Blase A. Carabello, MD, FACC

1. What is the most common cause of aortic stenosis (AS) in developed countries today, and what is the current thinking about its pathogenesis?

    Although rheumatic fever was once the most common cause of AS, today calcific disease of either bicuspid or tricuspid AS is the leading cause. Once considered a degenerative disease, it is now clear that calcific AS is an inflammatory process with many similarities to atherosclerosis. A normal aortic valve, and AS as a result of congenital bicuspid aortic valve, rheumatic AS, and calcific AS, are shown in Figure 30-1.

2. What is the pathophysiology of AS, and what effect does it have on the left ventricle (LV)?

    AS exerts a pressure overload on the LV. Normally, pressure in the LV and aorta are similar during systole, as the normal aortic valve permits free flow of blood from LV to aorta. However, in AS, the stenotic valve forces the LV to generate higher pressure to drive blood through the stenosis, causing a pressure difference (gradient) from LV to aorta. The LV compensates for this pressure overload by increasing its mass (left ventricular hypertrophy [LVH]). The ways in which the transvalvular gradient are measured and quantified are shown in Figure 30-2.

3. How is left ventricular hypertrophy compensatory?

    The Law of Laplace states that systolic wall stress (σ) is equal to:

    As the pressure term in the numerator increases, it is offset by an increase in thickness in the denominator, thus normalizing afterload. Because afterload is a key determinant of ejection, LVH helps to maintain ejection fraction and cardiac output.

4. Are there downsides to LVH?

    Yes. Although LVH is initially compensatory, as it progresses it takes on pathologic characteristics, leading to increased morbidity and mortality.

5. What are the classic symptoms of AS, and why are they important?

    The classic symptoms of AS are angina and syncope and those of heart failure (dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema, etc.). Their importance is graphically displayed in Figure 30-3. In the absence of symptoms, survival is nearly the same as that of an unaffected population. However, at the onset of symptoms there is a dramatic demarcation such that mortality increases to 2% per month, so that three-quarters of all AS patients are dead within 3 years of symptom onset unless proper therapy is instituted. It should be noted that when the data for this figure were compiled, the etiology of AS was usually rheumatic or congenital heart disease and the average age of the patients was 48 years. Since then the etiology of AS has changed (as noted above) and with it the age at symptom onset has increased by about 15 years.

6. What are findings of AS on physical examination?

    AS is usually recognized by the presence of a harsh systolic ejection murmur that radiates to the neck. In mild disease, the murmur peaks in intensity early in systole, peaking progressively later as severity of disease increases. The carotid upstrokes become delayed in timing and reduced in volume because the stenotic valve steals energy from the flow of blood as it passes the valve. The apical beat is forceful. Palpation of this strong apical beat with one examining hand while the other hand palpates the weakened delayed carotid upstroke is dynamic proof of the obstruction that exists between the LV and the systemic circulation. Because the severely stenotic aortic valve barely opens, there is little valve movement upon closing. Thus, the A2 component of S2 is lost, rendering a soft single second sound. An S4 is usually present in patients in sinus rhythm, reflecting impaired filling of the thickened, noncompliant LV.

7. How is echocardiography used to assess the patient with AS?

    Currently, echocardiography is the central tool in diagnosing the presence and severity of AS. In severe AS, the aortic valve is calcified and has limited mobility. The amount of LVH and the presence or absence of LV dysfunction can be established. Because

as the valve area decreases, velocity of flow must increase for flow to remain constant (Fig. 30-4). This increase in blood velocity at the valve orifice is detected by Doppler ultrasound. The severity of AS is assessed using the factors given in Table 30-1. In general, if a patient has the symptoms of AS and assessment indicates severe disease, then the symptoms are attributed to AS. However, it must be emphasized that the benchmarks listed here are only guidelines to severity, and some patients exhibit exceptions to them.

8. What other tests are useful in assessing AS?

    As noted earlier, the presence or absence of symptoms is a key determinant of outcome, yet in some patients an accurate history may be difficult to obtain. In such cases, more objective evidence of cardiac compromise, such as exercise intolerance, may be helpful. Although exercise stress testing should never be performed in symptomatic AS patients, stress testing may be very helpful in establishing more objective evidence of symptomatic status when the history is unclear. As many as one-third of AS patients may become symptomatic for the first time during stress testing. This phenomenon probably indicates a previous denial of symptoms or a lifestyle altered to avoid symptoms. Such stress testing, if undertaken, should only be done with careful physician supervision.

    Natriuretic peptides may also be useful in assessing the effects of AS on the heart. B-type natriuretic peptide (BNP) is released from the myocardium when sarcomere stretch increases to provide preload reserve. As such, increasing BNP indicates cardiac decompensation. Increasing BNP in AS patients is considered an ominous finding, although there is no agreement about what BNP level indicates the need for aortic valve replacement (AVR).

    In some cases, the severity of AS is still uncertain following echocardiography. Cardiac catheterization to obtain invasive hemodynamics, including the transvalvular pressure gradient and cardiac output, is then used to derive the valve area (see Chapter 14).

9. What is the therapy for AS?

    Because AS has many similarities to atherosclerosis, many have hypothesized that effective treatments for coronary disease might be able to retard the progression of AS. Although observational studies of the use of statins in AS have suggested those drugs might be effective, prospective trials have been, as yet, inconclusive.

    No effective medical therapy is effective in the chronic treatment of this disease. The mainstay of therapy for this mechanical problem is mechanical relief of the obstruction, in the form of AVR. In most patients, AVR is performed surgically. However, for selected patients at prohibitive or high risk for surgical AVR, transcatheter placement of the aortic valve (“TAVI” or “TAVR”) is now approved from the femoral and transapical approaches in the US (see Chapter 32, Prosthetic Heart Valves). It is almost certain that this field will evolve to have broader indications as devices become safer and easier to employ.

10. What are the class I indications for aortic valve replacement?

    According to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, AVR is indicated in the following situations:

11. What is the outcome after AVR?

    Survival of patients after AVR is dramatically improved compared with those who received only medical therapy.

12. What are the causes of aortic regurgitation?

    Abnormalities of either the aortic root or of the aortic valve leaflets can cause aortic regurgitation (AR). Common root abnormalities that cause AR include Marfan syndrome, annuloaortic ectasia, and aortic dissection. Leaflet abnormality causes include infective endocarditis, rheumatic heart disease, collagen vascular diseases, and previous use of anorectic drugs.

13. What is the pathophysiology of aortic regurgitation?

    The incompetent aortic valve allows ejected blood to return to the LV during diastole. This regurgitant volume is lost from the effective cardiac output. In turn, the LV must pump extra blood to make up for this loss; thus, AR constitutes an LV volume overload. Compensation comes from an increase in LV volume (eccentric hypertrophy). The larger LV can pump more blood to compensate for that lost to AR. Because all the stroke volume is pumped into the aorta during systole (while some leaks back into the LV during diastole), pulse pressure, which is dependent on stoke volume, widens as systolic pressure increases and diastolic pressure decreases. Thus, AR imparts not only a volume overload on the LV but also a pressure overload. Because of this second load, LV thickness in AR patients is slightly greater than normal. Increased wall thickness and the increased diastolic LV volume lead to increased LV diastolic filling pressure.

14. What are the symptoms of aortic regurgitation?

    Dyspnea and fatigue are the main symptoms of AR. Occasionally patients experience angina because reduced diastolic aortic pressure reduces coronary filling pressure, impairing coronary blood flow. Reduced diastolic systemic pressure may also cause syncope or presyncope.

15. What are the findings of AR on physical examination?

    Chronic AR produces myriad physical findings because of the large stroke volume pumped by the LV. The pulse pressure is wide. The dynamic LV apical beat is displaced downward and to the left and is often visible to an observer who is several feet away from the patient. A diastolic blowing murmur is present and is heard best along the left sternal border, with the patient sitting upward and leaning forward. A second murmur (Austin Flint) thought to be due to vibration of the mitral valve, caused by the impinging AR, is a low-pitched diastolic rumble heard toward the LV apex.

    The widened pulse pressure and high total stroke volume cause several physical signs of AR.

16. How is the diagnosis of AR confirmed?

    Although a chest radiograph is helpful in evaluating heart size and pulmonary congestion, echocardiography remains the mainstay of diagnosis. Cardiac size and function are evaluated using this technique. Often the anatomic abnormality responsible for the patient’s AR can be established. As shown in Figure 30-5, Doppler interrogation of the valve reveals the jet of blood leaking across the valve in diastole. Table 30-2 displays current criteria for establishing the severity of AR. Cardiac magnetic resonance imaging may also be useful in quantitating the magnitude of volume overload and in assessing left ventricular volume and mass.

17. How is AR managed?

    Patients with severe AR should been seen at least once a year or more often to evaluate symptomatic status and to perform repeat echocardiograms to assess LV size and function.

    AVR is indicated (ACC/AHA and European Society of Cardiology [ESC] class I recommendations) for the following patients:

AVR is considered reasonable (ACC/AHA and ESC class IIa recommendation) for asymptomatic patients with severe AR and with normal LV systolic function (LVEF more than 50%) but with severe LV dilation (end-diastolic dimension greater than 70-75 mm or end-systolic dimension greater than 50-55 mm).

As with AS, there is no proven medical therapy for AR, although vasodilator therapy can be considered in patients with severe AR who are not surgical candidates.

18. Is the presentation of acute AR different from that of chronic AR?

    Yes, dramatically. In acute AR, there has been no time for LV dilation so that the increased forward stroke volume and widened pulse pressure that drive the dynamic examination of a patient with chronic AR are absent. Thus, the examination of a patient with severe acute AR may be misleadingly bland, belying a potentially fatal condition. Acute AR occurs most commonly in the patient with infective endocarditis. When such patients develop evidence of heart failure, AR should be suspected, even if there is only a faint murmur or no murmur at all.

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