Rheumatic fever is an acute autoimmune disorder that results as a complication of streptococcal upper respiratory tract infections. Tissues involved in rheumatic fever include the lining and valves of the heart, skin, and connective tissue (Fig. 29-1). The group A β-hemolytic streptococcal organism is responsible for initial and recurrent attacks of rheumatic fever. Lymphatic channels from the tonsils are thought to transmit group A streptococci to the heart.

The incidence of rheumatic fever has declined to less than 1/100,000 in industrialized nations but remains higher than 100/100,000 in endemic, less developed countries.¹ Reasons for the decline in rheumatic fever include the use of antibiotics to treat and prevent streptococcal infections, as well as improved social conditions such as decreased crowding, better housing and sanitation, and access to health care. Rheumatic fever persists in underdeveloped countries in which socioeconomic conditions enable the spread of streptococcal bacteria and limit access to adequate health care. Acute rheumatic fever involves diffuse exudative and proliferative inflammatory reactions in the heart, joints, and skin.

Jones criteria, based on expert opinion rather than clinical trials, were introduced in 1944 for the diagnosis of rheumatic fever. Major diagnostic criteria include carditis, polyarthritis, chorea, erythema marginatum (pink skin rash), and subcutaneous nodules. Minor criteria include arthralgia, fever, and elevated C-reactive protein.¹

Carditis is the most important clinical manifestation of acute rheumatic fever, causing inflammation of the endocardium, myocardium, and pericardium. Myocarditis is characterized by interstitial inflammation that may affect cardiac conduction. Endocarditis causes extensive inflammatory changes, resulting in scarring of the heart valves and acute heart failure. Warty lesions of eosinophilic material build-up at the bases and edges of the valves. As the lesions progress, granulation tissue and subsequent vascularization develop, and fibrosis occurs. The annulus, cusps, and chordae tendineae are scarred and, as a result, they thicken and shorten. Acute heart failure develops because of interstitial myocarditis. Fibrinoid degeneration develops, followed by the appearance of Aschoff nodules, the characteristic pathologic lesion of acute rheumatic fever. As Aschoff nodules heal, fibrous scars remain. In severe cases, death from acute heart failure may result. Carditis frequently does not cause any symptoms and is detected only when the patient seeks help because of arthritis or chorea.

Auscultatory signs of aortic and mitral insufficiency are frequently apparent. In more than 90% of patients with carditis, the mitral valve is affected. When the mitral valve is affected, there may be a high-pitched, blowing, pansystolic murmur. A Carey Coombs murmur, a low-pitched, mid-diastolic murmur of short duration, may be noted at the apex. The Carey Coombs murmur may be attributed to swelling and stiffening of mitral valve leaflets, increased flow across the valve, and alteration in left ventricular compliance.

Rheumatic fever can be prevented by aggressive treatment of the initial episode of streptococcal pharyngitis: penicillin G, 500 mg as the first dose and then 250 mg four times daily for a duration of 10 days. If the patient is allergic to penicillin, erythromycin or cephalosporins may be used. Effective antibiotic treatment started less than 10 days after the onset of infection almost completely eliminates the risk of rheumatic fever.¹

Infective endocarditis is an endovascular infection that supports continuous bacteremia from the source of the infection, usually a vegetation on a heart valve.² While endocarditis is uncommon, affecting
only 10,000 to 20,000 people in the United States each year, it may result in serious complications such as stroke, need for surgery, and death.³ Although incidence of infective endocarditis is low, between 1.5 and 6 cases per 100 cases per year, morbidity and mortality are high.⁴ In intravenous drug users, the risk for endocarditis is 2% to 5% per patient-year.⁵ Rheumatic heart disease, calcific aortic stenosis, hypertrophic cardiomyopathy, congenital heart disease, and the presence of prosthetic heart valves predispose to endocarditis. Intravenous drug abusers are at risk for infective endocarditis caused by recurrent bacteremias related to injection from contaminated needles and localized infections at injection sites. Patients with long-term intravenous lines or dialysis catheters are also at increased risk. Acute endocarditis can also occur in normal heart valves from infection somewhere else in the body In patients with community-acquired, native valve endocarditis, Staphylococcus aureus exceeds streptococci as the causative pathogen.⁵ Pathogens that are most commonly responsible for subacute endocarditis include streptococci, enterococci, coagulase-negative staphylococci, and the HACEK group of organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella species, and Kingella kingae). Clinical presentations of endocarditis range from fever and malaise to symptoms related to systemic emboli (Table 29-1).

The pathologic process of endocarditis requires that several conditions exist to permit infection to grow in the heart and to promote an environment that supports growth on the endocardial surface. For endocarditis to develop, there is first endocardial injury with thrombus formation at the site. Transient or persistent bacteremia allows bacteria to adhere to the injured surface. Infected vegetations result and may fragment and embolize.⁵ The complications of infective endocarditis include congestive heart failure (CHF), paravalvular abscess formation, embolic events to the brain or other organs, sepsis, pericarditis, renal failure, and metastatic abscesses.⁴ The reduction in mortality for infective endocarditis over the past 30 years from 25% to 30% down to 10% to 20% may be largely related to aggressive surgical intervention in cases complicated by CHF, invasive abscesses, and prosthetic valve infections.⁶

Blood cultures are an essential diagnostic tool in infective endocarditis. Three separate sets of blood cultures drawn from different venipuncture sites, obtained over 24 hours, usually identify the organism. Patients with infective endocarditis whose cultures remain negative may have fastidious organisms or may have received intravenous antibiotics before blood samples were drawn. In acute endocarditis, antibiotic therapy should be started after blood cultures have been obtained using strict aseptic technique and optimal skin preparation.² The clinical approach in acute endocarditis includes appropriate antibiotics and monitoring for complications (Display 29-1). The usual course is 6 full weeks of intravenous antibiotics. Patients who do not respond well to standard antibiotic therapy may be referred for surgical valve replacement (Display 29-2).

Echocardiography is frequently used to verify the presence of vegetations on the valves (Fig. 29-2). Transesophageal echocardiography (TEE) provides better resolution and can identify smaller vegetations than transthoracic echocardiography (TTE).⁵ TEE is also useful to identify paravalvular leaks and annular abscesses seen in prosthetic valve endocarditis. Although TEE is more sensitive, some clinicians recommend to obtain TTE first and to perform TEE only if the TTE images are inadequate or suspicion of infective endocarditis remains high and the initial TTE was negative.⁷

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines now recommend antibiotic prophylaxis for patients with prosthetic cardiac valves or rings; previous endocarditis; unrepaired cyanotic congenital heart disease; repaired congenital heart disease with prosthetic material or residual defects adjacent to prosthetic device or patch; and cardiac transplant recipients.⁸

Degenerative changes of the tissue, such as myxomatous degeneration, calcification, and changes associated with Marfan syndrome, can cause valvular dysfunction. Trauma or infection may affect the supportive or subvalvular apparatus. Dilation of the ventricles caused by chronically elevated preloading may dilate an atrioventricular valve opening to the point that the leaflets no longer approximate and the valve becomes incompetent. Coronary heart disease (CHD) and myocardial infarction can affect the papillary muscles of the right and left ventricles, causing either dysfunction caused by ischemia or frank flail of atrioventricular valve leaflets caused by papillary muscle rupture. Systemic diseases such as lupus erythematosus and scleroderma may also cause valvular dysfunction (see Display 29-3).

The predominant cause of mitral stenosis is rheumatic fever. The mitral valve is the valve most often damaged by rheumatic carditis.⁹ Rheumatic fever causes thickening and decreased mobility of the mitral valve leaflets associated with fusion of the commissures and destruction of normal leaflet structure. Other conditions that simulate the physiology of mitral stenosis include left atrial myxoma, ball-valve left atrial thrombus, large left atrial endocarditis vegetations, or cor triatriatum (three atria).¹⁰

The rheumatic process causes the mitral valve to become fibrinous, resulting in leaflet thickening, commissural or chordal fusion, and calcification. As a result, the mitral valve apparatus becomes funnel shaped with a narrowed orifice. Fusion of the mitral valve commissures results in narrowing of the principal orifice, whereas interchordal fusion obliterates the secondary orifices.

Women have mitral stenosis more frequently than men. The normal mitral valve area is 4 to 6 cm². Once the cross-sectional area of the mitral valve is reduced to 2 cm² or less, a pressure gradient between the left atrium and left ventricle occurs. The reduced orifice impedes left atrial emptying. Increased left atrial pressure and dilation occurs along with left atrial hypertrophy in an attempt to maintain normal diastolic flow into the left ventricle. Increased left atrial pressure is transmitted to the pulmonary circuit, resulting
in pulmonary hypertension and pulmonary congestion. Left atrial enlargement may lead to atrial fibrillation and worsening of symptoms related to the loss of atrial kick.¹⁰ Patients have left-sided CHF without left ventricular dysfunction. Mitral stenosis has a sparing effect on the left ventricle. Symptoms of mitral stenosis are usually related to obstruction of the mitral valve rather than ventricular dysfunction. As pulmonary pressure increases, rightsided heart failure may occur.

Mild dyspnea on exertion occurs as the most common symptom of mild mitral stenosis (valve area of 1.6 to 2.0 cm²). As mitral stenosis becomes more severe (valve area of 1 to 1.5 cm²), dyspnea, fatigue, paroxysmal nocturnal dyspnea, and atrial fibrillation may occur. When mitral stenosis becomes severe (valve area of 1 cm² or less), symptoms include fatigue and dyspnea with mild exertion or rest. With advanced mitral stenosis, pulmonary hypertension and symptoms of right-sided heart failure occur (i.e., edema, hepatomegaly, ascites, elevated jugular venous pressure). Chest pain and hemoptysis may also occur. Increased left atrial pressure, atrial fibrillation, and stagnation of left atrial blood flow can result in the formation of mural thrombi, with resultant embolic events, including cerebral vascular accidents. Women who had previously been asymptomatic with mitral stenosis may become symptomatic and even experience severe hemodynamic decompensation during pregnancy due to increased cardiac output and increased heart rate. Tachycardia reduces diastolic filling time and worsens the mitral valve gradient while atrial fibrillation may precipitate pulmonary edema.¹¹

In severe mitral stenosis, on auscultation, there are four typical findings including (1) an accentuated S1; (2) an opening diastolic snap; (3) a middiastolic rumble noted best at the apex (in sinus rhythm), followed by presystolic accentuation; and (4) an increased pulmonic S₂ intensity associated with pulmonary hypertension (Table 29-2).

Patients with mitral stenosis may exhibit malar blush (pink discoloration of the cheeks). Patients with severe mitral stenosis may have weak pulses secondary to reduced cardiac output. The apical pulse is tapping in quality and is nondisplaced. A lower left parasternal lift or heave caused by right ventricular hypertrophy may be present. Cardiac rhythm is often irregularly irregular, indicating atrial fibrillation.

Echocardiography is used in the evaluation of mitral stenosis to (1) quantify the valve area and gradient; (2) quantify the degree of mitral insufficiency; (3) define the degree of left atrial enlargement; (4) assess mitral annular calcification; (5) assess pulmonary artery pressures and degree of pulmonary hypertension; and (6) evaluate right- and left-sided ventricular function. A TEE provides better detail of the mitral valve and better visualization of atrial thrombus than does TTE.¹²

Cardiac catheterization is used less in diagnosis of mitral stenosis as echocardiography techniques improve. Cardiac catheterization does allow for accurate assessment of valve area and can also identify associated mitral regurgitation. For patients with known or suspected CHD, coronary angiography can delineate coronary anatomy. Right heart catheterization can evaluate right heart and pulmonary artery pressures.

Electrocardiography is nonspecific and does not indicate the severity of mitral stenosis. If the patient remains in sinus rhythm and left atrial enlargement has occurred, characteristic P mitrale (broad, bifid P waves in leads II and V₁) may be identified. Right axis deviation and right ventricular hypertrophy may be noted in severe mitral stenosis. Atrial fibrillation is common in patients with long-standing mitral stenosis and is usually coarse in appearance.

Chest radiography correlates with the degree of mitral stenosis. As mitral stenosis becomes more severe, the chest radiograph demonstrates straightening of the left heart border caused by left
atrial enlargement, elevation of the left mainstem bronchus caused by distention of the left atrium, and distribution of blood flow from the lower to upper lobes. Although heart size remains normal, central pulmonary arteries become prominent. Kerley B lines and interstitial edema are often present.

Medical therapy for mitral stenosis is aimed at preventing the complications of systemic embolization and bacterial endocarditis as well as atrial fibrillation if it occurs.⁹ Patients who have asymptomatic mitral stenosis require only antibiotic prophylaxis. Patients with mild pulmonary congestion can be managed with diuretics alone. β-Blockers can be used to reduce heart rate and improve diastolic filling time. When patients have atrial fibrillation, digoxin, β-blockers, or calcium channel blockers can be used for ventricular response rate control. Patients with atrial fibrillation require anticoagulation to prevent thrombus formation in the atrium. Once the patient has symptoms of NYHA functional class III or IV despite adequate medical management, mechanical correction of mitral stenosis by balloon valvuloplasty or surgery should be performed.