europe. The second most common cause is calcification of a congenitally bicuspid aortic valve. Other rare causes of calcified aortic stenosis include Fabry disease, lupus erythematosus, Paget disease, and ochronosis with alkaptonuria. The most common etiology of aortic stenosis worldwide remains rheumatic heart disease.

Prevalence of aortic valve abnormalities increases due to age-related pathology in the ageing population.

Figure 6.3.1: Gross pathology of rheumatic heart disease: aortic stenosis. Aorta has been removed to show thickened, fused aortic valve leaflets and opened coronary arteries from above. Autopsy, CDC/Dr. Edwin P. Ewing, Jr.

The first detectable macroscopic modifications of the calcification process is named aortic valve sclerosis. [6] Aortic sclerosis, seen as calcification or focal leaflet thickening with normal valve function, was detected in 25% of people at 65 years of age, this increases to 48% in people aged >75% in a population-based echocardiographic study.[12] [13]

The prevalence of calcified aortic stenosis is estimated at 2 % of people 65 years of age, increasing to 3-9% after the age of 80 years.[2][13]

Calcified degenerative aortic valve stenosis was previously considered to be the result of a passive degenerative process due to long-term mechanical stress in combination with calcium accumulation. Recently this concept is revised. Calcified degenerative aortic stenosis is considered an active pathobiological process, including proliferative and inflammatory changes, lipid accumulation, renin-angiotensin system activation, valvular interstitial cell transformation, ultimately resulting in calcification of the aortic valve.[14][15] [16] [17] Risk factors for development of calcific aortic stenosis are similar to those for vascular atherosclerosis such as diabetes, hypertension, and cholesterol levels.[18] [19] Progressive calcification leads to immobilization of the cusps causing stenosis.

Severity of outflow obstruction gradually increases in aortic valve stenosis. Left ventricular output is maintained by adaptation of the increasingly hypertrophic left ventricle. This compensational mechanism serves to normalize the left ventricle wall stress. Left ventricular hypertrophy in combination with the prolonged systolic phase of the cardiac cycle results in increased myocardial oxygen demand. The mismatch between oxygen demand and supply is the main mechanism for angina in aortic stenosis.

As the stenosis progresses, the left ventricle becomes less compliant with subsequent limited preload reserve. Eventually, the left ventricle will decompensate with a decline in cardiac output and rise in pulmonary artery pressure.

Aortic stenosis is assessed by estimating the mean systolic pressure gradient and aortic valve area (AVA). The normal aortic valve area is 3-4 cm2. Mild aortic stenosis is defined as an aortic valve area 1.5 cm2, mean gradient less than 25 mm Hg, or jet velocity less than 3.0 m per second, moderate aortic stenosis as an area of 1.0 to 1.5 cm2, mean gradient 25 to 40 mmHg, or jet velocity 3.0 to 4.0 m per second. A valve area of <1 cm2, a mean gradient greater than 40 mm Hg, or jet velocity greater than 4.0 m per second implies severe aortic stenosis The valve area may decrease by as much as 0.12 ± 0.19cm2 per year.[20] In late stages of severe aortic stenosis, cardiac output declines due to systolic dysfunction of the left ventricle, with a decline in the transvalvular gradient.

Table 6.3.1: Standard values associated with aortic stenosis at varying levels of severity.

Aortic stenosis severity	Valve area	Mean pressure gradient	Jet velocity
Mild	1.5 \(cm^2\)	less than 25 mmHg	less than 3.0 m per second
Moderate	1.0 to 1.5 \(cm^2\)	25 to 40 mmHg	3.0 to 4.0 m per second
Severe	less than 1.0 \(cm^2\)	greater than 40 mmHg	greater than 4.0 m per second

Clinical Presentation

Symptoms of degenerative aortic stenosis manifest with progression of the disease. The first symptoms usually commence in the seventh or eight decade. Symptoms are typically noted on exertion. Dyspnoea on exertion is the most common encountered first symptom. Other symptoms are angina, precipitated by exertion and relieved by rest, syncope and heart failure. The findings on physical examination vary with the severity of the disease. On auscultation, a systolic ejection crescendo-decrescendo murmur, radiating to the neck is audible, often accompanied by a thrill. An elevated left ventricular pressure in patients with aortic stenosis, in conjunction with mitral annulus calcifications predisposes to rupture of mitral chordae tendineae, which may produce a regurgitant systolic murmur.[21] [22]

The first heart sound is usually normal or soft in patients with aortic stenosis. The second heart sound may be delayed due to prolongation of systolic ejection time. The S₂ also may be single because of superimposed aortic and pulmonic valve components, or the aortic valve component is absent or soft because the aortic valve is too calcified and has become immobile. If the aortic component is audible, this may give rise to a paradoxical splitting of S₂. A pronounced atrial contraction can give rise to a palpable and audible S4.

When stroke volume and systolic pulse pressures fall in severe aortic stenosis, a pulsus parvus (small pulse) may be present. A wide pulse pressure is also characteristic of aortic stenosis. A pulsus parvus et tardus (the arterial pulse is slow to increase and has a reduced peak) can be appreciated by palpating the carotid pulse of patients with severe aortic stenosis. The stenotic valve decreases the amplitude and delays the timing of the carotid upstroke. Rigidity of the vasculature may hamper this sign in the elderly.

Diagnostic options

Chest Radiography

In aortic stenosis, cardiac silhouette and pulmonary vascular distribution are normal unless cardiac decompensation is present. Post-stenotic dilatation of the ascending aorta is frequent. Calcification of the valve is found in almost all adults with severe aortic stenosis; however, fluoroscopy may be necessary to detect it. A late feature in patients with aortic valve stenosis is cardiomegaly. In patients with heart failure, the heart is enlarged, with congestion of pulmonary vasculature.

Electrocardiography

In approximately 85% of patients with aortic stenosis, left ventricle hypertrophy, with or without repolarization abnormalities is seen on electrocardiography (ECG). Left atrial enlargement, left axis deviation and conduction disorders are also common. Atrial fibrillation can be seen at late state and in older patients or those with hypertension.

Echocardiography

The best non-invasive diagnostic tool to confirm the diagnosis of aortic stenosis, assess the number of cusps and the annular size, is ultrasonic examination of the heart. Quantification of valvular calcification is possible. In 1998, the American college of cardiology/American Heart Association (ACC/AHA) task force [23] recommended the diagnostic use of echocardiography.

Echocardiographic imaging evaluates the severity and etiology of the primary valvular lesion, secondary lesions, and coexisting abnormalities. The size and function of the atria and ventricles can be evaluated as well as hemodynamic characteristics. Echocardiography is also performed for postprocedural evaluation of patients. Transthoracic echocardiography is recommended for re-evaluation of asymptomatic patients: every year for severe AS; every 1 to 2 years for moderate AS; and every 3 to 5 years for mild AS.[24]

To assess the severity of aortic stenosis, transvalvular gradients and maximum jet velocity is measured using Doppler echocardiography, and aortic valve area is calculated. The systolic gradient across the stenotic aortic valve depends on stroke volume, systolic ejection period, and systolic pressure in the ascending aorta. The stenotic valve area is inversely related to the square root of the mean systolic gradient. Due to their flow-dependency these measurements are most valuable in normotensive patients.

Valve thickening and calcification, as well as reduced leaflet motion can also be assessed using Doppler.

Computed tomography

Although the role of computed tomography (CT) in clinical management is currently not well defined, this imaging modality could improve assessment of the ascending aorta. CT has an established role in evaluating the presence and severity of aortic root and ascending aortic dilatation in patients with associated aortic aneurysms. The high sensitivity and specificity of CT in detecting high-grade coronary artery stenosis could be useful to preoperatively rule out coronary artery disease.

Both electron beam and multislice cardiac CT can be useful in quantifying valve calcification, which have been shown to correlate with echocardiographic assessment and clinical outcome. Prior to transcatheter aortic valve implantations, CT provides information concerning the aortic valve area, annulus size, and the distance between the aortic cusps and the coronary ostia.

Cardiac Magnetic Resonance Imaging

Cardiac MRI (CMR) has an established role in evaluating aortic root and ascending aorta anatomy. It can be used to measure the aortic valve area, but the role of CMR in the management of aortic stenosis is currently not well defined.

Cardiac Catheterization

Cardiac catheterization remains the gold standard to detect coronary artery disease. Currently, in patients with aortic stenosis, cardiac catheterization is most often performed to identify the presence of concomitant coronary artery disease (CAD). In patients with inconclusive noninvasive tests, hemodynamic abnormalities can be assessed by cardiac catheterization. Coronary angiography is recommended prior to aortic valve replacement.

Exercise Testing

Since aortic stenosis is a progressive disease, most common in the elderly population, many patients with aortic stenosis do not recognize gradually developing symptoms and cannot differentiate fatigue and dyspnea from aging and physical deconditioning. Lifestyle modification may mask symptoms. Although contraindicated in patients with severe aortic stenosis, Exercise testing is useful for risk stratification and eliciting symptoms. Under supervision, it is reasonable to propose exercise testing in patients >70 years who are still highly active.

Treatment

Medical Treatment

For many years the standard of care for patients with significant aortic valve stenosis has been to provide antibiotic prophylaxis against infective endocarditis. However, current AHA guidelines for prevention of infective endocarditis no longer recommend antibiotic prophylaxis for this group of patients. Exceptions are patients with a prior episode of endocarditis, patients with prosthetic valves or with additional complex cardiac lesions with a high risk for the development of endocarditis. Patients who have had rheumatic fever should still receive antibiotic prophylaxis against recurrences of rheumatic fever

No medical treatment has proven to delay the progression of aortic stenosis. Surgery is inevitable for symptomatic patients. Patients at prohibitive risk for intervention may benefit from medical treatment including digitalis, diuretics, ACE inhibitors, or angiotensin receptor blockers, if experiencing heart failure. Beta-blockers should be avoided in these circumstances.

Table 6.3.2: Current Guidelines for indications for aortic valve replacement

Class I	Class IIa	Class IIb	Class III
1. AVR is indicated for symptomatic patients with severe AS. (Level of Evidence: B) 2. AVR is indicated for patients with severe AS undergoing coronary artery bypass graft surgery (CABG). (Level of Evidence: C) 3. AVR is indicated for patients with severe AS undergoing surgery on the aorta or other heart valves. (Level of Evidence: C) 4. AVR is recommended for patients with severe AS and LV systolic dysfunction (ejection fraction less than 0.50). (Level of Evidence: C)	AVR is reasonable for patients with moderate AS undergoing CABG or surgery on the aorta or other heart valves (Level of Evidence: B)	1. AVR may be considered for asymptomatic patients with severe AS and abnormal response to exercise (e.g., development of symptoms or asymptomatic hypotension). (Level of Evidence: C) 2. AVR may be considered for adults with severe asymptomatic AS if there is a high likelihood of rapid progression (age, calcification, and CAD) or if surgery might be delayed at the time of symptom onset. (Level of Evidence: C) 3. AVR may be considered in patients undergoing CABG who have mild AS when there is evidence, such as moderate to severe valve calcification, that progression may be rapid. (Level of Evidence: C) 4. AVR may be considered for asymptomatic patients with extremely severe AS (aortic valve area less than 0.6 cm2, mean gradient greater than 60mmHg, and jet velocity greater than 5.0 m per second) when the patient’s expected operative mortality is 1.0% or less. (Level of Evidence: C)	AVR is not useful for the prevention of sudden death in asymptomatic patients with AS who have none of the findings listed under the Class IIa/IIb recommendations. (Level of Evidence: B)

Surgery

The infinitive treatment for aortic valve stenosis is aortic valve replacement.

The first cardiac valve surgery under direct vision was an aortic valve replacement, performed in 1960 by dr. Dwight Harken.[25] The aortic valve was replaced by a caged ball valve, which became the standard for aortic valve replacement.[26] [27]

A total of more than 70 different mechanical aortic valve models have been introduced in aortic valve replacement and implanted in humans in the past 5 decades. The mechanical prostheses can be divided into 3 large groups: the first generation of ball valves, second generation of tilting-disc valves, and the last generation of bileaflet valves.[28] Mechanical prosthesis are extremely durable but require continuous use of anticoagulants.

Biological valves include homografts and autografts, as well as stented bioprostheses. Stented bioprostheses are constructed of porcine valves or bovine pericardium sewn onto an artificial stent. All heterograft valvs are preserved with glutaraldehyde, to reduce the antigenicity of the tissue and prevent calcification. The fixation process can be performed at various pressures. Higher fixation pressures may lead to earlier calcification. First-generation bioprostheses were porcine valves, preserved with high-pressure fixation (60 to 80 mmHg) and placed in the annular position

Second-generation prostheses are of porcine or pericardial origin, and are treated with low- pressure (0.1 to 2 mmHg) or zero-pressure fixation. Several second-generation bioprostheses may be placed in the supra-annular position, which allows implantation of a slightly larger prosthesis. Third-generation prostheses are treated with zero- or low-pressure fixation and additional processes to reduce calcification.

In 1962 Donald Ross implanted the first aortic valve allograft. In 1967 he replaced a patient’s malfunctioning aortic valve with the patients own pulmonary valve. An aortic or pulmonary valve homograft was then used to replace the patient’s pulmonary valve. This procedure is known as the Ross Procedure. Currently, the Ross procedure may be considered for bicuspid aortic valve stenosis, in particular for young women of reproductive age.

Transcatheter Intervention

In 2002, the first transcatheter aortic valve implantation was performed by Dr. Alain Cribier [29]. A transcatheter aortic valve implantation is a less invasive treatment option for patients at prohibitive risk for conventional aortic valve replacement. In this technique, the native valve is not excised. After balloon valvuloplasty, the prosthetic valve is implanted in the aortic position, with the frame of the prosthesis covering the native valve. The bioprosthesis can be implanted retrograde or antegrade. Currently 4 different approaches may be used in this technique: transfemoral, retrograde; transapical, antegrade; transaortic, retrograde; and transsubclavian, retrograde. Transcatheter aortic valve implantation is assessed in randomized clinical trials and registries.

Prognosis

Aortic valve stenosis has a severe prognosis when any symptoms are present, with survival rates of only 15–50% at 5 years. Strongest predictors of poor outcome in the elderly population are high New York Heart Association (NYHA) class (III/IV), associated mitral regurgitation and left ventricular dysfunction. Survival is only 30% at 3 years with the combination of these three factors.