Dweik, Khaled

Background and Purpose Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small case series. This systematic review summarizes stroke presentation, imaging features, management, and outcomes in patients with NBTE-related stroke. Methods We conducted a patient-level systematic review of published case reports and case series. PubMed, MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception through August 2025 for studies reporting individual patients with NBTE-related stroke. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment (unfractionated heparin/low-molecular-weight heparin [UFH/LMWH], vitamin K antagonists [VKA], direct oral anticoagulants [DOACs], and/or valvular surgery), and outcomes. Multivariable regression was used to explore factors associated with recurrent stroke and mortality. Results We included 236 patients with NBTE and stroke from 218 studies (median age 56 years [IQR: 43–63], 63% female). Left hemispheric stroke syndromes predominated among clinical presentations (27%), and multi-vessel territory ischemic infarcts (>2 territories) were observed in 65%. Conventional vascular risk factors were infrequent (0%−21%), whereas deep vein thrombosis (43%) and systemic embolism (41%) frequently preceded or coincided with stroke onset. Malignancy (70%) and autoimmune disease (25%) were the main NBTE etiologies. Anticoagulation was initiated in 70%, and 21% underwent valvular surgery. Over a median follow-up of 2.0 months, stroke recurred in 43% and death occurred in 49% of patients. Malignant etiology (aOR 10.3, P < 0.001) and metastases (aOR 3.9, P < 0.001) were associated with increased mortality, while VKA use (aOR 0.08, P < 0.001) and autoimmune etiology (aOR 0.1, P < 0.001) were associated with lower mortality. Malignancy (aOR 2.8, P < 0.001) and DOAC use (aOR 5.2, P = 0.012) were associated with increased risk of recurrent stroke. Conclusion NBTE should be considered in stroke patients lacking conventional vascular risk factors, particularly those with malignancy or autoimmune disease. Malignancy and DOAC use were associated with higher recurrent stroke risk, while VKA use was associated with lower mortality; however, these anticoagulant-class findings should be considered hypothesis-generating and interpreted cautiously given the case-report evidence base, small treatment subgroups, potential confounding, and limited follow-up. What this study adds By synthesizing patient-level data from published case reports and case series, this review provides a stroke-focused characterization of NBTE, including clinical presentation, infarct topography, underlying etiologies, management strategies, recurrent cerebrovascular events, and mortality. The findings highlight multifocal infarction, malignancy-associated NBTE, and recurrent stroke despite anticoagulation as key clinical concerns, while emphasizing that observed associations with anticoagulant class should be viewed as hypothesis-generating rather than definitive treatment guidance

Background: Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small series. This systematic review aimed to comprehensively describe stroke presentation, imaging features, management, and outcomes in NBTE patients. Methods: A comprehensive search of EMBASE, PubMed, MEDLINE, Web of Science and PsycINFO databases was conducted through September 2023. Studies reporting individual cases or case series of NBTE-related stroke were included. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment modalities (unfractionated heparin/low molecular weight heparin (UFH/LMWH), warfarin, direct oral anticoagulants (DOACs), and valvular intervention), stroke recurrence, and mortality. Multivariate regression was performed to identify predictors of recurrent stroke and mortality. Results: A total of 129 patients from 118 studies were included (median age 56 [IQR:44-64], 62% females). Right (28%) and left (26%) hemispheric stroke syndromes accounted for the majority of clinical presentation, and multivessel ischemic infarcts (>2 territories) were observed in 66%. Conventional vascular risk factors were infrequent (1%-21%), while deep vein thrombosis and systemic embolism occurred in 59% and 38% of patients, respectively, either preceding or coinciding with stroke onset. Malignancy and autoimmune diseases were identified in 72% and 22%, respectively. Anticoagulation was initiated in 66% and 21% underwent valvular treatment. Over a median follow-up of 1.3 months, stroke recurrence and death occurred in 48% and 50%, respectively. Malignancy significantly increased mortality risk (OR 16.8, P<0.001), while autoimmune-related NBTE (OR 0.2, P=0.029), and anticoagulation with UFH/LMWH (OR 0.3, P=0.011) and VKA (OR 0.09, P=0.002) reduced mortality. Recurrent stroke was more likely in patients with malignancy (OR 16.8, P=0.001) and those receiving DOACs (OR 6.2, P=0.057) Conclusion: NBTE should be considered in stroke patients lacking conventional risk factors, particularly with underlying malignancy or autoimmune disease. Malignancy and DOAC use may increase the risk of recurrent strokes in this patient population.