Challenges in Infective Endocarditis

Cahill TJ, Baddour LM, Habib G, et al.
Challenges in Infective Endocarditis. J Am Coll Cardiol 2017;69:325-344.

Infective endocarditis (IE), defined as a focus of infection within the heart, is a rare but clinically significant disease. This review outlines the challenges posed by contemporary IE in developed countries. The following are points to remember:

  1. IE is an evolving disease:
    • IE affects 3-10 patients per 100,000 per year in the population at large, and the incidence is rising. Despite trends toward earlier diagnosis and surgical intervention, the 1-year mortality associated with IE has not improved over two decades.
    • Health care-acquired IE now accounts for >25% of all cases.
    • IE involving a cardiac implantable electronic device (CIED) or transcatheter aortic valve replacement (TAVR) is increasing, and these pose unique clinical challenges.
  2. Prevention of IE:
    • IE develops in three stages: bacteremia, adhesion, and colonization.
    • Preventative strategies historically have focused on bacteremia.
    • Between 2007 and 2009, guidelines in the United States (US) and Europe were substantially changed to restrict the use of antibiotic prophylaxis to lower the risk of IE, recommending antibiotic prophylaxis only in patients at the highest risk of adverse outcomes from IE. In the United Kingdom (UK), antibiotic prophylaxis was abandoned entirely.
    • Effects of guideline changes on the incidence of IE:
      • Data on any effect of guideline changes on the incidence of IE are conflicting. Some epidemiological studies in France and the US found no increase in the incidence of IE after guideline changes. In contrast, two nationwide epidemiological studies in the US and the UK identified statistically significant increases in the incidence of IE caused by streptococci.
      • In the UK, extended analysis showed that a decline in antibiotic prophylaxis use was temporally associated with a significant rise (above the projected trend) in the number of IE cases seen.
    • Prevention of health care-associated IE:
      • Health care-associated IE accounts for an increasing proportion of cases.
      • Risk factors include hemodialysis, cancer, diabetes mellitus, and the presence of a CIED.
      • Potential targets for prevention of health care-associated IE include reduction of health care-associated bacteremia, novel approaches to prevent bacterial adherence, and vaccines that target bacterial components.
  3. Diagnosis:
    • The modified Duke criteria, originally designed for research purposes, have a lower sensitivity for patients with prosthetic valve IE or CIED IE.
    • Imaging:
      • Transthoracic (TTE) and transesophageal echocardiography (TEE) remain the cornerstones of imaging for IE. TEE is indicated when TTE is positive or nondiagnostic, when complications are suspected, or when intracardiac device leads are present.
      • Cardiac computed tomography (CT) is a key adjunctive imaging modality when anatomy is not clearly delineated with echocardiography.
      • Combining CT imaging with metabolic imaging using 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) or leukocyte scintigraphy (radiolabeled leukocyte SPECT) to show regions of metabolic activity or inflammation, respectively, can be helpful among patients with Duke criteria suggesting “possible” IE, or with suspected cardiac device infection.
    • Microbiology:
      • Health care-associated organisms have increasingly defined the microbiology of contemporary IE. Staphylococcus aureus is now the most common organism, accounting for approximately 30% of cases, and is the most common cause of prosthetic valve IE. Coagulase-negative staphylococci account for approximately 10% of cases; oral streptococci approximately 20% of cases; other streptococci approximately 10%; and HACEK organisms, zoonoses, and fungi collectively account for <5%. Approximately 10-20% of patients have negative blood cultures.
  4. Management:
    • The optimal management of IE involves multiple hospital specialists, including cardiologists, surgeons, infectious disease physicians, microbiologists, nephrologists, neurologists, and radiologists.
    • Antibiotic therapy.
      • Effective antimicrobial clearance requires bactericidal antibiotic regimens, usually in combination.
      • There are increasing data to suggest that the use of aminoglycosides may cause harm without clear clinical benefit.
    • Surgery:
      • Surgery is performed for the specific indications of progressive valve and tissue damage, uncontrolled infection, and high risk of embolization. The objectives are to remove infected tissue, foreign material, and hardware; clear and debride paravalvular infection and cavities; and remove threatening sources of embolization.
      • Surgery currently is performed in 50-60% of patients with IE.
      • The emphasis on “early surgery” differs between European and US guidelines. The European Society of Cardiology guidelines distinguish emergency surgery (performed within 24 hours), urgent surgery (within a few days), and elective surgery (after 1-2 weeks of antibiotic therapy); in contrast, the American Heart Association guidelines define early surgery as “during the initial hospitalization and before the completion of a full course of antibiotics.”
      • There is no proven benefit in delaying surgery once an indication for intervention is established.
  5. Contemporary management challenges in IE:
    • IE after TAVR. There is a special management challenge in caring for IE complicating TAVR, in that the patients tend to be elderly and at high risk for surgery, but with a poor anticipated outcome if managed medically.
      • Management of TAVR-IE remains challenging; it remains to be proven whether it can be managed without removal of the infected implant.
    • Stroke and IE:
      • IE is complicated by stroke in 20-40% of cases, and stroke is an independent predictor of lower survival.
      • The role of surgery in prevention of stroke/embolization remains unresolved.
      • The optimal timing of surgery in patients who already have suffered a stroke remains contentious, in large part due to the risk of hemorrhagic transformation during anticoagulation for cardiopulmonary bypass.
    • Cardiac device infection:
      • The number of cardiac device infections in the US has increased out of proportion to the number of CIEDs implanted.
      • Cardiac device infection may involve the generator pocket, device leads, or endocardial (valve or nonvalve) surfaces, or any combination.
      • The diagnosis of cardiac device infections is made based on blood culture and echocardiography results. If echocardiography is negative or equivocal, leukocyte scintigraphy or  <sup>18</sup>FDG-PET/CT scans can be helpful.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Valvular Heart Disease, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Anti-Bacterial Agents, Anti-Infective Agents, Antibiotic Prophylaxis, Bacteremia, Cardiopulmonary Bypass, Cardiac Surgical Procedures, Diagnostic Imaging, Echocardiography, Transesophageal, Endocarditis, Heart Valve Diseases, Positron-Emission Tomography, Renal Dialysis, Risk Factors, Secondary Prevention, Staphylococcus aureus, Stroke, Tomography, Emission-Computed, Single-Photon, Transcatheter Aortic Valve Replacement

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