Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Device-guided paced respiration as an adjunctive therapy for hypertension in obstructive sleep apnea: a pilot feasibility study.

Data suggest that device-guided paced respiration (<10 breaths/min) may reduce blood pressure in hypertensive patients. We hypothesized that daily device-guided slow breathing may lower blood pressure in patients with hypertension and obstructive sleep apnea (OSA). In this one-arm pilot study, we enrolled 25 subjects with hypertension and OSA. Subjects were asked to perform device-guided paced respiration 30 min a day for 8 weeks. Our primary outcome was change in office systolic and diastolic blood pressures from baseline to 8 weeks. Twenty-four subjects completed the study. Mean baseline blood pressure was 140.0 ± 10.2 mmHg systolic and 82.7 ± 8.9 mmHg diastolic. Complete device data were available for 17 subjects. Mean device adherence was 81 ± 24% and 51% achieved a mean breath rate ≤10 breaths/min over 8 weeks. Three subjects had changes in their anti-hypertensive medications during the study. Among the remaining 21 subjects, mean difference in office blood pressure from baseline to 8 weeks was -9.6 ± 11.8 mmHg systolic (p ≤ 0.01) and -2.52 ± 8.9 mmHg diastolic (p = 0.21). Device-guided paced respiration may lower systolic blood pressure in patients with hypertension and OSA; however, our findings need to be confirmed with larger randomized controlled trials.

The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms.

Circadian rhythms of behavior and physiology can be entrained by daily cycles of restricted food availability, but the pathways that mediate food entrainment are unknown. The dorsomedial hypothalamic nucleus (DMH) is critical for the expression of circadian rhythms and receives input from systems that monitor food availability. Here we report that restricted feeding synchronized the daily rhythm of DMH activity in rats such that c-Fos expression in the DMH was highest at scheduled mealtime. During food restriction, unlesioned rats showed a marked preprandial rise in locomotor activity, body temperature and wakefulness, and these responses were blocked by cell-specific lesions in the DMH. Furthermore, the degree of food entrainment correlated with the number of remaining DMH neurons, and lesions in cell groups surrounding the DMH did not block entrainment by food. These results establish that the neurons of the DMH have a critical role in the expression of food-entrainable circadian rhythms.

Nocturnal bilevel positive airway pressure for the treatment of asthma.

Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We hypothesized that mimicking deep inspiration using nocturnal mechanical support would improve symptoms in patients with asthma. Subjects with asthma underwent usual care and bilevel positive airway pressure (PAP) therapy for 4 weeks, separated by 4 weeks, and methacholine challenge (PC20) and subjective assessments. 13 patients with asthma alone and 8 with asthma + OSA completed the protocol. Change in bronchoreactivity (ratio of Post/Pre PC20) was not significantly different during usual care and bilevel PAP [0.86 (IQR 0.19, 1.82) vs 0.94 (IQR 0.56, 2.5), p = 0.88], nor was the change in Asthma Control Test different: 0.1 ±â€¯2.2 vs. -0.2 ±â€¯2.9, p = 0.79, respectively. Bilevel PAP therapy for four weeks did not improve subjective or objective measures of asthma severity in patients with asthma or those with asthma and OSA, although there was heterogeneity in response.

The left atrial appendage morphology is associated with embolic stroke subtypes using a simple classification system: A proof of concept study.

BACKGROUND AND PURPOSE: The current left atrial appendage (LAA) classification system (cLAA-CS) categorizes it into 4 morphologies: chicken wing (CW), windsock, cactus, and cauliflower, though there is limited data on either reliability or associations between different morphologies and stroke risk. We aimed to develop a simplified LAA classification system and to determine its relationship to embolic stroke subtypes. METHODS: Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology was classified using the traditional system (in which CW = low risk) and a new system (LAA-H/L, in which low risk morphology (LAA-L) was defined as an acute angle bend or fold from the proximal/middle portion of the LAA and high risk morphology (LAA-H) was defined as all others). As a proof of concept study, we determined reliability for the two classification systems, and we assessed the associations between both classification systems with stroke subtypes in our cohort and previous studies. RESULTS: We identified 329 ischemic stroke patients with a qualifying chest CT (126 cardioembolic subtype, 116 embolic stroke of undetermined source (ESUS), and 87 non-cardioembolic subtypes). Intra- and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85, respectively) vs. cLAA-CS (0.50 and 0.40). The LAA-H/L led to classifying 69 LAA morphologies that met criteria for CW as LAA-H. In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter- and intra-rater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes. CONCLUSION: The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk identify patients with cardioembolic stroke subtypes. Larger studies are needed to validate these findings.

The Addition of Atrial Fibrillation to the Los Angeles Motor Scale May Improve Prediction of Large Vessel Occlusion.

BACKGROUND AND PURPOSE: There is evidence suggesting that Los Angeles Motor Scale (LAMS) ≥ 4 predicts large vessel occlusion (LVO). We aim to determine whether atrial fibrillation (AF) can improve the ability of LAMS in predicting LVO. METHODS: We included consecutive patients with a discharge diagnosis of ischemic stroke admitted within 24 hours from last known normal time who underwent emergent vascular imaging using a computerized tomography angiography (CTA) of the head and neck. LVO was defined as intracranial internal carotid artery, proximal middle cerebral artery (M1 or proximal M2 segment), or basilar occlusion. LAMS was determined in the emergency department upon arrival. Univariate and multivariable models were performed to identify predictors of LVO and to determine whether AF improves the ability of LAMS to predict LVO. RESULTS: Among 1,234 patients admitted with ischemic stroke, 862 underwent emergent vascular imaging (69.8%) out of which 374 (43.4%) had evidence of LVO and 207 (24%) underwent mechanical thrombectomy. In multivariable models, predictors of LVO were LAMS (OR 1.42 per one point increase 95% CI 1.29-1.57) and AF (OR 1.95 95% CI 1.26-3.02, P < .001). We developed the LAMS-AF that includes the LAMS score and adds two points if AF is present. In this analysis, LAMS-AF (AUC .78) had improved prediction over LAMS (AUC .76) in predicting LVO and lead to reclassification of 8/68 patients (11.8%) with LAMS = 3 group into the high-risk LVO group. CONCLUSION: In patients with LAMS = 3, using the LAMS-AF score may improve the ability of LAMS in predicting LVO. Larger studies are needed to confirm our findings.