Infective endocarditis occurs globally and is the infection of the endocardial surface of the native valve, prosthetic heart valve, or an implanted cardiac device such as a permanent pacemaker or a cardioverter defibrillator. Over the past few decades, there has been a change in both the host and the pathogen. Staphylococcus aureus has surpassed Streptococcus as the most common etiologic pathogen worldwide and especially in the developed world given its common association with health-care contact and invasive procedures. Changes in the host include older and sicker patients who carry a high burden of comorbidities. Resistance to antibiotics is another challenge threatening healthcare worldwide and seems to be growing.
Despite technological advances in diagnostic and therapeutic modalities, the overall mortality has not improved. Aortic valve infective endocarditis is a life-threatening disease associated with high mortality and morbidity. In this chapter, we will provide an overview of the infective endocarditis with a particular emphasis on the aortic valve endocarditis. The term native valve endocarditis denotes a cardiac infection that involves the leaflets of the valves, the endocardial surface, chordae tendinae, congenital defects, and anastomosis sites. Prosthetic valve endocarditis is defined by an infection involving the artificial valves, conduits, catheters, assist devices, pacemakers, defibrillators, or other artificial intracardiac structures.
The etiology of infective endocarditis has its basis on whether the valve is native or prosthetic and for prosthetic valve endocarditis, the etiology is dependent upon the timing with early phase defined as less than two months and late phase defined as greater than 12 months. The native valve infective endocarditis is most commonly caused by Streptococcus viridans and Staphylococcus aureus. For the early phase, prosthetic valve endocarditis causative agents include coagulase-negative staphylococci (Staphylococcus epidermidis) and Staphylococcus aureus whereas for late phase the key culprits include Streptococcus viridans and Staphylococcus aureus. Enterococci enter the bloodstream as a consequence of gastrointestinal or genitourinary tracts manipulation. Streptococcus bovis and Clostridium septicum are associated with colonic malignancies whereas HACEK group agents (Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella, Kingella) infect patients with poor dental hygiene or from needle contaminate with saliva in intravenous drug users. Fungal endocarditis is the gravest form of infective endocarditis, and the risk factors include prosthetic heart valves, intravenous drug use, and an immunocompromised state.
Infective endocarditis can community-acquired, or it can be related to healthcare exposure. The epidemiological trends and disease patterns of infective endocarditis have evolved across the globe. In developing countries, rheumatic heart disease remains the key risk factor, and affected patients are usually younger, and community-acquired, penicillin-sensitive streptococci typically cause the infection. In developed world degenerative valve disease, malignancy, intravenous drug use, diabetes mellitus, and congenital heart disease are the predominant risk factors, and the mean age of the patients is older than the ’70s. The cases of healthcare-acquired infective endocarditis due to Staphylococcal infection has surged over the past two decades owing to increase in the use of invasive procedures, cardiovascular implantable electronic devices, long-term intravenous lines, percutaneous, minimally invasive and prosthetic heart valves. There has been an increased incidence of infective endocarditis after minimally invasive aortic valve surgery or percutaneous transcatheter aortic valve replacement.
The pathophysiologic underpinning of infective endocarditis involves the following steps: bacteremia (spontaneous or hospital-acquired) that delivers the pathogen to the surface of the valve, adherence of the circulating pathogen to the prepared valve surface and ultimately the invasion of the valvular leaflets. Circulating pathogen do not adhere to the normal endothelium. Injury of the valve alters the architecture of the endothelial cells rendering them susceptible to colonization with bacteria.
History is crucial, and patients describe fevers, chills, dyspnea, orthopnea, night sweats, fatigue, and weight loss. Patients can also present with a transient ischemic attack, stroke, myocardial infarction, or heart failure symptoms. On physical exam, patients with aortic valve endocarditis may demonstrate an aortic insufficiency diastolic murmur (new or change in preexisting murmur) and signs of heart failure if aortic valve function is compromised. Other sequelae may include neurological findings such as vision loss, weakness, or peripheral stigmata of the disease as described above including splinter hemorrhages, Osler nodes, Roth spots, Janeway lesions, organomegaly, and hematuria if kidneys involved.
The Modified Duke Criteria are applicable in the evaluation of patients suspected of infective endocarditis. Three categories include definite infective endocarditis, possible infective endocarditis, or rejected infective endocarditis.
Major clinical criteria are defined as follows:
Minor clinical criteria are as follows:
Possible infective endocarditis criteria are when there are one major criterion and one minor criterion or three minor criteria present. Rejected infective endocarditis is defined when there is likely an alternative diagnosis, or there is no pathological evidence of IE with fewer than 4 days of antibiotic therapy or there is the resolution of clinical symptoms with fewer than 4 days of antibiotic therapy.
It is important to note that prior antibiotic therapy may mask the histopathological evidence of infective endocarditis. Vegetation on an echocardiogram is an oscillating intracardiac mass on the valve or supporting structures, in the path of regurgitant jets. Presence of abscess or partial dehiscence of prosthetic valve also fulfills echocardiographic criteria of infective endocarditis. A transthoracic echocardiogram should be validated by transesophageal echocardiogram in the evaluation for patients with suspected infective endocarditis whenever indicated.
Recommendations for antimicrobial therapy, according to the causative pathogen are complex and well summarized in the 2015 American Heart Association practice guidelines. Treatment for left-sided infective endocarditis (aortic and mitral) is similar, and the recommendations are based on the pathogen, its susceptibility, timeline (acute vs. subacute) and whether it is native or prosthetic valve infective endocarditis. Generally speaking, for subacute native valve infective endocarditis, S. viridans and enterococci need to be covered, and the usual treatment involves IV penicillin (2.4 g, every 4 hours) for up to 4 weeks with gentamicin (1 mg/kg, every 12 hours) for 2 weeks (for suspected aminoglycoside-susceptible enterococci).
Adjunctive therapy with aminoglycosides for native valve infective endocarditis is not recommended because of the risk of renal toxicity and because it doesn’t decrease mortality. Likewise, rifampin is not recommended because of the risk of hepatotoxicity. However, if the culprit is aminoglycoside-susceptible enterococci, then gentamicin can be added to the regimen. Additionally, for prosthetic valve infective endocarditis, the combination therapy of vancomycin and aminoglycoside or rifampin is acceptable. For acute native valve, infective endocarditis treatment S. aureus needs to be covered. The treatment includes nafcillin for methicillin-susceptible S. aureus (MSSA) or cefazolin if patients are allergic to nafcillin. For methicillin-resistant Staphylococcus aureus (MRSA), vancomycin is the recommended antibiotic. The alternative is daptomycin, which requires closer monitoring for dosing. Candida and Aspergillus may respond to medical therapy 5-fluorouracil and amphotericin B respectively, however, these patients frequently require surgical therapy. Among patients with mechanical valve endocarditis who have experienced a central nervous system embolic event, it is reasonable to discontinue for 2 weeks all forms of anticoagulation.
If medical therapy fails, surgical intervention is often necessary. Class I indications for surgery in patients with infective endocarditis include valvular dysfunction with symptoms of congestive heart failure, left-sided infective endocarditis caused by Staphylococcus aureus, fungal, or other highly resistant microorganisms, infective endocarditis with conduction defects or heart block, annular or aortic abscess, persistent infection 5 to 7 days after initiation of antibiotic therapy . For native valve endocarditis, eradication of the infected valvular tissue with subsequent valve repair or replacement is the primary therapy. For native valve endocarditis limited to the leaflets/cusps, repair should be performed whenever feasible (Class I) . For prosthetic valve endocarditis that spares the aortic root and annulus after radical resection, implantation of a new prosthetic valve (tissue or mechanical) is reasonable (Class IIa).However, if the annulus is destroyed or if the infection has spread beyond the aortic root, then reconstruction and the use of an allograft or a biologic tissue root is preferable to a prosthetic valved conduit (Class IIa).
The principal differential diagnoses for infective endocarditis include the following:
The in-hospital mortality for infective endocarditis is around 20%. Risk factors for increased mortality include advanced age, infective endocarditis caused by S. Aureus P. aeruginosa, Enterobacteriaceae, or fungi, a heavy burden of comorbidities (end-stage renal disease requiring hemodialysis, prosthetic valve endocarditis, severe heart failure, stroke, abscess, severe immunosuppression due to HIV infection, and development of perivalvular extension or a myocardial abscess). Embolic events to the brain are a significant cause of morbidity and mortality in patients with infective endocarditis. In a study of 1437 consecutive patients with left-sided endocarditis, the incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82 per 1000 patient days in the first week of therapy and fell to 1.71 per 1000 patient days in the second week suggesting that early initiation of antimicrobial therapy dramatically reduces risk of stroke.
Aortic valve endocarditis complications include congestive heart failure due to valve damage, annular abscess, mycotic aneurysms of the sinus of Valsalva which can result in pericarditis, hemopericardium, and cardiac tamponade, or fistulas to the cardiac chambers. Involvement of the conduction system may cause atrioventricular blocks. Neurologic complications include thromboembolic events and mycotic aneurysms from septic embolization of vegetations. Systemic embolization to other organs, including liver kidneys, and spleen results in end-organ damage.
Early recognition and timely management of infective endocarditis are imperative to ensure optimal clinical outcomes. Patients should receive education regarding the prognosis, risk factors, signs and symptoms, and management aspects of infective endocarditis.
Aortic valve infective endocarditis is a life-threatening condition with poor prognosis. Despite technological advances over the past few decades, the mortality remains high. Early recognition and prompt institution of antimicrobial therapy can help optimize patient outcomes. A multidisciplinary approach involves physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]
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