Heart, Pericardium, and Blood Vessels

Hypertrophic Cardiomyopathy

• Myocardial disease characterized by left ventricular hypertrophy in the absence of systemic hypertension, aortic valve stenosis, or overt infiltrative diseases

• Associated with normal systolic function and diastolic dysfunction; systolic dynamic obstruction of the left ventricular outflow tract occurs in 25%

• Estimated prevalence of unexplained left ventricular hypertrophy on echocardiography compatible with a diagnosis of hypertrophic cardiomyopathy is 1 in 500

• Clinical presentation varies from asymptomatic to congestive heart failure, syncope, dyspnea, chest pain, and sudden death

• Associated with sudden death in athletes during exercise

Dilated Cardiomyopathy

• Most common cause of congestive heart failure in young patients and one of the leading indications for heart transplantation

• Patient presentation related to systolic dysfunction and progressive cardiac chamber enlargement with secondary mitral or tricuspid regurgitation and arrhythmias

• Usually idiopathic, but can be caused by toxins, drugs, and metabolic derangements; can be associated with myocarditis, alcohol abuse, pregnancy, familial incidence, nutritional deficiencies, neuromuscular disorders, and endocrine abnormalities

• Idiopathic dilated cardiomyopathy is a diagnosis of exclusion; heart failure is out of proportion to the presence of any concomitant coronary artery disease, systemic hypertension, or valvular heart disease

Restrictive Cardiomyopathy

• Patients present with symptoms associated with diastolic dysfunction, reduced diastolic volume, and normal systolic function

• Causes include: (a) endomyocardial scarring (idiopathic restrictive cardiomyopathy, endomyocardial fibrosis, Löffler syndrome, and endocardial fibroelastosis), (b) storage disease (hemochromatosis, glycogen storage disease, Fabry disease), or (c) myocardial infiltrate (amyloidosis, sarcoidosis, and radiation fibrosis)

• Idiopathic restrictive cardiomyopathy

  • Rare entity with autosomal dominant transmission and associated with skeletal myopathy

• Endomyocardial fibrosis

  • Recognized as a tropical disease, occurring most often in sub-Saharan Africa, affecting children and young adults

• Löffler syndrome (Löffler endomyocarditis and endocarditis parietalis fibroplastica)

  • Occurs in older patients and in men (more often than women) who live in the temperate zone

  • Often associated with reactive or neoplastic eosinophilia

• Endocardial fibroelastosis

  • Classified as primary or secondary; secondary form is much more common

  • Primary form may be related to intrauterine myocardial injury with left ventricular dilation

  • Secondary form is most often associated with congenital heart disease involving the left ventricle such as aortic stenosis, hypoplastic left heart syndrome, and coarctation of the aorta

• Hemochromatosis

  • Primary hemochromatosis is an autosomal recessive disorder in which excessive iron absorption leads to iron overload

  • Secondary hemochromatosis is associated with ineffective erythropoiesis, chronic liver disease, or multiple blood transfusions

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

• Inherited heart muscle disease that may present with arrhythmias, heart failure, or sudden death

• Arrhythmias are usually of right ventricular origin associated with global or regional dysfunction of the right ventricle

• Increasingly recognized as an important cause of sudden cardiac death

• Clinical diagnosis is based on diagnostic criteria originally proposed in 1994 by the European Society of Cardiology and Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology and revised in 2010

Hypertrophic Cardiomyopathy

• Left ventricular hypertrophy, which may be symmetrical or asymmetrical

• Asymmetrical forms include thickening of subaortic ventricular septum (which is at least 1.5 times that of the left ventricular free wall), midventricular segment, or apical region

• Systolic anterior motion of the anterior mitral leaflet leads to a contact lesion in the septum, seen as an area of endocardial fibroelastosis

• Mechanical trauma to the anterior mitral leaflet and chordae results in thickening and fibrosis of the valve

• Foci of small scars often observed in the septum do not correspond to areas supplied by the major epicardial coronary arteries

Dilated Cardiomyopathy

• Increased cardiac weight with dilatation of the left or both ventricles, often with four-chamber dilation

• Normal or decreased left ventricular wall thickness due to chamber dilation

• Mural thrombi may be present

• Endocardial thickening is focal and may be related to organized thrombus or jet lesions from valvular regurgitation

• Valves are normal, or may exhibit secondary changes associated with insufficiency such as dilated annulus or thickening of free edges

• Coronary arteries are normal, or may exhibit mild atherosclerotic change within limits expected for the patient’s age

Restrictive Cardiomyopathy

• Idiopathic restrictive cardiomyopathy

  • Firm myocardium with normal left ventricular wall thickness

  • Normal left ventricular cavity size

  • Often biatrial dilation

  • Endocardium is not grossly thickened

• Endomyocardial fibrosis

  • Thick, white scarring of the left ventricular endocardium at the inflow tract and apex with encasement of papillary muscles and subvalvular apparatus, resulting in valvular regurgitation

  • Fibrosis of right ventricular apex seen in half of the cases

• Löffler syndrome

  • Fibrosis of endocardium, characteristically with large mural thrombi at the inflow tract and apex of both ventricles

• Endocardial fibroelastosis

  • Left ventricle is usually contracted but may be dilated

  • Diffusely thickened pearly white endocardium that may obscure trabeculae carneae

• Hemochromatosis

  • Left ventricular hypertrophy with rusty-brown discoloration of myocardium

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

• Replacement of right ventricular myocardium by adipose and fibrous tissue

• In early disease, these changes are segmental, and present in the apex, right ventricular inlet, and right ventricular outflow tract

• Progressive loss of myocardium leads to diffuse involvement with right ventricular dilation and localized ventricular aneurysms

• Left ventricular involvement usually minor and seen in advanced stages with preferential involvement of the posterolateral wall; less frequently there is equal biventricular involvement

Hypertrophic Cardiomyopathy

• Hypertrophy and disarray of myocytes with interstitial fibrosis ( Figure 18.1A and B )

  

• Disarray involves at least 10% of the myocardium and is maximal in the middle or deeper region of the interventricular septum

• Intramural small coronary arteries are dysplastic with narrowed lumens, due to medial hyperplasia with or without intimal thickening (see Figure 18.1C )

• Replacement fibrosis and myocardial scars

• Should not be diagnosed on the basis of a right ventricular endomyocardial biopsy as disarray is common in the trabeculae of the right ventricle

Dilated Cardiomyopathy

• Histopathologic findings are nonspecific

• Myocyte hypertrophy with enlarged hyperchromatic nuclei, mixed with myocyte atrophy and degeneration

• Varying extent of interstitial fibrosis sometimes associated with sparse inflammatory cell infiltrates

Restrictive Cardiomyopathy

• Idiopathic restrictive cardiomyopathy

  • Diffuse interstitial fibrosis that surrounds individual myocytes

• Endomyocardial fibrosis

  • Hyalinized collagen scarring of the endocardium with few mesenchymal cells

  • Fibrosis extends into the inner myocardium

• Löffler syndrome

  • Three stages have been described

  • Once the fibrotic stage is reached, the distinction between endomyocardial fibrosis and Löffler syndrome based on pathologic features may not be possible

    • Acute necrotic stage: shows intense eosinophilic infiltrate in myocardium with arteritis

    • Thrombotic stage: characterized by superimposed thrombosis on thickened endocardium and thrombi in intramyocardial vessels

    • Fibrotic stage: shows thick endocardium with loosely arranged vascularized fibrous tissue in the deepest layer; vessels show intimal thickening and perivascular fibrosis

• Endocardial fibroelastosis

  • Diffuse fibrosis of endocardium with prominent elastic fibers

• Hemochromatosis

  • Hemosiderin deposition within myocytes ( Figure 18.2A )

    

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

• Transmural extensive fatty replacement of the myocardium with fibrosis and myocyte atrophy ( Figure 18.3A )

  

• Lymphocytic infiltrates associated with myocyte damage may be present

Dilated Cardiomyopathy

• Electron microscopy: myocyte degeneration with myofibrillar loss in some myocytes and myocyte hypertrophy in others; dilation of T tubules, increased number of mitochondria, and increased glycogen, lipid vacuoles, myelin figures, and phagolysosomes

Toxic Cardiomyopathy

• Grading of endomyocardial biopsies for anthracycline-induced cardiotoxicity requires at least three pieces of myocardium and examination of 10 plastic-embedded semithin sections stained with toluidine blue

  • Grade 0: normal myocardium by light and electron microscopy

  • Grade 1: occasional isolated myocytes with myofibrillar loss or vacuolar degeneration (distended sarcoplasmic reticulum and T-tubular system) involving less than 5% of cells

  • Grade 1.5: scattered, single myocytes with myofibrillar loss or vacuolar degeneration affecting 5% to 15% of myocytes

  • Grade 2: clusters of affected myocytes affecting 16% to 25% of cells

  • Grade 2.5: 26% to 35% of myocytes affected

  • Grade 3: diffuse myocyte damage affecting more than 35% of cells; myocyte cell necrosis (total loss of contractile elements, loss of organelles, and mitochondrial and nuclear degeneration)

• Chloroquine and hydroxychloroquine cardiotoxicity

  • Electron microscopy: Sarcoplasm contains numerous myelin figures, curvilinear bodies, and secondary lysosomes

Metabolic Cardiomyopathy

• Fabry disease

  • Electron microscopy: electron-dense intracellular lamellar bodies or myelin figures corresponding to the accumulation of glycolipids

• Mitochondrial cardiomyopathy

  • Electron microscopy: proliferation of mitochondria, which are pleomorphic in size and shape and have abnormal cristae and paracrystalline inclusions

• Glycogen storage disease

  • Electron microscopy: markedly increased sarcoplasmic free glycogen; glycogen in lysosomes; vacuoles containing autophagic material

Hypertrophic Cardiomyopathy Versus Metabolic Cardiomyopathy

• Myocyte sarcoplasmic vacuolization or granularity should raise suspicion for storage disease and mitochondrial abnormalities, which cause phenotype similar to hypertrophic cardiomyopathy; electron microscopy is necessary for complete evaluation

• Fabry disease due to mutations in lysosomal α-galactosidase A

• Adult-onset glycogen storage disease with left ventricular hypertrophy and Wolff-Parkinson-White syndrome due to mutations in the γ2 regulatory subunit of the adenosine monophosphate–activated protein kinase (PRKAG2)

• X-linked hypertrophic cardiomyopathy (Danon disease) with skeletal myopathy and mental retardation due to mutations in lysosome-associated membrane protein (LAMP2)

• Mitochondrial cardiomyopathy due to mutations in mitochondrial DNA

Symmetrical Hypertrophic Cardiomyopathy Versus Physiologic Hypertrophy in Response to Exercise (“Athlete’s Heart”)

• Differentiation of physiologic cardiac hypertrophy induced by athletic training from those with structural disease may require extensive non-invasive and invasive clinical screening tests

Hypertrophic Cardiomyopathy Versus Age-Related Subaortic Bulging of the Interventricular Septum (Sigmoid or Catenoid Septum)

• Anatomic variant commonly seen in elderly patients, which may be accentuated by concomitant systemic hypertension, simulating asymmetrical hypertrophic cardiomyopathy

Hypertrophic Cardiomyopathy Versus Diseases Associated With Left Ventricular Hypertrophy in Infants and Young Children

• Infiltrative cardiomyopathies including type II Pompe disease, Hunter disease, and Hurler disease

• Noonan syndrome resulting from PTPN11 (protein- tyrosine phosphatase, nonreceptor type 11) gene mutation presenting with cardiofacial abnormalities, including pulmonic valve stenosis and atrial septal defect

  • Infants of insulin-dependent diabetic mothers

Restrictive Cardiomyopathy Versus Constrictive Pericarditis

• Diastolic filling is restricted in constrictive pericarditis by rigid, thickened pericardium with fibrous pericardial adhesions

• Endomyocardial biopsy has proved useful in establishing diagnosis of infiltrative cardiomyopathies

• A normal endomyocardial biopsy would direct the clinical workup to reevaluate the pericardium

Lymphocytic Myocarditis

• Frequently asymptomatic, or having a subclinical course that later progresses to dilated cardiomyopathy

• May present as chest pain, unexplained acute onset of congestive heart failure, ventricular arrhythmias, or sudden death

• Viruses are the most common cause of myocarditis, particularly in children

Giant Cell Myocarditis

• Typically affects young and middle-aged adults

• Most patients present with rapidly progressive heart failure, often with refractory ventricular arrhythmia, rarely with heart block or chest pain mimicking myocardial infarction

• Poor prognosis and often fatal if untreated

Eosinophilic Myocarditis

• Hypersensitivity myocarditis

  • Believed to be an allergic delayed hypersensitivity reaction to diverse pharmacologic drugs and nutritional supplements

  • Reported complication of smallpox vaccination in young individuals

  • Associated with prolonged continuous administration of vasopressors, particularly dobutamine

  • Signs and symptoms are nonspecific and include typical allergic reaction (fever, rash, and blood eosinophilia), arrhythmias, sudden death, and congestive heart failure

• Acute necrotizing eosinophilic myocarditis

  • Thought to represent the most severe form of hypersensitivity myocarditis but can also be associated with viral infections, cancer, connective tissue diseases, and Churg-Strauss syndrome

  • Presents with fulminant heart failure and can be rapidly fatal

• Hypereosinophilic syndrome

  • Characterized by eosinophilia in the blood and bone marrow and tissue infiltration with eosinophils in multiple organs

  • Predominantly affects males between 20 and 50 years old

  • Cardiac involvement is most common and can present with restrictive physiology

  • Mural thrombi are frequently formed and can lead to systemic embolization

Lymphocytic Myocarditis

• Focal to diffuse interstitial mononuclear cell infiltrate, predominantly lymphocytes, with associated myocyte necrosis ( Figure 18.4 )

  

• In endomyocardial biopsies, sparse lymphocytic infiltrate not associated with myocyte damage is diagnosed as borderline myocarditis, based on the Dallas criteria

• Repeat biopsies showing persistent lymphocytic infiltrate is called persistent myocarditis , a less intense infiltrate is resolving myocarditis , and absence of inflammatory infiltrate is resolved myocarditis

Giant Cell Myocarditis

• Multifocal-to-diffuse infiltrate consisting of lymphocytes and macrophages with multinucleated giant cells ( Figure 18.5A and B )

  

• Eosinophils are often present

• Occasional poorly formed granuloma-like structures may be seen

• Geographic areas of myocyte damage or necrosis with varying degrees of fibrosis are evident on low magnification

Eosinophilic Myocarditis

• Patchy interstitial and perivascular infiltrates consisting of many eosinophils mixed with histiocytes, lymphocytes, and plasma cells

• May involve the endocardium and epicardium

• Lesions are all of the same age

• Usually only minimal myocyte necrosis and interstitial fibrosis

• Acute necrotizing eosinophilic myocarditis shows intense and diffuse infiltrates with extensive myocyte necrosis

• Hypereosinophilic syndrome also shows eosinophilic infiltrates with myocyte necrosis

• Charcot-Leyden crystals can be seen

Lymphocytic Myocarditis

• Myocarditis associated with infectious agents including Lyme disease, leptospirosis, typhoid fever, syphilis, chlamydia and rickettsial infections, and AIDS

• Myocarditis associated with collagen vascular disease and autoimmune disorders

• Myocarditis associated with cancer immunotherapies including immune checkpoint inhibitors

• Toxic myocarditis

  • Includes toxin-induced myocardial injury (e.g., diphtheria exotoxin) and dose-related, direct toxic effects of drugs on the myocardium

  • Small foci of myocardial necrosis with contraction bands can be seen in patients who are on vasopressor agents, have elevated endogenous catecholamines, or are cocaine abusers

  • Inflammatory infiltrates are predominantly macrophages

  • Lesions are of varying ages

• Microbiologic, serologic, and clinical correlation help make the diagnosis

Giant Cell Myocarditis

• Sarcoidosis

  • Dense fibrous scars toward the base of the heart involving the septum more heavily than the free wall of the left or right ventricle can be seen in sarcoidosis

  • Characterized by well-formed granulomas and fibrosis with few or no eosinophils ( Figure 18.6 )

    

  • Generally lacks active myocyte necrosis

  • Rarely present as isolated cardiac involvement; lymph node or lung involvement almost always present

• Rheumatic myocarditis

  • Endocardial and interstitial Aschoff granulomas with giant cells

• Infectious granulomatous diseases

  • Giant cells may be seen in tuberculosis, cryptococcosis, syphilitic myocarditis, or measles myocarditis

  • Myocardial involvement is rarely isolated

  • Special stains for microorganisms should be performed

• Foreign-body reaction

  • Birefringent material under polarized light

  • Myocardial reaction to pacemaker leads, assist devices

Eosinophilic Myocarditis

• Parasitic infestation with peripheral eosinophilia (e.g., Trichinella species)

Neutrophilic Infiltrates

• Usually seen in systemic bacterial and fungal infections in the immunocompromised host or spread by direct extension

  • Focal neutrophilic infiltrates with myocyte necrosis and microabscesses

• Myocardial infarction

  • A zone of necrosis with neutrophilic infiltration at the periphery corresponding to a territory supplied by an epicardial coronary artery

Hyalinized Collagen

• May appear similar to amyloid on hematoxylin and eosin-stained sections but exhibits periodic banding pattern on polarization

• Congo red may have false-positive birefringence in collagen if staining method is not optimal

• Blue collagen fibers can be differentiated from the blue-gray hue of amyloid on Masson trichrome stain

Giant Cell Myocarditis

• Poorly formed granulomas with greater extent of myocyte necrosis and increased eosinophils compared with sarcoidosis

• Appears clinically distinct with a more fulminant course and shorter time from symptom onset to death or transplantation

Infectious Myocarditis

• Infectious etiology should be excluded by performing stains for fungi and mycobacteria

Myocardial Infarction

• Scarring and thinning of the ventricle may be mistaken for healed myocardial infarcts, but normal coronary arteries should rule out ischemic heart disease

Stenotic Valves With or Without Regurgitation

• Diffuse fibrous thickening with a variable amount of calcification

• No valvular tissue loss, perforations, or vegetations

• No valvular tissue excess

• Fusion of valve commissures

• Chordae tendineae are fibrotic, fused, and shortened

• Attached papillary muscle is normal

Purely Regurgitant Valves

• Usually mild and focal fibrous thickening and absent calcification

• Perforations or vegetations may be present

• Excess valvular tissue may be present

• No commissural fusion

• Chordae tendineae are elongated or ruptured

• Attached papillary muscle may be ruptured

Mitral Valve

• Mitral stenosis

  • Congenital

  • Acquired

    • Postinflammatory and rheumatic

    • Mitral annular calcification

• Mitral regurgitation

  • Congenital

  • Acquired

    • Mitral valve prolapse

    • Postinflammatory and rheumatic

    • Mitral annular calcification

    • Infective endocarditis

    • Ruptured papillary muscle

    • Papillary muscle dysfunction secondary to ischemia and infarct

    • Distortion of left ventricular geometry

Aortic Valve

• Aortic stenosis

  • Congenital

  • Acquired

    • Unicuspid aortic valve

    • Calcification of bicuspid aortic valve

    • Senile calcific aortic stenosis

    • Postinflammatory and rheumatic

• Aortic regurgitation

  • Congenital

  • Acquired

    • Bicuspid aortic valve

    • Postinflammatory and rheumatic

    • Infective endocarditis

    • Aortic dilation and aneurysm

    • Aortic dissection

Rheumatic Heart Disease

• Findings of acute rheumatic fever include pericardial friction rubs, weak heart sounds, tachycardia, and arrhythmias; usually occur 10 days to 6 weeks after the pharyngitis episode

• Findings in chronic rheumatic heart disease include evidence of valvular stenosis or regurgitation, congestive heart failure, arrhythmias, thromboembolic complications, and infective endocarditis; usually occur 20 to 25 years after the acute disease

Mitral Valve Prolapse

• Prevalence is estimated at 2% to 3% of the population, with equal distribution among men and women

• Most patients do not develop symptoms

• Prolapse occurs most commonly in the middle scallop of the posterior mitral valve leaflet as identified on echocardiography

• Commonly idiopathic

• Known association with connective tissue disorders including Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum

• Men appear to have a higher incidence of complications, which include severe mitral regurgitation, infective endocarditis, thromboembolic events, and sudden death

Calcific Aortic Valve Disease

• Senile calcific aortic stenosis is more common in males, with a peak incidence in the seventh and eighth decades of life

• Calcification of a congenital bicuspid aortic valve peaks in the fifth and sixth decades of life

• Calcific disease of the aortic valve results in left ventricular hypertrophy, with symptoms including angina, syncope, and congestive heart failure

Mitral Annular Calcification

• More common and more severe in women, primarily those older than 60 years

• Associated with aging, hypertension, diabetes, aortic stenosis, chronic renal disease, and atherosclerosis

• Often asymptomatic, but potential complications include acquired mitral stenosis or regurgitation, conduction system disturbances, endocarditis, and systemic embolism

Pure Aortic Regurgitation

• Pure aortic insufficiency can be due to lesions of the valve or the aorta

• Aortic root dilation is currently the most common cause of aortic insufficiency, followed by congenital bicuspid valve associated with ascending aortic aneurysm

Carcinoid Heart Disease

• Carcinoid syndrome is characterized by episodic bronchospasm, flushing of the skin, telangiectasia, and diarrhea, usually associated with gastrointestinal carcinoid tumors that have metastasized to the liver

• Cardiac involvement manifests as right-sided valvular disease that progresses to right-sided heart failure

• Valvular dysfunction results in pure regurgitation of the tricuspid valve and predominantly regurgitation of the pulmonic valve

• Left-sided involvement is rare and associated with the presence of right-to-left shunt, pulmonary metastases, or bronchial carcinoids

Rheumatic Heart Disease

• Involves, in descending order of frequency, mitral, aortic, tricuspid, and pulmonic valves

• Acute rheumatic fever may show small verrucous vegetations along the lines of closure

• Chronic rheumatic heart disease shows diffuse thickening and fibrous retraction of valve leaflets with or without calcification, fusion of the commissures, and shortened, fused, and thickened chordae ( Figure 18.8 )

  

• Narrowed valvular orifice due to commissural fusion

• Calcific deposits are found at the commissures, which may become ulcerated

Mitral Valve Prolapse

• Myxomatous degeneration may involve any valve but most frequently involves the posterior leaflet of the mitral valve

• Diffuse leaflet thickening and redundancy with increased surface area (see Figure 18.8 )

• Interchordal hooding or billowing (parachute) deformity may be seen

• Cut surface reveals abundant gray translucent myxoid material in the spongiosa layer affecting the base, midportion, and free edge of the leaflet

• Elongated chordae with irregular thickening are commonly seen, and sometimes rupture occurs

• Often with annular dilation

Calcific Aortic Valve Disease

• Senile calcific aortic stenosis shows fibrosis and calcification of the base and body of the cusps, often protruding into the sinuses of Valsalva and rarely involving the free edge ( Figure 18.9 )

  

• Calcification of a congenital bicuspid aortic valve typically begins in the median raphe or false commissure and extends to the body of the cusps

• Absent or minimal commissural fusion is seen in degenerative aortic valve stenosis

Mitral Annular Calcification

• Calcification develops in the annulus of the mitral valve, usually at the base of the posterior leaflet, forming a solid bar causing distortion and elevation of the posterior leaflet

• Lesion may also extend into the myocardium and medially into the septum, where it may cause disruption of the bundle of His

• Calcium mass may erode through the valve leaflet, ulcerate, and predispose to thrombosis and infection

• Central softening and liquefaction of the calcification may occur and should not be mistaken for an abscess

Pure Aortic Regurgitation

• Floppy valves are large, redundant, mildly thickened, and gelatinous in consistency

• In aortic regurgitation secondary to dilation of the aortic root, the aortic cusps can be normal, with only focal and minimal fibrosis in the body; free edges are thickened; commissures are not fused

Carcinoid Heart Disease

• White fibrotic plaques on the tricuspid and pulmonic valve, mural endocardium, and occasionally intima of great vessels

• Fibrous plaques located predominantly on the ventricular aspect of tricuspid valve and almost exclusively on the arterial aspect of pulmonic valve

• Plaques cause thickening and retraction of the leaflets

• Plaques may also cause adherence of the valve to the mural endocardium of the right ventricle or intima of the pulmonary artery

Rheumatic Heart Disease

• Acute rheumatic fever may show inflammation and Aschoff bodies in all layers of the heart, including valves and papillary muscles

• Aschoff bodies consist of foci of fibrinoid degeneration surrounded by lymphocytes, occasional plasma cells, and Anitschkow or Aschoff cells

• Anitschkow cells are macrophages with abundant cytoplasm and central round to oval vesicular nuclei with a central bar of condensed chromatin (caterpillar-like); may become multinucleated to form Aschoff giant cells

• Chronic rheumatic heart disease shows diffuse fibrosis, neovascularization, or calcification of the valve

• Focal chronic inflammatory cell infiltrate (mainly lymphocytic) may be seen

Mitral Valve Prolapse

• Accumulation of mucopolysaccharides in the spongiosa layer with disruption of the collagenous bundles in the fibrosa and fragmentation of elastic fibers

• Absence of neovascularization or inflammation

• Mucopolysaccharide infiltration of the chordae tendineae

Calcific Aortic Valve Disease

• Calcification begins in the fibrosa layer

• Lipid deposits, neovascularization, and chronic inflammatory cell infiltrates are commonly found

• Osseous metaplasia may develop in the calcium deposits

Mitral Annular Calcification

• Calcification may be associated with mild inflammation and foreign-body giant cells

Pure Aortic Regurgitation

• Fibrous thickening of the free edges

• Myxomatous degeneration with accumulation of mucopolysaccharides in the spongiosa

Carcinoid Heart Disease

• Plaque is cellular and contains fibroblasts, myofibroblasts, smooth muscle cells, and collagen embedded in a myxoid matrix

• Plaques have a stuck-on appearance on the underlying valve and endocardium, which are intact

• Usually there are no elastic lamellae (i.e., no fibroelastosis) within the carcinoid plaque

Nonbacterial Thrombotic Endocarditis

• Usually occurs in association with chronic inflammatory disease, hypercoagulable state, and underlying malignancy, especially adenocarcinomas

• Aseptic vegetation may embolize or serve as a substrate for infection

• Aortic and mitral valves are most commonly affected

• Right-sided lesions are usually associated with intravenous catheters

• Vegetations are present on the atrial surfaces of atrioventricular valves and ventricular surfaces of semilunar valves

• Small (1- to 5-mm), multiple, nondestructive vegetations are loosely attached to the underlying valve leaflets, usually on previously normal valves

• Composed of platelets mixed with fibrin and a few red blood cells

• Inflammatory reaction is absent

• Organization may be seen at the base of the lesion with fibroblastic proliferation

Libman-Sacks Endocarditis

• Occurs in patients with systemic lupus erythematosus (SLE)

• Only 6% to 20% of cases are symptomatic

• Rare source of emboli

• Most often develops on mitral and tricuspid valves

• Relatively adherent, sessile, small (3- to 4-mm), pink to yellow-tan vegetations occurring singly or in clusters on the atrial and ventricular surfaces of the valve, anywhere from the free edge to the base, with extension onto the endocardium, chordae tendineae, and papillary muscles

• Sterile vegetations consist of fibrin and mononuclear cells with fibroblastic proliferation and neovascularization

• Necrosis with hematoxylin bodies rarely seen

• Healed endocarditis results in fibrous plaque

Bioprosthetic Valves

• Stented bioprosthetic valves

  • Leaflets made from bovine pericardium or porcine aortic valve treated with a chemical preservative

  • Mounted on flexible plastic or titanium metal frame (stent) covered with synthetic fabric (sewing cuff); three stent posts (struts) further support the cusps

• Stentless bioprosthetic valve

  • Chemically treated porcine aortic valve and a portion of the aortic root reinforced with a pliable exterior cuff

• Sutureless bioprosthetic valve

  • Bovine pericardium leaflets in a self-anchoring and self-expanding nitinol alloy stent

Mechanical Valves

• Hinged bileaflet D-shaped tilting disks made of pyrolytic carbon

• Housing made of a short hollow tube with a sewing cuff

• Previous designs included caged ball, caged disk, and tilting disk

Homografts

• Cryopreserved human aortic roots

Percutaneously Implanted Prosthetic Heart Valves

Transcatheter Aortic Valve Implantation

• Expandable stent housing a trileaflet pericardial tissue valve that is delivered percutaneously via a catheter for patients with severe aortic stenosis who are not open surgery candidates

Thrombus Formation

• May become a source of thromboemboli or become infected

• May hinder or entrap leaflets at hinge points in mechanical valves

• Thrombi usually form in the outflow side of bioprosthetic valves, filling up the concave aspect of the cusps

Infection

• Infection at the sewing ring may progress to ring abscess and pseudoaneurysm, leading to valve dehiscence or paravalvular leak

• Infection of bioprosthetic valve cusps may be bacterial or fungal

Pannus Overgrowth

• Fibrous tissue overgrowth from the sewing ring extends to valvular cusps, resulting in stiff thickened cusps, commissural fusion, and stenosis

• Retraction of cusps results in insufficiency

Paravalvular Leak

• Early leaks are complications arising from suturing technique or separation from an annulus with calcification or infection

• Late paravalvular leak results from tissue retraction during healing

Structural Deterioration

• Most frequent cause of failure in bioprosthetic valves

  • Mineralization of tissue valves causes stiffening and often tearing of cusps

  • Connective tissue matrix degradation also leads to cuspal tears and cuspal stretching

  • Tears also occur at flexure sites and at commissural attachment sites to the stent and stent posts

• Fracture of metallic components of mechanical valves rarely occurs