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CARDIO ? VASCULAR SYSTEM DISEASES

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VALVULAR HEART DISEASE

? Valve pathology can lead to occlusion (stenosis) and/or regurgitation (insufficiency); acquired

aortic or mitral valve stenosis accounts for approximately two thirds of all valve diseases.

? Valve calcification typically results in stenosis; abnormal matrix synthesis and turnover leads to

myxomatous degeneration and insufficiency.

? Inflammatory valve diseases cause post-inflammatory neovascularization and scarring. Rheumatic

heart disease results from anti-streptococcal antibodies that cross-react with cardiac tissues; it most

commonly affects the mitral valve and is responsible for almost all cases of acquired mitral stenosis.

? Infective endocarditis can rapidly destroy normal valves, or can be indolent and minimally

destructive of previously abnormal valves. Systemic embolization can produce septic infarcts.

? Nonbacterial thrombotic endocarditis occurs on previously normal valves as a result of

hypercoagulable states; embolization is an important complication.

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Infective Endocarditis

Infective endocarditis (IE) is a microbial infection of the heart valves or the mural endocardium that

leads to the formation of vegetations composed of thrombotic debris and organisms, often

associated with destruction of the underlying cardiac tissues. The aorta, aneurysmal sacs, other

blood vessels, and prosthetic devices also may become infected. Although fungi, rickettsia (agents

of Q fever), and chlamydial species can cause endocarditis, the vast majority of cases are caused

by extracellular bacteria.

Infective endocarditis is classified into acute and subacute forms based on the tempo and severity of

the clinical course; the distinctions are related to the virulence of the responsible microbe and

whether underlying cardiac disease is present. Of note, a clear delineation between acute and

subacute endocarditis is not always possible, and many cases fall somewhere along the spectrum

between the two forms.

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? Acute endocarditis refers to tumultuous, destructive infections, frequently involving a highly virulent

organism attacking a previously normal valve. It is associated with of substantial morbidity and

mortality, even with appropriate antibiotic therapy and/or surgery.

? Subacute endocarditis refers to infections by organisms of low virulence affecting a previously

abnormal heart, especially scarred or deformed valves. The disease typically appears insidiously

and ? even if untreated ? follows a protracted course of weeks to months; most patients recover

after appropriate antibiotic therapy.

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Pathogenesis

Infective endocarditis can develop on previously normal valves, but cardiac abnormalities

predispose to such infections; rheumatic heart disease, mitral valve prolapse, bicuspid aortic valves,

and calcific valvular stenosis are all common substrates. Prosthetic heart valves now account for

10% to 20% of all cases of IE. Sterile platelet-fibrin deposits at sites of pacemaker lines, indwelling

vascular catheters, or endocardium damage by flow ?jets? stemming from preexisting cardiac

disease all can be foci for bacterial seeding and development of endocarditis.

The causative organisms differ depending on the underlying risk factors; 50% to 60% of cases

occurring on damaged or deformed valves are caused by Streptococcus viridans, a relatively banal

group of normal oral flora. By contrast, the more virulent S. aureus (common to skin) can attack

healthy as well as deformed valves and is responsible for 10% to 20% of cases overall; it also is the

major offender in infections occurring in intravenous drug abusers. Additional bacterial agents

include enterococci and the so-called ?HACEK group? (Haemophilus, Actinobacillus,

Cardiobacterium, Eikenella, and Kingella), all commensal in the oral cavity.

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MORPHOLOGY

In both acute and subacute forms of the disease, friable, bulky, and potentially destructive

vegetations containing fibrin, inflammatory cells, and microorganisms are present on the heart

valves. The aortic and mitral valve are the most common sites of infection, although the tricuspid

valve is a frequent target in the setting of intravenous drug abuse.

Vegetations may be single or multiple and may involve more than one valve; they can sometimes

erode into the underlying myocardium to produce an abscess cavity (ring abscess). Shedding of

emboli is common because of the friable nature of the vegetations. Since the fragmented

vegetations contain large numbers of organisms, abscesses often develop at the sites where emboli

lodge, leading to development of septic infarcts and aneurysms resulting from bacterial infection of

the arterial wall (mycotic aneurysms). Subacute endocarditis typically causes less valvular

destruction than acute endocarditis.

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Clinical Features

Fever is the most consistent sign of infective endocarditis. However, in subacute disease

(particularly in older adults), fever may be absent, and the only manifestations may be nonspecific

fatigue, weight loss, and a flulike syndrome; splenomegaly also is common in subacute cases.

By contrast, acute endocarditis often manifests with rapidly developing fever, chills, weakness, and

lassitude. Murmurs are present in 90% of patients with left-sided lesions. In those who are not

treated promptly, microemboli are formed, which can give rise to petechia, nail bed (splinter)

hemorrhages, retinal hemorrhages (Roth spots), painless palm or sole erythematous lesions

(Janeway lesions), or painful fingertip nodules (Osler nodes); diagnosis is confirmed by positive

blood cultures and echocardiographic findings.

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Prognosis depends on the infecting organism and the development of complications. Adverse

sequelae generally begin within the first weeks after onset of the infectious process and can include

glomerulonephritis due to glomerular trapping of antigen-antibody complexes, with hematuria,

albuminuria, or renal failure. Clinical features of septicemia, arrhythmias (suggesting extension to

underlying myocardium and conduction system), and systemic embolization bode ill for the patient.

Left untreated, IE generally is fatal. However, with appropriate long-term (6 weeks or more) antibiotic

therapy and/or valve replacement, mortality is reduced. For infections with low-virulence organisms

(e.g., Streptococcus viridans or Streptococcus bovis), the cure rate is 98%, and for enterococci and

Staphylococcus aureus infections, cure rates range from 60% to 90%; however, infections with

aerobic gram-negative bacilli or fungi are associated with fatality rate of approximately 50%.
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Nonbacterial Thrombotic Endocarditis

Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of sterile thrombi on

cardiac valves, typically in those with an underlying hypercoagulable state. Although NBTE can

occur in otherwise healthy individuals, a wide variety of diseases associated with general debility or

wasting are associated with an increased risk for NBTE ? hence the alternate term marantic

endocarditis.

In contrast to infective endocarditis, the sterile valvular lesions of NBTE are nondestructive. The

vegetations in NBTE are typically small (1 to 5 mm in diameter) and valvular damage is not a

prerequisite. Indeed, the condition usually occurs on previously normal valves. Rather,

hypercoagulable states are the usual precursor to NBTE; such conditions include chronic

disseminated intravascular coagulation, hyperestrogenic states, and those associated with

underlying malignancy, particularly mucinous adenocarcinomas.

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Endocarditis in Systemic Lupus Erythematosus:Libman-Sacks Endocarditis

Libman-Sacks endocarditis is characterized by the presence of sterile vegetations on the valves of

patients with systemic lupus erythematosus. It occurs in about 10% of patients with SLE.

The lesions probably develop as a consequence of immune complex deposition and thus exhibit

associated inflammation, often with fibrinoid necrosis of the valve adjacent to the vegetation;

subsequent fibrosis and serious deformity can result in lesions that resemble chronic rheumatic

heart disease.

These can occur anywhere on the valve surface, on the cords, or even on the atrial or ventricular

endocardium. Similar lesions can occur in the setting of anti-phospholipid antibody syndrome.
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Rheumatic Valvular Disease

Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease that

occurs after group A ?-hemolytic streptococcal infections (usually pharyngitis, but also occasionally

infections at other sites, such as skin). Rheumatic heart disease is the cardiac manifestation of

rheumatic fever. It is associated with inflammation of all parts of the heart, but valvular inflammation

and scarring produce the most important clinical features. The valvular disease principally takes the

form of deforming fibrotic mitral stenosis; indeed rheumatic heart disease is essentially the only

cause of acquired mitral stenosis.

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Pathogenesis

Acute rheumatic fever is a hypersensitivity reaction classically attributed to antibodies directed

against group A streptococcal molecules that cross-react with host myocardial antigens. In

particular, antibodies against M proteins of certain streptococcal strains bind to proteins in the

myocardium and cardiac valves and cause injury through the activation of complement and Fc

receptor?bearing cells (including macrophages).

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MORPHOLOGY

Acute rheumatic fever is characterized by discrete inflammatory foci within a variety of tissues. The

myocardial inflammatory lesions ? called Aschoff bodies ? are pathognomonic for rheumatic fever;

these are collections of lymphocytes (primarily T cells), scattered plasma cells, and plump activated

macrophages called Anitschkow cells associated with zones of fibrinoid necrosis.

Aschoff bodies can be found in any of the three layers of the heart ? pericardium, myocardium, or

endocardium (including valves). Hence, rheumatic fever is said to cause pancarditis, with the

following salient features:

? The pericardium may exhibit a fibrinous exudate, which generally resolves without sequelae.

? The myocardial involvement myocarditis ? takes the form of scattered Aschoff bodies within the

interstitial connective tissue.

? Valve involvement results in fibrinoid necrosis and fibrin deposition along the lines of closure

forming 1-to 2-mm vegetations ? verrucae that cause little disturbance in cardiac function.
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Clinical Features

Acute rheumatic fever occurs most often in children; the principal clinical manifestation is carditis.

Nevertheless, about 20% of first attacks occur in adults, with arthritis being the predominant feature.

Symptoms in all age groups typically begin 2 to 3 weeks after streptococcal infection and are

heralded by fever and migratory polyarthritis ? one large joint after another becomes painful and

swollen for a period of days.

The clinical signs of carditis include pericardial friction rubs and arrhythmias; myocarditis may be

sufficiently severe to cause cardiac dilation and resultant functional mitral insufficiency and CHF.

Nevertheless, less than 1% of patients die of acute rheumatic fever.

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Clinical Features

The diagnosis of acute rheumatic fever is made based on serologic evidence of previous

streptococcal infection in conjunction with two or more of the Jones criteria:

carditis;

migratory polyarthritis of large joints;

subcutaneous nodules;

erythematous annular rash (erythema marginatum) in the skin;

Sydenham chorea, a neurologic disorder characterized by involuntary purposeless, rapid

movements (also called St. Vitus dance).

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MYOCARDITIS

Myocarditis encompasses a diverse group of clinical entities in which infectious agents and/or

inflammatory processes target the myocardium. It is important to distinguish myocarditis from

conditions such as IHD, where the inflammatory process is secondary to some other cause of

myocardial injury.
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Pathogenesis

Viral infections are the most common cause of myocarditis, with coxsackieviruses A and B and other

enteroviruses accounting for a majority of the cases. Cytomegalovirus (CMV), human

immunodeficiency virus (HIV), influenza virus, and others are less common pathogens.

The protozoan Trypanosoma cruzi is the agent of Chagas disease. About 10% of the patients die

during an acute attack; others can enter a chronic immune-mediated phase with development of

progressive signs of CHF and arrhythmia 10 to 20 years later. Toxoplasma gondii (household cats

are the most common vector) also can cause myocarditis/

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Pathogenesis

Myocarditis occurs in approximately 5% of patients with Lyme disease, a systemic illness caused by

the bacterial spirochete Borrelia burgdorferi. Lyme myocarditis manifests primarily as self-limited

conduction system disease, frequently requiring temporary pacemaker insertion.

Noninfectious causes of myocarditis include systemic diseases of immune origin, such as systemic

lupus erythematosus and polymyositis. Drug hypersensitivity reactions affecting the heart

(hypersensitivity myocarditis) may occur with exposure to a wide range of agents; such reactions

typically are benign and only in rare circumstances lead to CHF or sudden death.
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MORPHOLOGY

In acute myocarditis, the heart may appear normal or dilated; in advanced stages, the myocardium

typically is flabby and often mottled with pale and hemorrhagic areas. Mural thrombi may be present.

Microscopically, myocarditis is characterized by edema, interstitial inflammatory infiltrates, and

myocyte injury. A diffuse lymphocytic infiltrate is most common.

If the patient survives the acute phase of myocarditis, lesions may resolve without significant

sequelae or heal by progressive fibrosis.

In hypersensitivity myocarditis, interstitial and perivascular infiltrates are composed of lymphocytes,

macrophages, and a high proportion of eosinophils.

Giant cell myocarditis is a morphologically distinctive entity characterized by widespread

inflammatory cell infiltrates containing multinucleate giant cells (formed by macrophage fusion).

Chagas myocarditis is characterized by the parasitization of scattered myofibers by trypanosomes

accompanied by an inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and

occasional eosinophils.
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Clinical Features

The clinical spectrum of myocarditis is broad; at one end, the disease is asymptomatic, and patients

recover without sequelae. At the other extreme is the precipitous onset of heart failure or

arrhythmias, occasionally with sudden death. Between these extremes are many levels of

involvement associated with a variety of signs and symptoms, including fatigue, dyspnea,

palpitations, pain, and fever.

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ARRHYTHMIAS

Aberrant rhythms can be initiated anywhere in the conduction system, from the sinoatrial (SA) node

down to the level of an individual myocyte; they are typically designated as originating from the

atrium (supraventricular) or within the ventricular myocardium.

Abnormalities in myocardial conduction can be sustained or sporadic (paroxysmal). They can

manifest as tachycardia (fast heart rate), bradycardia (slow heart rate), an irregular rhythm with

normal ventricular contraction, chaotic depolarization without functional ventricular contraction

(ventricular fibrillation), or no electrical activity at all (asystole).

Patients may be unaware of a rhythm disorder, or may note a ?racing heart? or palpitations

(irregular rhythm); loss of adequate cardiac output due to sustained arrhythmia can produce

lightheadedness (near syncope), loss of consciousness (syncope), or sudden cardiac death.