Previous studies have demonstrated that patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) may develop the latter. The prevalence of 20-43% for AF in patients with HFpEF and prevalence of 50- 60% for HFpEF in AF patients. The pathophysiology indicates that AF usually precedes HFpEF, but each disease can promote the progression of the other one. Multiple mechanisms have been posited, such as left atrial (LA) fibrosis and myopathy as well as volume/pressure overload. Moreover, the combination of AF and HFpEF is associated with an increased rate of mortality as the presence of AF worsens the hemodynamics of HF. The diagnosis of HFpEF in patients with AF is underestimated, as the symptoms, laboratory values, and imaging techniques can be skewed by the presence of AF. Unfortunately, there are limited randomized controlled trials that recommend guideline-based treatments, such as choosing between rate and rhythm control. This narrative review aims to illustrate and summarize the pathophysiology, diagnosis, and treatment in the current literature for patients with AF and HFpEF.
Objectives: Thrombolysis remains underutilized for Acute Ischemic Stroke (AIS) in healthcare systems in low- and middle-income countries. We aimed to investigate the factors associated with utilization of intravenous thrombolysis in an academic medical center in Lebanon. Materials and Methods: This is a retrospective, cross-sectional, singlecentered, chart review-based study of AIS patients presenting to the American University of Beirut Medical Center (AUBMC) between January 2015 and October 2019. Included patients were older than 18 years and presented to the Emergency Department (ED) within 48 hours from symptom onset. Patient, disease, and health system response characteristics were collected and those eligible for and those who received thrombolysis within 4.5 hours onset by guidelines criteria were identified by chart review. Descriptive statistics, bivariate and multivariate analyses were performed for association with thrombolysis administration. Results: Out of the 373 AIS patients, 17.4% were candidate for rTPA and of those, 38.5% did not receive treatment. Patients who were candidate for IV alteplase had a higher NIHSS (OR 1.22 [1.14-1.31], p<0.0001), total or partial anterior circulation stroke (OR 3.58 [1.49-8.6, p=0.004) as compared to posterior or lacunar strokes and a shorter duration since symptom onset (OR 0.14 [0.07- 0.27, p<0.0001). The multivariate analysis showed that thrombolysis among eligible patients associated with younger age (OR 1.05 [1.01-1.10], p=0.029), a higher NIHSS (OR 1.12 [1.01-1.25], p=0.041), and stroke code activation (OR 2.81 [1.16-6.81], P=0.022). Conclusion: A good proportion of eligible AIS patients did not receive thrombolysis. To increase thrombolysis use in low- and middle-income countries, more consistent stroke code activation and education on age and stroke severity in eligibility are needed.
Background: Intracranial Aneurysm (IA) is a serious disease with high mortality and high morbidity rates, but the pathophysiological mechanisms of IA remain unclear. This study aimed to identify the Differentially Expressed Genes (DEGs) between IA tissues and Superficial Temporal Artery (STA) tissues using bioinformatic analysis. Methods: To investigate the key genes that are important for IAs, we analyzed microarray datasets (GSE75436) from the Gene Expression Omnibus (GEO) database, including 15 IA samples and 15 normal STA samples. First, we used the GEO2R tool to screen for DEGs (P-value<0.01 and |log2 FC| ≥2) between IA and STA tissues. Subsequently, the Database for Annotation, Visualization, and Integrated Discover software was used to perform function and pathway enrichment analyses. Finally, protein-protein interaction network analysis was performed using the Search Tool for Retrieval of Interacting Genes and Cytoscape software. Real-Time Quantitative Polymerase Chain Reaction (RT-QPCR) was performed to prove our assumption. Results: A total of 829 DEGs, of which 399 were upregulated and 430 were downregulated, were identified. The upregulated genes were mostly associated with Staphylococcus aureus infection, amoebiasis, rheumatoid arthritis, phagocytosis, and tuberculosis. The downregulated genes were mainly involved in vascular smooth muscle contraction, calcium signaling, histidine metabolism, cGMP-PKG signaling, and cAMP signaling. From the DEGs, five genes were selected as hub genes on the basis of the connection degree, which is one of 12 calculation methods from a plugin of Cytoscape called cytoHubba. The PCR results demonstrated that the expression levels of the top five hub genes, namely, Tumor Necrosis Factor (TNF), interleukin 8 (IL-8), Protein Tyrosine Phosphatase Receptor Type C (PTPRC), interleukin 1β (IL-1β), and Toll-like receptor 4 (TLR 4), were significantly higher in the IA samples than in the STA samples. Conclusion: TNF showed higher expression in the IA samples than in the STA samples. Thus, this gene may be involved in the occurrence and development of IA. The immune response and inflammation play important roles in the progression of IA. However, the specific pathophysiological mechanism needs further study.
Purpose: Elevated level of Lipocalin-2 (LCN2), a new acute phase adipokine, was described after ischemic stroke. A number of researchers feel as though that LCN2 originated from the infiltrating neutrophils and other cells in brain after stroke. Others measured elevated LCN2 expression in arteriosclerotic plaque. Therefore we have investigated LCN2 relative gene expression level of blood neutrophil granulocytes in patients with ischemic stroke to assess if elevated LCN2 is the cause or consequence of ischemic stroke. Methods: Laboratory and anamnestic data were collected, which could have a role in development of thrombo-embolic events in patients with ischemic stroke. RNA based method was used to evaluate the relative gene expression level of LCN2. We calculated Odds Ratio (OR) and Confidence Interval (CI) for the association between LCN2 and ischemic stroke. Results: 34 samples were available for evaluation. The LCN 2 relative gene expression level was decreased in 12 cases. In this group, 91% of patients have Atrial Fibrillation (AF) at the time of hospitalisation. The mean LCN2 relative gene expression value was 64.25% (ranges: 34%-115%) in patients with AF. It was significantly lower than in patients with normal sinus rhythm (409.2%; ranges: 127%-1127%; p=0.0003). The elevated LCN2 relative gene expression level significantly (p=0.012) increases the risk of stroke (OR: 12.6) independently from other factors. Conclusions: High LCN2 expression level seems to have strong positive predictive value on ischemic stroke, and may be useful in thrombotic risk stratification of plaque vulnerability in these patients.
Cerebral Venous Thrombosis (CVT) is a relatively uncommon but important cause of stroke that tends to affect young adults, especially women. Head trauma with or without skull fracture was reported to be triggering factors for CVT, but the underlying pathophysiology was not well elucidated. Endothelial injury and coexistent hypercoagulability were supposed to contribute to CVT after head trauma without skull fracture. We report a 49-year-old female patient who presented with headache with vomiting after head trauma and was initially diagnosed as post-traumatic Intracerebral Hemorrhage (ICH), but subsequently, progressed to CVT that resulted in cerebral venous infarction with hemorrhagic transformation. Magnetic Resonance brain Venography (MRV) confirmed CVT in superior sagittal sinus as well as right transverse and sigmoid sinuses. She was treated with endovascular mechanical thrombectomy followed by anticoagulation. The coagulopathy panel was checked both in hospital and in outpatient clinic for evaluating the etiology underlying post-traumatic nonpyogenic CVT. Persistently elevated level of plasma Factor VIII was identified. We should consider that patients with recent head trauma history without skull fracture and coexistent hypercoagulability could develop CVT resulting in cerebral venous infarction with hemorrhagic transformation even when the patient showed no definite focal neurologic deficit or the patient’s initial CT scan revealed no intracranial hemorrhage.
