This chapter describes the pathophysiologic abnormalities in patients with common valvular heart diseases. Each of the conditions is discussed separately because unifying principles do not govern the behavior of all stenotic or regurgitant valves. Effective patient management requires accurate identification of the valvular lesion, a determination of its severity, and a clear understanding of the pathophysiologic consequences and natural history of the condition.
The evaluation of a patient with a suspected valvular lesion begins at the bedside with a careful history and physical examination from which the trained clinician can usually identify the type of abnormalities that are present. The severity of the valve lesions can then be further assessed from the electrocardiogram, chest radio graph, echocardiogram, and, in some cases, cardiac magnetic resonance imaging. In selected patients, additional investigation with exercise testing or cardiac catheterization may be necessary to define fully the significance of the condition and guide therapy.
Acute rheumatic fever (ARF) was once among the most common causes of valvular heart disease, but its incidence has waned considerably in the past half-century in industrialized societies. In the 1940s, the yearly incidence exceeded 200,000 cases in the United States, whereas the disease is now rare. The decline of this condition immediately preceded or coincided with the introduction of penicillin, as well as with the improvement of general health care and the relief from overcrowding. Although occasional local outbreaks occur, a major resurgence has not been seen in this country. Nevertheless, in developing parts of the world, ARF continues to be a scourge with fulminant consequences.
ARF is an inflammatory condition that primarily involves the heart, skin, and connective tissues. It is a complication of upper respiratory tract infections caused by group A streptococci and mainly occurs in children and young adults. During epidemics, approximately 3% of patients with acute streptococcal pharyngitis develop ARF 2 to 3 weeks after the initial throat infection. Although the pathogenesis remains unknown, it does not involve direct bacterial infection of the heart. Some proposed mechanisms include the elaboration of a toxin by the streptococci or autoimmune cross-reactivity between bacterial and cardiac antigens.
Pathologically in ARF, carditis (i.e., cardiac inflammation) may afflict all three layers of the heart (pericardium, myocardium, and endocardium). Histopathologic examination often demonstrates the Aschoff body ( Fig. 8.1), an area of focal fibrinoid necrosis surrounded by inflammatory cells, including lymphocytes, plasma cells, and macrophages, that later resolve to form fibrous scar tissue.
The most devastating sequelae result from inflammatory involvement of the valvular endocardium, which leads to chronic rheumatic heart disease characterized by permanent deformity and impairment of one or more cardiac valves. Symptoms of valvular dysfunction, however, generally do not become manifest until 10 to 30 years after ARF has subsided. This latency period may be considerably shorter with the more aggressive disease observed in developing countries.
Figure 8.1.Histopathologic appearance of an Aschoff body in acute rheumatic carditis.
Mononuclear inflammatory cells surround a center of focal necrosis.
(Courtesy of Dr. Frederick J. Schoen, Brigham and Women’s Hospital, Boston.)
The most common presenting symptoms of ARF are chills, fever, fatigue, and migratory arthralgias. The cardinal symptoms and clinical manifestations of the disease that establish the diagnosis are known as the Jones criteria ( Table 8.1). During the acute episode, carditis may be associated with tachycardia, decreased left ventricular contractility, a pericardial friction rub, a transient murmur of mitral or aortic regurgitation, or a mid-diastolic murmur at the cardiac apex (termed the Carey–Coombs murmur). These transient murmurs likely reflect turbulent flow across inflamed valve leaflets. Treatment of the acute episode includes the use of high-dose aspirin to reduce inflammation, penicillin to eliminate residual streptococcal infection, and therapy for complications such as congestive heart failure and pericarditis.
Table 8.1.Jones Criteria for Diagnosis Rheumatic Fevera
- Sydenham chorea (involuntary movements)
- Erythema marginatum (skin rash with advancing edge and clearing center)
- Subcutaneous nodules
- Minor criteria
- Evidence of streptococcal infection
During the chronic phase of this condition, stenosis or regurgitation of cardiac valves is common, most often affecting the mitral valve. Forty percent of patients with rheumatic heart disease will develop mitral stenosis. An additional 25% will develop aortic stenosis or regurgitation in addition to the mitral abnormality. Infrequently, the tricuspid valve is affected as well.
Recurrences of ARF in affected patients can incite further cardiac damage. Therefore, individuals who have experienced ARF should receive low-dose penicillin prophylaxis at least until early adulthood, by which time exposure and susceptibility to streptococcal infections have diminished.
Mitral Valve Disease
The most common cause of mitral stenosis (MS) is rheumatic fever. Approximately 50% of patients with symptomatic MS provide a history of ARF occurring, on average, 20 years before presentation. These patients display typical rheumatic deformity of the valve on echocardiographic and pathologic examinations as described below. Other rare causes of MS (less than 1%) include congenital stenosis of the mitral valve leaflets, prominent calcification extending from the mitral annulus onto the leaflets in elderly patients, or endocarditis with very large vegetations that obstruct the valve orifice.
Acute and recurrent inflammation produces the typical pathologic features of rheumatic MS. These include fibrous thickening and calcification of the valve leaflets, fusion of the commissures (the borders where the leaflets meet), and thickening and shortening of the chordae tendineae.
In early diastole in the normal heart, the mitral valve opens and blood flows freely from the left atrium (LA) into the left ventricle (LV), such that there is a negligible pressure difference between the two chambers. In MS, however, there is obstruction to blood flow across the valve such that emptying of the LA is impeded and there is an abnormal pressure gradient between the LA and LV ( Figs. 8.2 and 8.3).
As a result, the left atrial pressure is higher than normal, a necessary feature for blood to be propelled forward across the obstructed valve. The cross-sectional area of a normal mitral valve orifice is 4 to 6 cm2. Hemodynamically significant MS becomes apparent when the valve area is reduced to less than 2 cm2. Although left ventricular pressures are usually normal in MS, impaired filling of the chamber across the narrowed mitral valve may reduce LV stroke volume and cardiac output.
Figure 8.2.Pathophysiology of mitral stenosis.
In the normal heart, blood flows freely from the left atrium (LA) into the left ventricle (LV) during diastole. In mitral stenosis, there is obstruction to LA emptying. Thus, the LA pressure increases, which in turn elevates pulmonary and right-heart pressures
Figure 8.3.Hemodynamic profile of mitral stenosis.
The left atrial (LA) pressure is elevated, and there is a pressure gradient (shaded area) between the LA and left ventricle (LV) during diastole. Compare with schematic of normal tracing (see Fig. 2.1). Abnormal heart sounds are present: There is a diastolic opening snap (OS) that corresponds to the opening of the mitral valve, followed by a decrescendo murmur. There is accentuation of the murmur just before S1 owing to the increased pressure gradient when the LA contracts (presystolic accentuation)
The high left atrial pressure in MS is passively transmitted to the pulmonary circulation, resulting in increased pulmonary venous and capillary pressures (see Fig. 8.2). This elevation of hydrostatic pressure in the pulmonary vasculature may cause transudation of plasma into the lung interstitium and alveoli. The patient may therefore experience dyspnea and other symptoms of congestive heart failure. In severe cases, significant elevation of pulmonary venous pressure leads to the opening of collateral channels between the pulmonary and bronchial veins. Subsequently, the high pulmonary vascular pressures may rupture a bronchial vein into the lung parenchyma, resulting in coughing up of blood (hemoptysis).
The elevation of left atrial pressure in MS can result in two distinct forms of pulmonary hypertension: passive and reactive. Most patients with MS exhibit passive pulmonary hypertension, related to the backward transmission of the elevated LA pressure into the pulmonary vasculature. This actually represents an “obligatory” increase in pulmonary artery pressure that develops to preserve forward flow in the setting of increased left atrial and pulmonary venous pressures. Additionally, approximately 40% of patients with MS demonstrate reactive pulmonary hypertension with medial hypertrophy and intimal fibrosis of the pulmonary arterioles.
Reactive pulmonary hypertension serves a “beneficial” role because the increased arteriolar resistance impedes blood flow into the engorged pulmonary capillary bed and thus reduces capillary hydrostatic pressure (thereby “protecting” the pulmonary capillaries from even higher pressures). However, this benefit is at the cost of decreased blood flow through the pulmonary vasculature and elevation of the right-sided heart pressures, as the right ventricle pumps against the increased resistance. Chronic elevation of right ventricular pressure leads to hypertrophy and dilatation of that chamber and ultimately to right-sided heart failure.
Chronic pressure overload of the LA in MS leads to left atrial enlargement. Left atrial dilatation stretches the atrial conduction fibers and may disrupt the integrity of the cardiac conduction system, resulting in atrial fibrillation (a rapid irregular heart rhythm; see Chapter 12). Atrial fibrillation contributes to a decline in cardiac output in MS because the increased heart rate shortens diastole. This reduces the time available for blood to flow across the obstructed mitral valve to fill the LV, and, at the same time, further augments the elevated left atrial pressure.
The relative stagnation of blood flow in the dilated LA in MS, especially when combined with the development of atrial fibrillation, predisposes to intra-atrial thrombus formation. Thromboemboli to peripheral organs may follow, leading to devastating complications such as cerebrovascular occlusion (stroke). Thus, MS patients who develop atrial fibrillation require chronic anticoagulation therapy.
Clinical Manifestations and Evaluation
The natural history of MS is variable. The 10-year survival of untreated patients after onset of symptoms is 50% to 60%. Survival exceeds 80% in asymptomatic or minimally symptomatic patients at 10 years. Longevity is much more limited for patients with advanced symptoms and is dismal for those who develop significant pulmonary hypertension, with a mean survival less than 3 years.
The clinical presentation of MS depends largely on the degree of reduction in valve area. The more severe the stenosis, the greater the symptoms related to elevation of left atrial and pulmonary venous pressures.
The earliest manifestations are those of dyspnea and reduced exercise capacity. In mild MS, dyspnea may be absent at rest; however, it develops on exertion as LA pressure rises with the exercise-induced increase in blood flow through the heart and faster heart rate (i.e., decreased diastolic filling time). Other conditions and activities that increase heart rate and cardiac blood flow and, therefore, precipitate or exacerbate symptoms of MS, include fever, anemia, hyper-thyroidism, pregnancy, rapid arrhythmias such as atrial fibrillation, exercise, emotional stress, and sexual intercourse.
With more severe MS (i.e., a smaller valve area), dyspnea occurs even at rest. Increasing fatigue and more severe signs of pulmonary congestion, such as orthopnea and paroxysmal nocturnal dyspnea, occur. With advanced MS and pulmonary hypertension, signs of right-sided heart failure ensue, including jugular venous distention, hepatomegaly, ascites, and peripheral edema. Compression of the recurrent laryngeal nerve by an enlarged pulmonary artery or LA may cause hoarseness.
Less often, the diagnosis of MS is heralded by one of its complications: atrial fibrillation, thromboembolism, infective endocarditis, or hemoptysis, as described in the earlier section on pathophysiology.
On examination, there are several typical findings of MS. Palpation of the left anterior chest may reveal a right ventricular “tap” in patients with increased right ventricular pressure. Auscultation discloses a loud S1 (the first heart sound, which is associated with mitral valve closure) in the early stages of the disease. The increased S1 results from the high pressure gradient between the atrium and ventricle, which keeps the mobile portions of the mitral valve leaflets widely separated throughout diastole; at the onset of systole, ventricular contraction abruptly slams the leaflets together from the relatively wide position, causing the closure sound to be more prominent (see Chapter 2). In late stages of the disease, the intensity of S1 may normalize or become reduced as the valve leaflets thicken, calcify, and become immobile.
A main feature of auscultation in MS is a high-pitched “opening snap” (OS) that follows S2. The OS is thought to result from the sudden tensing of the chordae tendineae and stenotic leaflets on opening of the valve. The interval between S2 and the OS relates inversely to the severity of MS. That is, the more severe the MS, the higher the LA pressure and the earlier the valve is forced open in diastole. The OS is followed by a low-frequency decrescendo murmur (termed a diastolic rumble) caused by turbulent flow across the stenotic valve during diastole (see Fig. 8.3). The duration, but not the intensity, of the diastolic murmur relates to the severity of MS.
The more severe the stenosis, the longer it takes for the LA to empty and for the gradient between the LA and LV to dissipate. Near the end of diastole, contraction of the LA causes the pressure gradient between the LA and LV to rise again (see Fig. 8.3); therefore, the murmur briefly becomes louder (termed pre-systolic accentuation). This final accentuation of the murmur does not occur if atrial fibrillation has developed because there is no effective atrial contraction in that situation.
Murmurs caused by other valvular lesions are often found concurrently in patients with MS. For example, mitral regurgitation (discussed later in this chapter) frequently coexists with MS. Additionally, right-sided heart failure caused by severe MS may induce tricuspid regurgitation as a result of right ventricular enlargement. A diastolic decrescendo murmur along the left sternal border may be present owing to coexistent aortic regurgitation (because of rheumatic involvement of the aortic leaflets) or pulmonic regurgitation (because of MS-induced pulmonary hypertension).
The electrocardiogram in MS routinely shows left atrial enlargement and, if pulmonary hypertension has developed, right ventricular hypertrophy. Atrial fibrillation may be present. The chest radiograph reveals left atrial enlargement, pulmonary vascular redistribution, interstitial edema, and Kerley B lines resulting from edema within the pulmonary septae (see Chapter 3). With the development of pulmonary hypertension, right ventricular enlargement and prominence of the pulmonary arteries also appear.
Echocardiography is of major diagnostic value in MS. It reveals thickened mitral leaflets and abnormal fusion of their commissures with restricted separation during diastole. Left atrial enlargement can be assessed, and if present, intra-atrial thrombus may be visualized. The mitral valve area can be measured directly on cross-sectional views or calculated from Doppler echocardiographic velocity measurements.
Patients can be stratified into groups of disease severity based partly on the mitral valve area. A normal mitral valve orifice measures between 4 and 6 cm2. A reduced mitral valve area of <2 cm2 correlates with mild MS, and a valve area of 1.1 to 1.5 cm2 correlates with moderate MS. Severe MS is defined by a valve area of <1.0 cm2. Although cardiac catheterization is not necessary to confirm the diagnosis of MS, it is sometimes performed to calculate the valve area by direct hemodynamic measurements and to clarify whether significant mitral regurgitation, pulmonary hypertension, or coronary artery disease is present.
Diuretics are prescribed to treat symptoms of vascular congestion in MS. If atrial fibrillation has developed, a ß-blocker, a calcium channel antagonist with negative chronotropic properties (verapamil or diltiazem), or digoxin may be used to slow the rapid ventricular rate and thereby improve diastolic LV filling. Chronic anticoagulation therapy to prevent thromboembolism is recommended for patients with MS and atrial fibrillation, and for those in whom emboli have already occurred.
If symptoms of MS persist despite diuretic therapy and control of rapid heart rates, or if significant PA hypertension is present, mechanical correction of the stenosis is warranted. Percutaneous balloon mitral valvuloplasty is the treatment of choice for MS in appropriately selected patients. During this procedure, a balloon catheter is advanced from the femoral vein into the right atrium, across the atrial septum (by intentionally creating a small septal defect there), and through the narrowed mitral valve orifice. The balloon is then rapidly inflated, thereby “cracking” open the fused commissures.
The procedure is safest and most effective in the absence of complicating features, such as mitral regurgitation, extensive valve or subvalvular calcification, or atrial thrombus. The results of this procedure in randomized trials compare favorably with those of surgical treatment in anatomically appropriate patients. Approximately 5% of patients undergoing balloon mitral valvuloplasty are left with a residual atrial septal defect. Less frequent complications include cerebral emboli at the time of valvuloplasty, cardiac perforation, or the creation of mitral regurgitation requiring subsequent surgical replacement. The estimated event-free survival 7 years after valvuloplasty is 67% to 76%.
Surgical options are undertaken for correcting MS in individuals whose anatomy is not ideal for balloon valvuloplasty. These techniques include open mitral commissurotomy (an operation in which the stenotic commissures are separated under direct visualization) and, in severe disease, mitral valve replacement. Open mitral valve commissurotomy is effective, and restenosis occurs in fewer than 20% of patients over 10 to 20 years of follow-up.