Nika Samadzadeh Tabrizi MD, James Witten MD, Haytham Elgharably MD
Cleveland Clinic Foundation
April 24th, 2025
Abbreviations & Definitions
AATS – American Association for Thoracic Surgery
ACC/AHA – American College of Cardiology/American Heart Association
AV – Aortic valve
CIED – Cardiovascular implanted electronic device
CT – Computed tomography
EASE – Early Surgery versus Conventional Treatment in Infective Endocarditis
ESC – European Society of Cardiology
ICE-PCS – International Collaboration on Endocarditis–Prosthetic Valve Endocarditis
IE – Infective endocarditis
TEE – Transesophageal echocardiography
TTE – Transthoracic echocardiography
TV – Tricuspid valve
MV – Mitral valve
NVE – Native valve endocarditis
PET-CT – Positron emission tomography-computed tomography
PVE – Prosthetic valve endocarditis
STS – Society of Thoracic Surgeons
Indications & Guidelines for Management by Grade/Stage of Disease
Evaluation of IE
Society consensus guidelines were last published by the AATS in 2016,1 just following the publication of the 2015 ESC guidelines.2 In 2020 and 2023, respectively, the AHA/ACC3 and ESC4 provided updated guidelines to integrate emerging evidence in response to the rising incidence of IE, increasing antibiotic resistance, and advancements in diagnostic modalities.
Given the significant morbidity associated with IE, management should be centralized at specialized IE referral centers (Class I) and overseen by a dedicated Heart Team (Class I).4 Diagnosis of IE is based on major criteria – blood cultures, radiographic evidence of valvular involvement (regurgitation/vegetations) – and minor criteria, which encompass a range of clinical, microbial, and imaging findings. The diagnostic workup for patients with suspected IE is structured around four key objectives: 1) accurate identification of native/prosthetic valve IE, 2) pathogen identification to tailor antimicrobial therapy, 3) assessment of disease severity to inform surgical planning, and 4) risk stratification, including evaluation for distant embolic events and neurological complications to determine the overall prognosis and treatment approach. A summary of diagnostic modalities is outlined in Table 1.
Table 1. Preoperative evaluation.
| Recommendation | Class of Recommendation | |
|---|---|---|
| Modified Duke criteria | Criteria was updated in 2023 to the Duke-ISCVID criteria5 | I |
| Blood cultures | Identify causative organism to guide antimicrobial regimen or broad coverage if unknown | I |
| TTE | In all patients | I |
| TEE | Following non-diagnostic TTE, in the presence of intracardiac leads/prosthetic valve, or undergoing cardiac surgery | I |
| Coronary angiography | According to normal criteria (e.g., risk factors, prior bypass), with caution in the presence of AV vegetations (coronary CT angiography is an alternative) | I |
| Cardiac CT angiography | To confirm IE or suspected paravalvular complications | I |
| PET-CT scan | For suspected PVE (if echo and CT scan are inconclusive) | I |
| PET-CT scan | To detect cardiac device-related/endovascular graft-related IE | IIb |
| Radiolabeled leukocyte scintigraphy | For suspected PVE and non-diagnostic echocardiography/unavailable PET-CT | IIa |
| CT brain non-contrast | Screening in asymptomatic left-sided IE or right-sided IE with a patent foramen ovale | IIb |
| Brain MRI ± digital subtraction angiography | In the presence of neurologic deficits | I |
| Brain MRI ± digital subtraction angiography | Screening in asymptomatic patients (detects ~70% of silent emboli) | IIa |
| Brain MRI ± digital subtraction angiography | If extensive stroke >3 cm or hemorrhage à wait ≥ 3 weeks | IIb |
| Brain MRI ± digital subtraction angiography | No extensive stroke/hemorrhage à operate when clinically stable | IIb |
| Cerebral angiography | Following negative non-invasive imaging if neurologic symptoms or intracranial hemorrhage or for suspected mycotic aneurysm | IIa |
| Whole-body imaging (CT, PET/CT/MRI) | If symptoms suggest extracardiac complications | I |
| Whole-body imaging (CT, PET/CT/MRI) | Screening in asymptomatic patients | IIb |
| Polymerase chain reaction | Preoperatively (blood culture) | IIa ‡ |
| Polymerase chain reaction | Postoperatively (specimen) for suspected culture negative/dormant IE | I ‡ |
2023 ESC guidelines are demonstrated unless: ‡ reflects recommendations unique to 2016 AATS guidelines.
Surgical Indications
The decision to pursue surgical intervention is guided primarily by three critical factors: 1) the presence of heart failure secondary to structural pathology, such as valve dysfunction or fistula between cardiac chambers, 2) uncontrolled infection – often due to antibiotic-resistant or invasive pathogens, and 3) the risk of septic embolism, particularly in cases involving large vegetations. Summarized in Table 2, indications for surgery are primarily derived from expert consensus and observational studies.
Surgical intervention in the acute phase is more typical of left-sided IE, which tends to involve invasive species. Early surgical intervention for IE – defined as surgery during the initial hospitalization independent of completion of a full course of antibiotics – may be indicated emergently (within 24 hours) in patients presenting with severe acute regurgitation, fistula formation, or valve dysfunction leading to pulmonary edema or cardiogenic shock (Class I).4 Urgent surgery (within 3–5 days) is recommended for patients exhibiting symptoms or radiographic findings consistent with heart failure, locally uncontrolled infection (e.g., peri-annular abscess, conduction disturbance), or large vegetations particularly when associated with recurrent embolization (Class I).4
In contrast, right-sided IE, which predominantly affects the TV (90%), is typically associated with less invasive pathogens compared to left-sided IE. Thus, management starts with culture-directed antimicrobial therapy. However, surgical intervention is necessary in approximately 5–15% of cases and indicated for those with symptoms of right heart failure associated with TV dysfunction, larger vegetations with recurrent septic pulmonary emboli, or prosthetic valve endocarditis (PVE). The timing of surgical intervention as it relates to the pulmonary embolic burden is unclear. Not reflected in guidelines, longer wait times and increased pulmonary emboli can increase the pulmonary vascular resistance, which could deem surgical intervention prohibitive. Debulking of TV vegetations can be considered as a bridge-to-decision or bridge-to-surgery in patients with a history of intravenous drug use.6
If the indication for surgery is met, the same criteria apply to high-risk patients (intravenous drug users, chronic dialysis, cirrhosis), but require a thorough and individualized assessment (Class IIa).1
Summary Table 2. Surgical intervention for IE.
| Recommendation for Surgical Intervention | Class |
|---|---|
| All IE | |
| Heart failure symptoms (cardiogenic shock, pulmonary edema, hemodynamic instability) | I |
| Local extension/penetrating lesion (heart block, abscess, fistula, prosthetic dehiscence) | I |
| Persistent bacteremia or fever despite >5 days on appropriate antimicrobial regimen | I † |
| Early PVE (<6 months since valve replacement) | I |
| Relapsing bacteremia in PVE* | I † IIa ‡ |
| Recurrent emboli with persistent vegetations despite antibiotics | IIa †‡ |
| Embolic phenomenon with vegetation >1 cm | IIb ‡ |
| Right-Sided IE | |
| Recurrent emboli with persistent vegetations >2 cm despite antibiotics | I |
| Recurrent emboli with pulmonary insufficiency requiring ventilatory support | I |
| Left-sided structures involved | I |
| Persistent bacteremia or fever despite >7 days on appropriate antimicrobial regimen | IIa |
| Left-sided IE | |
| Highly virulent organism despite antibiotics (e.g., S. aureus, fungi) | I |
| Recurrent embolization with persistent vegetations ≥1 cm despite antibiotics | I |
| Relapsing bacteremia in NVE* | IIa |
| PVE | IIa ‡ |
| Recurrent embolization with persistent vegetations despite antibiotics | IIa |
| Vegetation ≥1 cm with severe stenosis/regurgitation in low-risk patients (regardless of embolization) | IIa |
| Vegetation ≥1.5 cm and no other indication for surgery (regardless of embolization) | IIb |
| CIED extraction (percutaneous preferred; open if percutaneous unsuccessful, destructive TV IE, vegetation >2 cm) | |
| Definite CIED-related IE à extraction without delay | I |
| Suspected CIED-related IE | I ‡ |
| No evidence of CIED-related IE | |
| Left- or right-sided valvular IE by S. aureus or fungi | IIa |
| Valvular IE, regardless of organism | IIa |
| Undergoing surgery for valvular IE, regardless of organism | IIb ‡ |
*Relapse is defined as recurrent bacteremia after completing a course of appropriate antibiotics with interval negative blood cultures.
2023 ESC guidelines are demonstrated unless: † reflects recommendations unique to 2020 AHA/ACC and ‡ 2016 AATS guidelines.
Surgical Approach
Surgical technique varies by the valve affected, presence of prosthetic devices and valves, degree of pathology, presence of invasive disease, and necessary concomitant operations. The 2016 AATS1,7 and 2023 ESC4 consensus guidelines are compiled and summarized in Table 3. When IE is confined to the cusps or leaflets, repair is preferred when possible (Class I). For IE involving the MV, the benefit of repair over replacement is well established. For TV, however, recent evidence suggests that repair is associated with better long-term survival and a lower risk of recurrence, reoperation, and permanent pacemaker placement, despite a higher risk of residual moderate-severe regurgitation.8 As a result, TV repair, when possible, is strongly encouraged by the 2016 AATS guidelines (Class I), which is not yet reflected by the 2023 ESC guidelines (Class IIa). Due to the invasive nature of IE involving the AV, repair is rarely possible in the acute setting, but it can occasionally be performed for small leaflet perforations after healed IE.
When valve replacement is needed, the choice of bioprosthetic versus mechanical valve does not appear to impact outcomes in appropriately selected patients.9 Our center prefers bioprosthetic over mechanical valves, in part to avoid the need for anticoagulation postoperatively in patients with embolic complications, particularly neurological complications, maintain access to the right ventricle should the patient require pacemaker placement in the case of TV replacement, and enable possible future valve-in-valve procedures. For AV IE requiring root replacement, using a homograft is preferred (Class I). Root replacement with a homograft is ideal in patients 30-60 years old due to a lower risk of recurrence and thromboembolism, favorable hemodynamics, and greater tissue strength, which is particularly relevant for fragile, infected tissue. The Ross procedure has also emerged as an alternative approach to AVR, demonstrating a lower risk of calcification and recurrence, which may be beneficial for younger patients <30 years old.10
Summary Table 3. Surgical approach.
| Recommendation | Class |
|---|---|
| Placement of epicardial lead recommended if patient is undergoing surgery, has complete heart block, and ≥1 of the following is present: Pre-operative conduction abnormality S. aureus infection Aortic root abscess TV involvement Previous valvular surgery | IIa ‡ |
| Median sternotomy | I |
| Radical debridement | I |
| Percutaneous mechanical aspiration for septic TV IE and high-prohibitive surgical risk | IIb |
| Valve repair whenever possible (e.g., confined to the cusps/leaflets) | I |
| TV repair with annuloplasty ring preferred over replacement, may require reconstructive repair with pericardial patch | I IIa ‡ |
| MV repair with annuloplasty ring, may require reconstructive repair with pericardial patch | I |
| Valve replacement when indicated (choice of mechanical/bioprosthetic according to normal criteria) | I |
| Avoid mechanical valves in intracranial bleeding/prior major stroke | I |
| TV if extensive tri-leaflet or septal leaflet involvement; use autologous pericardial/porcine valves (avoid homologous pericardial/bovine valves) due to higher resistance to calcification | I |
| MV annular reconstruction if annular destruction/invasion (autologous pericardium preferred) | IIa |
| Aortic root replacement when indicated is preferred using an allograft/biologic tissue, but bio/mechanical-Bentall are acceptable alternatives | IIa |
| Distal ascending aortic replacement is preferred with synthetic graft, or alternatively, valveless allograft | IIb |
2016 AATS guidelines are demonstrated unless: ‡ reflects recommendations unique to 2023 ESC guidelines
Supporting Evidence for Current Indications & Knowledge Gaps
- Early surgery to prevent embolism: Once there is an indication for surgery, there is little benefit in delaying the operation. According to the only randomized trial in this area, early surgery reduces the risk of embolism,11 with a significant survival advantage reported by a meta-analysis of 21 studies.12
- EASE Randomized Controlled Trial (2012)11 – The only randomized controlled trial for IE that compared surgery within 48 hours to conventional treatment (antibiotics and surgery during initial hospitalization or at follow-up) in 76 asymptomatic patients with left-sided IE and severe valvular disease or vegetation >1 cm. Early surgery was associated with a significantly lower incidence of embolic event (0% vs. 21%) at 6 months. All-cause mortality was not significantly different (3% vs. 5%).
- Early surgical management for PVE: Early PVE occurring within 6 months of valve replacement typically necessitates surgical intervention as it is closely associated with perioperative infections with invasive species (e.g., S. aureus). As a result, antibiotics alone have been associated with a high risk of recurrence and refractory bacteremia in several observational studies.13-15 To date, however, no trial involving PVE has been performed.
- ICE-PCS (2013)13 – Multicenter observational study (28 countries) that compared early surgery to medical therapy for patients with PVE. Early surgery was associated with lower in-hospital and 1-year mortality in the unadjusted analysis and after controlling for treatment selection bias. In particular, early surgery in a subgroup of patients with severe valvular dysfunction (new mitral or aortic regurgitation, vegetation, abscess, dehiscence, fistula), heart failure, or persistent bacteremia was associated with lower in-hospital (21% vs. 38%) and all-cause mortality (28% vs. 50%) at 1 year. However, all-cause mortality was not significantly different in the overall cohort after controlling for survivor bias.
- Note: The optimal management of late-stage PVE remains controversial due to the high perioperative mortality associated with acute surgery for PVE in early observational studies.13 However, given the rising incidence of PVE seen in up to 31% of patients16 and significant improvements in perioperative outcomes,17 this topic has regained attention. Currently, surgical indications for complicated PVE are according to usual criteria for NVE (e.g., heart failure, persistent/relapsing bacteremia, S. aureus);18 however, we believe that patients with PVE may benefit from an even lower threshold for surgical reintervention. This is because biofilm formation can insulate organisms from antibiotics, especially when involving prosthetic material,19 resulting in a high risk of IE recurrence with antimicrobial therapy alone.
- Transcatheter valve IE: While PVE following transcatheter valve replacement appears to occur at a similar incidence to that reported following surgical valve replacement, it carries a greater risk of mortality.20 Available evidence has been limited to small observational studies, with some suggesting no benefit of surgical intervention21,22 unless there is evidence of local extension.23 As a result, consensus guidelines in this setting are even less defined. Even when a surgical indication is met, only 16% of patients undergo surgery. 24 Recently, an analysis of the STS database compared the outcomes of patients undergoing AV replacement for surgical and transcatheter PVE and found no significant difference in operative mortality,25 suggesting reoperation in this setting may be safer than previously believed. As transcatheter volume increases in low- and intermediate-risk patients, the rates of transcatheter valve infections will increase, and the benefit/risk ratio of operative management is likely to favor surgery in appropriately selected patients.
- Timing of surgery in patients with neurologic complications: Cerebral insults from septic emboli present in nearly 40% of patients with IE, with silent emboli identified in as many as 80%.26 Timing of surgery in these patients is controversial, particularly for ischemic infarcts. Delayed surgery following hemorrhagic infarcts has been consistently associated with a lower risk of neurologic complications and mortality,27-29 which is reflected in the current 2023 ESC guidelines, recommending delayed surgery only for patients with significant hemorrhagic stroke (Class IIa).
- For ischemic strokes, available literature is conflicting, as the risk and impact of hemorrhage transformation are not clearly understood. Early retrospective studies suggested improved outcomes with delayed surgery, potentially due to a lower risk of hemorrhagic transformation,29,30 whereas more recent studies demonstrate a lower risk of recurrent cerebral emboli and overall mortality with early surgery and no difference in outcomes following surgery.27,31,32 As such, the 2020 ACC/AHA guidelines recommend delayed surgery (3-4 weeks) for patients with major ischemic infarct and extensive neurologic damage who are hemodynamically stable (Class IIb).3 Similarly, the 2016 AATS guidelines recommend delayed surgery (1-2 weeks) for ischemic infarcts, particularly if extensive (e.g., >3 cm area of infarction, multifocal); however, early surgery is also reasonable in patients with a strong indication for urgent surgery (Class IIa).1
Ongoing Trials/Recent Publications
The complexity of IE, variability of outcomes based on surgeon and center expertise, and its high-risk nature and rarity have contributed to the scarcity of randomized controlled trials.33 One noteworthy advancement in the field is the use of percutaneous mechanical aspiration in right-sided IE. According to a nationwide analysis of patients with right-sided IE in 2024,34 the rate of mechanical aspiration has increased nearly 5-fold from 2016 to 2020 (2.6%) and is predominantly performed in younger patients with fewer comorbidities. By enabling debulking of large vegetations in patients who are at a high-prohibitive surgical risk, this approach may reduce the risk of further embolic events. However, large observational studies and randomized trials are needed for widespread adoption.
Expert Commentary
Referral to evaluate a case of IE requires urgent attention and a multidisciplinary team evaluation. The existing pathology can progress rapidly, even if the patient is receiving antibiotics. This is related to the virulence factors produced by the organism, including antibiotic resistance, biofilm formation, and release of proteolytic enzymes that result in tissue destruction.35 The virulence factors of the causative organism should be considered in the decision-making for indication and timing for intervention. For instance, damaged valves will not heal, and prosthetic valves are less likely to be sterilized by antibiotics alone. A small vegetation on a prosthetic valve can grow into a circumferential abscess with valve dehiscence, resulting in acute decompensation that will complicate the perioperative course. PVE is commonly associated with invasive pathology. These procedures can be complex, which require familiarity with cardiac fibrous skeleton anatomy and complex reconstruction after radical debridement of the infection. Always prepare for a worse pathology than what the preoperative images show.36 NVE is not always benign and can present with invasive pathology, especially when caused by an aggressive organism. It can also be underestimated on preoperative imaging. Management of IE requires radical debridement of all ill-appearing tissues and removal of all foreign material to provide the best chance for cure and avoid recurrence. There is a learning curve for surgery for IE. Referral of complex endocarditis cases to specialized centers is advised to avoid worse outcomes.
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