Rheumatic Heart Disease

1 - Acute rheumatic fever - Schematic

The inflammatory lesions of acute rheumatic fever affect all three parts of the heart: endocardium (especially valves), myocardium, and epicardium. Endocardial involvement leads to the formation of vegetations (called verrucae) along the line of closure of the affected valve. The mitral valve is commonly affected, though in many cases multiple valves are involved. Myocardial involvement takes the form of myocarditis with widely disseminated focal inflammatory lesions (called Aschoff bodies) scattered about in the interstitium, often in a perivascular location. The pericarditis of acute rheumatic fever begins with similar inflammatory lesions of the epicardial connective tissues, and, in many cases, is associated with a fibrinous or serofibrinous exudate. The pericarditis of acute rheumatic fever usually resolves without lesions, but, in rare cases, it can result in a constrictive pericarditis with dense fibrous adhesions that bind the parietal to the visceral pericardium. Questions: What is the significance of the history of rheumatic fever as a child? What are the primary symptoms of acute rheumatic fever? The patient's childhood acute rheumatic fever (ARF) is the cause of her present day mitral stenosis (MS). Postrheumatic changes account for most cases of MS. The major clinical manifestations of ARF are migratory polyarthritis, carditis, subcutaneous nodules, erythema marginatum, and Sydenham chorea. The attack rate for ARF is approximately 3% following infection with group A beta-hemolytic streptococci.

Aschoff bodies

2 - Heart, acute rheumatic fever - Low power

This is a section of myocardium from a young patient with severe symptomatic acute rheumatic fever (ARF). There are widespread focal inflammatory lesions in the myocardium, predominantly in the interstitium. Many lesions are in perivascular connective tissue. Some form of cardiac injury has been extremely common in recent ARF outbreaks. Myocarditis may be subclinical or may manifest as progressive heart

failure.

Questions: What is the etiology of these inflammatory lesions? A hypersensitivity reaction induced by group A streptococci. Following a streptococcal infection (pharyngitis), antibodies to streptococcal M proteins develop. These antibodies cross-react with cardiac glycoprotein antigens. Explain their predominantly interstitial location. The glycoproteins with which the antibodies react are located predominantly within interstitial connective tissue.

Aschoff giant cell Aschoff cells Aschoff body

3 - Heart, Aschoff body - High power

Inflammatory lesions are found widely scattered in the valves, pericardium, and myocardium of patients who die of acute rheumatic fever (ARF). The cellular aggregate seen above is typical of the myocardial lesions found, and is called an Aschoff body (AB). The typical AB contains plump histiocytes (Aschoff cells), some of which are multinucleated (Aschoff giant cells). The predominance of histiocytic cells, some epithelioid, suggests that the AB is a form of granuloma. Aschoff bodies may also contain lymphocytes and plasma cells. A central zone of fibrinoid necrosis is seen in Aschoff bodies in early stages of ARF. Widespread fibrinoid necrosis and inflammation of the valve substance leads to damage of the overlying endothelial cells. With endothelial damage, thrombosis is initiated, and vegetations form along the closing edge of the valve where the leaflets slam together. This endocardial damage heals with dense fibrous scars, which progress over time to look like the valves in the images that follow. Questions: Is the cardiac dysfunction in patients with ARF attributable to valve dysfunction or myocardial damage? Myocardial damage. When does valvular damage become an issue for the patient? Years after the initial episode of ARF, when valvular scarring and deformity have imposed an excessive hemodynamic load on the heart.

Which valves are most likely to suffer damage and why? For unknown reasons, mitral and aortic valves are most commonly affected.

Stenotic mitral valve orifice Atrial thrombus

4 - Heart, rheumatic mitral valve, atrial changes - Gross, atrial endocardial surface
The mitral valve has been reduced to a narrow orifice. The left atrium is markedly dilated. Thrombi have formed on the atrial wall. Questions: What is the basis of thrombosis in this setting? In the dilated atrium with a stenotic mitral valve, the blood stagnates. Hence, stasis is a factor in thrombogenesis. In addition, there may be endocardial damage resulting from regurgitant jets; this, in turn, can also predispose to thrombosis. What EKG change might you find in this patient? Atrial fibrillation.

Why is this patient feeling so short of breath? Why is her left atrium enlarged? Why are her lungs abnormal? Why does she get short of breath at night? Does she have heart failure? What kind? The patient is feeling short of breath because she has severe mitral stenosis. There is fusion of the commissures and fibrotic closure of the mitral valve. As the cross-sectional area of the orifice of the affected valve grows smaller, there is progressive obstruction to blood flow from the left atrium to the left ventricle. Valve orifices smaller than 2 cm2 are usually symptomatic. Blood begins to back up first into the left atrium, which becomes enlarged. Pressure rises in the atrium and pulmonary vascular tree. Elevated pulmonary vascular pressure leads to pulmonary edema and explains her dyspneic symptoms. Eventually, the pressure backs up into the right heart. With longstanding severe mitral stenosis, permanent structural changes in the pulmonary vasculature may limit flow even after the valve is fixed. She has left heart failure.

Thickened mitral valve Fibrotic fused chordae

5 - Heart, rheumatic mitral valve, chordae changes - Gross

The fibrotic thickening of the valve leaflets can also be seen in this view of a mitral valve from a patient with postrheumatic mitral stenosis. This image also shows fusion and thickening of the chordae tendineae. Questions: What is the significance of atrial fibrillation in this patient? Atrial fibrillation is a dire consequence in patients with aortic as well as mitral stenosis. In the normal heart, left atrial contraction contributes little to left ventricular filling. In the case of mitral stenosis, the left atrium has a major responsibility for pumping blood across the tiny mitral orifice and filling the left ventricle. Atrial fibrillation takes away almost all of the beneficial effects of atrial contraction during diastole; cardiac output can acutely drop, precipitating acute pulmonary edema. Atrial fibrillation also predisposes to the formation of thrombi, as seen in the previous image.

Fused commissures Narrowed orifice

6 - Heart, rheumatic heart disease, rheumatic aortic stenosis - Gross

This valve depicts postrheumatic aortic stenosis. The severe cuspal thickening and fusion of the commissures have distorted the three cusps of the valve so that they appear as a single fused unit, fixed in an open but stenotic configuration. This valve would generate a complex murmur with components of both aortic stenosis (AS) and aortic insufficiency (AI).

Dilated right ventricle Stenotic aortic valve Dilated left atrium Stenotic mitral valve Hypertrophy of left ventricle

7 - Heart, rheumatic mitral and aortic stenosis - Gross, longitudinal section, cut surface
Both the mitral and the aortic valves are affected. Severe, long-standing, aortic stenosis has resulted in left ventricular hypertrophy. The severe left atrial dilation is a result of mitral stenosis. Questions: What is a possible explanation for the episode of syncope and temporary unilateral blindness in this patient? Atrial thromboemboli are a major potential complication of mitral stenosis. The episode of syncope and temporary unilateral blindness was probably an embolic event, the embolus arising from a left atrial thrombus.

Hemosiderinladen macrophages Congested capillaries in alveolar walls

8 - Lung, hemosiderin-laden macrophages - High power

Chronic left heart failure of many different etiologies is often associated with elevated left atrial pressure and elevated pulmonary venous and pulmonary capillary pressure. With mitral stenosis, left atrial pressures can be particularly high. When alveolar capillary pressure exceeds plasma oncotic pressure, fluid leaks out into the alveoli, and the patient develops pulmonary edema. With severe chronic pulmonary congestion, there can also be intermittent alveolar hemorrhage. These hemosiderin-laden macrophages are the residue of prior alveolar hemorrhage; they represent microscopic evidence of chronic severe left heart failure. Review: Hemodynamic Disorders Introductory Images 5 and 6 (lung, chronic passive congestion) and Hemodynamic Disorders Case 1, Images 10 and 12 (lung, chronic passive congestion). Questions: How would the microscopic picture differ in a patient with severe acute left heart failure? The patient would have acute passive congestion without hemosiderin deposition or alveolar septal fibrosis. Review: Hemodynamic Disorders Introductory Images 2 and 3 (lung, acute passive congestion and edema) and Hemodynamic Disorders Case 1, Image 11 (lung, acute congestion and edema).

Valve leaflet Atrial vegetation Ventricular vegetation Dark blue line of bacteria Abscess burrowing into LV

9 - Heart, bacterial endocarditis - Very low power

This is a mitral valve vegetation in bacterial endocarditis. There are destructive vegetations on both sides of the valve and an abscess-like process is burrowing into the myocardium. The bacteria are visible as a dark blue zone on the surface of the vegetations. Review: Hemodynamic Disorders Case 2, Images 6 and 7 (mitral valve, rheumatic heart disease/infective endocarditis). Questions: What would most likely be the causative organisms? What should be done to prevent endocarditis? List three general factors that predispose to endocarditis. Endocarditis is a possibility any time a valve is hemodynamically abnormal. In previously abnormal hearts, as in this case, streptococci, most often S viridans, are often causative. Staphylococci can also cause endocarditis and are often identified in cases of acute endocarditis. While most cases of infective endocarditis are due to gram-positive bacteria, gram-negative organisms, fungi, and a long list of other organisms have been reported. Patients with abnormal heart valves and congenital shunts should have antibiotic prophylaxis before procedures likely to produce bacteremia. Conditions that predispose to endocarditis include: (1) abnormal flow (hemodynamically abnormal valves, congenital shunts, etc), (2) bacteremia (instrumentation, IV drug abuse,

surgery), and (3) abnormal immune response (neutropenia, immunodeficiency, immunosuppression).

Zone of fibrin Zone rich in inflammatory cells Bacteriarich zone

10 - Heart, bacterial endocarditis - High power

This image shows the surface of the vegetation. The vegetation is composed of fibrin, inflammatory cells, and bacteria. The bacteria appear as a blue zone on the surface of the vegetation. Review: Hemodynamic Disorders Case 2, Images 7 and 8 (heart, mitral valve, infective endocarditis). Questions: What are the components of a vegetation? What are the predisposing conditions for their formation? A vegetation is an intracardiac thrombus. They often form on the valves. They form when the valves are hemodynamically abnormal and/or there is injury to the endocardium. This may occur due to diseases such as rheumatic fever, lupus, or congenital heart diseases. Hypercoagulable states sometimes associated with chronic illnesses can also predispose to cardiac vegetations.

Aortic valve cusps Vegetations Mitral valve

11 - Heart, nonbacterial thrombotic endocarditis - Gross

This is an example of nonbacterial thrombotic endocarditis on the aortic valve. The vegetations are small tan masses located along the lines of closure. This type of vegetation is usually small and loosely attached to the valve leaflet. Because they are loosely attached to the valve, they can break off and cause embolic phenomena. Occasionally, they can become infected with circulating bacteria, leading to infective endocarditis. Questions: What are some clinical conditions associated with nonbacterial thrombotic endocarditis? Chronic illness, malignancies, trauma to the valves from an indwelling catheter. Most of these seem to cause a hypercoagulable state.