tbuckley/cabot-search huggingface dataset:
Abstract 4125026: Effect Of Pressure-Controlled Intermittent Coronary Sinus Occlusion On Echocardiographic Features In Patients With STEMI: A Systematic Review And Meta-Analysis With Trial Squential Analysis
Authors: Adel Mouffokes, Youssef Soliman, Ahmed K. Awad, Basel Abdelazeem
Journal: Circulation (2024)

Introduction: Primary percutaneous coronary intervention (pPCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, pPCI is still associated with poorer outcomes particularly left ventricular dysfunction. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) is a novel therapeutic approach proposed to improve myocardial perfusion and its function in patients with STEMI. Therefore, we performed this meta-analysis to evaluate the effects of PiCSO on left ventricular function in STEMI patients. Methods: We performed a comprehensive search on PubMed, Scopus, and Web of Science. Our primary endpoints were left ventricular ejection fraction (LVEF%), left ventricular end diastolic volume (LVEDV), and left ventricular end systolic volume (LVESV). The secondary endpoint was infarct size. We performed Trial Squential Analysis (TSA), and we pooled our continuous data as mean difference (MD) and 95% confidence interval (CI) in the fixed effects model. Results: A total of four studies, with 335 patients, were included in the analysis. Our pooled analysis showed that PiCSO significantly increased LVEF% compared to pPCI (MD = 3.52, 95% CI [1.05, 6.00], P= 0.005). However, there was no significant difference between the two groups in terms of LVESV and LVEDV (MD = -1.1, 95% CI [-9.28, 7.08], P= 0.79; MD = -1.69, 95% CI [-9.14, 5.76], P= 0.66, respectively). With regard to infarct size, a significant reduction was observed in PiCSO group compared to pPCI (MD = -4.26, 95% CI [-7.39, -1.14], P= 0.007). The TSA curve crossed the conventional boundary for statistical significance, indicating that the available evidence reach the predetermined threshold. Conclusions: Our meta-analysis revealed that PiCSO could mitigate left ventricular dysfunction in STEMI patients by improving LVEF% and reducing infarct size. Nevertheless, PiCSO failed to show a positive impact on LVESV and LVEDV. Further large-scale studies are warranted to draw a definitive conclusion.
Abstract 4133170: Insulin resistance triggers histamine release from endothelial cells, which disrupts endothelial barrier function and causes vasoconstriction.
Authors: Masuma Akter Brishti, M Leo
Journal: Circulation (2024)

Diabetic vascular dysfunction is a serious health concern, affecting ~38 million people in the USA, according to the 2020 CDC-National Diabetes Statistics Reports. Type 2 diabetes (T2D) causes several vascular changes leading to major clinical consequences such as stroke and ~3-fold elevated risk of cardiovascular diseases (CVD) and the underlying causes of vascular dysfunction in T2D are complex. The anatomical position of endothelial cells (ECs) between the circulating blood and vessel walls makes them the first to encounter and respond to cellular stressors in the bloodstream. Here, we investigated the role of long-term increases in plasma histamine levels as observed in T2D and its effects on ECs and vascular contractility. The high-fat diet-low-dose streptozotocin protocol induced T2D in C57BL/6J mice. Endothelial cell function was analyzed using Western blotting, in vitro blood-brain barrier assays, histamine measurements, immunofluorescence, and pressurized artery myography. In our T2D model, EC-mediated histamine synthesis occurred after the onset of IR. A spike in plasma histamine levels was observed immediately following the onset of insulin resistance, followed by a brief plateau. A second spike in plasma histamine levels was noted four weeks later. In isolated control ECs, the addition of external histamine showed a concentration-dependent increase in histidine decarboxylase expression, and cellular histamine levels were observed, which was inhibited by the H2R blocker, famotidine. The tight junction marker, JAM-A (CD321), expression in diabetic cerebral arteries was ~42% less compared to the non-diabetic controls. Transendothelial Electrical Resistance testing showed a ~2-fold higher permeability with diabetic ECs than controls. Pressure myography on isolated cerebral arteries indicated that external histamine passed through the lumen of arteries from T2D mice 4 weeks after onset of IR constricted whereas control arteries dilated. Additionally, T2D mice cerebral artery myogenic tone at 60 mmHg was 70% greater compared to control arteries. These data indicate that the onset of IR triggers an increase in circulating histamine levels, which in turn stimulates histamine synthesis and release from endothelial cells leading to the loss of endothelial barrier function, blood-brain barrier leakage, and vasoconstriction. We are currently investigating the molecular pathways that precede the increase in circulating histamine levels during T2D.
Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters
Authors: Satomi Kagota, Kana Maruyama-Fumoto, Kazumasa Shinozuka
Journal: Circulation (2024)

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.
Abstract 4125263: Influence of sexual orientation-related nondiscrimination laws on 30-year CVD risk among sexual minority and heterosexual adults
Authors: Yashika Sharma, Morgan Philbin, Bethany Everett, Caleigh Dwyer, Anisha Bhargava, Danny Doan, Lauren Beach, Billy Caceres
Journal: Circulation (2024)

Introduction: Discriminatory policies are associated with worse mental health and substance use outcomes among sexual minority adults. Despite a higher risk of cardiovascular disease (CVD) than heterosexual adults, there is limited evidence on structural determinants of cardiovascular health among sexual minority adults. Therefore, we examined whether changes in sexual orientation-related nondiscrimination laws were associated with 30-year CVD risk among sexual minority and heterosexual adults. Hypothesis: We hypothesized that changes in sexual orientation-related nondiscrimination laws would be more strongly associated with 30-year CVD risk among sexual minority adults relative to exclusively heterosexual adults. Methods: We used longitudinal data from Waves III (2001-2002), IV (2008-2009), and V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health. We assessed changes in four state-level sexual orientation-related nondiscrimination laws (i.e., employment discrimination, same-sex marriage, hate crime statutes, and same-sex adoption) between Waves III and IV. Changes in sexual orientation-related nondiscrimination laws were categorized as unchanged (reference), improved, or worsened. We assessed 30-year CVD risk using the Framingham Risk Score at Wave V. We ran sex-stratified linear regression models adjusted for demographic factors to examine whether the association between change in nondiscrimination laws with 30-year CVD risk was moderated by sexual orientation (i.e., exclusively heterosexual, mostly heterosexual, homosexual/bisexual). Results: The sample included 3,827 participants with a mean age of 28.7 (±1.75) years, of whom 83.1% identified as exclusively heterosexual, 51% as female, and 15% as Black. Compared to heterosexual participants of the same sex, an improvement in nondiscrimination laws was associated with lower 30-year CVD risk among mostly heterosexual women (B -4.57, 95% CI = -8.06, -1.08) and homosexual/bisexual men (B -10.91, 95% CI = -19.33, -2.49). In contrast, compared to exclusively heterosexual women, a worsening of nondiscrimination laws was associated with higher 30-year CVD risk among homosexual/bisexual women (B 5.26, 95% CI = 0.30, 10.21). No differences were found between mostly heterosexual and exclusively heterosexual men. Conclusions: Findings suggest that efforts to enhance policies prohibiting sexual orientation-related discrimination may significantly reduce CVD risk among sexual minority adults.
Abstract 4125300: Prognostic Value of NT-proBNP and the H <sub>2</sub> FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial
Authors: Makoto Hibino, Subodh Verma, Adrian Quan, Pankaj Puar, Farhad Akhavein, Chao-Hung Wang, Andrew Yan, Kim Connelly, David Mazer, Hwee Teoh
Journal: Circulation (2024)

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP &lt; and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.
Abstract 4132820: S-nitrosylation of cardiac Cx43 hemichannels at Cys271 promotes arrhythmogenicity and myocardial injury upon cardiac stress in Duchenne Muscular Dystrophy
Authors: Manuel Munoz Camus, Jonathan Quan, Thao Nguyen, Janet Nuno, Adrian Sheehy, Pablo Gaete, Mauricio Lillo, Jorge Contreras
Journal: Circulation (2024)

Connexin-43 (Cx43) plays a critical role in the propagation of action potentials among cardiomyocytes and proper cardiac contractility. In healthy cardiomyocytes, Cx43 is located at the intercalated disk; however, Cx43 remodeling is observed in cardiac pathologies and is linked with arrhythmogenesis and sudden cardiac death. Utilizing a mouse model of Duchenne muscular dystrophy (DMD mdx ), we have previously demonstrated that cardiac Cx43 is laterally localized, forming undocked hemichannels that activate via S-nitrosylation in response to isoproterenol-evoked cardiac stress. This activation leads to the disruption of cardiac membrane permeability, triggered activity, and deadly arrhythmogenic behaviors. To establish the direct role of S-nitrosylated Cx43 in DMD cardiomyopathy, we developed a specific knock-in mouse line in which the single Cx43 site for S-nitrosylation, cysteine 271 (Cys271), was substituted with a serine (C271S +/- ). Here, we developed a DMD mdx :C271S +/- line (4–6 months old), exhibiting reduced levels of S-nitrosylated Cx43 after crossing DMDmdx mice and C271S +/- mouse lines to assess the effect of β-adrenergic stimulation-induced cardiac stress and heart dysfunction. We show that cardiac Cx43 remodeling was not prevented in DMD mdx :C271S +/- , similar to what was shown in DMD mdx mice via immunofluorescence analysis. In addition, DMD mdx mice displayed an increased number of deadly arrhythmogenic events, increased Ca 2+ signaling, and prolonged action potentials in Langendorff-perfused whole hearts via optical mapping, compared to wild-type and DMD mdx :C271S +/- mice. Similarly, isoproterenol treatment evoked severe myocardial injury, increased levels of plasmatic cardiac troponin I (cTnI), and 40% mortality in DMD mdx mice. Notably, DMD mdx :C271S +/- mice, similar to DMD mdx mice treated with the Cx43 hemichannel blocker Gap19, exhibited cardioprotection compared to the cardiac dysfunction observed in DMD mdx mice. Therefore, these findings strongly suggest that S-nitrosylation of Cx43 proteins at site Cys271 represents a fundamental NO-mediated mechanism involved in the induction of arrhythmias and myocardial injury in DMD mdx after β-adrenergic stress.
Abstract 4125533: Demographic Trends and Disparities in Mortality Related to Coexisting Heart Failure and Diabetes Mellitus Among Older Adults in the United States: A Large Database Analysis from 1999 to 2020
Authors: Aman Goyal, Humza Saeed, Abdullah ., Irum Naeem, Amna Zafar, Bilal Ahmad, Taimur Islam, Syed Saaid Rizvi, Nikita Kumari, Syed Ghazi Ali Kirmani, Fatima Mansoor, Amir Hassan, Adarsh Raja, Kamna Bansal
Journal: Circulation (2024)

Background: In the United States, over 38 million people have diabetes mellitus (DM) and more than 6 million have heart failure (HF). DM and HF often coexist, and each condition independently increases the likelihood of developing the other. Approximately 40% of individuals with HF also have DM, and this prevalence is even higher among older adults and hospitalized patients. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends associated with their coexistence has not been thoroughly explored. Methods: This study analyzed death certificates from the CDC WONDER database, specifically focusing on mortality caused by the simultaneous presence of HF and DM among individuals aged 75 years and older. The data covers the period from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, and race/ethnicity. Results: Between 1999 and 2020, a total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with an initial increase from 1999 to 2005 (APC: 0.80; 95% CI: -0.17 to 2.94), a significant decline from 2005 to 2011 (APC: -2.82; 95% confidence interval (CI): -5.47 to – 1.71), a subsequent increase from 2011 to 2018 (APC: 0.61; 95% CI: -0.59 to 2.18), and finally a steep increase from 2018 to 2020 (APC: 11.30; 95% CI: 6.98 to 14.11). Gender-based analysis revealed that older men had consistently higher AAMRs than older women (Men: 185; 95% CI: 184.3 to 185.6; vs Women: 135.4; 95% CI: 135 to 135.8). Furthermore, we found that AAMRs were the highest among non-Hispanic American Indian or Alaska natives (214.4; 95% CI: 207.5 to 221.4) followed by non-Hispanic African Americans (179.9; 95% CI: 178.5 to 181.4), Hispanics (159.5; 95% CI: 158 to 161.1), non-Hispanic White (152.9; 95% CI: 152.5 to 153.3), and non-Hispanic Asian or Pacific Islander populations (104.1; 95% CI 102.4 to 105.8) (Figure 1). Conclusion: The mortality rate due to coexisting HF and DM has increased in the elderly population over the past decade. Males and non-Hispanic American Indians or Alaskan Natives had the highest AAMRs in our study.
Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Arshama Dehghan, Katja Bartholdy, Fernando Giugni, Brian Claggett, Ihab Hajjar, Thomas Mosley, Priya Palta, Amil Shah
Journal: Circulation (2024)

Background: Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function. Objective: Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life. Methods: Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score. Results: Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p&lt;0.05; Table). Conclusion: Subclinical LV remodeling and dysfunction is associated with greater declines in cognitive function over 5 years in late life. Differential associations were observed by cognitive domains, with executive function decline most uniformly associated with impairments in cardiac structure/function.
Abstract 4125691: A machine learning approach to examining the associations of minority stressors and physical activity among sexual and gender minority adults
Authors: David Lopez Veneros, Ipek Ensari, Riya Bhilegaonkar, Yashika Sharma, Billy Caceres
Journal: Circulation (2024)

Introduction: Physical activity (PA) is an important modifiable factor for cardiovascular disease (CVD). Sexual and gender minority (SGM; e.g., lesbian/gay, bisexual, transgender) adults face higher risks of inadequate PA and CVD due to increased exposure to minority stressors, such as experienced and anticipated discrimination, which may influence SGM adults’ willingness to engage in PA. To our knowledge, researchers have not investigated the impact of minority stressors on objectively-measured PA among SGM adults. Goal: Using k-means clustering, we sought to identify whether clusters characterized by greater exposure to minority stressors were associated with lower moderate and vigorous PA (MVPA) and higher sedentary behavior among SGM adults. Methods: This daily diary study included an online sample of SGM adults living in the United States. Participants completed daily surveys about personally experienced discrimination and anticipated discrimination (i.e., expectation of experiencing discrimination) and wore wrist accelerometers for 28 days to objectively measure PA. We used k-means clustering to identify clusters based on reports of experienced and anticipated discrimination. We first determined the optimal number of clusters using established partition criteria. Next, we ran linear regression models (adjusted for demographic factors) to examine the associations of minority stress clusters with MVPA and sedentary time per week. Results: Among 42 SGM adults (mean age 27.0±7.7 years) with 1133 person-days of accelerometry data (~3% missing data), we identified four minority stress clusters: low anticipated/low experienced (LALE; reference group); low anticipated/high experienced (LAHE); high anticipated/low experienced (HALE); and high anticipated/high experienced discrimination (HAHE). Participants in the HALE cluster (n=12) engaged in 202 fewer minutes of MVPA than those in the LALE cluster (n=7). Participants in the LAHE cluster (n=10) had 123 fewer minutes of vigorous PA than those in the LALE cluster. No differences were identified for sedentary time. Conclusions: This is the first study to examine the association of minority stressors with objective PA among SGM adults. Participants in the HALE and LAHE clusters engaged in significantly lower PA than those with low levels of both experienced and anticipated discrimination. Findings underscore the importance of assessing minority stressors and the need for interventions to improve PA among SGM adults.