Chapter 29. Valvular Heart Disease

• Valvular heart disease may remain asymptomatic until an underlying serious illness causes rapid deterioration of health.
• Patients with valvular heart disease are at increased risk of bacterial endocarditis following invasive procedures.
• Aortic stenosis significantly increases the mortality of patients requiring noncardiac surgery.
• Aortic stenosis is a common comorbidity in elderly patients.
• Heart failure in a patient with hypertrophic cardiomyopathy should be treated with rate-slowing and negative inotropic agents.
• Acute regurgitant lesions are frequently medical emergencies and are not as well tolerated as chronic regurgitant lesions.
• Once left ventricular dysfunction occurs in a patient with mitral regurgitation, the lesion is severe and unlikely to improve with surgical correction; in fact, surgery may worsen left ventricular function.

Valvular heart disease is a common cause of morbidity and mortality in the U.S. Although the incidence of rheumatic fever has declined, many patients that acquired the disease years ago are now presenting with valvular abnormalities. In addition, degenerative diseases of the valves are becoming increasingly common as the population ages. Recognition of valvular diseases is important for proper management of seriously ill patients.

The cardiac physical examination is the essential first step in making the diagnosis of valvular heart disease. Patients presenting with signs and symptoms of cardiac illness, such as shortness of breath, pulmonary edema, angina pectoris, or syncope, should have a detailed examination of the cardiovascular system to ascertain the presence of valvular lesions. Assessment of patients prior to noncardiac surgery should include an evaluation for valvular lesions. Once valvular heart disease is suspected, a diagnostic work-up can be completed to determine the severity of the abnormality and quantitate the risk to the patient.

Many patients with valvular abnormalities remain asymptomatic until the onset of an underlying medical illness precipitates heart failure. Tachycardia due to arrhythmias, pain, blood loss, or hypoxia can suddenly precipitate pulmonary edema or low-output states in patients with previously compensated valvular disease. In these instances, prompt treatment of the critical illness is essential to avoid complications of the valvular lesion.

The lesions of valvular heart disease can be broadly categorized as stenotic and regurgitant. The impact of these abnormalities on left or right ventricular function will determine the clinical presentation and risk to the patient at times of critical illness. Traditionally, cardiac catheterization has been used to diagnose and quantify valvular stenosis or regurgitation. Advances in echocardiography have made this imaging modality highly accurate in assessing valvular structure and function.

The degree of stenosis of a valve can be measured by the Gorlin formula.1 The Gorlin formula uses the principle that flow equals area times velocity. The formula for calculating aortic valve stenosis can be stated as A = F/(C × V), where A is the valve area, F is aortic valve flow (calculated as cardiac output divided by the systolic ejection period in seconds multiplied by the heart rate), C is an empiric constant accounting for valvular energy loss and orifice contraction, and V is velocity. Velocity can be expressed as V = √2gh, where g is gravitational acceleration (980 cm/s2), and h is the measured pressure gradient. The Gorlin equation for aortic valve area can then be written as A = F/(C × 44h).

Considering the empirical nature of the Gorlin formula, the calculated valve areas have been useful in predicting prognosis and risk. Recently formulas calculating valve resistance have been devised. Resistance is less flow dependent and therefore less variable than aortic valve areas.2 Echocardiographic methods of calculating valve areas have shown good correlation with invasive methods.

Determination of the degree of valvular leakage by cardiac catheterization has depended on visualization of contrast opacifying the receiving chamber. Important determinants of the severity of regurgitation are the size and function of the receiving chamber, both of which can be estimated either by invasive or noninvasive means. Acute and chronic regurgitant lesions have markedly different presentations, in part owing to the inability of a receiving chamber to accommodate a sudden volume overload.

This chapter will review the etiology, pathophysiology, clinical presentation, diagnostic evaluation, and management of the major valvular lesions and hypertrophic cardiomyopathy. The physical examination will be highlighted, as it yields the first crucial clues to the presence of valvular disease. Management of prosthetic valve abnormalities will be covered as well.

Etiology and Pathophysiology

Over the past few decades, there has been a dramatic shift in the presentation of valvular aortic stenosis. The prevalence of rheumatic fever and rheumatic heart disease has decreased substantially in developed countries, and the advancing age of the population has increased the incidence of degenerative valvular lesions. At present, there are three major etiologies of valvular aortic stenosis: congenital malformations of the valve, which are usually suspected in younger patients; rheumatic aortic disease, which is usually accompanied by mitral valve disease; and calcific or degenerative changes of normal aortic valves, which are seen later in life.

Congenital aortic stenosis may present early in life when fusion of the valvular commissures is present at birth, or later in life after calcification of a congenitally bicuspid valve occurs. It is estimated that 1% to 2% of aortic valves are bicuspid, making this one of the most common congenital heart malformations.3 A bicuspid valve functions normally in younger people, but the leaflets are prone to earlier calcific and degenerative changes because of increased stress on the valve compared to a normal tricuspid valve. Calcific aortic stenosis of a bicuspid valve usually develops in middle or late adult life (Fig. 29-1).

Senile calcification of normal three-leaflet valves is an increasingly common cause of aortic stenosis in the elderly. Surgical series have reported the incidence of degenerative aortic stenosis at 10% to 30% of surgical cases,4 but this finding significantly underestimates the true prevalence of the condition in the elderly, since many patients are not referred for surgical correction. Because of its high prevalence, this disease represents a significant morbidity in patients presenting with life-threatening diseases.

As aortic stenosis progresses, the reduced orifice offers increased resistance to blood flow, represented by the transvalvular pressure gradient. The relationship between blood flow or cardiac output and the pressure gradient is not linear, but instead is related to the square root of the pressure gradient. Therefore small changes in cardiac output may have significant effects on the pressure gradient. Critical aortic stenosis is usually considered to exist when the mean pressure gradient exceeds 50 mm Hg or when the calculated orifice area is 0.75 cm2 or less.

Left ventricular outflow is initially maintained by hypertrophy of the left ventricle. Left ventricular volumes remain normal until late in the disease. In calcific aortic stenosis in which not all of the commissures are fused, the increase in left ventricular systolic pressure may maintain or even augment cardiac output. A fall in cardiac output, however, may make aortic stenosis more severe by preventing adequate opening of the valve. In patients with a relatively fixed aortic orifice, any sudden reduction in blood pressure or systemic vascular resistance, such as that seen in sepsis or with the use of vasodilating drugs, can lead to a precipitous fall in cardiac output and cardiac arrest.

The early symptoms of aortic stenosis are usually related to the left ventricular outflow obstruction. Symptoms of angina or syncope may develop during the early stages. Angina may be due to epicardial coronary artery disease or subendocardial ischemia. About 50% of patients with aortic stenosis and typical angina pectoris have normal coronary arteries. Syncope may be secondary to a vasodepressor response when an abrupt rise in left ventricular pressure with exertion is not accompanied by a corresponding rise in aortic pressure.5

Dyspnea is a late symptom of aortic stenosis and is frequently related to changes in left ventricular systolic or diastolic function. With the onset of left ventricular failure, cardiac output decreases, leading to a corresponding fall in the transvalvular pressure gradient. Left atrial, pulmonary, and right heart pressures all increase, presenting as pulmonary edema and heart failure. The left ventricle will then dilate to compensate for the falling output.

Correction of aortic stenosis brings about significant improvement in cardiac function and lowers elevated right heart pressures and left ventricular filling pressures. Left ventricular hypertrophy regresses early, sometimes eventually to a normal mass.6

Clinical Presentation

Patients with aortic stenosis may present with angina, syncope, or dyspnea on exertion. Some patients complain of nonspecific symptoms such as fatigue, dizziness, or palpitations. Many elderly and sedentary patients remain asymptomatic despite having critical aortic stenosis; the stenosis only becomes life threatening when they develop other critical illnesses or require elective or emergent surgery.

The physical examination can suggest hemodynamically significant aortic stenosis that will likely cause complications in patients who have critical illnesses or require surgery. A loud systolic murmur heard throughout the precordium with radiation to the neck is characteristic. This murmur usually has a crescendo/decrescendo pattern, although in critical aortic stenosis in which there is a significant delay in outflow, the murmur may be late-peaking or holosystolic. The murmur may be loud at the apex of the heart, mimicking mitral regurgitation. Severe aortic stenosis murmurs may be palpable. The aortic component of the second heart sound is typically soft or absent. An absent aortic closing sound may be the most sensitive finding for critical aortic stenosis, but it is not a common auscultatory sign.7 The carotid impulse is generally diminished in volume and has a delayed, slow-rising peak. The cardiac impulse is usually strong and is not significantly displaced unless the ventricle has dilated.

Diagnostic Evaluation

The electrocardiogram (ECG) usually shows left ventricular hypertrophy with a repolarization abnormality or strain pattern. A normal ECG virtually rules out the presence of critical aortic stenosis. The chest x-ray can show calcification of the valve, although cardiac enlargement is present only in the most severe cases, when left ventricular dilation is present.

Echocardiography can reliably diagnose aortic stenosis. There is a high correlation between transvalvular gradients and calculated aortic valve areas derived from Doppler echocardiography and those derived from angiography.8–10 Doppler methods permit direct noninvasive measurement of the pressure gradient across the aortic valve. The peak gradient is estimated by the modified Bernoulli equation, which states that the pressure drop in mm Hg is equal to four times the square of the velocity (Fig. 29-2). The aortic valve area can be calculated by the continuity equation, which is based on the law of conservation of mass, which states that for a fluid in a closed system, flow at all points must be equal. To calculate aortic valve area, flow is measured proximal to the aortic valve by calculating the area of the left ventricular outflow tract just below the valve, and the velocity at the same level. Velocity is also measured across the valve (Fig. 29-3). The continuity equation can be written as A1v1 = A2v2, where A1 is the area of the outflow tract, v1 is the velocity in the outflow tract, A2 is the aortic valve area, and v2 is the velocity at the aortic valve. A2 is the unknown and is solved for from the known measurements.

Cardiac catheterization can confirm the severity of aortic stenosis. Most patients presenting with early symptoms of aortic stenosis will have a normal cardiac output, normal right heart and pulmonary capillary wedge pressures, and a normal ejection fraction. The left ventricular end-diastolic pressure will be increased, with a prominent A wave reflecting a stiff left ventricular chamber. In advanced states, the cardiac output and ejection fraction will be depressed, with a corresponding increase in left atrial and pulmonary pressures. In patients anticipating surgery, the coronary arteries should be visualized, because of the high incidence of concomitant coronary artery disease in elderly patients.

Management

Aortic stenosis is a mechanical problem, so the only effective long-term treatment is correction of the obstruction to outflow with surgery. The onset of symptoms is an indication for surgery. The development of heart failure with aortic stenosis is associated with a high mortality, especially if the left ventricular ejection fraction is reduced. Patients with severe aortic stenosis and left ventricular dysfunction have a mean survival of only one year.11 Patients that present in heart failure must first have their symptoms stabilized and will then need an evaluation of the severity of the stenotic lesion and the degree of left ventricular dysfunction before proceeding with definitive aortic valve replacement surgery.

The left ventricular ejection fraction can be depressed in patients with aortic stenosis due to excessive systolic wall stress (afterload) seen in “true” aortic stenosis, or due to an intrinsic abnormality of myocardial contractility or cardiomyopathy referred to as “pseudo” or “relative” aortic stenosis.12 Aortic valve replacement in true aortic stenosis can lead to a significant improvement in the ejection fraction once the afterload excess is relieved. Aortic valve replacement may have minimal benefit in pseudo aortic stenosis since the depressed ejection fraction is a muscle contractile abnormality that may not improve with valve replacement.

Patients with severe aortic stenosis and low cardiac output may present with only a modest increase in the transvalvular pressure gradient, referred to as “low-gradient” aortic stenosis. It can be difficult to distinguish true aortic stenosis causing low cardiac output from a low cardiac output state due to a cardiomyopathy in association with only mild or moderate aortic stenosis. In patients with abnormal myocardial contractility, the low-flow state and low pressure gradient can lead to a calculated aortic valve area in the severe range. The standard valve area formula is less accurate and will underestimate the valve area in low flow states.13

One method to determine whether a patient is presenting with true fixed aortic stenosis or pseudo aortic stenosis due to left ventricular dysfunction is to calculate the aortic valve area at two different flow conditions by using dobutamine stress. Patients with true aortic stenosis will increase cardiac output and the transvalvular gradient with dobutamine, but the aortic valve area will remain unchanged.14 Patients with pseudo aortic stenosis will have an increase in valve area that is frequently outside of the severe range (>1.0 cm2) with dobutamine infusion. One protocol that has been used is intravenous dobutamine 5 μg/kg per minute and increased by 5 μg/kg per minute every 3 minutes until a maximal dose of 20 μg/kg per minute is obtained.14 The presence of contractile reserve with dobutamine (increased stroke volume and ejection fraction) is associated with a low operative risk and a good long-term prognosis, whereas operative mortality is high in the absence of contractile reserve.15

The development of heart failure in patients with aortic stenosis is an indication for surgery, which should be performed as soon as possible after medical stabilization. Diuretics are frequently used to relieve pulmonary congestion, but need to be used cautiously so as not to decrease stroke volume. It has been thought that vasodilators are contraindicated in aortic stenosis because they may lead to a precipitous drop in blood pressure, causing cardiac arrest. Recent experience with nitroprusside in patients with true aortic stenosis and depressed ejection fraction has shown that afterload reduction with this agent can lead to a significant increase in cardiac output and can be used as a therapeutic bridge to surgery.16 Therefore, current medical management of severe aortic stenosis with decreased cardiac function consists of the careful use of diuretics, with either positive inotropes (dobutamine) and/or afterload reduction (nitroprusside), being careful not to cause hypotension. Digitalis and angiotensin-converting enzyme inhibitors, as used in heart failure, can be carefully used as well.

The patient that presents with critical noncardiac disease and severe aortic stenosis is a challenging medical problem. The augmentation in cardiac output required for perfusion of tissues in disease states such as sepsis or profound anemia may not be adequate in patients with true fixed aortic stenosis. The need for urgent noncardiac surgery in patients with severe aortic stenosis puts a patient at a very high risk for cardiac complications, including myocardial infarction, congestive heart failure, and death.17

Percutaneous balloon aortic valvuloplasty is a procedure in which a balloon is placed across the stenotic valve and inflated, leading to stretching of the valve annulus and separation of the calcified and fused valve commissures. This can lead to an improvement in left ventricular function, a decrease in the transvalvular gradient, and an increase in the aortic valve area.18 Because of a high complication rate and a high rate of restenosis within 6 months, this procedure is not recommended as definitive therapy. This procedure can be used as a temporizing solution in patients with cardiogenic shock,19 or in the management of patients requiring major noncardiac surgery.20 After recovery, definitive aortic valve replacement surgery can be performed at a later date.

Recently a percutaneous implantable prosthetic heart valve made of three bovine pericardial leaflets mounted in a balloon-expandable stent was developed and implanted in a critically ill patient with aortic stenosis and cardiogenic shock, and it led to immediate hemodynamic improvement.21 Further studies are now in development for this promising new technology.

Etiology

Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac muscle characterized by myocardial hypertrophy out of proportion to the hemodynamic stress. Patients classically present with dynamic obstruction to left ventricular outflow. Valvular aortic stenosis and hypertension are usually absent. Left ventricular diastolic dysfunction is invariably present. The disease is uncommon, estimated to be present in about 2 of 1000 young adults.22 Because this condition can mimic valvular aortic stenosis, it will be considered in this section.

Pathophysiology

The pattern and extent of left ventricular hypertrophy differs among patients with hypertrophic cardiomyopathy. In most patients, hypertrophy involves the septum and portions of the anterolateral free wall of the left ventricle. Rare morphologic forms include isolated apical hypertrophy, which is seen predominantly in patients of Japanese descent. Histologic features include cardiac muscle cell disarray and fibrous tissue formation.

In a subset of patients with the severe form of HCM, left ventricular outflow tract obstruction occurs at rest and worsens with exertion. The left ventricle is hyperdynamic, usually with an increased ejection fraction. A pressure gradient can be demonstrated in the left ventricular outflow tract below the aortic valve that at times may exceed 100 mm Hg. The gradient is augmented by factors that increase contractility (such as exercise or premature ventricular contractions) or by factors that decrease ventricular volume. The gradient may represent true obstruction to left ventricular ejection, resulting from portions of the mitral valve apparatus moving across the outflow tract and contacting the hypertrophied septum in midsystole. The displacement of the mitral valve occurs because of Venturi effects generated by the increased ejection velocities in the narrowed outflow tract. As the anterior mitral valve leaflet is drawn toward the septum by these Venturi effects, concomitant mitral regurgitation is produced.

Most patients with HCM have diastolic function abnormalities whether or not they are symptomatic.23 Diastolic dysfunction is manifested by increased left ventricular filling pressures despite a normal ejection fraction. Isovolumic relaxation is prolonged, early diastolic filling is impaired, and atrial filling becomes an important component of cardiac output. Because of the importance of the atrial contribution to left ventricular filling, the acute onset of atrial fibrillation may cause clinical deterioration of patients with HCM.24

Clinical Presentation

Classic symptoms of HCM include exertional chest pain, dyspnea, fatigue, and syncope.24a,24b Most patients with HCM, however, are asymptomatic until an unrelated illness causes deterioration. Tachycardia, sudden blood loss, or atrial or ventricular arrhythmias can suddenly precipitate pulmonary edema and hemodynamic collapse. As the outflow obstruction worsens, mitral regurgitation increases, leading to high left atrial and pulmonary venous pressures. Blood pressure may fall as cardiac output is impaired.

The diagnosis of HCM can be made definitively by careful cardiac physical examination. The carotid pulse has a characteristic brisk upstroke followed by sudden cutoff as obstruction occurs. The left ventricular impulse is vigorous and sustained. A large palpable A wave is present (easily felt in the left lateral decubitus position). A systolic thrill is commonly palpated. The first and second heart sounds are typically normal. The systolic murmur of outflow obstruction is harsh and has a crescendo/decrescendo configuration. The murmur radiates throughout the precordium, but not to the neck. A second murmur of mitral regurgitation can be heard at the apex, with radiation to the axilla. The murmur of HCM increases significantly in intensity with the Valsalva maneuver, a response that can be used to differentiate the murmur reliably from valvular aortic stenosis (Table 29-1).

Diagnostic Evaluation

The electrocardiogram is almost always abnormal, with ST- and T-wave abnormalities, left ventricular hypertrophy, and predominant Q waves in the inferior or lateral leads. Giant negative T waves are characteristic of apical HCM of the Japanese type. The chest x-ray generally shows an enlarged cardiac silhouette. Echocardiography can make the diagnosis of HCM definitively and can quantitate the severity of the outflow tract obstruction. Classic features include a markedly hypertrophied interventricular septum, at times more than 20 mm thick (Fig. 29-4), systolic anterior motion of the mitral valve into the left ventricular outflow tract, premature closure of the aortic valve at the time of obstruction, and mitral regurgitation. Doppler echocardiography can accurately measure the magnitude of the outflow tract gradient. The modified Bernoulli equation is used to calculate the gradient in millimeters of mercury by the equation 4v2, where v is the maximum velocity measured in the outflow tract.

Cardiac catheterization can demonstrate the systolic pressure gradient in the left ventricle. The arterial pressure tracing may show a “spike and dome” configuration, representing the brisk outflow and sudden obstruction (Fig. 29-5). The pulmonary capillary wedge pressure is usually elevated, with a prominent A wave indicative of diastolic noncompliance. A large V wave may be present if mitral regurgitation is significant. A pressure gradient may be present in the right ventricular outflow tract as well.

Management

It is important to recognize HCM in patients presenting with pulmonary congestion, because management is substantially different than for other forms of heart failure. Pulmonary edema should be treated initially with diuretics to relieve congestion, but excessive preload reduction may aggravate the situation by accentuating the left ventricular outflow tract gradient. β agonists are contraindicated, because they may worsen outflow tract gradients, cause ischemia, and precipitate arrhythmias. Likewise, digitalis should be avoided unless used to treat atrial fibrillation.

The mainstay of treatment is use of β-adrenergic blockers and calcium channel blockers. β-receptor blockade slows the heart rate and blunts the chronotropic response to exercise or stress, thus preventing the increase in outflow tract obstruction. Patients presenting in pulmonary edema should be started on intravenous β blockers such as esmolol, which has the advantage of a short half-life. The heart rate should be slowed to the slowest tolerated rate that decreases the outflow tract gradient. Large doses of β blockers may be required. If the heart rate cannot adequately be slowed with β blockers, then calcium channel blockers such as verapamil may be added. Verapamil doses of 360 to 480 mg and higher are frequently used. Other negative inotropic agents such as disopyramide can also be used to limit the outflow tract gradient.25 The antiarrhythmic drug amiodarone has β-blocking activity and may improve survival in some patients with HCM.26

Atrial fibrillation may cause sudden deterioration of patients with HCM, as a result of both the increased heart rate and the loss of the atrial contribution to ventricular filling. Electrical cardioversion may be necessary acutely. Pharmacologic treatment may then be started to prevent recurrence. Agents that block the atrioventricular (AV) node, such as β blockers and calcium channel blockers, may be used prophylactically to prevent the sudden increase in heart rate should atrial fibrillation recur.

Surgical techniques for HCM have been developed that are aimed at eliminating the outflow tract gradient and reducing the amount of mitral regurgitation. Septal myotomy-myomectomy performed through the ascending aorta removes a portion of the hypertrophied interventricular septum, and has been associated with a significant reduction in outflow tract gradients and with symptomatic relief.27 Mitral valve replacement has also been found to reduce or eliminate the outflow tract gradient and to improve symptoms.28 Valve replacement may be especially helpful in patients with severe mitral regurgitation. There has been interest in pacemaker therapy with dual-chamber pacing of the right heart to decrease outflow tract gradients by changing the timing of depolarization of the interventricular septum to improve symptoms in patients with refractory disease.29 This therapy may be beneficial acutely with use of temporary pacing wires. Some studies have not shown any clinical benefit with pacing, and possible detrimental effects on ventricular filling and cardiac output.30 A new procedure using percutaneous septal ablation by infusing ethanol into the septal perforator branches of the left anterior descending artery has been studied.31–33 This technique causes infarction and thinning of the thickened proximal septum, reducing the outflow obstruction with improvement in symptoms. Long-term results of this procedure are under study. None of these techniques have been shown to reduce the incidence of sudden death associated with this disease.

Etiology

Aortic insufficiency (AI) may be secondary to diseases of the valve leaflets or to abnormalities of the aortic root (Table 29-2). AI can be classified as chronic or acute.34 Chronic AI may remain indolent for years and not require treatment until left ventricular dysfunction becomes evident. Acute severe AI, however, is a medical emergency with a high mortality and frequently requires early operative intervention. The three most common causes of acute AI are (1) infective endocarditis, (2) aortic dissection, and (3) rupture or prolapse of an aortic valve leaflet.35 The aortic valve is the valve most commonly involved after blunt chest trauma.36

Pathophysiology

The cardiac performance of patients with aortic insufficiency depends on the ability of the left ventricle to adapt to the volume overload. In chronic AI, the left ventricle gradually dilates with a shift in the pressure-volume relationship, so that any change in volume is accommodated at a lower pressure. In acute AI, the left ventricle is suddenly subjected to a large regurgitant volume for which it is not prepared. Left ventricular dilation is limited by the compliance of the ventricle and by the constraining pericardium. Therefore in acute AI, a small rise in volume may lead to a dramatic increase in left ventricular diastolic pressure. As a consequence, patients with acute AI usually present with signs and symptoms of pulmonary congestion.

If the patient survives the acute insult, the left ventricle and pericardium may adapt to the volume overload by dilating. Left ventricular wall stress is diminished by left ventricular hypertrophy. The increase in chamber size and diastolic volume leads to an augmentation of forward stroke volume despite high regurgitant volumes. Afterload is reduced because of the rapid runoff of blood from the aorta into the ventricle. Cardiac performance can be maintained in the normal range for many years despite the presence of severe AI. However, decompensation can occur at any time, owing to ischemia or other factors for which the heart cannot accommodate. Once left ventricular dysfunction develops, the disease tends to progress rapidly. Left ventricular volumes (left ventricular end-systolic dimension >50 mm, left ventricular end-diastolic dimension >70 mm) can be used to predict which patients are more likely to have progressive disease and the development of left ventricular failure.37

Clinical Presentation

Patients that present with acute AI are usually critically ill, with signs of pulmonary edema, diaphoresis, cyanosis, and peripheral vasoconstriction. The left ventricular end-diastolic pressure is markedly increased, at times equaling the aortic diastolic pressure, shortening the aortic regurgitant murmur. Patients are typically tachycardic without a wide pulse pressure or prominent peripheral signs of aortic insufficiency. Systolic pressure may be normal or low. The heart is not enlarged. The first heart sound may be soft, owing to premature closure of the mitral valve caused by the aortic regurgitant jet. The pulmonic component of the second heart sound may be loud, reflecting pulmonary hypertension. A gallop rhythm is usually present. Table 29-3 compares the features of acute versus chronic aortic regurgitation.

Diagnostic Evaluation

In acute AI, the electrocardiogram is usually normal, showing only sinus tachycardia. Left ventricular hypertrophy may be present in patients with chronic AI, and usually signifies severe regurgitation. The chest x-ray in acute AI usually shows pulmonary edema with a normal heart size. A widened mediastinum should raise the suspicion of acute aortic dissection as the cause of the aortic insufficiency. In chronic AI, the chest x-ray is likely to show cardiomegaly with a prominent left ventricle. The ascending aorta may be dilated.

Echocardiography is useful for detecting aortic insufficiency and determining its severity and for evaluating left ventricular performance. Aortic insufficiency may be suspected from the appearance of the valve leaflets on two-dimensional echocardiography, but Doppler techniques are the most sensitive for diagnosing AI and determining the severity of the leakage.38 The presence of AI is confirmed by Doppler echocardiography when an abnormal, high-velocity turbulent jet is detected just below the aortic valve during diastole. Color flow mapping is used to depict the origin and size of the regurgitant jet. The severity of the regurgitation can be estimated from the size of the regurgitant jet, from the size of the regurgitant orifice, or by calculation of the regurgitant volume or fraction. In patients with severe AI, the consequences of a significant increase in left ventricular pressure can be noted by premature closure of the mitral valve, diastolic mitral regurgitation, and premature closure of the aortic valve if left ventricular pressure transiently exceeds aortic pressure.

Transesophageal echocardiography (TEE) should be considered when endocarditis or an acute aortic dissection is suspected as the cause of aortic insufficiency. TEE can better evaluate valvular structure and is more sensitive for the diagnosis of endocarditic lesions than transthoracic echocardiography (Fig. 29-6). TEE has been shown to have a sensitivity comparable to that of magnetic resonance imaging (MRI) or computed tomography (CT) for detecting an acute aortic dissection,39 and it is more easily performed in an intensive care unit on an unstable critically ill patient.

Cardiac catheterization can provide definitive information about the degree of regurgitation, and it can be used to evaluate the aortic root and the status of the coronary arteries if surgery is indicated. Pulmonary artery catheterization is indicated in acute AI to help with management. The pulmonary artery wedge pressure is usually elevated, and pulmonary hypertension may be present. Stroke volume may be normal or increased.

Management

Acute aortic insufficiency is a medical emergency. Fulminant pulmonary edema is a common presentation, because the left ventricle cannot handle the sudden large increase in volume. It is important to determine the cause of the lesion, especially if endocarditis or an acute aortic dissection is suspected. Aortic valve replacement is indicated when the regurgitation is severe. Early aortic valve replacement has been shown to decrease mortality in patients with endocarditis.40 If heart failure can be medically managed, aortic valve replacement may be delayed until after completion of an antibiotic regimen.41

Patients presenting with acute pulmonary edema should be treated promptly with loop diuretics to relieve congestion. Inotropic agents are of limited value, because left ventricular function is usually hyperdynamic. Pressor agents are relatively contraindicated, because an increase in systemic vascular resistance will worsen the amount of regurgitation. Likewise, an intra-aortic balloon pump is absolutely contraindicated.42 Vasodilators can improve forward stroke volume by inducing dilation of the arterial vessels. An agent such as nitroprusside is ideal, because it can be rapidly titrated to effect. This drug should be administered with pulmonary artery catheter guidance so that the response to therapy can be followed closely. Nitroprusside has been shown to improve cardiac performance, enhance forward stroke volume, reduce the amount of regurgitation, and lower left ventricular filling pressures.43,44

Patients that can be stabilized should be treated with long-term vasodilator therapy. Vasodilator agents such as hydralazine, angiotensin-converting enzyme inhibitors (ACEIs), β blockers, and calcium channel blockers have been used.45 Recently, nifedipine has been shown to delay the need for aortic valve replacement in patients with asymptomatic chronic severe aortic insufficiency.46 Aortic valve replacement should be performed before irreversible changes occur in the left ventricle. The end-systolic dimensions and shortening characteristics of the left ventricle can be used to determine the optimal time for operative intervention.47 Aortic valve replacement for severe aortic insufficiency with a low left ventricular ejection fraction has a high perioperative mortality and an increased incidence of congestive heart failure after surgery, but many patients will sustain improvement in their cardiac function and a prolonged survival.48

Etiology

Rheumatic fever is the main cause of mitral stenosis, and in underdeveloped countries is a significant cause of morbidity and mortality in young people. Recent outbreaks of rheumatic fever and an influx of immigrants from countries where rheumatic fever is prevalent will ensure that this disease remains an important valvular condition in the United States as well.49 Other forms of mitral stenosis may be encountered, such as calcification of the mitral annulus so extensive as to involve the submitral apparatus and the valvular leaflets. This rare cause of mitral stenosis is seen in elderly patients and patients with long-standing renal failure.

Pathophysiology

Rheumatic mitral stenosis results from an inflammatory process that leads to fusion of the mitral commissures, chordae tendineae, or both. The disease tends to cause a slowly progressive degeneration of the valve, and many patients remain asymptomatic for decades after the initial infection. The normal mitral valve has an area of 4 to 6 cm2. When the valve has narrowed to 2 cm2, mild mitral stenosis is present. A valve area of 1 cm2 is thought to represent critical mitral stenosis. At this orifice size, a transvalvular gradient of approximately 20 mm Hg is required to maintain a normal cardiac output. As a consequence, left atrial pressure rises, leading eventually to pulmonary hypertension.

Any increase in heart rate will shorten diastolic filling time and diminish the time for blood to flow across the stenosed mitral valve. Tachycardia will augment the transvalvular pressure gradient and further increase left atrial pressure. That is why patients may suddenly present with pulmonary edema and the onset of atrial fibrillation.50 Patients with mild to moderate mitral stenosis may be asymptomatic at rest, but exercise may cause a dramatic rise in the transmitral gradient and left atrial pressure, leading to exertional dyspnea.51 In addition, the atrial contribution to left ventricular filling may account for 20% or more of total cardiac output. Loss of the atrial filling component can significantly worsen symptoms in patients with mitral stenosis.

As mitral stenosis becomes more severe, resting pulmonary artery pressures begin to increase. In critical mitral stenosis, pulmonary pressures may exceed systemic pressures. Pulmonary pressures greater than 70 mm Hg lead to elevated right ventricular and right atrial pressures, eventually causing right ventricular dilation and failure.

Clinical Presentation

Patients with rheumatic mitral stenosis may be asymptomatic for many years despite progressive narrowing of the valve. Symptoms initially occur with exercise. Patients may suddenly decompensate and present in pulmonary edema during an episode of respiratory infection, atrial fibrillation, or another condition associated with tachycardia. Sudden, profuse hemorrhage may occur from disruption of bronchial veins. Thromboembolism can be a serious complication, occurring most often in patients with chronic atrial fibrillation.

The physical examination in critically ill patients with mitral stenosis can be difficult. The left ventricle is usually normal in size, although it may be displaced leftward owing to right ventricular enlargement. The first heart sound is usually accentuated if the mitral leaflets remain pliable. As pulmonary hypertension develops, the pulmonic closing sound (P2) becomes accentuated. Other signs of pulmonary hypertension include a right ventricular heave, tricuspid regurgitation (a holosystolic murmur at the right or left sternal border with respiratory variation), and the Graham Steell murmur of pulmonic insufficiency. At the left ventricular apex, an opening snap may be heard, followed by the low-pitched rumbling murmur of mitral stenosis. In severe mitral stenosis, the murmur is heard throughout diastole, with presystolic accentuation of the murmur in patients who remain in sinus rhythm.

Diagnostic Evaluation

The electrocardiogram will typically show left atrial enlargement and signs of right ventricular hypertrophy in severe mitral stenosis. Atrial fibrillation is a common rhythm disturbance. The chest x-ray can show left atrial enlargement with upward displacement of the left mainstem bronchus by the enlarged atrium. The left atrial appendage may appear as a bulge between the aortic knob and the left ventricular silhouette. With pulmonary hypertension, the pulmonary arteries will be prominent, and the right ventricle may be enlarged. Calcification of the mitral annulus can frequently be detected.

Echocardiography and Doppler techniques have been used to assess and quantify the severity of mitral stenosis noninvasively. Two-dimensional echocardiography can delineate the anatomy of the mitral valve (Fig. 29-7). As the valve leaflets begin to open during diastole, the leaflet tips appear to remain tethered while the body of the leaflet continues to show mobility (doming), producing a characteristic deformity that is classic for rheumatic mitral stenosis. Planimetry of the cross-sectional valve area from the short axis view has correlated well with valve areas calculated invasively by the Gorlin formula.52 Doppler echocardiographic methods have also been used to quantify mitral valve areas by using a pressure half-time method (Fig. 29-8). The time required for the diastolic gradient to drop to half its initial peak reflects the severity of mitral stenosis.53 The noninvasively determined pressure half-time is defined as the time required for the early maximal inflow velocity to fall to a value equal to the maximum velocity divided by the square root of 2.54 The mitral valve area is then calculated by dividing the empirically derived number 220 by the pressure half-time.

Cardiac catheterization is used to verify the severity of the valve lesion and to measure right heart pressures. Left atrial puncture via a transseptal approach can directly measure left atrial pressure. Pulmonary capillary wedge pressures may be used as well, but at times they exaggerate the left atrial pressure and overestimate the severity of the mitral stenosis.55

Management

Patients presenting with pulmonary edema should undergo initial diuretic treatment to decrease lung congestion and improve oxygenation. For patients presenting in atrial fibrillation, control of heart rate is crucial. A combination of digoxin, β blockers, and/or calcium channel blockers may be required to achieve rate control. Use of intravenous esmolol or diltiazem can quickly bring about rate control and is preferred over intravenous digoxin. Patients in sinus rhythm may also benefit from β blockers to slow the heart rate and allow more time for diastolic filling of the left ventricle. Anticoagulation should be started in patients with atrial fibrillation to prevent thromboembolism (IV heparin and warfarin with a goal International Normalized Ratio [INR] of 2 to 3).

Once symptoms develop, mitral stenosis requires definitive management. That can be achieved by surgical mitral commissurotomy, mitral valve replacement, or catheter balloon commissurotomy. For patients with pure rheumatic mitral stenosis, catheter balloon commissurotomy has become the procedure of choice for relieving the stenosis and improving symptoms.56 The procedure is performed via a transseptal approach, and a balloon is passed across the mitral valve from the left atrium into the left ventricle. A small atrial septal defect remains following the procedure, but in most patients it closes or becomes smaller. Contraindications to catheter balloon commissurotomy include significant mitral regurgitation, a thrombus in the left atrium, unfavorable valve morphology, or only mild mitral stenosis. The procedure is highly successful with low mortality rates and greater than 60% of patients improving to New York Heart Association functional class I.57 If there are contraindications to catheter balloon commissurotomy, then surgical valvular repair would be necessary.

Etiology

There are multiple conditions that can cause acute or chronic mitral regurgitation (MR) involving the mitral valve leaflets, mitral annulus, chordae tendineae, or papillary muscles (Table 29-4). Involvement of the leaflets is usually due to rheumatic disease leading to shortening or retraction of one or both leaflets. Infective endocarditis, trauma, or systemic lupus erythematosus with Libman-Sacks endocarditis can lead to significant MR (Fig. 29-9). Finally, mitral valve prolapse can present with severe MR due to myxomatous change of the valve leaflets.

Abnormalities of the mitral annulus involve dilation and calcification. Severe dilation of the left ventricle, as seen in dilated cardiomyopathies, is associated with mitral regurgitation, although the amount of leakage tends to be less than that seen in primary valvular disorders. Calcification of the mitral annulus is a common degenerative change that when severe, may cause significant MR.

The chordae tendineae and papillary muscles may be involved in patients with ischemic heart disease. Myocardial ischemia or infarction may lead to papillary muscle dysfunction or frank rupture of the muscle head, causing acute severe MR. Ischemia of the papillary muscles may be transient, with improvement in the MR occurring after relief of the ischemia or revascularization therapy. On the other hand, patients with moderately severe to severe MR complicating an acute myocardial infarction have a high risk of mortality.58 Chordae tendineae may rupture in patients with infective endocarditis and in patients with myxomatous mitral valve prolapse. Mitral valve prolapse is becoming the most common etiology for patients requiring valvular surgery for mitral regurgitation.

Pathophysiology

In patients who develop acute MR, the left ventricle is initially unloaded, with the regurgitant volume ejected into the left atrium. The left ventricular wall tension is reduced, since acute MR reduces systolic ventricular pressure and volume. Early diastolic filling of the left ventricle is enhanced, causing small elevations in myocardial contractility and ejection fraction. Following initial compensation, the left ventricle dilates rapidly. The increase in left ventricular end-diastolic volume increases wall tension. Ejection indices will eventually decline to normal, reflecting impairment of myocardial function. Ejection fractions of 40% to 50% already reflect severe impairment of myocardial contractility. Ejection fractions less than 40% represent advanced cardiac dysfunction and indicate a patient who has a high operative risk and is unlikely to experience any improvement in function following correction of the problem.59

The compliance of the left atrium and the pulmonary venous system will determine the hemodynamic and clinical manifestations of mitral regurgitation. In patients in whom MR occurs suddenly, as with rupture of a chorda tendineae, left atrial compliance is normal. Left atrial size remains normal, but there is a marked elevation of left atrial pressure (large V wave), and pulmonary congestion is predominant. In contrast, in patients with long-standing chronic MR, massive enlargement of the left atrium occurs with normal or only slightly elevated left atrial pressures. Pulmonary artery pressures and pulmonary vascular resistance are normal or only slightly elevated. Atrial fibrillation is almost invariably present.60

Clinical Presentation

The symptoms of patients with mitral regurgitation depend on the acuity and severity of the disease. In patients with chronic MR, symptoms usually do not develop until the left ventricle begins to fail. By the time low-output symptoms, pulmonary congestion, or atrial fibrillation develops, permanent myocardial dysfunction may already be present. The onset of a critical illness may cause rapid deterioration in a previously stable patient if increased systemic vascular resistance augments the regurgitant fraction. Patients with acute MR may present with florid pulmonary edema and low cardiac output. Ischemic symptoms may also be present, since myocardial infarction with papillary muscle dysfunction and rupture is an important cause of acute MR.

On physical examination, the left ventricular impulse is usually dynamic and displaced, with a palpable early diastolic filling impulse (S3). The systolic murmur of mitral regurgitation begins at the first heart sound (frequently obscuring it) and extends throughout systole and beyond the second heart sound to mitral valve opening. The murmur is constant in intensity, is high-pitched, is loudest at the apex, and radiates to the axilla. The intensity of the murmur does not correlate with severity. Patients with acute MR may have barely audible brief murmurs. Murmurs of mitral valve prolapse may begin in mid or late systole and vary in position and intensity depending on left ventricular volume.61

Mitral regurgitation murmurs need to be differentiated from other systolic murmurs (Table 29-5). Tricuspid regurgitation frequently exhibits respiratory variation and does not radiate to the axilla. Ventricular septal defect murmurs tend to be harsher, to be located at the sternal border, and to be heard less well in the axilla. Aortic stenosis murmurs may radiate to the apex, but they are usually accompanied by a delayed carotid upstroke and a decreased intensity of the aortic component of the second heart sound.

Diagnostic Evaluation

The electrocardiogram in acute mitral regurgitation is usually normal, although it may show signs of acute myocardial infarction. Patients with chronic MR may have signs of left atrial enlargement, right ventricular hypertrophy, or atrial fibrillation. Chest x-ray shows cardiomegaly with left ventricular prominence, left atrial enlargement, and at times evidence of mitral annular calcification.

Two-dimensional echocardiography can help determine the etiology and severity of mitral regurgitation. The underlying cause of the regurgitation, such as rupture of a chorda tendineae, mitral valve prolapse with a flail leaflet, or valvular endocarditis, can readily be determined. Transesophageal echocardiography has improved the diagnostic acumen of echocardiographic studies, especially in determining the presence of valvular vegetations. Doppler echocardiography makes it possible to estimate the severity of MR from the distance the jet travels into the left atrium, the width of the jet at the mitral annulus, and the area of the color Doppler envelope in the left atrium.

Cardiac catheterization is useful in diagnosis and management. Left ventriculography showing opacification of the left atrium is used to quantify severity of the leakage. Effective or forward cardiac output is depressed in severe MR. The pulmonary wedge pressure will show a characteristically tall V wave, reflecting the filling of the left atrium by both pulmonary venous and regurgitant blood during ventricular systole. This tall V wave is frequently seen in the pulmonary artery tracing, and at times little difference between the pulmonary artery tracing and the wedge pressure tracing is evident. Successful treatment of MR will bring about a significant decline in the V wave.

Management

Patients presenting with acute mitral regurgitation should be treated with the same modalities used in patients who present with acute heart failure. Afterload reduction with vasodilators or noninvasive positive pressure ventilation62 will reduce the impedance to ejection into the aorta, diminish the amount of mitral regurgitation, increase forward output, and reduce pulmonary congestion.63 In acute presentations, nitroprusside can achieve these clinical goals and has the advantage of easy titration to blood pressure. If hypotension is present, positive inotropic agents such as dobutamine may need to be combined with the nitroprusside. Diuretics are used to relieve congestion. Digoxin may be useful if left ventricular dysfunction or atrial fibrillation is present. Chronic afterload reduction can then be initiated with ACEIs or other vasodilators.

Unless patients with acute severe MR are treated aggressively, death is almost certain. Emergency surgery should be considered in patients with acute pulmonary edema caused by acute MR due to myocardial infarction and papillary muscle rupture, rupture of a chorda tendineae with a flail mitral leaflet in the mitral valve prolapse syndrome, traumatic MR, or severe MR associated with valvular endocarditis.

Patients with chronic MR should be considered for surgery when they become symptomatic. Exercise testing can precipitate symptoms in patients that are asymptomatic at rest. Asymptomatic patients should be considered for surgical intervention when the ejection fraction falls below 50%, the end-systolic volume index exceeds 50 mL/m2, or pulmonary hypertension develops.64

The decision of whether to replace the mitral valve or to perform valvular reconstruction will depend on the degree of deformity of the valve leaflets and support structures. Mitral valve repair appears to be associated with a lower surgical mortality than is mitral valve replacement, although the patient populations differ.65 Mitral valve repair is most often used in patients with myxomatous mitral valve prolapse and a flail mitral leaflet or with papillary muscle rupture after an acute myocardial infarction. Repair procedures consist of annuloplasty with the use of a prosthetic ring or resection and repair of the valve. Replacement, reimplantation, or shortening of chordae tendineae is performed in selected patients. Patients who are not candidates for repair receive either a mechanical or bioprosthetic valve. Surgeons frequently leave the submitral apparatus in place, as doing so favors a return to a more normal cardiac function after surgery.66

Prosthetic Valves

There are two major types of prosthetic heart valve: mechanical valves, which are made of synthetic material, and tissue valves, which are composed at least in part of biologic tissue. The first mechanical valves were ball valves, such as the Starr-Edwards prosthesis. These valves have largely been replaced by the tilting disk valves, which offer a greater orifice area and less resistance to blood flow. Common examples of the disk valves are the Bjork-Shiley and St. Jude Medical valves. The two major types of tissue valves are stented porcine aortic valves (the Carpentier-Edwards and Hancock valves) and a trileaflet valve made with bovine pericardium (Ionescu-Shiley valve). Other tissue valves are under development, including ones that use cryopreserved aortic homografts.

The advantage of tissue valves is a lower risk of thromboembolism than with mechanical valves. Anticoagulation is frequently used during the first few months after implantation, until the sewing ring becomes endothelialized. Anticoagulation is not required after this time; the thromboembolism rate is estimated to be 1 to 2 episodes per 100 patient-years.67

The main problem with the tissue valves concerns durability. The tissue valves are prone to calcification, fibrosis, degeneration, fibrin deposition, and cuspal tears. Valve dysfunction is more common in younger patients and in patients with disordered calcium metabolism. Evidence of degeneration can usually be detected by 5 years after replacement.68 By 15 years, over 50% of tissue valves will have failed.69 Fortunately, valve failure is rarely sudden, and a second operation can frequently be done on an elective basis. Sudden cuspal tears can present as an acute regurgitant lesion.

Mechanical valves have the advantage of durability but require anticoagulation to prevent thromboembolism. Without anticoagulation, major systemic embolisms occur at a rate of about 2% to 3% per year.70 The incidence is higher for valves in the mitral than in the aortic position. With adequate anticoagulation, however, the incidence of thromboembolism is similar to that for tissue valves. The use of a small dose of aspirin plus warfarin anticoagulation may decrease the risk of thromboembolism further, but increases the risk of a bleeding complication.71

For patients who require noncardiac surgery and have a mechanical prosthetic valve, the anticoagulation regimen may be stopped for a few days with minimal risk. Minimizing the time off anticoagulants is essential to avoid thromboembolism. Heparin or low-molecular-weight dextran is frequently administered up to the time of surgery, to protect the patient. Heparin should then be restarted after surgery until warfarin treatment increases the International Normalized Ratio (INR) to the target level of 2.5 to 3.5.

Mechanical valve thrombosis is a serious complication and is associated with a high mortality.72 The tilting disk valves are particularly susceptible to this complication. Thrombosis of mechanical valves is especially common for valves in the tricuspid position, so tissue valves are usually used in this location.73 Inadequate anticoagulation or withdrawal of anticoagulation for surgical procedures accounts for most instances of thrombotic obstruction.74 Thrombosis of the valve may lead to leaflet entrapment with acute regurgitation and circulatory collapse. Some patients, however, may remain asymptomatic or develop gradually worsening symptoms.

Obstruction of a mechanical valve usually necessitates reoperation, although that may be associated with a high risk of operative mortality. Thrombolytic therapy has been used successfully for prosthetic valve obstruction, with a success rate of 73% reported for one series.75 Recurrence rates, however, have averaged 18% regardless of valve position.76

Prosthetic valve obstruction may be difficult to detect. Abnormal auscultatory findings, such as muffled opening or closing sounds or the presence of a new murmur, may indicate thrombosis. Doppler echocardiography can diagnose obstruction by detecting an increased transvalvular gradient. Transesophageal echocardiography can frequently visualize thrombosed mechanical valves that are not well seen with transthoracic approaches owing to signal scatter from the valve structures.

Prosthetic valve endocarditis is a serious complication that occurs in 1% to 9% of patients.77 Early prosthetic valve endocarditis occurs within 60 days of implantation and results from contamination during the perioperative period. Most contamination probably occurs intraoperatively from direct wound inoculation or via the cardiopulmonary bypass machine. Postoperative sources include intravenous lines, pacing wires, and chest tubes. Staphylococcus epidermidis and Staphylococcus aureus are the most common organisms. A preoperative diagnosis of native valve endocarditis represents an increased risk of prosthetic valve involvement following surgery. Mortality is high, with one survey reporting a 64% mortality.77

Late prosthetic valve endocarditis occurs owing to seeding of the valve by transient bacteremia arising from dental, gastrointestinal, or genitourinary tract procedures. Nosocomial bacteremia has been reported to cause prosthetic valve endocarditis in 11% of patients within 45 days after discovery of the bacteremia.78 The bacteria responsible are similar to those found in native valve endocarditis, with viridans streptococci the most common isolates. The prognosis of late prosthetic valve endocarditis is worse than that of native valve endocarditis, with mortality rates between 36% and 53%.79 Complications of prosthetic valve endocarditis include myocardial abscesses, dehiscence of the valve with perivalvular leakage, and embolization (Fig. 29-10). Immediate surgery is indicated in patients who are unstable or have significant prosthetic valve dysfunction.80

Antibiotic prophylaxis for medical and dental procedures is recommended for all patients with prosthetic valves. Procedures in which prophylaxis is recommended include bronchoscopy, sclerotherapy for esophageal varices, urethral catheterization if a urinary tract infection is present, incision and drainage of infected tissue, and vaginal delivery in the presence of infection.81 Antibiotic schedules are listed in Table 29-6.