Discuss the clinical presentation, laboratory findings, and pathologic changes in the heart throughout the first week in a patient with a myocardial infarction. (<300 words)

An acute myocardial infarction often presents with chest pain, substernal or precordial, which can radiate into the arms (left more than right) and neck. Sometimes there may be nausea and indigestion. Heart failure can be manifested with pallor, diaphoresis, syncope, palpitations, arrhythmias, and sudden death.

Laboratory findings begin in the first few hours, with appearance of CK-MB, which peaks in 6 to 8 hours. Total CK also increases over the first day, and both then disappear in 1 to 3 days. LDH begins to appear at the end of the first day, peaks over 2 to 4 days, then disappears over 1 to 2 weeks. LDH isoenzymes are helpful because LDH-1 increases over LDH-2 (a "flipped" pattern).

The gross appearance of the myocardium is often unremarkable for the first half day, but there is increasing pallor along with increasing central yellow to tan discoloration with a hyperemic border in the next few days. Maximum softness occurs at 3 to 5 days. The lesion is firmer and whiter by the end of the first week. Microscopically, the earliest changes appear in 12 to 24 hours with edema, microhemorrhages, and contraction bands. Over the next few days, there is increasing loss of nuclei and cross striations, infiltration by neutrophils, hemorrhage, and coagulative necrosis. Toward the end of the first week, there is increasing infiltration by mononuclear cells, particularly macrophages.

Complications include arrhythmias with possible sudden death early in the course or congestive failure and shock with larger infarctions. Later, there may be myocardial rupture, usually from days 3 to 7 when the muscle is the softest, with papillary muscle rupture and valvular insufficiency, and possible cardiac tamponade from left ventricular wall rupture. Mural thrombi may form over the infarct and embolize.

Describe clinical and pathologic findings in a patient with rheumatic heart disease. (<250 words)

(Example 1)

Rheumatic heart disease follows infection, usually pharyngeal, with group A beta hemolytic streptococci. Cross-reacting antibodies are formed which produce acute rheumatic fever several weeks following the strep throat. At this point, streptococci cannot be cultured, but the anti-streptolysin O titer is usually elevated. The autoantibodies can produce inflammation of epicardium, myocardium, and endocardium. The pericarditis is usually fibrinous. The myocarditis may occasionally lead to cardiac failure. Microscopically, a peculiar granulomatous inflammatory reaction with characteristic Aschoff nodules is found. The most significant involvement is usually of the heart valves. With acute rheumatic fever, there can be small verrucous vegetations formed at valve closure lines. The valves most often involved include mitral alone, mitral and aortic, aortic alone, and mitral with aortic and tricuspid, in that order.

Rheumatic heart disease manifests years later, often following a number of episodes of acute rheumatic fever in childhood, with valvular disease. The chordae tendineae of the mitral (or tricuspid) valve become thickened and shortened, and the cusps of any affected valve become very fibrotic and thickened. This deformation of the valve can produce stenosis and/or insufficiency. If mitral stenosis predominates, then there is left atrial dilation and left heart failure with pulmonary congestion and edema. With aortic stenosis, there is marked left ventricular hypertrophy and left heart failure. Valvular insufficiency leads to marked cardiac hypertrophy and dilation. Patients may require eventual prosthetic valve placement.

Describe clinical and pathologic findings in a patient with rheumatic heart disease. (<250 words)

(Example 2)

Rheumatic heart disease (RHD) begins as acute rheumatic fever (ARF) following an upper respiratory infection with group A beta streptococci. The clinical diagnosis of ARF is made with modified Jones criteria that include the presence of two major or one major and two minor criteria. Major criteria include carditis, polyarthritis, chorea, subcutaneous nodules, and erythema marginatum. Minor criteria include arthralgia, fever, and previous ARF or RHD. Laboratory findings can include elevated acute phase reactants, leukocytosis, and a characteristic elevation of the anti-streptolysin O titer. A history of a postive strep throat culture also supports the diagnosis. It is best to effectively treat strep throat to prevent this disease. The use of antibiotic therapy has reduced the incidence of ARF in the United States considerably. Strep throat is still common among persons in colder climates and in crowded conditions.

Years following one or more bouts of ARF, the patient develops RHD when one or more valves becomes thickened and calcified, leading to valvular stenosis, insufficiency, or a combination of both. The diastolic rumble of mitral stenosis, the holosystolic murmur of mitral insufficiency, and the systolic ejection murmur of aortic stenosis are the most common auscultory findings. The damaged valves are more prone to develop infective endocarditis. The valve damage leads to congestive heart failure. Mitral stenosis can lead to the appearance of a markedly enlarged left atrium which predisposes to mural thrombosis and potential embolization in the systemic circulation.

Describe clinical and pathologic findings in a patient with rheumatic heart disease. (<250 words)

(Example 1)

Rheumatic heart disease follows infection, usually pharyngeal, with group A beta hemolytic streptococci. Cross-reacting antibodies are formed which produce acute rheumatic fever several weeks following the strep throat. At this point, streptococci cannot be cultured, but the anti-streptolysin O titer is usually elevated. The autoantibodies can produce inflammation of epicardium, myocardium, and endocardium. The pericarditis is usually fibrinous. The myocarditis may occasionally lead to cardiac failure. Microscopically, a peculiar granulomatous inflammatory reaction with characteristic Aschoff nodules is found. The most significant involvement is usually of the heart valves. With acute rheumatic fever, there can be small verrucous vegetations formed at valve closure lines. The valves most often involved include mitral alone, mitral and aortic, aortic alone, and mitral with aortic and tricuspid, in that order.

Rheumatic heart disease manifests years later, often following a number of episodes of acute rheumatic fever in childhood, with valvular disease. The chordae tendineae of the mitral (or tricuspid) valve become thickened and shortened, and the cusps of any affected valve become very fibrotic and thickened. This deformation of the valve can produce stenosis and/or insufficiency. If mitral stenosis predominates, then there is left atrial dilation and left heart failure with pulmonary congestion and edema. With aortic stenosis, there is marked left ventricular hypertrophy and left heart failure. Valvular insufficiency leads to marked cardiac hypertrophy and dilation. Patients may require eventual prosthetic valve placement.

Describe clinical and pathologic findings in a patient with rheumatic heart disease. (<250 words)

(Example 2)

Rheumatic heart disease (RHD) begins as acute rheumatic fever (ARF) following an upper respiratory infection with group A beta streptococci. The clinical diagnosis of ARF is made with modified Jones criteria that include the presence of two major or one major and two minor criteria. Major criteria include carditis, polyarthritis, chorea, subcutaneous nodules, and erythema marginatum. Minor criteria include arthralgia, fever, and previous ARF or RHD. Laboratory findings can include elevated acute phase reactants, leukocytosis, and a characteristic elevation of the anti-streptolysin O titer. A history of a postive strep throat culture also supports the diagnosis. It is best to effectively treat strep throat to prevent this disease. The use of antibiotic therapy has reduced the incidence of ARF in the United States considerably. Strep throat is still common among persons in colder climates and in crowded conditions.

Years following one or more bouts of ARF, the patient develops RHD when one or more valves becomes thickened and calcified, leading to valvular stenosis, insufficiency, or a combination of both. The diastolic rumble of mitral stenosis, the holosystolic murmur of mitral insufficiency, and the systolic ejection murmur of aortic stenosis are the most common auscultory findings. The damaged valves are more prone to develop infective endocarditis. The valve damage leads to congestive heart failure. Mitral stenosis can lead to the appearance of a markedly enlarged left atrium which predisposes to mural thrombosis and potential embolization in the systemic circulation.

Discuss clinical and pathologic findings seen in a patient with either myocarditis or cardiomyopathy. (<250 words)

Cardiomyopathy can be divided into three main classes: dilated, hypertrophic, and restrictive. The clinical and pathologic manifestations of each class can be different.

Dilated cardiomyopathy presents with clinical signs and symptoms of both right and left heart failure. Symptoms of right heart failure include: peripheral edema, liver congestion, and ascites. Left heart failure would manifest with dyspnea from pulmonary congestion, syncope, and orthostatic hypotension. Grossly, both the right and left ventricles are flabby and dilated, while microscopically the myocardium shows bizarre large myocytes and interstitial fibrosis. Dilated cardiomyopathy may be idiopathic (sporadic or familial) or secondary to toxins such as alcohol.

Hypertrophic cardiomyopathy is an idiopathic manifestation of ventricular septal hypertrophy that leads to obstruction of the left outflow tract. This leads to clinical signs similar to aortic stenosis. Sudden death may occur during exercise. On physical examination, one may note a prolonged carotid systolic pulse or laterally shifted PMI from an enlarged left ventricle. Examination of the heart will show an asymmetrical hypertrophy of the ventricular septum, with part of the septum protruding into the outflow tract.

Restrictive cardiomyopathy may be idiopathic or may be secondary to a systemic disease process such as amyloidosis. The amyloid infiltrates the myocardium and can be identified with Congo red stain. The clinical signs include a possible pulsus paradoxus where the measured systolic blood pressure on inspiration is more than 10 torr below the systolic pressure on expiration. Restrictive cardiomyopathy eventually hinders diastolic filling and contractility.

Describe features of non-bacterial thrombotic endocarditis. (<100 words)

(Example 1)

Non-bacterial thrombotic endocarditis is characterized by sterile, small vegetations along the lines of closure of the valves. Malignancies with hypercoagulable states (Trousseau's syndrome) and chronic debilitating diseases all predispose to these lesions. The worst complication associated with this type of endocarditis is embolization. Secondary infection is also possible. Symptoms of the endocarditis are frequently associated with the embolization and can include stroke if the cerebral circulation is involved, myocardial infarction if coronaries are involved, or systemic manifestations from peripheral embolization.

(Example 2)

Non-bacterial thrombotic endocarditis (NBTE) is a disorder that may accomany malignancies or chronic severe disease states in which a hypercoagulable state is present. The vegetations composed of platelets and fibrin form on any of the valve leaflets. They are usually smaller than the vegetations of infective endocarditis, and no infectious agent is present. The vegetations of NBTE are prone to embolize and may cause infarctions.

Discuss clinical and pathologic features of one of congenital heart disease (<250 words)

(Example 1)

Many types of congenital heart disease (CHD) can be categorized as cyanotic or acyanotic. Cyanotic forms of CHD have a right-to-left shunt that mixes arterial oxygenated and venous unoxygenated blood. A classic example is tetralogy of Fallot, with pulmonic stenosis/atresia, ventricular septal defect, overriding aorta, and right ventricular hypertrophy. Another is truncus arteriosus which occurs when the spiral septum does not completely separate the aortic and pulmonic outflows. Transposition of the great vessels from failure of truncal and aortopulmonary septa formation results in parallel circulations, since the aorta arises from right ventricle and pulmonic trunk from left ventricle, and is incompatible with life unless a shunt exists. Cyanotic CHD must be surgically corrected early.

Acyanotic CHD includes defects that result in a left-to-right shunt. These include endocardial cushion defects, atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). ASD's and small VSD's may not be symptomatic. About half of VSD's, including most of the 10% in the muscular septum, will spontaneously close. These defects predispose the patient to infective endocarditis. Larger, more severe defects such as VSD's in the membranous septum, may result in shunting that produces pulmonary hypertension so severe that eventually there is shunt reversal (Eisenmenger's complex). Many of these defects are easily correctible with surgery.

(Example 2)

Congenital heart disease (CHD) can take many forms. CHD can be an isolated single defect or consist of multiple defects. CHD is often seen with malformation syndromes or chromosomal abnormalities. For example, endocardial cushion defects are frequently seen with Down syndrome (trisomy 21). Heart defects may be found in utero with ultrasound or diagnosed soon after birth. Fetal hydrops can be a consequence. Severe defects such as hypoplastic left heart syndrome, in which there is reduction in left ventricular/left atrial size along with hypoplasia or atresia of mitral and aortic valves, are generally not survivable and cardiac transplantation can be considered. With total anomalous pulmonary venous return (TAPVR), the pulmonary veins do not enter the left atrium and drain to right atrium or some vein draining to the right atrium. Patients with TAPVR can survive, but right heart failure eventually occurs. Some isolated defects, such as an atrial septal defect or small ventricular septal defect, are not severe and the patient may live a normal life, because the shunt is not great. A murmur can be heard with auscultation. However, cardiac defects predispose a patient to infective endocarditis. Some defects are not apparent or symptomatic until later in adult life. For example, a bicuspid aortic valve functions near normally, but can calcify and become stenotic in middle age. An aortic coarctation with narrowing of the aorta past the ductus, leads to differences in upper and lower extremity pulse pressures and to enlarged collaterals.

Discuss clinical and pathologic features of one of rheumatic heart disease (<250 words)

(Example 1)

Rheumatic heart disease results from pharyngitis caused by group A beta hemolytic streptococci. The streptococcal organisms elicit an immune response with cross-reactivity of antibodies to cardiac tissues (cell wall M-proteins). The result is acute rheumatic fever (ARF) that occurs 1 to 3 weeks following the pharyngitis. No organisms are present, but the anti-streptolysin O titer is elevated. There can be a fibrinous pericarditis, a myocarditis with Aschoff nodules and Anitschkow cells, and an endocarditis with small verrucous vegetations on valve closure margins. These vegetations rarely embolize.

More severe and repeated bouts of ARF predispose to development of rheumatic heart disease, with onset of symptoms years later as a consequence of valvular scarring. The most commonly affected valve, the mitral, shows thickened and shortened chordae tendineae, and the valve itself becomes fibrotic, often with a classic "fish mouth" shape with both insufficiency and stenosis. The mitral and aortic, aortic, or mitral, aortic, and tricuspid valves can also be involved, in that order. Mitral stenosis can lead to left atrial dilation with mural thrombosis as well as pulmonary edema. Aortic involvement can lead to left ventricular hypertrophy. The damaged valves predispose the patient to infective endocarditis.

(Example 2)

Rheumatic heart disease is preceded by bouts of acute rheumatic fever (ARF) which is generally seen in children. Acute rheumatic fever can be diagnosed with Jones criteria, including 2 major or 1 major and 2 minor criteria. Major criteria include carditis, polyarthritis, Sydenham's chorea, erythema marginatum, and subcutaneous nodules. Minor criteria include fever, arthralgia, previous ARF, or elevation of the sed rate or C reactive protein. Supporting evidence for ARF includes a history of recent streptococcal infection, typically a throat culture with group A beta hemolytic Streptococcus. An elevated anti-streptolysin O titer is present.

Patients with ARF rarely die, unless there is a severe myocarditis. Many years following ARF, adults can present with congestive heart failure, and heart murmurs may be present, indicative of valvular damage from ARF. Valve involvement includes mitral, mitral and aortic, aortic, and aortic, mitral, and tricuspid valves. The pulmonic valve is rarely affected. Valves become fibrotic with either stenosis, insufficiency, or both as a result. The valvular damage requires that patients receive antibiotic prophylaxis before procedures that could produce a bacteremia, because infective endocarditis could result. Worsening CHF may require that the diseased valve(s) be replaced with a prosthesis.