Difference between revisions of "Heart valves"

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==Infective endocarditis==
==Infective endocarditis==
:''Bacterial endocarditis'' and ''subacute bacterial endocarditis'' redirect here.
{{Main|Infective endocarditis}}
*Abbreviated ''IE''.
===General===
*Infection of the endocardium - often involves the valves (which are covered by endocardium).
*Before the time of antibiotics -- 100% fatal.
 
====Organisms====
Most common organism overall:
*''Staphylococcus aureus''.<ref name=pmid12092480>{{Cite journal  | last1 = Petti | first1 = CA. | last2 = Fowler | first2 = VG. | title = Staphylococcus aureus bacteremia and endocarditis. | journal = Infect Dis Clin North Am | volume = 16 | issue = 2 | pages = 413-35, x-xi | month = Jun | year = 2002 | doi =  | PMID = 12092480 }}</ref>
 
Organisms associated with particular clinical scenarios:
*IV drug users / normal valves = ''Staphylococcus aureus''.<ref name=Ref_PCPBoD8_298>{{Ref PCPBoD8|298}}</ref>
*Previously damaged valve = ''Streptococcus viridans''.
*Prosthetic valves = ''Staphylococcus epidermidis''.<ref name=pmid19660339>{{Cite journal  | last1 = Alonso-Valle | first1 = H. | last2 = Fariñas-Alvarez | first2 = C. | last3 = García-Palomo | first3 = JD. | last4 = Bernal | first4 = JM. | last5 = Martín-Durán | first5 = R. | last6 = Gutiérrez Díez | first6 = JF. | last7 = Revuelta | first7 = JM. | last8 = Fariñas | first8 = MC. | title = Clinical course and predictors of death in prosthetic valve endocarditis over a 20-year period. | journal = J Thorac Cardiovasc Surg | volume = 139 | issue = 4 | pages = 887-93 | month = Apr | year = 2010 | doi = 10.1016/j.jtcvs.2009.05.042 | PMID = 19660339 }}</ref>
 
Organisms that less commonly cause ''IE'' are known as the ''HACEK group'':<ref name=Ref_PCPBoD8_298>{{Ref PCPBoD8|298}}</ref>
*'''''H'''aemophilus'' (''Haemophilus parainfluenzae'', ''Haemophilus aphrophilus'', ''Haemophilus paraphrophilus'').
*'''''A'''ctinobacillus'' (''Actinobacillus actinomycetemcomitans'', ''Aggregatibacter aphrophilus'').
*'''''C'''ardiobacterium hominis.
*'''''E'''ikenella corrodens''. †
*'''''K'''ingella'' (''Kingella kingae'').
 
Notes:
* † ''Enterococci'' are not included in this list but are lumped with the ''HACEK organisms''.<ref name=Ref_PCPBoD8_298>{{Ref PCPBoD8|298}}</ref>
 
Others:
*''Stenotrophomonas maltophilia'' (previously ''Pseudomonas maltophilia'') - Gram-negative bacillus,<ref>{{Cite journal  | last1 = Gautam | first1 = V. | last2 = Ray | first2 = P. | last3 = Vandamme | first3 = P. | last4 = Chatterjee | first4 = SS. | last5 = Das | first5 = A. | last6 = Sharma | first6 = K. | last7 = Rana | first7 = S. | last8 = Garg | first8 = RK. | last9 = Madhup | first9 = SK. | title = Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia and Burkholderia cepacia complex). | journal = Indian J Med Microbiol | volume = 27 | issue = 2 | pages = 128-33 | month =  | year =  | doi = 10.4103/0255-0857.49425 | PMID = 19384035 }}</ref> rarely causes endocarditis,<ref name=pmid23021356>{{Cite journal  | last1 = Carrillo-Córdova | first1 = JR. | last2 = Amezcua-Guerra | first2 = LM. | title = Autoimmunity as a possible predisposing factor for Stenotrophomonas maltophilia endocarditis. | journal = Arch Cardiol Mex | volume = 82 | issue = 3 | pages = 204-7 | month =  | year =  | doi = 10.1016/j.acmx.2012.03.001 | PMID = 23021356 }}</ref> high mortality.<ref>{{Cite journal  | last1 = Fontenier | first1 = G. | last2 = Freschard | first2 = R. | last3 = Mourot | first3 = M. | title = Study of the corrosion in vitro and in vivo of magnesium amodes involved in an implantable bioelectric battery. | journal = Med Biol Eng | volume = 13 | issue = 5 | pages = 683-9 | month = Sep | year = 1975 | doi =  | PMID = 1186330 }}</ref>
 
====Clinical====
*Diagnosed (clinically) using the ''Duke criteria''.<ref>[http://www.medcalc.com/endocarditis.html http://www.medcalc.com/endocarditis.html]</ref><ref>{{cite journal |author=Durack DT, Lukes AS, Bright DK |title=New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service |journal=Am. J. Med. |volume=96 |issue=3 |pages=200-9 |year=1994 |month=March |pmid=8154507 |doi= |url=}}</ref>
**Positive blood cultures.
**Cardiac involvement - vegetation.
**+/-Febrile.
 
Subdivided into:
#Acute IE.
#*Classically due to ''Staphylococcus aureus''.
#Subacute IE.
#*Classically due to ''Streptococcus viridans''.
 
Treatment:<ref name=pmid23968767>{{Cite journal  | last1 = Gaca | first1 = JG. | last2 = Sheng | first2 = S. | last3 = Daneshmand | first3 = M. | last4 = Rankin | first4 = JS. | last5 = Williams | first5 = ML. | last6 = O'Brien | first6 = SM. | last7 = Gammie | first7 = JS. | title = Current Outcomes for Tricuspid Valve Infective Endocarditis Surgery in North America. | journal = Ann Thorac Surg | volume =  | issue =  | pages =  | month = Aug | year = 2013 | doi = 10.1016/j.athoracsur.2013.05.046 | PMID = 23968767 }}</ref>
*Usually medical management.<ref name=pmid16506645>{{Cite journal  | last1 = Chait | first1 = RD. | last2 = Midwall | first2 = J. | title = Tricuspid valvectomy: long-term survival and surgical options. | journal = Clin Cardiol | volume = 29 | issue = 2 | pages = 83-4 | month = Feb | year = 2006 | doi =  | PMID = 16506645 | URL = http://onlinelibrary.wiley.com/doi/10.1002/clc.4960290210/pdf }}</ref>
*Valve replacement.
*Valve repair.
*Valvectomy - for tricuspid valve.
 
===Gross===
*Location - left-sided involvement (mitral, aortic) more common than right-sided involvement (pulmonic, tricuspid).
**This is reversed in IV drug users.<ref name=Ref_PCPBoD8_298>{{Ref PCPBoD8|298}}</ref><ref name=pmid16401952>{{Cite journal  | last1 = Mathura | first1 = KC. | last2 = Thapa | first2 = N. | last3 = Rauniyar | first3 = A. | last4 = Magar | first4 = A. | last5 = Gurubacharya | first5 = DL. | last6 = Karki | first6 = DB. | title = Injection drug use and tricuspid valve endocarditis. | journal = Kathmandu Univ Med J (KUMJ) | volume = 3 | issue = 1 | pages = 84-6 | month =  | year =  | doi =  | PMID = 16401952 }}</ref>
*+/-Valvular destruction.
**More common in acute IE.
*+/-Distant emboli, e.g. [[splenic infarct]].
**More common in acute IE.
*+/-Valvular vegetations.
**Irregular ball of loosely adherent tissue - dull, irregular surface.
**On the ventricular aspect in aortic valve IE.
**Larger in acute IE.
 
Image:
*[http://www.flickr.com/photos/11462589@N05/1126726482/ Infective endocarditis - aortic valve (flickr.com)].
 
===Microscopic===
*Inflammatory infiltrate (key feature @ low power):
**+/-Plasma cells - subacute.
**+/-Neutrophils - typically abundant, may be rare in subacute.<ref>URL: [http://emedicine.medscape.com/article/216650-overview#a0104 http://emedicine.medscape.com/article/216650-overview#a0104]. Accessed on: 26 November 2013.</ref>
*Microorganisms - '''key feature''' (diagnostic).
**Hard to see (even at high power).
 
===Stains===
*[[GMS stain]] (Gomori Methenamine-silver stain).
**Look for [[fungi]].
*[[Gram stain]].
**Look for bacteria.
 
===Sign out===
<pre>
TRICUSPID VALVE, VALVECTOMY:
- FRAGMENTS OF VALVE WITH INFECTIVE ENDOCARDITIS -- ABUNDANT COCCI
  ORGANISMS IDENTIFIED.
- THIN RIM OF CARDIAC MUSCLE WITHOUT APPARENT PATHOLOGY.
</pre>
 
<pre>
MITRAL VALVE, VALVE REPLACEMENT:
- FRAGMENTS OF VALVE WITH INFECTIVE ENDOCARDITIS -- ABUNDANT COCCI
  ORGANISMS IDENTIFIED.
</pre>
 
====No microorganisms====
<pre>
AORTIC VALVE (BICUSPID), VALVE REPLACEMENT:
- BICUSPID VALVE WITH CALCIFIC AORTIC STENOSIS AND MILD ENDOCARDITIS.
- NO MICROORGANISMS APPARENT.
</pre>
 
====Micro====
The sections show valve tissue with an attached vegetation with abundant cocci organisms
and neutrophils. No calcification is apparent.
 
=====No microorganisms=====
The sections show valve tissue with marked calcification, scattered neutrophils and plasma cells. No microorganisms are identified with routine stains.


=Non-infective conditions=
=Non-infective conditions=

Revision as of 16:10, 3 July 2014

Heart valves are the domain of the cardiac surgeon and their bread & butter.

Clinical

General

  • Insufficiency (regurgitant flow) - murmur in diastole.
  • Stenosis (decreased flow area) - murmur in systole.

Pathology

Which valves cause the most trouble?

  • Mostly those on the left side (subjected to higher pressures), i.e. mitral valve (or left atrioventricular v.) and aortic valve.

Aortic stenosis - cause?

  • Mostly "calcific aortic stenosis".

Quick approach to valves

Gross

  • Calcification?
    • Consider calcific stenosis.
  • Vegetations?
    • Consider infective endocarditis.
  • Thin (see-through)?
    • Consider myxomatous change.

Microscopic

  • Inflammation?
    • Consider endocarditis.
  • Anitschkow's cells (caterpillar cells)?
    • Rheumatic heart disease.
  • Aschoff bodies?
    • Rheumatic heart disease.
  • Thickening of spongiosa (layer)?
    • Myxomatous change?

Normal morphology

Aortic valve

General

  • Covered by endothelium.
  • Mostly avascular (nutrients supplied by diffusion).

Gross

Terminology:

  • Base - closest to the aortic wall.
  • Free edge - closest to the centre of the valve/interacts with other valve cusps.

Cusps:

  • Left - has LMCA ostium.
  • Right - has RCA ostium.
  • Posterior (non-coronary cusp).

Microscopic

Three layers (from proximal (ventricular side) to distal (valsalva side)):[1]

  1. Ventricularis.
    • Elastic tissue.
  2. Spongiosa.
    • Loose connective tissue.
  3. Fibrosa.
    • Mostly collagen, thickest part in a normal valve.

Notes:

  • The loading of the ventricular aspect is tensile and the valsalva side compressive. Thus, it makes sense that the tissue on the ventricular aspect is good in tensile loading and the tissue on the valsalva side good in compression. The elastic tissue can be thought of as rebar... the collagen as concrete.

Image:

Mitral valve

Gross

  • Cordae tendinae.
    • Should be thin.
    • No fusion.

Microscopic

Similar to the aortic valve - layers:

  1. Atrialis.[3]
  2. Spongiosa.
  3. Fibrosa.

Degenerative conditions

Calcific aortic stenosis

  • Abbreviated CAS.

Localized dystrophic heart valve amyloidosis

General

  • Common:
  • Not seen in acute disease and healed endocarditis.[6]

Hypothesis:

Microscopic

Features:[6]

  • Pink amorphous material - key feature.
    • Usually around the calcific foci.

DDx:

Stains

  • Congo red +ve.

Dystrophic amyloid:[6]

  • Alcian blue -ve.
  • Periodic acid-Schiff -ve.

Myxomatous degeneration

General

Gross

Features:[10]

  • No commissural fusion.
    • Commissural fusion typical of rheumatic heart disease.
  • Thickened.
  • Rubbery consistency.
  • Reactive/secondary changes.
    • Fibrosis due to prolapse/abnormal contact of valve with other structures.
    • Clots/organized thrombus - due to stasis.

Microscopic

  • Thinning of fibrosa layer.
  • Thickening of spongiosa layer with mucoid (myxomatous) material. (key feature).
  • +/-Secondary changes (due to valvular dysfunction): thrombi, fibrosis.

Staining

  • Movat stain.
    • Acid fuchsin, alcian blue, crocein scarlet, elastic hematoxylin, pathology consultation, and saffron.[11][12]

Interpretation of Movat stain:[12]

  • Black = nuclei and elastic fibers.
  • Yellow = collagen and reticular fibers.
  • Blue = mucin, ground substance.
  • Red (intense) = fibrin.
  • Red = muscle.

Image:

Infective conditions

Rheumatic heart disease

Rheumatic fever redirects here.
  • Abbreviated RHD.

General

  • Classically leads to mitral valve stenosis.
    • Rheumatic fever accounts for 99% of mitral stenosis.[13]
      • Caused by Streptococcus pyogenes.[14]
  • Disease less frequent today - as streptococcal pharynigits is treated.

Gross

  • "Fish-mouth appearance".
  • Significant valvular thickening.
  • Thickening and shortening of the cordae tendinae.

DDx:

  • Thickening of the cordae tendinae due to micronodular cirrhosis.[16]

Images

Microscopic

Features:[17]

  • Caterpillar cells (AKA Anitschkow cells)
    • Abundant eosinophilic cytoplasm.
    • Moderately-poorly defined cell border.
    • Well-defined central ovoid nucleus with a prominent wavy ribbon-like chromatin -- looks vaguely like a caterpillar with some imagination.
    • Pathognomonic for rheumatic fever.
  • Aschoff bodies - usually in the heart itself:
    • Jumbled collagen, eosinophilic.
    • Surrounded by lymphocytes (T cells) +/- plasma cells.

Notes:

  • Anitschkow cells are thought to be histocytes and Aschoff bodies are thought to be granulomas.[18]
    • This is disputed.[19]

Images

IHC

Features (Aschoff bodies & Anitschkow cells):[18]

  • S100 -ve.
  • Muscle specific actin -ve.
  • Desmin -ve.
  • NF -ve.
  • Vimentin +ve.
  • CD45 +ve (weak).

Infective endocarditis

Non-infective conditions

Mitral valve prolapse

  • Abbreviated MVP.
  • AKA floppy mitral valve.[20]

General

  • Classically young women.
  • Afflicts ~ 3% of population in the USA.[21]

Clinical:

  • Pansystolic murmur.
  • +/-Left ventricular hypertrophy - secondary to MVP.

Complications:[21]

Gross

Features - any of the following:[23]

  1. "Intrachordal hooding" = ballooning/bulging of leaflet between chordal attachments.
  2. Hooding or doming of the body of the leftlet into the left atrium.
    • Extreme concavity of the valve when seen from the left ventricle.
  3. Elongated leaflets/large valve area.
  4. Dilated valve annulus.
  • Thickening of the valve.
  • +/-Left ventricular hypertrophy.

Note - location:

  • Posterior leaflet pathology more common than anterior leaflet pathology.[23]

Image:

Microscopic

Features:[23][21]

  • Increased thickness of spongiosa layer.
  • Thinning of the fibrosa layer.
  • +/-Fibrin deposition - atrial aspect.

DDx:

Nonbacterial thrombotic endocarditis

  • Abbreviated NBTE.
  • AKA marantic endocarditis.[24]

General

Associations:

  • Cardiac catheterization.[25]
  • Embolization.[24]
  • Malignancy - leading cause, usu. adenocarcinoma.[26]

Note:

  • Marantic = wasting away.

Gross

  • Round non-destructive vegetations, usually at the line of closure.[27]

Microscopic

Features:

  • Vegetation without inflammation and microorganisms.

Libman-Sacks endocarditis

General

  • Associated with systemic lupus erythematosus.
    • Seen in approximately in 1/10 SLE cases by echocardiography.[28]
  • Affects the mitral and aortic valves.[29]
    • Mitral valve most commonly affected.[30]
  • It has been suggested that it may be a manifestation of APLA syndrome.[29][30]

Clinical:

  • Usually regurgitation.

Gross

  • Vegetations anywhere on the valve surface[28] - often seen on both sides (flow surface & non-flow surface).[31]
  • Flat, pale brown/tan, usually small.[32]

Images:

Microscopic

Features:[citation needed]

  • Fibrin.
  • No microorganisms.
  • No inflammation.

Biscupid aortic valve

General

  • Aortic valve usually tricuspid.
  • Most common congenital heart defect.[33]
    • 1-2% of general population.[34]
      • Male:female ~ 2:1.[35]
  • Inherited in autosomal dominant pattern.
    • NOTCH1 gene - implicated.[36]

Significance:

Gross

Features - either:

  1. Raphe does not reach the free margin of the cusp.[38]
  2. No raphe - uncommon (~7% of cases).[39]

Note:

  • Raphe ~ suture or seam.[40]

Images:

Microscopic

Features - section through raphe:

  • "No evidence of fusion."[38]
  • Elastic fibres through-out (not interrupted by fibrous tissue). (???)

Note:

  • The clinical impression and gross pathologic impression of bicuspid valve should concur.

DDx:

Sign out

AORTIC VALVE, REPLACEMENT:
- BICUSPID AORTIC VALVE WITH CALCIFIC STENOSIS.

Micro

The sections show valve tissue with marked calcification of the fibrosa layer. No neutrophils are identified. No microorganisms are identified with routine stains.

Heart valve tumours

Papillary fibroelastomas are the most common tumour of the valve.

Other

Subvalvular membrane

Subvalvular aortic membrane redirects here.

General

Clinical:

  • Symptoms of aortic stenosis.
  • No ejection sound (as in aortic valvular stenosis).[43]

Microscopic

Features:

Note:

  • Similar to valvular tissue.

Stains

Sign out

SUBVALVULAR MEMBRANE, AORTA, EXCISION:
- BENIGN PAUCICELLULAR FIBROUS TISSUE CONSISTENT WITH SUBVALVULAR MEMBRANE.

See also

References

  1. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 558. ISBN 0-7216-0187-1.
  2. URL: http://www.e-heart.org/pages/01_cardiac_structure/01_Cardiac_Structure_MV_003.htm. Accessed on: 20 December 2012.
  3. Chesler, E.; King, RA.; Edwards, JE. (Mar 1983). "The myxomatous mitral valve and sudden death.". Circulation 67 (3): 632-9. PMID 6821906.
  4. Kristen, AV.; Schnabel, PA.; Winter, B.; Helmke, BM.; Longerich, T.; Hardt, S.; Koch, A.; Sack, FU. et al. "High prevalence of amyloid in 150 surgically removed heart valves--a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions.". Cardiovasc Pathol 19 (4): 228-35. doi:10.1016/j.carpath.2009.04.005. PMID 19502085.
  5. 5.0 5.1 Falk, E.; Ladefoged, C.; Christensen, HE. (Jan 1981). "Amyloid deposits in calcified aortic valves.". Acta Pathol Microbiol Scand A 89 (1): 23-6. PMID 7223424.
  6. 6.0 6.1 6.2 6.3 Cooper, JH. (Jul 1983). "Localized dystrophic amyloidosis of heart valves.". Hum Pathol 14 (7): 649-53. PMID 6190729.
  7. URL: http://emedicine.medscape.com/article/759004-overview. Accessed on: 8 June 2010.
  8. Leong SW, Soor GS, Butany J, Henry J, Thangaroopan M, Leask RL (October 2006). "Morphological findings in 192 surgically excised native mitral valves". Can J Cardiol 22 (12): 1055-61. PMID 17036100.
  9. Wigle ED, Rakowski H, Ranganathan N, Silver MC (1976). "Mitral valve prolapse". Annu. Rev. Med. 27: 165–80. doi:10.1146/annurev.me.27.020176.001121. PMID 779595.
  10. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 591. ISBN 0-7216-0187-1.
  11. URL: http://www.mayomedicallaboratories.com/test-catalog/Overview/9832. Accessed on: 8 June 2010.
  12. 12.0 12.1 Modified Movat's Pentachrome Stain. University Penn Medicine. URL: http://www.med.upenn.edu/mcrc/histology_core/movat.shtml. Accessed on: January 29, 2009.
  13. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 594. ISBN 0-7216-0187-1.
  14. Chopra, P.; Gulwani, H. (Oct 2007). "Pathology and pathogenesis of rheumatic heart disease.". Indian J Pathol Microbiol 50 (4): 685-97. PMID 18306530.
  15. URL: http://en.wikipedia.org/wiki/Ellipse. Accessed on: 13 November 2010.
  16. Rose, Alan G. (2008). Atlas of Gross Pathology with Histologic Correlation (1st ed.). Cambridge University Press. pp. 25. ISBN 978-0521868792.
  17. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 593. ISBN 0-7216-0187-1.
  18. 18.0 18.1 Love, GL.; Restrepo, C. (Jul 1988). "Aschoff bodies of rheumatic carditis are granulomatous lesions of histiocytic origin.". Mod Pathol 1 (4): 256-61. PMID 3070554.
  19. Stehbens, WE.; Zuccollo, JM. (May 1999). "Anitschkow myocytes or cardiac histiocytes in human hearts.". Pathology 31 (2): 98-101. PMID 10399163.
  20. Boudoulas, H.; Wooley, CF. (2001). "Floppy mitral valve/mitral valve prolapse/mitral valvular regurgitation: effects on the circulation.". J Cardiol 37 Suppl 1: 15-20. PMID 11433820.
  21. 21.0 21.1 21.2 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 296. ISBN 978-1416054542.
  22. Franchitto, N.; Bounes, V.; Telmon, N.; Rougé, D. (Jul 2010). "Mitral valve prolapse and out-of-hospital sudden death: a case report and literature review.". Med Sci Law 50 (3): 164-7. PMID 21133272.
  23. 23.0 23.1 23.2 Virmani, R.; Atkinson, JB.; Forman, MB. (Aug 1988). "The pathology of mitral valve prolapse.". Herz 13 (4): 215-26. PMID 3049284.
  24. 24.0 24.1 Borowski, A.; Ghodsizad, A.; Cohnen, M.; Gams, E. (Jun 2005). "Recurrent embolism in the course of marantic endocarditis.". Ann Thorac Surg 79 (6): 2145-7. doi:10.1016/j.athoracsur.2003.12.024. PMID 15919332.
  25. Young, RS.; Zalneraitis, EL.. "Marantic endocarditis in children and young adults: clinical and pathological findings.". Stroke 12 (5): 635-9. PMID 7303049.
  26. Dickens, P.; Chan, AC. (Apr 1991). "Nonbacterial thrombotic endocarditis in Hong Kong Chinese.". Arch Pathol Lab Med 115 (4): 359-61. PMID 2012496.
  27. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 567. ISBN 978-1416031215.
  28. 28.0 28.1 Plastiras, SC.; Pamboucas, CA.; Tektonidou, M.; Toumanidis, ST. (Mar 2010). "Real-time three-dimensional echocardiography in evaluating Libman-Sacks vegetations.". Eur J Echocardiogr 11 (2): 184-5. doi:10.1093/ejechocard/jep172. PMID 19946116.
  29. 29.0 29.1 Lee, JL.; Naguwa, SM.; Cheema, GS.; Gershwin, ME. (Jun 2009). "Revisiting Libman-Sacks endocarditis: a historical review and update.". Clin Rev Allergy Immunol 36 (2-3): 126-30. doi:10.1007/s12016-008-8113-y. PMID 19089657.
  30. 30.0 30.1 Hojnik, M.; George, J.; Ziporen, L.; Shoenfeld, Y. (Apr 1996). "Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome.". Circulation 93 (8): 1579-87. PMID 8608627.
  31. Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 567. ISBN 978-1416031215.
  32. URL: http://library.med.utah.edu/WebPath/CVHTML/CV122.html. Accessed on: 6 March 2013.
  33. Siu SC, Silversides CK (June 2010). "Bicuspid aortic valve disease". J. Am. Coll. Cardiol. 55 (25): 2789–800. doi:10.1016/j.jacc.2009.12.068. PMID 20579534.
  34. 34.0 34.1 34.2 Vallely MP, Semsarian C, Bannon PG (October 2008). "Management of the ascending aorta in patients with bicuspid aortic valve disease". Heart Lung Circ 17 (5): 357-63. doi:10.1016/j.hlc.2008.01.007. PMID 18514024.
  35. Tzemos, N.; Therrien, J.; Yip, J.; Thanassoulis, G.; Tremblay, S.; Jamorski, MT.; Webb, GD.; Siu, SC. (Sep 2008). "Outcomes in adults with bicuspid aortic valves.". JAMA 300 (11): 1317-25. doi:10.1001/jama.300.11.1317. PMID 18799444.
  36. Garg, V.; Muth, AN.; Ransom, JF.; Schluterman, MK.; Barnes, R.; King, IN.; Grossfeld, PD.; Srivastava, D. (Sep 2005). "Mutations in NOTCH1 cause aortic valve disease.". Nature 437 (7056): 270-4. doi:10.1038/nature03940. PMID 16025100.
  37. Braverman, AC.; Güven, H.; Beardslee, MA.; Makan, M.; Kates, AM.; Moon, MR. (Sep 2005). "The bicuspid aortic valve.". Curr Probl Cardiol 30 (9): 470-522. doi:10.1016/j.cpcardiol.2005.06.002. PMID 16129122.
  38. 38.0 38.1 Rose, Alan G. (2008). Atlas of Gross Pathology with Histologic Correlation (1st ed.). Cambridge University Press. pp. 2. ISBN 978-0521868792.
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