1. Infective Endocarditis

2. Goals for Today
Recognize the risk factors, signs, and symptoms of infectious endocarditis.
Understand the many approaches to diagnosing infectious endocarditis.
Appreciate the necessity of rapid treatment.
Anticipate possible complications.
Bring it all together with an actual patient case!

3. Definition
Infectious Endocarditis (IE): an infection of the heart’s endocardial surface
Classified into four groups:
Native Valve IE
Prosthetic Valve IE
Intravenous drug abuse (IVDA) IE
Nosocomial IE

4. Further Classification
Acute
Affects normal heart valves
Rapidly destructive
Metastatic foci
Commonly Staph.
If not treated, usually fatal within 6 weeks
Subacute
Often affects damaged heart valves
Indolent nature
If not treated, usually fatal by one year

5. Pathophysiology
Turbulent blood flow disrupts the endocardium making it “sticky”
Bacteremia delivers the organisms to the endocardial surface
Adherence of the organisms to the endocardial surface
Eventual invasion of the valvular leaflets
IE often occurs when there is an underlying cardiac abnormality that creates a high-low pressure gradient.
The resultant turbulent blood flow disrupts the endocardial surface by peeling away the endothelium.
The body’s natural response to endothelial damage is to repair it by laying down a sticky platelet-fibrin meshwork, which is a nidus for infection.
Temporary bacteremia delivers the offending organism to the endocardial surface where is sticks to the platelet-fibrin meshwork. This festers into an infection that eventually invades the cardiac valves.
The pathophysiology is slightly different with IVDA. It has been postulated that repeated injections of drugs and particulate material causes microtrauma to the cardiac valves, thereby starting the infection cascade.

6. Epidemiology
Incidence difficult to ascertain and varies according to location
Much more common in males than in females
May occur in persons of any age and increasingly common in elderly
Mortality ranges from 20-30%
There is an estimated 10-15,000 new cases of IE diagnosed in the U.S. each year, although the exact incidence of IE is difficult to ascertain. IE is a relatively uncommon disease, is not a reportable disease, and different case definitions have existed throughout the years. Furthermore, the incidence varies greatly depending on geographic regions.
IE is more common among males. The male:female ratio varies from 2:1 to 9:1 depending on the source.
In the past, IE was a disease of children and young adults. It predominantly affected children with congenital heart disease and adults with rheumatic heart disease. Today, IE commonly affects the elderly, with almost 50% of cases in the U.S. occurring in patients over the age of 60. This may be due to the decreasing incidence of rheumatic heart disease and the increasing proportion of elderly in the U.S.
Mortality from IE remains high, and ranges from 20-30% despite newer antibiotics and surgical options.

7. Risk Factors Intravenous drug abuse
Artificial heart valves and pacemakers
Acquired heart defects
Calcific aortic stenosis
Mitral valve prolapse with regurgitation
Congenital heart defects
Intravascular catheters
The top three risk factors for IE include, IVDA, prosthetic heart valves, and structural heart disease.
IVDA – one large study of IVDAs found that the use of cocaine was associated with a higher risk of IE than other injectable drugs. The most significant risk factor for right-sided IE is IVDA, although left sided disease is quite common among IVDAs. The most common infecting organism is clearly S. aureus, particularly in right-sided infection.
Prosthetic valve IE comprises a small proportion of all cases of IE and occurs in only 1% of all patients with artificial heart valves. The greatest risk is in the first year following valve replacement.
Structural heart disease – approximately ¾ of all cases of IE occur in patients with preexisting structural heart abnormalities. The most common underlying heart abnormalities include mitral valve prolapse with mitral regurgitation and aortic stenosis.
The most common congenital heart defects include Tetralogy of Fallot, bicuspid aortic valves, coarctation of the aorta, VSDs, and patent ductus arteriosus. In general, the higher the gradient of the valvular insufficiency, the higher the risk of IE.
One of the greatest risk factors of all is a prior episode of IE. Some studies have documented recurrence as high as 9%.

8. Infecting Organisms Common bacteria Not so common bacteria S. aureus
Streptococci
Enterococci
Not so common bacteria
Fungi
Pseudomonas
HACEK
Staphlococcal and Streptococcal organisms comprise over 80% of all infecting organisms.

9. Symptoms Acute Subacute High grade fever and chills SOB
Arthralgias/ myalgias
Abdominal pain
Pleuritic chest pain
Back pain
Subacute
Low grade fever
Anorexia
Weight loss
Fatigue
Arthralgias/ myalgias
Abdominal pain
N/V
The onset of symptoms is usually ~2 weeks or less
from the initiating bacteremia

10. Signs Fever Heart murmur
Nonspecific signs – petechiae, subungal or “splinter” hemorrhages, clubbing, splenomegaly, neurologic changes
More specific signs - Osler’s Nodes, Janeway lesions, and Roth Spots

11. Petechiae Nonspecific Often located on extremities or mucous membranes
dermatology.about.com/.../
blpetechiaephoto.htm
Harden Library for the Health Sciences
hardin/
md/cdc/3184.html
Photo credit, Josh Fierer, M.D.
medicine.ucsd.edu/clinicalimg/ Eye-Petechiae.html

12. Splinter Hemorrhages Nonspecific Nonblanching
Subungal hemorrhages that extend the entire length of the nail or are primarily located at the proximal end of the nail (near the cuticle) are like due to trauma.
Nonspecific
Nonblanching
Linear reddish-brown lesions found under the nail bed
Usually do NOT extend the entire length of the nail

13. Osler’s Nodes More specific Painful and erythematous nodules
American College of Rheumatology
webrheum.bham.ac.uk/.../ default/pages/3b5.htm
Hand10/Hand10dx.html
More specific
Painful and erythematous nodules
Located on pulp of fingers and toes
More common in subacute IE

14. Janeway Lesions More specific Erythematous, blanching macules
Nonpainful
Located on palms and soles

15. The Essential Blood Test
Blood Cultures
Minimum of three blood cultures1
Three separate venipuncture sites
Obtain 10-20mL in adults and 0.5-5mL in children2
Positive Result
Typical organisms present in at least 2 separate samples
Persistently positive blood culture (atypical organisms)
Two positive blood cultures obtained at least 12 hours apart
Three or a more positive blood cultures in which the first and last samples were collected at least one hour apart
If you suspect the pt has subacute IE or is not critically ill, then the three samples can be collected over hours and antibiotics can be held until all three samples have been drawn.
However, if the pt is acutely ill, critical, or unstable, the three cultures should be obtained over a 1 hour time span before beginning empiric therapy.
There is no need to collect anaerobic blood cultures since virtually all cases of IE are caused by aerobic organisms.
There is little additional diagnostic yield to collecting more than three blood cultures unless the pt was previously on antibiotics. In one study of 206 cases of IE, the initial blood culture was positive in 96% of streptococcal IE and one of the first two cultures were positive 98% of the time. For pt’s with IE cause by organisms other than strep, one of the first two blood culture was positive in 100% of the cases.
The estimated diagnostic yield of a blood culture increases by about 3% per mL of blood cultured. One study found that the detection rate for bacteremia increased from 69% to 92% when at least 5mL of blood were used for culture.
The most common cause of negative cultures in patients with IE is prior antibiotic use.

16. Additional Labs CBC ESR and CRP Complement levels (C3, C4, CH50) RF
Urinalysis
Baseline chemistries and coags
CBC – Look for a normochromic normocytic anemia and/or a leukocytosis.
ESR and CRP - Look for an elevated erythrocyte sedimentation rate and/or an elevated C-reactive protein which are present % of the time.
RF - Occasionally there will be an elevated levels of Rheumetoid Factor, particularly in patients who have been infected for six weeks or more. (Minor Duke’s Criteria)
UA - Urinalysis may reveal microscopic or gross hematuria, proteinuria, and pyuria. These findings along with a low serum complement level indicate a glomerulonephritis or “immunologic phenomena”. (Minor Duke’s Criteria)

17. Imaging Chest x-ray EKG Echocardiography
Look for multiple focal infiltrates and calcification of heart valves
EKG
Rarely diagnostic
Look for evidence of ischemia, conduction delay, and arrhythmias
Echocardiography
CXR – A chest xray can contain multiple diagnostic clues such as calcification of heart valves, which should raise suspicion in a febrile patient without an obvious source. More commonly, the chest xray may reveal septic pulmonary emboli in a patient with right-sided IE (Minor Duke’s Criteria).
EKG – An EKG alone cannot diagnose IE but it may show evidence of some of the disease’s complications. For example, EKG with ST changes may indicate ischemia or infarction from septic emboli. Arrhythmias such as heart block may indicated extension of the infection from the valves into the septum and surrounding cardiac tissue.

18. Indications for Echocardiography
Transthoracic echocardiography (TTE)
First line if suspected IE
Native valves
Transesophageal echocardiography (TEE)
Prosthetic valves
Intracardiac complications
Inadequate TTE
Fungal or S. aureus or bacteremia
TTE and TEE are complementary for evaluating cardiac hemodynamics and anatomy, but TEE has superior sensitivity, especially in detecting native valve vegetations, prosthetic valve vegetations, and local extension of infection. However, it is significantly more expensive and invasive.
If there is any suspicion of IE, get a TTE.
If there is staph or fungal bacteremia, a TEE should probably be obtained.
If there is a high clinical suspicion for IE and the TTE is negative, you should proceed to a TEE.
If there is a concern for intracardiac complications, a TEE is warranted.
It’s important to remember that the negative predictive value of a TEE is between 96-98%, meaning that a TEE cannot definitively rule out endocarditis. If the initial TEE is negative in a patient with a high clinical suspicion for IE, a repeat examiniation should be done if the pt does not improve.

19. Making the Diagnosis Pelletier and Petersdorf criteria (1977)
Classification scheme of definite, probable, and possible IE
Reasonably specific but lacked sensitivity
Von Reyn criteria (1981)
Added “rejected” as a category
Added more clinical criteria
Improved specificity and clinical utility
Duke criteria (1994)
Included the role of echocardiography in diagnosis
Added IVDA as a “predisposing heart condition”
Pelletier and Petersdorf criteria – 3 case categories:
Definite – histologic evidence of endocardial vegetations on examination of tissue
Probable - uniformly positive blood cultures with know underlying heart disease or embolic phenomena OR negative blood cultures in pts with fever, new regurgitant valvular heart murmur, and embolic phenomena
Possible - uniformly positive blood cultures with know underlying heart disease or embolic phenomena OR negative blood cultures with fever and known underlying heart disease and embolic phenomena
Von Reyn criteria – modified the above criteria to improve specificity and clinical utility.
Duke Criteria – relies upon major and minor clinical and pathologic criteria to classify cases as definite, possible, and rejected

20. Modified Duke Criteria
Definite IE
Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess
Histologic evidence of vegetation or intracardiac abscess
Possible IE
2 major
1 major and 3 minor
5 minor
Rejected IE
Resolution of illness with four days or less of antibiotics
Multiple studies have validated the Duke criteria. When applied and reapplied over the entire evaluation, these criteria are sensitive and specific and very rarely erroneously reject a true endocarditis.

21. Treatment Parenteral antibiotics Surgery Surveillance blood cultures
High serum concentrations to penetrate vegetations
Prolonged treatment to kill dormant bacteria clustered in vegetations
Surgery
Intracardiac complications
Surveillance blood cultures

22. Complications Four etiologies Embolic Local spread of infection
Metastatic spread of infection
Formation of immune complexes – glomerulonephritis and arthritis

23. Embolic Complications
Occur in up to 40% of patients with IE
Predictors of embolization
Size of vegetation
Left-sided vegetations
Fungal pathogens, S. aureus, and Strep. Bovis
Incidence decreases significantly after initiation of effective antibiotics
Systemic emboli are among the most common complications of IE, occurring in up to 40% of patients. Subclinical emboli are often found on autopsy.

24. Embolic Complications
Stroke
Myocardial Infarction
Fragments of valvular vegetation or vegetation- induced stenosis of coronary ostia
Ischemic limbs
Hypoxia from pulmonary emboli
Abdominal pain (splenic or renal infarction)

25. Septic Pulmonary Emboli

26. Septic Retinal Embolus

27. Local Spread of Infection
Heart failure
Extensive valvular damage
Paravalvular abscess (30-40%)
Most common in aortic valve, IVDA, and S. aureus
May extend into adjacent conduction tissue causing arrythmias
Higher rates of embolization and mortality
Pericarditis
Fistulous intracardiac connections

28. Local Spread of Infection
Acute S. aureus IE with perforation of the
aortic valve and aortic valve vegetations.
Acute S. aureus IE with mitral valve ring
abscess extending into myocardium.

29. Metastatic Spread of Infection
Metastatic abscess
Kidneys, spleen, brain, soft tissues
Meningitis and/or encephalitis
Vertebral osteomyelitis
Septic arthritis

30. Poor Prognostic Factors
Female
S. aureus
Vegetation size
Aortic valve
Prosthetic valve
Older age
Diabetes mellitus
Low serum albumen
Apache II score
Heart failure
Paravalvular abscess
Embolic events

31. What do these patients have in common?
Pt. A: 65 y/o female with PMH of esophageal cancer who presents to clinic with deyhdration, cough, SOB, and “oozing” near her mediport site.
Pt. B: 30 y/o male IVDA with a several weeks of fatigue and low grade fevers.
Pt. C: 24 y/o female IVDA with severe N/V/abd pain and fevers up to 104 for two weeks. Pt also c/o cough with DOE.

32. All these patients have MRSA endocarditis!

33. Patients A, B, and C Try to classify each patient’s IE.
Which of these patients likely has acute IE? Which has subacute IE?
What was the likely etiology of each patient’s bacteremia?

34. Patient C: History 2 wks of high fever, cough, green sputum, and DOE.
2 wks of N/V (5x/day), diarrhea (20x/day), and diffuse abdominal pain.
Diagnosed with PNA after a (-) LP and (+) CXR and an outside ER. Given PO abx but didn’t fill Rx.
Last IVDA 3 wks ago.

35. Patient C: History Which symptoms does Patient C have that suggest IE?
Does Patient C have any symptoms you can’t explain?

36. Patient C: Exam
Vitals: T 104.7, BP 100/50, HR 130, RR 48, 94% on 3L FM
Pale, distressed
Petechia to palate, dry mucus membranes
2/6 SEM at 4th intercostal space with radiation to axilla
Diffuse wheezing and crackles
Diffuse abdominal pain and right flank pain without rebound or guarding
Multiple track marks, otherwise neg. skin exam

37. Patient C: Exam Which signs does Patient C exhibit that suggest IE?
Does Patient C have any signs you can’t explain?

38. Patient C: Labs WBC 20, H/H of 9/27, Platelets 66
pH 7.45, pO2 54, pCO2 27
Albumen 1.7
UA: 2+ protein,3+ blood
EKG: WNL except sinus tachycardia
CXR: enlarged right heart, bilateral infiltrates with nodularity
Chest CT: multiple pulmonary abscesses

39. Patient C: Labs Can you explain these results?
Are there other lab values you would like to know?

40. Patient C: Diagnosis Blood Cx: three out of three bottles grew MRSA.
Initial TTE: tricuspid valve not well visualized but severe regurg. with PA systolic pressure of 55 mmHg.
Repeat TTE (~2 wks after coding!): oscillating mass on at least two leaflets of tricuspid valve that prolapse into R atrium during systole as well as thickened pulmonary valve with possible vegetation.

41. Patient C: Diagnosis What major Duke criteria does Patient C meet?
What minor Duke criteria does Patient C meet?

42. Patient C: Today s/p chest tube with removal
2 separate episodes of respiratory failure with intubation (now extubated)
1 episode of V. fib with cardioversion and a lidocaine gtt. (now weaned off after 1 episode of lidocaine toxicity)
CT surgery evaluated the pt and felt she wasn’t a surgical candidate.
She is currently still requiring 3L oxygen and c/o N/V and SOB on telemetry.

43. Summary IVDA and the elderly are at greatest risk of developing IE.
The signs and symptoms of IE are nonspecific and varied.
A thorough but timely evaluation (including serial blood cultures, adjunct labs, and an echo) is crucial to accurately diagnose and treat IE.
Beware of life-threatening complications.