Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: A scoping review.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the accumulation of transthyretin (TTR) protein in the myocardium. The aim of this scoping review is to provide a descriptive summary of the clinical trials and observational studies that evaluated the clinical efficacy and safety of various agents used in ATTR-CM, with a goal of identifying the contemporary gaps in literature and to reveal future research opportunities. METHODS AND RESULTS: The search was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search using several databases for observational and clinical trials investigating the treatment modalities for ATTR-CM was undertaken. We extracted data including study characteristics, primary endpoints, and adverse events from each study. A total of 19 studies were included in our scoping review. 8 were clinical trials and 11 were observational analyses. The drugs evaluated included tafamadis, acoramidis, revusiran, TUDCA and doxycycline, diflusinil, inotersan, eplontersen, and patisiran. Tafamidis has shown to be efficacious in the management of ATTR-CM, particularly when initiated at earlier stages. RNA interference and antisense oligonucleotide drugs have shown promising impacts on quality of life. Additionally, this review identified gaps in the literature, particularly among long-term outcomes, comparative effectiveness, and the translation of research into economic contexts. CONCLUSIONS: Multiple pharmacological options are potential disease-modifying therapies for ATTR-CM. However, many gaps exist in the understanding of these various drug therapies, warranting further research. The future directions for management of ATTR-CM are promising in regard to improving prognostic implications.

Rural-urban stroke mortality gaps in the United States.

INTRODUCTION: Disparities in stroke outcomes, influenced by the use of systemic thrombolysis, endovascular therapies, and rehabilitation services, have been identified. Our study assesses these disparities in mortality after stroke between rural and urban areas across the United States (US). METHODS: We analyzed the CDC data on deaths attributed to cerebrovascular disease from 1999 to 2020. Data was categorized into rural and urban regions for comparative purposes. Age-adjusted mortality rates (AAMR) were computed using the direct method, allowing us to examine the ratios of rural to urban deaths for the cumulative population and among demographic subpopulations. Linear regression models were used to assess temporal changes in mortality ratios over the study period, yielding beta-coefficients (ß). RESULTS: There was a total of 628,309 stroke deaths in rural regions and 2,556,293 stroke deaths within urban regions. There were 1.13 rural deaths for each one urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.41). The rural-urban mortality ratio in Hispanic populations decreased from 1.32 rural deaths for each urban death per 100,000 population in 1999 to 0.85 in 2020 (ß = -0.011, ptrend < 0.001). For non-Hispanic populations, mortality remained stagnant with 1.12 rural deaths for each urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.543). Regionally, the Southern US exhibited the highest disparity with a urban-rural mortality ratio of 1.19, followed by the Northeast (1.13), Midwest (1.04), and West (1.01). CONCLUSIONS: Our findings depict marked disparities in stroke mortality between rural and urban regions, emphasizing the importance of targeted interventions to mitigate stroke-related disparities.

A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.

United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

BACKGROUND: US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD). GOALS: We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US). METHODS: We performed a cross-sectional analysis using the CDC repository. We queried death certificates to find ALD-related deaths from 1999 to 2020, which included demographic information such as gender, race/ethnicity, and area of residence. We estimated age-adjusted mortality rates (AAMR) per 100,000 population and compared the AAMRs across border and non-border regions. We also explored yearly mortality shifts using log-linear regression models and calculated the average annual percentage change (AAPC) using the Monte Carlo permutation test. RESULTS: In all, 11,779 ALD-related deaths were identified in border regions (AAMR 7.29) compared with 361,523 in non-border regions (AAMR 5.03). Border male (AAMR 11.21) and female (AAMR 3.77) populations were higher compared with non-border male (AAMR 7.42) and female (2.85) populations, respectively. Border non-Hispanic populations (AAMR 7.53) had higher mortality compared with non-border non-Hispanic populations (4.79), while both populations experienced increasing mortality shifts (AAPC +1.7, P<0.001 and +3.1, P<0.001, respectively). Border metropolitan (AAMR 7.35) and non-metropolitan (AAMR 6.76) regions had higher mortality rates compared with non-border metropolitan (AAMR 4.96) and non-metropolitan (AAMR 5.44) regions. CONCLUSIONS: Mortality related to ALD was higher in border regions compared with non-border regions. Border regions face significant health disparities when comparing ALD-related mortality.

Impact of Sarcoidosis on In-hospital Outcomes Among Patients with Atrial Fibrillation: A Nationwide Readmissions Database Analysis.

Sarcoidosis is a disease that involves multiple organs, including the cardiovascular system. While cardiac sarcoidosis has been increasingly recognized, the impact of sarcoidosis on atrial fibrillation (AF) is not well established. This study aimed to analyze the impact of sarcoidosis on in-hospital outcomes among patients who were admitted for a primary diagnosis of AF. Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged ≥18 years who were admitted for AF between 2017-2020. We stratified the cohort into two groups depending on the presence of sarcoidosis diagnosis. The in-hospital outcomes were assessed between the two groups via propensity score analysis. A total of 1031 (0.27%) AF patients with sarcoidosis and 387,380 (99.73%) AF patients without sarcoidosis were identified in our analysis. Our propensity score analysis of 1031 (50%) patients with AF and sarcoidosis and 1031 (50%) patients with AF but without sarcoidosis revealed comparable outcomes in early mortality (1.55% vs. 1.55%, P = 1.000), prolonged hospital stay (9.51% vs. 9.70%, P = .874), non-home discharge (7.95% vs. 9.89%, P = .108), and 30-day readmission (13.29% vs. 13.69%, P = .797) between the two groups. The cumulative cost of hospitalization was also similar in both groups ($12,632.25 vs. $12,532.63, P = .839). The in-hospital adverse event rates were comparable in both groups. Sarcoidosis is not a risk factor for poorer in-hospital outcomes following AF admission. These findings provide valuable insights into the effectiveness of the current guideline for AF management in patients with concomitant sarcoidosis and AF.

Influence of social vulnerability index on Medicare beneficiaries' expenditures upon discharge.

Medicare beneficiaries' healthcare spending varies across geographical regions, influenced by availability of medical resources and institutional efficiency. We aimed to evaluate whether social vulnerability influences healthcare costs among Medicare beneficiaries. Multivariable regression analyses were conducted to determine whether the social vulnerability index (SVI), released by the Centers for Disease Control and Prevention (CDC), was associated with average submitted covered charges, total payment amounts, or total covered days upon hospital discharge among Medicare beneficiaries. We used information from discharged Medicare beneficiaries from hospitals participating in the Inpatient Prospective Payment System. Covariate adjustment included demographic information consisting of age groups, race/ethnicity, and Hierarchical Condition Category risk score. The regressions were performed with weights proportioned to the number of discharges. Average submitted covered charges significantly correlated with SVI (ß = 0.50, p < 0.001) in the unadjusted model and remained significant in the covariates-adjusted model (ß = 0.25, p = 0.039). The SVI was not significantly associated with the total payment amounts (ß = -0.07, p = 0.238) or the total covered days (ß = 0.00, p = 0.953) in the adjusted model. Regional variations in Medicare beneficiaries' healthcare spending exist and are influenced by levels of social vulnerability. Further research is warranted to fully comprehend the impact of social determinants on healthcare costs.

Interpreting a Delayed Workup of Idiopathic Inflammatory Myopathy.

Idiopathic inflammatory myopathies are a widely heterogeneous group of muscle diseases and encompass multiple clinicopathologic entities. Our case presentation describes a 70-year-old male who presented with progressively worsening dyspnea, along with worsening proximal muscle weakness in the bilateral lower extremities. Extensive clinical evaluation revealed a creatine kinase level of 105 IU/L, severe and chronic widespread myopathy seen on electromyography (EMG), and asymmetric but widespread muscle atrophy with fibro-fatty replacement seen on ultrasonography. Muscle biopsy specimen from the left deltoid was suboptimal but demonstrated characteristics that could be consistent with several clinicopathologic diagnoses, including sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myositis (IMNM), antisynthetase syndrome (AS), and direct toxin-induced myopathy. Electron microscopy revealed tubulofilamentous inclusion associated with autophagic debris, finally rendering an accurate diagnosis. This case summary highlights the testing workflow required to diagnose a patient with an inflammatory myopathy and outlines the difficulty in establishing a diagnosis when the workup for an inflammatory myopathy is delayed and the muscle biopsy is suboptimal.

Trends in comorbid chronic kidney disease and atrial fibrillation-related cardiovascular mortality in the United States.

Background: The impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood. Methods: We conducted analyses of comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology. Results: Age-adjusted mortality rates (AAMR) per 100,000 increased from 0.39 in 1999 to 1.65 in 2020. Non-Hispanic populations (1.01) and nonmetropolitan areas (1.08) had higher AAMRs compared to Hispanic (0.62) and metropolitan (0.97) areas. Midwestern (1.11) and Western (1.13) US regions recorded the highest AAMRs. Conclusions: These findings highlight the need for interventions to address AF death disparities in patients with CKD.

Impact of social vulnerability on comorbid COVID-19 and acute myocardial infarction mortality in the United States.

The trajectory of several cardiovascular diseases (CVD), including acute myocardial infarction (AMI), has been adversely impacted by COVID-19, resulting in a worse prognosis. The Social Vulnerability Index (SVI) has been found to affect certain CVD outcomes. In this cross-sectional analysis, we investigated the association between the SVI and comorbid COVID-19 and AMI mortality using the CDC databases. The SVI percentile rankings were divided into four quartiles, and age-adjusted mortality rates were compared between the lowest and highest SVI quartiles. Univariable Poisson regression was utilized to calculate risk ratios. A total of 5779 excess deaths and 1.17 excess deaths per 100,000 person-years (risk ratio 1.62) related to comorbid COVID-19 and AMI were attributable to higher social vulnerability. This pattern was consistent across the majority of US subpopulations. Our findings offer crucial epidemiological insights into the influence of the SVI and underscore the necessity for targeted therapeutic interventions.

Ischemic heart disease mortality in individuals with inflammatory bowel disease: A nationwide analysis of disparities in the United States.

INTRODUCTION: Inflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US). METHODS: Mortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. RESULTS: Age-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08). CONCLUSION: Disparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

County-level variation in healthcare coverage and ischemic heart disease mortality.

BACKGROUND: Healthcare coverage has been shown to have implications in the prevalence of coronary artery disease. We explore the impact of lack of healthcare coverage on ischemic heart disease (IHD) mortality in the US. METHODS: We obtained county-level IHD mortality and healthcare coverage data from the CDC databases for a total of 3,119 US counties. The age-adjusted prevalence of current lack of health insurance among individuals aged 18 to 64 years were obtained for the years 2018 and 2019 and were placed into four quartiles. First (Q1) and fourth quartile (Q4) had the least and highest age-adjusted prevalence of adults without health insurance, respectively. IHD mortality rates, adjusted for age through the direct method, were obtained for the same years and compared among quartiles. Ordinary least squares (OLS) regression for each demographic variable was conducted with the quartiles as an ordinal predictor variable and the age-adjusted mortality rate as the outcome variable. RESULTS: We identified a total of 172,942 deaths related to ischemic heart disease between 2018 and 2019. Overall AAMR was higher in Q4 (92.79 [95% CI, 92.35-93.23]) compared to Q1 (83.14 [95% CI, 82.74-83.54]), accounting for 9.65 excess deaths per 100,000 person-years (slope = 3.47, p = 0.09). Mortality rates in Q4 for males (126.20 [95% CI, 125.42-126.98] and females (65.57 [95% CI, 65.08-66.05]) were higher compared to Q1 (115.72 [95% CI, 114.99-116.44] and 57.48 [95% CI, 57.04-57.91], respectively), accounting for 10.48 and 8.09 excess deaths per 100,000 person-years for males and females, respectively. Similar trends were seen among Hispanic and non-Hispanic populations. Northeastern, Southern, and Western regions had higher AAMR within Q4 compared to Q1, with higher prevalence of current lack of health insurance accounting for 49.2, 8.15, and 29.04 excess deaths per 100,000 person-years, respectively. CONCLUSION: A higher prevalence of adults without healthcare coverage may be associated with increased IHD mortality rates. Our results serve as a hypothesis-generating platform for future research in this area.

Mortality trends, disparities, and social vulnerability in cardiac arrest mortality in the young: A cross-sectional analysis.

BACKGROUND: Cardiac arrest (CA) is a leading cause of death in the United States (US). Social determinants of health may impact CA outcomes. We aimed to assess mortality trends, disparities, and the influence of the social vulnerability index (SVI) on CA outcomes in the young. METHODS: We conducted a cross-sectional analysis of age-adjusted mortality rates (AAMRs) related to CA in the United States from the Years 1999 to 2020 in individuals aged 35 years and younger. Data were obtained from death certificates and analyzed using log-linear regression models. We examined disparities in mortality rates based on demographic variables. We also explored the impact of the SVI on CA mortality. RESULTS: A total of 4792 CA deaths in the young were identified. Overall AAMR decreased from 0.20 in 1999 to 0.14 in 2020 with an average annual percentage change of -1.3% (p = .001). Black (AAMR: 0.30) and male populations (AAMR: 0.14) had higher AAMR compared with White (AAMR: 0.11) and female (AAMR: 0.11) populations, respectively. Nonmetropolitan (AAMR: 0.29) and Southern (AAMR: 0.26) regions were also impacted by higher AAMR compared with metropolitan (AAMR: 0.11) and other US census regions, respectively. A higher SVI was associated with greater mortality risks related to CA (risk ratio: 1.82 [95% CI, 1.77-1.87]). CONCLUSIONS: Our analysis of CA in the young revealed disparities based on demographics, with a decline in AAMR from 1999 to 2020. There is a correlation between a higher SVI and increased CA mortality risk, highlighting the importance of targeted interventions to address these disparities effectively.

Atrial fibrillation mortality trends in individuals with heart failure.

Atrial fibrillation (AF) frequently occurs concurrently with heart failure (HF). The two conditions can exacerbate each other, resulting in higher morbidity and mortality. In our analysis, we evaluated mortality trends related to AF in individuals with underlying HF. Cross-sectional analyses were performed using publicly available data from the Center for Disease Control and Prevention database to compare AF-related age-adjusted mortality rates across age, gender, racial/ethnic, and geographic subgroups. Mortality trends were evaluated by fitting log-linear regression models followed by calculation of the average annual percentage change (AAPC) using the Monte Carlo permutation test. We identified a total of 55,917 deaths within the United States from AF with comorbid HF between 1999 and 2020. Males, older adults, White populations, and non-metropolitan regions had higher age-adjusted mortality compared to females, younger adults, Black populations, and metropolitan regions, respectively. The AAPC among younger adults was significantly higher compared to older adults. Our results demonstrate existing disparities among age, gender, racial, and geographic subgroups related to AF mortality among individuals with comorbid HF. Although decreased overall mortality was observed within younger populations compared to older populations, the prominent AAPC seen in younger populations warrants further investigation. Detection of AF among younger adults with comorbid HF should prompt the intensification of preventative and treatment measures.