Cardiomyopathy-Associated Hospital Admissions Among Methamphetamine Users: Geographical and Social Disparities.

Background: Methamphetamine is an emerging drug threat. The disparity in cardiomyopathy-associated hospital admissions among methamphetamine users (CAHMA) over the decade remains unknown. Objectives: The purpose of this study was to determine the trends and prevalence of CAHMA by age, sex, race, and geographical region. Methods: We used data from 2008 to 2020 from the National Inpatient Sample database. We identified 12,845,919 cardiomyopathy-associated hospital admissions; among them, 222,727 were diagnosed as methamphetamine users. A generalized linear model with binomial link function was used to compute the prevalence ratio and 95% CI. Those who used other substances along with methamphetamine were excluded from the analysis. Results: CAHMA increased by 231% (P trend <0.001) from 2008 to 2020. CAHMA increased 345% for men (P trend <0.001) and 122% for women (P trend <0.001), 271% for non-Hispanic White (P trend <0.001), 254% for non-Hispanic Black (p trend <0.001), 565% for Hispanic (P trend <0.001), and 645% for non-Hispanic Asian (P trend <0.001) population. CAHMA also increased significantly in the West region (530%) (P trend <0.001) and South region (200%) (P trend <0.001) of the United States. Men, Hispanic population, age groups 26 to 40 and 41 to 64 years, and Western regions showed a significantly higher uptrend than their counterparts (P trend <0.001). Conclusions: CAHMA have increased significantly in the United States. Men, Hispanics, non-Hispanic Asian, age groups 41 to 64. and western regions showed a higher proportional increase highlighting gender-based, racial/ethnic, and regional disparities over the study period.

Transcatheter Versus Surgical Aortic Valve Replacement in Recipients of Solid Organ Transplants and Liver Cirrhosis: A Propensity-Matched Analysis of National Readmission Data.

Transcatheter aortic valve replacement (TAVR) continues to grow in the United States. There are limited data on recipients of solid organ transplant (SOT) and patients with liver cirrhosis who undergo aortic valve replacement (AVR). Our study aims to evaluate outcomes in these populations. Using the national readmission database (2016 to 2020), we identified recipients of SOT and patients with liver cirrhosis without previous liver transplants who were admitted for severe aortic stenosis and underwent either TAVR or surgical AVR (SAVR). We used multivariable regression for adjusted analysis and the propensity score matching model, implementing complete Mahalanobis distance matching within the Propensity Score Caliper (0.2) to match TAVR and SAVR cohorts for outcomes. Of 3,394 hospitalizations for AVR in recipients of SOT, 2,181 underwent TAVR, and 1,213 underwent SAVR. On propensity-matched analysis, SAVR was associated with more adverse events than was TAVR, including in-hospital mortality (5.2% vs 1.1%, adjusted odds ratio [aOR] 4.49, p <0.001), acute kidney injury (43.7% vs 10.2%, p <0.001), cardiogenic shock (9.0% vs 1.6%, p <0.001), sudden cardiac arrest (15.9 vs 6.0%, p <0.001), major adverse cardiac and cerebrovascular events (28% vs 10.4%, p <0.001), and net adverse events (72.8 vs 37.6%, p <0.001). A greater median length of stay (10 vs 2 days, p <0.001) and adjusted cost ($80,842 vs $57,014, p <0.001) were also observed. The readmission rates were the same for both cohorts after a 6-month follow-up. Similarly, in 14,763 hospitalizations for AVR in liver cirrhosis, 7,109 patients underwent TAVR, and 7,654 underwent SAVR. In propensity-matched cohorts (n = 2,341), SAVR was found to be associated with greater adverse events, including in-hospital mortality (19.8% vs 10%), stroke (6.7% vs 2%), acute kidney injury (67.7% vs 30.3%), cardiogenic shock (41.9% vs 19.9%), sudden cardiac arrest (31.8% vs 13.2%, aOR 2.89), major adverse cardiac and cerebrovascular events (66.2% vs 35.7%), and net adverse events (86% vs 59.5%) (p <0.001). A greater median length of stay (16 vs 3 days) and cost ($500,218 vs $263,383) were also observed (p <0.001). However, the rate of readmissions at 30-day (9% vs 11.1%) and 180-day intervals (33.4% vs 39.8%) was lower for the SAVR cohort (p <0.05). In recipients of SOT and patients with liver cirrhosis, SAVR is associated with greater short-term mortality, adverse events, and healthcare burden than is TAVR. TAVR is a relatively safer alternative to SAVR in these patient populations, although further studies are warranted to compare the long-term outcomes.

Social-geographic disparities in suicidal ideations among methamphetamine users in the USA.

IMPORTANCE: Methamphetamine use is a growing public health concern nationwide. Suicide is the second leading cause of death in 2019 for US citizens aged 10-14 years and 25-34 years and is also a significant public health concern. Understanding the intersection of methamphetamine use and suicidal ideation (SI) is necessary to develop public health and policy solutions that mitigate these ongoing severe public health issues. OBJECTIVE: Our objective was to examine SI in methamphetamine users to allow us to determine prevalence and trends by age, sex, race, and geographical region. DESIGN, SETTINGS, AND PARTICIPANTS: Using data collected between 2008 and 2019 from the National Inpatient Sample (NIS) database, we identified hospital admissions (HA) of patients ≥18 years of age with a primary or secondary diagnosis of SI who were also diagnosed as methamphetamine users. Those who used other substances with methamphetamine were excluded from the analysis. MAIN OUTCOME AND MEASURES: To determine the trend and prevalence of hospital admissions due to SI and SI among methamphetamine users, we used trend weights to calculate the national estimates and performed design-based analysis to account for complex survey design and sampling weights on data collected between 2008 and 2019 in the US. RESULTS: The prevalence ratio (PR) of hospitalizations with concurrent SI and methamphetamine use increased 16-fold from 2008 to 2019. The most significant increase occurred between 2015 and 2016; the PR doubled from 6.07 to 12.14. The PR of hospitalizations with concurrent SI and methamphetamine use was highest in patients aged 26-40 (49.08%) and 41-64 (28.49%). Patients aged 41-64 showed the most significant increase from 2008 to 2019 (15.8-fold). While non-Hispanic White patients comprised most of these hospitalizations (77.02%), non-Hispanic Black patients showed the highest proportional increase (39.1-fold). The Southern and Western regions in the US showed the highest PR for these hospitalizations (34.86% and 34.31%, respectively). CONCLUSION AND RELEVANCE: Our findings indicate that SI in methamphetamine users has been increasing for some time and is likely to grow. In addition, our results suggest that these patients are demographically different. Both conditions are associated with a lesser likelihood of seeking and receiving care. Therefore, when addressing increased SI or methamphetamine use, learning more about patients who share both conditions is necessary to ensure proper care.

Exposure to Stress Alters Cardiac Gene Expression and Exacerbates Myocardial Ischemic Injury in the Female Murine Heart.

Mental stress is a risk factor for myocardial infarction in women. The central hypothesis of this study is that restraint stress induces sex-specific changes in gene expression in the heart, which leads to an intensified response to ischemia/reperfusion injury due to the development of a pro-oxidative environment in female hearts. We challenged male and female C57BL/6 mice in a restraint stress model to mimic the effects of mental stress. Exposure to restraint stress led to sex differences in the expression of genes involved in cardiac hypertrophy, inflammation, and iron-dependent cell death (ferroptosis). Among those genes, we identified tumor protein p53 and cyclin-dependent kinase inhibitor 1A (p21), which have established controversial roles in ferroptosis. The exacerbated response to I/R injury in restraint-stressed females correlated with downregulation of p53 and nuclear factor erythroid 2-related factor 2 (Nrf2, a master regulator of the antioxidant response system-ARE). S-female hearts also showed increased superoxide levels, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (Ptgs2) expression (a hallmark of ferroptosis) compared with those of their male counterparts. Our study is the first to test the sex-specific impact of restraint stress on the heart in the setting of I/R and its outcome.

Using the social vulnerability index to assess COVID-19 vaccine uptake in Louisiana.

Using data from the Louisiana Department of Public Health, we explored the spatial relationships between the Social Vulnerability Index (SVI) and COVID-19-related vaccination and mortality rates. Publicly available COVID-19 vaccination and mortality data accrued from December 2020 to October 2021 was downloaded from the Louisiana Department of Health website and merged with the SVI data; geospatial analysis was then performed to identify the spatial association between the SVI and vaccine uptake and mortality rate. Bivariate Moran's I analysis revealed significant clustering of high SVI ranking with low COVID-19 vaccination rates (1.00, p < 0.001) and high smoothed mortality rates (0.61, p < 0.001). Regression revealed that for each 10% increase in SVI ranking, COVID-19 vaccination rates decreased by 3.02-fold (95% CI = 3.73-2.30), and mortality rates increased by a factor of 1.19 (95% CI = 0.99-1.43). SVI values are spatially linked and significantly associated with Louisiana's COVID-19-related vaccination and mortality rates. We also found that vaccination uptake was higher in whites than in blacks. These findings can help identify regions with low vaccination rates and high mortality, enabling the necessary steps to increase vaccination rates in disadvantaged neighborhoods.

Contemporary diagnosis and management of severe tricuspid regurgitation.

Many novel percutaneous interventions are being developed for application in the tricuspid valve position. At the present time in the United States, there are no commercially available transcathter devices for this application. This article reviews the growing evidence for diagnosing, imaging, and treating severe tricuspid regurgitation as well as the surgical and transcatheter options that are under current development and in various stages of clinical trials.

Review of Prosthetic Paravalvular Leaks: Diagnosis and Management.

PURPOSE OF REVIEW: Paravalvular leak (PVL) is a relatively uncommon complication associated with prosthetic valve implantation. PVL can occasionally lead to serious adverse consequences such as congestive heart failure, infective endocarditis, and hemolytic anemia. Surgical re-operation carries a high mortality risk. RECENT FINDINGS: Transcatheter closure therapy provides a viable alternative for the treatment of this disorder with reasonable procedural and clinical success. The recent advent of hybrid imaging modalities has increased procedural success. This article summarizes the pathophysiology, clinical characteristics, and treatment modalities surroundings prosthetic paravalvular leak.

Glucocorticoid Inhibition of Estrogen Regulation of the Serotonin Receptor 2B in Cardiomyocytes Exacerbates Cell Death in Hypoxia/Reoxygenation Injury.

Background Stress has emerged as an important risk factor for heart disease in women. Stress levels have been shown to correlate with delayed recovery and increased mortality after a myocardial infarction. Therefore, we sought to investigate if the observed sex-specific effects of stress in myocardial infarction may be partly attributed to genomic interactions between the female sex hormones, estrogen (E2), and the primary stress hormones glucocorticoids. Methods and Results Genomewide studies show that glucocorticoids inhibit estrogen-mediated regulation of genes with established roles in cardiomyocyte homeostasis. These include 5-HT2BR (cardiac serotonin receptor 2B), the expression of which is critical to prevent cardiomyocyte death in the adult heart. Using siRNA, gene expression, and chromatin immunoprecipitation assays, we found that 5-HT2BR is a primary target of the glucocorticoid receptor and the estrogen receptor α at the level of transcription. The glucocorticoid receptor blocks the recruitment of estrogen receptor α to the promoter of the 5-HT2BR gene, which may contribute to the adverse effects of stress in the heart of premenopausal women. Using immunoblotting, TUNEL (terminal deoxynucleotidal transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling), and flow cytometry, we demonstrate that estrogen decreases cardiomyocyte death by a mechanism relying on 5-HT2BR expression. In vitro and in vivo experiments show that glucocorticoids inhibit estrogen cardioprotection in response to hypoxia/reoxygenation injury and exacerbate the size of the infarct areas in myocardial infarction. Conclusions These results established a novel mechanism underlying the deleterious effects of stress on female cardiac health in the setting of ischemia/reperfusion.

Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. OBJECTIVE: To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. METHODS: We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight-adjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. RESULTS: A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P = .31 by Chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33-1.37; P = .28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. CONCLUSION: In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.

Decreased availability of nitric oxide and hydrogen sulfide is a hallmark of COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of symptoms. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is increasingly associated with cardiovascular complications requiring hospitalizations; however, the mechanisms underlying these complications remain unknown. Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitters that regulate key cardiovascular functions. METHODS: Blood samples were obtained from 68 COVID-19 patients and 33 controls and NO and H2S metabolites were assessed. H2S and NO levels were compared between cases and controls in the entire study population and subgroups based on race. The availability of gasotransmitters was examined based on severity and outcome of COVID-19 infection. The performance of H2S and NO levels in predicting COVID-19 infection was also analyzed. Multivariable regression analysis was performed to identify the effects of traditional determinants of gasotransmitters on NO and H2S levels in the patients with COVID-19 infection. RESULTS: Significantly reduced NO and H2S levels were observed in both Caucasian and African American COVID-19 patients compared to healthy controls. COVID-19 patients who died had significantly higher NO and H2S levels compared to COVID-19 patients who survived. Receiver-operating characteristic analysis of NO and H2S metabolites in the study population showed free sulfide levels to be highly predictive of COVID-19 infection based on reduced availability. Traditional determinants of gasotransmitters, namely age, race, sex, diabetes, and hypertension had no effect on NO and H2S levels in COVID-19 patients. CONCLUSION: These observations provide the first insight into the role of NO and H2S in COVID-19 infection, where their low availability may be a result of reduced synthesis secondary to endotheliitis, or increased consumption from scavenging of reactive oxygen species.

Associations between calf, thigh, and arm circumference and cardiovascular and all-cause mortality in NHANES 1999-2004.

BACKGROUND AND AIMS: Prior studies have described an association between calf circumference and cardiovascular disorders. We evaluated the associations between calf, thigh, and arm circumference and cardiovascular and all-cause mortality. METHODS AND RESULTS: We performed a retrospective cohort study of 11,871 patients in the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to determine the association between calf circumference and cardiovascular and all-cause mortality using univariate and multivariate Cox proportional hazards. We additionally examined the association between thigh and arm circumference and mortality. In the multivariable Cox regression for the female stratum, each centimeter increase in calf circumference was associated with a hazard ratio of 0.88 (95% CI 0.84-0.92), and a hazard ratio of 0.90 (95% CI 0.85-0.95) for cardiovascular death. In the model with males, the hazard ratio for higher calf circumference was 0.92 (95% CI 0.88-0.96) for all-cause mortality and 0.94 (95% CI 0.89-0.99) for cardiovascular death. There was a statistically significant association between higher thigh circumference and lower risk of all-cause and cardiovascular mortality. Arm circumference was not similarly associated with mortality in the multivariate model. CONCLUSION: Calf and thigh circumference may provide important prognostic information regarding cardiovascular and all-cause mortality. Future prospective studies should examine the role of extremity circumference and cardiovascular events.