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MD Consult: Books: Goldman: Cecil Medicine: Chapter 75 – VALVULAR HEART DISEASE

Goldman: Cecil Medicine, 23rd ed.

Copyright © 2007 Saunders, An Imprint of Elsevier


Blase A. Carabello

The cardiac valves permit unobstructed forward blood flow through the heart when they are open while preventing backward flow when they are closed. Most valvular heart diseases cause either valvular stenosis with obstruction to forward flow or valvular regurgitation with backward flow. Valvular stenosis imparts a pressure overload on the left or right ventricle because these chambers must generate higher than normal pressure to overcome the obstruction to pump blood forward. Valvular regurgitation imparts a volume overload on the heart, which now must pump additional volume to compensate for what is regurgitated. When valve disease is severe, these hemodynamic burdens can lead to ventricular dysfunction, heart failure, and sudden death ( Table 75-1 ). In almost every instance, definitive therapy for severe valvular heart disease is mechanical restoration of valve function.

TABLE 75-1   — 

  Aortic Stenosis Mitral Stenosis Mitral Regurgitation Aortic Regurgitation

   Idiopathic calcification of a bicuspid or tricuspid valve

   Rheumatic fever
   Annular calcification

   Mitral valve prolapse
   Ruptured chordae
   Ischemic papillary muscle dysfunction or rupture
   Collagen vascular diseases and syndromes
   Secondary to LV myocardial diseases

   Annuloaortic ectasia
   Marfan syndrome
   Ankylosing spondylitis
   Aortic dissection
   Collagen vascular disease

   Pressure overload on the
   LV with compensation by LV hypertrophy
   As disease advances, reduced coronary flow reserve causes angina
   Hypertrophy and afterload excess lead to systolic and diastolic LV dysfunction

   Obstruction to LV inflow increases left atrial pressure and limits cardiac output, thus mimicking
   LV failure. Mitral valve obstruction increases the pressure work of the right ventricle
   Right ventricular pressure overload is augmented further when pulmonary hypertension develops

   Places volume overload on the LV.
   Ventricle responds with eccentric hypertrophy and dilation, which allow increased ventricular stroke volume
   Eventually, however, LV dysfunction develops if volume overload is uncorrected

   Total stroke volume causes hyperdynamic circulation, induces systolic hypertension, and causes pressure and volume overload.
   Compensation is by concentric and eccentric hypertrophy
   Because cardiac dilation has not developed, hyperdynamic findings are absent. High diastolic LV pressure causes mitral valve preclosure and potentiates LV ischemia and failure

   Heart failure




   Systolic ejection murmur radiating to the neck
   Delayed carotid upstroke
   S4, soft or paradoxical S2

   Diastolic rumble after an opening snap
   Loud S1
   Right ventricular lift
   Loud P2

   Holosystolic apical murmur radiating to the axilla, S3
   Displaced PMI

   Diastolic blowing murmur
   Hyperdynamic circulation
   Displaced PMI
   Quincke pulse
   DeMusset’s sign
   Short diastolic blowing murmur
   Soft S1
Electrocardiogram LAA LAA LAA LAA
Chest radiograph Boot-shaped heart Straightening of left heart border Cardiac enlargement Chronic
Aortic valve calcification on lateral view

   Double density at right heart border
   Kerley B lines
   Enlarged pulmonary arteries

   Cardiac enlargement
   Uncoiling of the aorta
   Pulmonary congestion with normal heart size
Echocardiographic findings

   Concentric LVH
   Reduced aortic valve cusp separation
   Doppler shows mean gradient ≥50 mm Hg in most severe cases

   Restricted mitral leaflet motion
   Valve area ≤1 cm2 in most severe cases
   Tricuspid Doppler may reveal pulmonary hypertension

   LV and LAA in chronic severe disease
   Doppler: large regurgitant jet

   LV enlargement
   Large Doppler jet PHT <400 msec
   Small LV
   Mitral valve preclosure
Catheterization findings

   Increased LVEDP
   Transaortic gradient 50 mm Hg
   AVA ≤0.7 in most severe cases

   Elevated pulmonary capillary wedge pressure
   Transmitral gradient usually >10 mm Hg in severe cases MVA <1 cm2

   Elevated pulmonary capillary wedge pressure
   Ventriculography shows regurgitation of dye into LV

   Wide pulse pressure
   Aortography shows regurgitation of dye into LV
   Usually unnecessary
Medical therapy

   Avoid vasodilators
   Digitalis, diuretics, and nitroglycerin in inoperable cases

   Diuretics for mild symptoms
   Anticoagulation in atrial fibrillation
   Digitalis, β-blockers, verapamil, or diltiazem for rate control

   Vasodilators in acute disease
   No proven therapy in chronic disease (but vasodilators commonly used)

   Vasodilators in chronic asymptomatic disease with normal left ventricular function
Indications for surgery Appearance of symptoms in patients with severe disease (see text)

   Appearance of more than mild symptoms
   Development of pulmonary hypertension
   Appearance of persistent atrial fibrillation

   Appearance of symptoms
   EF <0.60
   ESD ≥45 mm

   Appearance of symptoms
   EF <0.55
   ESD ≥55 mm
   Even mild heart failure
   Mitral valve preclosure

AVA = aortic valve area; EF = ejection fraction; ESD = end-systolic diameter; LAA = left atrial enlargement; LV = left ventricle; LVEDP = left ventricular end-diastolic pressure; LVH = left ventricular hypertrophy; MVA = mitral valve area; PHT = pressure half-time; PMI = point of maximal impulse; PND = paroxysmal nocturnal dyspnea; RVH = right ventricular hypertrophy.



Bicuspid and Other Congenitally Abnormal Aortic Valves

Approximately 1% of the population is born with a bicuspid aortic valve, with a male preponderance ( Chapter 68 ). Although this abnormality does not usually cause a hemodynamic disturbance at birth, bicuspid aortic valves tend to deteriorate with age. Approximately a third of these valves become stenotic, another third become regurgitant, and the remainder cause only minor hemodynamic abnormalities. When stenosis develops, it usually occurs when patients are in their 40s, 50s, and 60s.

Sometimes, congenital aortic stenosis from a unicuspid, bicuspid, or even abnormal tricuspid valve causes symptoms during childhood and requires correction by adolescence. Occasionally, these congenitally stenotic aortic valves escape detection until adulthood.

Tricuspid Aortic Valve Stenosis

In some patients born with apparently normal tricuspid aortic valves, thickening and calcification develop similar to what occurs in bicuspid valves. When aortic stenosis develops in previously normal tricuspid aortic valves, it usually does so in the 60s to 80s. Although stenosis and calcifications of bicuspid and tricuspid aortic valves were formerly considered to be degenerative processes, it is clear that this type of aortic stenosis arises from an active inflammatory process similar to that of coronary heart disease. This concept is supported by many pieces of evidence. First, the initial lesion of aortic stenosis is similar to the plaque of coronary disease. Second, both diseases have hypertension and hyperlipidemia as risk factors. Third, there is excellent correlation between calcification of the aortic valve and calcification of the coronary arteries. Fourth, patients with the most severe aortic stenosis have the highest levels of C-reactive protein.

Rheumatic Valvular Heart Disease

Rheumatic valve disease is now a rare cause of aortic stenosis in developed countries. In virtually every case, the mitral valve is also detectably abnormal.


Relationship to Symptoms

The presence or absence of the classic symptoms of aortic stenosis—angina, syncope, and the symptoms of heart failure—is the key to the natural history of the disease. Before the onset of symptoms, survival is similar to that for the normal population, and sudden death is rare, occurring in less than 1% of asymptomatic patients. When the classic symptoms develop, however, survival declines precipitously. Approximately 35% of patients with aortic stenosis are initially evaluated for angina. Of these, 50% are dead in 5 years unless aortic valve replacement is performed. Approximately 15% have syncope; of these, 50% are dead in only 3 years unless the aortic valve is replaced. Of the 50% with symptoms of heart failure, 50% are dead in 2 years without aortic valve replacement. In all, only 25% of patients with symptomatic aortic stenosis survive 3 years in the absence of valve replacement, and the annual risk for sudden death ranges from 10% in patients with angina to 15% with syncope to 25% with heart failure. Prompt recognition of symptoms and evaluation for possible severe aortic stenosis are crucial in managing the disease.

The normal aortic valve area is 3 to 4 cm2, and little hemodynamic disturbance occurs until the orifice is reduced to about a third of normal, at which point a systolic gradient develops between the left ventricle and aorta. Left ventricular (LV) and aortic pressure is normally nearly equal during systole. In aortic stenosis, intracavitary LV pressure must increase above aortic pressure, however, to produce forward flow across the stenotic valve and to achieve acceptable downstream pressure (see Fig. 56-1 ). There is a geometric progression in the magnitude of the gradient as the valve area narrows. Given a normal cardiac output, the gradient rises rapidly from 10 to 15 mm Hg at valve areas of 1.5 to 1.3 cm2 to about 25 mm Hg at 1.0 cm2, 50 mm Hg at 0.8 cm2, 70 mm Hg at 0.6 cm2, and 100 mm Hg at 0.5 cm2. The rate of progression of aortic stenosis varies widely from patient to patient; it may remain stable for many years or increase by more than 15 mm Hg per year.

A major compensatory response to the increased LV pressure associated with aortic stenosis is the development of concentric LV hypertrophy. The Laplace equation—stress (s) = pressure (p) × radius (r)/2 × thickness (th)—indicates that the force on any unit of LV myocardium (afterload) varies directly with ventricular pressure and radius and inversely with wall thickness. As pressure increases, it can be offset by increased LV wall thickness (concentric hypertrophy). The determinants of LV ejection fraction are contractility, preload, and afterload. By normalizing afterload, the development of concentric hypertrophy helps preserve ejection fraction and cardiac output despite the pressure overload. Although hypertrophy clearly serves a compensatory function, it also has a pathologic role and is in part responsible for the classic symptoms of aortic stenosis.


In general, angina ( Chapter 70 ) results from myocardial ischemia when LV oxygen (and other nutrient) demand exceeds supply, which is predicated on coronary blood flow. In normal subjects, coronary blood flow can increase five- to eightfold under maximum metabolic demand, but in patients with aortic stenosis this reserve is limited. Reduced coronary blood flow reserve may be caused by a relative diminution in capillary ingrowth to serve the needs of the hypertrophied left ventricle or by a reduced transcoronary gradient for coronary blood flow because of the elevated LV end-diastolic pressure. Restricted coronary blood flow reserve appears to be responsible for angina in many patients who have aortic stenosis despite normal epicardial coronary arteries. In other patients, angina is due to increased oxygen demand when inadequate hypertrophy allows wall stress, a key determinant of myocardial oxygen consumption, to increase.


Syncope ( Chapters 61 and 427 ) generally occurs because of inadequate cerebral perfusion. In aortic stenosis, syncope is usually related to exertion. It may result when exertion causes a fall in total peripheral resistance that cannot be compensated by increased cardiac output because output is limited by the obstruction to LV outflow; this combination reduces systemic blood pressure and cerebral perfusion. In addition, high LV pressure during exercise may trigger a systemic vasodepressor response that lowers blood pressure and produces syncope. Cardiac arrhythmias, possibly caused by exertional ischemia, also cause hypotension and syncope.

Heart Failure

In aortic stenosis, contractile dysfunction (systolic failure) and failure of normal relaxation (diastolic failure) occur and cause symptoms ( Chapter 57 ). The extent of ventricular contraction is governed by contractility and afterload. In aortic stenosis, contractility (the ability to generate force) is often reduced. The mechanisms of contractile dysfunction may include abnormal calcium handling, microtubular hyperpolymerization causing an internal viscous load on the myocyte, and myocardial ischemia. In some cases, contractile function is normal, but the hypertrophy is inadequate to normalize wall stress and excessive afterload results. Excessive afterload inhibits ejection, reduces forward output, and leads to heart failure.

The increased wall thickness that helps normalize stress increases diastolic stiffness. Even if muscle properties remain normal, higher filling pressure is required to distend a thicker ventricle. As aortic stenosis advances, collagen deposition also stiffens the myocardium and adds to the diastolic dysfunction.


Physical Examination

The diagnosis of aortic stenosis is usually first suspected when the classic systolic ejection murmur is heard during physical examination ( Chapter 48 ). The murmur is loudest in the aortic area and radiates to the neck. In some cases, the murmur may disappear over the sternum and reappear over the LV apex, thereby giving the false impression that a murmur of mitral regurgitation is also present (Gallivardan’s phenomenon). The intensity of the murmur increases with cycle length because longer cycles are associated with greater aortic flow. In mild disease, the murmur peaks in intensity in early or mid-systole. As the severity of stenosis worsens, the murmur peaks progressively later in systole. Perhaps the most helpful clue to the severity of aortic stenosis by physical examination is the characteristic delay in the carotid pulse with a diminution in its volume (see Fig. 48-2 ); in elderly patients, however, increasing carotid stiffness may pseudonormalize the carotid upstrokes. The LV apical impulse in aortic stenosis is not displaced but is enlarged and forceful. The simultaneous palpation of a forceful LV apex beat and a delayed and weakened carotid pulse is a persuasive clue that severe aortic stenosis is present. The S1 in aortic stenosis is generally normal. In congenital aortic stenosis when the valve is not calcified, S1 may be followed by a systolic ejection click. In calcific disease, S2 may be single and soft when the aortic component is lost because the valve neither opens nor closes well. In some cases, delayed LV emptying secondary to LV dysfunction may create paradoxical splitting of S2. An S4 gallop is common. In advanced disease, pulmonary hypertension and signs of right-sided failure are common.

Because of the dire consequences of missing the diagnosis of aortic stenosis, the physician must have a low threshold for obtaining an echocardiogram whenever aortic stenosis cannot be excluded by physical examination. In asymptomatic patients with suspicious murmurs, early diagnosis allows the patient and physician to be more vigilant regarding possible early signs and symptoms and to guide the use of prophylactic regimens to prevent bacterial endocarditis ( Chapter 76 ).

Diagnostic Testing

The electrocardiogram (ECG) in patients with aortic stenosis usually shows LV hypertrophy ( Chapter 52 ). In some cases of even severe aortic stenosis, however, LV hypertrophy is absent on the ECG, possibly because of the lack of LV dilation. Left atrial abnormality is common because the stiff left ventricle increases left atrial afterload and causes the left atrium to dilate.

The chest radiograph in aortic stenosis is generally nondiagnostic. The cardiac silhouette is not usually enlarged but may assume a boot-shaped configuration. In advanced cases, there may be signs of cardiomegaly and pulmonary congestion; aortic valve calcification may be seen in the lateral view.

Echocardiography ( Chapter 53 ) is indispensable to assess the extent of LV hypertrophy, systolic ejection performance, and aortic valve anatomy ( Fig. 75-1 ). Doppler interrogation of the aortic valve makes use of the modified Bernoulli equation (gradient = 4 × velocity2) to assess the severity of the stenosis ( Chapter 53 ). As blood flows from the body of the left ventricle across the stenotic valve, the flow rate must accelerate for the volume to remain constant. Doppler interrogation of the valve can be performed to detect this increase in velocity for estimation of the valve gradient. The peak aortic flow velocity in patients with preserved LV systolic function is a useful clinical guide to prognosis. In patients with a flow velocity of 3.0 mL/sec or less, symptoms are unlikely to develop in the next 5 years; by comparison, in patients with a flow velocity of 4.0 mL/sec or greater, symptoms usually develop within 2 years.

FIGURE 75-1  Doppler echocardiogram from a patient with aortic stenosis. The left panel shows thickened aortic valve leaflets that dome into the aorta with restricted opening in systole. The right panel shows a miniaturized apical four-chamber view at the top with a Doppler cursor through the aorta, whereas the bottom panel shows a continuous-wave spectral Doppler signal with a peak velocity of 3 m/sec. The peak valve gradient can be calculated as 4 × 32, or 36 mm Hg. AO = aorta; LA = left atrium; LV = left ventricle; RV = right ventricle.  (Courtesy of Dr. Anthony DeMaria.)

Although exercise testing is contraindicated in symptomatic patients with aortic stenosis because of the high risk for complications, cautious exercise testing is gaining favor in asymptomatic patients. Such testing often reveals latent symptoms or hemodynamic instability that have gone unrecognized during the patient’s normal daily activities. Exercise-induced hypotension or symptoms are indications for aortic valve replacement in patients with severe aortic stenosis; in patients with mild to moderate aortic stenosis, another source of exercise limitation should be sought.

Brain natriuretic peptide levels may be higher in patients who will become symptomatic in a short time span. However, use of this biomarker to indicate the need for valve replacement is premature.

Cardiac catheterization for performance of coronary arteriography is usually undertaken before surgery because most patients with aortic stenosis are of the age at which coronary disease is common. When echocardiography shows severe aortic stenosis and the patient has one or more of the classic symptoms of the disease, formal invasive documentation of the severity of the stenosis is not necessary, and coronary angiography need not be performed in young adults. When the hemodynamic diagnosis is unclear, however, right-sided and left-sided heart catheterization should be performed to determine the transaortic valvular pressure gradient and cardiac output, which are used to calculate the aortic valve area by the Gorlin formula:

where CO is cardiac output (mL/min), SEP is the systolic ejection period (sec), HR is the heart rate, and h is the mean gradient.


Invasive Therapy

Valve Replacement Surgery

The only proven effective therapy for aortic stenosis is aortic valve replacement. Once the symptoms of aortic stenosis develop, the 3-year mortality is 75% without aortic valve replacement. When the valve is replaced, however, survival returns nearly to normal. Even octogenarians benefit from valve replacement unless other comorbid factors preclude surgery, so aortic valve replacement should not be denied simply on the basis of age. Valve replacement should also not be denied because the ejection fraction is reduced; the excess afterload imposed by the stenotic valve is relieved with valve replacement, and a depressed ejection fraction usually improves dramatically after surgery. The exception to this rule is a severely reduced ejection fraction in the face of only a small aortic valve gradient; in this case the severity of the aortic stenosis may be overestimated because the failing left ventricle has difficulty opening a mildly to moderately stenotic valve. In such patients, LV muscle dysfunction either has another cause or is often so severe that it does not recover after valve replacement. Evidence indicates, however, that even some well-selected patients in this category, such as patients who demonstrate increased cardiac output during dobutamine infusion, may benefit from aortic valve replacement.

Balloon Aortic Valvotomy

In acquired calcific aortic stenosis, leaflet restriction results from heavy calcium deposition in the leaflets themselves and is not due to commissural fusion. Balloon aortic valvotomy is relatively ineffective in improving aortic stenosis; it generally results in a residual gradient of 30 to 50 mm Hg and a valve area of 1.0 cm2. Mortality after this procedure is similar to that in untreated patients. The only occasional indication for balloon aortic valvotomy is palliative in cases in which aortic valve replacement is impossible because of comorbidity or is impractical when immediate temporary relief is required because of the demands of other noncardiac conditions.

Percutaneous Aortic Valve Replacement

Early trials indicate the feasibility of replacing the aortic valve percutaneously in patients too ill to undergo surgery. In this procedure, the native valve is dilated as described earlier. After dilation, a stented valve is inserted over a balloon into the aortic annulus. The balloon is expanded to secure the valve and its stent, which is intended to help prevent restenosis.

Medical Therapy

The only medical therapy indicated in patients with aortic stenosis is antibiotic prophylaxis to prevent bacterial endocarditis ( Chapter 76 ). Otherwise, the patient is either asymptomatic and requires no therapy or is symptomatic and requires surgery. In patients with heart failure awaiting surgery, diuretics can be used cautiously to relieve pulmonary congestion. Nitrates may also be used cautiously to treat angina pectoris. Although vasodilators, especially angiotensin-converting enzyme inhibitors, have become a cornerstone of therapy for heart failure, they are not recommended for aortic stenosis. With fixed valvular obstruction to outflow, vasodilation reduces pressure distal to the obstruction without increasing cardiac output and may cause syncope. Statins do not slow the progression of calcific aortic stenosis. When surgery and valvoplasty are unsuccessful or impossible, digitalis and diuretics can be used to improve symptoms with the understanding that they will not improve life expectancy.



In almost all cases of acquired mitral stenosis, the cause is rheumatic heart disease. Occasionally, severe calcification of the mitral annulus can lead to mitral stenosis in the absence of rheumatic involvement. Mitral stenosis is three times more common in women and usually develops in the 40s and 50s. Although the disease has become rare in developed countries because of the waning incidence of rheumatic fever, mitral stenosis is still prevalent in developing nations, where rheumatic fever is common.


At the beginning of diastole, a transient gradient between the left atrium and left ventricle normally initiates LV filling. After early filling, left atrial and LV pressures equilibrate. In mitral stenosis, obstruction to LV filling increases left atrial pressure and produces a persistent gradient between the left atrium and the left ventricle (see Fig. 56-1 ). The combination of elevated left atrial pressure (and pulmonary venous pressure) and restriction of inflow into the left ventricle limits cardiac output. Although myocardial involvement from the rheumatic process occasionally affects LV muscle function, the muscle itself is normal in most patients with mitral stenosis. However, in approximately a third of patients with mitral stenosis, LV ejection performance is reduced despite normal muscle function because of reduced preload (from inflow obstruction) and increased afterload as a result of reflex vasoconstriction caused by reduced cardiac output.

Because the right ventricle generates most of the force that propels blood across the mitral valve, the right ventricle incurs the pressure overload of the transmitral gradient. In addition, secondary but reversible pulmonary vasoconstriction develops, thus further increasing pulmonary artery pressure and the burden on the right ventricle. As mitral stenosis worsens, right ventricular (RV) failure develops.



Patients with mitral stenosis usually remain asymptomatic until the valve area is reduced to about a third its normal size of 4 to 5 cm2. Then the symptoms typical of left-sided failure—dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea—develop. As the disease progresses and RV failure occurs, ascites and edema are common. Hemoptysis, which is common in mitral stenosis but uncommon in other causes of left atrial hypertension, develops when high left atrial pressure ruptures the anastomoses of small bronchial veins. In some cases, a large left atrium may impinge on the left recurrent laryngeal nerve and cause hoarseness (Ortner’s syndrome) or may impinge on the esophagus and cause dysphagia.

Physical Examination

Although mitral stenosis produces typical and diagnostic findings on physical examination, the diagnosis is missed frequently because the auscultatory findings may be subtle. Palpation of the precordium finds a quiet apical impulse. If pulmonary hypertension and RV hypertrophy have developed, the examiner notes a parasternal lift. S1 is typically loud and may be the most prominent physical finding of the disease. A loud S1 is present because the transmitral gradient holds the mitral valve open throughout diastole until ventricular systole closes the fully opened valve with a loud closing sound. In far-advanced disease, the mitral valve may be so damaged, however, that it neither opens nor closes well, so S1 may become soft. S2 is normally split; the pulmonic component is increased in intensity if pulmonary hypertension has developed. Left-sided S3 and S4 gallop sounds, which represent the ventricular and atrial components of rapid LV filling, are exceedingly rare in mitral stenosis because obstruction at the mitral valve prevents rapid filling. S2 is usually followed by an opening snap. The distance between S2 and the opening snap provides a reasonable estimation of left atrial pressure and the severity of the mitral stenosis. The higher the left atrial pressure, the sooner the left atrial pressure and the falling LV pressure of early ventricular relaxation equilibrate. At this equilibration point, the mitral valve opens, and the opening snap occurs. When left atrial pressure is high, the opening snap closely (0.06 second) follows S2. Conversely, when left atrial pressure is relatively normal, the snap occurs later (0.12 second) and may mimic the cadence of an S3 gallop. The opening snap is followed by the classic low-pitched early diastolic mitral stenosis rumble, which increases in length as the mitral stenosis worsens. This murmur may be inaudible if the patient has a relatively low resting cardiac output. Modest exercise, such as isometric handgrip, may accentuate the murmur’s intensity. If the patient is in sinus rhythm, atrial systole may produce a presystolic accentuation of the murmur. If pulmonary hypertension has developed, the pulmonic component of S2 increases in intensity to become as loud or louder than the aortic component. With pulmonary hypertension, a diastolic blowing murmur of pulmonary insufficiency (Graham Steell’s murmur) is often heard, although in many cases a coexistent murmur of mild aortic insufficiency is mistaken for this murmur. Neck vein elevation, ascites, and edema are present if RV failure has developed.

Noninvasive Evaluation

If the patient is in sinus rhythm, left atrial abnormality is generally present on the ECG. Atrial fibrillation is common, however. If pulmonary hypertension has developed, there is often evidence of RV hypertrophy.

On the chest radiograph, left atrial enlargement produces straightening of the left heart border and a double density at the right heart border as a result of the combined silhouettes of the right atrium and left atrium. Pulmonary venous hypertension produces increased vascularity. Kerley B lines, which represent thickening of the pulmonary septa secondary to chronic venous engorgement, may also be seen.

The echocardiogram produces excellent images of the mitral valve and is the most important diagnostic tool in confirming the diagnosis ( Fig. 75-2 ). Transthoracic echocardiography or, if necessary, transesophageal echocardiography makes the diagnosis in nearly 100% of cases and accurately assesses severity. Mitral stenosis, similar to aortic stenosis, can be quantified by assessing the transvalvular gradient with the modified Bernoulli principle. The stenosis is considered mild when the calculated or planimetered valve area is more than 1.75 cm2, moderate at 1.25 to 1.75 cm2, moderately severe at 1.0 to 1.25 cm2, and severe at less than 1.0 cm2.

FIGURE 75-2  Mitral stenosis. An en fosse view of a stenotic mitral valve in the short-axis view of the left ventricle is shown on the left. Planimetry for the mitral valve orifice yielded an area of 1.09 cm2. The M-mode echocardiogram on the right has been aligned with the appropriate structures on the left. It shows the restricted opening of the mitral valve in diastole associated with the classic diastolic rumbling murmur. RV = right ventricle.  (From Assey ME, Usher BW, Carabello BA: The patient with valvular heart disease. In Pepine CJ, Hill JA, Lambert CR [eds]: Diagnostic and Therapeutic Cardiac Catheterization, 3rd ed. Baltimore, Williams & Wilkins, 1998, p 709.)

During echocardiography, the suitability of the valve for balloon valvotomy can also be assessed (see later). If even mild tricuspid regurgitation is present, the systolic gradient across the tricuspid valve can be used to gauge pulmonary artery pressure, which is an important prognostic factor in mitral stenosis because the prognosis worsens as pulmonary pressure increases.

Invasive Evaluation

Cardiac Catheterization

Cardiac catheterization is usually unnecessary to assess the severity of mitral stenosis. Because many patients with mitral stenosis are of an age when coronary disease might be present, however, coronary arteriography is generally performed if cardiac surgery is anticipated or if the patient has coexistent angina. In these cases, it is common to perform left-sided and right-sided heart catheterization to confirm the transmitral gradient and to calculate the valve area from the Gorlin formula (see earlier).

Prevention and Treatment

Mitral stenosis can be prevented by appropriate antibiotic treatment of β-hemolytic streptococcal infections ( Chapters 312 and 313 ).

Medical Therapy

Asymptomatic patients with mitral stenosis and sinus rhythm require no therapy. Symptoms of mild dyspnea and orthopnea can be treated with diuretics alone. When symptoms worsen to more than mild or if pulmonary hypertension develops, mechanical correction of the stenosis is preferable to medical therapy because it improves longevity in severely symptomatic patients.

Patients with mitral stenosis in whom atrial fibrillation develops usually decompensate because the rapid heart rate reduces diastolic filling time, increases left atrial pressure, and decreases cardiac output. The heart rate must be controlled promptly, preferably with an infusion of diltiazem or esmolol for acute atrial fibrillation or with a β-blocker, a calcium-channel blocker, or oral digoxin in chronic atrial fibrillation ( Chapter 63 ).

Conversion to sinus rhythm is routinely recommended either pharmacologically or with direct-current countershock ( Chapter 63 ) after anticoagulation is therapeutic. It should be noted that patients with rheumatic atrial fibrillation have been excluded from trials of echocardiogram-guided cardioversion without anticoagulation and trials of rate control versus rhythm control for the chronic management of atrial fibrillation. If sinus rhythm cannot be maintained, mechanical therapy for the mitral stenosis is generally recommended in the hope that sinus rhythm can be restored after the obstruction to atrial outflow is corrected. However, the cause of atrial fibrillation in patients with mitral stenosis probably includes atrial rheumatic inflammation, so restoration of sinus rhythm is unpredictable even after mechanical intervention.

Because patients with concomitant mitral stenosis and atrial fibrillation have an extraordinarily high risk for systemic embolism, they should undergo chronic anticoagulation with warfarin at an international normalized ratio (INR) target of 2.5 to 3.5. Anticoagulation is warranted in all patients unless there is a serious contraindication to its use.

Mechanical Therapy

When symptoms progress past early functional class II, that is, symptoms with more than ordinary activity, or if pulmonary hypertension develops, the prognosis is worse unless the mitral stenosis is relieved. In most instances, an excellent result can be achieved with percutaneous balloon valvotomy. In contrast to aortic stenosis, in mitral stenosis there is fusion of the valve leaflets at the commissures. Balloon dilation produces a commissurotomy and a substantial increase in valve area that appears to persist for at least a decade and provides improvement comparable to that of closed or open commissurotomy in suitable patients.[1] Suitability for balloon valvotomy is determined partially during echocardiography. Patients with pliable valves, little valvular calcification, little involvement of the subvalvular apparatus, and less than moderate mitral regurgitation are ideal candidates. Even when valve anatomy is not ideal, however, valvotomy may be attempted in patients with advanced age or in situations in which comorbid risk factors increase surgical risk. In otherwise healthy patients with unfavorable valve anatomy, surgery to perform an open commissurotomy or valve replacement is undertaken.



The mitral valve is composed of the mitral annulus, the leaflets, the chordae tendineae, and the papillary muscles. Abnormalities in any of these structures may lead to mitral regurgitation. The most common cause of mitral regurgitation in the United States is mitral valve prolapse, which is responsible for approximately two thirds of all cases and comprises many diseases, including myxomatous degeneration of the valve. Myocardial ischemia leading to papillary muscle dysfunction or infarction is the next most common cause and accounts for approximately a fourth of all cases. Annular calcification, endocarditis, collagen vascular disease, and rheumatic heart disease are less common causes. Use of the weight loss agents dexfenfluramine and fenfluramine has been implicated in causing valve damage in a few patients who received these drugs.

Mitral regurgitation can be subdivided on the basis of chronicity. Common causes of severe acute mitral regurgitation include ruptured chordae tendineae, ischemic papillary muscle dysfunction or rupture, and infective endocarditis. Chronic severe mitral regurgitation is more likely to be due to myxomatous degeneration of the valve, rheumatic heart disease, or annular calcification.


The pathophysiology of mitral regurgitation can be divided into three phases ( Fig. 75-3 ). In acute mitral regurgitation of any cause, the sudden option for ejection of blood into the left atrium “wastes” a portion of the LV stroke volume as backward rather than forward flow. The combined regurgitant and forward flow causes volume overload of the left ventricle and stretches the existing sarcomeres toward their maximum length. Use of the Frank-Starling mechanism is maximized, and end-diastolic volume increases concomitantly. The regurgitant pathway unloads the left ventricle in systole because it allows ejection into the relatively low-impedance left atrium and thereby reduces end-systolic volume. Although increased end-diastolic volume and decreased end-systolic volume act in concert to increase total stroke volume, forward stroke volume is subnormal because a large portion of the total stroke volume is regurgitated into the left atrium. This regurgitant volume increases left atrial pressure, so the patient experiences heart failure with low cardiac output and pulmonary congestion despite normal LV contractile function.

FIGURE 75-3  Mitral regurgitation. A and B, Normal physiology (N) (A) is compared with the physiology of acute mitral regurgitation (AMR) (B). Acutely, the volume overload increases preload (sarcomere length [SL]), and end-diastolic volume (EDV) increases from 150 to 170 mL. Unloading of the left ventricle by the presence of the regurgitant pathway decreases afterload (end-systolic stress [ESS]), and end-systolic volume (ESV) falls from 50 to 30 mL. These changes result in an increase in the ejection fraction (EF). Because 50% of the total left ventricular (LV) stroke volume (regurgitant fraction [RF]) is ejected into the left atrium (LA), however, forward stroke volume (FSV) falls from 100 to 70 mL. At this stage, contractile function (CF) is normal. C, Chronic compensated mitral regurgitation (CCMR). In CCMR, eccentric cardiac hypertrophy has developed, and EDV has increased substantially. Increased EDV combined with normal contractile function permits ejection of a larger total stroke volume and a larger forward stroke volume than in the acute phase. Left atrial enlargement permits lower left atrial pressure. Because the radius term in the Laplace equation has increased with increasing LV volume, afterload and ESV return to normal. D, Chronic decompensated mitral regurgitation (CDMR). In this stage, contractile dysfunction causes a large increase in ESV with a fall in total and forward stroke volume. Additional LV enlargement leads to worsening mitral regurgitation. The relatively favorable loading conditions in this phase still permit a normal EF, however, despite contractile dysfunction.  (From Carabello BA: Mitral regurgitation: Basic pathophysiologic principles. Mod Concepts Cardiovasc Dis 1988;57:53-57.)

In many cases, severe acute mitral regurgitation necessitates emergency surgical correction. Patients who can be managed through the acute phase may enter the phase of compensation. In this phase, eccentric LV hypertrophy and increased end-diastolic volume, combined with normal contractile function, allow ejection of a sufficiently large total stroke volume to permit forward stroke volume to return toward normal. Left atrial enlargement allows accommodation of the regurgitant volume at a lower filling pressure. In this phase, the patient may be relatively asymptomatic even during strenuous exercise.

Although severe mitral regurgitation may be tolerated for many years, the lesion eventually causes LV dysfunction. The now damaged ventricle has impaired ejection performance, and end-systolic volume increases. Greater LV residual volume at end-systole increases end-diastolic volume and end-diastolic pressure, and the symptoms of pulmonary congestion may reappear. Additional LV dilation may worsen the amount of regurgitation by causing further enlargement of the mitral annulus and malalignment of the papillary muscles. Although there is substantial contractile dysfunction, the increased preload and the presence of the regurgitant pathway, which tends to normalize afterload despite ventricular enlargement, augment the ejection fraction and may maintain it in a relatively normal range.

The causes of LV contractile dysfunction in patients with mitral regurgitation may relate to loss of contractile proteins and abnormalities in calcium handling. In at least some cases, contractile dysfunction is reversible by timely mitral valve replacement.


The standard symptoms of left-sided heart failure should be sought ( Chapter 57 ). An attempt to discover potential causes should be made by questioning for a prior history of a heart murmur or abnormal findings on cardiac examination ( Chapter 48 ), rheumatic heart disease, endocarditis ( Chapter 76 ), myocardial infarction ( Chapter 72 ), or the use of anorexigenic drugs.

Physical Examination

Volume overload of the left ventricle displaces the apical impulse downward and to the left. S1 may be reduced in intensity, whereas S2 is usually physiologically split. In severe mitral regurgitation, S2 is followed by S3, which does not indicate heart failure but reflects rapid filling of the left ventricle by the large volume of blood stored in the left atrium during systole. The typical murmur of mitral regurgitation is a holosystolic apical murmur that often radiates toward the axilla ( Chapter 48 ). There is a rough correlation between the intensity of the murmur and the severity of the disease, but this correlation is too weak to use in clinical decision making because the murmur may be soft when cardiac output is low. In contrast to aortic stenosis, murmur intensity does not usually vary with the RR interval. In acute mitral regurgitation, the presence of a large v wave may produce rapid equilibration of left atrial and LV pressure, thereby reducing the driving gradient and shortening the murmur. Pulmonary hypertension may develop and produce right-sided signs, including an RV lift, an increased P2, and if RV dysfunction has developed, signs of right-sided heart failure.

Noninvasive Evaluation

The ECG usually shows LV hypertrophy and left atrial abnormality. The chest radiograph typically shows cardiomegaly; the absence of cardiomegaly indicates either that the mitral regurgitation is mild or that it has not been chronic enough to allow cardiac dilation to occur.

Echocardiography shows the extent of left atrial and LV enlargement ( Chapter 53 ). Ultrasonic imaging of the mitral valve is excellent and offers clues to the mitral valve abnormalities responsible for the regurgitation. Color flow Doppler interrogation of the valve ( Fig. 75-4 ) helps assess the severity of regurgitation, but because this technique images flow velocity rather than actual flow, it is subject to errors in interpretation. The Doppler technique is excellent for excluding the presence of mitral regurgitation and for distinguishing between mild and severe degrees. Although newer techniques may quantify regurgitation more precisely, they are not yet in widespread use, and standard color flow Doppler examination may not be sufficient for exact quantification of mitral regurgitation or to determine whether the severity of the lesion is sufficient to cause eventual LV dysfunction. When the severity of mitral regurgitation is in doubt or if mitral valve surgery is being contemplated, cardiac catheterization ( Chapter 56 ) is helpful in resolving the severity of the lesion; coronary arteriography should be included in patients older than 40 years or with symptoms suggesting coronary disease ( Chapter 70 ).

FIGURE 75-4  Two-dimensional echocardiogram of mitral regurgitation with Doppler flow mapping superimposed on a portion of the image. The color information is represented in the sector of the imaging plane extending from the apex of the triangular plane to the two small arrows at the bottom of the image plane. Mitral regurgitation (MR) is indicated (open arrows) and extends from the mitral valve leaflets toward the posterior aspect of the left atrium (LA) during systole. The mosaic of colors representing the mitral regurgitant signal is typical of high-velocity turbulent flow. The low-intensity orange-brown signal represents flow directed away from the transducer on the chest wall, and the blue shades represent blood in the left ventricular outflow tract moving toward the transducer. AO = aorta; LV = left ventricle; RV = right ventricle.


Medical Therapy

Severe Acute Mitral Regurgitation

In severe acute mitral regurgitation, the patient is usually symptomatic with heart failure or even shock. The goal of medical therapy is to increase forward cardiac output while concomitantly reducing regurgitant volume ( Chapter 58 ). Arterial vasodilators reduce systemic resistance to flow and preferentially increase aortic outflow and simultaneously decrease the amount of mitral regurgitation and left atrial hypertension. If hypotension already exists, vasodilators such as nitroprusside lower blood pressure further and cannot be used. In these cases, intra-aortic balloon counterpulsation ( Chapter 108 ) is preferred if the aortic valve is competent. Counterpulsation increases forward cardiac output by lowering ventricular afterload while augmenting systemic diastolic pressure.

Chronic Symptomatic Mitral Regurgitation

In patients with symptomatic mitral regurgitation, angiotensin-converting enzyme inhibitors reduce LV volume and improve symptoms. Mitral valve surgery rather than medical therapy is generally preferred, however, in most symptomatic patients with mitral regurgitation. When atrial fibrillation is present, long-term anticoagulation should achieve the same INR goal as for mitral stenosis.

Chronic Asymptomatic Mitral Regurgitation

Vasodilators have had little effect in reducing LV volume or improving normal exercise tolerance in patients with mitral regurgitation, perhaps because afterload is not usually increased in those with chronic asymptomatic mitral regurgitation. Thus, there is no definitive indication to begin afterload reduction before symptoms appear.

Surgical Therapy

The timing of mitral valve surgery must weigh the risks of the operation and placement of a prosthesis, if one is inserted, versus the risk for irreversible LV dysfunction if surgery is delayed unwisely. For most other types of valve disease, surgical correction usually requires placement of a prosthetic valve, but in patients with mitral regurgitation the native valve can often be repaired. Because conservation of the native valve obviates the risks associated with a prosthesis, the option of mitral valve repair should influence the patient and physician toward earlier surgery.

Types of Mitral Valve Surgery

Mitral Valve Repair

When feasible, mitral valve repair is the preferred operation. Repair restores valve competence, maintains the functional aspects of the apparatus, and avoids the insertion of a prosthesis. Repair is most applicable in cases of posterior chordal rupture; anterior involvement and rheumatic involvement make repair more difficult. Currently, the percentage of mitral valve surgeries that are valve repair varies from 0 to 95% at different hospital centers. In all cases, the feasibility of repair depends on the pathoanatomy that is causing the mitral regurgitation and the skill and experience of the operating surgeon.

Mitral Valve Replacement with Preservation of the Mitral Apparatus

In this procedure, a prosthetic valve is inserted, but continuity between the native leaflets and the papillary muscles is maintained. This procedure has the advantage of ensuring mitral valve competence while preserving the LV functional aspects of the mitral apparatus. Even if only the posterior leaflets and chordae are preserved, the patient benefits from improved postoperative ventricular function and better survival. In many cases it is possible to preserve the anterior and posterior chordal attachments, although anterior continuity can be associated with LV outflow tract obstruction. Although the patient benefits from restored mitral valve competence and maintenance of LV function, insertion of a prosthesis still carries all prosthesis-associated risks.

Mitral Valve Replacement without Preservation of the Mitral Apparatus

When the native valve cannot be repaired or the chordae preserved, such as in severe rheumatic deformity, the mitral valve leaflets and its apparatus are removed and a prosthetic valve is inserted. Although this operation almost guarantees mitral valve competence, the mitral valve apparatus is responsible for coordinating LV contraction and for helping maintain the efficient prolate ellipsoid shape of the left ventricle. Destruction of the apparatus leads to a sudden fall in LV function and a decline in postoperative ejection fraction that is often permanent.

Timing of Surgery

Symptomatic Patients

Most patients with symptoms of dyspnea, orthopnea, or fatigue should undergo surgery regardless of which operation is performed because they already have lifestyle limitations from their disease. The mere presence of symptoms may worsen the prognosis despite relatively well preserved LV function. The onset or worsening of symptoms is a summary of the patient’s pathophysiology and may give a broader view of cardiovascular integrity than possible with any single measurement of pressure or function.

Asymptomatic Patients with Normal Left Ventricular Function

Surgery has increasingly been considered in asymptomatic patients who have normal LV function but echocardiographic findings indicating that valve repair is likely to be successful. Although these patients are at low risk without surgery, the risk associated with valve repair is less than 1%, and this approach avoids the risks of later valve replacement, which may be required if the valvular disease progresses. Valve repair obviates the need for protracted, expensive follow-up and provides a durable correction of the lesion. This approach is sensible, however, only if it is certain that valve repair can be performed because insertion of a prosthesis carries unacceptable risk in this low-risk group.

Asymptomatic Patients with Left Ventricular Dysfunction

The onset of LV dysfunction in patients with mitral regurgitation may occur without causing symptoms. Early surgery is warranted to prevent the muscle dysfunction from becoming severe or irreversible. Regardless of whether valve repair or replacement is eventually performed, survival is prolonged to or toward normal if surgery is performed before the ejection fraction declines to less than 0.60 or before the left ventricle is unable to contract to an end-systolic dimension of 45 mm. Patients with severe mitral regurgitation should be monitored yearly with a history, physical examination, and echocardiographic evaluation of LV function. When the patient reports symptoms or echocardiography shows the onset of LV dysfunction, surgery should be undertaken.

Asymptomatic Elderly Patients

Patients older than 75 years may have poor surgical results, especially if coronary disease is present or if mitral valve replacement rather than repair must be performed. Although elderly patients with symptoms refractory to medical therapy may benefit from surgery, there is little compelling reason to commit elderly asymptomatic patients to a mitral valve operation.



Mitral valve prolapse occurs when one or both of the mitral valve leaflets prolapse into the left atrium superior to the mitral valve annular plane during systole. The importance of mitral valve prolapse varies from patient to patient. In some cases, prolapse is simply a consequence of normal LV physiology without significant medical impact, such as in situations that produce a small left ventricle (e.g., the Valsalva maneuver or an atrial septal defect), in which reduction of ventricular volume causes relative lengthening of the chordae tendineae and subsequent mitral valve prolapse. At the other end of the spectrum, severe redundancy and deformity of the valve, which occurs in myxomatous valve degeneration, increases the risk for stroke, arrhythmia, endocarditis, and progression to severe mitral regurgitation.



Most patients with mitral valve prolapse are asymptomatic. In some cases, however, mitral valve prolapse is associated with symptoms, including palpitations, syncope, and chest pain. In some cases, chest pain is associated with a positive thallium scintigram indicating the presence of true ischemia despite normal epicardial coronary arteries, perhaps because excessive tension on the papillary muscles increases oxygen consumption and causes ischemia. Palpitations, syncope, and presyncope, when present, are linked to autonomic dysfunction ( Chapters 61 , 427 , and 445 ), which seems to be more prevalent in patients with mitral valve prolapse.

Physical Examination

On physical examination, the mitral valve prolapse syndrome produces the characteristic findings of a midsystolic click and a late systolic murmur. The click occurs when the chordae tendineae are stretched taut by the prolapsing mitral valve in midsystole. As this occurs, the mitral leaflets move past their coaptation point, permit mitral regurgitation, and cause the late systolic murmur (see Table 48-6 ). Maneuvers that make the left ventricle smaller, such as the Valsalva maneuver, cause the click to appear earlier and the murmur to be more holosystolic and often louder (see Table 48-6 ). In some cases of echocardiographically proven mitral valve prolapse, neither the click nor the murmur is present; in other cases, only one of these findings is present.

Noninvasive Evaluation

Echocardiography is useful to prove that prolapse is present, to image the amount of regurgitation and its physiologic effects, and to discern the pathoanatomy of the mitral valve. Although an echocardiogram is not necessary to diagnose prolapse in patients with the classic physical findings, the echocardiogram adds significant prognostic information because it can detect patients who have specifically abnormal valve morphology and in whom most of the complications of the disease occur.

In the 1990s it became clear that the mitral annulus did not exist in a single plane but had a saddleback shape. Prolapse shown in the four-chamber echocardiographic view should be confirmed in the parasternal long-axis view. Echocardiographic diagnoses made before the understanding that the mitral valve plane was multidimensional (circa 1987) may have been made in error.


Because most patients with mitral valve prolapse are asymptomatic, therapy is unnecessary. Patients with mitral valve prolapse and its characteristic murmur should observe standard endocarditis prophylaxis ( Chapter 76 ). Those with otherwise normal valve leaflets who are shown to prolapse during echocardiography and who do not have a heart murmur do not require endocarditis precautions. Patients with clearly abnormal valves but no murmur fall into a middle category of endocarditis risk in which a firm recommendation about prophylaxis cannot be made. In patients with palpitations and autonomic dysfunction, β-blockers are often effective in relieving symptoms. Low-dose aspirin therapy has been recommended for patients with redundant leaflets because these patients have a slightly increased risk for stroke. No data from large studies are available to support this contention, however. If severe mitral regurgitation develops, the therapy is the same as for other causes of mitral regurgitation.


Most patients with mitral valve prolapse have a benign clinical course; even for complication-prone patients with redundant and misshapen mitral leaflets, complications are relatively rare. Approximately 10% of patients with thickened leaflets experience infective endocarditis, stroke, progression to severe mitral regurgitation, or sudden death. The progression to severe mitral regurgitation varies with gender and age, and men are approximately twice as likely to progress as women. By 50 years of age, only approximately 1 in 200 men requires surgery to correct mitral regurgitation. By the age of 70, the risk increases to approximately 3%.



Aortic regurgitation is caused either by abnormalities of the aortic leaflets or by abnormalities of the proximal aortic root. Leaflet abnormalities causing aortic regurgitation include a bicuspid aortic valve, infective endocarditis, and rheumatic heart disease; anorexigenic drugs have also been implicated. Common aortic root abnormalities that cause aortic regurgitation include Marfan syndrome ( Chapter 281 ), hypertension-induced annuloaortic ectasia, aortic dissection ( Chapter 78 ), syphilis ( Chapter 341 ), ankylosing spondylitis ( Chapter 286 ), and psoriatic arthritis ( Chapter 286 ). Acute aortic regurgitation is usually caused by infective endocarditis ( Chapter 76 ) or aortic dissection.


As with mitral regurgitation, aortic regurgitation imparts a volume overload on the left ventricle because the left ventricle must pump the forward flow entering from the left atrium and the regurgitant volume returning through the incompetent aortic valve. Also as with mitral regurgitation, the volume overload is compensated for by the development of eccentric cardiac hypertrophy, which increases chamber size and allows the ventricle to pump a greater total stroke volume and a greater forward stroke volume. Ventricular enlargement also allows the left ventricle to accommodate the volume overload at a lower filling pressure. In contrast to mitral regurgitation, the entire stroke volume is ejected into the aorta in aortic regurgitation. Because pulse pressure is proportional to stroke volume and elastance of the aorta, the increased stroke volume increases systolic pressure. Systolic hypertension leads to afterload excess, which does not generally occur in mitral regurgitation. Ventricular geometry also differs between mitral and aortic regurgitation because the afterload excess in aortic regurgitation causes a modest element of concentric hypertrophy, as well as severe eccentric hypertrophy.

In acute aortic insufficiency, such as might occur in infective endocarditis, severe volume overload of the previously unprepared left ventricle results in a sudden fall in forward output while precipitously increasing LV filling pressure. It is probably this combination of pathophysiologic factors that leads to rapid decompensation, presumably because the severely diminished gradient for coronary blood flow causes ischemia and progressive deterioration in LV function. In acute aortic insufficiency, reflex vasoconstriction increases peripheral vascular resistance. In compensated chronic aortic insufficiency, vasoconstriction is absent, and vascular resistance may be reduced and contribute to the hyperdynamic circulation observed in these patients.

Clinical Manifestations

The most common symptoms from chronic aortic regurgitation are those of left-sided heart failure, that is, dyspnea on exertion, orthopnea, and fatigue. In acute aortic regurgitation, cardiac output and shock may develop rapidly. The onset of symptoms in patients with chronic aortic regurgitation usually heralds the onset of LV systolic dysfunction. Some patients with symptoms have apparently normal systolic function, however, and the symptoms may be attributed to diastolic dysfunc-tion. Other patients may have ventricular dysfunction yet remain asymptomatic.

Angina may also occur in patients with aortic insufficiency but less commonly than in those with aortic stenosis. The cause of angina in aortic regurgitation is probably multifactorial. Coronary blood flow reserve is reduced in some patients because diastolic runoff into the left ventricle lowers aortic diastolic pressure while increasing LV diastolic pressure—these two influences lower the driving pressure gradient for flow across the coronary bed. When angina occurs in aortic regurgitation, it may be accompanied by flushing. Other symptoms include carotid artery pain and an unpleasant awareness of the heartbeat.


Physical Examination

Aortic regurgitation produces a myriad of signs because a hyperdynamic, enlarged left ventricle ejects a large stroke volume at high pressure into the systemic circulation. Palpation of the precordium finds a hyperactive apical impulse displaced downward and to the left. S1 and S2 are usually normal. S2 is followed by a diastolic blowing murmur heard best along the left sternal border with the patient sitting upright. In mild disease, the murmur may be short and heard only in the beginning of diastole when the gradient between the aorta and the left ventricle is highest. As the disease worsens, the murmur may persist throughout diastole. A second murmur, a mitral valve rumble, is heard at the LV apex in patients with severe aortic insufficiency. Although the cause is still debated, this Austin Flint murmur is probably produced as the regurgitant jet impinges on the mitral valve and causes it to vibrate.

In chronic aortic regurgitation, the high stroke volume and reduced systemic arterial resistance result in a wide pulse pressure, which may generate a number of signs, including Corrigan’s pulse (sharp upstroke and rapid decline of the carotid pulse), de Musset’s sign (head bobbing), Duroziez’s sign (combined systolic and diastolic bruits created by compression of the femoral artery with the stethoscope), and Quincke’s pulse (systolic plethora and diastolic blanching in the nail bed when gentle traction is placed on the nail). Perhaps the most reliable of physical signs indicating severe aortic regurgitation is Hill’s sign, an increase in femoral systolic pressure of 40 mm Hg or more when compared with systolic pressure in the brachial artery.

In contrast to chronic aortic insufficiency with its myriad of clinical signs, acute aortic insufficiency may have a subtle manifestation. The eccentric hypertrophy, which compensates for chronic aortic insufficiency, has not yet had time to develop, and the large total stroke volume responsible for most of the signs of chronic aortic insufficiency is absent. The only clues to the presence of acute aortic insufficiency may be a short diastolic blowing murmur and reduced intensity of S1. This latter sign occurs because high diastolic LV pressure closes the mitral valve early in diastole (mitral valve preclosure) so that when ventricular systole occurs, only the tricuspid component of S1 is heard.

Noninvasive Evaluation

The ECG in patients with aortic insufficiency is nonspecific but almost always demonstrates LV hypertrophy. The chest radiograph shows an enlarged heart, often with uncoiling and enlargement of the aortic root.

Echocardiography ( Chapter 53 ) is the most important noninvasive tool for assessing the severity of aortic insufficiency and its impact on LV geometry and function ( Fig. 75-5 ). During echocardiography, the LV end-diastolic dimension, end-systolic dimension, and fractional shortening are determined. Aortic valve anatomy and aortic root anatomy can be assessed and the cause of the aortic regurgitation can often be determined. Color flow Doppler examination of the aortic valve helps quantify the severity of aortic regurgitation by assessing the depth and width to which the diastolic jet penetrates the left ventricle. Another way to assess the severity of aortic regurgitation is the pressure half-time method: continuous-wave Doppler interrogation of the aortic valve displays the decay of the velocity of retrograde flow across the valve. In mild aortic insufficiency, the gradient across the valve is high throughout diastole, and its rate of decay is slow, with production of a long Doppler half-time (the time that it takes the velocity to decay from its peak to that value divided by the square root of 2). In severe aortic regurgitation, there is rapid equilibration between pressure in the aorta and pressure in the left ventricle, and the Doppler half-time is short. If mitral valve preclosure is detected in acute aortic insufficiency, urgent surgery is necessary. In cases in which the severity of aortic insufficiency is in doubt, catheterization to perform aortography is useful in resolving the issue.

FIGURE 75-5  Echocardiogram of a patient with aortic regurgitation caused by infective endocarditis. The left panel shows a linear vegetation (arrow) prolapsing into the left ventricular outflow tract from the aortic valve leaflet in diastole. AO = aorta; LA = left atrium; LV = left ventricle; RV = right ventricle. The right panel is a color flow Doppler exhibiting turbulent blood flow filling the left ventricular tract during diastole.  (Courtesy of Dr. Anthony DeMaria.)


Medical Therapy

Asymptomatic Patients with Normal Left Ventricular Function

Because aortic regurgitation increases LV afterload, which decreases cardiac efficiency, afterload reduction with nifedipine and other vasodilators, including angiotensin-converting enzyme inhibitors and hydralazine, improves hemodynamics in the short term. Although initial data suggested that such therapy could delay or reduce the need for aortic valve surgery without any adverse effects when surgery is finally performed, more recent data suggest no benefit from such therapy. These discrepant results from relatively small trials preclude firm recommendations.

Symptomatic Patients or Patients with Left Ventricular Dysfunction

Patients who are symptomatic or manifest LV dysfunction should not be treated medically, except for short-term stabilization, but should undergo aortic valve surgery as soon as feasible.

Surgical Therapy

Acute Aortic Regurgitation

When any of the symptoms or signs of heart failure develop, even if mild, medical mortality is high and approaches 75%. Therapy with vasodilators, such as nitroprusside, may temporarily improve the patient’s condition before surgery but is never a substitute for surgery. In patients with acute aortic regurgitation caused by bacterial endocarditis ( Chapter 76 ), surgery may be delayed to permit a full or partial course of antibiotics, but persistent, severe aortic regurgitation requires emergency valve replacement. Even when blood cultures have been positive recently and antibiotic therapy has been of brief duration, the valve reinfection rate is low, 0 to 10%, with valve replacement or valve repair. Emergency surgery should not be withheld simply because the duration of antibiotic therapy has been brief.

Chronic Aortic Regurgitation

Asymptomatic patients who manifest evidence of LV dysfunction benefit from surgery. Because loading conditions differ between aortic and mitral regurgitation, the objective markers for the presence of LV dysfunction also differ. In aortic regurgitation, when the ejection fraction is less than 0.55 or the end-systolic dimension is greater than 55 mm, postoperative outcome is impaired, presumably because these markers indicate that LV dysfunction has developed. Surgery should be performed before these benchmarks are reached.

Patients with advanced symptoms are at increased risk for a suboptimal surgical outcome regardless of whether they have evidence of LV dysfunction. Patients should undergo aortic valve replacement before symptoms impair lifestyle.

Although some patients may be able to undergo successful aortic valve repair to restore aortic valve competence, most patients require insertion of an aortic valve prosthesis.



Tricuspid regurgitation is usually secondary to a hemodynamic load on the right ventricle rather than a structural valve deformity. Diseases that cause pulmonary hypertension, such as chronic obstructive airway disease or intracardiac shunts, lead to RV dilation and subsequent tricuspid regurgitation. Because most of the force that is needed to fill the left ventricle is provided by the right ventricle, LV dysfunction leading to elevated LV filling pressure also places the right ventricle under a hemodynamic load and can eventually lead to RV failure and tricuspid regurgitation. In some instances, tricuspid regurgitation may be caused by pathology of the valve itself. The most common cause of primary tricuspid regurgitation is infective endocarditis, usually stemming from drug abuse and unsterile injections. Other causes include carcinoid syndrome, rheumatic involvement of the tricuspid valve, myxomatous degeneration, RV infarction, and mishaps during endomyocardial biopsy.


The symptoms of tricuspid regurgitation are those of right-sided heart failure and include ascites, edema, and occasionally right upper quadrant pain. On physical examination, tricuspid regurgitation produces jugular venous distention accentuated by a large v wave as blood is regurgitated into the right atrium during systole. Regurgitation into the hepatic veins causes hepatic enlargement and liver pulsation. RV enlargement is detected as a parasternal lift. Ascites and edema are common.

The definitive diagnosis of tricuspid regurgitation is made during echocardiography. Doppler interrogation of the tricuspid valve shows systolic disturbance of the right atrial blood pool. Echocardiography ( Chapter 53 ) can also be used to determine the severity of pulmonary hypertension, measure RV dilation, and assess whether the valve itself is intrinsically normal or abnormal.


Therapy for secondary tricuspid regurgitation is generally aimed at the cause of the lesion. If LV failure has been responsible for RV failure and tricuspid regurgitation, the standard therapy for improving LV failure ( Chapter 58 ) lowers LV filling pressure, reduces secondary pulmonary hypertension, relieves some of the hemodynamic burden of the right ventricle, and partially restores tricuspid valve competence. If pulmonary disease is the primary cause, therapy is directed toward improving lung function. Vasodilators, so useful in the treatment of left-sided heart failure, are often ineffective in treating pulmonary hypertension itself. Medical therapy directed at tricuspid regurgitation is usually limited to diuretic use.

Surgical intervention for the tricuspid valve is rarely entertained in isolation. However, if other cardiac surgery is planned in a patient with severe tricuspid regurgitation, ring annuloplasty or tricuspid valve repair is frequently attempted to ensure postoperative tricuspid competence. Tricuspid valve replacement is often not well tolerated and is rarely performed except when severe deformity, as is often seen in endocarditis or carcinoid disease, precludes valve repair.



Pulmonic stenosis is a congenital disease resulting from fusion of the pulmonic valve cusps ( Chapter 68 ). It is usually detected and corrected during childhood, but occasionally cases are diagnosed for the first time in adulthood. Symptoms of pulmonic stenosis include angina and syncope. Occasionally, symptoms of right-sided heart failure develop. During physical examination, the uncalcified valve in pulmonic stenosis produces an early systolic ejection click on opening. During inspiration, the click diminishes or disappears because increased flow into the right side of the heart during inspiration partially opens the pulmonic valve in diastole so that systole causes less of an opening sound. The click is followed by a systolic ejection murmur that radiates to the base of the heart. If the transvalvular gradient is severe, RV hypertrophy develops and produces a parasternal lift.

The diagnosis of pulmonic stenosis is confirmed by echocardiography, which quantifies the transvalvular gradient and the degree of RV hypertrophy and dysfunction.


In asymptomatic patients with a gradient less than 25 mm Hg, no therapy is required. If symptoms develop or the gradient exceeds 50 mm Hg, balloon commissurotomy is effective in reducing the gradient and relieving symptoms.

Postoperative Care of Patients with Substitute Heart Valves

Different types of prosthetic valves ( Fig. 75-6 ) have different advantages and disadvantages ( Table 75-2 ). After a prosthetic valve has been inserted, a baseline echocardiogram should be obtained to provide a reference point in the event that valve dysfunction is suspected at a later date. Echocardiography does not need to be repeated unless there is a change in clinical status or physical findings. The major causes of valve dysfunction are infective endocarditis, clot, and valve degeneration. Dysfunction is manifested most commonly by valvular regurgitation, but valvular stenosis can also occur with a clot, vegetations, or degeneration, especially degeneration of a bioprosthesis.

Whenever a patient with a prosthetic heart valve has a temperature higher than 100° F, endocarditis must be excluded by blood culture; for fever with signs of sepsis, broad-spectrum antibiotics must be begun while awaiting culture results. For patients with bioprosthetic valves, mechanical prostheses, and homografts, endocarditis prophylaxis should be instituted at the time of procedures that are associated with a high risk for bacteremia ( Chapter 76 ). Whether prophylaxis is necessary for pulmonary autografts is currently unclear, but physicians usually prescribe prophylaxis for these patients.

By 15 years after surgery, a randomized trial showed no differences in mortality in patients with mechanical valves versus tissue valves in the mitral position. In the aortic position, all-cause mortality was worse for bioprostheses (79%) than for mechanical prostheses (66%), with much of the increased mortality related to a higher rate of bioprosthetic valve failure.[2]

All patients with a mechanical heart valve require anticoagulation. Recommended INR values range from 2.0 for a young normotensive patient in sinus rhythm with an aortic valve prosthesis to 3.5 for a patient with atrial fibrillation and a mitral valve prosthesis. Aspirin, 325 mg, is recommended in addition to warfarin to reduce the risk for valve thrombosis in patients who have mechanical prosthetic valves that are at higher risk for thromboembolic complications.

FIGURE 75-6  Different types of commonly used prosthetic valves. A, Starr-Edwards caged ball mitral prosthesis. B, Starr-Edwards aortic prosthesis. C, St. Jude Medical bileaflet prosthesis. D, Medtronic-Hall tilting disc valve. E, Carpentier-Edwards bioprosthesis.  (From Wernly JA, Crawford MH: Choosing a prosthetic heart valve. Cardiol Clin 1991;9:329-338.)

TABLE 75-2   — 

Type of Valve Advantages Disadvantages
Bioprosthesis (Carpentier-Edwards, Hancock) Avoids anticoagulation in patients with sinus rhythm Durability limited to 10–15 yr
    Relatively stenotic
Mechanical valves (St. Jude, Medtronic-Hall, Starr-Edwards) Good flow characteristics in small sizes Require anticoagulation
Homografts and autografts Anticoagulation not required Surgical implantation technically demanding
  Durability increased over that of bioprostheses  
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