%0 Journal Article %J Stroke %D 2020 %T Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage. %A Biffi, Alessandro %A Urday, Sebastian %A Kubiszewski, Patryk %A Gilkerson, Lee %A Sekar, Padmini %A Rodriguez-Torres, Axana %A Bettin, Margaret %A Charidimou, Andreas %A Pasi, Marco %A Kourkoulis, Christina %A Schwab, Kristin %A DiPucchio, Zora %A Behymer, Tyler %A Osborne, Jennifer %A Morgan, Misty %A Moomaw, Charles J %A James, Michael L %A Greenberg, Steven M %A Viswanathan, Anand %A Gurol, M Edip %A Worrall, Bradford B %A Testai, Fernando D %A McCauley, Jacob L %A Falcone, Guido J %A Langefeld, Carl D %A Anderson, Christopher D %A Kamel, Hooman %A Woo, Daniel %A Sheth, Kevin N %A Rosand, Jonathan %K Aged %K Anticoagulants %K Apolipoprotein E4 %K Cerebral Hemorrhage %K Female %K Humans %K Magnetic Resonance Imaging %K Male %K Middle Aged %K Neuroimaging %K Recurrence %X

BACKGROUND AND PURPOSE: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the () gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest.

METHODS: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and genotype predict ICH recurrence. We then developed and validated a combined -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis.

RESULTS: Cortical superficial siderosis, cerebral microbleed, and ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all <0.05). Combining genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH.

CONCLUSIONS: Combining MRI and genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

%B Stroke %V 51 %P 2153-2160 %8 2020 07 %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/32517581?dopt=Abstract %R 10.1161/STROKEAHA.120.028310 %0 Journal Article %J Stroke %D 2018 %T Cardioembolic Stroke Risk and Recovery After Anticoagulation-Related Intracerebral Hemorrhage. %A Murphy, Meredith P %A Kuramatsu, Joji B %A Leasure, Audrey %A Falcone, Guido J %A Kamel, Hooman %A Sansing, Lauren H %A Kourkoulis, Christina %A Schwab, Kristin %A Elm, Jordan J %A Gurol, M Edip %A Tran, Huy %A Greenberg, Steven M %A Viswanathan, Anand %A Anderson, Christopher D %A Schwab, Stefan %A Rosand, Jonathan %A Shi, Fu-Dong %A Kittner, Steven J %A Testai, Fernando D %A Woo, Daniel %A Langefeld, Carl D %A James, Michael L %A Koch, Sebastian %A Huttner, Hagen B %A Biffi, Alessandro %A Sheth, Kevin N %X

Background and Purpose- Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods- We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHADS-VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results- In multivariable analyses, the CHADS-VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79-0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHADS-VASc score (odds ratio, 1.89; 95% CI, 1.32-2.70). We found an interaction between CHADS-VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P=0.011). Conclusions- Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.

%B Stroke %V 49 %P 2652-2658 %8 2018 Nov %G eng %N 11 %1 https://www.ncbi.nlm.nih.gov/pubmed/30355194?dopt=Abstract %R 10.1161/STROKEAHA.118.021799