Valvular Heart Disease

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Valvular Heart Disease

• Anjali Shinde, MD
• Mount Sinai Hospital
• Chicago

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Outline

• Valvular degeneration associated with
  calcification
• Calcific aortic stenosis and calcific stenosis of
  congenitally bicuspid aoritc valve
• Mitral annular calcification
• Mitral valve prolapse
• Rheumatic heart disease
• Infective endocarditis
• Non infected vegetations
• Carinoid heart disease
• Complications of artificial valves

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Valvular heart disease

• Congenital or acquired.
• Stenosis- failure of a valve to open completely,
  impedes forward flow. usually a chronic
  abnormality of the valve cusp that becomes
  clinically evident after many years
• Insufficiency-failure of a valve to close
  completely, allowing reversed flow. Valvular
  insufficiency may appear acutely.
• Single valve involvement (isolated disease)
  more than one valve (combined disease).
• Functional regurgitation- incompetence of a valve
  from abnormality in one of its support
  structures.
• Eg. dilation of the right or left ventricle can
  pull the ventricular papillary muscles down and
  outward, thereby preventing proper closure of
  otherwise normal mitral or tricuspid leaflets.
  Functional mitral valve regurgitation is common
  in IHD (ischemic mitral regurgitation).

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Valvular heart disease

• Most frequent causes of the major functional
  valvular lesions are
• Aortic stenosis calcification of anatomically
  normal and congenitally bicuspid aortic valves
• Aortic insufficiency dilation of the ascending
  aorta, usually related to hypertension and aging
• Mitral stenosis rheumatic heart disease
• Mitral insufficiency myxomatous degeneration
  (mitral valve prolapse)

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Etiology of acquired heart disease
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Clinical consequences of valve dysfunction

• Clinical consequences vary depending on
• - valve involved
• - degree of impairment
• - how fast it develops
• -rate and quality of compensatory mechanisms
• Eg. sudden destruction of an aortic valve cusp
  by infection (infective endocarditis) can cause
  acute, massive regurgitation that can be rapidly
  fatal. In contrast, rheumatic mitral stenosis
  usually develops indolently over years, and its
  clinical effects are often remarkably well
  tolerated.
• Certain conditions can complicate valvular heart
  disease by increasing the demands on the heart
  for example, pregnancy can exacerbate valve
  disease and lead to an unfavorable maternal or
  fetal outcome.
• Valvular stenosis or insufficiency produces
  secondary changes, both proximal and distal to
  the affected valve.
• -Valvular stenosis leads to pressure overload
  of the heart
• -Valvular insufficiency leads to volume
  overload of the heart
• -Ejection of blood through narrowed stenotic
  valves can produce high speed "jets" of
  blood that injure the endocardium where they
  impact.

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1. Valvular degeneration associated with
calcification
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Valvular degeneration associated with
calcification

• Most common valvular abnormality- acquired aortic
  stenosis- consequence of age-associated "wear and
  tear" of either anatomically normal valves or
  congenitally bicuspid valves
• Aortic stenosis of previously normal valves
  (termed senile calcific aortic stenosis) is seen
  in seventh to ninth decades of life, whereas
  stenotic bicuspid valves tend to present in
  patients 50 to 70 years of age
• Morphology-Heaped-up calcified masses within the
  aortic cusps that protrude through the outflow
  surfaces into the sinuses of Valsalva,
  preventing the opening of the cusps
• Microscopically, layered architecture of the
  valve is largely preserved. An earlier,
  hemodynamically inconsequential stage of the
  calcification process is called aortic valve
  sclerosis.
• In contrast to rheumatic (and congenital) aortic
  stenosis , commissural fusion is not usually
  seen.

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Valvular degeneration associated with
calcification
A, Calcific aortic stenosis of a previously
normal valve (viewed from aortic aspect). Nodular
masses of calcium are heaped up within the
sinuses of Valsalva (arrow). Note that the
commissures are not fused, as in postrheumatic
aortic valve stenosis B, Calcific aortic
stenosis of a congenitally bicuspid valve. One
cusp has a partial fusion at its center, called a
raphe (arrow).
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Valvular degeneration associated with
calcification (calcific aortic stenosis)-
clinical features

• Obstruction to left ventricular outflow leads to
  gradual narrowing of the valve and an increasing
  pressure gradient across the calcified valve
  producing concentric left ventricular (pressure
  overload) hypertrophy.
• The hypertrophied myocardium tends to be ischemic
  (as a result of diminished microcirculatory
  perfusion, often complicated by coronary
  atherosclerosis), and angina pectoris may appear.
  
• Both systolic and diastolic myocardial function
  may be impaired eventually, cardiac
  decompensation and CHF may ensue. The onset of in
  aortic stenosis heralds cardiac decompensation
  and carries a poor prognosis
• 50 with angina will die within 5 years, and 50
  with CHF will die within 2 years, if the
  obstruction is not alleviated by surgical valve
  replacement.
• Medical therapy is ineffective in severe
  symptomatic aortic stenosis. In contrast,
  asymptomatic patients with aortic stenosis
  generally have an excellent prognosis

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Calcific Stenosis of Congenitally Bicuspid Aortic
Valve (BAV)

• Prevalence is approximately 1, most frequent
  congenital cardiovascular malformation
• Responsible for approximately 50 of cases of
  aortic stenosis in adults
• Usually uncomplicated early in life, late
  complications of BAV include aortic stenosis or
  regurgitation, infective endocarditis, and aortic
  dilation and/or dissection.
• In a congenitally bicuspid aortic valve, there
  are only two functional cusps, usually of unequal
  size, with the larger cusp having a midline
  raphe, resulting from incomplete commissural
  separation during development less frequently
  the cusps are of equal size and the raphe is
  absent.
• The raphe is frequently a major site of calcific
  deposits
• Clinical course is similar to acquired calcific
  aortic stenos
• BAVs may also become incompetent as a result of
  aortic dilation, cusp prolapse, or infective
  endocarditis.
• Valves can also become bicuspid because of an
  acquired deformity (e.g., rheumatic valve
  disease) and have a fused commissure that
  produces a conjoined

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Mitral Annular Calcification

• Degenerative calcific deposits develop in the
  peripheral fibrous ring (annulus) of the mitral
  valve.
• Grossly- irregular, stony hard, occasionally
  ulcerated nodules behind the leaflets
• Generally does not affect valvular function or
  otherwise become clinically important.
• In unusual cases, mitral annular calcification
  may lead to (1) regurgitation by interfering with
  physiologic contraction of the valve ring, (2)
  stenosis by impairing opening of the mitral
  leaflets, or (3) arrhythmias and occasionally
  sudden death by penetration of calcium deposits
  to a depth sufficient to impinge on the
  atrioventricular conduction system.
• Patients can have increased risk of stroke, from
  thrombi calcific nodules can be nidus for
  infective endocarditis.
• Mitral annular calcification is most common in
  women over age 60 and individuals with mitral
  valve prolapse or elevated left ventricular
  pressure (as in systemic hypertension, aortic
  stenosis, or hypertrophic cardiomyopathy)

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Mitral annular calcification
C and D, Mitral annular calcification, with
calcific nodules at the base (attachment margin)
of the anterior mitral leaflet (arrows). C, Left
atrial view. D, Cut section of myocardium
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2. Mitral valve prolapse
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MITRAL VALVE PROLAPSE (MYXOMATOUS DEGENERATION OF
THE MITRAL VALVE)

• One or both mitral valve leaflets are "floppy"
  and prolapse, or balloon back, into the left
  atrium during systole.
• The key histologic change in the tissue is called
  myxomatous degeneration.
• MVP affects approximately 3 of adults in the
  United States
• Often an incidental finding on physical
  examination (particularly in young women), but in
  a small minority of affected individuals may lead
  to serious complications.

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MITRAL VALVE PROLAPSE (MYXOMATOUS DEGENERATION OF
THE MITRAL VALVE)

• Morphology-
• - Interchordal ballooning (hooding) of the
  mitral leaflets
• -Leaflets are often enlarged, redundant, thick,
  and rubbery.
• - Tendinous cords may be elongated, thinned, or
  even ruptured,
• - Annulus may be dilated.
• - Tricuspid, aortic, or pulmonary valves may
  also be affected.
• Secondary changes reflect the stresses and injury
  incident to the billowing leaflets
• (1) fibrous thickening of the valve leaflets,
  particularly where they rub against each other
• (2) linear fibrous thickening of the left
  ventricular endocardial surface where the
  abnormally long cords snap or rub against it
• (3) thickening of the mural endocardium of the
  left ventricle or atrium as a consequence of
  friction-induced injury induced by the
  prolapsing, hyper-mobile leaflets
• (4) thrombi on the atrial surfaces of the
  leaflets or the atrial walls
• (5) focal calcifications at the base of the
  posterior mitral leaflet.
• Mild myxomatous degeneration can also occur in
  mitral valves secondary to regurgitation of other
  etiologies (e.g., ischemic dysfunction).

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Myxomatous degeneration of the mitral valve. A,
Long axis of left ventricle demonstrating hooding
with prolapse of the posterior mitral leaflet
into the left atrium (arrow). The left ventricle
is on right in this apical four-chamber view. B,
Opened valve, showing pronounced hooding of the
posterior mitral leaflet with thrombotic plaques
at sites of leaflet-left atrium contact (arrows).
C, Opened valve with pronounced hooding from
patient who died suddenly (double arrows)
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Mitral valve prolapse- pathogenesis and clinical
features

• Unknown in most cases.
• Discovered incidentally by detection of a
  midsystolic click on physical examination.
• Associated with heritable disorders of connective
  tissue including Marfan syndrome,
• Most patients asymptomatic, minority have chest
  pain mimicking angina, dyspnea, and fatigue and
  the condition
• Diagnosis confirmed by echocardiography
• Complications (1) infective endocarditis (2)
  mitral insufficiency, sometimes with chordal
  rupture (3) stroke or other systemic infarct,
  resulting from embolism of leaflet thrombi or
  (4) arrhythmias
• Risk of complications very low when MVP is
  discovered incidentally in young asymptomatic
  patients, Risk higher in men, older patients,
  and those with arrhythmias or mitral
  regurgitation.
• If at high risk for serious complications, valve
  surgery is treatment

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3. Rheumatic heart disease
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RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE

• Rheumatic fever (RF) - acute, immunologically
  mediated, multisystem inflammatory disease that
  occurs a few weeks after an episode of group A
  streptococcal pharyngitis.
• Acute rheumatic carditis is a frequent
  manifestation during the active phase of RF and
  may progress over time to chronic rheumatic heart
  disease (RHD),
• RHD is characterized by deforming fibrotic
  valves, particularly mitral stenosis,
• Incidence and mortality rate of RF and RHD have
  declined remarkably in many parts of the world
  over the past century, as a result of improved
  socioeconomic conditions and rapid diagnosis and
  treatment of streptococcal pharyngitis.
• In developing countries, and in many crowded,
  economically depressed urban areas in the Western
  world, RHD remains an important public health
  problem
• Rheumatic fever only rarely follows infections by
  streptococci at other sites, such as the skin.

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RHD- morphology- acute RF

• During acute RF, f ocal inflammatory lesions are
  found in various tissues.
• Distinctive lesions occur in the heart, called
  Aschoff bodies, which consist of foci of
  lymphocytes (primarily T cells), occasional
  plasma cells, and plump activated macrophages
  called Anitschkow cells (pathognomonic for RF).
  These macrophages have abundant cytoplasm and
  central round-to-ovoid nuclei in which the
  chromatin is disposed in a central, slender, wavy
  ribbon (hence the designation "caterpillar
  cells"), and may become multinucleated.
• During acute RF, diffuse inflammation and Aschoff
  bodies may be found in any of the three layers of
  the heart, causing pericarditis, myocarditis, or
  endocarditis (pancarditis).

Aschoff body
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RHD- morphology- acute RF

• Inflammation of the endocardium and the
  left-sided valves results in fibrinoid necrosis
  within the cusps or along the tendinous cords.
  Overlying these necrotic foci are small (1- to
  2-mm) vegetations, called verrucae, along the
  lines of closure.
• Subendocardial lesions, perhaps caused by
  regurgitant jets, may induce irregular
  thickenings called MacCallum plaques, usually in
  the left atrium. The cardinal anatomic changes of
  the mitral valve in chronic RHD are leaflet
  thickening, commissural fusion and shortening,
  and thickening and fusion of the tendinous cords

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RHD- morphology- chronic phase

• In chronic disease the mitral valve is virtually
  always involved.
• The mitral valve is affected alone in 65 to 70
  of cases, and along with the aortic valve in
  another 25 of cases.
• Tricuspid valve involvement is infrequent, and
  the pulmonary valve is only rarely affected.
• Fibrous bridging across the valvular commissures
  and calcification create "fish mouth" or
  "buttonhole" stenoses.
• With tight mitral stenosis, the left atrium
  progressively dilates and may have mural thrombi
  in the appendage or along the wall which can
  embolize

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RHD- morphology- chronic phase

• Long-standing congestive changes in the lungs
  may induce pulmonary vascular and parenchymal
  changes- right ventricular hypertrophy.
• Microscopically, in the mitral leaflets there is
  organization of the acute inflammation and
  subsequent diffuse fibrosis and
  neovascularization.
• Aschoff bodies are rarely seen in surgical
  specimens or autopsy tissue from patients with
  chronic RHD, as a result of the long times
  between the initial insult and the development of
  the chronic deformity.

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• .A, Acute rheumatic mitral valvulitis
  superimposed on chronic rheumatic heart disease.
  Small vegetations (verrucae) are visible along
  the line of closure of the mitral valve leaflet
  (arrows). Previous episodes of rheumatic
  valvulitis have caused fibrous thickening and
  fusion of the chordae tendineae.
• B, Microscopic appearance of Aschoff body in a
  patient with acute rheumatic carditis. The
  myocardial interstitium has a circumscribed
  collection of mononuclear inflammatory cells,
  including some large macrophages with prominent
  nucleoli and a binuclear macrophage, associated
  with necrosis
• C and D, Mitral stenosis with diffuse fibrous
  thickening and distortion of the valve leaflets
  and commissural fusion (arrows, C), and
  thickening of the chordae tendineae (D). Note
  neovascularization of anterior mitral leaflet
  (arrow, D). E, Rheumatic aortic stenosis,
  demonstrating thickening and distortion of the
  cusps with commissural fusion

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RHD- pathogenesis and clinical features

• Acute rheumatic fever results from immune
  responses to group A streptococci, which
  cross-react with host tissues.
• Antibodies directed against the M proteins of
  streptococci cross-react with self antigens in
  the heart. CD4 T cells specific for
  streptococcal peptides also react with self
  proteins in the heart, and produce cytokines that
  activate macrophages (found in Aschoff bodies)
• Clinical Features RF is characterized by major
  manifestations (1) migratory polyarthritis of
  the large joints, (2) pancarditis, (3)
  subcutaneous nodules, (4) erythema marginatum of
  the skin, and (5) Sydenham chorea, a neurologic
  disorder with involuntary rapid, purposeless
  movements.
• Diagnosis is established by Jones criteria
• evidence of a preceding group A streptococcal
  infection, with the presence of two of the major
  manifestations listed above
• or one major and two minor manifestations
  (nonspecific signs and symptoms that include
  fever, arthralgia, or elevated blood levels of
  acute-phase reactants).

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Jones Criteria for Rheumatic fever

• Rheumatic fever Revised Jones criteria JONES
  PEACE Major criteriaJoints migratoryO
  (heart shaped) Carditis new onset
  murmurNodules, subcutaneous extensor
  surfacesErythema marginatumSydenham's chorea
  Minor criteriaPR interval, prolongedESR
  elevatedArthralgiasCRP elevatedElevated
  temperature (fever) Need 2 major or 1 major and
  2 minor criteria, plus evidence of recent GAS
  infection (throat cx, rapid antigen test, or
  rising strep antibody titer).

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RF- pathogenesis and clinical features

• Acute RF typically appears 10 days to 6 weeks
  after an episode of pharyngitis caused by group A
  streptococci in about 3 of infected patients
• Most often between ages 5 and 15
• Pharyngeal cultures for streptococci are negative
  by the time the illness begins
• Antibodies to one or more streptococcal enzymes,
  such as streptolysin O and DNase B, can be
  detected in the sera of most patients with RF
• Predominant clinical manifestations are carditis
  and arthritis, the latter more common in adults
  than in children.

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RF- pathogenesis and clinical features

• Clinical features related to acute carditis
  include pericardial friction rubs, weak heart
  sounds, tachycardia, and arrhythmias
• Myocarditis may cause cardiac dilation-
  functional mitral valve insufficiency or heart
  failure. (Approximately 1 of patients die from
  fulminant RF)
• Arthritis typically begins with migratory
  polyarthritis (accompanied by fever) which
  subsides spontaneously, leaving no residual
  disability
• After an initial attack there is increased
  vulnerability to reactivation of the disease with
  subsequent pharyngeal infections, and the same
  manifestations are likely to appear with each
  recurrent attack. Damage to the valves is
  cumulative.
• Clinical manifestations appear years or even
  decades after the initial episode of RF and
  depend on which cardiac valves are involved.
• Sequalae- Cardiac murmurs, cardiac hypertrophy
  and dilation, heart failure, arrhythmias
  (particularly atrial fibrillation in the setting
  of mitral stenosis), thromboembolic
  complications, and infective endocarditis
• Long-term prognosis is highly variable. Surgical
  repair or prosthetic replacement of diseased
  valves has greatly improved the outlook for
  persons with RHD

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4. Infective endocarditis
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INFECTIVE ENDOCARDITIS

• Infection characterized by colonization or
  invasion of the heart valves or the mural
  endocardium by microbes leading to the formation
  of vegetations of thrombotic debris and organisms
• Associated with destruction of the underlying
  cardiac tissues. The aorta, aneurysmal sacs,
  other blood vessels, and prosthetic devices can
  also become infected.
• Most cases are caused by bacterial infections
  (bacterial endocarditis). Fungi can also cause
  endocarditis
• Acute infective endocarditis is caused by
  infection of a previously normal heart valve by a
  highly virulent organism that produces
  necrotizing, ulcerative, destructive lesions.
• Acute infective endocardtitis is difficult to
  cure with antibiotics and usually requires
  surgery
• Death within days to weeks ensues in many
  patients with acute IE, despite treatment.
• In subacute IE, the organisms are of lower
  virulence. and cause insidious infections of
  deformed valves that are less destructive. The
  disease may pursue a protracted course of weeks
  to months, and can be cured with antibiotics.

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Types of valvular vegetations
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Infective endocarditis- etiology and pathogenesis

• Predisposing factors- rheumatic heart disease
  was the major antecedent disorder, but more
  common now are mitral valve prolapse,
  degenerative calcific valvular stenosis, bicuspid
  aortic valve (whether calcified or not),
  artificial (prosthetic) valves, and unrepaired
  and repaired congenital defects.
• The causative organisms differ somewhat in the
  major high-risk groups. Endocarditis of native
  but previously damaged or otherwise abnormal
  valves is caused most commonly (50 to 60 of
  cases) by Streptococcus viridans, which is part
  of the normal flora of the oral cavity.
• In contrast, more virulent S. aureus organisms
  commonly found on the skin can infect either
  healthy or deformed valves and are responsible
  for 10 to 20 of cases overall
• S. aureus is the major offender in intravenous
  drug abusers with IE.
• Other remaining bacteria includes enterococci and
  the so-called HACEK group (Haemophilus,
  Actinobacillus, Cardiobacterium, Eikenella, and
  Kingella), all commensals in the oral cavity.
• Prosthetic valve endocarditis is caused most
  commonly by coagulase-negative staphylococci
  (e.g., S. epidermidis).
• Other agents causing endocarditis include
  gram-negative bacilli and fungi. In about 10 to
  15 of all cases of endocarditis, no organism can
  be isolated from the blood ("culture-negative"
  endocarditis).

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Infective endocarditis- Morphology

• Hallmark of IE is the presence of friable, bulky,
  potentially destructive vegetations containing
  fibrin, inflammatory cells, and bacteria or other
  organisms on the heart .
• Vegetations sometimes erode into the underlying
  myocardium and produce an abscess (ring abscess).
  
• Emboli may be shed from the vegetations at any
  time
• Embolic fragments may contain large numbers of
  virulent organisms, abscesses often develop at
  the sites where the emboli lodge, leading to
  sequelae such as septic infarcts or mycotic
  aneurysms
• Aortic and mitral valves are the most common
  sites of infection,
• Valves of the right heart may also be involved in
  intravenous drug abusers
• Vegetations of subacute endocarditis are
  associated with less valvular destruction than
  those of acute endocarditis
• Microscopically, the vegetations of typical
  subacute IE often have granulation tissue
  indicative of healing at their bases. With time,
  fibrosis, calcification, and a chronic
  inflammatory infiltrate can develop.

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Infective (bacterial) endocarditis. A,
Endocarditis of mitral valve (subacute, caused by
Streptococcus viridans). The large, friable
vegetations are denoted by arrows. B, Acute
endocarditis of congenitally bicuspid aortic
valve (caused by Staphylococcus aureus) with
extensive cuspal destruction and ring abscess
(arrow). C, Histologic appearance of vegetation
of endocarditis with extensive acute inflammatory
cells and fibrin. Bacterial organisms were
demonstrated by tissue Gram stain. D, Healed
endocarditis, demonstrating mitral valvular
destruction but no active vegetations.
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Infective endocarditis- clinical features

• Fever is the most consistent sign of IE.
• Acute endocarditis has a stormy onset with
  rapidly developing fever, chills, weakness, and
  lassitude.
• In the elderly, and the only manifestations may
  be nonspecific fatigue, loss of weight, and a
  flu-like syndrome.
• Complications of IE generally begin within the
  first few weeks of onset. They may be
  immunologically mediated - glomerulonephritis
  caused by the deposition of antigen-antibody
  complexes
• Murmurs are present in 90 of patients
• Duke criteria provide a standardized assessment
  of individuals with suspected IE that takes into
  account predisposing factors, physical findings,
  blood culture results, echocardiographic
  findings, and laboratory information.
• Earlier diagnosis and effective treatment has
  nearly eliminated some previously common clinical
  manifestations of long-standing IE-for example,
  micro-thromboemboli (manifest as splinter or
  subungual hemorrhages), erythematous or
  hemorrhagic nontender lesions on the palms or
  soles (Janeway lesions), subcutaneous nodules in
  the pulp of the digits (Osler nodes), and retinal
  hemorrhages in the eyes (Roth spots).

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Diagnostic Criteria for Infective Endocarditis

• Duke Criteria, requires either pathologic or
  clinical criteria if clinical criteria are used,
  2 major, 1 major 3 minor, or 5 minor criteria
  are required for diagnosis
• Major
• -Microorganisms, demonstrated by culture or
  histologic examination, in a vegetation, embolus
  from a vegetation, or intracardiac
  abscess-Histologic confirmation of active
  endocarditis in vegetation or intracardiac
  abscess
• -Blood culture(s) positive for a characteristic
  organism or persistently positive for an unusual
  organism-Echocardiographic identification of a
  valve-related or implant-related mass or abscess,
  or partial separation of artificial valve-New
  valvular regurgitaion
• Minor
• -Predisposing heart lesion or intravenous drug
  use-Fever-Vascular lesions, including arterial
  petechiae, subungual/splinter hemorrhages,
  emboli, septic infarcts, mycotic aneurysm,
  intracranial hemorrhage, Janeway
  lesions-Immunological phenomena, including
  glomerulonephritis, Osler nodes, Roth spots,
  rheumatoid factor-Microbiologic evidence,
  including a single culture positive for an
  unusual organism-Echocardiographic findings
  consistent with but not diagnostic of
  endocarditis, including worsening or changing
  of a preexistent murmur

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5. Non infected vegetations
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NONINFECTED VEGETATIONS Non bacterial
thrombotic endocarditis

• NBTE is characterized by the deposition of small
  sterile thrombi on the leaflets of the cardiac
  valves 1 to 5 mm, single or multiple along
  lines of closure of valves
• Histologically, they are bland thrombi loosely
  attached to the underlying valve not invasive,
  no inflammatory reaction
• These can be a source of systemic emboli that
  produce infarcts in the brain, heart, or
  elsewhere
• NBTE is often encountered in debilitated
  patients, such as those with cancer or sepsis
  (syn. marantic endocarditis)
• Frequently occurs concomitantly with deep venous
  thromboses, pulmonary emboli, or other findings
  consistent with an underlying systemic
  hypercoagulable state
• Association with mucinous adenocarcinomas, which
  may relate to the procoagulant effects of
  tumor-derived mucin or tissue factor,
• NBTE can be a part of the Trousseau syndrome of
  migratory thrombophlebitis
• Endocardial trauma from an indwelling catheter,
  is a predisposing condition, and right-sided
  valvular and endocardial thrombotic lesions
  frequently track along the course of Swan-Ganz
  pulmonary artery catheters.

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NONINFECTED VEGETATIONS Non bacterial
thrombotic endocarditis
Nonbacterial thrombotic endocarditis (NBTE). A,
Nearly complete row of thrombotic vegetations
along the line of closure of the mitral valve
leaflets (arrows). B, Photomicrograph of NBTE,
showing bland thrombus, with virtually no
inflammation in the valve cusp (c) or the
thrombotic deposit (t). The thrombus is only
loosely attached to the cusp (arrow).
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Endocarditis of Systemic Lupus Erythematosus
(Libman-Sacks Disease)

• Mitral and tricuspid valvulitis with small,
  sterile vegetations, called Libman-Sacks
  endocarditis, is occasionally encountered in SLE.
  
• Fibrosis and serious deformities can result that
  resemble chronic rheumatoid heart disease and
  require surgery.
• Thrombotic heart valve lesions with sterile
  vegetations or rarely fibrous thickening commonly
  occur with the antiphospholipid syndrome, mitral
  valve is more frequently involved than the aortic
  valve regurgitation is the usual functional
  abnormality.

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Endocarditis of Systemic Lupus Erythematosus
(Libman-Sacks Disease)

• Lesions are small (1-4 mm in diameter) single or
  multiple, sterile, pink vegetations often with a
  warty (verrucous) appearance.
• Located on the undersurfaces of the
  atrioventricular valves, on the valvular
  endocardium, on the chords, or on the mural
  endocardium of atria or ventricles.
• Histologically the vegetations consist of a
  finely granular, fibrinous eosinophilic material
  that may contain hematoxylin bodies, homogeneous
  remnants of nuclei damaged by anti-nuclear
  antigen bodies. An intense valvulitis may be
  present, characterized by fibrinoid necrosis of
  the valve substance that is often contiguous with
  the vegetation.

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CARCINOID HEART DISEASE

• Carcinoid heart disease- cardiac manifestation of
  the systemic syndrome caused by carcinoid tumors
• Carcinoid symdrome is characterized by episodic
  flushing of the skin, cramps, nausea, vomiting,
  and diarrhea
• Generally involves the endocardium and valves of
  the right heart.
• Cardiac lesions are present in one half of
  patients
• Bioactive mediators released into the portal
  circulation by gut carcinoid tumors are
  metabolized by the liver and do not reach the
  heart in high concentration and do not produce
  carcinoid heart disease, unless there are
  extensive hepatic metastases
• In contrast, primary carcinoid tumors in organs
  outside of the portal system of venous drainage
  that empty directly into the inferior vena cava
  (e.g., ovary and lung) can induce the syndrome
• Cardiac changes occur on the right side because
  of inactivation of both serotonin and bradykinin
  during passage through the lungs (by monoamine
  oxidase present in the pulmonary vascular
  endothelium)

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6. Carcinoid heart disease
46
Carcinoid syndrome-Morphology

• Firm plaquelike endocardial fibrous thickenings
  on the inside surfaces of the cardiac chambers
  and the tricuspid and pulmonary valves
• The plaquelike thickenings are composed
  predominantly of smooth muscle cells and sparse
  collagen fibers embedded in an acid
  mucopolysaccharide-rich matrix material. Elastic
  fibers are not present in the plaques.
• Although the mechanisms of the fibrosis are not
  understood, it appears that the clinical and
  pathologic findings relate to the elaboration by
  carcinoid tumors of a variety of bioactive
  products, such as serotonin , kallikrein,
  bradykinin, histamine, prostaglandins, and
  tachykinins.
• Plasma levels of serotonin and urinary excretion
  of the serotonin metabolite 5-hydroxyindoleacetic
  acid correlate with the severity of the right
  heart lesions

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Carcinoid heart disease- clinical features

• Most common cardiac manifestation is tricuspid
  insufficiency, followed by pulmonary valve
  insufficiency, sometimes stenosis can occur
• Left-sided valvular disease can occur if there is
  patent foramen ovale with right to left shunting
  or primary or metastatic carcinoid tumor
  involving the lung
• Left-sided valvular abnormalities can also be
  seen with drugs that have serotonergic
  activity-fenfluramine (part of the "fen-phen"
  combination of appetite suppressants), some
  antiparkinsonian drugs, and methysergide or
  ergotamine, used to treat migraine headaches

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7. Artificial valves
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ARTIFICIAL VALVES

• Replacement of damaged cardiac valves with
  prostheses is a common and often lifesaving mode
  of therapy
• Artificial valves are primarily of two types
• (1) mechanical prostheses, consisting of
  different kinds of rigid mechanical valves,
  such as caged balls, tilting disks, or hinged
  semicircular flaps that are composed of
  nonphysiologic material
• (2) tissue valves, usually bioprostheses,
  consisting of chemically treated animal tissue,
  especially porcine aortic valve tissue,

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COMPLICATIONS OF ARTIFICIAL VALVES

• Approximately 60 of substitute valve recipients
  develop a serious prosthesis-related problem
  within 10 years postoperatively.
• Thromboembolic complications- necessitates
  long-term anticoagulation in all individuals with
  mechanical valves,
• Infective endocarditis- vegetations of prosthetic
  valve endocarditis are usually located at the
  prosthesis-tissue interface, and often cause the
  formation of a ring abscess, which can eventually
  lead to a paravalvular regurgitant blood leak if
  the prosthetic valve-tissue junction is
  disrupted. In addition, vegetations may directly
  involve the tissue of bioprosthetic valvular
  cusps. The major organisms causing such
  infections are staphylococcal skin contaminants
  (e.g., S. epidermidis), S. aureus, streptococci,
  and fungi.
• Structural deterioration- can cause failure of
  contemporary mechanical valves. Bioprostheses
  often eventually become incompetent due to
  calcification and/or tearing
• Intravascular hemolysis due to high shear forces,
• Paravalvular leak due to inadequate healing,
• Obstruction due to overgrowth of fibrous tissue
  during the healing process.

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Complications of artificial heart valves. A,
Thrombosis of a mechanical prosthetic valve. B,
Calcification with secondary tearing of a porcine
bioprosthetic heart valve, viewed from the inflow
aspect.