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Emerging clinical parameters may help predict outcomes
Myung H. Park, MD
VOL 110 / NO 2 / AUGUST 2001 / POSTGRADUATE MEDICINE
CME learning objectives
This is the first of four articles on valvular heart disease.
This page is best viewed with a browser that supports tables.
Preview: In determining the optimal time to intervene in
asymptomatic patients with aortic stenosis, physicians need to take into account
the clinical course of the disease, the risks of surgical intervention, and the
long-term consequences of prosthetic valves. In this article, Dr Park reviews
the pathology of aortic stenosis, methods of diagnosis, and predictors to help
identify patients who may benefit from early surgical intervention.
Park MH. Timely intervention in asymptomatic aortic stenosis: emerging
clinical parameters may help predict outcomes. Postgrad Med 2001;110(2):28-39
The past 20 years have brought tremendous improvements in the clinical outcomes of patients with aortic valve stenosis. Factors responsible for the clinical advancements include more effective noninvasive monitoring of valvular lesions with Doppler echocardiography and improved surgical techniques and devices. However, there is no effective medical therapy for aortic stenosis. Therefore, given the slow progression of the disease and the long latent period in asymptomatic patients (1), watchful waiting is the only clinical course of action. When symptoms appear, prompt aortic valve replacement is indicated. The biggest challenge is determining the right time to intervene in patients with severe aortic stenosis who remain asymptomatic.
This article reviews the current understanding of aortic stenosis, methods of diagnosis, and the clinical outcomes of patients with asymptomatic severe disease who undergo conservative treatment. Also discussed are the clinical and hemodynamic predictors that may aid in identifying patients at risk for rapid progression and death who may benefit from early surgical intervention.
Several causes of valvular aortic stenosis have been described (table 1). In developed countries, the most common cause of acquired aortic stenosis is an idiopathic disease that results from degeneration and calcification of the aortic leaflets (a process that can occur on bileaflet or trileaflet valves) (3). Bicuspid aortic valve stenosis occurs in about 1% of the US population and is more likely to occur in men than in women. The valve opens normally at birth, but progressive degeneration leads to stenosis in about one third of affected patients, usually by the fifth or sixth decade of life (4).
For reasons that remain unclear, when the disease is acquired in previously normal tricuspid aortic valves, stenosis develops later in life (figure 1: not shown). Some investigators have found that early lesions in aortic stenosis are characterized by subendothelial thickening on the aortic side of the leaflet due to accumulation of cellular lipid infiltrate and extracellular mineralization (5). Furthermore, the risk factors for coronary artery disease and the development of aortic stenosis are definitely associated (6).
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Table 1. Causes of aortic valve stenosis |
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Congenital Acquired Adapted from Rahimtoola (2).
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The main hemodynamic perturbation of aortic stenosis is increased pressure load to the left ventricle, which is calculated using Laplace's law:
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Wall stress (afterload) = |
(pressure X radius of curvature of wall) |
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(2 X wall thickness) |
The heart responds to increased left ventricular pressure with myocardial hypertrophy, a basic adaptive mechanism to compensate for an increased mechanical load and maintain systolic function. When the rise in ventricular pressure exceeds the ability of the increase in wall thickness to compensate, an increase in afterload results and left ventricular performance is impaired. This process, known as afterload mismatch, is largely responsible for systolic dysfunction in aortic stenosis (7).
Left ventricular hypertrophy also alters diastolic properties, resulting in abnormal myocardial relaxation and passive filling processes. Increases in interstitial fibrosis and myocardial stiffness also contribute to diastolic dysfunction in patients with aortic stenosis (8). Thus, although heart failure is usually a result of abnormal systolic function, diastolic dysfunction also may be present in some patients. Clinical heart failure in those with normal left ventricular systolic function is a result of diastolic dysfunction.
The other major consequence of concentric hypertrophy is reduction of coronary blood flow reserve, which is partly due to endocardial compression caused by increased diastolic filling pressure (9). Limited flow reserve is a mechanism that precipitates ischemia during exertion in patients with aortic stenosis regardless of significant coronary artery disease.
Diagnosis of asymptomatic aortic stenosis is based on physical examination findings and results of echocardiography and cardiac catheterization. Exercise testing, inadvisable in patients with moderate to severe symptoms, may be safely performed in some asymptomatic or mildly symptomatic patients.
Physical examination
Aortic stenosis is often first suspected when a systolic ejection
murmur radiating to the neck is detected during physical examination. In mild
aortic stenosis, when the cardiac output is normal, the murmur may be loud and
associated with a thrill, and typically it peaks in early to mid systole. It
often disappears over the sternum and then reappears in the apical area,
mimicking mitral valve regurgitation (Gallavardin's phenomenon). As the disease
progresses, the murmur peaks later and later until it becomes loudest at the end
of systole. The murmur becomes softer and loses its intensity with severe
disease as systolic dysfunction diminishes cardiac output.
The severity of aortic stenosis can be estimated by palpation of the carotid arteries. In mild aortic stenosis, carotid upstrokes are well preserved. As the valvular size diminishes, more force is lost at the stenotic valve and the carotid upstroke becomes reduced in amplitude and delayed in timing (parvus et tardus). The second heart sound may become soft and single as the A2 component is lost because of reduced leaflet mobility.
Echocardiography and cardiac catheterization
The echocardiogram is the most important tool for confirming the
diagnosis of aortic stenosis and for assessing disease severity. Two-dimensional
echocardiography shows thickened and calcified aortic valve leaflets with
reduced motions. Anatomic distinction between bicuspid and tricuspid valves can
be made when the amount of calcification is small. The ability to assess the
overall left ventricular size, degree of hypertrophy, and function is also
crucial.
The transvalvular gradient and the valve area can be estimated by Doppler examination. The aortic valve area is calculated by using Torricelli's principle, in which F is the flow, A is the orifice area, and V is the velocity (10): F = A X V
Because flow is the product of the cross-sectional area and velocity, velocity must increase for flow to remain constant as the bloodstream reaches a narrowing.
Direct Doppler velocity measurement can be converted to gradient by using the modified Bernoulli equation: Gradient = 4 X V2
Alternatively, V can be used to directly calculate the valve area by using the continuity equation (11):
A1 X V1 = A2 X V2
Although the severity of aortic stenosis usually can be assessed by noninvasive techniques, a coronary angiogram often is obtained as part of preoperative assessment before valve replacement. Because patients with aortic stenosis share risk factors for coronary artery disease and are often elderly, they are at high risk for having significant coronary lesions (7,8). In addition, the presence of angina pectoris in these patients is a poor indicator of the presence of coronary artery obstruction. Coronary disease may be present in as many as 25% of aortic stenosis patients with no complaints of angina and as many as 80% of patients with angina (12).
When the severity of aortic stenosis cannot be determined by noninvasive testing, or if test results are incongruous with clinical presentation, the pressure gradient and cardiac output are determined by invasive testing. The instantaneous gradient measured by Doppler (which records the maximal difference between the instantaneous left ventricular and aortic pressures) is not the same as the peak-to-peak gradient obtained by cardiac catheterization (a nonsimultaneous measurement determined by the difference between the peak left ventricular and aortic systolic pressures) (13). The Doppler-derived peak instantaneous gradient is thus always higher than the peak-to-peak gradient, and the difference between the two values decreases as the absolute gradient increases (14).
Exercise testing
In patients with symptoms obviously attributable to aortic stenosis, exercise
testing should not be undertaken because of the increased risk of complications
(15). However, in asymptomatic to mildly symptomatic patients, moderate,
symptom-limiting exercise can be performed safely and may provide valuable
information for determining timing for surgical intervention. Several
investigators have reported no significant complications with exercise testing
in patients with moderate to severe stenosis (16,17). Exercise testing may be
especially useful in patients with vague symptoms when there is doubt whether
complaints are related to the stenotic valve; it is also useful if the
distinction between asymptomatic and symptomatic states is unclear. If exercise
testing confirms that the patient has normal exercise capacity and remains free
of symptoms, continued conservative management is warranted. However, the
precipitation of typical symptoms at a low workload supports further evaluation
and the planning of surgical treatment.
In 1968, Ross and Braunwald (1) published the landmark paper that outlined the natural history of aortic stenosis. The survival rate of patients with asymptomatic aortic stenosis is nearly normal until the symptoms of angina, syncope, or heart failure develop (figure 2: not shown). About 35% of patients who become symptomatic present with angina, and unless valvular replacement is performed, 50% survive for only 5 years. In the 15% who present with syncope, 50% survive for 3 years. The presence of symptoms of heart failure in patients with aortic stenosis portends a grim prognosis (mean survival, <2 years).
The "critical" valve area (the point at which the stenotic valve causes symptoms) differs from person to person. Depending on the extent of hypertrophy, left ventricular function, and cardiac output; body size; and problems inherent in calculating valve area, symptoms can develop when the valve area is between 0.6 and 0.8 cm2 (16). In large patients or those who have high cardiac output, symptoms can occur with a valve area between 0.8 and 1.0 cm2. When the valve area is greater than 1.0 cm2, another source of symptoms should be investigated, especially if the mean transvalvular gradient is 30 mm Hg or less (tables 2 and 3) (18). Use of only the aortic valve gradient, as defined by Doppler or catheterization, to assess disease severity may be inaccurate because it does not take the cardiac output into account (19). A borderline gradient may result from low cardiac output; in this case, the valve area should be measured.
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Table 2. Suggested conservative guidelines for relating severity of aortic stenosis to Doppler gradients* |
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Peak gradient (mm Hg) |
Mean gradient (mm Hg) |
Severe aortic stenosis |
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>80 |
>70 |
Highly likely |
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60-79 |
50-69 |
Probable |
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<60 |
<50 |
Uncertain |
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*In adults with normal cardiac output and normal average heart rate. Tables 2 and 3 adapted from Rahimtoola (18). |
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Table 3. Suggested grading of degree of aortic stenosis |
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Aortic stenosis |
AVA (cm2) |
AVA index (cm2/m2) |
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Mild |
>1.5 |
>0.9 |
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Moderate |
>1.0-1.5 |
>0.6-0.9 |
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Severe* |
<1.0 |
<0.6 |
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AVA, aortic valve area. *Patients with AVAs that are borderline values between the moderate and severe grades (0.9 to 1.1 cm2; 0.55 to 0.65 cm2/m2) should be considered individually. |
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The crucial issues are if and when asymptomatic patients with severe aortic stenosis should be referred for surgical treatment. Several researchers have attempted to answer this question by examining the outcome of conservatively managed asymptomatic patients with severe aortic stenosis.
The earliest observation was published by Contratto and Levine in 1937 (20). They followed the clinical course of 180 patients with valvular aortic stenosis for more than 25 years and concluded that in asymptomatic patients, sudden death was rare and often followed the development of symptoms. This clinical finding was emphasized 30 years later by Ross and Braunwald (1), who reported that sudden death occurred predominantly in symptomatic patients. In asymptomatic patients with acquired aortic stenosis, the risk of sudden death was reported to be 3% to 5%. On the basis of these findings, the investigators recommended that patients with acquired aortic stenosis defer surgical treatment until symptom onset.
Many of the previously mentioned observations and recommendations still apply today. Turina and colleagues (21) retrospectively studied 73 patients with aortic stenosis who underwent cardiac catheterization between 1963 and 1983. Of this cohort, 17 patients had asymptomatic severe aortic stenosis defined by the Gorlin formula-derived aortic valve area of less than 0.9 cm2. None of the patients died or required surgical treatment during the first 2 years. At 5 years, 75% of the patients were alive without the benefit of surgical intervention, a survival rate of 94%.
Kelly and colleagues (22) followed the clinical course of 51 asymptomatic patients with severe aortic stenosis for a mean of 17 months. Severe aortic stenosis was defined as a Doppler-derived peak systolic pressure gradient of at least 50 mm Hg. During the study, 21 patients (41%) began experiencing symptoms. Eight patients in the asymptomatic population died, but only two of them died of cardiac causes (heart failure in one and sudden cardiac death in the other). Both patients had had symptoms for at least 3 months before death. This and the previous study group (21) concluded that the clinical course of patients with severe aortic stenosis can be followed safely until symptoms develop.
In a 20-month study, Pellikka and associates (23) likewise followed the course of 113 asymptomatic patients with severe aortic stenosis defined as a Doppler-derived peak gradient of at least 64 mm Hg. Similar to the findings of Kelly and colleagues (22), 37 patients (33%) began to experience symptoms during the follow-up period. Twenty patients (18%) required aortic valve replacement. Three patients died of causes attributable to aortic stenosis (two of sudden cardiac death and one of heart failure); all three patients had had symptoms for at least 3 months before death. The probability of remaining free of cardiac events (eg, aortic valve replacement, death) was 93% at 1 year and 74% at 2 years. Although these findings confirmed the benign nature of asymptomatic aortic stenosis (risk of sudden cardiac death, <2%), this study, as well as the two previously cited studies (21,22), found that aortic stenosis appears to progress very rapidly from symptom development to sudden death in some asymptomatic patients (22,23).
Furthermore, it has been shown that patients may die while awaiting surgical treatment (24) and that such intervention performed in an urgent manner or in patients with severe symptoms has a significantly higher operative mortality rate than when performed in patients with mild symptoms (25). Thus, the possibility that patients may not recognize symptoms immediately makes it desirable to identify those patients in whom symptoms are likely to develop and who are likely to require surgery within a short time.
Several investigators have searched for predictors of clinical outcomes to help identify asymptomatic patients at increased risk. Among the group studied by Pellikka and associates (23), a baseline peak flow velocity of 4.5 m/sec or greater and an ejection fraction of less than 50% were independent predictors of subsequent cardiac events. For 2 1/2 years, Otto and associates (16) followed the course of 123 patients with initial average mean gradients of 30 mm Hg. Four patients died of heart failure, and 48 patients (39%) required aortic valve replacement. No patients died suddenly. Interestingly, as in Pellikka's study, baseline peak flow velocity was a significant predictor of clinical outcome. The likelihood of surviving 2 years without valve replacement was only 21% for a jet velocity at entry of greater than 4 m/sec compared with 66% for a jet velocity of 3 to 4 m/sec and 84% for a jet velocity of less than 3 m/sec (16). The rate of change in jet velocity and the functional status score were also significant predictors of outcome.
Most recently, Rosenhek and associates (26) followed the course of 126 patients with severe asymptomatic aortic stenosis (defined by an average jet velocity of 5 m/sec) for 22 months. Four patients died of congestive heart failure, one of endocarditis, and one of sudden cardiac death. Except for the sudden death, all deaths were preceded by symptoms. Fifty-nine patients (40%) underwent aortic valve replacement.
Multivariate analysis identified age, extent of aortic valve calcification, and rate of progression of aortic jet velocity as predictors of clinical outcome. Patients 50 years old or younger had significantly longer event-free survival than older patients. The extent of aortic valve calcification was a strong predictor of cardiac events (26) (figure 3: not shown). Patients with moderate or severe calcifications had very similar outcomes, and all deaths occurred among these patients. Patients without calcifications had the best outcomes. The difference in aortic jet velocity between the patients who had cardiac events during follow-up and those who did not was statistically significant (4.66+0.62 m/sec versus 4.41+0.38 m/sec; P=.003). However, the rate of progression of aortic jet velocity was a much stronger predictor and was significantly higher in patients who had cardiac events than in those who did not (0.45+0.38 m/sec per year versus 0.14+0.18 m/sec per year; P<.001). In this cohort, the combination of calcification and a rapid increase in aortic jet velocity indicated highest risk. For patients with moderate or severe calcification and an increase of at least 0.3 m/sec within 1 year, 79% either required surgical treatment because of new symptoms or died within 2 years.
Given the importance of timeliness in detecting symptoms of aortic stenosis, it generally is recommended that the patient and the family be given an easily understandable list of symptoms to watch for. Furthermore, patients need to be educated about the expected course of the disease. Arrangements should also be made between the patient, the primary care physician, and the cardiologist to allow the patient to be seen as soon as possible after symptoms emerge. For asymptomatic patients, the usual interval for follow-up is 6 months to 1 year; however, this should be dictated by the severity and the rate of progression of the disease. On the basis of recent data correlating echocardiographic findings to clinical outcome (26), a yearly echocardiogram may be vital in managing asymptomatic severe aortic stenosis (though not generally recommended by recent guidelines (27)).
Aortic valve replacement is rarely justified for asymptomatic patients with hemodynamically significant stenosis, because the clinical course is benign and the risk for sudden cardiac death is low. Although imperfect, certain clinical parameters are emerging as possible predictors of outcome. Factors such as a baseline jet flow velocity of greater than 4 m/sec, a rate of change of jet velocity of at least 0.3 m/sec per year, and moderate to severe aortic valve calcification may allow physicians to identify patients at risk for rapid disease progression and sudden death.
Dr Park is director of the Cardiac Transplant Service and Pulmonary Hypertension Program, Ochsner Heart and Vascular Institute, New Orleans. Correspondence: Myung H. Park, MD, Ochsner Heart and Vascular Institute, 1514 Jefferson Hwy, New Orleans, LA 70121. E-mail: mpark@ochsner.org.
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Proper treatment requires consideration of all clues
Mahesh S. Mulumudi, MD; Krishnamoorthy Vivekananthan, MD
VOL 110 / NO 2 / AUGUST 2001 / POSTGRADUATE MEDICINE
The authors disclose no financial interest in this article.
This is the second of four articles on valvular heart disease.
This page is best viewed with a browser that supports tables.
Proactive management can improve outlook
Robert L. Scott, MD, PhD
VOL 110 / NO 2 / AUGUST 2001 / POSTGRADUATE MEDICINE
CME learning objectives
This is the third of four articles on valvular heart disease.
This page is best viewed with a browser that supports tables.
Preview: Mitral regurgitation, which involves retrograde flow of blood
from the left ventricle into the left atrium, is a relatively common disorder,
particularly in older patients. Numerous causes have been identified, and this
valve abnormality should be considered in all patients who have evidence of
systolic heart failure. Repair of the valve, rather than valve replacement, now
is the procedure of choice for many patients. In this article, Dr Scott reviews
physical findings, diagnostic studies, and proactive management of this complex
disorder.
Scott RL. Native mitral valve regurgitation: proactive management can improve
outlook. Postgrad Med 2001;110(2):57-63
Mitral regurgitation occurs as either a chronic or an acute condition, with symptoms varying according to the chronicity and severity of the disease process (table 1). Competence of the mitral valve is dependent upon the structural and functional integrity of its constituent components, which include the anterior and posterior leaflets, annulus, chordae tendineae, papillary muscles, and wall of the left ventricle. The mitral valve apparatus plays an active role in contraction of the left ventricle. A structurally intact apparatus contributes about 10% to the ejection fraction.
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Table 1. Some causes of mitral regurgitation |
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Chronic regurgitation
Infectious causes
Structural causes
Acute regurgitation
Infectious causes
Structural causes
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The characteristic murmur of chronic mitral regurgitation is holosystolic, best heard at the cardiac apex and radiating to the axilla. The murmur is reduced by maneuvers that decrease preload (eg, standing, administration of amyl nitrite). Conversely, the intensity of the murmur is increased by squatting and leg elevation. In addition to pulmonary congestion, a third heart sound is often heard if left ventricular failure is present. The apical impulse is displaced laterally because of left ventricular enlargement. If pulmonary hypertension is present, evidence of right ventricular failure is often seen, manifesting as hepatomegaly, ascites, elevated jugular venous pulse wave, and peripheral edema.
The findings in acute mitral regurgitation relate to the degree of left ventricular failure. Both pulmonary hypertension and an S3 gallop are often noted, although the apical impulse may not be displaced.
No unique electrocardiographic characteristics are associated with mitral regurgitation, but features related to the cardiac abnormalities are evident. Voltage criteria for both left atrial enlargement and left ventricular hypertrophy may be noted in patients who have chronic mitral regurgitation. The radiographic findings depend on the degree of chamber enlargement and left ventricular failure. Enlargement of the left atrium, left ventricle, and right ventricle are commonly seen with chronic mitral regurgitation. Pulmonary edema is often evident with acute mitral regurgitation in the absence of chamber enlargement.
Role of echocardiography
Two-dimensional echocardiography and Doppler flow studies allow enhanced
assessment of the severity of mitral regurgitation and its mechanism. This is
particularly true with transesophageal echocardiography, given the relative
proximity of the esophagus to the heart. Assessment of the motion of the mitral
valve leaflets, as well as the direction of the color flow Doppler, helps
determine the mechanism of mitral regurgitation (1).
Using echocardiography, the severity of mitral regurgitation can be evaluated by several methods (2). Color Doppler studies are convenient, and the largest detected regurgitant color jet can correlate with disease severity. However, this is markedly load- dependent and thus not reliable. The diameter of the jet immediately downstream from the orifice of the regurgitant jet also correlates with severity of mitral regurgitation (3).
The regurgitant fraction or regurgitant stroke volume across the mitral valve is another useful measure for assessing the severity of disease. Comparative analysis of Doppler regurgitant fraction with combined left ventricular angiography and thermodilution studies has shown good correlation among these techniques (4).
The regurgitant stroke volume is the product of the regurgitant time velocity integral from continuous wave Doppler and the effective regurgitant orifice area. The regurgitant orifice area is independent of load and can be calculated as the quotient of the maximal regurgitant flow rate divided by the maximal regurgitant flow velocity (5). This is also load-dependent and thus can underestimate disease severity. Three-dimensional echocardiography provides additional anatomic information about the mitral valve apparatus and regurgitant flows. However, this technology is still being evaluated.
One of the more recent advances in valve assessment involves use of proximal isovelocity surface area (PISA) studies (6). These are based on the premise that the regurgitant flows proximal to the valve orifice are of the same velocity as those through the valve. PISA can help distinguish between moderate and severe mitral regurgitation. However, it assumes that the flow convergence zone has a hemispheric conformation, which is not necessarily true. PISA is also fairly tedious and operator-dependent, making routine use of questionable utility.
When to consider ventriculography
Left ventriculography is an effective method for accurately quantitating
mitral regurgitation (7). The quantitation is based on the relative amount of
contrast flow from the left ventricle back into the left atrium. This is best
appreciated in two different angiographic views: a 30° right anterior oblique
position and a 60° left anterior oblique and 20° cranial position. It is also
important that the catheter avoid direct contact with the papillary muscles and
the mitral valve.
The degree of regurgitation ranges from mild filling of the left atrium (1+) to severe, complete filling of the left atrium back into the pulmonary veins (4+). The left ventricular end-diastolic pressure (LVEDP) should also be measured before ventriculography is performed. The introduction of contrast medium may further increase the LVEDP, causing possible hemodynamic compromise. Patients with elevated LVEDP should be given nitroglycerin or diuretics, or both, before ventriculography is performed.
Hemodynamic assessment
Right-sided heart catheterization is a valuable tool in management of patients
with decompensated heart failure, complicated myocardial infarction, or
cardiogenic shock. Patients with acute mitral regurgitation generally have
hemodynamic evidence of severe left ventricular failure, manifested by low
cardiac output, elevated pulmonary artery wedge pressure, and pulmonary
hypertension.
The pulmonary capillary wedge tracings typically show an elevated V wave, which is a manifestation of regurgitant filling of the left atrium. The size of the V wave can correlate with the severity of the mitral regurgitation. With chronic, compensated mitral regurgitation, the hemodynamic assessment may be unremarkable.
Exercise testing
Exercise testing with echocardiographic evaluation is useful in assessing the
severity of mitral regurgitation and determining the timing of surgery (8).
Cardiopulmonary exercise testing is routinely used to determine
transplant-listing status and can also be used to assess the degree of
decompensation in mitral regurgitation. Patients who achieve anaerobic threshold
with a peak maximum oxygen consumption of less than 14 mL/kg per minute or a
peak maximum consumption of less than 50% of the age-predicted value should be
considered for operative repair or replacement of the mitral valve.
The choice of management depends in large part on the severity of symptoms and the general health outlook for each patient.
Medical treatment
The principal goal of medical management of chronic
mitral regurgitation is to prevent left ventricular failure and prevent or delay
the need for mitral valve surgery. The key element is relief of left ventricular
wall stress and prevention of adverse remodeling. In a study of 143 asymptomatic
patients with isolated, severe aortic regurgitation and normal left ventricular
systolic function (9), vasodilator therapy with nifedipine, a calcium channel
antagonist, was shown to delay valvular deterioration and the need for valve
replacement. However, no data are yet available from large, prospective,
randomized trials in patients undergoing medical treatment of mitral
regurgitation.
Schön and associates (10) demonstrated significant reductions in regurgitant fraction and left ventricular size in 12 patients with moderate to severe isolated, chronic mitral regurgitation treated with the angiotensin-converting enzyme (ACE) inhibitor quinapril hydrochloride. ACE inhibitors certainly should be considered first-line therapy in patients with concomitant left ventricular dysfunction.
Systemic hypertension in patients with chronic mitral regurgitation should be aggressively treated with antihypertensive agents. Blood pressure goals should be no greater than 139 mm Hg systolic and 89 mm Hg diastolic, as set forth in the guidelines of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (11). If concomitant ischemia is present, treatment may attenuate the severity of regurgitation.
Surgical intervention
When surgical intervention is warranted, the paramount concern is whether
repair of the mitral valve is likely to be as safe and effective as replacement
of the valve. This question is not easily answered, since outcome depends on
several factors, including the cause of left ventricular dysfunction (ischemic
versus nonischemic), the severity of left ventricular and right ventricular
dysfunction, and the integrity of the mitral valve apparatus (12).
Given that the mitral valve apparatus plays an integral role in left ventricular systolic function, the rationale for preservation, if at all possible, becomes clear. In the past, conventional wisdom was to replace the mitral valve in patients with preserved systolic function. In contrast, patients with poor systolic function were limited to medical therapy or transplantation. However, with the advent of improved surgical and myocardial preservation techniques, there has been a paradigm shift in the treatment of severe mitral regurgitation in patients who have left ventricular dysfunction.
One of the recent pioneers in this field, Steven F. Bolling, MD, and his associates performed mitral valve repair in 48 patients with left ventricular dysfunction (ejection fraction, <25%) and severe mitral regurgitation (13). Within the cohort, 24 patients (50%) had nonischemic regurgitation and 40 (83%) were classified as New York Heart Association (NYHA) class IV. The 1-year survival rate was 82%, and the 2-year survival rate was 71%. NYHA classification improved from a preoperative average of 3.9 to a postoperative average of 2.0. Peak oxygen consumption also improved from 14.5 mL/kg per minute before repair to 18.6 mL/kg per minute after. All repairs were done using a remodeling ring annuloplasty.
Bishay and associates (14) performed mitral valve surgery in 44 patients with left ventricular systolic dysfunction (mean ejection fraction, 28%) and severe mitral regurgitation. Isolated repair was used in 35 patients and valve replacement in 9. Significant improvements in echocardiographic and clinical parameters, including ejection fraction and NYHA classification, were evident in these patients. All repairs used annuloplasty techniques, and replacements were performed with subvalvular preservation.
In another study, information on mitral valve repair and replacement was reviewed for 710 consecutive patients referred for mitral valve surgery (15). Among these patients, 169 underwent mitral valve repair and 160 had mitral valve replacement. Survival rates at 1, 5, and 10 years were higher in patients undergoing mitral valve repair than in those who had mitral valve replacement. Factors predicting poor outcome included increased age (>75 years), right ventricular systolic dysfunction (ejection fraction, <20%), left ventricular systolic dysfunction (ejection fraction, <45%), mitral valve replacement, and left ventricular enlargement (12,15).
Data indicate that replacement of the mitral valve with preservation of the annular papillary structure can result in postoperative left ventricular systolic function comparable to that with valvular repair (16). This is particularly relevant because repair of the mitral valve is not always feasible.
With respect to the components of the subvalvular apparatus, preservation of the posterior leaflet is probably most important in maintaining left ventricular systolic function (17). Preservation of the anterior leaflet is also feasible. However, obstruction of the left ventricular outflow tract is possible if too much of the anterior leaflet is left intact.
Patients who have no symptoms and those with acute, severe mitral regurgitation often present special challenges for the primary care physician. What are the preferred approaches to management?
Asymptomatic patients
A key problem in management of mitral regurgitation is what to do for the
patient who has no symptoms. Such patients often subconsciously reduce their
activities to avoid problems with dyspnea or fatigue, thereby making it
difficult to assess the degree of impairment. Symptoms also are related to the
degree of adverse remodeling, as evidenced by dilatation of the left ventricle.
Cardiopulmonary stress testing should be used when there are questions about the
degree of impairment.
Asymptomatic patients (NYHA class I) with mild mitral regurgitation and no pulmonary hypertension or left ventricular enlargement (left ventricular end-systolic diameter, >45 mm) can be followed clinically on a yearly basis. If clinical deterioration is apparent, repeat echocardiographic examination is appropriate (18). Concomitant pulmonary hypertension and atrial fibrillation increase the morbidity associated with mitral regurgitation and justify early operative intervention.
Any evidence of ventricular enlargement or systolic dysfunction in an asymptomatic patient with mild to moderate mitral regurgitation should prompt referral to a cardiologist. Asymptomatic patients with severe mitral regurgitation should be reevaluated every 6 months, and echocardiography should be done annually to monitor left ventricular enlargement and function (figure 1: not shown) (18).
Acute regurgitation
Severe, acute mitral regurgitation is often a medical emergency requiring
prompt surgical treatment. When appropriate, nonsurgical acute interventions
include hemodynamic stabilization with placement of an intra-aortic balloon pump
and vasodilator therapy with nitroglycerin, nitroprusside, or milrinone lactate
(Primacor).
The goal of the acute therapy is to reduce ventricular wall stress and improve forward flow. Expedient diagnosis using either angiography or echocardiography is crucial. Patients often require coronary angiography if ischemia is suspected as a precipitating factor. When mitral regurgitation occurs with an acute infarct, prognosis tends to be poor (19). Acute percutaneous revascularization can be helpful in temporizing the situation by reducing the infarct size and restoring blood flow to the mitral valve.
With severe, acute mitral regurgitation, mechanical complications (eg, flail leaflet, ruptured chordae, ruptured papillary muscle) should be considered. Both transthoracic and transesophageal echocardiography can provide prompt anatomic diagnosis and determine the most effective surgical approach (1).
The operative mortality with ischemic mitral regurgitation is high, compared with that associated with nonischemic mitral regurgitation (20). Surgical options include mitral valve repair or replacement. The choice depends on the integrity of the mitral valve apparatus and the degree of left ventricular dysfunction.
Mitral regurgitation is a common valvular abnormality that can result in substantial morbidity. Primary care physicians should maintain a high index of suspicion for this disorder, especially in patients with symptoms of heart failure. The paramount concern is early identification of patients with mitral regurgitation and prompt referral to a cardiologist when symptoms occur or if evidence of ventricular enlargement or reduction in ejection fraction is found.
Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Although no standard medical treatment has been established for mitral regurgitation, use of ACE inhibitors is appropriate. Patients presenting with severe, acute mitral regurgitation from papillary muscle rupture should be evaluated for ischemia and treated expediently. The preferred operative procedure in patients with severe mitral regurgitation and left ventricular dysfunction is mitral valve repair, if possible, or mitral valve replacement with posterior chordal preservation, if feasible.
Dr Scott is director, heart failure services, and medical director, coronary care unit, Ochsner Heart and Vascular Institute, New Orleans. Correspondence: Robert L. Scott, MD, PhD, Ochsner Heart and Vascular Institute, 1514 Jefferson Hwy, BH 326, New Orleans, LA 70121. E-mail: rscott@ochsner.org.
A high index of suspicion is important to reduce risks
Ananth K. Prasad, MD; Hector O. Ventura, MD
VOL 110 / NO 2 / AUGUST 2001 / POSTGRADUATE MEDICINE
CME learning objectives
This is the fourth of four articles on valvular heart disease.
This page is best viewed with a browser that supports tables.
Preview: Valvular heart disease is often first recognized during
pregnancy, when increased demands on the heart trigger symptoms. The profound
hemodynamic changes associated with pregnancy have marked effects on patients
with this disease and require special attention and care. In this article, Drs
Prasad and Ventura discuss possible causes, clinical manifestations, and
management of valvular heart disease during pregnancy.
Prasad AK, Ventura HO. Valvular heart disease and pregnancy: a high index of
suspicion is important to reduce risks. Postgrad Med 2001;110(2):69-88
The decline in rheumatic fever in the United States has led to a decrease in the incidence of valvular heart disease in pregnancy and its associated maternal and fetal mortality. Nonetheless, valvular heart disease related to congenital abnormalities continues to pose unique challenges in diagnosis and management, especially in pregnant women.
To understand the consequences of valvular heart disease during pregnancy, it is important to review the hemodynamic changes that occur in all pregnant women. First, blood volume increases, starting at the sixth week and rising rapidly until midpregnancy. Thereafter, the rise continues but at a much slower rate. The increase in blood volume ranges from about 20% to 100%, with an average of 50%. Proportionately, plasma volume increases much more than erythrocyte mass, which can lead to physiologic anemia. An estrogen-mediated stimulation of the renin-angiotensin system that results in sodium and water retention appears to be the mechanism underlying the blood volume increase.
Similarly, cardiac output increases steadily during pregnancy up to about 34 weeks of gestation, when it begins to fall. The average increase in cardiac output is about 45% by 24 weeks of gestation. The increase is due to both the expansion in blood volume and the augmentation of stroke volume and heart rate. Thus, early in pregnancy, an increase in stroke volume (20% to 30%) is responsible for the increase in cardiac output. Later in pregnancy, the rise is related to an acceleration of heart rate (25%), since stroke volume decreases as a result of vena caval compression. In addition, cardiac output rises still higher and heart rate increases during labor and delivery. After delivery, when vena caval compression is relieved, there is a surge of venous return that augments cardiac output and places additional burden on the heart.
Other hemodynamic changes associated with pregnancy are a 21% decrease in systemic vascular resistance and a 34% decrease in pulmonary vascular resistance; there is no change in left ventricular contractility. Pregnant women tend to maintain normal left ventricular filling pressures because of left ventricular dilatation with an increase in left ventricular mass, as measured by echocardiography (1).
Symptoms of normal pregnancy can mimic those of valvular heart disease. Specifically, women with normal pregnancies may have exertional dyspnea, orthopnea, fatigue, lower extremity edema, and presyncope. Physical examination can also be confusing in a woman whose pregnancy is progressing normally. For example, a and v waves are prominent on jugular venous pressure studies, pulse pressure is increased, and the maximal apical impulse is laterally displaced. The first heart sound is accentuated, and the pulmonary component of the second heart sound is also increased. The third heart sound is heard in about 80% of pregnant women, whereas the fourth heart sound is rarely heard. The universal early ejection flow systolic murmur of less than grade 3/6 along the left sternal border is heard in 90% of pregnant women and may be enhanced by anemia.
The presence of certain physical signs in pregnant women should raise suspicion of cardiac abnormalities. These include a loud fourth heart sound, a diastolic murmur, a grade 3/6 or greater systolic murmur, a fixed split of the second heart sound, and an opening snap. The presence of one or more of these signs should signal the need for echocardiographic evaluation.
Pregnant women with valvular heart disease are no more likely to have bacterial endocarditis than nonpregnant women with such heart disease. However, prophylactic therapy does seem warranted when valvular heart disease is present (see box below) (2,3). Similarly, women who require anticoagulant therapy during pregnancy need special care (see box below) (4,5).
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gastrointestinal procedures |
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Category |
Drug and dosage |
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Table 1. Recommended antibiotic prophylaxis for high-risk women undergoing genitourinary or |
|
|
High-risk patient |
Ampicillin, 2 g IM or IV, |
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|
|
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High-risk patient who has penicillin allergy |
Vancomycin HCl (Vancocin,
Vancoled), 1 g IV over 2 hr, |
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Most pregnant women with valvular heart disease can be managed medically. However, severe symptomatic disease may pose a threat to the survival of both mother and fetus. In this situation, valve replacement may be the only option (6).
When needed, valve replacement is best performed during the second trimester. It is important to point out that this procedure involves cardiopulmonary bypass and its associated complications. Hypothermia during bypass can increase the chance of fetal bradycardia and death, and anesthetic agents used during surgery may have teratogenic effects, according to anecdotal reports. Blood pressure during cardiopulmonary bypass should be carefully maintained to ensure adequate placental perfusion. Fetal heart monitoring is an excellent way to assess placental perfusion.
Pregnancy in women who have prosthetic valves carries a high risk of morbidity and mortality for both mother and fetus. The hypercoagulable state increases the likelihood of thrombosis and thromboembolic complications associated with artificial heart valves. Pregnancy outcome has been good when patients were managed with heparin for the first 12 weeks, followed by warfarin sodium (Coumadin) anticoagulation. The fetal outcome has been better with bioprosthetic valves, compared with mechanical prostheses, in both aortic and mitral positions (table 2) (7).
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Table 2. Outcome of pregnancy in women with mechanical or biological prostheses |
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|
Study |
No. of pregnancies |
Live births (%) |
Thromboembolic complications |
|
|
|
|
|
Valve thrombosis (%) |
Emboli (%) |
|
|
||||
|
Mechanical valves |
||||
|
Hanania |
95 |
53 |
11 |
9 |
|
Sbarouni |
151 |
73 |
9 |
5 |
|
Born |
35 |
63 |
8 |
3 |
|
|
||||
|
Bioprosthetic valves |
||||
|
Hanania |
60 |
80 |
0 |
0 |
|
Sbarouni |
63 |
83 |
0 |
0 |
|
Born |
25 |
100 |
0 |
5 |
|
|
||||
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Adapted from Baughman (7). |
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From 1970 through 1983, the rate of maternal heart disease was 1.3 per 100 deliveries, with 60% of cases being rheumatic in origin. Mitral stenosis is the most common chronic rheumatic valvular lesion in pregnancy. Since the natural history of rheumatic mitral stenosis typically includes a 20- to 25-year asymptomatic period, symptoms often first appear during pregnancy. Congenital fusion of the commissures, or "parachute mitral valve," and left atrial myxoma are other causes of mitral stenosis during pregnancy.
Symptoms related to mitral stenosis reflect an increased pressure gradient across the mitral valve. This pressure gradient is a function of both the cross-sectional area of the valve and the flow through the valve. The rise in cardiac output during pregnancy increases the pressure gradient.
Hemodynamic abnormalities in a pregnant woman with mitral stenosis depend on the severity of the disease but normally include increased left atrial pressure associated with elevation of both pulmonary venous and arterial pressures. This results in pulmonary edema, pulmonary hypertension, and right ventricular failure. In addition, an increase in heart rate caused by exercise, fever, or emotional stress decreases diastolic left ventricular filling time and further elevates left atrial pressure and reduces cardiac output. This increase in pressure also predisposes pregnant women to development of atrial arrhythmias. Furthermore, loss of atrial contractility associated with a rapid ventricular response has devastating effects and can lead to pulmonary edema.
Clinical presentation
Pregnant women with mitral stenosis present clinically with symptoms of both
left-sided heart failure and right ventricular failure, depending on the
severity and duration of the valvular disease. Symptoms of left-sided heart
failure are more common and include orthopnea, paroxysmal nocturnal dyspnea, and
dyspnea on exertion. Unless the patient has long-standing valve disease,
symptoms of right ventricular failure are less common and include peripheral
edema and ascites, which in pregnancy are difficult to recognize as being
related to valvular heart disease.
Careful examination should include a search for an opening snap and a diastolic rumbling murmur with presystolic accentuation, which are classic auscultatory findings in mitral stenosis. The presence of elevated jugular venous pressure, hepatomegaly, a loud pulmonary component of the second heart sound, and right ventricular heave on examination also supports a diagnosis of mitral stenosis.
Diagnostic assessment
Echocardiography is the diagnostic study of choice for evaluation of mitral
stenosis in pregnant women and both confirms the diagnosis and helps determine
the severity of the stenosis. In addition, the echocardiogram allows assessment
of pulmonary pressures, right ventricular function, mitral regurgitation, and
the configuration of the subvalvular apparatus, which is important in
determining the success of percutaneous mitral balloon valvuloplasty (PMBV).
Invasive diagnostic testing is rarely indicated in pregnant women with mitral
stenosis.
Medical management
Most pregnant women with mitral stenosis can be managed medically. Since an
increased preload contributes to the exacerbation of heart failure, it is
prudent to restrict salt and fluid intake. Diuretics should be used judiciously
to avoid hypotension and increased heart rate. Use of beta-blocking drugs to
slow the heart rate can dramatically improve symptoms (8). Digoxin (Lanoxin) is
not very effective because the adrenergically driven increased heart rate
overrides its effect.
Balloon valvuloplasty
PMBV is an invasive procedure that is being used more
often because of its proven safety. However, PMBV is contraindicated in women
who have moderate to severe mitral regurgitation, calcified mitral valve, or
clot in the left atrium. In addition, even though PMBV is considered a fairly
safe procedure, it should be used cautiously to avoid radiation exposure during
the first trimester.
Surgical intervention
In early investigations, open commissurotomy and valve replacements carried a
maternal mortality rate of about 5% and a fetal mortality rate of 20% to 30%.
Many factors (eg, anesthetic agents used, hypothermia during surgery) can
adversely affect the outcome. Improved cardiopulmonary bypass techniques have
resulted in improved outcomes. A recent study of 168 pregnant women who
underwent open commissurotomy showed no maternal mortality and a fetal mortality
of 1.8% (9). Prosthetic mitral valve replacement is now a feasible option in
patients who are not candidates for either PMBV or open commissurotomy.
Labor and delivery
In view of the increase in cardiac output during labor and after
delivery, it is important to plan management carefully. Vaginal delivery is
possible in most patients with mitral stenosis. However, optimal management may
require invasive hemodynamic studies in patients with moderate to severe
stenosis. Oxygen should be given to reduce pulmonary pressures, and fluid
restriction and use of diuretics and epidural anesthesia are recommended as
well. Vigorous manual uterine massage and oxytocin (Pitocin, Syntocinon)
infusion can reduce the risk of excessive blood loss.
This condition is usually well tolerated in pregnancy, presumably because of left ventricular unloading secondary to the physiologic fall in systemic vascular resistance. The cause of mitral regurgitation during pregnancy has changed over the years. In the past, it was usually a consequence of rheumatic fever, but today it is more often related to mitral valve prolapse complicated by ruptured chordae tendineae. Other possible causes are Libman-Sacks endocarditis, infective endocarditis, Marfan syndrome and pseudoxanthoma elasticum, Ehlers-Danlos syndrome, and dilated cardiomyopathy.
Mitral regurgitation leads to a progressive increase in the volume of blood going to the left ventricle, which results in enlargement of both the left ventricle and the left atrium. Moreover, left ventricular cavity dilatation is associated with mitral valve annular dilatation and asynergic contraction of the papillary muscle, which exacerbate mitral regurgitation.
Increased left ventricular volume and left atrial enlargement are associated with an elevation of pulmonary venous and arterial pressures, leading to pulmonary hypertension and right-sided heart failure. Because of the decrease in left ventricular afterload associated with mitral regurgitation, systolic wall stress is also lowered. These changes are more pronounced in pregnancy because of a reduction in systemic vascular resistance.
Symptoms and physical examination
Mitral regurgitation during pregnancy is usually well tolerated. Symptoms may
include dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea. The
apical impulse of the left ventricle is shifted outward, and a holosystolic
murmur is heard at the apex on auscultation. The murmur radiates toward the
axilla and increases during expiration. Some pregnant women with mitral
regurgitation present with atrial fibrillation associated with heart failure and
cardiomegaly.
If tricuspid regurgitation is associated with mitral regurgitation, peripheral edema might be present, a right ventricular heave may be noted on palpation, and a systolic murmur may be heard along the left lower sternal border on auscultation. Unlike the murmur of mitral regurgitation, the tricuspid regurgitation murmur increases with inspiration.
Assessment and diagnosis
Doppler echocardiography is useful in diagnosis of chronic mitral
regurgitation. The following information can be obtained from these studies:
Management
In symptomatic pregnant patients with mitral regurgitation, hydralazine
hydrochloride (Apresoline), diuretics, and digoxin can be used when systolic
function is impaired. If severe symptomatic mitral regurgitation due to mitral
valve prolapse is found, surgical mitral valve repair may be a good option
because it avoids the need for anticoagulant therapy. Mitral valve replacement
can be done as a last resort. In most cases, maternal and neonatal outcomes are
good. However, women with pulmonary arterial pressure greater than 50 mm Hg are
at increased risk for complications.
Symptomatic aortic valve disease is less common than mitral valve disease in pregnant women. In the United States, congenital aortic stenosis secondary to membrane on the bicuspid aortic valve appears to be the predominant cause. In contrast, rheumatic heart disease is the most common cause in developing countries. During pregnancy, women with bicuspid aortic valves are at risk for aortic dissection related to the effects of hormones on connective tissue.
The pressure gradient across the aortic valve is responsible for the hemodynamic changes in aortic stenosis. The increase in left ventricular systolic pressure needed to maintain sufficient pressure in arterial circulation leads to increased stress on the ventricular wall. To compensate for this, left ventricular hypertrophy develops, which can result in diastolic dysfunction, fibrosis, diminished coronary flow reserve, and late systolic failure.
An increase in stroke volume and a fall in peripheral resistance are largely responsible for the increase in the gradient across the aortic valve. The clinical consequences of the increased aortic gradient depend on the degree of preexisting left ventricular hypertrophy and left ventricular systolic function. When compensatory changes in the left ventricle are inadequate to meet the demands imposed by the need for increased cardiac output late in pregnancy, symptoms develop. This usually occurs with moderate to severe aortic stenosis.
Clinical findings
Clinical presentation and symptoms depend on the degree
of aortic stenosis. Women with aortic valve areas more than 1.0 cm2
tolerate pregnancy well and are asymptomatic. However, women with more severe
aortic stenosis may have symptoms of left-sided heart failure (dyspnea on
exertion). Syncope or presyncope is rare, and pulmonary edema is even more
unusual. However, arrhythmias are sometimes present.
Because symptoms of aortic stenosis are similar to those of normal pregnancy, diagnosis of this condition is challenging. Physical findings vary with the severity of the disease. The left ventricular impulse is sustained and displaced laterally. A systolic ejection murmur is heard along the right sternal border and radiates toward the carotid arteries, and a systolic ejection click is heard. A fourth heart sound may be present, suggesting abnormal diastolic function. The presence of pulsus parvus et tardus suggests hemodynamically significant aortic stenosis.
Assessment and diagnosis
Diagnosis can be confirmed with echocardiography. The aortic gradient and
valve area can be calculated by Doppler flow studies. In addition,
echocardiography can detect left ventricular hypertrophy. Estimation of ejection
fraction and left ventricular dimensions may be useful to predict outcome during
pregnancy, labor, and delivery. Women with an ejection fraction less than 55%
are at high risk for development of heart failure during pregnancy. Cardiac
catheterization is indicated if the clinical picture is consistent with severe
aortic stenosis, if noninvasive data are inconclusive, and if percutaneous
balloon valvuloplasty is needed. Fetal echocardiography is indicated if the
mother has congenital aortic stenosis, since the risk that the fetus has similar
anomalies is 15%.
Management
The severity of the condition and its symptoms largely determines management
of aortic stenosis. Most asymptomatic patients and those who have mild to
moderate stenosis can be managed with medical therapy and close monitoring. It
is important to maximize cardiac output and fetal blood flow by avoiding intense
exercise, potent vasodilators, and diuretics. In patients with low ejection
fractions, digoxin can be used, provided drug levels are monitored regularly.
Percutaneous balloon valvuloplasty and aortic valve replacement are options for management. Balloon valvuloplasty can be used as a bridge to valve replacement in women who are too ill to undergo surgery. The risk of death in nonpregnant patients managed in centers experienced in this technique is about 5%. In pregnancy, balloon valvuloplasty carries added risk because circulation to the fetus is stopped for a short time during the procedure. However, several studies of balloon valvuloplasty for severe aortic stenosis during pregnancy suggest favorable outcomes for both mother and fetus (10).
Balloon valvuloplasty is not the preferred treatment in patients with calcified aortic valves or in the presence of significant aortic regurgitation. In those circumstances, valve replacement is indicated. The choice of a bioprosthetic versus a mechanical valve should be individualized. Bioprosthetic valves avoid the need for long-term anticoagulant therapy.
Labor and delivery
Vaginal delivery is preferred unless there is an obstetric indication for
cesarean section. Avoidance of severe vasodilatation and maintenance of an
adequate fluid balance are paramount so that cardiac output is not compromised.
Low epidural anesthesia may be used to minimize vasodilatory effects, and
antibiotic prophylaxis should be given to patients with previous endocarditis.
In general, outcomes for both the mother and the fetus are favorable. However,
some evidence suggests that as many as 20% of women who have severe aortic
stenosis choose to have therapeutic abortion.
Aortic insufficiency in pregnancy can be either acute or chronic. The acute form is caused by aortic dissection, bacterial endocarditis, or malfunction of a prosthetic valve. Because the left ventricle has no time to adapt to volume overload, pulmonary edema and cardiogenic shock often occur. Acute aortic insufficiency should be considered a surgical emergency, and valve replacement is urgent, even in pregnancy.
Another condition that requires emergency surgery is proximal aortic dissection with aortic insufficiency. Marfan syndrome, bicuspid aortic valve, and hypertension add to deleterious hormonal effects and are predisposing conditions for aortic dissection.
In pregnant women, chronic aortic insufficiency is often associated with a bicuspid aortic valve or rheumatic heart disease. The gradual increase in left ventricular volume overload allows the left ventricle to adapt by increasing left ventricular end-diastolic diameter. This adaptation appears to maintain the forward flow unless systolic dysfunction sets in. Therefore, as with mitral insufficiency, chronic aortic insufficiency is well tolerated during pregnancy.
Clinical presentation
Patients with chronic aortic insufficiency usually
present with dyspnea, decreased exercise tolerance, and chest pain.
Some patients have syncope due to arrhythmias and left ventricular dysfunction.
Pregnant women tolerate aortic regurgitation well because of the normal
peripheral vasodilatation during pregnancy, which improves hemodynamic
parameters in aortic insufficiency.
On the other hand, women with aortic insufficiency and either New York Heart Association functional class I or II symptoms or systolic ventricular dysfunction do not tolerate pregnancy well. Findings on physical examination are typical of hyperdynamic circulation. Such findings may complicate diagnosis, since a hyperdynamic state also can be associated with normal pregnancy. Physical findings include a wide pulse pressure, brisk carotid pulse, and mildly displaced apical impulse. An early diastolic murmur on the left sternal border and soft second heart sounds are clear clues to aortic insufficiency.
Assessment
Transthoracic echocardiography and Doppler flow studies are helpful in making
a diagnosis and assessing the severity of aortic insufficiency. Transesophageal
echocardiography can be used to detect vegetation in bacterial endocarditis and
aortic dissection. Cardiac catheterization is usually not indicated, but
magnetic resonance imaging can be helpful in diagnosis of aortic dissection. Fetal
echocardiography is indicated in women with congenital abnormalities of the
aortic valve or Marfan syndrome.
Management
In patients with chronic aortic regurgitation, management depends on the
severity of the disease and symptoms. In asymptomatic patients, close monitoring
is all that is needed. Symptomatic patients can be treated with vasodilators,
including hydralazine, nitrates, and diuretics. Digoxin may be beneficial in
patients who have systolic dysfunction. Use of angiotensin-converting enzyme
inhibitors is contraindicated during pregnancy.
Pulmonary stenosis is usually congenital and may be associated with Noonan's syndrome or tetralogy of Fallot. Symptoms are present only with moderate or severe stenosis. Pregnancy is well tolerated in asymptomatic patients and those with mild pulmonary stenosis.
With this disorder, the gradient across the valve leads to increased right ventricular pressure, prominent a waves on jugular venous pressure studies, right ventricular heave, pulmonary ejection click, systolic thrill over the pulmonary area, and the typical ejection systolic murmur that is louder during inspiration. Diagnosis is made by clinical examination and confirmed by echocardiography. The incidence of fetal congenital heart disease in babies born to mothers who have pulmonary valve stenosis is about 20%, and fetal echocardiography should be performed in all at-risk infants (11).
Tricuspid stenosis in women of childbearing age is usually congenital. In contrast, tricuspid insufficiency may be due to primary valvular disease (eg, endocarditis-induced valve damage, Ebstein's anomaly).
Ebstein's anomaly is associated with atrial septal defect, which can lead to right-to-left shunt. Most pregnant women who have this anomaly have atypical chest pain, dyspnea, and palpitations. Physical examination reveals one or more systolic clicks and a systolic murmur along the left sternal border, which increases with inspiration. Right bundle branch block, atrial fibrillation, or delta waves as seen in the Wolff-Parkinson-White syndrome can be detected by electrocardiography.
In addition, echocardiography is an important tool for evaluating Ebstein's anomaly and may show apical displacement of the tricuspid valve, atrial septal defect, and tricuspid regurgitation. Ambulatory electrocardiography should be performed because atrial and reentry arrhythmias are common with this condition. Fetal echocardiography is also indicated.
Vigorous exercise should be avoided by these women, especially if cyanosis is associated or signs of right-sided heart failure are found. Diuretics may be useful, but vasodilators and digoxin are not beneficial. In patients with symptomatic arrhythmias and abnormal conduction pathways before pregnancy, radiofrequency ablation should be considered before conception.
Pregnant women who have valvular disease represent a major challenge for physicians involved in their care. Careful history taking and physical examination, along with a judicious use of diagnostic tools (mainly echocardiography), can lead to better management and ultimately to excellent outcomes for both mother and baby.
The incidence of endocarditis is no different in pregnant women with valvular heart disease than in nonpregnant women who have such heart disease. Streptococcal organisms are the most common cause of subacute bacterial endocarditis, but acute endocarditis is usually due to more virulent organisms, such as Staphylococcus aureus, Streptococcus pneumoniae, and Neisseria gonorrhoeae. A high degree of suspicion is needed for diagnosis. Transthoracic echocardiography can be helpful but is not as sensitive as transesophageal echocardiography.
The American College of Cardiology and the American Heart Association do not recommend prophylactic treatment of bacterial endocarditis for women undergoing uncomplicated vaginal delivery or cesarean section. However, if vaginal infection is present, bacterial endocarditis prophylaxis should be started promptly. In addition, antibiotic prophylaxis seems appropriate for women in other high-risk categories. These include pregnant women who have any of the following:
Pregnancy involves a state of hypercoagulability caused by increased levels of various clotting factors and increased blood viscosity. Systemic anticoagulation poses major problems during pregnancy in women with prosthetic heart valves, venous or arterial thromboembolism, or atrial fibrillation with valvular heart disease.
Warfarin sodium (Coumadin) is contraindicated early in pregnancy because of its teratogenic effects (eg, nasal and musculoskeletal hypoplasia, mental impairment, chondrodysplasia punctata, epithelial and central nervous system abnormalities). Also, warfarin crosses the placenta and increases risk of fetal hemorrhage. The critical time for development of embryopathy is between 6 and 12 weeks' gestation.
Unfractionated heparin does not cross the placenta and has little effect on the fetus. However, long-term intravenous use poses logistic problems. Experience with low-molecular-weight heparin in this situation is minimal but suggests this drug is effective in preventing thromboembolism. Furthermore, low-molecular-weight heparin is associated with low neonatal mortality and low incidences of premature delivery, spontaneous abortion, and intrauterine fetal death. However, it can cause significant osteoporosis in pregnant women.
On the basis of the data available, most authorities recommend stopping warfarin as soon as possible and using systemic heparin therapy for the first 12 weeks of pregnancy. Heparin can be given subcutaneously in a dose of 10,000 units every 12 hours to maintain partial thromboplastin time at 2 to 2.5 times the control value. After 12 weeks' gestation, warfarin therapy can be reinstituted.
Dr Prasad is a third-year fellow in cardiology and Dr Ventura is director, cardiovascular disease training program, and education consultant cardiologist, Ochsner Heart and Vascular Institute, New Orleans. Correspondence: Hector O. Ventura, MD, Ochsner Heart and Vascular Institute, 1514 Jefferson Hwy, New Orleans, LA 70121. E-mail: hventura@ochsner.org.