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.

Cancer and left atrial enlargement in patients with ischemic stroke.

BACKGROUND: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain. METHODS: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS). RESULTS: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25). CONCLUSIONS: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy.

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.

Cognitive impairment and liver fibrosis in non-alcoholic fatty liver disease.

Background: Data regarding the prevalence and phenotype of cognitive impairment in non-alcoholic fatty liver disease (NAFLD) are limited. Objective: We assessed the prevalence and nature of cognitive deficits in people with NAFLD and assessed whether liver fibrosis, an important determinant of outcomes in NAFLD, is associated with worse cognitive performance. Methods: We performed a prospective cross-sectional study. Patients with NAFLD underwent liver fibrosis assessment with transient elastography and the following assessments: Cognitive Change Index, Eight-Item Informant Interview to Differentiate Aging and Dementia Questionnaire (AD8), Montreal Cognitive Assessment (MoCA), EncephalApp minimal hepatic encephalopathy test and a limited National Institutes of Health Toolbox battery (Flanker Inhibitory Control and Attention Test, Pattern Comparison Test and Auditory Verbal Learning Test). We used multiple linear regression models to examine the association between liver fibrosis and cognitive measures while adjusting for relevant covariates. Results: We included 69 participants with mean age 50.4 years (SD 14.4); 62% were women. The median liver stiffness was 5.0 kilopascals (IQR 4.0-6.9), and 25% had liver fibrosis (≥7.0 kilopascals). Cognitive deficits were common in people with NAFLD; 41% had subjective cognitive impairment, 13% had an AD8 >2, 32% had MoCA <26 and 12% had encephalopathy detected on the EncephalApp test. In adjusted models, people with liver fibrosis had modestly worse performance only on the Flanker Inhibitory Control and Attention Task (ß=-0.3; 95% CI -0.6 to -0.1). Conclusion: Cognitive deficits are common in people with NAFLD, among whom liver fibrosis was modestly associated with worse inhibitory control and attention.

Rates of Acute Brain Injury Among Severely Hypertensive Patients Seen in the Emergency Department.

Background: Identifying patients with acute brain injury among patients who present to the Emergency Department (ED) with severe hypertension can be challenging. We explored rates of brain injury in a cohort of ED patients with severe hypertension in whom acute target-organ damage was or was not initially suspected. Methods: We conducted a retrospective chart-review study at two different hospitals within the same urban health system. Consecutive adult patients seen from 10/1/2020 to 5/1/2022 with a systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥120 mmHg were included. Results: A total of 972 patients met our eligibility criteria. The average age was 59 years (SD: 16.5), 454 (46.7%) were women, and 582 (59.9%) were non-White. A total of 186/972 (19.1%) patients were initially thought to have acute target-organ damage in the ED with 97/186 (52.2%) diagnosed with stroke or TIA. The remaining 786/972 (80.9%) patients were not initially diagnosed with target-organ damage (hypertensive urgency [HU]). Of the 786 patients with HU, a head CT was obtained in 216/786 (27.7%) and brain MRI in 74/786 (9.4%). Of the HU patients with a brain MRI, 23/74 (31.1%) had acute abnormalities; most abnormalities on brain MRI (17/23 [73.9%]) were not seen on preceding head CT. Conclusions: In a multicenter study of ED patients, nearly 1 in 5 patients though to have HU who eventually underwent brain MRI had unexpected acute neurological findings, though brain MR was obtained in only 9%.

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.

The International Classification of Diseases, 10 th Edition, Clinical Modification (ICD-10-CM) Code I16.0 Accurately Identifies Patients with Hypertensive Urgency.

Objective: Hypertensive urgency, defined as acutely elevated BP without target organ damage, is associated with an increased risk of adverse cardiovascular events and accounts for a substantial proportion of national emergency department (ED) visits. To advance research in this space, we sought to validate the new ICD-10-CM diagnostic code for hypertensive urgency within a single healthcare system. Methods: We performed a retrospective chart-review study of ED encounters at Weill Cornell Medicine from 2016 â€" 2021. We randomly selected 25 encounters with the ICD-10-CM code I16.0 as the primary discharge diagnosis and 25 encounters with primary ICD-10-CM discharge diagnosis codes for benign headache disorders. A single board-certified vascular neurologist reviewed all 50 encounters while blinded to the assigned ICD-10-CM codes to identify cases of hypertensive urgency. We calculated the sensitivity, specificity, and positive predictive values of the ICD-10-CM code I16.0 with 95% confidence intervals (CI). Results: Out of 50 randomly selected ED encounters, 24 were adjudicated as hypertensive urgency. All encounters adjudicated as hypertensive urgency had been assigned the ICD-10-CM discharge diagnosis code of I16.0. All 25 of the encounters adjudicated as headache were assigned an ICD-10-CM discharge diagnosis code for a benign headache disorder. The ICD-10-CM code for hypertensive urgency, I16.0, was thus found to have a sensitivity of 100% (95% CI: 86-100%), specificity of 96% (95% CI: 80-100%), and positive predictive value of 96% (95% CI: 78-99%). Conclusion: We found that the new ICD-10-CM code for hypertensive urgency, I16.0, can reliably identify patients with this condition.

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.

Characteristics of Patients with Unrecognized Sleep Apnea Requiring Postoperative Oxygen Therapy.

Surgical patients with obstructive sleep apnea (OSA) have increased risk of perioperative complications. The primary objective is to determine the characteristics of surgical patients with unrecognized OSA requiring oxygen therapy for postoperative hypoxemia. The secondary objective is to investigate the characteristics of patients who were responsive to oxygen therapy. This was a post-hoc multicenter study involving patients with cardiovascular risk factors undergoing major non-cardiac surgery. Patients ≥45 years old underwent Type 3 sleep apnea testing and nocturnal oximetry preoperatively. Responders to oxygen therapy were defined as individuals with ≥50% reduction in oxygen desaturation index (ODI) on postoperative night 1 versus preoperative ODI. In total, 624 out of 823 patients with unrecognized OSA required oxygen therapy. These were mostly males, had larger neck circumferences, higher Revised Cardiac Risk Indices, higher STOP-Bang scores, and higher ASA physical status, undergoing intraperitoneal or vascular surgery. Multivariable regression analysis showed that the preoperative longer cumulative time SpO2 < 90% or CT90% (adjusted p = 0.03), and lower average overnight SpO2 (adjusted p < 0.001), were independently associated with patients requiring oxygen therapy. Seventy percent of patients were responders to oxygen therapy with ≥50% ODI reduction. Preoperative ODI (19.0 ± 12.9 vs. 14.1 ± 11.4 events/h, p < 0.001), CT90% (42.3 ± 66.2 vs. 31.1 ± 57.0 min, p = 0.038), and CT80% (7.1 ± 22.6 vs. 3.6 ± 8.7 min, p = 0.007) were significantly higher in the responder than the non-responder. Patients with unrecognized OSA requiring postoperative oxygen therapy were males with larger neck circumferences and higher STOP-Bang scores. Those responding to oxygen therapy were likely to have severe OSA and worse preoperative nocturnal hypoxemia. Preoperative overnight oximetry parameters may help in stratifying patients.