Aortic Valve Endocarditis

Etiology

The microbiologic etiology of infective endocarditis varies according to whether the infection involves a native or prosthetic valve and, in prosthetic valve endocarditis, the timing of infection following valve implantation. Native valve endocarditis is most commonly caused by Streptococcus viridans species and Staphylococcus aureus. Acute bacterial endocarditis is most commonly caused by S aureus, whereas subacute presentations are more commonly caused by viridans streptococci, including Streptococcus mutans.[2]

In prosthetic valve endocarditis, the causative organisms vary with the time elapsed since valve implantation. Early prosthetic valve endocarditis, occurring within the first 2 months after surgery, is most commonly caused by coagulase-negative staphylococci, particularly Staphylococcus epidermidis, which accounts for approximately 30% to 35% of cases, followed by S aureus, responsible for 20% to 24% of infections. Late prosthetic valve endocarditis, occurring more than 12 months after implantation, is most frequently caused by viridans streptococci and S aureus.

The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria define typical infective endocarditis pathogens as microorganisms whose isolation from blood cultures strongly suggests infective endocarditis. These organisms include most streptococcal species (excluding Streptococcus pyogenes and Streptococcus pneumoniae), Staphylococcus lugdunensis, Enterococcus faecalis, Granulicatella species, Abiotrophia species, and Gemella species. In prosthetic valve endocarditis, additional typical organisms include coagulase-negative staphylococci, Corynebacterium striatum, Corynebacterium jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, Mycobacterium chimaera, and Candida species.

Specific risk factors are associated with particular pathogens. Enterococcal endocarditis commonly follows gastrointestinal or genitourinary tract manipulation, while Streptococcus bovis bacteremia and endocarditis are strongly associated with colorectal neoplasia. Clostridium septicum endocarditis is also linked to underlying colonic malignancy. Poor dental hygiene predisposes patients to infection with viridans streptococci and members of the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella).

At the same time, intravenous drug use may introduce oral flora through saliva-contaminated needles. S aureus, gram-negative bacilli, and Candida species more frequently cause healthcare-associated and nosocomial infections. Fungal endocarditis, most commonly caused by Candida species, is associated with particularly high morbidity and mortality and occurs most often in patients with prosthetic valves, intravenous drug use, or immunocompromising conditions.

Epidemiology

Infective endocarditis may be classified as either community-acquired or healthcare-associated, and its epidemiology has changed substantially over recent decades. In developing countries, rheumatic heart disease remains the predominant predisposing condition, with affected patients generally being younger and infections most commonly caused by community-acquired, penicillin-sensitive streptococci.[1] In contrast, patients in developed countries are typically older, often with a mean age exceeding 70 years, and frequently have underlying degenerative valvular disease, congenital heart disease, malignancy, diabetes mellitus, prosthetic heart valves, or a history of intravenous drug use.

The microbiologic profile of infective endocarditis has also evolved, with S aureus emerging as the leading causative organism worldwide, replacing streptococcal species as the predominant pathogen in many regions. Contemporary cohorts demonstrate an increasing proportion of prosthetic valve infections and a greater need for surgical intervention, reflecting the growing complexity of the patient population and disease severity. Healthcare-associated infective endocarditis has increased significantly during the past 2 decades, largely due to the expanding use of invasive medical procedures, cardiovascular implantable electronic devices, long-term intravascular catheters, prosthetic heart valves, and other intracardiac devices.[6] The incidence of infective endocarditis has also risen following minimally invasive aortic valve procedures and transcatheter aortic valve replacement, emphasizing the importance of vigilant surveillance, prompt diagnosis, and individualized management strategies in these higher-risk populations.[6][7]

Pathophysiology

The pathophysiology of aortic valve infective endocarditis involves a complex sequence of events that includes endothelial injury, microbial seeding during bacteremia, pathogen adherence, vegetation formation, host inflammatory responses, and progressive valvular destruction. The process begins when circulating microorganisms gain access to the bloodstream through spontaneous bacteremia or healthcare-associated exposures. Under normal conditions, pathogens do not readily adhere to intact endocardial endothelium.

However, endothelial injury caused by turbulent blood flow from congenital or acquired valvular abnormalities, such as a bicuspid aortic valve, aortic stenosis, or aortic insufficiency, disrupts the endothelial surface and exposes subendothelial collagen and tissue factor.[8] This injury promotes the formation of sterile platelet-fibrin deposits known as nonbacterial thrombotic endocardial lesions, which serve as a nidus for microbial colonization.[8] Once bacteremia occurs, microorganisms such as S aureus, viridans streptococci, or enterococci can adhere to these lesions and become encased within a matrix of fibrin and platelets, forming vegetations.

The protective environment of the vegetation limits immune system access and impairs antibiotic penetration, allowing persistent infection. In aortic valve endocarditis, vegetations typically develop on the aortic aspect of the valve leaflets. Progressive enlargement of vegetations can result in leaflet perforation, cusp destruction, and valvular dysfunction, leading to acute or chronic aortic regurgitation and, less commonly, obstruction of valvular flow.

The host inflammatory response further contributes to tissue injury. Activated neutrophils and macrophages release cytokines and proteolytic enzymes that promote local tissue destruction and weaken valvular structures. As infection progresses, extension beyond the valve leaflets may involve the aortic annulus, aortic root, and adjacent myocardium, resulting in complications such as annular abscesses, perivalvular leaks, pseudoaneurysms, or fistulous communications between cardiac chambers and vascular structures. Vegetations may also fragment and embolize, particularly when large and friable, producing systemic embolic complications, including septic emboli to the lungs, ischemic stroke, myocardial infarction, splenic infarction, renal infarction, or peripheral arterial embolization. Severe valvular destruction causing acute aortic regurgitation can rapidly precipitate heart failure and cardiogenic shock, making urgent surgical intervention necessary in many patients.

History and Physical

The diagnosis of infective endocarditis remains challenging because of its highly variable clinical presentation. Clinicians should consider infective endocarditis in any patient presenting with unexplained fever, sepsis, or positive blood cultures without an identifiable source of infection, particularly when predisposing risk factors such as prosthetic heart valves, congenital heart disease, intracardiac devices, or prior endocarditis are present. Clinical manifestations range from an acute, rapidly progressive illness to a more indolent subacute or chronic disease characterized by nonspecific constitutional symptoms, often leading to delays in diagnosis. Infective endocarditis may also present with complications that mimic rheumatologic, neurologic, autoimmune, or malignant conditions. Maintaining a high index of suspicion and involving a multidisciplinary endocarditis team early in the course of evaluation can facilitate timely diagnosis and management.[7][9]

Common symptoms include fever, chills, fatigue, malaise, anorexia, weight loss, night sweats, dyspnea, and orthopnea. Data from the European Infective Endocarditis Registry demonstrated that fever is present in approximately 77.7% of patients, making it the most frequent presenting symptom. Patients may also present with manifestations of systemic embolization or cardiac complications, including transient ischemic attack, ischemic stroke, myocardial infarction, or symptoms of acute or chronic heart failure. Confusion, delirium, lethargy, pallor, and arrhythmias may also occur, particularly in advanced disease. 

Physical examination findings vary according to the severity and duration of infection. Heart murmurs are present in approximately 64.5% of patients and may represent a new valvular lesion or a change in a preexisting murmur. In aortic valve endocarditis, a new or worsening diastolic murmur of aortic regurgitation is a characteristic finding and may be accompanied by signs of heart failure when significant valvular dysfunction is present. Registry data indicate that heart failure occurs in approximately 27.2% of patients, while cardiac conduction abnormalities are observed in 11.5%.

Peripheral manifestations of infective endocarditis reflect both vascular and immunologic phenomena. Petechiae involving the skin, oral mucosa, or conjunctivae may be present, along with splenomegaly and evidence of immune complex-mediated disease such as glomerulonephritis.[10] Classic peripheral stigmata include splinter hemorrhages beneath the fingernails or toenails, Osler nodes, Janeway lesions, and Roth spots. Although these findings are less common in the modern era, they remain associated with severe S aureus infections and subacute streptococcal endocarditis.[10] Hematuria may occur with renal involvement.[10]

Neurologic complications are particularly common and may be the presenting manifestation of the disease. Signs of embolic stroke, including focal weakness, sensory deficits, visual disturbances, or aphasia, occur in approximately one-third of patients with infective endocarditis. Overall, embolic events are reported in approximately 25.3% of patients and should prompt consideration of endocarditis in the appropriate clinical setting. Atypical presentations are more frequently encountered in older adults and immunocompromised individuals, necessitating a low threshold for diagnostic testing in these high-risk populations.[9]

Evaluation

The diagnosis of infective endocarditis relies on a combination of clinical suspicion, microbiologic evidence, and imaging findings demonstrating involvement of native or prosthetic heart valves or other intracardiac prosthetic material. Because the clinical presentation is often nonspecific, a structured diagnostic approach is essential. Echocardiography remains the cornerstone of diagnosis, while advanced imaging modalities such as computed tomography (CT), positron emission tomography-computed tomography (FDG PET/CT), and magnetic resonance imaging (MRI) are increasingly incorporated into contemporary diagnostic algorithms due to their ability to identify cardiac lesions, detect extracardiac complications, evaluate sources of bacteremia, and provide prognostic information. 

The 2023 Duke–International Society for Cardiovascular Infectious Diseases (ISCVID) criteria provide the current framework for diagnosing infective endocarditis and classify cases as definite, possible, or rejected.[2] Either pathological or clinical criteria may establish a diagnosis of infective endocarditis. Definite infective endocarditis by pathological criteria requires evidence of active endocarditis lesions or identification of microorganisms from vegetation, embolized material, intracardiac devices, prosthetic valves, or ascending aortic grafts in patients with aortic valve involvement. Definite infective endocarditis by clinical criteria is diagnosed when 2 major criteria, 1 major criterion plus 3 minor criteria, or 5 minor criteria are present.[2]

Major clinical criteria include positive blood cultures with typical organisms (at least 2 sets) or atypical organisms (at least 3 sets) known to cause infective endocarditis; a single positive blood culture for Coxiella burnetii; laboratory evidence of specific pathogens such as Coxiella burnetii, Bartonella species, or Tropheryma whipplei through polymerase chain reaction, nucleic acid testing, or elevated antibody titers; imaging evidence of vegetation, abscess, prosthetic valve dehiscence, or new valvular regurgitation on echocardiography or CT; abnormal FDG PET/CT uptake involving a valve, aortic graft, prosthetic valve, or cardiac device; and direct intraoperative visualization of infective endocarditis.[2]

Minor clinical criteria include predisposing cardiac conditions, intracardiac electronic devices, intravenous drug use, prior infective endocarditis, previous valve repair, fever greater than 38 °C (100.4 °F), vascular phenomena such as arterial emboli, septic pulmonary infarcts, cerebral abscesses, splenic abscesses, mycotic aneurysms, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions, immunologic phenomena including glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor, microbiologic evidence that does not meet major criteria, a new regurgitant murmur without confirmatory imaging, and abnormal PET/CT findings involving recently implanted prosthetic valves, grafts, or devices within 3 months of implantation.[2]

Possible infective endocarditis is diagnosed when 1 major criterion and 1 minor criterion, or 3 minor criteria, are present. Rejected infective endocarditis is defined as follows: an alternative diagnosis better explains the clinical presentation; no pathological evidence of infective endocarditis after fewer than 4 days of antibiotic therapy; symptoms resolve with fewer than 4 days of antibiotics; or the clinical findings fail to meet criteria for possible infective endocarditis. Blood cultures remain fundamental to diagnosis and should be obtained before initiation of antimicrobial therapy whenever possible. Prior antibiotic exposure may sterilize blood cultures and obscure histopathologic evidence of infection, making diagnosis more difficult. When surgery is performed before a definitive diagnosis has been established, excised tissue and vegetations should undergo microbiologic and histopathologic analysis to confirm infection.[2]

Echocardiography is the preferred initial imaging modality. Transthoracic echocardiography should be followed by transesophageal echocardiography (TEE) when clinical suspicion remains high or when additional anatomical detail is required. Echocardiographic findings consistent with infective endocarditis include an oscillating intracardiac mass attached to a valve or supporting structures, abscess formation, partial prosthetic valve dehiscence, new valvular regurgitation, myocardial abscesses, and valvular or paravalvular defects. TEE is particularly valuable for identifying complications such as abscesses and prosthetic valve involvement.[2]

Electrocardiography (ECG) may reveal conduction abnormalities in approximately 10% of patients. Prolongation of the PR interval or a new conduction block may indicate extension of infection into the interventricular septum or the conduction system and is generally considered a poor prognostic sign necessitating urgent intervention. Neurologic symptoms warrant brain imaging, typically with CT or MRI, to evaluate for ischemic stroke, intracranial hemorrhage, cerebral abscesses, or other embolic complications. 

Advanced imaging modalities play an increasingly important role when echocardiographic findings are inconclusive or when complications are suspected. Cardiac CT is particularly useful for evaluating aortic valve anatomy, coronary anatomy, and paravalvular complications, including abscesses, pseudoaneurysms, fistulas, and prosthetic valve dehiscence. Study results suggest that cardiac CT may surpass TEE in detecting certain perivalvular and periprosthetic complications and can provide critical information for surgical planning. Whole-body CT can identify septic emboli and occult sources of infection, while MRI is especially valuable for detecting neurologic and spinal complications associated with infective endocarditis.[5][11][12]

FDG PET/CT has been incorporated into both the 2023 Duke-ISCVID criteria and contemporary European Society of Cardiology guidelines. Although less sensitive than echocardiography for detecting vegetations, FDG PET/CT is particularly valuable for prosthetic valve endocarditis, cardiac device infections, and identifying metastatic infectious foci. In prosthetic valve infective endocarditis, intense focal, multifocal, or heterogeneous FDG uptake constitutes a major diagnostic criterion. In native valve or cardiac device-associated infective endocarditis, any abnormal FDG uptake is considered clinically significant. Integration of PET with CT angiography further enhances diagnostic accuracy by combining metabolic and anatomic assessment, facilitating detection of active infection, extracardiac embolic events, congenital heart disease-associated infections, and aortic graft infections.[5][11][12]

Treatment / Management

Management of infective endocarditis requires a multidisciplinary approach centered on prolonged pathogen-directed antimicrobial therapy and, when indicated, timely surgical intervention. Antibiotic selection depends on the causative organism, antimicrobial susceptibility profile, infection acuity, and whether the infection involves a native or prosthetic valve. Treatment is typically initiated in the hospital and may be completed in the outpatient setting once the patient is clinically stable, afebrile, and blood cultures have become negative. Although treatment duration varies with the pathogen and clinical scenario, therapy generally ranges from 2 to 6 weeks, with approximately 4 weeks recommended for native-valve endocarditis and 6 weeks for prosthetic-valve endocarditis.[13] 

The 2015 American Heart Association guidelines provide organism-specific recommendations for the management of viridans group streptococci, Streptococcus gallolyticus (formerly S bovis), Abiotrophia, Granulicatella, enterococci, staphylococci, HACEK organisms, non–HACEK gram-negative bacilli, fungal endocarditis, and culture-negative endocarditis. Viridans streptococci, Abiotrophia, and Granulicatella infections are generally treated with penicillin G or ceftriaxone, with gentamicin reserved for selected cases of resistance; vancomycin is used in patients with severe β-lactam allergies.

Enterococcal endocarditis is commonly treated with ampicillin plus ceftriaxone or gentamicin. HACEK organisms typically respond to ceftriaxone monotherapy, although ampicillin or ciprofloxacin may be appropriate in selected circumstances. Methicillin-susceptible S aureus infections are treated with nafcillin or cefazolin, whereas methicillin-resistant S aureus infections are generally treated with vancomycin or daptomycin.[13]

Routine adjunctive aminoglycoside therapy is no longer recommended for native valve infective endocarditis because it increases nephrotoxicity without improving survival outcomes. Similarly, routine rifampin use is discouraged because of hepatotoxicity concerns. Exceptions include aminoglycoside-susceptible enterococcal infections and selected cases of prosthetic valve endocarditis, in which combination regimens incorporating gentamicin and/or rifampin may still be appropriate. Fungal endocarditis, most commonly caused by Candida or Aspergillus species, is associated with poor outcomes and frequently requires a combination of antifungal therapy and surgical intervention. In patients with mechanical prosthetic valve endocarditis who experience a central nervous system embolic event, temporary discontinuation of anticoagulation for approximately 2 weeks may be reasonable.[13][14]

Culture-negative endocarditis presents a unique diagnostic and therapeutic challenge. Common causes include prior antibiotic exposure, inadequate microbiologic sampling, fastidious organisms, and fungal pathogens. Potential etiologic agents include Coxiella burnetii, Bartonella species, Brucella species, and Tropheryma whipplei.

A careful history should assess epidemiologic risk factors and prior antimicrobial exposure, followed by appropriate serologic and molecular testing. Empiric treatment should initially target the most likely pathogens based on whether the infection is acute or subacute and whether it involves a native or prosthetic valve. Suggested regimens include vancomycin plus cefepime for acute native valve disease; vancomycin plus ampicillin-sulbactam for subacute native valve disease; vancomycin, cefepime, rifampin, and gentamicin for prosthetic valve endocarditis occurring within one year of surgery; and vancomycin plus ceftriaxone for prosthetic valve infections occurring more than 1 year after valve implantation.[13]

Surgery is required in many patients and should not be viewed as a treatment failure but rather as an integral component of therapy in appropriately selected cases. Class I indications for surgery include severe valvular dysfunction resulting in heart failure, left-sided infective endocarditis caused by S aureus, fungal or other highly resistant microorganisms, annular or aortic root abscess formation, new conduction abnormalities or heart block, recurrent septic embolization despite appropriate antibiotic therapy, persistent sepsis despite antimicrobial treatment, rupture of a sinus of Valsalva aneurysm, and persistent infection despite 5 to 7 days of appropriate antibiotic therapy.[15](B3)

The primary surgical principles include complete excision of infected and necrotic tissue, eradication of abscess cavities, and reconstruction of damaged cardiac structures. Intraoperative transesophageal echocardiography is a class I recommendation for assessing the extent of infection and confirming the adequacy of repair or replacement. Median sternotomy remains the standard surgical approach in most cases. Surgical exposure of the aortic valve is typically obtained through a low transverse or oblique aortotomy. 

For native aortic valve endocarditis confined to the valve leaflets or cusps, valve repair should be performed whenever feasible (class I recommendation) because it preserves native valve architecture and avoids prosthetic material.[15] When replacement is necessary, valve selection between mechanical and bioprosthetic prostheses generally follows standard valve replacement guidelines. However, patient-specific considerations, such as a recent stroke or intracranial hemorrhage, may influence decision-making.(B3)

Management becomes substantially more complex when infection extends beyond the valve leaflets. In native valve endocarditis involving the annulus, radical debridement is essential, followed by reconstruction of the resulting defect. Small- to moderate-sized annular defects may be repaired using autologous or bovine pericardial patches, whereas larger defects often require Dacron patch reconstruction.

When more than 50% of the annulus is involved, an aortic homograft is generally preferred. Aortic root abscesses are among the most challenging complications because infection may extend into the fibrous trigones, the interventricular septum, the atria, or the pulmonary artery. Extensive disease frequently necessitates complete aortic root replacement with coronary artery reimplantation. In cases involving destruction of the intervalvular fibrosa, aortic homografts may provide favorable outcomes and facilitate complex reconstruction.

For prosthetic aortic valve endocarditis in which the aortic root and annulus remain intact following radical debridement, implantation of a new mechanical or bioprosthetic valve is reasonable (class IIa).[15] However, when infection destroys the annulus or extends beyond the aortic root, reconstruction using an allograft or biologic tissue root is generally preferred over a prosthetic valved conduit (class IIa).[15] Historically, cryopreserved homografts were widely used and demonstrated favorable infection control, but concerns regarding calcification, structural degeneration, and reoperation have reduced their routine use. Contemporary practice increasingly favors biologic stentless valves, which offer broad availability and favorable durability, although successful implantation requires significant surgical expertise. (B3)

Annular abscesses occur in approximately 12% to 50% of patients with aortic valve endocarditis and are associated with nearly double the short-term mortality rate and an increased risk of recurrent infection. Consequently, complete surgical debridement and patch reconstruction remain the cornerstone of treatment. Although local antibiotic delivery systems have been proposed to reduce recurrence, evidence suggests that complete surgical eradication of infected tissue is the most important determinant of long-term success. Future strategies may include antibiotic-eluting or bacteria-resistant patches and prosthetic valves designed to further reduce the risk of recurrent endocarditis in these high-risk individuals.

Differential Diagnosis

The differential diagnosis of infective endocarditis includes several infectious, inflammatory, autoimmune, neoplastic, and thrombotic conditions that may present with fever, cardiac murmurs, systemic embolization, or valvular vegetations on imaging. Distinguishing these entities from infective endocarditis is critical because management strategies differ substantially. Nonbacterial thrombotic endocarditis (NBTE), formerly known as marantic endocarditis, is one of the most important considerations. NBTE is characterized by sterile platelet-fibrin vegetations that typically form along the valve leaflets and are commonly associated with hypercoagulable states, advanced malignancy, and chronic systemic illnesses. Unlike infective endocarditis, blood cultures are negative, and there is no microbial invasion of the valvular tissue. 

Libman-Sacks endocarditis is another form of sterile valvular vegetation that occurs in association with systemic lupus erythematosus and antiphospholipid antibody syndrome. The characteristic verrucous vegetations are typically found on either side of the valve leaflets and may mimic infective endocarditis clinically or echocardiographically. Systemic vasculitides and connective tissue disorders may also resemble infective endocarditis because of overlapping constitutional symptoms, elevated inflammatory markers, cardiac manifestations, and embolic phenomena.

Conditions such as antineutrophil cytoplasmic antibody-associated vasculitis or systemic lupus erythematosus can present with fever, malaise, weight loss, and multisystem involvement, necessitating careful clinical, serologic, and microbiologic evaluation. Fever of unknown origin remains an important diagnostic consideration, particularly in patients presenting with prolonged constitutional symptoms and nonspecific laboratory abnormalities. Because infective endocarditis is a classic cause of fever of unknown origin, a thorough evaluation is required to distinguish it from other infectious, inflammatory, autoimmune, and neoplastic etiologies. 

Cardiac tumors, particularly atrial myxomas, may mimic infective endocarditis by causing constitutional symptoms, embolic events, murmurs, and intracardiac masses identified on imaging studies. Echocardiographic characteristics and the absence of microbiologic evidence of infection help differentiate these entities. Acute rheumatic fever with carditis may also resemble infective endocarditis, particularly in younger patients presenting with fever and new valvular dysfunction. Clinical features such as migratory polyarthritis, chorea, erythema marginatum, subcutaneous nodules, and evidence of recent group A streptococcal infection help distinguish acute rheumatic fever from infective endocarditis. 

Prognosis

The prognosis of infective endocarditis remains guarded despite significant advances in diagnostic imaging, antimicrobial therapy, and surgical management. In-hospital mortality has remained relatively unchanged over the past 2 decades, ranging from approximately 15% to 30%, with an overall mortality of about 20% during hospitalization and nearly 30% at 6 months after diagnosis.[14] The persistently high mortality reflects the increasing age of affected patients, the growing burden of comorbid conditions, the emergence of antimicrobial-resistant pathogens, and the rising incidence of healthcare-associated infections.[14] 

Multiple factors, including the virulence of the causative organism, the presence of complications, underlying patient comorbidities, and the timing of medical and surgical intervention, influence prognostic outcomes. Infective endocarditis caused by S aureus, Pseudomonas aeruginosa, Enterobacteriaceae, or fungal pathogens is associated with substantially higher mortality rates.[14] Additional predictors of poor outcome include advanced age, prosthetic valve endocarditis, end-stage renal disease requiring hemodialysis, severe heart failure, ischemic stroke, intracardiac or myocardial abscess formation, severe immunosuppression such as human immunodeficiency virus infection, and perivalvular extension of infection.[14] Prosthetic valve endocarditis generally carries a worse prognosis than native valve endocarditis because of the increased risk of prosthetic valve dehiscence and perivalvular complications. Conversely, right-sided infective endocarditis in intravenous drug users is associated with lower mortality, estimated at approximately 10%.

Neurologic complications remain a major source of morbidity and mortality. Cerebral embolization is particularly common in left-sided infective endocarditis and is associated with adverse clinical outcomes. In a study of 1437 consecutive patients with left-sided infective endocarditis, the incidence of stroke among patients receiving appropriate antimicrobial therapy was 4.82 per 1000 patient-days during the first week of treatment and decreased to 1.71 per 1000 patient-days during the second week, highlighting the importance of prompt diagnosis and early initiation of effective antimicrobial therapy in reducing embolic risk.[16]

Healthcare-associated and nosocomial infective endocarditis have become increasingly prevalent, particularly in developed countries, and are often caused by multidrug-resistant organisms. These infections frequently occur in medically complex individuals and are associated with higher rates of complications, perioperative morbidity, and mortality. Early identification of high-risk individuals and timely implementation of multidisciplinary management strategies, including urgent surgical intervention when indicated, may improve both short-term and long-term outcomes.

Complications

Aortic valve infective endocarditis is associated with numerous potentially life-threatening complications resulting from valvular destruction, local extension of infection, and systemic embolization. Cardiac complications are among the most common and serious adverse outcomes. Progressive valvular damage may lead to acute or chronic aortic regurgitation and congestive heart failure, which remains the leading cause of mortality in patients with infective endocarditis. Extension of infection beyond the valve leaflets can result in annular abscess formation, myocardial abscesses, and destruction of surrounding cardiac structures. Involvement of the cardiac conduction system may produce atrioventricular block or other conduction abnormalities, often indicating invasive perivalvular disease.[17]

Local extension of infection may also lead to the development of mycotic aneurysms involving the sinus of Valsalva. These aneurysms can rupture or erode into adjacent structures, resulting in pericarditis, hemopericardium, cardiac tamponade, or fistulous communications between the aorta and cardiac chambers, including the right or left ventricle.[17] Such complications frequently require urgent surgical intervention because of their association with rapid hemodynamic deterioration. 

Neurologic complications are common and arise primarily from septic embolization of valvular vegetations. Embolic events may result in transient ischemic attacks, ischemic stroke, cerebral abscesses, or mycotic intracranial aneurysms. Rupture of these aneurysms can cause intracranial hemorrhage and sudden death, contributing substantially to the morbidity and mortality associated with infective endocarditis.[17]

Systemic embolization may affect multiple organ systems, leading to infarction, abscess formation, or end-organ dysfunction involving the kidneys, spleen, liver, and, less commonly, the lungs, in cases of right-sided or paradoxical embolization. Renal injury may result from embolic infarction, immune-complex glomerulonephritis, or septic emboli, while splenic involvement may manifest as infarction or abscess formation. Acute coronary syndrome is a rare but potentially catastrophic complication of infective endocarditis, occurring most frequently in association with aortic valve infection and severe aortic regurgitation. Coronary ischemia may result from septic coronary embolization or extrinsic compression of a coronary artery by a periannular abscess, potentially leading to myocardial infarction and hemodynamic collapse.[18]