Endocarditis

Epidemiology

  • Incidence: 10-15k new cases of infective endocarditis are diagnosed each year in the US
  • Incidence of Prosthetic Valve Infective Endocarditis: account for 10-20% of infective endocarditis cases
    • Overall Incidence: 0.1% to 2.3% per patient-year

Risk Factors for Infective Endocarditis

  • Age >60 y/o
    • Valvular Heart Disease is Increasingly Prevalent in the Older Patients
    • Older Patients are Undergoing More Invasive Procedures
  • Chronic Hemodialysis (see Hemodialysis, [[Hemodialysis]])
  • History of Infective Endocarditis
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
  • Intravascular Device
  • Intravenous Drug Abuse (IVDA) (see Intravenous Drug Abuse, [[Intravenous Drug Abuse]])
    • Overall Incidence: 1-5% per year
    • Tricuspid Valve is Infected in >70% of Cases
    • Most Cases Have No Pre-Existing Heart Disease
  • Male Sex
  • Poor Dentition/Dental Infection
  • Prosthetic Heart Valve
  • Structural Heart Disease
    • Congenital Heart Disease
    • Valvular Heart Disease

Etiology

Non-Infective Endocarditis

Infective Endocarditis

Most Commonly Associated Organisms

  • General Comments: Staphylococcus and Streptococcus account for the majority of infective endocarditis cases
  • Staphylococcus (see Staphylococcus, [[Staphylococcus]])
  • Streptococcus (see Streptococcus, [[Streptococcus]])
    • Viridans Group Streptococci (see Viridans Group Streptococci, [[Viridans Group Streptococci]]): account for 17% of infective endocarditis cases
    • Other Streptococci: accounts for 5% of infective endocarditis cases
  • Enterococcus (see Enterococcus, [[Enterococcus]]): accounts for 11% of infective endocarditis cases

Other Organisms

  • Abiotrophia (see Abiotrophia, [[Abiotrophia]])
    • Abiotrophia Defectiva
  • Bartonella (see Bartonella, [[Bartonella]])
    • Bartonella Henselae (Cat Scratch Disease) (see Bartonella Henselae, [[Bartonella Henselae]])
    • Bartonella Quintana (Formerly Known as Rochalimaea Quintana, Rickettsia Quintana, Rickettsia Weigli, Rickettsia Volhynia, and Rickettsia Pediculi) (see Bartonella Quintana, [[Bartonella Quintana]]): associated with body lice in homeless patients
  • Brucella (see Brucella, [[Brucella]]): infective endocarditis due to Brucella occurs predominantly in regions where it is endemic
  • Gram-Negative Rods: account for 2% of infective endocarditis cases
    • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
      • Physiology: adheres less readily to heart valves than Gram-positive organisms
    • Klebsiella Pneumoniae (see Klebsiella Pneumoniae, [[Klebsiella Pneumoniae]])
      • Physiology: adheres less readily to heart valves than Gram-positive organisms
    • Pseudomonas Aeruginosa (see xxxx, [[xxxx]])
      • Epidemiology: increased risk with intravenous drug abuse and HIV infection
    • Salmonella (see Salmonella, [[Salmonella]])
      • Epidemiology: increased risk with intravenous drug abuse and HIV infection
  • Granulicatella (see Granulicatella, [[Granulicatella]])
    • Granulicatella Adiacens
    • Granulicatella Elegans
  • Fungi: account for 2% of infective endocarditis cases
  • HACEK Organisms: account for 2% of infective endocarditis cases
  • Listeria (see Listeria, [[Listeria]])
    • Epidemiology: increased risk with HIV infection

Physiology

  • xxx

Diagnosis

Electrocardiogram (EKG) (see Electrocardiogram, [[Electrocardiogram]])

  • xxx

Blood Culture (see Blood Culture, [[Blood Culture]])

  • May Be Positive

Transthoracic Echocardiogram (TTE) (see Echocardiogram, [[Echocardiogram]])

  • May Be Diagnostic

Transesophageal Echocardiogram (TEE) (see Echocardiogram, [[Echocardiogram]])

  • More Invasive Than TTE
  • More Sensitive Than TTE for Detecting Vegetations, Periannular Extension, and Abscess
  • Specificity:

    • May be less specific than TTE: may detect Lambl’s excrescences (normal valvular strands that may be confused with findings of endocarditis)
    • May distinguish between patients with uncomplicated Staph aureus bacteremia and endocarditis: 25% of patients with Staph aureus bacteremia were found to have unsuspected endocarditis by TEE (Fowler, 1997. J Am Coll Cardiol; 30: 1072-1078)
    • TEE may help determine whether 2 or 4 wks of therapy is needed in cases of uncomplicated Staph aureus bacteremia with prompt resolution of fever and resolution of bacteremia with catheter removal (Rosen, 1999, Ann Intern Med; 130: 810: 820)
    • TEE is more cost-effective than TTE or empiric therapy in patients with probability of endocarditis of 4-60%, with unexplained Staph aureus or Strep bacteremia (Heidenreich, 1999, Am J Med; 107: 198-208)

Duke Diagnostic Criteria

  • Definite endocarditis: either 2 major , 1 major + 3 minor, OR 5 minor criteria
  • Possible endocarditis: either 1 major + 1 minor OR 3 minor criteria

Major Criteria

  • Typical organism (Staph aureus) grown from 2 blood c/s
  • Any organism grown persistently from blood c/s
  • Positive serology or single positive blood c/s for Coxiella burnetti (Q fever agent)
  • Evidence of endocardial involvement on Echo (oscillating intracardiac mass, abscess, or new partial dehiscence of prosthetic valve)
  • Physical exam with new valular regurg murmur (change in murmur is not sufficient)

Minor Criteria

  • Predisposing heart condition or IVDA
  • Fever >38 °C
  • Embolic phenomena (major arterial emboli, septic pulmonary infarct, mycotic aneurysm, IC bleed, conjunctival hemorrhages, Janeway lesions)
    • Petechiae or splinter hemorrhages are not sufficient
  • Immunologic phenomena (GLN, Osler’s nodes, Roth spots, positive RF)
  • Serologic evidence of infection or positive blood c/s not meeting the major criteria
    • Single positive blood c/s for Staph epi is not sufficient

Clinical Manifestations

Cardiovascular Manifestations

Atrioventricular Heart Blocks

  • General Comments: in cases with valve ring abscess
    • Periannular Extension Occurs in 10-40% of Infective Endocarditis Cases
      • Periannular Extension Occurs in 56-100% of Prosthetic Valve Infective Endocarditis Cases: it accounts for high mortality in this group
    • Periannular Extension is Most Common in Aortic Valve Endocarditis: abscess expands near the membranous septum and atrioventricular node (which may result in heart block)
  • First Degree Atrioventricular Block (First Degree Heart Block) (see First Degree Atrioventricular Block, [[First Degree Atrioventricular Block]])
  • Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I, [[Second Degree Atrioventricular Block-Mobitz Type I]])
  • Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II, [[Second Degree Atrioventricular Block-Mobitz Type II]])
  • Third Degree Atrioventricular Block (Third Degree Heart Block, Complete Heart Block) (see Third Degree Atrioventricular Block, [[Third Degree Atrioventricular Block]])

Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])

  • Epidemiology
    • Congestive heart failure complicating infective endocarditis has the greatest impact on prognosis of all complications
    • Congestive heart failure complicating infective endocarditis is usually due to valvular regurgitation
  • Physiology
    • Congestive Heart Failure Due to Intracardiac Shunt Associated with a Fistulous Tract (see Intracardiac and Extracardiac Shunt, [[Intracardiac and Extracardiac Shunt]])
    • Congestive Heart Failure Due to Prosthetic Valve Dehiscence or Obstruction
    • Congestive Heart Failure Due to Severe Mitral/Aortic Regurgitation: presentation may be acute with perforation of native/bioprosthetic valve leaflet or rupture of infected mitral chordae
      • Echocardiogram: elevated left ventricular end-diastolic pressure (LV-EDP) or significant pulmonary hypertension
    • Congestive Heart Failure Due to Valve Obstruction by Vegetations: less common

Heart Murmur (see Heart Murmurs, [[Heart Murmurs]])

  • xxx

Sinus of Valsalva Aneurysm with/without Rupture (see Sinus of Valsalva Aneurysm, [[Sinus of Valsalva Aneurysm]])

  • Physiology: with involvement of aortic valve

Tamponade (see Tamponade, [[Tamponade]])

  • Physiology: may occur with fistulous tract formation into the pericardial space

Dermatologic Manifestations

  • Janeway Lesions (see xxxx, [[xxxx]]): painless dark spots on palms or soles
  • Osler’s Nodes (see xxxx, [[xxxx]]): painful nodules on pads of the digits
  • Vesicular-Bullous Skin Lesions (see Vesicular-Bullous Skin Lesions, [[Vesicular-Bullous Skin Lesions]])

Neurologic Manifestations

General Comments

  • Incidence of Neurologic Events: occur in 20-40% of infective endocarditis cases
    • Most Events are Due to Embolization of Vegetations
    • Most Commonly Associated with Infective Endocarditis Due to Staphylococcus Aureus
  • Neurologic Events May Be Silent

Neurologic Presentations

Systemic Embolic Manifestations

  • Epidemiology
    • Incidence of Systemic Embolization: 22-50% of cases of infective endocarditis
    • Timing of Systemic Embolization: most events occur before the diagnosis is made or within the first 2 wks
      • Risk Falls Dramatically During/After the First 2-3 wks of Successful Antibiotic Therapy
    • Highest Rate of Embolic Complications is Associated with Left-Sided Infective Endocarditis
    • Risk of Systemic Embolization is Highest with Large (10-15 mm) Mobile Vegetations
  • Organisms with the Highest Risk for Systemic Embolization in Infective Endocarditis
  • Physiology
    • Vegetations may persist on the valve, even after cure
  • Clinical: may be clinically silent in 25% of cases (detected only by imaging studies)
    • Bowel Embolism
    • Coronary Artery Emboli
    • Hepatic Embolism
    • Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]]): central nervous system accounts for 65% of all emboli in infective endocarditis (90% of which are to the middle cerebral artery)
    • Peripheral Vascular Embolism
    • Septic Pulmonary Embolism (see Septic Embolism, [[Septic Embolism]])
    • Splenic Embolism

Ophthalmologic Manifestations

  • Roth Spots (see Roth Spots, [[Roth Spots]]): pale areas surrounded by hemorrhage on funduscopic exam

Other Manifestations

Sepsis (see Sepsis, [[Sepsis]])

  • xxx

Treatment

Antibiotic Therapy

  • xxxx

Native valve:
1) PCN-susceptible Strep viridans/Strep bovis/other Strep:
a) PCN or ceftriaxone x 4 wks
b) PCN or cetriaxone + low-dose gent x 2 wks
c) Vanco x 4 wks
2) Relatively PCN-resistant Strep viridans/Strep bovis/other Strep:
a) PCN or ceftriaxone x 4 wks + low-dose gent x 2 wks
b) Vanco x 4 wks
3) Susceptible enterococcus/resistant Strep:
a) PCN or amp or vanco + low-dose gent x 4 wks (x 6 wks, if symptoms present for >3 mo)
4) Methicillin-sensitive Staph:
a) Naf or ox or cefazolin or vanco x 4-6 wks + low-dose gent x 3-5 days
5) Methicillin-resistant Staph:
a) Vanco x 4-6 wks + low-dose gent x 3-5 days
6) HACEK:
a) Ceftriaxone x 4 wks or amp + low-dose gent x 4 wks
7) Culture-negative:
a) Vanco +low-dose gent x 4 wks +/- ceftriaxone

Prosthetic valve: early prosthetic valve endocarditis (within 2 mo of surgery) usually requires replacement, while late endocarditis may be treated medically
1) PCN-susceptible Strep viridans/Strep bovis/other Strep:
a) PCN x 6 wks + low-dose gent x 2 wks
2) Relatively PCN-resistant Strep viridans/Strep bovis/other Strep:
a) PCN x 6 wks + low-dose gent x 2-4 wks
3) Susceptible enterococcus/resistant Strep:
a) PCN or amp or vanco + low-dose gent x 6 wks
4) Methicillin-sensitive Staph:
a) Naf or ox or cefazolin or vanco + PO rifampin (add after a few days to prevent selecting for resistance) x 6 wks + low-dose gent x 2 wks
5) Methicillin-resistant Staph:
a) Vanco x 6 wks + PO rifampin (add after few days) + low-dose gent x 2 wks
6) HACEK:
a) Ceftriaxone x 6 wks or amp + low-dose gent x 6 wks
7) Culture-negative:
a) Vanco +low-dose gent x 6 wks +/- ceftriaxone

Surgery

Clinical Factors in Considering Surgery

  • Approximately 50% of All Patients with Endocarditis Will Ultimately Require Surgery
  • Negative Blood Cultures are Not Required for Surgery

Indications for Surgery in Infective Endocarditis [MEDLINE]

  • Cerebrovascular Complications
    • Silent Neurological Complication
    • Transient Ischemic Attack (TIA) (see Transient Ischemic Attack, [[Transient Ischemic Attack]])
    • Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident, [[Ischemic Cerebrovascular Accident]]): provided that cerebral hemorrhage has been excluded and neurological complications are not severe (such as presence of coma)
      • Surgery is contraindicated for at least one month after intracranial hemorrhage (unless neurosurgical or endovascular intervention can be performed to reduce the hemorrhagic risk)
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
    • General Comments
      • Surgery should be performed immediately, irrespective to antibiotic therapy, in patients with persistent pulmonary edema and/or cardiogenic shock
      • Surgery can be delayed for days-weeks in cases where heart failure can be medically managed
      • In infective endocarditis complicated by heart failure, surgery significantly decreases the mortality rate: best results are obtained when surgery is performed within 1 wk of presentation
    • Congestive Heart Failure Due to Intracardiac Shunt Associated with a Fistulous Tract (see Intracardiac and Extracardiac Shunt, [[Intracardiac and Extracardiac Shunt]])
    • Congestive Heart Failure Due to Prosthetic Valve Dehiscence or Obstruction
    • Congestive Heart Failure Due to Severe Mitral/Aortic Regurgitation: with echocardiographic signs of elevated left ventricular end-diastolic pressure (LV-EDP) or significant pulmonary hypertension
    • Congestive Heart Failure Due to Valve Obstruction by Vegetations: less common
    • Congestive Heart Failure/Tamponade Due to Fistulous Tract Formation Into Pericardial Space (see Tamponade, [[Tamponade]])
  • Difficult Organisms
    • Aspergillus (see Aspergillus, [[Aspergillus]])
    • Brucella (see Brucella, [[Brucella]]): aggressive organisms
    • Candida (see Candida, [[Candida]])
    • Gram-Negative Rods
    • Methicillin-Resistant Staphylococcus Aureus (MRSA) (see Staphylococcus Aureus, [[Staphylococcus Aureus]]): resistant organism
    • Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])
    • Q Fever (Coxiella Burnetii) (see Q Fever, [[Q Fever]])
    • Staphylococcus Aureus on Left-Sided Native Valve (Most Cases) (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Staphylococcus Aureus on Prosthetic Valve (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Staphylococcus Lugdunensis (see Staphylococcus Lugdunensis, [[Staphylococcus Lugdunensis]]): aggressive coagulase-negative organism
    • Vancomycin-Resistant Enterococcus (VRE) (see Enterococcus, [[Enterococcus]]): resistant organism
  • Periannular Extension
    • Fistulous Tract
    • Myocardial Abscess
  • Persistent Sepsis (see Sepsis, [[Sepsis]])
    • Fever/Positive Blood Cultures Persisting for 5-7 Days Despite Appropriate Antibiotics: assuming that vegetations and other surgically-amenable lesions persist and that extracardiac sources of sepsis are excluded
    • Relapsing Endocarditis: especially when caused by organisms other than sensitive Streptococci or in patients with prosthetic valves
  • Prosthetic Valve Endocarditis
    • Virtually All Cases of Early Prosthetic Valve Endocarditis
    • Virtually All Cases of Prosthetic Valve Endocarditis Caused by Staphylococcus Aureus
    • Late Prosthetic Valve Endocarditis with Congestive Heart Failure Du eto Prosthetic Dehiscence or Obstruction
  • Systemic Embolization: in these cases, surgery must be performed early, since risk of embolization is highest during the first days of therapy
    • Large Vegetations (>10 mm) After One or More Clinical or Silent Embolic Events After Initiation of Antibiotic Therapy
    • Large Vegetations and Other Predictors of a Complicated Course
    • Recurrent Emboli Despite Appropriate Antibiotic Therapy
    • Very Large Vegetations (>15 mm) Without Embolic Complications, Especially if Valve-Sparing Surgery is Likely: controversial indication

Clinical Efficacy

  • Outcomes After Surgical Treatment of Native and Prosthetic Valve Endocarditis (Ann Thorac Surg, 2012) [MEDLINE]
    • Surgical Treatment is Associated with a 90% Hospital Survival Rate
    • 30-Day Outcomes Were Better for Native Valve Endocarditis Than for Prosthetic Valve Endocarditis
    • Long-Term Outcomes are Similar for Both Native Valve and Prosthetic Valve Endocarditis
    • Staphylococcus Aureus Was Associated with Significantly Higher Mortality Compared to Other Pathogens
  • Comparison of Early Surgery vs Conventional Treatment in Endocarditis (NEJM, 2012) [MEDLINE]
    • Early Surgery Decreases Embolic Events and All-Cause Mortality

Special Considerations

  • Right-Sided Endocarditis: a more conservative approach is recommended, with surgery being indicated only if fever persiste despite 3 weeks of treatment (in the absence of lung abscess) [MEDLINE]

Infective Endocarditis Prophylaxis

  • xxx

Prophylaxis: controversial, as risk of endocarditis related to dental procedures (other than tooth extraction) is low (Strom, 1998)
1) Dental/oral/resp/esoph procedure: amox 2 g PO 1 hr pre (or clinda 600 mg PO or cephalexin 2 g PO or azithro/clarithro 500 mg PO) or amp 2 g IV 30 min pre (or clinda 600 mg IV or cefazolin 1 g IV)
2) GU/other GI procedure:
a) High-risk: amp 2 IV + gent 1.5 mg/kg IV (<120 mg) 30 min pre and amp 1 g IV (or amox 1 PO) 6 hrs post
-Alt: vanco 1 g IV over 1-2 hrs + gent 1.5 mg/kg IV to finish 30 min pre
b) Mod-risk: amox 2 g PO 1 hr pre (or amp 2 g IV 30 min pre)
-Alt: vanco 1 g IV over 1-2 hrs to finish 30 min pre


Prognosis

  • Strep endocarditis: 10% mortality
  • Staph endocarditis: 35% mortality
  • Prosthetic valve endocarditis: 25-50% mortality
  • 33% of MV endocarditis and 66% of AV endocarditis require valve replacement within 5 yrs even if cured of first episode of endocarditis

References

  • Surgical treatment of endocarditis. Prog Cardiovasc Dis. 1997;40:239–264 [MEDLINE]
  • Surgery for infective endocarditis: who and when? Circulation 2010; 121:1141-1152 [MEDLINE]
  • Outcomes after surgical treatment of native and prosthetic valve infective endocarditis.  Ann Thorac Surg 2012; 93:489-493 [MEDLINE]
  • Early surgery versus conventional treatment for infective endocarditis.  N Engl J Med 2012; 366:2466-2473 [MEDLINE]
  • HACEK endocarditis: state-of-the-art. Expert Rev Anti Infect Ther. 2016 Mar 8 [MEDLINE]