Amar Krishnaswamy and Brian P. Griffin
NORMAL AORTIC VALVE ANATOMY
Normal aortic valves are tricuspid—with right, left, and noncoronary cusps—and have a valve area of 2 to 3 cm2. However, congenital variations in this anatomy are relatively common, particularly bicuspid valves. Most commonly, bicuspid valves result from fusion of the right and left coronary cusps, although any two cusps may be fused. More rare are unicuspid and quadricuspid valves, with one and four cusps, respectively (Fig. 33.1). Although some congenitally abnormal valves function normally and are clinically silent, they more frequently result in symptomatic aortic stenosis (AS) or aortic insufficiency (AI) by middle age.
FIGURE 33.1 Transesophageal echocardiography short-axis images of bicuspid aortic valve (A) and unicuspid valve(B)
AORTIC STENOSIS
AS is one of the most frequent valve pathologies encountered in clinical cardiology. The etiology can be varied and may include subvalvular, valvular, or supravalvular lesions, but the pathophysiologic and hemodynamic responses to fixed outflow obstruction are usually predictable.
Pathophysiology of Aortic Stenosis
AS, regardless of degree, creates a pressure overload on the left ventricle (LV). Over time, the ventricle develops a compensatory concentric hypertrophy, which allows LV wall stress, or afterload, to remain normal, despite increased systolic pressures. This relationship is expressed by the law of Laplace, which states that wall stress is proportional to the chamber radius divided by its thickness. Thus, in compensated AS, left ventricular hypertrophy (LVH) functions to normalize after load and helps to maintain normal LV contractile function. The hypertrophy does, however, lead to increased LV mass and end-diastolic pressures, which in turn may precipitate diastolic heart dysfunction and myocardial ischemia. The degree of hypertrophy may vary dramatically among individuals, and gender differences have also been noted. Classically, women develop more hypertrophy with a small-to-normal LV cavity size, whereas men develop a lesser degree of hypertrophy, a dilated LV cavity, and earlier systolic dysfunction.1 Ultimately, compensatory mechanisms fail and patients develop symptoms due to progressive diastolic dysfunction, systolic dysfunction, compromised cardiac output, or myocardial ischemia.
Etiologies of Aortic Stenosis
There are multiple etiologies of AS, the most common of which are discussed below.
Degenerative AS is the most common etiology of AS in the United States. Once believed to be a passive process of calcification due to years of “wear and tear,” degenerative AS is now understood to be a dynamic process involving a robust inflammatory response of macrophages, T cells, and fibroblasts. The exact precipitants for AS are not clear, but observational evidence suggests the process may share some risk factors with atherosclerosis. In retrospective studies, statins have attenuated progression of AS2,3; however, no prospective studies have shown that medical therapy is effective in delaying progression of AS.
Rheumatic heart disease is a common cause of AS in less developed countries, but its incidence in developing countries has declined over the past 30 years.
Congenital valve disease may result in bicuspid or unicuspid valves, which are a frequent cause of symptomatic AS in younger patients (see Fig. 33.1). Bicuspid valves (BAV) have a prevalence of 1% to 2% in the population and are associated with other congenital abnormalities (especially coarctation) in 20% of cases. Up to 80% of patients with coarctation have BAV. Bicuspid valves are also associated with aortic root dilatation and an aortopathy that resembles cystic medial necrosis. Unicuspid valves are inherently stenotic and usually cause symptoms by the third decade of life. Like bicuspid valves, unicuspid valves also are associated with an aortopathy.
Radiation heart disease may occur in patients who have a history of mediastinal radiation as treatment for lymphoma, breast, or esophageal cancers. The risk of valve disease is increased in patients who have received >30 Gy of radiation and generally presents 15 to 20 years after exposure. There is a greater tendency toward aortic valve disease, followed by mitral and then tricuspid valve disease. Due to this distribution of valve involvement, it is thought that flow may play a role in the valvular disease. Usually, radiation-associated aortic disease is mixed stenosis and regurgitation. Subvalvular AS is a rare form of AS and may be due to a tunnel of muscular tissue or a discrete band or membrane. Sub-valvular stenosis should be suspected in any patient who has symptoms of AS or high LV outflow velocities on echo cardiography but whose aortic valve is structurally normal. Sub-valvular stenosis also presents as a component of the Shone complex: multiple left-sided heart obstructions, including supravalvular mitral stenosis, parachute mitral valve, subvalvular AS, BAV, and aortic coarctation. Additionally, subaortic stenosis may be associated with a patent ductus and ventricular septal defects (VSDs). Over time, the jet from subvalvular stenosis will damage the native aortic valve and will lead to AI. For this reason, early surgical repair of asymptomatic subvalvular stenosis is often recommended. Supravalvular AS is a rare variant of AS that is classically associated with Williams syndrome (child-like facies, peripheral pulmonary stenosis, hypercalcemia) and familial dyslipidemias. A mutation in the gene for elastin has been linked to Williams syndrome. Other cardiovascular associations of supravalvular stenosis include coarctation of the thoracic or abdominal aorta and renal artery stenosis.
Clinical Findings in Aortic Stenosis
The history of patients with AS varies with the etiology of the stenosis. Patients with rheumatic heart disease or bicuspid aortic valves frequently have a long history of a heart murmur. They also are more likely to present with symptomatic disease at a younger age. In contrast, patients with degenerative AS usually are older, in their seventh or eighth decade, and may present with symptoms without prior knowledge of aortic valve pathology.
The symptoms of AS are most frequently the direct result of the heart’s compensatory changes. Initially, patients develop diastolic heart dysfunction, which often manifests as exertional dyspnea. With stress, patients with AS may become significantly symptomatic because their cardiac output cannot augment adequately and left ventricular end-diastolic pressure (LVFDP) markedly increases. Dyspnea and early fatigability result. As the AS progresses, the classic symptoms of angina, syncope, and heart failure develop. This triad of symptoms has been well studied and allows a rough estimate of disease severity and prognosis: if untreated, survival in patients with angina approximates 5 years, with syncope is 3 years, and with heart failure is <2 years.
Angina is very common in severe AS and may be due to concomitant coronary disease, demand ischemia, or both. Interestingly, up to 50% of patients with angina and severe AS have no obstructive coronary disease. The angina is usually typical substernal pain, worsened with exertion or stress, and relieved with rest. Anginal equivalents, such as dyspnea on exertion, are also common. Syncope or presyncope most often results from exertional cerebral hypoperfusion; with exercise, the systemic arterial tree vasodilates, but the cardiac output remains relatively fixed. Arrhythmias may also precipitate syncope, especially atrial fibrillation or ventricular tachycardia. Congestive heart failure (CHF) symptoms such as pulmonary edema, paroxysmal nocturnal dyspnea, and orthopnea are late findings in AS and signify advanced disease with very poor prognosis if untreated.
Less common manifestations of AS include cardiac cachexia in very advanced cases and gastrointestinal bleeds from atriovenous (AV) malformations (Heyde Syndrome). Cardiac cachexia and debilitation result from a profound, longstanding low-output state. The mechanism for gastrointestinal bleeding from arteriovenous malformations is presumed to be destruction of large multimers of von Willebrand factor as they are sheared through the aortic valve. These larger multimers are apparently critical to the initial phases of hemostasis.
The Physical Exam
Vascular Findings The carotid pulsations in patients with severe AS are characterized by a delayed and weakened upstroke, the pulsus parvus et tardus. In long-standing critical AS, the peripheral pulses also may be weak, and signs of poor perfusion may be present.
Cardiac Findings On palpation, one may feel a systolic thrill in cases of severe AS. The apex may be laterally displaced if the heart has begun to dilate. The cardiac exam in AS is notable for a crescendo-decrescendo murmur, heard best in the right upper sternal border (RUSB) and radiating to the carotids. Occasionally, the murmur may instead radiate to the apex and mimic mitral regurgitation (MR); this is known as the Gallavardin phenomenon. As AS progresses, the murmur peaks increasingly later in systole until S2 is obliterated, suggesting severe disease. The grade of the murmur correlates with severity of the stenosis, and the presence of a thrill (Grade IV/VI) suggests critical stenosis. An S4 is also frequently appreciated. An ejection click suggests the presence of a bicuspid aortic valve.
The physical exam may be useful in differentiating valvular AS from hypertrophic cardiomyopathy (HCM) and subaortic stenosis. In HCM, the carotid pulsation is on time and is bifid, with a two-component, “spike and dome” contour. This is caused by the presystolic closure of the aortic valve. The point of maximal cardiac impulse (PMI) pulsation in HCM patients classically has three components, which correspond to atrial filling and the two components of systolic ejection. The murmur in HCM can be differentiated from AS by several maneuvers. Decreasing either preload or afterload will accentuate the murmur of HCM, but will soften the murmur of valvular AS. Thus, a Valsalva maneuver or arising from squatting to standing will accentuate a HCM murmur, but will decrease the murmur of AS. Amyl nitrate will similarly decrease afterload and preload, resulting in marked increase in the HCM murmur.
The murmur of subvalvular stenosis resembles valvular AS. Clues that the murmur might be due to subvalvular stenosis include a younger patient age, the presence of AI, and the absence of an ejection click. In supravalvular AS, blood flow preferentially is directed into the innominate artery, so the murmur of supravalvular stenosis classically radiates to the right neck and subclavian and may be associated with a thrill over the right carotid. The blood pressure in the right arm may be slightly higher than in the left. Careful auscultation of the lung fields may reveal murmurs associated with peripheral pulmonary stenosis.
Key Diagnostic Studies
Electrocardiogram The electrocardiogram (ECG) in patients with severe AS may show LVH with concomitant strain pattern, left atrial (LA) abnormality, or interventricular conduction delay. Transient third-degree heart block has been described, and has been ascribed to aortic annular calcification impinging on the AV nodal conduction system.
Chest X-Ray The chest x-ray (CXR) is often normal in patients with AS, especially because LVH frequently is unaccompanied by dilation early in the disease. With advanced disease, LVH and enlargement, aortic dilation, and aortic valvular calcification may be appreciated.
Transthoracic Echocardiogram Echocardiography has become the gold standard for diagnosis and quantification of aortic valve disease. Key data that are attained from a transthoracic echocardiogram (TTF) assessment include the following.
LV Size and Systolic Function. Systolic function is usually normal until late in the disease. The LV will show variable hypertrophy, with overall normal size.
Diastolic Function. Early in the disease process, LV compliance decreases and the atrial component of diastolic filling becomes increasingly prominent. Over time, LA pressure rises, and ultimately, patients with long-standing AS may develop restrictive diastolic filling patterns.
Assessing Aortic Valve Morphology. Echocardiography is paramount in identifying the etiology of AS. Standard transthoracic images usually can identify bicuspid or unicuspid valves, can suggest a rheumatic etiology, or can quantify the degree of valvular calcification.
Assessing the Severity of AS. There are several methods to estimate the severity of AS. Multiple methods should be used in each patient to ensure accurate data.
Jet velocity: Peak aortic valve jet velocity provides a rough measure of valve severity and also provides a measure of prognosis. A normal outflow velocity is approximately 1 m/s. Studies have suggested that asymptomatic patients with outflow gradients in excess of 4 m/s will most likely develop symptoms within 2 years.4
Valve gradients: Peak transaortic valve gradients can be estimated using the jet velocity and the modified Bernoulli equation: peak gradient = 4v2, where v is the peak velocity across the valve. Mean gradients are calculated using the velocity time integral (VTI).
Aortic valve area (AVA): AVA most frequently is estimated using planimetry on a parasternal short-axis image of the aortic valve or by using the continuity equation (Fig. 33.2).
FIGURE 33.2 Pulse-wave Doppler flow through the LVOT (A) and continuous-wave Doppler flow through the aortic valve (B). The continuous-wave flow allows simple calculation of the peak transaortic gradient: peak = 4v2, where v is equal to the maximum flow across the aortic valve. In this case, v = 5.6 m/s, and the peak gradient is given as 126 mm Hg. The AVA can be calculated from the continuity equation, ALVOT(VTI)LVot = AAV(VTI)AV, where A is area and VTI is the velocity time integral, or the flow velocity integrated over the systolic ejection period. In this example, assuming the LVOT diameter is 2 cm,
The dimensionless index: The dimensionless index refers to the ratio of the left ventricular outflow VTI to the aortic valve VTI. This ratio allows for a quick, semiquantitative assessment of valve stenosis. An index <25% is consistent with severe stenosis.
Several caveats must be kept in mind when using echocardiography to assess the severity of AS. First, Doppler echocardiography can underestimate the peak AS gradient if the echo beam is not accurately aligned with the aortic outflow. Therefore, multiple echo windows must be assessed to find the highest transvalvular velocities. Additionally, the modified Bernoulli equation assumes a left ventricular outflow tract (LVOT) velocity of 1 m/s, which may not always be true. If the true LVOT velocity is >1 m/s, then the modified Bernoulli equation will overestimate stenosis severity. Finally, continuous-wave Doppler cannot assess stenoses in series, such as dynamic LVOT obstruction and valvular AS, or subvalvular and valvular AS. In such instances, the use of the continuity equation can be erroneous. Care must also be taken not to confuse the Doppler signals of AS and MR. Generally, MR velocity is 4 to 5 m/s, and the Doppler signal begins at the start of systole (i.e., no period of isovolumic contraction).
Invasive Assessment of the Aortic Stenosis
Echocardiography usually is sufficient to determine the severity of AS; however, invasive assessment of AS is sometimes necessary, particularly in cases in which clinical symptoms are not congruent with echo data (see American College of Cardiology/American Heart Association [ACC/AHA] Guidelines5). During right heart catheterization, Fick cardiac outputs are preferable to thermodilution because they are more reliable in low-output states. During left heart catheterization, simultaneously measured LV and ascending aortic pressures are ideal, although a pullback gradient may be used if the patient is in sinus rhythm. The femoral artery waveform should not be used to estimate aortic pressures. The AVA can be estimated with the Hakki equation: AVA = CO/√(peak or mean transvalvular gradient). A formal calculation can be done with the Gorlin equation (Fig. 33.3).
FIGURE 33.3 Simultaneous pressure recordings of the LV and aorta. Peak-to-peak gradient is approximately 53 mm Hg. If one knows the cardiac output (CO), the AVA can be estimated with the Hakki equation: AVA = CO/(peak gradient)1/2. Assume that the CO = 4 L/m. Then
(Courtesy of D. Vivek.)
Invasive hemodynamic assessment measures a peak LV-to-peak aortic gradient across the aortic valve, which is invariably lower than the peak gradient on echocardiography. This is due to the fact that Doppler echocardiography measures the peak instantaneous velocity. The mean transvalvular gradients by echo and catheterization correlate well, however. Occasionally, Doppler gradients greatly exceed gradients on catheterization, which may be due to the phenomenon of pressure recovery. In effect, substantial turbulent flow of blood through the valve may cause the pressure in the aorta to be artificially low immediately distal to the valve. Several centimeters into the proximal aorta, however, laminar flow is restored, and pressure “recovers.” Doppler echocardiography detects the maximum pressure gradient between the LV and the proximal aorta. Pressure recovery usually is not an issue with native aortic valves but can be problematic especially with smaller prosthetic valves.
Classifications of Severity of Aortic Stenosis
Normal AVA: 2 to 3 cm2
Mild AS: AVA > 1.5 cm2, mean gradient <25 mm Hg
Moderate AS: 1.0 to 1.5 cm2, mean gradient 25 to 40 mm Hg
Severe AS: <1.0 cm2, mean gradient >40 mm Hg
Treatment of Patients with Aortic Stenosis
Asymptomatic Patients
Patients with AS who have no symptoms may be managed expectantly, as the risk of adverse events—for example, sudden death, cardiac death, or all-cause mortality—is very low in asymptomatic patients.6Endocarditis prophylaxis is no longer indicated for patients with AS, though is reasonable (Class IIa) for patients with previous endocarditis or prosthetic material.7 Vasodilators should be used with extreme caution due to concerns of diminishing preload. The ACC guidelines provide a Class I indication for serial echocardiography every 3 to 5 years for patients with mild AS, and every 1 to 2 years for patients with moderate AS. For patients with severe AS, surveillance echocardiography is recommended on an annual basis, or even more frequently if clinically indicated.5 Stress echocardiography may be helpful in assessing patients with asymptomatic AS to evaluate functional capacity and assess for abnormal blood-pressure response or unrecognized symptoms (Class IIb indication). Patients with symptomatic AS should not have stress testing (Class III).
Patients with mild AS are encouraged to keep physically active and may participate in competitive sports. For patients with moderate AS, aerobic activity is permissible; however, competitive contact sports or heavy lifting is not advised. Patients with severe AS should not engage in strenuous activity or competitive sports.
Progression of AS is highly variable, but on average, valve area decreases approximately 0.1 cm2/y. Progression of AS has been associated with risk factors for coronary artery disease (CAD) (diabetes, hypercholesterolemia, hypertension) in observational studies, and thus treatments of these conditions may be important is AS therapy as well. A more rapid rate of change (>0.3 m/s/y increase in velocity)8 or a peak jet velocity >4 m/s suggest that patients have <2 years before symptoms will develop.4,8 Heavily calcified valves are also associated with a higher likelihood of symptomatic disease.
Any patient with severe AS should be aware that dyspnea, angina, or presyncope merits prompt evaluation. Symptoms of AS may be insidious, however, and patients may be unaware of a decline in functional capacity. In such cases, stress echocardiography can be useful to assess functional capacity, ventricular function, transvalvular gradients with stress, and the pulmonary artery (PA) pressure responses to stress. Such variables may alter the threshold to pursue aortic valve replacement (AVR).
Patients with Rheumatic Fever
Rheumatic fever is an important cause of both aortic and mitral valve disease. Its prevalence has decreased over the past 30 years, largely because of better diagnosis and treatment of group A streptococcal pharyngitis. Acute rheumatic fever is recognized as a serious complication of pharyngeal streptococcal infections, and is due to an autoimmune phenomenon triggered by group A streptococcal M proteins, which mimic cardiac myosin.
Primary prevention of rheumatic fever includes prompt diagnosis of group A streptococcal infections and treatment with appropriate antibiotics, usually a penicillin derivative or macrolide. Patients who develop acute rheumatic fever require long-term secondary prophylaxis, usually with monthly intramuscular injections of benzathine penicillin (Table 33.1).
TABLE
33.1 Recommendations for Secondary Prophylaxis of Rheumatic Fever
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1-e142, with permission from Elsevier.
Symptomatic Patients
For patients with severe AS who develop symptoms, experience a decline in LV systolic function <50%, or are undergoing other open heart surgery (OHS), AVR is recommended as a Class I indication.5 The risk of AVR increases with patient age; however, because the prognosis for untreated, severe symptomatic AS is abysmal, chronologic age alone should not be used to exclude patients from valve surgery. Low ejection fraction, heart failure, renal failure, female gender, and atrial fibrillation also are adverse predictors in patients undergoing aortic valve surgery. Transcatheter aortic valve implantation (TAVI) has emerged as an attractive alternative procedure to surgical AVR, and initial results in patients unable to undergo surgery are promising.9
AVR is reasonable (Class IIa) for patients with moderate AS undergoing OHS for a different reason, and may be considered (Class IIb) for patients with asymptomatic severe AS and abnormal exercise testing or features concerning for rapid progression (age, calcification, and CAD). AVR may also be considered (Class IIb) for patients with asymptomatic and “extremely severe” AS (AVA <0.6 cm2, mean gradient >60 mm Hg, or jet velocity >5 m/s) if the operative mortality is <1% (Table 33.2).5
TABLE
33.2 Indications for Aortic Valve Surgery in Patients with Severe AS
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1-e142, with permission from Elsevier.
Valve Replacement Options
Mechanical Valves Mechanical prostheses have excellent longevity but require systemic anticoagulation. For patients with normal ejection fractions, contemporary bileaflet or single-leaflet valves require an INR of 2 to 3. Older-generation valves should be anticoagulated to an INR of 2.5 to 3.5. Additionally, any patient with atrial fibrillation, depressed LV function, prior thromboembolism, or a hypercoagulable state should have a target INR of 2.5 to 3.5. Mechanical valves should especially be considered in younger patients (<65 years of age), patients with renal disease, and those with calcium-handling metabolic disorders. Younger women who wish to have children are better served with a biologic valve until after their child-bearing years.
Biologic Valves Porcine valve or bovine pericardial tissue valves do not require anticoagulation, but have shorter life spans than mechanical valves. In older patients, tissue valves may be expected to last 10 to 15 years, but have an expected lifespan of <10 years in younger patients. Therefore, tissue valves should be considered for patients >age 65 years, and in patients for whom anticoagulation is problematic. All patients with tissue valves should be treated with aspirin (81 mg daily).
Homografts Cadaveric homografts are the valve of choice for patients with active infective endocarditis because they may resist infection more than tissue or mechanical valves. Additionally, they do not require long-term anticoagulation. However, the durability of homografts is no better than that of tissue valves and reoperation is much more challenging with homografts than with mechanical or other tissue valves.
Ross Procedure The Ross procedure transplants the pulmonic valve into the aortic position and places a homograft in the pulmonic position. This operation may be appropriate at experienced centers for younger patients who have not completed their growth cycle, as studies suggest that the native pulmonic valve (autograft) may grow with the patient when implanted at the aortic position. However, in the long term it creates double-valve pathology from a single-valve problem, and therefore has a limited role in aortic valve disease.
Balloon Valvuloplasty Balloon aortic valvuloplasty may be a very effective therapy for children or very young adults with congenital, noncalcific AS (Table 33.3). In adults with severe AS, however, the results of BAV are not durable. Patients may experience short-term (<6 months) symptomatic and hemodynamic benefit from balloon valvuloplasty; however, most redevelop significant symptoms by 6 to 12 months postprocedure. BAV may be considered (Class IIb) for palliation in nonsurgical patients or for temporizing symptoms until a definitive valve surgery can be performed—for example, in patients with cardiogenic shock who are too ill to undergo immediate surgery. The guidelines do not recommend BAV for patients with asymptomatic severe AS undergoing noncardiac surgery. In contemporary practice, BAV has become more commonplace as a strategy for bridging patients until TAVI can be performed as part of a clinical trial. Current guideline indications for valvuloplasty in adult, calcific AS are limited and are listed in Table 33.4.
TABLE
33.3 Recommendations for Balloon Valvuloplasty in Young Patients with Noncalcific AS
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1-e142, with permission from Elsevier.
TABLE
33.4 Indications for Balloon Valvuloplasty in Adult Patients with Severe, Calcific AS
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1-e142, with permission from Elsevier.
Transcatheter Aortic Valve Implantation More than one-third of patients with severe AS may be denied surgical AVR due to advanced age, significant LV dysfunction, previous chest surgery or radiation, or other comorbidities. TAVI has emerged as a therapeutic option for patients who present a high surgical risk. Currently used devices include the Edwards Sapien Valve (Edwards Lifesciences) and CoreValve ReValving System (Medtronic). These bioprosthetic valves sit within a stent and are deployed across the native aortic valve. Valve implantation is usually conducted via a transfemoral or transapical approach. Results of the PARTNER (Placement of Aortic Transcatheter Valves) trial cohort randomized to medical therapy versus TAVI showed a remarkable, 20% absolute mortality decrease with TAVI (30.7 vs. 50.7%, p 0.001).9 Results of the TAVI versus surgical AVR cohort are eagerly anticipated. Both the Sapien and CoreValve have received the European Conformity (CE) Mark. In the United States, however, the Sapien valve is placed only under the auspices of ongoing clinical trials, and trials of the CoreValve are yet to begin in the United States. 0.001).9 Results of the TAVI versus surgical AVR cohort are eagerly anticipated. Both the Sapien and CoreValve have received the European Conformity (CE) Mark. In the United States, however, the Sapien valve is placed only under the auspices of ongoing clinical trials, and trials of the CoreValve are yet to begin in the United States.
LOW-GRADIENT AORTIC STENOSIS VERSUS PSEUDOSTENOSIS
Patients with “low-flow, low gradient” AS typically have a left ventricular ejection fraction (LVEF) <35%, mean gradient <30 mm Hg, and calculated AVA < 1 cm2, and present a challenging diagnostic dilemma. Because gradients across the valve are proportional to flow and inversely proportional to valve area, an abnormally low flow state can cause low gradients regardless of valve stenosis. In patients who have LV dysfunction, low transvalvular gradients, and suspected severe AS, it is critically important to determine if the poor cardiac output is due in part to severe AS, because these patients will benefit from AVR. However, if there is intrinsic myocardial dysfunction, the LV may not generate sufficient flow to maximally open a mildly stenotic valve. In such patients, the measured gradients may overestimate stenotic severity, leading to “pseudostenosis.” These patients have a poor prognosis and do not require AVR.
Dobutamine echocardiography has been used to differentiate low-gradient AS from pseudostenosis and to assess LV contractile reserve. In the presence of true stenosis, dobutamine will increase or normalize cardiac output, improve LV contractile function and ejection fraction, and lead to increased transvalvular gradients. In true AS, the dimensionless index and valve area will not change significantly with increased cardiac output. The presence of LV contractile reserve is also an important prognosticator, as the operative mortality of patients with contractile reserve is far better than those without (11% vs. 62% for AVR + CABG).10
Conversely, in patients with pseudostenosis, an increase in cardiac output will augment LVOT velocities more so than transvalvular velocities, leading to an increase in both the dimensionless index and the calculated valve area. Therefore, after administration of dobutamine, indications to proceed to AVR include a significant increase in transvalvular gradients, an increase in LVEF > 5%, and no significant change in the dimensionless index or calculated AVA.
AORTIC INSUFFICIENCY
Pathophysiology of Aortic Insufficiency
Whereas AS is purely an LV pressure overload, AI provokes both pressure and volume overload, creating the largest increase in afterload of any valvular condition. The volume overload is a direct result of the AI. In turn, the regurgitation leads to an increased stroke volume through a relatively fixed outflow orifice and into the relatively high-pressure aorta, resulting in chronic pressure overload. Initially, LV compliance rises and the cavity dilates to maintain adequate forward stroke volume. Concomitantly, the LV hypertrophies eccentrically to minimize wall stress. LVEDP thus remains normal early in the disease. As the AI progresses, the ventricle progressively dilates and outpaces hypertrophy, leading to increased end-diastolic pressure (EDP) and after-load. Ultimately, the LVEF declines, and irreversible myocardial dysfunction results.
Etiology of Aortic Insufficiency
It is useful to divide causes of AI into primary (valvular) and secondary (aortic) causes.
Valvular Causes of Aortic Insufficiency
Bicuspid aortic valves are a common cause of AI, and especially are associated with aortic root dilatation.
Infective endocarditis can cause acute AI, particularly in patients with preexisting valve pathology, such as a bicuspid valve.
Rheumatic heart disease can cause AS, AI, or a combination of both.
Radiation heart disease can cause AS, AI, or a combination of both.
Subaortic stenosis is a rare cause of severe AI. The turbulent jet flow caused by the subvalvular stenosis frequently leads to progressive destruction of the aortic valve.
Drugs: Anorectic drugs such as fenfluramine and phentermine have been shown to cause thickening of aortic and mitral valve leaflets, leading to regurgitation. Likewise, ergots have been shown to cause a similar pathology.
Secondary Causes of Aortic Insufficiency
Aortic root dilatation: There are multiple causes of aortic root dilatation that may lead to severe AI. Some of the most clinically relevant include bicuspid aortic valve and Marfan disease, both of which cause root dilatation via cystic medial necrosis. Aortitis due to syphilis and collagen-vascular disease (e.g., Takayasu disease, ankylosing spondylitis, giant cell arteritis) also may precipitate AI.
Aortic dissection: Type A aortic dissections are a major cause of severe acute AI.
VSD: Supracristal VSDs can lead to AI by causing aortic leaflet prolapse. Even if they are small, these VSDs should be closed early on to prevent aortic valve pathology.
Clinical Findings
Acute Aortic Insufficiency
Acute AI most often results from infective endocarditis, trauma, or aortic dissection. On history, patients may have conditions that predispose them to these complications, such as a bicuspid valve, Marfan disease, or a known aortic aneurysm. The physical exam frequently shows profound hemodynamic compromise, with hypotension, tachycardia, and heart failure. It may be difficult to appreciate a diastolic murmur, because aortic diastolic pressure and LVEDP equilibrate very rapidly. Thus, unlike chronic AI, the murmur is only early diastolic. Because the LV does not have time to dilate and increase stroke volume, physical findings of a displaced PMI and wide pulse pressure are absent.
Chronic Aortic Insufficiency
Chronic AI, even when severe, is usually well tolerated for many years. Thus, many patients have AI diagnosed before the onset of symptoms. Early symptoms most often include dyspnea on exertion and a decline in exercise capacity. More progressive disease may lead to frank symptoms of heart failure, particularly as the LV function begins to decline. As with AS, patients with chronic AI may develop angina, regardless of obstructive coronary lesions.
Physical Exam
Vascular Findings
The peripheral vascular hallmark of severe AI is a widened pulse pressure characterized by a brisk systolic upstroke followed by a rapid diastolic collapse, which corresponds to reversal of flow in the aorta. Multiple eponyms have been ascribed to this phenomenon, and include Corrigan pulses (“waterhammer” carotid pulsation) and Quincke pulses (systolic blushing of the nail beds). A bisferiens carotid pulsation, with two systolic peaks, may also be appreciated in severe AI.
Cardiac Findings
On palpation, one may appreciate a laterally displaced PMI or a thrill. The classic AI auscultatory signs include a diminished mitral closing sound, and a decrescendo, blowing, holodiastolic murmur, appreciated best at end-expiration with the patient leaning forward. Classically, a diastolic murmur at the right sternal border indicates aortic dilation with secondary AI, and a left sternal border (LSB) location indicates primary valvular AI. A soft systolic murmur may also be heard at the aortic position as a result of increased flow across the valve. Occasionally, severe AI creates a lowpitched, mitral stenosis–like murmur, the Austin–Flint murmur. The exact mechanism of this murmur is not clear, but it occurs when the AI jet hits the anterior leaflet of the mitral valve. An ejection click suggests a bicuspid valve.
Key Studies
Electrocardiogram
The ECG classically shows LVH.
Chest X-Ray
Chronic severe AI leads to an increase in LV size and mass. Thus, the CXR frequently shows cardiomegaly with an enlarged LV. The aorta may be aneurysmal in patients with secondary AI.
Echocardiography
As with most valvular disease, the most useful noninvasive assessment is with Doppler echocardiography. When assessing a patient with substantial AI, there are several key considerations.
1. LV size and ejection fraction: In patients with severe, asymptomatic AI, both LV size and function must be carefully monitored, because both parameters may guide decisions for valve surgery.
2. Aortic pathology: Particularly in patients with secondary AI, a careful assessment for aortic pathology is mandatory. In many patients, progressive dilation of the aorta dictates AVR and aortic surgery before the AI becomes severe.
3. Aortic valve morphology: Careful assessment of the valve itself may give clues to the etiology of regurgitation. Bicuspid valves, leaflet prolapse, presence of vegetations, and rheumatic canges all can be diagnosed or suggested by transthoracic images.
4. Assessing the severity of AI: There are multiple methods for assessing AI severity. No single measurement is definitive, so several methods should be used to evaluate the AI severity.
a. Regurgitant jet width (vena contracta) in the parasternal long-axis view: A vena contracta width >50% of the LVOT width suggests severe AI.
b. Presence of a proximal isovelocity surface area (PISA): a PISA suggests at least moderate AI, and allows calculation of a regurgitant orifice area (ROA). An ROA >0.3 cm2 suggests severe AI.
c. Pressure half-time (PHT): PHT refers to how fast the pressure gradient across the aortic valve in diastole is reduced by half. Rapid reduction in the pressure gradient (PHT < 250 milliseconds) suggests severe AI, whereas slow degradation of the gradient (PHT > 400 milliseconds) suggests milder disease. PHT is dependent on multiple variables, including systemic vascular resistance and LV and aortic compliance, and thus changes in these variables reduce the utility of PHT.
d. Diastolic flow reversal in the descending aorta: If the reversed flow is pan-diastolic and exceeds 25 cm/s, severe AI is likely (Fig. 33.4).
e. M-mode echocardiography: On classic M-mode imaging, fluttering of the mitral valve is seen with moderate to severe AI. Fluttering may be seen in both acute and chronic AI. In severe acute AI, premature closure of the mitral valve is also seen. Diastolic MR may be noted on color M-mode or color Doppler (Fig. 33.5).
FIGURE 33.4 Continuous-wave Doppler flow profile in the descending aorta, showing flow reversal at approximately 30 cm/s. This profile suggests severe AI.
FIGURE 33.5 M-mode image through the mitral valve in a patient with severe acute AI. Classic findings shown include fluttering of the anterior leaflet (fl) and early closure of the mitral valve (c').
Treatment of Aortic Insufficiency
Acute Aortic Insufficiency
Because acute severe AI is poorly tolerated, emergency or urgent surgery is advised. If a delay is necessary before surgery, IV vasodilators become the treatment of choice. Increasing the heart rate will decrease the diastolic period, and may temporize the hemodynamic effects of acute severe AI. Intra-aortic balloon pumps are absolutely contraindicated in severe AI.
Chronic Aortic Insufficiency
Asymptomatic Patients Chronic AI is usually well tolerated for years before symptoms develop. In asymptomatic patients with normal LV function and severe compensated AI, the progression rate to symptoms is 4% per year, and the progression to LV dysfunction is 1.3% per year. The risk of sudden death is very low in asymptomatic patients (<0.2% per year). Once LV dysfunction develops, symptoms will likely follow within 3 years. Once symptoms develop, the rate of mortality increases to 10% per year.
Medical Treatment
Medical therapy for patients with severe AI includes afterload reduction with vasodilators in certain situations. Vasodilators carry an ACC/AHA Class I recommendation for patients with severe AI and symptoms of LV dysfunction who are unable to undergo surgery, and a Class IIa recommendation for short-term therapy prior to AVR.5 They also should be used in patients with AI who have hypertension. Vasodilators may be considered (Class IIb) in asymptomatic patients with severe AI and normal LV function but LV cavity dilation. They are not indicated (Class III) for patients with mild or moderate AI and normal LV function (Table 33.5). Dihydropyridine calcium channel blockers are first-line agents, although angiotensin receptor inhibitors (ACE) inhibitors are frequently used as well. Endocarditis prophylaxis is no longer indicated for patients with AI, though is reasonable (Class IIa) for patients with previous endocarditis or prosthetic material.7 For patients with mild–moderate AI, yearly exams and biannual echocardiograms are sufficient follow-up if clinical symptoms are stable. For patients with severe AI, follow-up with echocardiography should be done every 6 months with a close eye toward declining LV function and/or LV cavity dilation.
TABLE
33.5 Indications for Vasodilator Therapy in Patients with Severe AI
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1-e142, with permission from Elsevier.
For patients with mild–moderate secondary AI due to aortic root dilatation (>4.5 cm), beta-blockers can be used carefully to decrease aortic wall stress. Relative bradycardia, however, may worsen the AI.
Indications for Surgery
Patients with severe AI who have symptoms, LV dilatation or dysfunction, or (in the case of secondary AI) who have enlarging aortas should undergo valve surgery. ACC/AHA indications for aortic valve surgery for AI are listed in Table 33.6.5 Class I indications for AVR include symptomatic patients with severe AI (irrespective of LV function), asymptomatic patients with LV dysfunction (EF < 50%), or patients with severe AR undergoing CABG or aortic surgery. AVR is reasonable (Class IIa) for asymptomatic patients with severe AI and normal LV function but evidence of LV dilation (left ventricular internal dimension in diastole [LVIDd] >7.5 cm or left ventricular internal dimension in systole [LVIDs] >5.5 cm). Patients with moderate AI undergoing CABG or aortic surgery may be considered for AVR (Class IIb), as well as asymptomatic patients with severe AR and LV dilation (LVIDd >7.0 cm or LVIDs >5.0 cm) if there is evidence of progressive dilation, decreasing exercise tolerance, or abnormal hemodynamic response to exercise.
TABLE
33.6 Indications for Aortic Valve Surgery in Patients with Al
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1–e142, with permission from Elsevier.
For patients with aortic root dilatation and significant AI, progression of the aortic diameter >45 mm is generally accepted as an indication (Class IIa) for aortic root and aortic valve surgery.5 Lower thresholds (>40 mm) may be considered (Class IIb) for patients with Marfan syndrome or bicuspid aortic valves, particularly if the rate of aortic dilatation is accelerating (>0.5 cm/year).11
Surgical options for AI include valve repair or replacement. Valve repair may be considered for noncalcified bicuspid valves with substantial AI. Repair results for regurgitant t rileaflet valves have been disappointing. For valve replacement, the decision to use mechanical versus bioprosthetic valves is based on a number of considerations (see discussion above, for AS). By guidelines, patients younger than age 65 years, and patients with end-stage renal disease or other disorders that affect calcium metabolism, should receive mechanical valves.
PULMONIC VALVE DISEASE
Pulmonic Stenosis
Pulmonic stenosis (PS) is nearly always a congenital defect, although very rare cases of acquired disease have been reported with rheumatic heart disease, carcinoid heart disease, and rubella. PS may be a component of more complex congenital diseases, where it is often associated with a VSD; most frequently, however, PS is an isolated congenital defect.12 Noonan syndrome is classically associated with isolated PS.
PS may be due to valve doming in the setting of commissural thickening, valve dysplasia in the setting of valve thickening and annular hypoplasia, or unicuspid/bicuspid valve pathology (often seen with tetralogy of Fallot).
History and Physical Exam
Symptoms with PS are rare unless the transvalvular gradient exceeds 50 mm Hg, so mild–moderate stenosis is often subclinical. When symptoms are present, they relate to decreased cardiac output and usually include fatigue, dyspnea on exertion, and decreased functional capacity. With more severe disease, presyncope and syncope may develop.
The hallmark of PS on jugular venous examination is a prominent A wave, which reflects increased right ventricular (RV) end-diastolic pressure.
The classic auscultatory findings include a widely split S2, and a crescendo–decrescendo systolic murmur at the pulmonic position. When murmurs are associated with peripheral pulmonary stenoses, they may be heard over the lateral chest wall, the axillae, or in the back. An ejection click may also be appreciated, which moves earlier in systole as the severity of stenosis increases. Signs of severe stenosis include a late-peaking systolic murmur, decreasing intensity of P2, and the complete disappearance of the ejection click. Unlike other right-sided valvular lesions, respiration tends to decrease the intensity of the murmur. Clinical signs of right ventricular hypertrophy (RVH) or RV failure do not present until late in the disease.
Diagnostic Studies
The CXR classically shows asymmetric PA enlargement, with a prominent left PA. The heart size is usually normal.
The key finding on echocardiography is the transpulmonic gradient, which is calculated from the peak jet velocity across the pulmonic valve. PS is likely to be severe when the pulmonic jet velocity exceeds 3 m/s (estimated peak gradient 36 mm Hg), at which point cardiac catheterization is recommended (Class I) for further evaluation and consideration of balloon valvuloplasty. Follow-up echocardiography is recommended for surveillance every 5 to 10 years.
Cardiac catheterization is recommended for patients whose echocardiogram is suggestive of severe PS (Class I). Guidelines for treatment (i.e., balloon valvuloplasty) are based upon peak-to-peak gradient across the PV obtained at catheterization.
Treatment of Pulmonic Stenosis
Endocarditis prophylaxis is no longer indicated for patients with PS, but is reasonable (Class IIa) for patients with cyanotic congenital heart disease or prosthetic material.7 For patients with elevated gradients or with symptoms, balloon valvotomy is the treatment of choice. Indications for balloon valvotomy are listed in Table 33.7. Class I indications for intervention include symptoms with a peak-to-peak gradient at catheterization of >30 mm Hg, or a peak-to-peak gradient >40 mm Hg even without symptoms. Balloon valvotomy for PS with a peak-to-peak gradient 30 to 39 mm Hg is reasonable (Class IIb).5
TABLE
33.7 Recommendations for Valve Intervention in Patients with PS
From Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e1–e142, with permission from Elsevier.
Pulmonary Insufficiency
The main etiologies of significant pulmonary insufficiency (PI) are annular dilation due to pulmonary hypertension, dilation of the PA (which may be idiopathic or secondary to Marfan syndrome), a late complication of tetralogy of Fallot repair, or a primary valve disorder, caused by carcinoid, rheumatic disease, or endocarditis.
Mild PI is quite common in normal hearts, and even moderately severe PI is hemodynamically well tolerated. Over long periods of time, however, severe PI may create a volume and pressure overload on the RV, which leads eventually to RV dilation and failure.
Physical Findings
Pulmonic insufficiency is frequently very difficult to appreciate on physical exam, particularly if the pulmonary pressures are normal. On chest palpation, one may appreciate a hyperdynamic RV. On auscultation, PI may be heard as a low-pitched diastolic murmur along the LSB, which accentuates with respiration.
In the setting of pulmonary hypertension, PI results in a Graham–Steel murmur, a high-pitched, decrescendo murmur heard best along the LSB. It immediately follows an accentuated P2. With respiration, this murmur also increases in intensity.
Diagnostic Studies
The CXR may variably show RV enlargement.
Key data to be obtained from transthoracic echocardiography include RV size and function, PA size and pressures, and the degree of PI. Stress echocardiography may be used to assess RV function and reserve.
Treatment for Pulmonary Insufficiency
PI usually requires valve surgery only if there is progressive evidence of RV dilatation and failure. Biologic prostheses or homografts are favored because of lower associated thrombotic risk as compared to mechanical prostheses at this position.
REFERENCES
1. Otto C. Aortic stenosis. In: Otto C, ed. Valvular Heart Disease. 2nd ed. Philadelphia: Elsevier; 2004:197–246.
2. Bellamy MF, Pellikka PA, Klarich KW et al. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol. 2002;40:1723–1730.
3. Novaro GM, Tiong IY, Pearce GL, et al. Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis. Circulation. 2001;104:2205–2209.
4. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95(9):2262–2270.
5. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118:e523–e661.
6. Kelly TA, Rothbart RM, Cooper CM, et al. Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. Am J Cardiol. 1988;61(1):123–130.
7. Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118: 887–896.
8. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343(9):611–617.
9. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597–1607.
10. Monin JL, Quere JP, Monchi M, et al. Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics. Circulation. 2003;108: 319–324.
11. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology,American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons,and Society for Vascular Medicine. J Am Coll Cardiol. 2010;55:e27–e129.
12. Otto C. Right-sided valve disease. In: Otto C. Valvular Heart Disease. 2nd ed. Philadelphia: Elsevier; 2004:415–436.
QUESTIONS AND ANSWERS
Questions
1. A 42-year-old man with hypertension, but no prior cardiac history, presents with increasing dyspnea on exertion. Physical exam reveals a heart rate of 75 beats/min (bpm) and blood pressure of 175/67. The jugular venous pattern (JVP) is unremarkable. S1 is soft, S2 is normal, and there is an early systolic sound. There is a soft II/VI systolic ejection murmur (SEM) at right upper sternal border (RUSB) radiating to the neck, and a III/VI decrescendo, holodiastolic murmur near LLSB. There is also a low-pitched diastolic rumble heard at the apex. The PMI is laterally displaced. Carotid pulsations are brisk and have a rapid upstroke, immediately followed by a second systolic pulsation. Femoral pulses are normal, and are slightly delayed compared to the radial pulse.
Which of the following findings would you not expect to see on transthoracic echocardiography?
a. Fluttering of the anterior mitral leaflet on M-mode echocardiography
b. Mitral stenosis
c. Bicuspid aortic valve,
d. Dilated left ventricle (LV) cavity
e. Coarctation of the aorta
2. You see a 17-year-old male adolescent in clinic, who is referred to you for evaluation of a murmur. He is well developed and physically active. His heart rate is 62 beats/min (bpm), and his blood pressure is 110/70. His JVP is normal. The cardiac exam shows normal S1 and S2. There is no third heart sound. There is a III/VI SEM at the RUSB, which radiates to the carotids, and a soft diastolic murmur along the left sternal border (LSB). With Valsalva, the murmur softens. The carotid pulses are slightly delayed. Which of the following diagnoses is most likely?
a. Bicuspid aortic valve
b. Supravalvular aortic stenosis (AS)
c. Subvalvular AS
d. Hypertrophic cardiomyopathy (HCM)
3. You see a 25-year-old woman in clinic for a murmur. She is mildly mentally retarded but is sociable and conversational. Her eyes are widely spaced and her ears are low set. Her neck is webbed, and you note that she is rather short. Her JVP has a prominent A wave. She has a pectus excavatum deformity of her chest. Cardiac exam reveals a sternal lift and a III/VI SEM at the LUSB, radiating to the left neck, which decreases with inspiration. You cannot appreciate any clicks. Which of the following statements is not true regarding this woman’s condition?
a. The mode of transmission is autosomal dominant.
b. The genetic defect is linked to elastin.
c. This valvular abnormality is not easily treated with valvuloplasty.
d. ASD is a commonly associated cardiac abnormality.
4. A 75-year-old man with prior bypass surgery is referred to you for shortness of breath and heart failure symptoms. He has a past history of hypertension and chronic obstructive pulmonary disease (COPD). His FEV1 is 1.6 L. He also complains of occasional exertional angina. A recent adenosine nuclear scan revealed a fixed defect in the inferior wall, but no reversible defects. On gated images, the ejection fraction was 25%.
On physical exam, his heart rate is 80 bpm and his blood pressure is 110/80. He appears fatigued and somewhat frail. His JVP is elevated to 10 cm. He has bibasilar rales on pulmonary exam. Cardiac exam shows a normal S, and a paradoxically split S2. There is a harsh III/VI systolic ejection murmur at the left sternal border (LSB), which peaks very late in systole and radiates to the carotids. A II/VI holosystolic murmur is appreciated at the apex that radiates to the axilla. Carotid pulsations are delayed.
You order an echocardiogram that confirms the severe LV systolic dysfunction. His LV is mildly dilated. The entire inferior and basal posterior walls are akinetic and thinned. The LAD and LCx territory is hypokinetic and hypertrophied. The aortic valve is heavily calcified and has poor leaflet excursion. Peak and mean gradients across the aortic valve are 27 and 17 mm Hg, respectively. By continuity, the aortic valve area (AVA) is 0.8 cm2. There is 2+ mitral regurgitation (MR) due to posterior leaflet restriction. What is your next step in this patient’s management?
a. Suggest left heart catheterization to pursue percutaneous balloon valvuloplasty.
b. Refer for cardiac surgery for aortic valve replacement (AVR) and MV repair.
c. Institute diuretic therapy and afterload reduction to treat his congestive heart failure (CHF).
d. Order dobutamine stress echocardiography.
5. A 37-year-old woman with an active history of IV drug abuse presents to the emergency department with abrupt-onset shortness of breath. She is tachycardic to 110 bpm and has a systolic blood pressure of 95 mm Hg. Her boyfriend reports that over the past 7 days she has been febrile and anorectic. He also adds that the patient was “born with an abnormal” aortic valve. Which of the following findings is inconsistent with acute aortic insufficiency (AI)?
a. Diminished S1 on auscultation
b. Diastolic MR on echocardiography
c. A holodiastolic murmur heard at the LSB.
d. Premature closure of the mitral valve on two dimensional (2-D) echocardiography
6. Which of the following patients requires endocarditis prophylaxis?
a. A 34-year-old man with bicuspid aortic valve (AV) and moderate AS undergoing dental extraction
b. A 43-year-old man with mechanical AVR undergoing routine colonoscopy
c. A 65-year-old woman with bioprosthetic AVR undergoing dental extraction
d. All of the choices
e. B and C
7. Which of the following patients would meet criteria for AVR?
a. A 70-year-old woman undergoing CABG with normal left ventricular ejection fraction (LVEF) and Pk/Mn AV gradients of 45/25 mm Hg
b. A 35-year-old man with bicuspid aortic valve and asymptomatic severe AI, normal LV systolic function, and LVIDs 6.0 cm
c. A 75-year-old asymptomatic man with AVA 0.8 cm2, Pk/Mn AV gradients 80/50 mm Hg, normal LV function, and moderate concentric left ventricular hypertrophy (LVH)
d. A and B
e. All of the choices
8. Which of the following patient(s) is/are not indicated for balloon aortic valvuloplasty?
a. An 85-year-old woman with severe symptomatic AS who is unwilling to undergo AVR
b. A 75-year-old man with severe AS and exertional dyspnea who is unable to undergo surgical AVR due to comorbid conditions
c. An 80-year-old man with severe AS who requires surgery for an incarcerated hernia
d. A 78-year-old woman with severe AS and cardiogenic shock
e. A and C
9. Which of the following scenarios describes appropriate, guideline-indicated follow-up of a patient with AS?
a. Annual transthoracic echocardiogram (TTE) in a 34-year-old woman with bicuspid AV and mean AV gradient 30 mm Hg
b. TTE every 2 years in a 60-year-old man with mean AV gradient 18 mm Hg
c. TTE every 2 years in an asymptomatic 73-year-old woman with mean AV gradient 45 mm Hg
d. Stress TTE in a 68-year-old symptomatic man with mean AV gradient 40 mm Hg
10. A patient comes to see you in clinic due to exertional dyspnea. His PMD was concerned due to a harsh systolic murmur heard on exam. On your exam, there is a harsh, 3/6 systolic murmur heard at the apex radiating to the axilla. Carotid exam reveals preserved upstrokes and no bruits. Based on your exam, you diagnose severe MR. You obtain an echocardiogram. The result is reported as normal LVEF with mild concentric LVH and severe AS with Pk/Mn gradients of 100/60 mm Hg. What is the likely source of discrepancy between your physical exam and the echocardiogram?
a. The findings are not discrepant; the murmur in patients with severe AS may be heard at the apex and is known as Gallavardin phenomenon.
b. The continuous wave (CW) Doppler signal measured on the echocardiogram begins at the onset of ventricular systole as seen on the rhythm strip.
c. The CW Doppler signal measured on the echocardiogram begins approximately 80 milliseconds after the onset of ventricular systole seen on the rhythm strip.
d. The murmur heard on exam is the Austin-Flint murmur and is therefore confirmatory of the echocardiographic findings.
Answers
1. Answer B: This patient is fairly young and has hypertension with a wide pulse pressure. The cardiac exam suggests a diagnosis of bicuspid aortic valve (younger patient with AI and an ejection click) with significant AI. The holodiastolic murmur is characteristic of chronic AI, and the displaced PMI suggests longstanding disease that has dilated the LV. Likewise, bounding carotids and a bisferiens pulse are classic findings of AI. BAV usually results from fusion of the right and left coronary cusp leaflets, which then causes a posteriorly directed AI jet. This jet frequently hits the anterior leaflet of the mitral valve, which is manifested on M-mode echocardiography as fluttering of the anterior mitral leaflet and on exam as an Austin–Flint murmur. A history of hypertension in a young patient with AI should prompt an evaluation for aortic coarctation, because up to 20% of patients with BAV also have coarctation. On physical exam, the slightly weaker and delayed femoral pulsations suggest that coarctation might be present.
2. Answer C: This patient has typical exam findings of subvalvular stenosis. In practice, subvalvular stenosis can easily be mistaken for native-valve AS. In younger patients, bicuspid or unicuspid valves are the main differential diagnoses—both of which can have findings of AS and AI. However, the absence of any ejection sound argues against aortic valvular pathology. HCM should also be considered in a patient this age; the slight delay in the carotids and the failure of the murmur to augment with Valsalva make HCM less likely.
3. Answer B: This patient has Noonan syndrome, an autosomal dominant disease characterized by mild mental retardation, characteristic facial features, and a variety of cardiac abnormalities—the most common of which are pulmonary stenosis, peripheral pulmonary stenosis, ASDs, and HCM. The physical exam findings are typical of pulmonic stenosis (PS) with increased A wave, RV left, and a systolic ejection murmur. Unlike other cases of congenital PS, patients with Noonan syndrome tend to have dysplastic pulmonary leaflets that do not cause an ejection click. They also are frequently not amenable to balloon valvuloplasty. Mutations in the gene for elastin are associated with supravalvular AS.
4. Answer D: This patient has low-gradient AS with moderately severe LV dysfunction. His chief complaint is consistent with AS, but could be secondary to CHF or COPD. His physical exam, with narrow pulse pressure, paradoxically split S2, and SEM radiating to the carotids, all suggest AS. Loss of A2 is also consistent with severe AS. The nuclear stress test argues against ischemia. A relatively small fixed defect on nuclear study and preserved wall thickness in the left coronary territory both suggest that the LV dysfunction may be out of proportion to coronary artery disease (CAD), and may be secondary to valvular disease. For patients with low-gradient AS, dobutamine echo can be very helpful in assessing true stenosis versus pseudostenosis. In this patient, we would expect dobutamine to result in an increased EF (contractile reserve), increased gradients across the valve, and a valve area that remained severe. If he has pseudostenosis and a cardiomyopathy unrelated to the valve disease, dobutamine will increase cardiac output but will not result in significant increases in the transaortic gradient or AVA. Patients with LV dysfunction who have contractile reserve and severe AS should undergo AVR. This patient has no contraindications to surgery, and thus valvuloplasty should not be considered definitive treatment.
5. Answer C: Acute AI typically has a brief, early diastolic murmur. Rapid equilibration of aortic and LVED pressures causes termination of the murmur by middiastole. All of the remaining answers are typical of acute AI. A diminished S1 may be seen in acute or chronic AI.
6. Answer C: The guidelines provide a Class IIa indication for endocarditis prophylaxis in patients with prosthetic valve material undergoing dental procedures that disrupt the gingiva or the periapical region or perforate the oral mucosa. Bicuspid AS alone is no longer an indication for prophylaxis in the most recent endocarditis guidelines. Nondental procedures (TEE, EGD, colonoscopy) do not require prophylaxis without active infection.
7. Answer D: In patients with moderate AS who are undergoing open heart surgery (OHS), it is reasonable (Class IIa) to perform concomitant AVR. In asymptomatic patients with severe AI, the presence of LV cavity dilation (LVIDd > 7.5 cm, LVIDs >5.5 cm) is a reasonable indication (Class IIa) for AVR even in the presence of normal LV function. Patients with asymptomatic severe AS may be considered (Class IIb) for isolated AVR if the AS is thought to be “extremely severe” on the basis of AVA < 0.6 cm2, mean gradient >60 mm Hg, or peak AV jet velocity >5 m/s; the patient in (c) does not meet these criteria and is therefore a Class III (not recommended) indication for AVR.
8. Answer E: Balloon aortic vavuloplasty may be considered (Class IIb) as a palliative treatment for symptomatic patients with severe AS unable to undergo traditional surgical AVR, or as a bridging strategy for patients who are too high risk for surgical AVR at a given point in time. It is not indicated (Class III), however, for patients as an alternative to surgical AVR (a) or for patients requiring urgent noncardiac surgery (c). Utmost caution is required on the part of the anesthesia team to avoid hypotension in patients with severe AS undergoing noncardiac surgery, as preload dependence is imperative in maintaining hemodynamic stability.
9. Answer A: The ACC guidelines provide a Class I indication for serial echocardiography every 3 to 5 years for patients with mild AS and every 1 to 2 years for patients with moderate AS. For patients with severe AS, surveillance echocardiography is recommended on an annual basis, or even more frequently if clinically indicated. Patients with symptomatic AS should not have stress testing (Class III).
10. Answer B: A common misinterpretation during echocardiography is the mistaken sampling by CW Doppler of the MR envelope as the aortic outflow. MR velocity is usually in the range of 4 to 5 m/s and characteristically begins at the time of ventricular systole. In contrast, aortic outflow begins after the period of isovulmetric contraction, which on average is approximately 80 milliseconds. Gallavardin phenomenon is present when the musical component of the AS murmur is heard at the apex; it does not typically radiate to the axilla, and this patient did not have evidence of AS. The Austin-Flint murmur is a diastolic murmur of MS heard in patients with severe AI and is thought to be due to premature closure of the MV during diastole due to the eccentric jet of AI hitting the anterior MV leaflet.