Main features of endocarditis | Medcomic/Jorge Muniz
Contents
Introduction
https://www.youtube.com/watch?v=9JUdjT7idXM
Multisystem disease that results from infection, usually bacterial, of the endocardial surface of the heart.
History:
Sir William Osler, 1st Baronet, FRS FRCP (1849 – 1919) was a Canadian physician and one of the four founding professors of Johns Hopkins Hospital.
Infective endocarditis has been recognized as a pathological entity for hundreds of years and as an infectious process since the 19th century. In his landmark 1885 Gulstonian Lectures on malignant endocarditis, Sir William Osler presented a unifying theory in which susceptible patients developed ‘mycotic’ growths on their valves followed by “transference to distant parts of microbes”. The intervening 130 years have witnessed dramatic growth in our understanding of IE as well as fundamental changes in the disease itself. Medical progress, novel at-risk populations and the emergence of antimicrobial resistance have led to new clinical manifestations of IE.
Epidemiology
Global epidemiology of causative pathogens involved in endocarditis: The causative agents of infective endocarditis differ geographically. | CoNS, Coagulase-negative staphylococci; HACEK, Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species; Strep, streptococcal species; VGS, viridans group streptococci. | Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, Karchmer AW, Olaison L, Pappas PA, Moreillon P, Chambers ST, Chu VH, Falcó V, Holland DJ, Jones P, Klein JL, Raymond NJ, Read KM, Tripodi MF, Utili R, Wang A, Woods CW, Cabell CH, International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Arch Intern Med. 2009 Mar 9; 169(5):463-73.
Aetiology
Risk factors:
Rheumatic heart disease (M/C predisposing cardiac condition for IE)
M/C involved site: Mitral valve
Prosthetic valves (20%) and cardiac devices (7%): Permanent pacemakers and cardioverter-defibrillators
Pathogenesis of endocarditis: a) Pathogens gain access to the bloodstream, for example via an intravenous catheter, injection drug use or from a dental source. b) Pathogens adhere to an area of abnormal cardiac valve surface. c) Some pathogens, such as S. aureus, obtain intracellular access to the valve endothelium. d) The infected vegetation is created by burying of the proliferating organism within a protective matrix of serum molecules. e) Vegetation particles can detach and disseminate to form emboli. These may lead to complications such as ischemic stroke, mycotic aneurysms and infarcts or abscesses at remote sites. | Werdan, K., Dietz, S., Löffler, B., Niemann, S., Bushnaq, H., Silber, R. E., … Müller-Werdan, U. (2014). Mechanisms of infective endocarditis: pathogen-host interaction and risk states. Nature reviews. Cardiology, 11(1), 35–50. doi:10.1038/nrcardio.2013.174Mechanisms of infective endocarditis: a) Valve colonization as a consequence of mechanical injury. 1) Nonbacterial thrombotic endocarditis. 2) Bacteria bind to coagulum and colonize it during transient bacteraemia. Adhered monocytes release tissue factor and cytokines. 3) More platelets are attracted and become activated and the vegetation grows. 4) Endothelial cells are infected and can be lysed by bacterial products, or bacteria can persist inside the cells. b) Valve colonization as a consequence of an inflammatory endothelial lesion. 1) Activated endothelial cells express integrins that promote the local deposition of fibronectin; bacteria such as S. aureus adhere to this protein. 2) Bacteria are internalized and endothelial cells release tissue factor and cytokines, causing blood clotting and promoting the extension of inflammation and vegetation formation. 3) Infected endothelial cells can be lysed by bacterial products or bacteria can persist inside the cells. | Werdan K, et al. Mechanisms of infective endocarditis: pathogen-host interaction and risk states. Nat Rev Cardiol. 2014;11:35–50.
This figure shows one portion (called a leaflet) of the mitral valve of the heart. The valve has been excised surgically in the course of treating endocarditis. There is a large mass or vegetation on the valve, and it is surrounded by bleeding into the valve tissue that has resulted from valve damage. | Cabell, C. H., Abrutyn, E. and Karchmer, A. W. (2003) ‘Bacterial Endocarditis’, Circulation, 107(20), p. e185 LP-e187. Available at: http://circ.ahajournals.org/content/107/20/e185.abstract.
Complication
Immune complex deposition in the kidney:
Glomerulonephritis
Embolisation:
Organ infarction
Infected valve → Impaired function
Cardiac valve insufficiency
Regurgitation
Metastatic lesions
Acute arthritis
Splenic, mesenteric, brain, perivalvular abscess
Osteomyelitis
End-organ manifestations of endocarditis A) CT scans of pyogenic brain abscess and embolic stroke with haemorrhagic conversion. B) CT scan demonstrating multiple septic pulmonary emboli. C) CT scan demonstrating peripheral wedge-shaped splenic infarcts. D) Roth spots on funduscopic exam. E) Infarcts affecting multiple fingers. F) Explanted mitral valve with vegetation. G) Explanted aortic valve leaflet with vegetation and perforation. H) Pacemaker lead with vegetation. Roth spots photo courtesy of Walter B. Holland, MD. | Eisenbarth, G. S., & Gottlieb, P. A. (2004). Autoimmune Polyendocrine Syndromes. New England Journal of Medicine, 350(20), 2068–2079. https://doi.org/10.1056/NEJMra030158
Clinical Features
Infection:
Fever (7-10 days)
Chills, rigour, night sweats
General malaise, weakness
Loss of appetite, weight loss
Amenorrhoea (females)
Vasculitis:
Monoarticular arthralgia (Only in acute endocarditis as part of septicemia)
Diffuse myalgia
Petechiae (50%)
Immune complex formation:
Roth’s spots (white-centred retinal haemorrhages secondary to septic emboli within the retina)
Osler Nodes (3–5%): Tender raised red lesions on hands & feet
Embolisation:
Splinter haemorrhages: Small red streaks under nails
Janeway lesions (3–5%): Small non-tender, red macules/nodules on palms/soles)
Fundoscopic view of macula and optic disc showing numerous Roth spots. | Ramaswamy A, Tarabishy A, Gugliotti D, Harte B, Roth Spots—More than Meets the Eye. J. Hosp. Med 2011;6;369-369. doi:10.1002/jhm.782
Osler’s nodes in the palm and finger. | Hirai, T., & Koster, M. (2013). Osler’s nodes, Janeway lesions and splinter haemorrhages. BMJ Case Reports, 2013, bcr2013009759. https://doi.org/10.1136/bcr-2013-009759
Janeway lesions. | Hirai, T., & Koster, M. (2013). Osler’s nodes, Janeway lesions and splinter haemorrhages. BMJ Case Reports, 2013, bcr2013009759. https://doi.org/10.1136/bcr-2013-009759
Splinter haemorrhage. | Hirai, T., & Koster, M. (2013). Osler’s nodes, Janeway lesions and splinter haemorrhages. BMJ Case Reports, 2013, bcr2013009759. https://doi.org/10.1136/bcr-2013-009759
Petechiae in the conjunctiva. | Hirai, T., & Koster, M. (2013). Osler’s nodes, Janeway lesions and splinter haemorrhages. BMJ Case Reports, 2013, bcr2013009759. https://doi.org/10.1136/bcr-2013-009759
Case study:
A 34-year-old man presented to the eye emergency department with reduced vision in the right eye that had developed that morning. He was well, apart from episodes of dizziness and dyspnea after exercise during the previous 4 months. These episodes had started 1 week after the patient had undergone a dental treatment. Previous extensive investigations had been inconclusive. His retinal appearance and symptoms prompted referral to the cardiology team, which admitted him that day. He was afebrile but had a pansystolic murmur and a solitary splinter hemorrhage on the right thumb. Echocardiography revealed moderate-to-severe mitral-valve regurgitation, with thickening and signs of vegetations. The ejection fraction was 65%. The other values were normal. Four sets of blood cultures yielded Streptococcus viridans, and intravenous antibiotics were started immediately. His symptoms improved, and his visual acuity gradually improved from 20/200 at presentation to 20/20 8 months after presentation. His right fundal appearance is shown, at presentation (Panel A), 3 days later (Panel B), and 3 months later (Panel C). The presence of white-centered hemorrhages (Roth spots) should prompt the consideration of possible infective endocarditis. A comparison of Panel A and Panel B (3 days apart) shows how quickly such spots can change. Monitoring of the patient’s mitral-valve regurgitation, which was started after complete resolution of the endocarditis, is ongoing. | Mahroo, O. A., & Graham, E. M. (2014). Roth Spots in Infective Endocarditis. New England Journal of Medicine, 370(25), e38. https://doi.org/10.1056/NEJMicm1312093
Diagnosis
Modified Duke’s criteria:
Requirement (M=Major, m=minor):
Definite endocarditis = (2M) or (1M + 3m) or (5m)
Possible endocarditis = (1M + 1m) or (3m)
Rejected IE:
Firm alternative diagnosis for symptoms
Or sustained resolution of manifestation with antibiotic therapy for ≤ 4 days,
Or No pathological evidence of IE at surgery/autopsy, after antibiotic therapy for ≤ 4 days
Major criteria:
Positive blood culture
2 separate positive blood cultures
Persistent positive blood cultures taken > 12 hours apart
≥ 3 positive cultures taken over > 1 hour
Endocardial involvement
Positive echocardiogram
New valvular regurgitation
Minor criteria:
Predisposing valvular or cardiac abnormality
IV drug misuse
Pyrexia
≥ 38°C
Embolic phenomenon
Vasculitic phenomenon
Blood cultures suggestive organism
Suggestive echocardiographic findings
Blood culture
Imaging:
Transthoracic echocardiogram (TTE)
Cardiac MRI
PET-CT
Imaging modalities for diagnosis of endocarditis: a) Transthoracic echocardiography demonstrating native mitral valve vegetation. b) Cardiac MRI, systolic frame demonstrating vegetations in the sub-tricuspid valve chordal apparatus with adherent thrombus (white asterisk) and posterior mitral valve leaflet (black asterisk). c) PET-CT – In this patient, infection of a prosthetic aortic valve was suspected but echocardiography was inconclusive. Using PET-CT, inflammatory leukocytes are visualized after taking up radiolabeled glucose, demonstrating an area of active infection on the aortic valve. | Ao, aorta; LV, left ventricle; Veg, vegetation. Pacemaker lead images courtesy of Gail Peterson, MD. | Holland, T. L., Baddour, L. M., Bayer, A. S., Hoen, B., Miro, J. M., & Fowler Jr, V. G. (2016). Infective endocarditis. Nature Reviews. Disease Primers, 2, 16059. https://doi.org/10.1038/nrdp.2016.59
Pierce, D., Calkins, B. C., & Thornton, K. (2012). Infectious endocarditis: diagnosis and treatment. American family physician, 85(10), 981–986.
Antibiotic prophylaxis:
Pierce, D., Calkins, B. C., & Thornton, K. (2012). Infectious endocarditis: diagnosis and treatment. American family physician, 85(10), 981–986.
Surgical management:
Indications:
Fungal infection
Antibiotic-resistant bacteria
Left-sided IE caused by gram-negative bacteria
Persistent infection with positive blood cultures after one week of antibiotic therapy
One or more embolic events during the first two weeks of antibiotic therapy
Summary:
Holland, T. L., Baddour, L. M., Bayer, A. S., Hoen, B., Miro, J. M., & Fowler Jr, V. G. (2016). Infective endocarditis. Nature Reviews. Disease Primers, 2, 16059. https://doi.org/10.1038/nrdp.2016.59
