Endocarditis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2] Maliha Shakil, M.D. [3]

Endocarditis was first described in 1554. The inflammatory process associated with endocarditis was discovered in 1799. Vegetations were first discovered to be associated with endocarditis in 1806.

Important landmarks in the history of endocarditis include the following:^[1][2][3][4]

• In 1554: Earliest report of endocarditis in medical books.
• In 1669: Accurately description of tricuspid valve endocarditis.
• In 1646: Description of unusual “outgrowths” from autopsy of a patient with endocarditis; detected murmurs by placing a hand on patient’s chest.
• In 1708: Description of unusual structures in entrance of aorta.
• In 1715: Description of abnormality in aortic valve and mitral valve.
• In 1749: Description of valvular lesions.
• In 1769: Link between infectious disease and endocarditis established; association with spleen observed.
• In 1784: Intracardiac abnormalities accurately drawn.
• In 1797: Relationship between rheumatism and heart disease established.
• In 1799: Inflammatory process associated with endocarditis described.
• In 1806: Described unusual structures in the heart as “vegetations,” syphilitic virus as a causative agent of endocarditis, and theory of antiviral treatment of endocarditis.
• In 1809: Vegetations were described as not “outgrowths” or “buds” but particles adhering to the heart wall.
• In 1816: Invention of cylindrical stethoscope used to listen to heart murmurs; the link between venereal disease and endocarditis dismissed.
• In 1832: Laennec’s observations observed.
• In 1835-40: Named endocardium and endocarditis; described symptoms; herbal tea and bloodletting described as treatment regimen; the link between acute rheumatoid arthritis and endocarditis established.
• In 1852: Consequences of embolization of vegetations throughout body described. Described cutaneous nodules (named “Osler’s nodes” by Libman).
• In 1858-71: Examined fibrin vegetation associated with endocarditis by microscope; coined term “embolism;” discussed role of bacteria, vibrios, and micrococci in endocarditis.
• In 1861: Virchow’s theory on emboli described.
• In 1862: Granulations or foreign elements in blood and valves described.
• In 1868-70: Described infected arterial blood as originating from the heart; proposed scarlet fever as a cause of endocarditis.
• In 1869: Established “parasites” on skin transported to the heart and attached to endocardium; named Mycosis endocarditis.
• In 1872: Microorganisms in vegetations of endocarditis are described.
• In 1878: All cases of endocarditis were infectious in origin.
• In 1878: Combined experimental physiology and infection to produce an animal model of endocarditis in rabbit; noted valve had to be damaged before bacteria grafted onto the valve.
• In 1878: Micrococci enter vessels that valves were fitted into; valves exposed to abnormal mechanical attacks over long period created favorable niche for bacterial colonization.
• In 1879: Virchow’s student; employed early animal model of endocarditis.
• In 1879: Proposed etiology of endocarditis was based on infectious model and treatment should focus on eliminating “parasitic infection”
• In 1880: Working with Pasteur, proposed use of routine blood cultures.
• In 1881-86: Believed endocarditis could appear during various infections; noted translocation of respiratory pathogen from pulmonary lesion to valve through blood.
• In 1883: Believed microorganisms were result, not cause, of endocarditis.
• In 1884: Named disease “infective endocarditis“.
• In 1886: Demonstrated various bacteria introduced to bloodstream could cause endocarditis on valve that had previous lesion.
• In 1885: Synthesized work of others relating to endocarditis.
• In 1899: Described streptococcal, staphylococcal, pneumococcal, and gonococcal endocarditis.
• In 1903: First described “endocarditis lenta”.
• In 1909: Credited by Osler as first to observe cutaneous nodes (named “Osler’s nodes” by Libman) in patients with endocarditis.
• In 1909: Analyzed 150 cases of endocarditis and published diagnostic criteria relating to signs and symptoms.
• In 1910: Described initial classification scheme to include “subacute endocarditis,” with clinical signs/symptoms; absolute diagnosis required blood cultures.
• In 1981: Beth Israel criteria based on strict case definitions described.
• In 1994: New criteria utilizing specific echocardiographic findings.
• In 1995: Antibiotic treatment of adults with infective endocarditis caused by streptococci, enterococci, staphylococci, and HACEK microorganisms described.
• In 1996: Modified Duke Criteria to allow serologic diagnosis of Coxiella burnetii.
• In 1997: Guidelines for preventing bacterial endocarditis established.
• In 1997: Modifications to Duke criteria for clinical diagnosis of native valve and prosthetic valve endocarditis suggested: Analysis of 118 pathologically proven cases.
• In 1998: Guidelines for antibiotic treatment of streptococcal, enterococcal, and staphylococcal endocarditis established.
• In 1998: Antibiotic treatment of infective endocarditis due to viridans streptococci, enterococci, and other streptococci established; recommendations for surgical treatment of endocarditis.
• In 2000: Updated and modified Duke Criteria.
• In 2002: Duke Criteria to include a molecular diagnosis of causal agents.
• In 2001-3: Etiology of Bartonella spp., Tropheryma whipplei, and Coxiella burnetii in endocarditis described.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Endocarditis may be classified based on the underlying pathophysiology of the process (infective vs. non-infective), the onset of the disease (acute vs. subacute or short incubation vs. long incubation), results of the cultures (culture-positive vs. culture-negative), the nature of the valve (native vs. prosthetic) and the valve affected (aortic, mitral, or tricuspid valve).

Endocarditis may be classified into 8 subtypes based on:^[1][2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2] Ogheneochuko Ajari, MB.BS, MS [3]

The majority of cases of infective endocarditis are due to bacteria. Common causes of infective endocarditis include Streptococcus viridans, Staphylococci, and Enterococcus.

• Staphylococcus aureus^[1]
• Streptococcus viridans
• Coagulase negative Staphylococci
• Candida albicans
• Clostridium septicum
• Enterococcus
• HACEK organisms
• Pseudomonas
• Streptococcus bovis
• Streptococcus pneumoniae

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Endocarditis must be differentiated from other causes of a fever of unknown origin (FUO) such as pulmonary embolism, deep vein thrombosis, lymphoma, drug fever, cotton fever, and disseminated granulomatoses.^[1]

Endocarditis must be differentiated from other causes of a fever of unknown origin such as:^[1]

• Lymphoma
• Pulmonary embolism
• Deep vein thrombosis
• Drug fever
• Cotton fever
• Disseminated granulomatoses such as tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, and sarcoidosis

A drug fever will resolve with discontinuation of the offending agent. There may be elevated urine eosinophils and a peripheral eosinophilia as well.

The symptoms of cotton fever resemble those of sepsis and patients may be initially misdiagnosed upon admission to a hospital. However sepsis is a serious medical condition which can lead to death, whereas cotton fever, if left alone, will usually resolve itself spontaneously within 12-24 hours. Symptoms usually appear with 10-20 minutes after injection and in addition to fever may include headaches, malaise, chills, nausea and tachycardia. The fever itself usually reaches 38.5 – 40.3°C (101 – 105°F) within the first hour.^[2]

Table 1; Differentiating psittacosis from other diseases

Key;

+, occurs in some cases

++, occurs in many cases,

+++, occurs frequently

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Common risk factors for endocarditis include prosthetic heart valves, valvular heart disease, congenital heart disease, intravenous drug use, age-related degenerative valvular lesions, immunosuppression, and colon cancer.

Common risk factors in the development of infective endocarditis are:

• Prosthetic heart valves^[1]
• Valvular heart disease (mitral valve prolapse is the most common valvular lesion that predisposes to endocarditis)^[2][3]
• Intravenous drug abuse^[4]
• Intracardiac devices, such as implantable cardioverter-defibrillators^[5]
• Age-related degenerative valvular lesions
• Hemodialysis^[6]
• Congenital heart disease^[7]
• History of rheumatic heart disease^[8]
• Diabetes mellitus^[9][10]
• Colon cancer^[11]

Common risk factors in the development of nonbacterial thrombotic endocarditis include:

• Hypercoagulable state such as pregnancy and systemic bacterial infection ^[12][13]
• Malignancy especially mucin-producing adenocarcinomas (most commonly associated with pancreatic adenocarcinomas)^[14]
• Systemic lupus erythematosus^[15]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

The incidence of native valve infective endocarditis is approximately 1.7-6.2 cases per 100,000 individuals per year in the United States and Europe. The prevalence of infective endocarditis among IV drug users ranges from 10 to 15%.The incidence of endocarditis increases with age; the median age of patients is 47 to 69 years. There is an increased incidence of infective endocarditis in persons 65 years of age and older. Males are more commonly affected with endocarditis than females. The male to female ratio is approximately 1.7:1.

• The incidence of native valve infective endocarditis is approximately 1.7-6.2 cases per 100,000 individuals per year in the United States and Europe.^[1]

• The incidence of infective endocarditis increases with age; the median age of patients is 47 to 69 years.
• There is an increased incidence of infective endocarditis in persons 65 years of age and older.
• The incidence of nonbacterial thrombotic endocarditis increases with age; the median age of patients is 40 to 70 years.^[2]

• Males are more commonly affected with endocarditis than females.^[1]
• The male to female ratio is approximately 1.7:1.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

If left untreated, patients with endocarditis may progress to develop congestive heart failure. Complications of endocarditis can occur as a result of the locally destructive effects of the infection. These complications include perforation of valve leaflets causing congestive heart failure, abscesses, and disruption of the heart’s conduction system. Endocarditis may also cause embolization to the brain (causing a stroke), to the coronary artery (causing a heart attack), to the lung (causing pulmonary embolism), to the spleen (causing a splenic infarct), and to the kidney (causing a renal infarct). Prognosis of endocarditis is generally poor and the overall mortality rate for both native and prosthetic valve endocarditis ranges from 20-25%. The mortality rate for right-sided endocarditis in injection drug users is approximately 10%. The 5-year survival rate for native valve endocarditis is 70-80% and 50-80% for prosthetic valve endocarditis.

• If left untreated, patients with endocarditis may progress to develop congestive heart failure.^[1]

Complications of infective endocarditis include:^[1][2]

1. Murmur
2. A new aortic diastolic murmur suggests dilatation of the aortic annulus or eversion, rupture, or fenestration of an aortic leaflet
3. The sudden onset of a loud mitral pansystolic murmur suggests rupture of chordae tendineae or fenestration of a mitral valve leaflet
4. Congestive heart failure
5. Cardiac rhythm disturbances including AV block
6. Pericarditis (uncommon)

1. Petechiae of the conjunctiva, oropharynx, skin, and legs
2. Linear subungual splinter haemorrhages of the lower or middle nail bed
3. Osler’s nodes
4. Janeway lesions

1. Myalgias
2. Arthralgias
3. Arthritis
4. Low back pain
5. Rheumatoid factor is elevated in up to 50% of patients with endocarditis for >6 weeks
6. Clubbing of fingers is present in < 15% of patients

1. Petechial hemorrhages
2. Flame-shaped hemorrhages
3. Roth’s spots
4. Cotton-wool exudates in the retina

1. Significant arterial emboli occur in 30%–50% of patients, causing the following:
   • Stroke
   • Monocular blindness
   • Acute abdominal pain, ileus, and melena
   • Pain and gangrene in the extremities
2. CNS emboli are common
3. Coronary emboli, often asymptomatic, can cause myocardial infarction
4. Pulmonary emboli are common in right-sided endocarditis, causing pulmonary infarcts or focal pneumonitis

1. Splenomegaly is observed in 15%–30% of patients
2. Splenic infarcts occur in up to 40% of patients
3. Splenic abscesses occur in ~ 5% of patients

1. Microscopic hematuria occurs in ~ 50% of patients
2. Embolic renal infarction
3. Diffuse membranoproliferative glomerulonephritis

Occur in any artery in 2%–8% of patients, causing the following:

1. Pain or headache
2. Pulsatile mass
3. Fever
4. Sudden expanding hematoma
5. Signs of major blood loss

1. Neurologic complications occur in 25%–40% of cases
2. Strokes caused by cerebral embolisms in ~15% of cases, causing the following:

   • Altered level of consciousness
   • Seizures
   • Fluctuating focal neurologic signs

3. Cerebral aneurysms occur in 1%–5% of cases, causing the following:

   • Headache
   • Focal signs
   • Acute intracerebral or subarachnoid hemorrhage caused by rupture
   • Mild meningeal irritation resulting from slow leakage

4. Brain abscesses may occur in acute endocarditis caused by Staphylococcus aureus
5. Seizures

Among those patients at high risk, careful monitoring should be undertaken to detect the early development of complications such as:

1. Valvular dysfunction, usual insufficiency of the mitral or aortic valves
2. Myocardial or septal abscesses
3. Congestive heart failure
4. Metastatic infection
5. Embolic phenomenon

• The prognosis of endocarditis is generally poor and the overall mortality rate for both native and prosthetic valve endocarditis ranges from 20-25%.
• The mortality rate for right-sided endocarditis in injection drug users is approximately 10%.^[1]
• The 5-year survival rate for native valve endocarditis is 70-80% and 50-80% for prosthetic valve endocarditis.^[2]

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