Heart
Endocarditis
Noninfective endocarditis

Author: R. Amita, M.D. (see Authors page)

Revised: 19 March 2018, last major update April 2014

Copyright: (c) 2014-2018, PathologyOutlines.com, Inc.

PubMed Search: Noninfective endocarditis [title]

Cite this page: Amita, R. Noninfective endocarditis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/heartnontumornoninfecendo.html. Accessed July 21st, 2018.
Definition / general
  • First described by Zeigler in 1888, who called it "thromboendocarditis"
  • In 1936, Gross and Friedberg coined the term "nonbacterial thrombotic endocarditis" (NBTE)
  • Defined as vegetations on the valve surface, rich in fibrin and platelet aggregates but devoid of inflammation or infective organisms
Terminology
  • Also called marantic endocarditis
Diagrams / tables

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Differences between NBTE and infective endocarditis

Epidemiology
  • NBTE is uncommon but underestimated as symptoms are often attributed to other diseases
Sites
  • Cardiac valves and endocardial surface
Pathophysiology
  • Thrombotic endocarditis develops due to endothelial damage and subsequent exposure of the subendothelial connective tissue to circulating platelets
  • The factors involved in pathogenesis can be divided into initiating NBTE and subsequent development of vegetation
  • Factors implicated in initiation are: (a) immune complexes, (b) hypoxia, (c) hypercoagulability and (d) carcinomatosis
    • Immune complexes: Libman-Sacks endocarditis is the prototype
    • Hypoxia: studied by Nakanishi et al. in a rodent model (Virchows Arch 1998;433:375)
    • Hypercoagubility: Trousseau first noted the association between thrombosis and malignancy
      • Histological evidence of disseminated intravascular coagulopathy (DIC) has been found in 50% patients with NBTE
    • Carcinomatosis: mucin producing adenocarcinoma from the gut, lung and ovary and acute promyelocytic leukemia are commonly associated with NBTE
Risk Factors
  • Advanced stage malignancy: solid organ or hematological
  • Chronic diseases: tuberculosis, uremia, AIDS
  • Connective tissue disorders with hypercoaguable state: SLE patients with APLA positive
  • Trauma from indwelling pulmonary catheter or central venous catheter, snake bite, late effect of radiation therapy
Clinical features
  • There are no pathognomonic signs and symptoms that allow for the confident diagnosis of NBTE
  • Patients can present with:
    • Cardiac failure
      • Secondary to valvular dysfunction (most commonly mitral regurgitation), leading to dyspnea, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, lethargy
    • Cerebrovascular embolism
      • Focal weakness or numbness, visual loss, dysphasia, dysarthria, dysphagia, memory loss
    • Systemic thromboembolism
      • Pain, coldness and numbness of the peripheries, or acute abdominal syndromes with pain and vomiting
    • Secondary infective endocarditis
      • Fever, weight loss, night sweats, lethargy, chest pain
Diagnosis
  • Requires a high degree of clinical suspicion in a patient treated for infective endocarditis (IE) and not clinically improving
  • Mckay and Wahler proposed a triad for diagnosis of NBTE:
    1. Presence of a disease process known to be associated with NBTE
    2. Presence of heart murmur and
    3. Evidence of multiple systemic emboli
  • Main differential diagnosis is Infective endocarditis - distinction is important
Laboratory
  • Exclude DIC: full blood count, prothrombin time, partial thromboplastin time, fibrinogen, thrombin time, D dimers and cross linked fibrin degradation products
    • These may be normal, but in the presence of risk factors, an abnormal result should alert the physician to a diagnosis of NBTE
  • Multiple blood cultures to rule out any infective cause
  • Immunological assays for antiphospholipid syndrome (APS)
  • Polymerase chain reaction (PCR) for rapid and reliable detection of culture negative endocarditis by fastidious organisms
Radiology description
  • Transoesophageal echo (TEE) has a higher sensitivity (90%) than transthoracic echo (TTE), especially for vegetations of < 5 mm
  • Cardiac MRI using TrueFISP gradient echo sequence allows the morphology of small heart structures such as valves to be examined in detail (J Comput Assist Tomogr 1996;20:613)
  • Diffusion weighted MRI (DWI) can differentiate cardioembolic stroke caused by infective endocarditis from that of NBTE due to the lack of a cellular component in NBTE emboli
Prognostic factors
  • Dependent on underlying disease activity and associated renal and myocardial dysfunction
Case reports
Treatment
  • Treatment is difficult - correction of the underlying cause is of paramount importance
  • In patients with potentially curable cancer, coagulopathy should be corrected and, if there is no contraindication, these patients should be anticoagulated with heparin
  • There are no guidelines for surgical intervention in patients with NBTE - decision is based upon individual case
Clinical images

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Mitral valve with masses

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Mitral valve with mass

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Enlarging mitral valve mass

Gross description
  • NBTE vegetations are typically small, friable, white or tan masses, < 1 cm in diameter, broad based and irregular, usually along lines of valve closure on leaflets which may be normal or previously damaged
  • Vary from tiny lesions to large and exuberant masses
  • Based on morphology, Allen and Sirota proposed a macroscopic classification of NBTE:
    • Type 1:
      • Small, < 3 mm univerrucal, firmly attached to the valve
    • Type 2:
      • Large, > 3mm univerrucal, adherent to the valve
    • Type 3:
      • Small, 1 - 3mm multiverrucal, friable
Gross images

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Typical finding

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Vegetations of NBTE

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Typical appearances

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Large NBTE vegetations

Microscopic (histologic) description
  • NBTE consists of degenerating platelets interwoven with strands of fibrin and forming a bland, featureless eosinophilic mass except for a few trapped leucocytes
  • Three stages have been described in the evolution of NBTE vegetations: (eMedicine: Libman-Sacks Endocarditis Workup [Accessed 28 February 2018])
    • Active verrucae: Consist of clumps of fibrin on and within the valvular leaflet tissue which is focally necrotic, with plasma cells and lymphocytes
    • Combined active and healed lesions: Contain vascularized, fibrous tissue adjacent to fibrinous and necrotic areas
    • Healed lesions: Consist of dense, vascularized, fibrous tissue
Microscopic (histologic) images

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Uniform eosinophilic appearance

Differential diagnosis