Review

Cerebrovascular complications in infective endocarditis: Challenges and considerations in management

Vikyath Satish, MD, Maisha Maliha, MD, Abhyuday Chauhan, MD, Nieves del Mar Morales-Gomez, MD, Safwan Gaznabi, MD, Daniel Lorenzatti, MD, Justin Johannesen, MD, Carlos A. Gongora, MD, Annalisa Filtz, MD, Mario J. Garcia, MD, Leandro Slipczuk, MD, PhD and Aldo L. Schenone, MD
Cleveland Clinic Journal of Medicine August 2025, 92 (8) 491-501; DOI: https://doi.org/10.3949/ccjm.92a.24087

ABSTRACT

Many patients with infective endocarditis experience neurologic complications such as ischemic strokes, intracranial hemorrhages, or infectious intracranial aneurysms. Although data are scarce, in this review we examine how best to predict, prevent, and manage these serious complications and how they affect the appropriate timing of valve surgery for infective endocarditis.

KEY POINTS

  • Embolic strokes in patients with infective endocarditis usually occur within 2 weeks of endocarditis diagnosis.

  • Risk factors for embolic events include a history of embolism, Staphylococcus aureus infection, and vegetations that are located on the mitral valve, larger than 10 mm, highly mobile, and rapidly growing.

  • Transient ischemic attacks, ischemic strokes with favorable features, and microhemorrhages should not delay otherwise-indicated valve surgery.

  • Cerebral hemorrhage or microbleeds should prompt investigations to exclude infectious aneurysms that could be treated with early endovascular or surgical interventions.

  • Valve surgery for infective endocarditis, if indicated, should be postponed for at least a month after a hemorrhagic stroke with unfavorable features.

While infective endocarditis primarily affects the endocardium and cardiac valves, it often manifests with significant cerebrovascular complications ranging from ischemic strokes and hemorrhages to infectious intracranial aneurysms, which are markers of severe disease and contribute to increased morbidity and mortality.1 Although these complications are common and serious, data remain scarce regarding how best to prevent, predict, and manage them.

This review synthesizes current knowledge on preventing, predicting, and managing the cerebrovascular complications of infective endocarditis, drawing primarily from guidelines from the American College of Cardiology and American Heart Association,1 European Society of Cardiology,2 and American Association for Thoracic Surgery.3 It also integrates insights from emerging studies to provide a more comprehensive and up-to-date perspective.

CEREBROVASCULAR COMPLICATIONS ARE COMMON

Cerebrovascular complications occurred in 35% to 80% of patients with infectious endocarditis in various studies, with nearly one-third of patients having asymptomatic complications detected only on imaging.2,4–6

Ischemic strokes account for most of these complications.6,7 Notably, up to half of these strokes may be silent and detectable only through brain imaging.2

Although infective endocarditis can affect either side of the heart, most cases involve the left-sided valves, posing a risk for embolic ischemic strokes. In contrast, right-sided infective endocarditis, often associated with intravenous drug use or cardiac implantable electronic devices, can lead to pulmonary embolism and pulmonary valve stenosis and insufficiency. An exception is paradoxical embolization from the right side of the heart to the left through a patent foramen ovale, which is beyond the scope of this article. The emboli from left-sided infective endocarditis lodge in the middle cerebral artery in about 25% to 50% of cases.8–11

Two-thirds of clinically apparent embolic events are minor, causing either transient ischemic attacks or small infarcts, but the remaining third involve multiple territories or result in extensive strokes (Figure 1).6

Figure 1
Figure 1

Minor (low-risk) cerebrovascular complications in infective endocarditis. (A) Numerous bilateral foci (arrows) of discrete cortical restricted diffusion on magnetic resonance diffusion-weighted imaging, consistent with punctate embolic ischemic infarcts. No acute intraparenchymal hemorrhage is seen. (B) Small infectious aneurysm (arrow) at a distal branch of the left middle cerebral artery (1 mm neck, 1.5 mm height, 1.5 mm width) on invasive cerebral angiography. (C) Bilateral microhemorrhages (arrows) on brain magnetic resonance susceptibility-weighted imaging.

Symptomatic hemorrhagic events, including parenchymal and subarachnoid bleeds, are less common than ischemic strokes, accounting for 4% to 18% of strokes.6,12 These can result from infectious vasculitis, vessel fragility, hemorrhagic conversion of ischemic stroke, or rupture of infectious intracranial aneurysms. Primary brain bleeds are more common than hemorrhagic conversion of ischemic stroke or aneurysm rupture. Notably, silent cerebral microhemorrhages are highly prevalent and can be detected in up to 57% of patients with infective endocarditis, averaging 8 microbleeds per patient.5 While several studies have explored whether cerebral microhemorrhages predict overt brain hemorrhage in infective endocarditis, the evidence remains inconclusive.4–7,13–15

Infectious intracranial aneurysms are uncommon, occurring in 2% to 6.5% of patients with infective endocarditis, but increase the risks of morbidity and death16,17 (Figure 2). They result from septic embolization of the vasa vasorum in cerebral vessels, leading to rapid degradation of the vessel wall due to release of inflammatory cytokines. Streptococcus viridans is the most common causative organism, accounting for about one-fourth of cases, followed by Staphylococcus aureus, accounting for less than one-fifth.18,19 These aneurysms are often located in distal branches of the middle cerebral artery in bacterial infections, and in extracranial vessels in fungal infections.17,20–22 They have an unpredictable course and carry a high mortality rate if they rupture.1

Figure 2
Figure 2

Major (high-risk) cerebrovascular complications of infective endocarditis. (A) Large area of restricted diffusion (*) on magnetic resonance diffusion-weighted imaging within the left occipital lobe, compatible with a large acute posterior cerebral artery territory infarct. (B) Large (8 × 6 mm) left middle cerebral artery infectious aneurysm (arrow) on invasive cerebral angiography. (C) Large parenchymal cerebral hemorrhage (*) secondary to a ruptured 4-mm infectious aneurysm arising from a distal right M4 branch (left arrow) with small left occipital infectious aneurysms (right arrow).

PREDICTING THE RISK OF EMBOLIC STROKES

Embolic strokes in patients with infective endocarditis usually occur within 2 weeks of diagnosis, with the highest risk (10–20-fold) at or near the time of hospital admission and initiation of antibiotics.6–8 The risk significantly declines after 1 to 2 weeks of antimicrobial therapy.7 Risk factors include the following:

  • Prior embolic events during the course of infective endocarditis

  • S aureus endocarditis, which is associated with double the rate of brain embolism compared with other organisms7,8,23,24; in one study, the rate was 43.3% vs 20%.6 Streptococcus bovis and enterococci have also been implicated in increasing the risk of embolization in infective endocarditis.6,8

  • Large (> 10 mm) or very large (> 30 mm) vegetations, rapid vegetation growth, high mobility, and mitral valve involvement.6,8 Each millimeter increase in vegetation diameter is associated with an estimated 10% increase in embolic stroke risk.25 Notably, even after 1 to 2 weeks of antibiotic therapy, large and very large vegetations continue to pose a substantial risk of embolic events.6,8 Several risk calculators are available:

The Embolic Risk French Calculator is based on 6 risk factors: age, diabetes, atrial fibrillation, embolism before antibiotic intervention, vegetation length, and infection with S aureus. Developed and validated in a multicenter cohort study and demonstrating good predictive accuracy,23 it is widely used.

The Mayo Clinic Nomogram, while helpful, has not demonstrated the same level of validation across diverse cohorts.26

The Italian Study on Endocarditis Score, while helpful, fails to fully capture the complexity of embolic risk as comprehensively as the Embolic Risk French Calculator.24

The European Society of Cardiology EUROb-servational Research Programme provides valuable insights but lacks a specific, validated risk calculator for embolic events.27

Although current guidelines primarily rely on vegetation size and prior embolism history to determine the need for surgery, risk-prediction tools that incorporate clinical, microbiologic, and echocardiographic parameters provide better predictions of embolic events and should be considered in clinical practice.23,24,28

LESS DATA ON PREDICTING CEREBRAL HEMORRHAGE OR INFECTIOUS INTRACRANIAL ANEURYSMS

Compared with embolic stroke, less data exist regarding the predictors of cerebral hemorrhage in patients with infective endocarditis. Cerebral microhemorrhages have uncertain predictive value for hemorrhagic stroke, owing to conflicting evidence.2 Conversion from ischemic to hemorrhagic stroke in patients with infective endocarditis is influenced by factors such as fungal infection, male sex, rheumatic heart disease, and anticoagulant therapy.6,12,29 In a systematic review, the risk intracerebral hemorrhage in patients receiving intravenous thrombolytics for stroke was 4.14 times higher than in those treated with thrombectomy,30 raising concerns about the safety of giving thrombolytics to treat ischemic stroke in patients with infective endocarditis. Similarly, no definitive clinical or imaging profile exists to identify patients who will develop infectious aneurysms.1

TO PREVENT STROKES: START ANTIBIOTICS, CONSIDER SURGERY

Starting antibiotics promptly and, in appropriate cases, taking the patient to surgery early (within 3–5 days) are the only established methods to prevent new or recurrent strokes in left-sided infective endocarditis.23,31

Antibiotics reduce the risk of stroke, with a noticeable decrease in new or recurrent strokes typically occurring after 1 to 2 weeks of treatment.2

The EASE (Early Surgery Versus Conventional Treatment for Infective Endocarditis) trial31 showed that early surgery in patients with left-sided infective endocarditis with severe valvular dysfunction and vegetations larger than 10 mm reduced the incidence of the composite endpoint of in-hospital death and embolic events within 6 weeks by effectively decreasing the risk of systemic emboli. When surgery is indicated to prevent embolism, it has the most benefit when performed early after admission, during the initial high-risk stroke period.

Considering this evidence, the major societies recommend early surgery to prevent embolic stroke in patients with left-sided infective endocarditis with large, highly mobile vegetations with or without recurrent embolic events despite appropriate antibiotic therapy (Table 1).1–3

View this table:
TABLE 1

Indications for surgery in infective endocarditis to prevent cerebrovascular complications

Other medical strategies have not demonstrated similar benefits. Specifically, neither aspirin nor anticoagulation has demonstrated a protective effect against cerebrovascular complications in infective endocarditis.6,32 Given the limited evidence supporting current recommendations for antithrombotic therapy and anticoagulation in infective endocarditis, decisions regarding these therapies should be discussed within the endocarditis team.

Should anticoagulation be discontinued?

Historically, anticoagulation was presumed to be associated with a higher risk of intracranial hemorrhage in infective endocarditis. However, recent evidence suggests that in carefully selected patients with uncomplicated infective endocarditis who have a preexisting indication for anticoagulation and no evidence of cerebrovascular complications, continuing anticoagulation may not significantly alter the risk of stroke, intracranial hemorrhage, or death at 10 weeks.6,33 Therefore, continuing anticoagulation in these uncomplicated cases may be considered if the anticipated benefits outweigh the risks. In such circumstances, unfractionated heparin is favored over oral anticoagulants because its anticoagulant effect can be rapidly reversed in the event of hemorrhage.2

Conversely, anticoagulation should be discontinued in patients with infective endocarditis and intracranial hemorrhage. Also, anticoagulation should be withheld for at least 2 weeks after an embolic stroke to mitigate the risk of hemorrhagic transformation.1 However, continuing anticoagulation may be considered in carefully selected patients with mechanical prosthetic valves following a small or asymptomatic cerebral infarct. This decision should be made after thoroughly assessing the potential risks and benefits, weighing the need to prevent thromboembolic complications associated with prosthetic valves against the risk of hemorrhage. Such patients require close clinical observation and serial neuroimaging to confirm the stability of the infarct while on anticoagulation therapy.2

ROLE OF BRAIN IMAGING

In patients with symptoms, brain imaging is mandatory for all patients with infectious endocarditis who present with suspected cerebrovascular complications based on clinical evaluation (Table 2).1–3

View this table:
TABLE 2

Diagnostic imaging in patients with suspected cerebrovascular complications of infective endocarditis

It is common practice to perform an urgent noncontrast computed tomography (CT) scan of the brain to rule out catastrophic complications such as a brain hemorrhage. However, brain magnetic resonance imaging (MRI) with and without gadolinium contrast is recommended for a comprehensive evaluation, especially if the initial noncontrast CT scan is unremarkable.2 If MRI is unavailable, not feasible, or contraindicated, a CT scan with and without contrast is an acceptable alternative.2 CT angiography and CT perfusion imaging of the brain should be performed if mechanical thrombectomy is planned for an embolic stroke resulting from large-vessel occlusion.2

In patients without cerebrovascular symptoms, the role of brain imaging is more controversial. Although the American College of Cardiology/American Heart Association1 and European Society of Cardiology guidelines2 do not recommend routine brain imaging in this population, the American Association for Thoracic Surgery3 considers it reasonable to screen for cerebrovascular events, especially before surgery and in patients with cardiac lesions that pose a high risk of embolization. This perspective is further bolstered by recent studies demonstrating that routine brain imaging with either brain CT or MRI may affect treatment decisions for up to a quarter of patients, including choices about the need for and timing of surgery.34,35

Although noncontrast brain CT is frequently used as a primary tool for screening for asymptomatic cerebrovascular complications in patients with left-sided infective endocarditis and is considered sufficient by some experts, it is less sensitive than contrast CT or MRI for detecting certain cerebrovascular complications.35 Clinicians should weigh the benefits of noncontrast CT (rapidity, convenience) against the risks of missed diagnoses.

Embolic strokes and cerebral microhemorrhages are the most frequent abnormal findings on brain imaging in patients with infective endocarditis.36 Finding small cerebral embolisms may support early surgical intervention, while microhemorrhages should not automatically preclude or delay surgery in patients with existing surgical indications for it.14

Suspected aneurysm. Vascular imaging is not routinely recommended in patients with infective endocarditis. However, if an infectious intracranial aneurysm is suspected, CT angiography or magnetic resonance angiography can be used for initial screening. Some diagnostic clues include a thunderclap headache, focal neurologic deficits, seizures, altered mental status, meningismus, and brain hemorrhage or microhemorrhages on initial neuroimaging. As most patients with infectious aneurysms present with neurologic symptoms or brain bleeding on neuroimaging, screening with CT angiography or magnetic resonance angiography may be deferred in those who have no symptoms and have unremarkable initial neuroimaging.37

Digital subtraction angiography should be reserved for cases in which an aneurysm is detected on CT angiography or magnetic resonance angiography, cases of acute brain hemorrhage, cases of persistent neurologic deficits despite negative noninvasive imaging, or for mechanical thrombectomy. Magnetic resonance angiography at high Tesla (3 T) is an effective alternative to digital subtraction angiography and is associated with fewer procedural complications.35 However, digital subtraction angiography remains the gold standard for detecting infectious intracranial aneurysms, particularly those smaller than 3 mm.35 Even in patients at high risk, the yield of digital subtraction angiography for detecting infectious aneurysms is low (4.6% to 17.6%), and no reliable predictors of rupture exist to guide treatment or assess perioperative risk.37–39

MANAGEMENT: A TEAM EFFORT

An endocarditis team should manage patients diagnosed with infective endocarditis, where available.1,2 This multidisciplinary team comprises cardiologists, infectious disease specialists, radiologists, cardiac surgeons, nurses, and social workers. It can also include neurologists, neurosurgeons, and vascular surgeons to manage complications. This collaborative approach has been shown to improve outcomes and reduce mortality.2,40,41

Managing embolic strokes

The cornerstones of managing embolic strokes in infective endocarditis are to start antibiotics promptly and consider surgery early (Table 3).1–3 Evidence suggests that early surgery, even in the setting of stroke, is safe and does not increase mortality or perioperative complications.42–44 Postoperative hemorrhagic conversion after preoperative stroke is reported in 2% to 7% of cases.2 Identifying an embolic stroke should not delay but rather facilitate timely cardiac surgery when indicated (Table 4).1–3

View this table:
TABLE 3

Timing of valve surgery in patients with infective endocarditis and cerebrovascular complications

View this table:
TABLE 4

Timing of indicated valve surgery following cerebrovascular complications of infective endocarditis

The exception to early surgery is in patients with significant neurologic injury (a large infarct or poor prognosis), in whom the risks may outweigh the benefits. In such cases, a multidisciplinary endocarditis team approach is crucial for determining the optimal management strategy.3 Figure 3. Interventions for cerebrovascular complications of infective endocarditis. (A) Mechanical thrombectomy. Left, computed tomography angiography demonstrating acute embolic stroke with complete occlusion of the proximal right internal carotid artery (ICA) to the level of the clinoid ICA segment and right M1 part of the middle cerebral artery (MCA) in the setting of endocarditis. Middle, the patient underwent successful mechanical thrombectomy with restitution of flow (right). (B) Decompression of hemorrhage and embolization of aneurysm. Left, computed tomography demonstrating large intracranial hemorrhage (*) due to a ruptured infectious aneurysm in the M4 MCA, requiring emergent decompression craniectomy. Middle and right images, the patient underwent successful liquid embolization of the aneurysm (arrows).

Figure 3
Figure 3

Interventions for cerebrovascular complications of infective endocarditis. (A) Mechanical thrombectomy. Left, computed tomography angiography demonstrating acute embolic stroke with complete occlusion of the proximal right internal carotid artery (ICA) to the level of the clinoid ICA segment and right M1 part of the middle cerebral artery (MCA) in the setting of endocarditis. Middle, the patient underwent successful mechanical thrombectomy with restitution of fl ow (right). (B) Decompression of hemorrhage and embolization of aneurysm. Left, computed tomography demonstrating large intracranial hemorrhage (*) due to a ruptured infectious aneurysm in the M4 MCA, requiring emergent decompression craniectomy. Middle and right images, the patient underwent successful liquid embolization of the aneurysm (arrows).

Antiplatelet therapy, anticoagulation, and thrombolysis are not indicated for infective endocarditis–related strokes in the absence of other indications.32,45 Mechanical thrombectomy may be considered in select cases.

Managing intracranial bleeding

Antiplatelet and anticoagulant therapy must be suspended in the event of intracranial bleeding in patients with infective endocarditis. Cerebral hemorrhage or microbleeds should prompt investigations to exclude infectious aneurysms as treatable bleeding sources. Although certain features of cerebral microhemorrhages—such as a count of 5 or more, lobar or infratentorial location, and contrast enhancement—have been associated with a higher risk of intracranial hemorrhage in various studies,14,46–48 the European guidelines do not explicitly identify these characteristics as predictors of hemorrhage or as contraindications for cardiac surgery.2 This emphasizes the inconclusive evidence and lack of consensus regarding cerebral microhemorrhages in infective endocarditis, highlighting the need to assess the risk profile and timing of indicated surgery on a case-by-case basis.

Overt intraparenchymal, intraventricular, or subarachnoid hemorrhages, unlike ischemic stroke or microhemorrhages, are generally an absolute contraindication for immediate surgery (Table 4). High mortality and rebleeding rates have been observed with early surgery in patients with intracranial hemorrhage,6,49 and guidelines recommend postponing cardiac surgery for at least a month, if feasible.1–3 However, limited retrospective data suggest potential benefits of early surgery (within 2 weeks) after hemorrhagic stroke in select cases without worsening neurologic outcomes.15,50,51

The optimal timing should be patient-centered, and a multidisciplinary approach involving an endocarditis team is appropriate for complex cases. If surgery is delayed, a repeat CT or MRI should be performed 1 to 2 weeks after the hemorrhage (or sooner if clinical deterioration occurs) to assess the stability of imaging findings and to reconsider the timing of surgery.2

Managing infectious aneurysms

Managing infectious aneurysms involves antibiotics plus, for some, endovascular procedures or surgical interventions (Table 4). While some studies suggest comparable outcomes between antibiotics alone and invasive procedures, others report worse outcomes with conservative management when intervention is indicated.52 Intervention is recommended for ruptured aneurysms, those not responding to antibiotics, and large or expanding aneurysms prior to valve surgery (Figure 3).2,50,53

Endovascular therapy is often preferred because it has high success and low morbidity rates, especially for distal aneurysms with favorable anatomy (ie, located in noneloquent brain areas) and without significant mass effect from bleeding.4,54 Detachable coils are preferred for proximal aneurysms, while distal aneurysms that are difficult to access with microcatheters may be managed with acrylic glue or autologous clot injections.4

The urgency of cardiac surgery is a critical factor in decision-making. While neurosurgical clipping often requires a 2-week delay, cardiac surgery can be performed as soon as the same day of endovascular repair (Table 4).2

TAKE-HOME POINTS

  • Cerebrovascular complications, including ischemic stroke, hemorrhage, and infectious intracranial aneurysms, significantly increase morbidity and mortality rates in infective endocarditis.

  • A multidisciplinary endocarditis team is crucial for guiding treatment decisions, interpreting cerebrovascular imaging, and determining the timing of surgery in patients with or at risk for these complications.

  • Transient ischemic attacks, microhemorrhages, and nondisabling ischemic strokes should not delay indicated cardiac surgery. However, immediate cardiac surgery is generally contraindicated in the event of overt intracranial bleeding. Endovascular intervention may be considered prior to cardiac surgery for ruptured or expanding infectious aneurysms.

  • Despite the frequency of these neurologic complications, the level of evidence to guide their management remains low, highlighting an urgent need for more robust research in this area.55

DISCLOSURES

Dr. Slipczuk has disclosed receiving institutional grants from Amgen and Philips Healthcare. Dr. Schenone has disclosed teaching and speaking and serving as a primary investigator for a funded quality improvement program for Bristol-Meyers Squibb. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

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