Endocarditis and stroke-Dr Pallav Jain

1. ENDOCARDITIS AND STROKE
MODERATOR: DR. BHARAT BHUSHAN
PRESENTER: DR.PALLAV JAIN

2. INTRODUCTION
Main forms of endocarditis have been described:
 Infective endocarditis,
 Nonbacterial thrombotic endocarditis (most commonly
associated with malignancy,SLE)

3. Infective endocarditis
Is an infection of the inner surface of the heart, usually
the valves
The highest rates are often observed among patients with
 prosthetic valves
 intracardiac devices
 unrepaired congenital heart disease
 chronic rheumatic heart diseases
 age-related degenerative valve diseases
 DM
 HIV
 IVDA
 hemodialysis

4. Nonbacterial thrombotic
endocarditis (NBTE)
Rare condition that refers to a spectrum of noninfectious
lesions of the heart valves that is most commonly seen in
advanced malignancy, systemic lupus erythematosus.
 Mechanism-endothelial injury in the setting of a
hypercoagulable state is thought to be critical for the
development of NBTE

5.  Compared to vegetations in infective endocarditis,
vegetations in NBTE are easily dislodged since there is
little inflammatory reaction at the site of attachment.
 Thus, in NBTE there is a greater tendency for
vegetations to embolize and cause extensive infarction.

6.  Despite diagnostic and therapeutic improvements, mortality
from IE remains high.
 In-hospital mortality ranges from 15 to 22 percent, while five-
year mortality hovers around 40 percent.

7.  Neurologic sequelae are the most frequent extra cardiac
complications of IE, occurring in anywhere from 25% to
70% of cases.
 Mortality is higher in those with neurological
complications than in those without.

8. Clinical manifestations of neurologic
disease
 Ischemic or hemorrhagic stroke
 infected intracranial aneurysm
 Meningitis
 brain abscess
 spinal epidural abscess
 encephalopathy
 mononeuropathy
 seizure
 Conversely, complications may be completely silent, and
clinically inevident neurologic disease has been shown to
occur in 30% of cases with IE by imaging evaluation.

9.  Stroke in IE tends to occur most frequently in the early phase
of IE.
 In fact, stroke may be a presenting symptom of IE.
 Neurologic complications in patients with endocarditis are the
most challenging problems
 Because of the conflicting nature of their pathophysiology
(i.e., an embolic event with hemorrhagic transformation)

10. Risk factors
●Size of vegetation –
Larger vegetations- More likely to embolize
vegetations >10 mm are especially concerning.
Vegetations that are visible on both transthoracic and
transesophageal echocardiography (TEE) are more likely to
embolize than those seen only on TEE.
●Location of vegetation –
The risk of cerebral embolism is highest from mitral valve lesions,
especially those on the anterior mitral leaflet.
Most systemic emboli arise from the mitral or aortic valve

11.  Organism –
The infectious organism may also influence the risk of septic
emboli.
Staphylococcus aureus endocarditis is associated with a higher
risk of embolization than other bacterial organisms
Candida endocarditis is also associated with a higher risk of
embolization -larger vegetations with this organism.

12. ●Antibiotic treatment –
The risk of embolism markedly decreases in the weeks
following initiation of effective antibiotic therapy.
●Coexistent conditions –
Patients with IE frequently have coexistent conditions that
pose a risk of thromboembolism.
These include presence of a prosthetic valve (particularly
mechanical) and atrial fibrillation.

13. Acute ischemic stroke
 Most common -acute ischemic stroke-20% to 40%
 Asymptomatic ischemia recognized by neuroimaging studies occurs
in another 30% to 40% of patients.
 Mechanism- embolic.
 Cerebral emboli result from dislodgment or fragmentation of cardiac
vegetations
 Vessel occlusion- results in various degrees of ischemia and
infarction, depending on the vessels and the collateral blood flow.

14.  Ischemic strokes in IE -Most commonly occur in the middle
cerebral artery territory
 Result of the high percentage of blood volume in these
territories.
 However, multifocal infarction is also common and frequently
involves the end arterial territories of cerebral vessels

15. Presentation
 Focal deficits
 Encephalopathy
 Seizures

16. PATTERNS
Four acute stroke patterns were identified:
1- single lesion,
2- territorial infarction,
3- disseminated punctate lesions, and
4 -numerous small (10 mm) and medium (10 to 30 mm) or
large (30 mm) lesions in multiple territories.
NBTE exhibited pattern 4
IE exhibited patterns 1, 2, 3, and 4

19. Management of AIS
 Antibiotic therapy is critical in order to reduce the risk of
primary and secondary ischemic stroke in bacterial
endocarditis.
 Early antibiotic therapy reduces risk of embolization
dramatically

20.  Antibiotic treatment duration should range based on the valve
affected and cause of the IE.
 native valve IE- two to six weeks for IE due to common
microorganisms to
 prosthetic valve IE - six weeks.

21. ANTICOUGLATION THERAPY
Anticoagulation is not recommended as an intervention for
stroke prevention in patients with IE.
In most patients with IE on anticoagulation who develop an
acute ischemic stroke, it is suggested to discontinue
anticoagulant therapy for at least two weeks due to the risk of
hemorrhagic transformation.

22. If anticoagulation is absolutely indicated
Oral anticoagulant agent be replaced with heparin for two weeks, in
patients already receiving oral anticoagulant therapy, presenting with
IE complicated by ischemic, non-hemorrhagic stroke with monitoring
of coagulation profile.

23. INDICATIONS FOR ANTICOUGLATION
Atrial fibrillation
 IE with a CHADS2 score of 2 or greater.
 mitral stenosis with IE regardless of the CHADS2 score.

24. Prosthetic valve endocarditis
 Are at risk for thromboembolism as well as for valve obstruction
from valve thrombosis.
 For smaller strokes in patients with prosthetic valve
endocarditis, such as asymptomatic punctuate infarcts seen only
on magnetic resonance imaging (MRI), we may continue
anticoagulation using heparin with serial surveillance imaging.

25. NBTE
 Patients with NBTE with or without evidence of systemic
emboli are routinely anticoagulated provided there is no
contraindication (eg, central nervous system bleeding).
 known fragile nature of vegetations and the high rates of
recurrent and extensive embolization in this population

26.  The risk of anticoagulation is hemorrhagic conversion of
embolic events.
 Computed tomography of the brain should be performed in
patients before anticoagulation to rule out intracranial
hemorrhage.
 Therapeutic dose subcutaneous low molecular weight (LMW)
heparin or intravenous unfractionated heparin should be used,
rather than warfarin ora direct thrombin or factor Xa inhibitor
(eg, dabigatran, apixaban, edoxaban, rivaroxaban).

27. ANTI-PLATELET THERAPY
Due to increased risk of hemorrhagic stroke in acute IE , it is advised
to suspend antiplatelet therapy during treatment of IE.
 It is suggested not to start aspirin or other antiplatelet agents for
patients with IE who have an acute ischemic stroke or TIA.
 However, if patient require antiplatelet therapy for another medical
condition it is not absolutely necessary to discontinue antiplatelet
therapy in those patients with IE without cerebral hemorrhage

28. Thrombolysis
Thrombolysis is contraindicated in patients with IE who have a
stroke given the
risk of hemorrhagic transformation
anticoagulant treatment in a subset of patients due to prosthetic
valves.

29. Mechanical thrombectomy
 Endovascular therapies with intra-arterial thrombolysis, with or
without mechanical thombectomy, may be an option.
 Endovascular treatment avoids the systemic effects of fibrinolysis
 Recent case reports describe the successful treatment.
 However, the scientific evidence for this treatment modality is not
enough since it has not been probed in randomized clinical trials.

31. Cerebral hemorrhage
 Hemorrhagic stroke accounts for approximately 30 percent of
cerebrovascular complications of IE.
 Hemorrhage in the brain in the setting of IE usually presents in
the parenchyma or subarachnoid space.

32. Parenchymal hemorrhage can be
caused by
 Hemorrhagic conversion of a prior ischemic infarct
 microhemorrhage with or without progression to clinical
hemorrhage due to vascular friability,
 rupture of an infectious aneurysm.
 Cerebral hemorrhage may be the first manifestation of IE and
should be suspected in a febrile patient with sudden coma
and/or neurologic deficit.

33. Risk of hemorrhage
 Who are on anticoagulant drugs
 Treated with anticoagulation or antiplatelet agents early after
diagnosis.
 Infection as well as concomitant medications may prolong
(INR)
 Brain hemorrhage is more frequent during the bacteremic
phase of S. aureus IE

34. Cerebral microhemorrhage
 Increasingly acknowledged as a silent complication of
endocarditis and recently has been implicated in predicting
overt hemorrhage.
 Cerebral microhemorrhage has been detected in 57% of cases
with IE
 Microbleeds may also be due to a subacute process, either due
to an immunologic vasculitis and/or an embolic process in the
vasa vasorum.

35.  Cortical localization of microbleeds may reflect a preferential
mode of entry of septic material through the blood brain
barrier at the cortico-pial junction.
 Can also occur in deeper brain areas.

36. Clinical presentation
 Focal deficits
 headache
 encephalopathy
 Seizure

37. Management
 All anticoagulant and antiplatelet agents should be
immediately discontinued for at least two weeks in patients
with intracerebral hemorrhage, including hemorrhagic stroke
or hemorrhagic transformation of an embolic stroke.
 In patients with mechanical valve unfractionated heparin
should be reinitiated as soon as possible
 In patients who develop an intracerebral hemorrhage while
anticoagulated, anticoagulation should also be reversed.

38. Intracranial infectious aneurysms
 Relatively rare complications of infectious endocarditis, found in
only 2% to 4% of patients with IE
 Accounting for 5% to 12% of patients having IE with neurological
manifestations.
 However, the actual incidence is probably higher, as they can be
clinically silent and subsequently resolve with antibiotic therapy.

39.  If imaging is not obtained, IIAs can go undetected.
 Infectious intracranial aneurysms are more common than
infected aneurysms in other locations in the body.
 The mechanism is likely destruction of the vessel wall
through interaction of organisms with the immune
inflammatory response of host.

40.  Infectious intracranial aneurysms in the setting of bacterial
endocarditis are typically distal (e.g., involving segment 2, 3,
or 4 of the MCA or PCA)
 In about 25 percent of cases they are more than one.
 They are typically fusiform in shape but can be saccular
 Fungal aneurysms may have a predilection for proximal
vessels such as the internal carotid and basilar arteries.

41. Presentation
Nonruptured
 ICMA are responsible for
 fever
 headache
 seizures
 and focal deficit.

42. Ruptured ICMA
Have sudden arachnoid or intracerebral bleeding
 Headache
 seizures
 focal deficits
 encephalopathy
 Ophthalmoplegia
 rarely proptosis

43. MANAGEMENT
 Conventional angiography remains the gold standard for
diagnosis of IIAs
 Because of their frequent distal location within the cerebral
arterial tree.
 CTA and MRA can detect intracranial saccular aneurysms
greater than 5mm with good reliability.

44. Management of IIAs
depends on
 size,
 location,
 expertise of the managing clinicians, and
 whether there has been rupture.
 It is likely that the most important feature in IIAs is whether
they have ruptured.

45. Unruptured
 Patients with unruptured aneurysms should receive
antibiotics with serial imaging performed to document the
resolution of the aneurysm.
 Anticoagulation, antiplatelet, and thrombolytic therapy
should not be used in the setting of a known IIA, as there
would be very few scenario in which the risk of aneurysm
rupture is outweighed by the need for acute
anticoagulation.

46.  Endovascular or surgical treatment should be considered if an
unruptured aneurysm is very large (e.g., greater than 10mm in length)
or if it is not resolving or is enlarging despite treatment with
antimicrobials.
 Endovascular therapy should be considered when there is no mass
effect

47. Endovascular therapy
 Are less invasive alternatives that may be more
appropriate in patients who are unfit for surgery due to
cardiac disease.
 Detachable coils are preferred for proximal aneurysms,
while distal aneurysms that are not accessible to
microcatheters can be managed with acrylic glue or
autologous clot injections.

48.  If endovascular intervention is unfeasible, clip reconstruction
or proximal vascular occlusion with or without bypass is
recommended.
 in the presence of mass effect neurosurgery is probably the
best choice

49. Ruptured aneurysm
 For ruptured aneurysms, surgical or endovascular intervention
should be considered, but the choice between endovascular vs.
surgical is complex and should be individualized.

50. Surgical procedures
 Clipping- the surgical procedure favored in noninfectious
aneurysms, may be technically difficult, as IIAs tend to be
fusiform with poorly defined necks and friable walls.
 Proximal ligation is therefore often necessary.

51. EFFECT OF NEUROLOGICAL
COMPLICATIONS
 Neurologic complications may have consequences on the management
of patients with IE.
 They also can affect medical therapy by changing the type and length
of antibiotic or anticoagulant therapy.
 Moreover, neurologic complications may influence indications,
timing, and type of cardiac surgery.
 Finally, they may require specific approach, such as interventional
neuroradiology to treat IIA.

52. Issues regarding cardiac surgery
 Neurologists are concerned - relative hypotension and full
anticoagulation with heparin during cardiopulmonary bypass
 exacerbate neurologic injury either by infarction extension or by
hemorrhagic conversion.
 These effects are probably determined by the size of the infarct
and its clinical relevance.

53.  Acute ischemic stroke
 Early surgical intervention after a clinical stroke of small size,
defined as less than 15 mm in diameter, appears to be safe.
 The presence of silent infarctions on imaging or clinical
ischemic strokes of small size should not delay surgical
intervention.

54.  The timing of surgery in the presence of larger infarctions is
more controversial.
 The decision to proceed to early surgery in larger infarctions
must be weighed in light of the
 surgical indications,
 perioperative risk factors
 likelihood of additional embolic events that would further
compromise both neurologic function and surgical safety.

55.  In general, after a large ischemic stroke, it is preferred to
postpone intervention to 4 weeks if safe to do so,
 At the same time it is better to monitor closely for changes in
severity of the clinical scenario.

56. Intracerebral hemorrhage
 It is advised to be more conservative and delaying valve
replacement by at least 4 weeks,
 except in the setting of minor petechial hemorrhage for which
we may be more aggressive.

57. Infected intracranial aneurysms
 The decision of how best to manage infected intracranial
aneurysms should be evaluated on a case-by-case approach
with the aid of neurosurgery, interventiona neuroradiology, and
cardiac surgery
 Postpone cardiac surgery for 1 to 2 weeks following
aneurysmal repair IIA

58. SUMMARY
 Stroke is a common embolic complication of infective
endocarditis.
 The most important treatment to prevent stroke in endocarditis
is the initiation of antibiotic therapy.
 The available limited data do not establish a benefit from
anticoagulant or aspirin therapy in reducing the risk of
embolism in patients with IE.
 Moreover, neurologic complications may influence
indications, timing, and type of cardiac surgery.

59. Thank you

60. REFERENCES
• Brian Silver, Bacterial Endocarditis and Cerebrovascular
Disease, JUNE 2016 PRACTICAL NEUROLOGY
• Aneesh B. Singhal, Acute Ischemic Stroke Patterns in
Infective and Nonbacterial Thrombotic Endocarditis
(Stroke. 2002;33:1267-1273.)
• Nicholas A. Morris .Neurologic Complications in Infective
Endocarditis:, The Neurohospitalist 2014, Vol. 4(4) 213-
222
• www.uptodate.com