Cardiac

Pathogenesis

• Infective endocarditis usually preceeded by predisposing cardiac lesion.
  • Pre-existing damage  --> accumulation of platelets and fibrin --> produces nonbacterial thrombotic endocarditis (NBTE)
  • Risk factors of NBTE:
    • Rheumatic heart disease
    • Congenital heart disease (bicuspid aorta, VSD, coarctation of aorta, Tetralogy of Fallot).
    • Mitral valve prolapse
    • Degenerative heart disease (calcific aortic valve)
    • Prosthetic Valve
  • Cardiac conditions (such as aortic stenosis) create flow abnormalities - venturi effect.
    • The gerater the pressure gradient, the higher the risk.
    • Pressure gradient creates post-stenotic pressure drop (venturi effect, like water going past opening beween the rocks... see pooling of debris downstream).
    • Vegetations form on downstream of low-pressure side of valve lesion.
      • Aortic stenosis --> vegetations on aortic coronary cusp.
      • Mitral regurg --> atrial vegetations.
      • Tricuspid regurg --> rare (only IV drug users).
    • Bacteria enter the endocardium --> induce platelet aggregation --> platelet-fibrin complex--> protective environment for bacteria (WBC cannot enter).
    • Alternate from biologically active to dormat phase.
    • Prosthetic valves serve as perfect sites for bacterial adherence.

Organisms

• Organisms responsible for infective endocarditis are "sticky".  (adhere to inert surfaces + endocardium)
• Strep express dextran to adhere to tooth enamel. (cause dental carries).
   
• 1. Native valve:  (Bacteria that seed NBTE or native endocardium)
  • Streptococci: (most common)
    • Strep viridans sp. (alpha hemolysis)    [most common >50%]
      • #1 cause of bacterial endocarditis.
      • Express adhesin FimA, and high levels of dextran 
      • S. mutans and S. sanguis most commonly cause endocarditis.
    • Group D strep (S. bovis)     [2nd most common]
      • Enters bloodstream via GI tract - colonic carcinoma portal.
  • Staphylococci (2nd most common)
    • S. aureus
      • Adheres to fibrinogen and fibronectin
  • ​HACEK group
    • Haemophius aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae.
    • All require CO2 for growth, may not be detected in blood cultures (discarted after 7days)
       
• 2. IV Drug Users
  • Staph aureus
  • Gram-negative aerobic bacilli (including Pseudomonas)
  • Fungi (C. albicans - IV drugs and prosthetic valves).
  • Multiple organisms.
    • (Can be mouth flora organisms too b/c ppl spit on the needle to clean it)
       
• 3. Prosthetic Valves:
  • Early - nosocomial
    • S. aureus
    • Coag-negative staph
    • Gram-neg bacilli
    • Fungi
  • Late - >2mo post-op (mouth and skin flora)
    • S. viridans
    • Coag-negative staph
    • S. aureus
    • G- bacilli
    • Fungi

• Bacterial source:
  • Mucosal surface damage --> transient bacteremia.
    • Mouth Mucosa:
      • Dental extractions, periodontal surgery, gum chewing, tooth brushing.
      • Tonsillectomy
    • GU
      • Urethral dilatation
      • TURP
      • Cystoscopy.
    • GI
      • GI procedures.
    • Plumonary
      • Pulmonary procedures.

• Symptoms:

  • Non-specific symptoms begin 2 weeks after bacteremia.
  • Often takes 5 weeks to diagnose.
     
  • Subacute
    • Usually non-specific.
    • Low-grade fever  ~38, maybe chills (night sweats uncommon).
    • Fatigue, anorexia, weakness, malaise, weight loss.
    • Back pain!!! 
  • Acute (hours to days)
    • Commonly associated with S.aureus, enterococci, and occasionally S. pneumo.
    • Fever >40, Rigers, 
    • Rapid diagnosis needed to decrease valvular destruction and embolic complications!!!

• Physical findings:

  • Fever (95%)
  • Heart murmur (almost always) - often unchanging (unless leaflet destroyed w/ S. aureus) or chordae tendinae rupture.
    • New aortic regurg murmur = bad sign.  ---> CHF develops.
      • (High pitched diastolic murmur along radiating along L sternal border)
      • If vegetation large enough can cause aortic stenosis!
  • Embolic phenomena (50%)
    • Fundoscopy = Roth spots, retinal hemorrhages.
    • Petechial hemorrhages (conjunctiva)  (also thrombocytopenia, cardiac surgery)
    • Petechiae on bucchal mucosa, palate, extremities.
    • Splinter hemorrhages.
    • Osler nodes (pea sized subq painful erythematous nodules -
      • Check pads of fingers, toes, and thenar eminence.
    • Janeway lesions (S. aureus infection).
  • Splenomegaly? splenic tenderness
    • Infarction by septic emboli.
  • Joints - effusions (uncommon)
  • Peripheral pulses (if pulses gone + limb pain --->> ARTERIOGRAPHY)
  • If neuro symptoms (CT /MRI head).
    • No contarct --> embolic infarction, intracerebral hemorrhage, brain abscess.

• Labs

  • Non-specific.
  • Blood cultures (do X2 preferrably 20min apart !!!!)  and then once again before starting abx.
  • Anemia of chronic disease (70-90% of cases)
    • Low serum iron, low TIBC
  • If elevated WBC count --> myocardial abscess?
  • ESR almost always elevated. (IF NEGATIVE --> EXCLUDES INFECTIVE ENDOCARDITIS)
    • CRP also elevated.
  • Rheumatological Labs:   (not necessary)
    • Mimic connective tissue disorders b/c vegetation seeds bacterial chronically.
    • High ESR/CRP
    • Rheumatoid Factor +
    • High Igg, cryoglobulins, immune complexes
    • Low complement
  • Urinalysis: proteinuria (50-65%), hematuria (30-50%)
• Imaging:
  • XRay --> R-sided "cannonball-like" infiltrates may be detected. (pulmonary emboli)
• ECG --> watch for conduction defect (infection spread to conduction system).
• Blood cultures
  • Most infections --> intermittent bactermias (pneumonia, pyelo)
  • Endocarditis --> constant low-level bactermia.
  • If suspect HACEK group - ask lab to hold culture for 4 weeks (usually throw out after 7 days).  (also subculture in chocolate agar with 5% CO2)
  • Sensitivity: 85-95% on first culture, and 95-100% on second.
  • Third blood culture documents constancy of bactermia.
• Echocardiography
  • Trans-Thoracic Echo TTE (sens 44-63%) for detecting vegeations.
  • Trans-Esophageal Echo TEE (sens 94-100%)
    • (more accurate for extravascular extenions and valve perforations)
• Duke Criteria
  • Definitive diagnosis of infective endocarditis in absence of valve tissue pathology is difficult.
  • 
  • Echocardiographic minor criteria --> removed from minor. 

• Treatment

  • Often requires combination of surgery and antibiotics

  • Antibiotics

    • Some considerations:
      • Need cidal antibiotics b/c bacterial in fibrin cannot be accessed by neutrophils.
      • Need long periods of time (b/c some bacteria are latent, and B-lactams/vanco require growth)
        • Often need 4-6 weeks of tx.  (Except uncomplicated S. viridans)
      • Often B-lactam + aminoglycoside used for synergistic effects (rapid killing)
      • In General:
        • B-lactam: MSSA, S.viridans, Strep. pneumo
        • Vancomycin: MSSA, MRSA, CNSt
        • Ampicillin: Enterococci
        • Rifamping: MSSA, MRSA, CNSt, Strep (Enters biofilms and clots well, but weak, NEVER monotherapy)
        • Aminoglycoside: Synergy in killing (I guess stops B-lactamase production).
      • B-lactams preferred b/c MORE CIDAL than Vancomycin (takes time)
      • Empiric: combination of PenG and gentamycin is synergistic (rapid killing)
        • Acute-empiric 
          • Vancomycin + Amp + Gentamycin
        • Culture-negative:
          • Ampicillin + gentamycin  (need to cover slow-growting HACEK that take >9 days to culture)
        • Prosthetic valve -empiric:
          • Form biofilm - hard to treat.  Often need valve replaced
          • Vanco + Gentamycin + Rifampin
            • Vanco covers coag-neg staph  (4-6wks?)
            • Gent - synergy          (2 weeks)
            • Rif - penetrates clot/biofilms well  (6 weeks)
        • IV Drug users with uncomplicated tricuspid valve and S.aureus
          • Cloxacillin + tobramycin (2 weeks)
          • If HIV+
            • Ciprofloxacin 750mg BID + rifampin 300mg BID x4 weeks.  (provided S.aureus is cipro sensitive)
        • Strep viridans  (2 weeks!)
          • PenG OR amp+gent are first line.
          • Ceftriaxone + gent + vanco 2nd line.
        • Enterococcus
          • Ampicillin
          • PenG + gentamycin
        • MSSA
          • Cloxacillin
          • Cefazolin
        • MRSA
          • Vancomycin or Daptomycin (non-inferior to vanco)
        •  

  • Surgery

    • Often not curative alone (esp if prosthetic valve).  Surgical prosthetic valve replacement or debridement of valve improves survival.

    • Indications For Surgery:   1. Moderate-to-severe CHF  (most frequent indication)  Death can be sudden. 2. More than one systemic embolus 3. Uncontrolled Infection (often S. aureus, r/o extravascular focus) 4. Resistant organisms or fungal infection (fungal endocarditis mortality - 90%) 5. Perivalvular/myocardiac abscess (can use abx for some small abscesses)

    •  

• Complications

  • 1. Cardiac  (30-50%)
    • CHF (most common)
    • Regurgitation (leaflet destruction), stenosis, Perivalvular extension.  Conduction problems.
  • 2. Neurologic (25-35%)
    • Embolic Strokes, Intra-cerebral hemorrhage, encephalopathy, meningitis, meningoencephalitis, brain abscess.  
  • 3. Renal Complications (~33%, 1/3 of pts)
    • High in elderly and thrombocytopenia.
    • Caused by:
      • Immune-complex glomerulonephritis  (membranoproliferative disease)
        • Hematuria, mild proteinuria, red cell casts. (improves rapidly with abx)
      • Renal emboli
      • Drug-induced intersticial nephritis.
  • 4. Systemic Emboli
    • Almost 2/3 are CNS emboli (b/c 1st and 2nd branches of aorta are CNS)
    • R-sided endocarditis (IV drug use) --> pulmonary emboli or abscesses.
  • 5. Mycotic Aneurisms
    • Infectious emboli lodged in arterial bifurcations (occlude vasa vasorum of vessel lumen --> damage of musclar layer --> aneurism--> risk of rupture).
    • Commonly in:
      • Middle cerebral artery (hemorrhagic stroke)
      • Abdominal aorta      (intra-abdominal hemorrhage)
      • Mesenteric artery