Coronary artery disease and heart failure: Late-breaking trials presented at American Heart Association scientific session 2023.

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure (HF). The dapagliflozin in patient with acute myocardial infarction (DAPA-MI) trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo, with no difference in cardiovascular outcomes. The MINT trial showed that in patients with acute MI and anemia (Hgb < 10 g/dL), a liberal transfusion goal (Hgb ≥ 10 g/dL) was not superior to a restrictive strategy (Hgb 7-8 g/dL) with respect to 30-day all-cause death and recurrent MI. The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy, percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure. The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist, placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year. The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥ 6 months after cardiac transplantation. Providing patients being treated for HF with reduced ejection fraction (HFrEF) with specific out-of-pocket (OOP) costs for multiple medication options at the time of the clinical encounter may reduce 'contingency planning' and increase the extent to which patients are taking the medications decided upon. The primary outcome, which was cost-informed decision-making, defined as the clinician or patient mentioning costs of HFrEF medication, occurred in 49% of encounters with the checklist only control group compared with 68% of encounters in the OOP cost group.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation.

In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity: Insights from national inpatient sample 2020.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular diseases independently of other risk factors. However, data on its effect on cardiovascular outcomes in coronavirus disease 2019 (COVID-19) hospitalizations with varied obesity levels is scarce. Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels. AIM: To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity. METHODS: COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease -10 CM codes in the 2020 National Inpatient Sample database. Overweight and Obesity Classes I, II, and III (body mass index 30-40) were compared. Major adverse cardiac and cerebrovascular events (MACCE) (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) were compared between groups. Multivariable regression analyses adjusted for sociodemographic, hospitalization features, and comorbidities. RESULTS: Our analysis comprised 13260 hospitalizations, 7.3% of which were overweight, 24.3% Class I, 24.1% Class II, and 44.3% Class III. Class III obesity includes younger patients, blacks, females, diabetics, and hypertensive patients. On multivariable logistic analysis, Class III obese patients had higher risks of MACCE, inpatient mortality, and respiratory failure than Class I obese patients. Class II obesity showed increased risks of MACCE, inpatient mortality, and respiratory failure than Class I, but not significantly. All obesity classes had non-significant risks of MACCE, inpatient mortality, and respiratory failure compared to the overweight group. CONCLUSION: Class III obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class I. Using the overweight group as the reference, unfavorable outcomes were not significantly different. Morbid obesity had a greater risk of MACCE regardless of the referent group (overweight or Class I obese) compared to overweight NAFLD patients admitted with COVID-19.

Impact of D-dimer on in-hospital mortality following aortic dissection: A systematic review and meta-analysis.

BACKGROUND: The utility of D-dimer (DD) as a biomarker for acute aortic dissection (AD) is recognized. Yet, its predictive value for in-hospital mortality remains uncertain and subject to conflicting evidence. AIM: To conduct a meta-analysis of AD-related in-hospital mortality (ADIM) with elevated DD levels. METHODS: We searched PubMed, Scopus, Embase, and Google Scholar for AD and ADIM literature through May 2022. Heterogeneity was assessed using I 2 statistics and effect size (hazard or odds ratio) analysis with random-effects models. Sample size, study type, and patients' mean age were used for subgroup analysis. The significance threshold was P < 0.05. RESULTS: Thirteen studies (3628 patients) were included in our study. The pooled prevalence of ADIM was 20% (95%CI: 15%-25%). Despite comparable demographic characteristics and comorbidities, elevated DD values were associated with higher ADIM risk (unadjusted effect size: 1.94, 95%CI: 1.34-2.8; adjusted effect size: 1.12, 95%CI: 1.05-1.19, P < 0.01). Studies involving patients with a mean age of < 60 years exhibited an increased mortality risk (effect size: 1.43, 95%CI: 1.23-1.67, P < 0.01), whereas no significant difference was observed in studies with a mean age > 60 years. Prospective and larger sample size studies (n > 250) demonstrated a heightened likelihood of ADIM associated with elevated DD levels (effect size: 2.57, 95%CI: 1.30-5.08, P < 0.01 vs effect size: 1.05, 95%CI: 1.00-1.11, P = 0.05, respectively). CONCLUSION: Our meta-analysis shows elevated DD increases in-hospital mortality risk in AD patients, highlighting the need for larger, prospective studies to improve risk prediction models.

STAT1 regulates neutrophil gelatinase B-associated lipocalin induction in influenza-induced myocarditis.

Influenza is a significant public health and economic threat around the world. Epidemiological studies have demonstrated a close association between influenza pandemics and cardiovascular mortality. Moreover, it has been shown that there is a decrease in cardiovascular mortality in high-risk patients following vaccination with the influenza vaccine. Here, we have investigated the role of anti-viral STAT1 signaling in influenza-induced myocarditis. Wild-type mice (C57BL/6) were infected with either influenza A/PR/8/34 or control, and cellular response and gene expression analysis from the heart samples were assessed 7 days later. The expression of interferon response genes STAT1, STAT2, Mx1, OASL2, ISG15, chemokines CCL2, CCL3, CXCL9 and CXCL10, and the frequency of neutrophils (CD45+CD11b+Ly6G+) and CD4+ T cells (CD45+CD4+) were all significantly increased in influenza-infected mice when compared to vehicle controls. These data suggest that influenza infection induces interferons, inflammatory chemokines, and cellular recruitment during influenza infection. We further investigated the role of STAT1 in influenza-induced myocarditis. The frequency of neutrophils and the levels of lipocalin 2 were significantly increased in STAT1-/- mice when compared to WT controls. Finally, we investigated the role of Lcn2 in viral-induced myocarditis. We found that in the absence of Lcn2, there was preserved cardiac function in Lcn2-/- mice when compared to WT controls. These data suggest that the absence of Lcn2 is cardioprotective during viral-induced myocarditis.

Key hypertension breakthroughs and emerging trends from the AHA's scientific sessions.

We aim to summarize selected late-breaking science on hypertension management strategies and disease presented at the 2023 American Heart Association (AHA) conference. The trials discussed below encompass stricter goals of blood pressure management and were expanded into different population groups from different countries with varied socioeconomic backgrounds and settings, collectively advancing our understanding of hypertension treatment and its impact on public health. We summarized the china rural health care project (CRHCP), a four-year study involving over 34,000 participants in rural China, emphasizing the potential of stricter blood pressure goals in lowering the incidence of all-cause dementia and cognitive impairment. Next, we explore the US-based CARDIA-SSBP study, which highlights the impact of dietary sodium on systolic blood pressure in middle-aged individuals. Through a randomized-order cross-over design, the study provides compelling evidence supporting the effectiveness of sodium reduction as a non-pharmacological approach to blood pressure control. The UK-based POP-HT trial offers critical insights into postpartum women with a history of hypertensive pregnancy. The trial emphasizes the benefits of self-monitoring and physician-optimized antihypertensive titration, showcasing significant blood pressure reductions in the intervention group. Furthermore, the KARDIA-1 study introduces us to Zilebesiran, an innovative RNA interference drug. This phase 2 study highlights its potential for achieving sustained blood pressure reductions and its favorable safety profile, marking a significant step forward in hypertension treatment. Lastly, we expand the practical application of the previously conducted landmark SPRINT trial, which showed cardiovascular benefit with intensive SBP control to less than 120 mm Hg in high-risk non-diabetic patients with hypertension compared with routine BP control to <140 mm Hg. The ESPRIT trial and the IMPACTS trial build upon the SPRINT trial, demonstrating the effects of intensive blood pressure lowering in Asian hypertensive patients and in 36 health care clinics in medically underserved states in the US: Louisiana and Mississippi. The IMPACTS trial and the "Hypertension Treatment in Nigeria Program" demonstrate the effectiveness of implementing comprehensive blood pressure control strategies in real-world settings. These studies highlight the feasibility and scalability of such interventions, especially in low-resource environments, and their potential to significantly improve public health outcomes.

Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection.

Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory "cytokine storm" is thought to play a role in influenza-induced lung pathogenesis. Empagliflozin is a drug primarily used to lower blood glucose in type II diabetes patients by inhibiting the sodium-glucose cotransporter-2 (SGLT-2) found in the proximal tubules in the kidneys. In this study, we have investigated the effects of empagliflozin on the pulmonary immune response to influenza infection. C57BL/6 mice (wild type) were infected with influenza A/PR/8/34 and treated with empagliflozin, and the disease outcomes were analyzed. Empagliflozin treatment decreased the expression of the inflammatory cytokines IL-1ß, IL-6, and CCL2; the percentage of inflammatory monocytes and inducible NO synthase-positive macrophages; and IFN response genes Stat1 and CXCL9 during influenza infection. Further, empagliflozin treatment decreases the expression of IL-6, CCL2, and CCL5 in RAW264.7 macrophages and bone marrow-derived macrophages. However, empagliflozin treatment increased influenza viral titer during infection. Despite fostering an increased viral burden, treatment with empagliflozin decreases the mortality in wild type and high fat diet-induced atherosclerotic LDLR-/- mice. Based on our findings, empagliflozin may have therapeutic implications for use in patients to prevent lung damage and acute respiratory illness.

In-hospital Outcomes of Aspiration Pneumonia Hospitalizations With Acute Heart Failure: A Nationwide Analysis.

Background and Objectives: There is a paucity of data regarding the impact of acute heart failure (AHF) on the outcomes of aspiration pneumonia (AP). Methods: Using National Inpatient Sample datasets (2016 to 2019), we identified admissions for AP with AHF vs. without AHF using relevant International Classification of Diseases, Tenth Revision codes. We compared the demographics, comorbidities, and outcomes between the two groups. Results: Out of the 121,097,410 weighted adult hospitalizations, 488,260 had AP, of which 13.25% (n=64,675) had AHF. The AHF cohort consisted predominantly of the elderly (mean age 80.4 vs. 71.1 years), females (47.8% vs. 42.2%), and whites (81.6% vs. 78.5%) than non-AHF cohort (all p<0.001). Complicated diabetes and hypertension, dyslipidemia, obesity, chronic pulmonary disease, and prior myocardial infarction were more frequent in AHF than in the non-AHF cohort. AP-AHF cohort had similar adjusted odds of all-cause mortality (adjusted odds ratio [AOR], 0.9; 95% confidence interval [CI], 0.78-1.03; p=0.122), acute respiratory failure (AOR, 1.0; 95% CI, 0.96-1.13; p=0.379), but higher adjusted odds of cardiogenic shock (AOR, 2.2; 95% CI, 1.30-3.64; p=0.003), and use of mechanical ventilation (MV) (AOR, 1.3; 95% CI, 1.17-1.56; p<0.001) compared to AP only cohort. AP-AHF cohort more frequently required longer durations of MV and hospital stays with a higher mean cost of the stay. Conclusions: Our study from a nationally representative database demonstrates an increased morbidity burden, worsened complications, and higher hospital resource utilization, although a similar risk of all-cause mortality in AP patients with AHF vs. no AHF.

Predicting Risk of Cardiac Arrest in Young Asian Americans: Insights from an Artificial Neural Network Analysis of the Nationwide Cohort.

We used the Artificial Neural Network (ANN) model to identify predictors of Sudden Cardiac Arrest (SCA) in a national cohort of young Asian patients in the United States. The National Inpatient Sample (2019) was used to identify young Asians (18-44-year-old) who were hospitalized with SCA. The neural network's predicted criteria for SCA were selected. After eliminating missing data, young Asians (n = 65,413) were randomly divided into training (n = 45,094) and testing (n = 19347) groups. Training data (70%) was used to calibrate ANN while testing data (30%) was utilized to assess the algorithm's accuracy. To determine ANN's performance in predicting SCA, we compared the frequency of incorrect prediction between training and testing data and measured the area under the Receiver Operating Curve (AUC). The 2019 young Asian cohort had 327,065 admissions (median age 32 years; 84.2% female), with SCA accounting for 0.21%. The exact rate of error in predictions vs. tests was shown by training data (0.2% vs 0.2%). In descending order, the normalized importance of predictors to accurately predict SCA in young adults included prior history of cardiac arrest, sex, age, diabetes, anxiety disorders, prior coronary artery bypass grafting, hypertension, congenital heart disease, income, peripheral vascular disease, and cancer. The AUC was 0.821, indicating an excellent ANN model for SCA prediction. Our ANN models performed excellently in revealing the order of important predictors of SCA in young Asian American patients. These findings could have a considerable impact on clinical practice to develop risk prediction models to improve the survival outcome in high-risk patients.

Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne virus endemic to a vast geographical area spanning from Africa to the shores of the Mediterranean Sea and north to the Balkans. The infection carries a high case fatality rate, which prompts the development of new treatment and prophylactic measures. This review explores the different treatment and prophylactic measures found in recent literature. For this purpose, we used Medical Subject Headings (MeSH) as well as PubMed advanced search. The inclusion criteria included full-text studies conducted on humans and in the English language. We found that plasma exchange was associated with a decrease in mortality rates. Similarly, the use of immunoglobulins proved effective in decreasing the severity and mortality risk. Ribavirin use was determined as a post-exposure prophylaxis drug with no statistically significant difference in oral or intravenous routes of administration. More studies should be conducted on CCHF as the number of outbreaks and endemic areas seem to be on the rise. For the time being, supportive therapy along with adjuvant antivirals appear to be the main course of management of CCHF. However, the need for definitive therapeutic agents and guidelines is warranted.