Infective endocarditis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

All patients with bacteremia should be suspected of potentially having IE, particularly those with an audible murmur. The classic new or worsening cardiac murmur is rare. Patients who develop new regurgitant murmurs are at increased risk of developing congestive heart failure. Elderly or immunocompromised patients may present atypically, without fever. As the population ages, IE is becoming more frequent in patients ages over 70 years, with trends toward worsening outcomes.[61] Diagnosis in older people is often made later in the course of the disease as a result of more indolent presentations, and this undoubtedly contributes to poorer outcomes. While it is uncommon in pregnancy, IE should be considered in pregnant patients who present with fever accompanied by cardiac signs, including tachycardia, new or changing heart murmurs and evidence of septic emboli.[7][24] The same risk factors for IE pertain to pregnant patients as nonpregnant patients.[7][24]

Initial laboratory studies should include basic complete blood count (CBC) and electrolyte panel, at least two sets of blood cultures (ideally taken >6 hours apart if clinical status allows), and urinalysis. Blood cultures are recommended to be taken prior to initiation of antibiotics.[20] All patients should have an initial ECG, and subsequently an echocardiogram must be obtained.[6][7][62][63][Figure caption and citation for the preceding image starts]: A transthoracic echo showing large mobile vegetations on the anterior and posterior leaflets of the tricuspid valveFoley JA, Augustine D, Bond R, et al. Lost without Occam's razor: Escherichia coli tricuspid valve endocarditis in a non-intravenous drug user. BMJ Case Rep. 2010 Aug 10;2010. pii: bcr0220102769 [Citation ends]. com.bmj.content.model.Caption@42cf9c11 [Figure caption and citation for the preceding image starts]: Image from transesophageal echocardiogram. White arrow indicates vegetation on the patient's aortic valveTeoh LS, Hart HH, Soh MC, et al. Bartonella henselae aortic valve endocarditis mimicking systemic vasculitis. BMJ Case Rep. 2010 Oct 21;2010. pii: bcr0420102945 [Citation ends]. com.bmj.content.model.Caption@4e7ee911

The American Heart Association and the American College of Cardiology recommend using the Modified Duke Criteria in patients with suspected IE.[20] [ Endocarditis Diagnostic Criteria - Modified Duke Criteria Opens in new window ]

Acute

Patients often present with signs and symptoms of peripheral or central emboli, or with evidence of decompensated congestive heart failure. Therefore, urgent evaluation for IE is important for any patients who present with fever in conjunction with headache, meningeal signs, stroke symptoms, chest pain, dyspnea on exertion, orthopnea, or paroxysmal nocturnal dyspnea; and for any patients with unexplained fever who are at high risk of IE (e.g., congenital or acquired valvular disease, previous IE, prosthetic heart valves, congenital or heritable heart malformations, immunodeficiency, injection drug use).[20] Arthralgias and back pain may also result from peripheral septic emboli. Classic immunologic features (e.g., Osler nodes, Roth spots) are uncommon, due to rapid onset of disease process.

Subacute

Patients present with fever and chills, nonspecific constitutional symptoms (night sweats, malaise, fatigue, anorexia, weight loss, myalgias), or palpitations. Physical exam is often nonspecific, but subacute presentations are more likely to exhibit classic exam findings such as Janeway lesions (hemorrhagic, macular, painless plaques with a predilection for the palms and soles), Osler nodes (small, painful, nodular lesions usually found on the pads of the fingers or toes) splinter hemorrhages (commonly noted in the nails of the upper and lower extremities), or cutaneous infarcts. Palatal petechiae may also be present. Fundoscopy may detect Roth spots (oval, pale, retinal lesions surrounded by hemorrhage). Skin exam should include assessment for evidence of intravenous drug use. Subacute IE must always be in the differential diagnosis of a patient with progressive fever and constitutional symptoms.[Figure caption and citation for the preceding image starts]: Janeway lesionsFrom the collection of Sanjay Sharma, St George’s University of London, UK; used with permission [Citation ends]. com.bmj.content.model.Caption@6c0efc74 [Figure caption and citation for the preceding image starts]: Janeway lesionsFrom a private collection; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Osler nodeFrom the collection of Sanjay Sharma, St George’s University of London, UK; used with permission [Citation ends]. com.bmj.content.model.Caption@5b77e54e [Figure caption and citation for the preceding image starts]: Osler's nodesFrom a private collection; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Cutaneous infarctsFrom the collection of Sanjay Sharma, St George’s University of London, UK; used with permission [Citation ends]. com.bmj.content.model.Caption@275ac218 [Figure caption and citation for the preceding image starts]: Roth spotsFrom the collection of Sanjay Sharma, St George’s University of London, UK; used with permission [Citation ends].

IE in the intensive care unit (ICU)

There are multiple challenges to diagnosing IE in the ICU. Presentation is often atypical, and may be concealed by other pathology. Furthermore, transthoracic echocardiogram (TTE) is likely to be less diagnostically accurate, owing to the practical difficulties of scanning in the ICU. Hence, transesophageal echocardiogram (TEE) must be considered at an earlier stage in the diagnostic process.

Laboratory tests

Blood cultures are the most important laboratory test for confirming IE. At least three sets of blood cultures from different venipuncture sites should be taken, the first and last samples taken at least one hour apart (ideally >6 hours apart if clinical status allows).[6][7] Blood culture results taken this way are positive in 90% of patients with IE.[20] Cultures should not be taken from indwelling lines, to minimize risk of contamination.

However, empiric antibiotic therapy should not be delayed while waiting to take three sets of blood cultures if the patient is unwell (e.g., with sepsis).[64] The volume of blood sent for culture is more important than the number of sets of cultures.[65] The most common cause of culture-negative endocarditis is antibiotic therapy preceding blood cultures.[66]

Do not routinely request extended incubation of blood cultures in suspected endocarditis.[20][67]

Other initial laboratory studies should include basic CBC and electrolyte panel, C-reactive protein (CRP), and urinalysis. If the patient is febrile, laboratory signs of infection (such as elevated CRP or leukocytosis), anemia, and microscopic hematuria support a diagnosis of IE. However, these are not specific for the diagnosis of IE.

In practice, CRP is also useful as a baseline test and to monitor response to treatment. Elevated CRP >40 mg/L is an independent risk factor for embolic events in patients with IE.[68] Testing for rheumatoid factor and measuring erythrocyte sedimentation rate and complement levels may also be helpful. Urinalysis is used to evaluate renal involvement. In addition, electrolyte panel, glucose, and liver function tests are used to mark progress of the disease, and to assess vital organ function and systemic effects of infection.

Emerging tests

Mean platelet volume (MPV) is associated with platelet activation which occurs in the setting of endothelial damage. Increased MPV has been shown to be an independent predictor of embolic events in patients with IE.

Anti‐beta-2‐glycoprotein I antibodies enhance activation of platelets and the coagulation cascade and have been associated with increased risk of embolic events.

D-dimer and troponin I have also been linked to increased embolic risk but are nonspecific and may be surrogate markers for severity of illness rather than independent predictors of embolic events.[68]

Echocardiography

Echocardiography should be performed in all patients with suspected IE.[6][7][62][63][69] Echocardiography is important not only for confirming or ruling out the diagnosis but also for evaluation of complications and prognosis.[62] The decision to obtain a TTE rather than TEE is often difficult and has been considered by various guidelines.[6][7][62][63][69] The American Heart Association and the American College of Cardiology recommend that any patient suspected of having native valve IE should be screened with TTE to evaluate for the presence of a vegetation, and to assess any effects on valvular function.[20] If negative, and suspicion still remains, patients should undergo TEE.[15][63] TEE is the preferred form of echocardiography in people with prosthetic material suspected to have IE.[15][63] TEE is also indicated in patients with a positive TTE, but where complications are suspected or likely, and before cardiac surgery during active IE. 3-dimensional echocardiography can provide additional anatomic information and may be used in concert with traditional 2-dimensional echocardiography.[70] When TEE is contraindicated or not feasible, intracardiac echocardiography may be an alternative for diagnosing IE.[71]

ECG

An ECG should be undertaken, as progression of the infection may lead to conduction system disease.[72] Conduction abnormalities secondary to IE (mainly first-, second-, and third-degree atrioventricular block) are uncommon but are associated with worse prognosis and higher mortality compared with patients without conduction abnormalities.[73]

Cardiac computed tomography (CT)

CT imaging is used for the diagnosis of native and prosthetic valve IE and for detection of complications of IE, including abscesses, pseudoaneurysms, and fistulae.[74][75] CT has been found to compare favorably with TTE in detecting valvular abnormalities in patients with IE, but it may miss small defects (e.g., small leaflet perforations [≤2 mm diameter], small vegetations <10 mm).[7][76] Whole-body and brain CT can be used to look for distant lesions, systemic complications of IE, and septic emboli, as well as having a role in detecting extracardiac sources of bacteremia and potentially alternate diagnoses in patients where IE has been excluded.[6][7] CT angiography is a sensitive and specific test for detecting mycotic arterial aneurysms; magnetic resonance imaging (MRI) is superior for assessment of neurologic complications in terms of imaging, but is limited by accessibility and availability.[6][7]

Head MRI

MRI is of less diagnostic value than CT, but is the imaging modality of choice when investigating the cerebral complications of IE, with studies consistently reporting cerebral infarcts in up to 80% of patients.[7][77][78] MRI reveals cerebral lesions in 50% of patients who do not demonstrate neurologic symptoms.[79] MRI is also used to assess spinal involvement in IE, including spondylodiscitis and vertebral osteomyelitis.[7]

Nuclear imaging and photon emission tomography (PET)

Single-PET/CT and 18F-fluorodeoxyglucose PET/CT may be particularly useful in patients with “possible IE” defined according to Duke criteria, in the demonstration of infectious embolic events, and in cases of suspected prosthetic valve IE where echocardiography is not diagnostic.[20][75][80][81][82][83][84]