Aortic Valve Endocarditis Surgical Treatment

Etiology

For native valve endocarditis and IE, the most common microorganisms are Streptococcus viridans and S aureus.[1] For prosthetic valve endocarditis in the early phase (less than 2 months), typical agents include coagulase-negative staphylococci, Staphylococcus epidermidis (30%-35%), and S aureus (20%-24%). In the late phase (more than 12 months), the typical etiologic agents are S viridans and S aureus.[1] For acute bacterial endocarditis, the most common agent is S aureus, whereas for subacute bacterial endocarditis, the most common agent is Streptococcus mutans.

Candidal infectious endocarditis usually presents in patients with prosthetic valves, those who use intravenous drugs, and immunocompromised individuals.[1] Gastrointestinal or genitourinary manipulation is a risk factor for Streptococcus bovis or enterococcal IE. Poor dental hygiene risks streptococci and the HACEK group agents (Haemophilus, Aggregatibacter [previously Actinobacillus], Cardiobacterium, Eikenella, Kingella). In contrast, nosocomial agents include S aureus, gram-negative agents, and Candida spp. 

Epidemiology

Epidemiological studies indicate that the profile of IE has shifted significantly worldwide. S aureus has emerged as the most common causative organism, supplanting previously predominant pathogens. Additionally, the demographic and clinical characteristics of affected patients have evolved, with an increased mean age, a higher proportion of prosthetic valve infections, and a greater number of surgeries performed for IE management.[8] There has also been a noticeable rise in IE incidence following minimally invasive aortic valve surgeries and percutaneous transcatheter aortic valve replacement procedures, highlighting the need for vigilant postprocedural monitoring and tailored management strategies.[9][10]

Pathophysiology

IE of the aortic valve is a life-threatening condition caused by microorganisms, most commonly bacteria, colonizing and subsequently infecting the valvular endocardial surface. The pathophysiology of aortic valve endocarditis involves a complex interplay between endothelial injury, microbial adherence, immune response, and structural damage.

Endothelial Injury and Microbial Adherence

Endothelial injury, often caused by turbulent blood flow from congenital or acquired valve abnormalities such as a bicuspid aortic valve, aortic stenosis, or insufficiency, exposes the subendothelial collagen and tissue factor. This injury initiates the formation of a nonbacterial thrombotic endocardial lesion, which consists of fibrin and platelets. These lesions provide an ideal site for bacterial adhesion. Bacteremia, often resulting from dental, surgical, or other invasive procedures, allows circulating pathogens, particularly S aureus, S viridans, or enterococci, to attach to the nonbacterial thrombotic endocardial lesion.

Colonization and Vegetation Formation

Once adhered, bacteria become encased in a fibrin and platelet matrix, forming vegetations. This environment shields the bacteria from immune surveillance and antibiotics, making the infection more difficult to eradicate. In aortic valve endocarditis, vegetation typically forms on the aortic side of the valve leaflets. As the vegetation grows, it can cause mechanical destruction of the valve, leading to aortic regurgitation or stenosis, further compromising hemodynamic function.

Immune Response and Tissue Damage

The host immune response to infection exacerbates the damage. Neutrophils and macrophages release inflammatory cytokines and proteolytic enzymes, contributing to local tissue destruction and weakening of the aortic valve. Over time, the infection may extend beyond the valve leaflets to the adjacent myocardium and aortic root, leading to complications such as ring abscesses, perivalvular leaks, or fistulae between cardiac chambers or the aorta.

Complications and Embolization

The vegetations can embolize, particularly in cases of large, friable vegetations, leading to systemic embolic events such as stroke, myocardial infarction, or embolism to peripheral organs (eg, kidneys, spleen). Additionally, severe aortic regurgitation due to valve destruction can cause acute heart failure, which is a frequent indication for urgent surgical intervention.

History and Physical

IE remains challenging to diagnose due to its diverse clinical presentations. Consideration should be given to IE in any patient with sepsis or an unexplained fever, particularly when risk factors are present. Manifestations can vary widely, appearing as an acute, rapidly progressing infection or a subacute or chronic condition with mild or absent fever and vague symptoms, complicating the initial diagnosis. Furthermore, IE may present with complications that mimic various medical conditions, including rheumatologic, neurological, and autoimmune disorders or even malignancies. These diverse presentations can lead to evaluations for other diseases before arriving at an IE diagnosis. Maintaining a high level of suspicion for IE is crucial, especially when fever and positive blood cultures are present without a clear source of infection. Early involvement of a multidisciplinary endocarditis team is strongly recommended to guide disease management.

Data from the European Infective Endocarditis Registry reveal that the most common clinical signs of IE include fever (77.7%), heart murmur (64.5%), and heart failure (27.2%).[11] Embolic complications were present in 25.3% of patients, while cardiac conduction abnormalities were found in 11.5%.[4] Although classic peripheral stigmata, such as splinter hemorrhages and Osler nodes, are less frequently seen today, they may still occur in severe infections caused by S aureus or subacute IE, typically due to Streptococcus spp. Vascular and immunological manifestations, such as Roth spots and glomerulonephritis, remain common.[12]

Atypical presentations are more frequent in elderly or immunocompromised individuals, necessitating a high index of suspicion and a low threshold for testing to rule out IE, especially in high-risk groups like those with congenital heart disease or prosthetic valves.[13] Educating these patients about their risk and the symptoms of IE is crucial so they can seek timely advice from specialized centers.[14] The most common symptoms include fever, anorexia, weight loss, malaise, and night sweats.[1] Physical examination findings often reveal a murmur, petechiae on the skin, oral mucosa or conjunctivae, and splenomegaly.[1] Peripheral findings of IE include splinter hemorrhages, usually seen under the fingernails or toenails, as well as Osler nodes and Janeway lesions.[1]

Evaluation

The diagnosis of IE is primarily based on clinical suspicion, supported by microbiological evidence and imaging that confirms cardiac lesions related to IE. A critical diagnostic criterion is detecting the involvement of the heart valves (native or prosthetic) or intracardiac prosthetic material. Echocardiography is the preferred initial imaging method. However, additional techniques such as computed tomography (CT) scans, positron emission tomography (PET), and magnetic resonance imaging (MRI) are increasingly incorporated into the diagnostic approach due to their ability to confirm IE, evaluate local complications, detect distant lesions, and trace the source of bacteremia in patients with secondary IE. Moreover, imaging findings play a crucial role in determining prognosis.[15]

The classification of IE is based on the Modified Duke Criteria, which provides a structured framework for evaluating patients suspected of having IE. The criteria classify cases into 3 categories: definite, possible, and rejected.[16] Definite IE can be further subdivided into 2 types:

• Definite IE by pathological criteria
  • Definite IE by pathological criteria is confirmed when microorganisms are identified in an excised vegetation or an abscess specimen or if histological evidence shows active endocarditis within the vegetation or abscess. 
• Definite IE by clinical criteria
  • Definite IE by clinical criteria is met when 2 major criteria, 1 major criterion plus 3 minor criteria, or 5 minor criteria are fulfilled according to the Modified Duke Criteria.[16][17][18]
    • The primary clinical criteria include:
      • Multiple positive blood cultures
      • A single positive culture for Coxiella burnetii
      • Evidence of endocardial involvement, such as new valvular regurgitation or echocardiographic findings of vegetation, abscess, or dehiscence [18]
    • Minor clinical criteria encompass the following:
      • Predisposing heart conditions or intravenous drug use
      • Fever greater than 38 °C (100.4 °F)
      • Vascular phenomena like arterial emboli, septic pulmonary infarcts, or Janeway lesions
      • Immunologic phenomena such as Osler nodes, Roth spots, or rheumatoid factor
      • Positive blood cultures that do not meet the significance criteria [18]

Possible IE is diagnosed when 1 major criterion and 1 minor criterion, or 3 minor criteria, are present.[16] Rejected IE is defined when an alternative diagnosis is more likely, there is no pathological evidence of IE after less than 4 days of antibiotic therapy, or clinical symptoms resolve within 4 days of antibiotic therapy.[16] The echocardiographic criteria for IE include an oscillating intracardiac mass on valves or supporting structures in the path of regurgitant jets, an abscess, or partial prosthetic valve dehiscence.[16] A transthoracic echocardiogram (TTE) should be corroborated by a transesophageal echocardiogram (TEE) to evaluate suspected IE comprehensively. In cases where no definitive diagnosis is established until surgery, tissue specimens should be obtained for histological analysis to confirm the presence of endocarditis.

Advanced imaging modalities, such as CT, MRI, and positron emission tomography-computed tomography (PET-CT), are highly recommended in patients with suspected or confirmed IE due to their ability to provide comprehensive diagnostic information. Cardiac CT is particularly valuable for diagnosing IE and its cardiac complications, including perivalvular and periprosthetic abscesses, pseudoaneurysms, and fistulas. Study results indicate that cardiac CT offers superior accuracy compared to TEE in detecting these complications, especially in cases of native valve endocarditis and prosthetic valve endocarditis when TEE is inconclusive or not feasible. Cardiac CT is also crucial in guiding surgical decisions, offering detailed anatomical views that inform the extent of surgical resection or reconstruction needed.[19]

Whole-body and brain CT are essential tools for detecting distant lesions and sources of bacteremia. These imaging studies allow clinicians to identify systemic complications of IE, such as septic emboli, which serve as minor diagnostic criteria and can contribute to establishing a definitive diagnosis or excluding IE. Furthermore, MRI is indispensable in detecting neurological complications and spinal lesions related to IE. The high-resolution imaging capability of MRI makes it ideal for evaluating ischemic or hemorrhagic strokes, which are often observed in patients with IE with septic embolization to the brain.[20]

Integrating PET-CT with CT angiography (PET/CTA) provides a novel approach for assessing IE's metabolic activity and anatomical abnormalities. The combination of fluorodeoxyglucose F 18 uptake measurement with anatomical visualization enables the detection of active infection sites and distant embolic events, aiding in the management of complex cases, such as those with congenital heart disease or aortic grafts. This multimodal imaging approach improves diagnostic precision and influences therapeutic strategies, ultimately optimizing patient outcomes.[21]

Treatment / Management

Management of IE primarily involves prolonged courses of bactericidal antibiotics. The choice of regimen, whether single or combination therapy and the duration of treatment (ranging from 2 to 6 weeks) depend on the pathogen’s susceptibility and resistance profile and whether the patient has native or prosthetic valve endocarditis. Treatment typically begins in the hospital and is often completed on an outpatient basis once the patient is afebrile and blood cultures are negative. However, antibiotic therapy may not be sufficient for all cases. Surgery becomes necessary under Class I indications, which include valvular dysfunction leading to heart failure, left-sided IE caused by S aureus, fungal or resistant microorganisms, conduction abnormalities such as heart block, annular or abscess formation, or persistent infection after 5 to 7 days of antibiotic therapy.[2](B3)

Surgical management of IE focuses on aggressive debridement of all infected and necrotic tissue, followed by reconstructive surgery. Intraoperative TEE is a Class I recommendation for evaluating the extent of damage.[2] With some exceptions, median sternotomy is also a Class I recommendation.[2] Surgical access to the aortic valve is typically achieved through a low transverse or oblique aortotomy. For native valve IE, the goal is to eradicate infected tissue and repair or replace the valve. Repair should be prioritized when infection is limited to the valve leaflets or cusps (Class I).[2] In cases requiring replacement, valve selection—whether mechanical or bioprosthetic—follows standard criteria (Class I), except in patients with contraindications such as intracranial hemorrhage or stroke (Class IIa).[2](B3)

For native aortic valve endocarditis involving the annulus, radical resection of infected tissue is crucial, followed by reconstructive surgery. Small to moderate defects may be repaired with autologous or bovine pericardial patches, while larger defects necessitate a Dacron patch.[22] An aortic homograft is preferred if more than 50% of the annulus is affected.[23] Aortic root abscess presents a significant challenge due to the extensive damage it can inflict on nearby structures, including the fibrous trigones, interventricular septum, atria, and pulmonary artery.[22] The severity of the infection often necessitates complete replacement of the aortic root, coupled with reimplantation of the coronary arteries to restore functionality. In cases where intervalvular fibrosis is present, an aortic homograft is the preferred treatment option, offering a favorable outcome in complex reconstructions where standard prosthetic valves might not suffice.[24] This approach helps manage the infection while addressing the structural damage caused by the abscess. For prosthetic aortic valve endocarditis that spares the aortic root and annulus after radical resection, implanting a new prosthetic valve (tissue or mechanical) is reasonable (Class IIa).[2] However, with the destruction of the annulus or if the infection has spread beyond the aortic root, reconstruction and using an allograft or a biologic tissue root is preferable to a prosthetic valved conduit (Class IIa).[2](B3)

Annular abscesses are a serious complication of aortic valve endocarditis, occurring in 12% to 50% of cases and doubling short-term mortality rates. Recurrence of IE is also more frequent in patients with annular abscesses.[4] As such, eradicating the infection through radical surgical debridement followed by patch reconstruction is critical. While local antibiotics have been proposed to reduce the risk of recurrence, the likelihood of residual disease is low following complete surgical abscess removal. However, mixing antibiotics with fibrin glue in the remaining abscess cavity may only offer temporary protection, and the glue could hinder antibiotic penetration into surrounding tissues, reducing the treatment's effectiveness. Although local antibiotic application has successfully prevented sternal wound infections, developing antibiotic-eluting or bacteria-resistant patches and valve prostheses may offer a more robust solution to prevent recurrent endocarditis in this high-risk group.[25]

Differential Diagnosis

Differential diagnoses for aortic valve endocarditis include:

• Nonbacterial thrombotic endocarditis
  • Marantic endocarditis causes small sterile vegetations on the valve leaflets and is linked to hypercoagulable states and some malignancies.
• Libman–Sacks endocarditis
  • This condition causes verrucous vegetations and is associated with systemic lupus erythematosus.
• Vasculitis
• Connective tissue disease
• Fever of unknown origin

Prognosis

The prognosis of IE is influenced by a myriad of factors, making it a challenging disease to manage and treat effectively. In-hospital mortality for IE has remained relatively stable over the past 2 decades, ranging from 15% to 30%, and various patient characteristics have been identified as contributing factors to this elevated risk of death. The overall in-hospital mortality is around 20%, whereas the 6-month mortality is approximately 30%, underscoring the fatal nature of this condition.[26] The virulence of the causative organism, complications, patient comorbidities, and the timing of medical or surgical interventions largely determine prognostic outcomes.

Causative organisms such as S aureus, Pseudomonas aeruginosa, Enterobacteriaceae, and fungi are associated with significantly higher mortality rates. Certain patient-specific factors also contribute to a poorer prognosis, including advanced age, prosthetic valve endocarditis, hemodialysis, severe heart failure, stroke, the presence of an intracardiac abscess, severe immunosuppression (eg, human immunodeficiency virus infection), or perivalvular extension with myocardial abscess formation.[1][26] Prosthetic valve endocarditis carries a worse prognosis compared to native valve endocarditis due to the increased risk of perivalvular complications and prosthetic valve dehiscence. Conversely, right-sided IE in intravenous drug users typically has a lower mortality rate, around 10%, reflecting the less complex nature of the disease in this subgroup.[27]

Despite technological advances in diagnostic imaging, antimicrobial therapy, and surgical techniques, the mortality rate for IE has not significantly decreased. This persistence is attributed to multiple factors, including the increasing age of affected patients, the higher prevalence of comorbid conditions, changing epidemiological trends, and the emergence of more resistant pathogens.[1][26] Nosocomial infections, often caused by multi-drug resistant organisms, now represent a greater proportion of IE cases, especially in developed countries. Additionally, the need for complex interventions in high-risk populations can contribute to elevated perioperative mortality and morbidity. Early recognition of high-risk individuals could provide opportunities for timely interventions, such as urgent or emergency surgery, which may improve overall outcomes and long-term prognosis.[4]

Complications

Cardiac complications include congestive heart failure caused by valvular damage from the infection, annular abscess, the extension of infection into the conduction system leading to atrioventricular blocks, mycotic aneurysms of the sinus of Valsalva, which can result in pericarditis, hemopericardium, and cardiac tamponade, or fistulas to the cardiac chambers including the right or left ventricle.[1] Neurologic complications include thromboembolic events and mycotic aneurysms from septic embolization of vegetations; these aneurysms can rupture and cause intracranial hemorrhage and sudden death.[1] Other complications include systemic embolism to the end organs, including the liver, the lungs, the kidneys, and the spleen.[1]