Michael R. Carr, Stanford T. Shulman
Rheumatic involvement of the cardiac valves is the most important sequela of acute rheumatic fever (ARF) and also the 2nd most common major manifestation after arthritis (see Chapter 210.1 ). The valvular lesions begin as small verrucae composed of fibrin and blood cells along the borders of 1 or more of the heart valves. The mitral valve is affected most often, followed in frequency by the aortic valve. Isolated aortic valve disease is rare and generally seen with concomitant mitral valve involvement. Right-sided heart manifestations are quite rare and are virtually only associated with left-sided valve disease. As the inflammation subsides, the verrucae tend to disappear and leave scar tissue. With repeated attacks of rheumatic fever, new verrucae form near the previous ones, and the mural endocardium and chordae tendineae become involved. A single episode of acute rheumatic carditis often results in complete healing of the valvular lesions, while repeated episodes, especially involving previously affected valves, result in chronic rheumatic heart disease (RHD ), which is the rationale for secondary prophylaxis.
The diagnosis of ARF requires the fulfillment of the Jones criteria (see Chapter 210.1 ), with carditis being a major criterion. Previously, the diagnosis of RHD was based on cardiac auscultatory findings of mitral or aortic valve involvement, which was insensitive for early valve injury. This was based on endocarditis or valvulitis being seen more frequently in ARF compared with pericarditis or myocarditis, both of which lack more readily apparent physical examination findings. Screening large, high-risk populations with echocardiography demonstrated a substantially greater number of patients with RHD than those detected by auscultation alone. Because access to echocardiography is often available, the current version of the Jones Criteria focused on the concept of subclinical carditis (SCC) detected by echocardiography. SCC is defined as echocardiographic evidence of mitral or aortic valvulitis in the absence of auscultatory findings and not consistent with physiologic mitral or aortic insufficiency (Table 465.1 ). Echocardiography with Doppler should be performed for all cases of confirmed or suspected ARF. Additional recommendations are that echocardiography should be performed in moderate- to high-risk patient populations if ARF is considered likely, and that echocardiography can be used to exclude cardiac findings consistent with ARF in patients with cardiac murmurs thought to be suggestive of rheumatic carditis. Additionally, serial echocardiography should be considered in patients with diagnosed or suspected ARF even if there is no evidence of valvulitis by echocardiography at diagnosis. The echocardiographic finding of SCC now fulfills the major criterion for carditis.
Table 465.1
Echocardiographic Findings in Rheumatic Valvulitis
| PATHOLOGIC MITRAL REGURGITATION* | PATHOLOGIC AORTIC REGURGITATION* |
|---|---|
* All 4 criteria need to be met.
Adapted from Gewitz MH, Baltimore RS, Tani LY, etal: On behalf of the American Heart Association Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association, Circulation 131:1806–1818, 2015.
Mitral insufficiency is the result of structural changes that may include some loss of valvular substance and/or changes to the subvalvular apparatus, including elongation of the chordae, both of which can lead to valve dysfunction. During ARF with severe cardiac involvement, heart failure is caused by a combination of mitral insufficiency coupled with a pancarditis , involving the pericardium and myocardium in addition to the endocardium/valve. Because of the increased volume load from the mitral insufficiency and the inflammatory process, the left ventricle dilates. The left atrium also enlarges to accommodate the regurgitant volume. Increased left atrial pressure results in pulmonary congestion and symptoms of left-sided heart failure. Spontaneous improvement often occurs with time, even in patients in whom mitral insufficiency is severe at the onset. The resultant chronic lesion is most often mild or moderate in severity, and the patient is often asymptomatic. More than half of patients with acute mitral insufficiency no longer have an audible mitral insufficiency murmur 1 yr later, although they still may demonstrate insufficiency on echocardiography. In patients with severe chronic mitral insufficiency, pulmonary artery pressure (PAP) becomes elevated, the right ventricle and atrium become enlarged, and right-sided heart failure subsequently develops.
The physical signs of mitral insufficiency depend on its severity. With mild disease, signs of heart failure are not present, the precordium is quiet, and auscultation reveals a high-pitched holosystolic murmur at the apex that radiates to the axilla. With severe mitral insufficiency, signs of acute or chronic heart failure may be noted. The heart is enlarged, with a heaving apical left ventricular (LV) impulse and often an apical systolic thrill . The second heart sound (S2 ) may be accentuated if pulmonary hypertension is present. A third heart sound or gallop is generally prominent. A holosystolic murmur is heard at the apex with radiation to the axilla. A short mid-diastolic rumbling murmur is caused by increased blood flow across the mitral valve as a result of the significant insufficiency. Therefore, auscultation of a diastolic murmur, often referred to as relative mitral stenosis (Carey-Coombs murmur ), does not necessarily mean that true mitral stenosis is present. The latter lesion takes many years to develop and is characterized by a diastolic murmur of greater length, usually with presystolic accentuation.
The electrocardiogram and chest radiographs are normal if the mitral insufficiency is mild. With more severe insufficiency, the ECG shows prominent, longer duration and often bifid P waves, signs of LV hypertrophy, and associated right ventricular (RV) hypertrophy if pulmonary hypertension is present. On chest radiograph, prominence of the left atrium and ventricle can be seen, the former of which is better seen on lateral projections. Congestion of the perihilar vessels, a sign of pulmonary venous hypertension, may also be evident. Calcification of the mitral valve is rare in children. Echocardiography in the acute phase may demonstrate enlargement of the left atrium and ventricle. LV systolic function can be impaired if there is also a component of myocardial inflammation. Mitral annular dilation, chordal elongation, and at times, evidence of chordal rupture resulting in a flail leaflet may be noted. The leaflet tips demonstrate a nodular appearance and prolapse of the anterior mitral valve leaflet tip (much more often than the posterior leaflet) is seen. Doppler evaluation demonstrates the severity of the mitral regurgitation. Chronic mitral insufficiency from RHD is characterized on echocardiography by leaflet and chordal thickening, chordal fusion, and restricted leaflet motion. These changes often lead to stenosis, but poor coaptation of the abnormal leaflets can also lead to variable degrees of regurgitation. Cardiac catheterization and left ventriculography are considered only if diagnostic questions are not completely resolved by noninvasive assessment, or in rare cases with a concern for significantly elevated PAP.
Severe mitral insufficiency may result in cardiac failure that may be precipitated by progression of the rheumatic process, recurrent episodes of ARF, the onset of atrial fibrillation (AF) or other arrhythmias, or infective endocarditis. The effects of chronic mitral insufficiency may become manifest after many years and include LV and RV failure and atrial and ventricular arrhythmias.
In patients with mild mitral insufficiency, prophylaxis against recurrences of rheumatic fever is all that is required, in addition to the typical treatment for ARF (see Chapter 210.1 ). For more significant insufficiency, corticosteroids are added in the acute phase. Treatment of complicating heart failure (see Chapter 469 ), arrhythmias (Chapter 462 ), and infective endocarditis (Chapter 464 ) is described elsewhere. Afterload-reducing agents—angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may reduce the regurgitant volume, attenuate pathologic compensatory mechanisms, and preserve left ventricular function, but these have not been proven to alter the natural history of the disease process. Diuretics may also provide some symptomatic and clinical benefit in select cases. In rare cases, phosphodiesterase inhibitors such as milrinone may be used in the acute stage, because of their inotropic, lusitropic, and systemic vascular dilating effects. Surgical treatment is indicated for patients who, despite adequate medical therapy, have persistent heart failure, dyspnea with moderate activity, and progressive cardiomegaly, often with pulmonary hypertension. Although annuloplasty provides good results in some children and adolescents, valve replacement may be required, which can be more complicated in younger children. In patients with a prosthetic mitral valve replacement, prophylaxis against bacterial endocarditis is warranted for dental procedures, as the routine antibiotics taken by these patients for rheumatic fever prophylaxis are insufficient to prevent endocarditis. Additionally, current recommendations suggest selecting a different class of antibiotic for such procedures, rather than increasing the dose of the antibiotic taken for rheumatic fever prophylaxis. Lastly, it is important to remember that all attempts should be made at maximizing medical management of severe mitral insufficiency during the acute phase of the disease process, before considering surgical intervention, since surgery carries a poorer prognosis and an increased risk for reoperation when performed during the acute phase.
Mitral stenosis of rheumatic origin results from fibrosis of the mitral ring, commissural adhesions, and contracture of the valve leaflets, chordae, and papillary muscles over time. This is a chronic process and often takes ≥10 yr for the lesion to become fully established, although the process may occasionally be accelerated. In the developed world, rheumatic mitral stenosis is seldom encountered before adolescence and is not usually recognized until adult life. Significant mitral stenosis results in increased left atrial pressure and subsequent enlargement and hypertrophy of the left atrium, pulmonary venous hypertension, increased pulmonary vascular resistance, and eventually overt pulmonary hypertension (see Chapter 460 ). RV hypertrophy and right atrial dilation ensue and are followed by RV dilation, tricuspid regurgitation, and clinical signs of right-sided heart failure.
Generally, the correlation between symptoms and the severity of obstruction is good. Patients with mild stenosis are asymptomatic. More severe degrees of obstruction are associated with exercise intolerance and dyspnea. Critical lesions can result in orthopnea, paroxysmal nocturnal dyspnea, and overt pulmonary edema, as well as atrial arrhythmias. When pulmonary hypertension has developed, RV dilation may result in functional tricuspid insufficiency, hepatomegaly, ascites, and edema. Hemoptysis caused by rupture of bronchial or pleurohilar veins and, occasionally, pulmonary infarction may occur.
Jugular venous pressure is increased in severe disease with heart failure, tricuspid valve disease/regurgitation, or severe pulmonary hypertension. In mild disease, heart size is normal; however, moderate cardiomegaly is typical with severe mitral stenosis. Cardiac enlargement can be massive when AF and heart failure supervene. A parasternal RV lift is palpable when PAP is high. The principal auscultatory findings are a loud first heart sound, an opening snap of the mitral valve, and a long, low-pitched, rumbling mitral diastolic murmur with presystolic accentuation at the apex. The mitral diastolic murmur may be virtually absent in patients who are in significant heart failure from the elevated LV filling pressures. A holosystolic murmur secondary to tricuspid insufficiency may be audible at the left lower sternal border. In the presence of pulmonary hypertension, the pulmonic component of S2 is accentuated. An early diastolic murmur may be caused by associated rheumatic aortic insufficiency or pulmonary valvular insufficiency secondary to pulmonary hypertension.
ECGs and chest radiographs are normal if the stenosis is mild; as the severity increases, prominent and notched P waves and varying degrees of RV hypertrophy become evident. AF or other atrial arrhythmias are common late manifestations. Moderate to severe lesions are associated with radiographic signs of left atrial enlargement and prominence of the pulmonary artery and right-sided heart chambers; calcifications may be noted in the region of the mitral valve. Severe stenosis is associated with a redistribution of pulmonary blood flow so that the apices of the lung have greater perfusion (the reverse of normal). Lastly, horizontal lines in the lower lung periphery, called Kerley B lines , may be evident. Echocardiography demonstrates thickening of the mitral valve and chordal apparatus, as well as restricted motion of the valve. The typical “elbow” or “dog leg” appearance of the anterior leaflet of the mitral valve can aid in the distinction of a rheumatic valve from the various forms of congenital mitral stenosis. Left atrial dilation is common; color Doppler flow across the mitral valve shows a narrow jet with flow acceleration, and variable degrees of tricuspid insufficiency can be seen from left atrial hypertension. Doppler can estimate the transmitral pressure gradient but can underestimate the gradient if there is LV dysfunction. Cardiac catheterization quantitates the diastolic gradient across the mitral valve well, allows for the calculation of cross-sectional valve area in older children, and assesses the degree of PAP elevation.
Intervention is indicated in patients with clinical signs and hemodynamic evidence of severe obstruction, but before the onset of severe manifestations. Pharmacologic therapy (diuretics and β-blockers) can be considered but is generally used only for symptom control and much less often in children. Surgical valvotomy or balloon catheter mitral valvuloplasty generally yields good results; valve replacement is avoided unless absolutely necessary. Balloon valvuloplasty is indicated for symptomatic, stenotic, pliable, noncalcified valves of patients without significant atrial arrhythmias or thrombi.
In acute rheumatic aortic insufficiency, poor coaptation of the leaflets or leaflet prolapse is seen. Chronic rheumatic aortic insufficiency leads to sclerosis of the valve and results in distortion and retraction of the cusps. In both settings, regurgitation of blood leads to LV volume overload with dilation and hypertrophy of the left ventricle, as it attempts to compensate for the excessive volume load. Combined mitral and aortic insufficiency in the acute phase of ARF is much more common than aortic involvement alone.
Symptoms are unusual except in severe aortic insufficiency, or in the presence of significant concomitant mitral valve involvement or myocardial dysfunction. The large stroke volume and forceful LV contractions may result in palpitations. Sweating and heat intolerance are related to excessive vasodilation. Dyspnea on exertion can progress to orthopnea and pulmonary edema; angina may be precipitated by heavy exercise. Nocturnal attacks with sweating, tachycardia, chest pain, and hypertension may occur.
The pulse pressure is wide with bounding peripheral pulses (water-hammer or Corrigan pulse ). Systolic blood pressure is elevated, and diastolic pressure is lowered. In severe aortic insufficiency, the heart is enlarged, with an LV apical heave. A diastolic thrill may be present. The typical murmur begins immediately with S2 and continues until late in diastole. The murmur is heard over the upper left and mid-left sternal border with radiation to the apex and upper right sternal border. Characteristically, it has a high-pitched blowing quality and is easily audible in full expiration with the diaphragm of the stethoscope placed firmly on the chest and the patient leaning forward. An aortic systolic ejection murmur is frequently heard because of the increased stroke volume. An apical presystolic murmur (Austin Flint murmur ) resembling that of mitral stenosis is sometimes heard and is caused by the large regurgitant aortic flow in diastole preventing the mitral valve from opening fully.
Chest radiographs demonstrate enlargement of the left ventricle and aorta. The ECG may be normal, but in advanced cases it reveals signs of LV hypertrophy with a strain pattern and prominent P waves. Echocardiography shows a dilated left ventricle and diastolic mitral valve flutter or oscillations caused by aortic regurgitant flow hitting the valve leaflets. The aortic valve may demonstrate irregular or focal thickening, decreased systolic excursion, a coaptation defect, and leaflet prolapse. Doppler evaluation demonstrates the degree of aortic insufficiency. Magnetic resonance angiography (MRA) can be useful in quantitating regurgitant volume, as well as assessing LV size and systolic function. Cardiac catheterization is generally only necessary when echocardiographic or axial imaging data are equivocal.
Mild and moderate degrees of aortic insufficiency are well tolerated. Unlike mitral insufficiency, aortic insufficiency does not generally regress. Patients with combined lesions during the episode of ARF may have only aortic involvement 1-2 yr later. Treatment consists of ACE inhibitors or ARBs and prophylaxis against ARF recurrence. Surgical intervention, which is typically aortic valve replacement, but occasionally can involve aortic valve repair, should be done well in advance of the onset of heart failure, pulmonary edema, and angina or when signs of decreasing myocardial performance become evident, as manifested by increasing LV dimensions and decreasing systolic function on echocardiography. Surgery is considered when early symptoms are present, ST-T wave changes are seen on the ECG, or evidence of decreasing LV ejection fraction is noted.
Primary tricuspid valve involvement is rare during both the acute and chronic stages of rheumatic fever. Tricuspid insufficiency is more common secondary to RV dilation, resulting from significant left-sided cardiac lesions. The clinical signs of tricuspid insufficiency include prominent pulsations of the jugular veins, systolic pulsations of the liver, and a blowing holosystolic murmur at the lower left sternal border that increases in intensity during inspiration. Concomitant signs of mitral or aortic valve disease, with or without AF, are common. In these cases, signs of tricuspid insufficiency often decrease or even disappear when heart failure produced by the left-sided valvular lesions is successfully treated. Tricuspid valvuloplasty may be required in very rare cases.
Pulmonary insufficiency secondary to ARF is rare and usually occurs on a functional basis secondary to pulmonary hypertension and is a late finding with severe mitral stenosis. The murmur (Graham Steell murmur ) is similar to that of aortic insufficiency, but peripheral arterial signs (bounding pulses) are absent. The correct diagnosis is confirmed by two-dimensional echocardiography and Doppler studies.