Infective Endocarditis: Best Practices for Treating Neurologic Complications

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Treatment of neurologic complications in infective endocarditis may come second to cardiovascular needs.
Treatment of neurologic complications in infective endocarditis may come second to cardiovascular needs.

Infective endocarditis (IE) affects an estimated 3 to 9 individuals per 100,000 annually in industrialized countries, and rates are more than twice as high in females compared with males. Although roughly 50% of cases occur in patients with no previous incidence of valve disease, the highest rates have been observed among those with a history of IE; those with unrepaired cyanotic congenital heart disease, intracardiac devices or prosthetic valves, or age-related degenerative valvular lesions; and those undergoing hemodialysis.1 Additional risk factors include chronic rheumatic heart disease and comorbidities such as HIV and diabetes.

Etiology and Outcomes

Mortality rates associated with IE range from 16% to 25%, with the highest rates observed among patients with nosocomial healthcare-associated IE (NHCA-IE).2 However, non-nosocomial HCA-IE (NNHCA-IE) is a recently introduced category that applies to patients who acquire IE during extensive exposure to outpatient medical care, as with intravenous therapies or wound care, rather than during hospitalization. This type now contributes to an estimated 9.3% to 15.7% of IE episodes.3

Together, both types of HCA-IE account for more than one-third of cases among patients with native valve IE and no intravenous drug use history, according to a prospective observational study that examined HCA-IE prevalence and outcomes in 28 countries.4 The investigators reported that NNHCA-IE in particular was more than twice as common in the United States compared with other regions, which they note may be partly the result of the increasing number of people undergoing hemodialysis and the overall use of outpatient medical care. The top cause of HCA-IE was Staphylococcus aureus (vs viridans group streptococci in community-acquired IE), with methicillin-resistant S aureus identified as the cause of more than half of cases.

An estimated 20% to 40% of those with IE will have cerebrovascular complications, which puts them at higher risk for mortality than those without cerebrovascular complications.5 The most common of these complications are ischemic and hemorrhagic stroke, which together affect approximately one-third of those with IE and often occur before IE has been diagnosed, according to Steven R. Messe, MD, a vascular neurologist and associate professor of neurology at the Hospital of the University of Pennsylvania in Philadelphia. “The ischemic strokes are due to embolization of the infected valve vegetations, and these infarcts are at high risk of hemorrhagic conversion,” he told Neurology Advisor. “Emboli may directly seed the vessel wall with bacteria, leading to mycotic aneurysms which can rupture and cause subarachnoid hemorrhage.” In addition, meningitis, brain abscesses, or encephalopathy may develop.6

A 2013 study described in Circulation identified the following independent risk factors for neurologic complications in IE: S aureus etiology (hazard ratio [HR] 2.47), vegetation size ≥3 cm (HR 1.91), involvement of the mitral valves (HR 1.29), and anticoagulant therapy (HR 1.31), which was linked with a higher incidence of hemorrhagic events (HR 2.71).7

Treatment

A multidisciplinary team of clinicians, including specialists in cardiology, cardiac surgery, infectious disease, and neurology should be involved in the treatment of patients with IE.1 “These are always difficult cases,” said Dr Messe, who offered the following best-practice tips on treating neurologic complications in patients with IE:

  • First, treating aggressively with appropriate antimicrobial medications as quickly as possible is of paramount importance. [Editor's note: Study results show that appropriate intravenous antibiotics reduced the risk for neurologic complications by more than 50%.8 It is recommended that 2 to 3 routine blood cultures be drawn before initiation to identify the causative microorganism.1]
  • In general, Dr Meese recommends avoiding anticoagulation, given the risk for hemorrhage. If there is a mechanical valve present, particularly if it is in the mitral position, that can be a tough call. 
  • Magnetic resonance (MR) imaging is very helpful, as diffusion-weighted imaging will detect acute infarct, while fluid-attenuated inversion recovery and susceptibility-weighted imaging may detect small amounts of intraparenchymal or subarachnoid brain hemorrhage or mycotic aneurysms not seen on head computed tomography (CT). 
  • Dr Meese generally recommends a CT angiogram over MR angiogram to look for mycotic aneurysms, which are often found in distal vessels and may be treatable using endovascular coiling. However, kidney function may preclude performing CT contrast, in which case the MR angiogram is satisfactory. If there is a high index of suspicion, a conventional angiogram is certainly reasonable. 
  • If surgery is indicated, the timing of the procedure is always a challenge. If there has been a stroke, wait at least 2 weeks, if possible, before performing valve replacement. However, many patients who need surgery cannot wait that long, at which point surgery must occur when necessary.

Early vs Delayed Surgery

Uncontrolled infection, heart failure, and prevention of embolic events have been cited as indications for surgery.1 Early surgery is controversial because of potential associated risks, including “worsening of preoperative cerebral ischemia due to perioperative hypotension on bypass or in intensive care, as well as the risk of hemorrhagic transformation or new intracranial bleeding due to anticoagulation while on bypass,” according to researchers of a 2016 study.8 Although European guidelines recommend a delay in surgery of at least 1 month in patients with hemorrhage, several recent studies have investigated the issue of surgery timing, with the overall conclusion that early surgery may not be as risky as previously believed, even in cases complicated by hemorrhage.

For example, one study found no difference in mortality or neurologic outcomes between patients who underwent early or delayed surgery (within ≤7 vs >7 days of stroke diagnosis), and other recent research showed that patients with IE with non-severe stroke who underwent surgery within 14 days of diagnosis had lower mortality rates than those receiving initial antibiotic treatment without early surgery (P =.007).5,8 In findings from 2013, however, patients with IE with hemorrhage who underwent surgery within 4 weeks of the event had higher mortality rates than patients whose surgery occurred later (75% vs 40%, respectively).7

“The optimal surgical timing is unknown and may well have to be individualized based on embolic risk factors including age, diabetes, atrial fibrillation; the size, mobility, and location of vegetations; changing size of the embolism on antibiotics; previous embolism; and organisms such as Staphylococcus aureus,” the authors of the 2016 study concluded.8 Future research on the topic should continue to elucidate timing considerations, and it “would also be helpful to learn more about when anticoagulation may safely be considered,” said Dr Messe.

References

  1. Hoen B, Duval X. Infective endocarditis. N Engl J Med. 2013; 368:1425-1433.
  2. Wu K-S, Lee SS-J, Tsai H-C, et al. Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome. BMC Infect Dis. 2011;11:221.
  3. Hagiya H, Tanaka T, Takimoto K, et al. Non-nosocomial healthcare-associated left-sided Pseudomonas aeruginosa endocarditis: a case report and literature review. BMC Infect Dis. 2016;16:431.
  4. Benito N, Miró JM, de Lazzari E, et al; International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) Investigators. Health care–associated native valve endocarditis in patients with no history of injection drug use: current importance of non-nosocomial acquisition. Ann Intern Med. 2009;150(9):586-594.
  5. Murai R, Funakoshi S, Kaji S, et al. Outcomes of early surgery for infective endocarditis with moderate cerebral complications. J Thorac Cardiovasc Surg. 2017;153(4):831-840.e8.
  6. Novy E, Sonneville R, Mazighi M, et al. Neurological complications of infective endocarditis: new breakthroughs in diagnosis and management. Med Mal Infect. 2013; 43(11-12):443-450.
  7. García-Cabrera E, Fernández-Hidalgo N, Almirante B, et al; Group for the Study of Cardiovascular Infections of the Andalusian Society of Infectious Diseases; Spanish Network for Research in Infectious Diseases. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation. 2013; 127(23):2272-2284.
  8. Oh THT, Wang TKM, Pemberton JA, Raudkivi PJ. Early or late surgery for endocarditis with neurological complications. Asian Cardiovasc Thorac Ann. 2016; 24(5):435-440.
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