A 72-year-old Caucasian female patient with known hypertension, dyslipidemia, type II diabetes, and atrial fibrillation presented with fever, chills, confusion, right facial droop, and right arm weakness. Her physical exam was notable for irregular rhythm with no focal neurologic signs. Laboratory investigations were notable for white blood cell count of 19.0 x 109 per L, C-reactive protein of 10.4 mg/dl, and erythrocyte sedimentation rate of 78 mm/hr. Magnetic resonance imaging showed punctate areas of acute infarction within posterior circulation and into the watershed region. Transthoracic echocardiogram showed an echodense mass attached to the posterior leaflet of mitral valve (Video 1, Figure 1). Transesophageal echocardiogram showed a larger mass with a fairly mobile component (Video 2, Figure 2). Blood cultures grew Staphylococcus aureus. The patient's home medication list included rosuvastatin, metoprolol, aspirin, metformin, glyburide, and warfarin. The patient was diagnosed with infective endocarditis (IE) and was started on vancomycin.
Video 1: Two-Dimensional Transthoracic Echocardiography in Parasternal Long Axis View.
Figure 1: Two-Dimensional Transthoracic Echocardiography in Parasternal Long Axis View.
Arrowhead is pointing to an echodense mass (measuring 1.6 x 0.68 cm) originating from the posterior mitral valve leaflet (PML) and projecting into left atrium (LA). AML = anterior mitral valve leaflet; AO = aorta; LVOT = left ventricular outflow tract.
Video 2: Two-Dimensional Transesophageal Echocardiography in Midesophageal View
Figure 2: Two-Dimensional Transesophageal Echocardiography in Midesophageal View
Arrowhead is pointing to the echodense mass measuring 1.64 x 0.7 cm. A mobile mass 0.95 x 0.52 cm is attached to PML. LV = left ventricle.
Which of the following statements is correct regarding anticoagulation therapy?
Show Answer
The correct answer is: C. Discontinue warfarin now and reevaluate after the patient's condition is more stable.
It is important to note that although the correct answer is reasonable, no randomized controlled trials have been published to support that approach with evidence. There are a number of observational studies available, which are prone to bias. Neurological complications are the most frequent extra-cardiac complications of IE.1 They have a negative impact on the outcome and are associated with early mortality (45 vs. 24%, p < 0.001).2 Asymptomatic brain infarction occurs in the majority of patients with IE. Magnetic resonance imaging series of 130 patients with IE demonstrated that 82% of patients had brain lesions (including ischemic and hemorrhagic), but only 12% were symptomatic.3 Acute ischemic stroke clinically manifests in 20-40% of patients with IE.1,4,5,6 The underlying mechanism includes embolic events due to fragmentation of vegetations often involving multiple arterial territories.6 Six factors are associated with embolic risk: age, diabetes, atrial fibrillation, embolism before antibiotics, vegetation length, and Staphylococcus aureus infection.7,8 A large vegetation more than 10-15 mm in length, greater mobility of vegetation, and mitral valve involvement were associated with higher cardioembolic risk.8 Hemorrhagic stroke in patients with IE can be caused by conversion of ischemic stroke (in 27% of cases), progression of microhemorrhages, and rupture of an infectious aneurysm.1,5 The risk of hemorrhage is higher in patients who are on anticoagulants at the time of presentation.9 A case series of 269 patients with native valve IE demonstrated that both ischemic and hemorrhagic cerebrovascular accidents were significantly higher among anticoagulated patients (20 vs. 8%, p < 0.01). Of note, the mortality rate was similar in both groups.10 García-Cabrera et al. conducted a retrospective analysis of 1,345 cases of IE of mechanical valves and demonstrated that hemorrhagic complications were significantly associated with anticoagulant therapy (hazard ratio 2.71; 95% confidence interval, 1.54-4.76; p = 0.001).
The decision to continue anticoagulation therapy in IE remains controversial especially in cases of prosthetic valve endocarditis. The current recommendations from American Heart Association include the following:
Discontinuation of all forms of anticoagulation in patients with mechanical valve IE who have experienced a central nervous system embolic event for at least 2 weeks is reasonable (Class IIa, Level of Evidence C). Accordingly, the answer C is correct.
Initiation of aspirin or other antiplatelet agents as adjunctive therapy in IE is not recommended (Class III, Level of Evidence B).
The continuation of long-term antiplatelet therapy at the time of development of IE with no bleeding complications may be considered (Class IIb, Level of Evidence B).11
The European Society of Cardiology states that decision for management of anticoagulation therapy in IE patients should be made by the endocarditis team individually. It believes that it may be reasonable to do bridging therapy with heparin in unstable patients before a surgical decision is made. They recommend replacing oral anti-vitamin K anticoagulants with unfractionated or low molecular weight heparin for 1-2 weeks under close monitoring in patients with ischemic stroke without hemorrhage (Class IIa, Level of Evidence C).12 Of note, the recommendation is based on a low level of evidence, and the role of bridging therapy with heparin has not been studied in patients with IE.12
To our knowledge, there is no study published to demonstrate the exact timeline of restarting anticoagulation therapy. We suggest stopping anticoagulant therapy temporarily as soon as the clinical diagnosis of IE due to Staphylococcus aureus is confirmed.
References
Morris NA, Matiello M, Lyons JL, Samuels MA. Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery. Neurohospitalist 2014;4:213-22.
García-Cabrera E, Fernández-Hidalgo N, Almirante B, et al. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation 2013;127:2272-84.
Duval X, Iung B, Klein I, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study. Ann Intern Med 2010;152:497-504,W175.
Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis 2008;47:23-30.
Sonneville R, Mirabel M, Hajage D, et al. Neurologic complications and outcomes of infective endocarditis in critically ill patients: the ENDOcardite en REAnimation prospective multicenter study. Crit Care Med 2011;39:1474-81.
Novy E, Sonneville R, Mazighi M, et al. Neurological complications of infective endocarditis: new breakthroughs in diagnosis and management. Med Mal Infect 2013;43:443-50.
Hubert S, Thuny F, Resseguier N, et al. Prediction of symptomatic embolism in infective endocarditis: construction and validation of a risk calculator in a multicenter cohort. J Am Coll Cardiol 2013;62:1384-92.
Aherrera JA, Abola MT, Balabagno MM, et al. Prediction of Symptomatic Embolism in Filipinos With Infective Endocarditis Using the Embolic Risk French Calculator. Cardiol Res 2016;7:130-9.
Tornos P, Almirante B, Mirabet S, Permanyer G, Pahissa A, Soler-Soler J. Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy. Arch Intern Med 1999;159:473-5.
Delahaye JP, Poncet P, Malquarti V, Beaune J, Garé JP, Mann JM. Cerebrovascular accidents in infective endocarditis: role of anticoagulation. Eur Heart J 1990;11:1074-8.
Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015;132:1435-86.
Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015;36:3075-128.
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