QuestionSBA
QuestionChoice
Peripheral oedema is a non-specific finding for many conditions including heart failure, liver cirrhosis and nephrotic syndrome. Infective endocarditis may cause acute valvular heart failure and subsequently peripheral oedema, but it is not specific finding, which is what the question is asking.
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Peripheral oedema
QuestionChoice
A malar flush is a purple-red discolouration overlying the malar eminence, and in a cardiac examination, is associated with mitral stenosis and pulmonary hypertension secondary to this. Mitral stenosis presents as a mid-diastolic murmur over the mitral area, and is not usually caused by infective endocarditis, but rheumatic fever. Other features include a parasternal heave due to right ventricular hypertrophy and a loud second heart sound. This patient has no past medical history, and has clinical features of aortic regurgitation.
53308
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Malar flush
QuestionChoice
Rheumatic fever is caused by group A beta-haemolytic streptococci (S. pyogenes), and one of the major Jones diagnostic criteria is that of painless subcutaneous nodules.
Rheumatic fever can cause permanent damage to heart valves (rheumatic heart disease); it is rare in the developed world due to effective antimicrobial treatment of beta-haemolytic group A streptococcal infections. This patient is presenting acutely with a new murmur and fever, and as such infective endocarditis is the most likely diagnosis.
53310
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Subcutaneous painless nodules
QuestionChoice
A displaced apex beat can occur in a variety of conditions that result in left ventricular dilation, including a volume overloaded left ventricle as in mitral or aortic regurgitation, chronic right-left shunt, eventual decompensation in concentric hypertrophy secondary to pressure overload, or dilated cardiomyopathy. This patient may develop a displaced apex beat, but it is not specific.
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Displaced apex beat
QuestionChoice
This patient has aortic regurgitation caused by infective endocarditis, as indicated by the presence of fever and a new murmur. Her risk factors include current intravenous drug use. De Musset's sign is a rhythmic head nodding or bobbing in-sync with each heart beat, which is associated with aortic regurgitation. She also has a wide pulse pressure, which is also associated with aortic regurgitation. This patient should have an urgent echocardiogram.
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De Musset's sign
QuestionComment
Could the subcutaneous painless nodules not be Janeway lesions (i.e. supportive of endocarditis)?
20488
QuestionComment
This was my thinking too
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Monoclonal Serpiginous
QuestionComment
Janeway lesions are cutaneous and painless
Oslers nodes are subcutaneous and painful
25471
User
subscriber
Edema Dominant
User
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DNA Haemophilus
QuestionComment
May be being pedantic but think the question may benefit from some rephrasing: "Which clinical sign is most likely to be seen in this patient?". 

The question asks for the a specific sign for the diagnosis. The diagnosis is infective endocarditis, not aortic regurgitation (which has other causes).
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;-;
Concept
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# Summary

Infective endocarditis (IE) is a rare infection of the inner surface of the heart (endocardium), usually the valves. Various risk factors contribute to its development, including age, sex, intravenous drug use, poor dentition, valvular disease, congenital heart disease, prosthetic valves, and certain medical conditions like HIV. Symptoms can be diverse and non-specific including fevers, night sweats, weight loss, and myalgia. Diagnosis is based on the modified Duke Criteria, which include major and minor criteria. Treatment involves prolonged courses of intravenous antibiotics, and surgical intervention may be necessary in certain cases. Complications can be severe, and without appropriate treatment, IE can lead to heart failure and death. Prevention through antibiotic prophylaxis is no longer recommended.

# Definition 

Infective endocarditis (IE) is the infection of the inner surface of the heart (endocardium), usually the valves. 

# Epidemiology 

Infective endocarditis is a rare disease, impacting approximately 2-6 per 100,000 people every year. There are many risk factors implicated in the development of IE. 

Risk factors for IE: 

* Age >60 years
* Male sex
* IVDU: predisposition to _Staph. aureus_ infection and right-sided valve disease e.g. tricuspid endocarditis.
* Poor dentition and dental infections
* Valvular disease: rheumatic heart disease, mitral valve prolapse, aortic valve disease and any other valvular pathology.  
* Congenital heart disease: bicuspid aortic valve, pulmonary stenosis, and ventricular septal defects.
* Prosthetic valves
* Previous history of infective endocarditis
* Intravascular devices: central catheters and shunts.
* Haemodialysis
* HIV infection

Antibiotics have previously been prescribed to at-risk patients undergoing interventional procedures, frequently in dentistry, with the rationale that resultant bacteraemia could threaten to cause infective endocarditis. However, the evidence for this is inconclusive, and **NICE therefore do not advise antibiotic prophylaxis for IE.**

# Pathophysiology

A damaged endocardium can contribute to the development of IE. When part of the endocardium is damaged, the heart valve forms a local blood clot known as non-bacterial thrombotic endocarditis (NBTE). The platelets and fibrin deposits that form as part of the clotting process allows bacteria to stick to the endocardium leading to the formation of vegetations. The valves do not have a dedicated blood supply and so the body is unable to launch an appropriate immune response to the vegetations. The combination of damaged endocardium, vegetation development, and lack of an appropriate immune response results in infective endocarditis. 

# Classification 

IE can be considered according to different classification systems. 

## Acute vs. Subacute vs. Chronic IE 

IE can be considered according to duration of symptoms. 

* *Acute IE*: patient has signs or symptoms for days up to 6 weeks. Theoretically, a fulminant illness with rapid progression and so is most likely due to *S.aureus* infection. 
* *Subacute IE*: patients has signs or symptoms for 6 weeks up to 3 months. 
* *Chronic IE*: patients has signs or symptoms that persist for longer than 3 months. 

## Valve Type 

IE can be considered according to the type of valve involved. 

- *Native-valve endocarditis*: patient without prosthetic valve implant. 
- *Prosthetic-valve endocarditis*: 
	- Early prosthetic valve endocarditis occurs within 1 year of surgery. This is usually due to intra-operative contamination or post-operative nosocomial contamination. 
	- Late prosthetic valve endocarditis occurs beyond 1 year of surgery. This is usually due to community-acquired infections. 

# Common organisms  

The most common organisms involved in infective endocarditis (in order of incidence) are:

* _Staph. aureus_: now the most common cause of IE. Coagulase positive.
* _Strep. viridans_: used to be the most common cause of IE. Implicated in patients with poor dental hygiene. 
* Enterococci
* Coagulase negative _staphylococci_ e.g. _staph. epidermidis_: common culprit of prosthetic valve endocarditis. 
* _Strep. bovis_: important link with colorectal cancer. Need to consider colonoscopy and biopsy in these patients.
* Fungal 
* HACEK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella): culture negative causes of IE. 
* Non-infective: marantic endocarditis (malignancy - pancreatic cancer), Libman-Sacks endocarditis (SLE). 

# Symptoms

Clinical features of IE are diverse and variable. It may present acutely with a rapid deterioration or it can present subacutely/chronically with non-specific symptoms. 

* Common presenting symptoms: 
	* Fever: most common symptom. 
	* Night sweats 
	* Anorexia 
	* Weight loss 
	* Myalgia

* Others: 
	* Headache 
	* Arthalgia
	* Abdominal Pain 
	* Cough 
	* Pleuritic pain  

# Signs

**Systemic signs**: 

* Febrile 
* Cachectic 
* Clubbing
* Splenomegaly  

**Cardiac**: 

* Murmur: fever + new murmur is infective endocarditis until proven otherwise. 
* Bradycardia: aortic root abscess tracks down to the AVN causing heart block. 

**Vascular phenomena**: 

* Septic emboli: abdominal pain due to splenic infarct/abscess, focal neurology due to stroke, gangrenous fingers. 
* Janeway lesions: painless haemorrhagic cutaneous lesions in the palms and soles.  
* Splinter haemorrhages

**Immunological phenomena**: due to immune-complex deposition. 

* Osler's nodes: painful pulp infarcts on end of fingers. 
* Roth spots: boat-shaped retinal haemorrhages with pale centres seen on fundoscopy. 
* Glomerulonephritis: identified on urine dip. 

# Differential Diagnoses

* Non-infectious endocarditis/Nonbacterial thrombotic endocarditis (NBTE)
	* Similarities: both present with new murmurs and both may have constitutional symptoms including fevers and weight loss. 
	* Differences: blood cultures will likely be positive  in infective endocarditis and may identify microorganisms that are commonly associated with IE. NBTE is often associated with advanced malignancy (pancreatic cancer and marantic endocarditis), SLE (Libman Sacks endocarditis) or hypercoagulable states and will not have positive blood cultures. 

* Rheumatic Fever
	* Similarities: may both present with similar symptoms including fever, heart murmur and joint pain. 
	* Differences: rheumatic fever is an autoimmune response triggered by a Group A strep infection and ASOT titres may be high. In comparison, infective endocarditis will likely have positive blood cultures that identify a particular micro-organism. 


# Modified Duke Criteria 

For the diagnosis of IE, the modified Duke Criteria needs to be followed. 

A useful mnemonic to remember the criteria is **'BE FIVE PM'**:

* Major Criteria: 
	* **B**lood Cultures
	* **E**vidence of Endocardial Involvement: **E**cho

* Minor Criteria: 
	* **F**ever
	* **I**mmunological phenomena
	* **V**ascular phenomena
	* **E**chocardiogram minor criteria
	* **P**redisposing features
	* **M**icrobiological evidence that does not meet major criteria. 

For a definitive diagnosis of IE two major criteria, or one major and three minor criteria, or all five minor criteria must be present. 

## Major Criteria 

**Blood culture positive for IE**

* 2x separate positive blood cultures showing typical microorganisms consistent with IE (S viridans, S bovis, HACEK organisms, enterococcus). 
* Persistent bacteraemia with 2x blood cultures >12 hours apart or =>3 positive blood cultures with less specific microorganisms (S.aureus or S. epidermidis). 
* Single positive blood culture for Coxiella burnetti or positive antibody titre

**Evidence of endocardial involvement with imaging positive for IE**

* Echocardiogram (1st line TTE, then TOE) demonstrating vegetation, abscess, partial dehiscence of prosthetic valve or new valvular regurgitation. 
* Abnormal activity around site of prosthetic valve implantation on PET-CT
* Paravalvular lesions on cardiac CT

## Minor Criteria 

* **Fever**: >38.0 degrees celsius. 
* **Immunological phenomena**: Roth spots, Olser's nodes, immune complex-mediated glomerulonephritis, positive rheumatoid factor.
* **Vascular phenomena**: Evidence of septic embolis (splenic infarct/abscess), Janeway lesions, conjunctival haemorrhages, mycotic aneurysm, intracranial haemorrhage. 
* **Echocardiogram minor criteria**: not meeting above criteria. 
* **Predisposing features**: known valvular disease, IVDU, prosthetic valves etc. 
* **Microbiological evidence that does not meet major criteria**: blood culture not meeting major criteria, or serological evidence of active infection with organism consistent with IE

# Investigations

Bedside:

- **ECG**: increasing prolongation of PR interval suggests development and worsening of aortic root abscess. 
- **Urine dip**: look for haematuria which may suggest development of glomerulonephritis. 

Blood tests:

- **Routine bloods**: significant elevation of inflammatory markers and acute phase response is in line with infective endocarditis. If subacute/chronic process there may be a normocytic anaemia. 
- **Blood cultures**: required as per the modified Duke criteria. At least 3 sets of blood cultures taken at different times and sites. 

Imaging:

- **Echocardiogram**: 
	* **1st line**: transthoracic echocardiogram 
	* **2nd line**: transoesophageal echocardiogram; more invasive, but better view of mitral valve lesions and aortic root abscesses. It is the most sensitive diagnostic test. 
- **PET CT**: used to look for evidence of septic emboli. 

# Management

## Medical 

Mainstay of treatment for infective endocarditis is a prolonged course of IV antibiotics (approximately 6/52). Patients commonly require midline insertion to enable administration of IV antibiotics long-term. 

Examples of antibiotic choice demonstrated below: 

**Blind Therapy** when the organism and sensitivities are not yet known: 

* Native valve: amoxicillin (+/- gentamicin) 
* Pen-allergy/MRSA: vancomycin (+/- gentamicin) 
* Prosthetic valve: vancomycin + rifampicin + gentamicin 

**Native Valve S. aureus IE**

* 1st line: flucloxacillin 
* 2nd line: vancomycin + rifampicin 

**Prosthetic Valve S. aureus IE**

* 1st line: flucloxacillin + rifampicin + gentamicin 


**Strep viridans IE**

* 1st line: benzylpenicillin 
* 2nd line: vancomycin + gentamicin 

**HACEK IE**: 1st line: ceftriaxone 

## Surgical 

Despite the main-stay of treatment for IE being medical management. The following scenarios are indications for surgical intervention: 

* Haemodynamic instability
* Severe heart failure
* Severe sepsis despite antibiotics/failed medical therapy
* Valvular obstruction
* Infected prosthetic valve
* Persistent bacteraemia
* Repeated emboli
* Aortic root abscess

**Common exam question**: PR interval prolongation in a patient with Infective Endocarditis is an indication for surgery as it can be secondary to aortic root abscess

# Complications

Complications of infective endocarditis can also be the initial presenting complaint

* Acute valvular insufficiency causing heart failure
* Neurologic complications e.g. stroke, abscess, haemorrhage (mycotic aneurysm)
* Embolic complications causing infarction of kidneys, spleen or lung
* Infection e.g. osteomyelitis, septic arthritis


Without timely and appropriate treatment, IE can rapidly lead to heart failure and death. The mortality rate within the first 30 days has been estimated at approximately 20%. Long-term survival for IE has been estimated at 50% at 10 years. The mortality in IE remains high.  


# NICE Guidelines

[NICE Guidelines on Prophylactic Antibiotics in IE](https://www.nice.org.uk/guidance/cg64/ifp/chapter/infective-endocarditis)

# References 

[American Heart Association Summary on Heart Valves and Endocarditis](<https://www.heart.org/en/health-topics/heart-valve-problems-and-disease/heart-valve-problems-and-causes/heart-valves-and-infective-endocarditis#:~:text=What%20is%20infective%20endocarditis%3F,greater%20risk%20of%20developing%20it.>)
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De Musset's sign, which is a rhythmic bobbing of the head, suggests severe aortic regurgitation.
A 34-year-old woman presents to A&E with a three day history of fevers and joint pains. She denies any unwell contacts. She has a history of intravenous drug use but no other past medical history. Her vital signs are: HR 101bpm, RR 17 breaths per minute, O2 saturations of 98% on air, BP 157/61mmHg, and temperature 39.5. On examination, there is an early diastolic murmur on auscultation of the aortic area.

Which of the following clinical signs is specific to his diagnosis?
a