Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.

Atrial fibrillation and short-term outcomes after cancer-related ischemic stroke.

INTRODUCTION: Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes. RESULTS: Among 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%). DISCUSSION AND CONCLUSION: In cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays.

Risk of Major Adverse Cardiovascular Events After Emergency Department Visits for Hypertensive Urgency.

BACKGROUND: Chronic hypertension is an established long-term risk factor for major adverse cardiovascular events (MACEs). However, little is known about short-term MACE risk after hypertensive urgency, defined as an episode of acute severe hypertension without evidence of target-organ damage. We sought to evaluate the short-term risk of MACE after an emergency department (ED) visit for hypertensive urgency resulting in discharge to home. METHODS: We performed a case-crossover study using deidentified administrative claims data. Our case periods were 1-week intervals from 0 to 12 weeks before hospitalization for MACE. We compared ED visits for hypertensive urgency during these case periods versus equivalent control periods 1 year earlier. Hypertensive urgency and MACE components were all ascertained using previously validated International Classification of Diseases, Tenth Revision Clinical Modification codes. We used McNemar test for matched data to calculate risk ratios. RESULTS: Among 2 225 722 patients with MACE, 1 893 401 (85.1%) had a prior diagnosis of hypertension. There were 4644 (0.2%) patients who had at least 1 ED visit for hypertensive urgency during the 12 weeks preceding their MACE hospitalization. An ED visit for hypertensive urgency was significantly more common in the first week before MACE compared with the same chronological week 1 year earlier (risk ratio, 3.5 [95% CI, 2.9-4.2]). The association between hypertensive urgency and MACE decreased in magnitude with increasing temporal distance from MACE and was no longer significant by 11 weeks before MACE (risk ratio, 1.2 [95% CI, 0.99-1.6]). CONCLUSIONS: ED visits for hypertensive urgency were associated with a substantially increased short-term risk of subsequent MACE.

Association between elevated fibrosis-4 index of liver fibrosis and risk of hemorrhagic stroke.

BACKGROUND: Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke. METHODS: We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use. RESULTS: Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually. CONCLUSIONS: Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke.

Misdiagnosis of Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome in the Emergency Department.

Background Cerebrovascular dysregulation syndromes, posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), are challenging to diagnose because they are rare and require advanced neuroimaging for confirmation. We sought to estimate PRES/RCVS misdiagnosis in the emergency department and its associated factors. Methods and Results We conducted a retrospective cohort study of PRES/RCVS patients using administrative claims data from 11 states (2016-2018). We defined patients with a probable PRES/RCVS misdiagnosis as those with an emergency department visit for a neurological symptom resulting in discharge to home that occurred ≤14 days before PRES/RCVS hospitalization. Proportions of patients with probable misdiagnosis were calculated, characteristics of patients with and without probable misdiagnosis were compared, and regression analyses adjusted for demographics and comorbidities were performed to identify factors affecting probable misdiagnosis. We identified 4633 patients with PRES/RCVS. A total of 210 patients (4.53% [95% CI, 3.97-5.17]) had a probable preceding emergency department misdiagnosis; these patients were younger (mean age, 48 versus 54 years; P<0.001) and more often female (80.4% versus 69.3%; P<0.001). Misdiagnosed patients had fewer vascular risk factors except prior stroke (36.3% versus 24.2%; P<0.001) and more often had comorbid headache (84% versus 21.4%; P<0.001) and substance use disorder (48.8% versus 37.9%; P<0.001). Facility-level factors associated with probable misdiagnosis included smaller facility, lacking a residency program (62.2% versus 73.7%; P<0.001), and not having on-site neurological services (75.7% versus 84.3%; P<0.001). Probable misdiagnosis was not associated with higher likelihood of stroke or subarachnoid hemorrhage during PRES/RCVS hospitalization. Conclusions Probable emergency department misdiagnosis occurred in ≈1 of every 20 patients with PRES/RCVS in a large, multistate cohort.

Cancer and the Risk of Perioperative Arterial Ischemic Events.

BACKGROUND AND AIMS: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischemic events. METHODS: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006-2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 U.S. states between 2016-2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery. RESULTS: Among 5,609,675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischemic event rate was 0.96% among patients with disseminated cancer versus 0.48% among patients without (HR, 2.01; 95% CI, 1.90-2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischemic events (HR, 1.37; 95% CI, 1.28-1.46). Among 1,341,658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischemic event was diagnosed in 0.74% of patients with cancer versus 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27-1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischemic events (HR, 1.31; 95% CI, 1.21-1.42). CONCLUSIONS: Cancer is an independent risk factor for perioperative arterial ischemic events.