Ventricular Tachycardia in Patients With Takotsubo Cardiomyopathy: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction  The purpose of this study was to determine the prevalence of ventricular tachycardia (VT) among patients admitted with takotsubo cardiomyopathy (TCM) as well as to analyze the predictors of VT and the predictors of mortality among patients admitted with TCM. Methods Data were obtained from the National Inpatient Sample (NIS) database from January 2016 to December 2019. Patients with a primary diagnosis of TCM were selected using ICD-10 code I51.81. Subsequently, the study population was divided into patients who developed VT vs. patients who did not develop this complication. We then used multivariate logistic regression to assess the predictors of VT in our patient cohort as well as the predictors of mortality among patients admitted with TCM. Results  Of 40114 patients with TCM, 1923 developed VT (4.8%) during their hospital stay. Predictors of VT include atrial fibrillation (AF) (adjusted odds ratio (aOR): 1.592; 95% confidence interval (CI): 0.00-1.424; p=0.001), congestive heart failure (aOR: 1.451; 95% CI: 1.307-1.610; p=0.001), coagulopathy (aOR: 1.436; 95% CI: 1.150-1.793; p=0.001), and patients who self-identify in the race category as Other (aOR: 1.427; 95% CI: 1.086-1.875; p=0.011). Female sex was found to be protective against VT (aOR: 0.587; 95% CI: 0.526-0.656; p=0.001). Predictors of mortality among patients admitted with TCM include, among other factors, age (aOR: 1.014; 95% CI: 1.011-1.018; p=0.001), Asian or Pacific Islander race (aOR: 1.533; 95% CI: 1.197-1.964; p=0.001), Black race (aOR: 1.242; 95% CI: 1.062-1.452; p=0.007), VT (aOR: 1.754; 95% CI: 1.505-2.045; p=0.001), and AF (aOR: 1.441; 95% CI: 1.301-1.597; p=0.001). Some comorbidities that were protective against mortality in TCM include tobacco use disorder (aOR: 0.558; 95% CI: 0.255-0.925; p=0.028) and obstructive sleep apnea (aOR: 0.803; 95% CI: 0.651-0.990; p=0.028). The female sex was found to be protective against mortality (aOR: 0.532; 95% CI: 0.480-0.590; p=0.001).  Conclusion  In a large cohort of women admitted with TCM, we found the prevalence of VT to be 4.8%. Predictors of VT included conditions such as AF and congestive heart failure. The female sex was found to be protective against VT and protective against mortality among patients admitted with TCM.

The Impact of Congestive Heart Failure on Outcomes in Patients Hospitalized With Preeclampsia.

INTRODUCTION: The purpose of this study was to determine the prevalence of congestive heart failure (CHF) among patients admitted with preeclampsia as well as to analyze the independent association of CHF with in-hospital outcomes among women with preeclampsia. METHODS: Data were obtained from the National (Nationwide) Inpatient Sample (NIS) from January 2016 to December 2019. We assessed the independent association of CHF with outcomes in patients admitted with preeclampsia. Predictors of mortality in patients admitted with preeclampsia were also analyzed. RESULTS: Women with preeclampsia in the United States between 2016 and 2019 were included in our analysis. A total of 256,010 cases were isolated, comprising 1150 patients with preeclampsia and CHF (0.45%). Multivariate analysis demonstrated that CHF in patients with preeclampsia was independently associated with several outcomes, among them cardiac arrest (adjusted OR (aOR) 4.635, p=0.004), ventricular tachycardia (aOR 17.487, p<0.001), pulmonary embolism (aOR 6.987, p<0.001), and eclampsia (aOR 2.503, p=0.011). Conversely, we found CHF to be protective against postpartum hemorrhage (aOR 0.665, p=0.003). Among the predictors of mortality in preeclampsia are age (aOR 1.062, p=0.022), Asian or Pacific Islander race (aOR 4.695, p=0.001), and CHF (aOR 25.457, p<0.001).  Conclusions: In a large cohort of patients admitted with preeclampsia, we found the prevalence of CHF to be 0.45%. CHF was associated with several adverse outcomes as well as increased length of stay.

Meta-Analysis of APP Expression Modulated by SARS-CoV-2 Infection via the ACE2 Receptor.

Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (Aß) plaques from improper amyloid-beta precursor protein (APP) cleavage. Following studies of inflammation caused by coronavirus-2019 (COVID-19) infection, this study investigated the impact of COVID-19 on APP expression. A meta-analysis was conducted utilizing QIAGEN Ingenuity Pathway Analysis (IPA) to examine the link between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the modulation of APP expression upon virus binding the Angiotensin-converting enzyme-2 (ACE2) receptor. A Core Analysis was run on the infection by severe acute respiratory syndrome (SARS) coronavirus node, which included molecules affected by SARS-CoV-2, revealing its upstream regulators. Intermediary molecules were found between the upstream regulators and ACE2 and between ACE2 and APP. Activation of the upstream regulators downregulated the expression of ACE2 with a Z-score of -1.719 (p-value = 0.086) and upregulated APP with a Z-score of 1.898 (p-value = 0.058), showing a less than 10% chance of the results occurring by chance and pointing to an inverse relationship between ACE2 and APP expression. The neuroinflammation signaling pathway was the fifth top canonical pathway involved in APP upregulation. The study results suggest that ACE2 could be downregulated by SARS-CoV-2, resulting in APP upregulation, and potentially exacerbating the onset and progression of AD.

Network Meta-analysis on the Changes of Amyloid Precursor Protein Expression Following SARS-CoV-2 Infection.

SARS-CoV-2 infection begins with the attachment of its spike (S) protein to angiotensin-converting enzyme-2 (ACE2) followed by complex host immune responses with cardiovascular and neurological implications. Our meta-analyses used QIAGEN Ingenuity Pathway Analysis (IPA) and Knowledge Base (QKB) to investigate how the expression of amyloid precursor protein (APP) was modulated by attachment of SARS-CoV-2 S protein in the brain microvascular endothelial cells (BMVECs) and during COVID-19 in progress. Published 80 host response genes reported to be modulated in BMVECs following SARS-CoV-2 S protein binding were used to identify key canonical pathways and intermediate molecules mediating the regulation of APP production following the attachment of S protein to endothelial cells. This revealed that the attachment of SARS-CoV-2 S protein may inhibit APP expression in the BMVECs. Our results shed light on the molecular mechanisms by which SARS-CoV-2 infection may potentiate the incidence of stroke by inhibiting the production of APP in the BMVECs. We also analyzed molecules associated with COVID-19, which revealed six upstream regulators, TNF, IFNG, STAT1, IL1ß, IL6, and STAT3. The upstream regulators mediate the increased production of APP via intermediators, with eleven regulated by all six upstream regulators. These COVID-19 upstream regulators increased APP expression with a statistically significant Z-score of 3.705 (p value = 0.000211). These findings have revealed molecular mechanisms by which COVID-19 disease may lead to long-term neurological manifestations resulting from the elevated APP expression in line with immune response in the host. Altogether, our study revealed two distinct scenarios which may have differential impact on APP expression.

Meta-Analysis of Methamphetamine Modulation on Amyloid Precursor Protein through HMGB1 in Alzheimer's Disease.

The deposition of amyloid-beta (Aß) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer's disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the "Molecule Activity Predictor" feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.