Cardiac

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    Infective Endocarditis

    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

    Screen shot 2013-09-25 at 10.51.29 PM.png

     

     

    • 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.
      • Screen shot 2013-09-25 at 11.22.04 PM.png
      • 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. 1. Moderate-to-severe CHF  (most frequent indication)  Death can be sudden.
          1. 2. More than one systemic embolus
          2. 3. Uncontrolled Infection (often S. aureus, r/o extravascular focus)
          3. 4. Resistant organisms or fungal infection (fungal endocarditis mortality - 90%)
          4. 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

     

    Prophylaxis Indications for Dental Procedures

    • The following are indications for dental procedures involving gingival manipulation.
      • Antimicrobial Prophylaxis For Dental Procedures

         

        Remember 4 groups that need abx prophylaxis: 

           1. Presence of prosthetic cardiac valve or prosthetic material used for valve repair

           2. Previous IE

           3. Some congenital heart defects

           4. Post-cardiac transplant valvulopathy

         

         

        AHA Guidelines 2007

        • Prosthetic cardiac valve (Bioprosthetic or mechanical)
        • History of infective endocarditis
        • Unrepaired cyanotic congenital heart disease
        • Congenital heart disease repair with prosthetic material or device for the first 6 months after intervention
        • Presence of palliative shunts and conduits
        • Cardiac valvulopathy in cardiac transplant recipients.

         

         

    • Choice of Antibiotic:
      • Streptococcus (esp Viridans) group goverage required
        • Penicillins....
        • If allergic to penicillins, use macrolides (clinda, azithro, clarithro)
      • Give as single dose 30-60min before the procedure.
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