tbuckley/cabot-search huggingface dataset:
Abstract 4137309: Superior Ventricular Longitudinal Strain Is Linked To Metabolic Adaptations, Protective Ventricular Remodeling Among Older Women And Clinical Outcomes.
Authors: JIE JUN WONG, Shuang Leng, XIAODAN ZHAO, Glades Tan, Hongzhou Zhang, Jean Paul Kovalik, Fei Gao, Hai Ning Wee, Kee Voon Chua, Jianhong Ching, Ru Tan, Liang Zhong, Angela Koh
Journal: Circulation (2024)

Background: Superior left ventricular (LV) systolic function among older women over men has been linked to differences in aging-related ventricular remodeling. Global longitudinal strain (LVGLS) is particularly susceptible to early aging perturbations and may precede systolic failure. Combining cardiovascular magnetic resonance (CMR) with metabolomics, we investigated LVGLS in parallel with markers of myocardial biosynthesis and metabolism pathways to explore the mechanisms and sex dimorphisms of cardiac aging. Methods: Community adults without cardiovascular disease (CVD) underwent serum metabolomics profiling and simultaneous CMR. Prospective clinical outcomes were tracked from 2014 to 2021. Multiple logistic regression adjusted for significant baseline variables. Results: Among 202 participants (46% women, 70.2±8.8 years), participants with better LVGLS were characterized by smaller LV chambers (LVESVi 30.0±14.2 vs 22.0±5.6ml/m 2 , adj. p &lt;0.001; LVEDVi 70.9±19.9 vs 64.0±10.2ml/m 2 , p=0.001 adj. p=0.054) and mass (LVMi 51.5±14.5 vs 43.9±8.8g/m 2 , adj. p=0.008) accompanied by lower levels of several long-chain acylcarnitines species (C12:2-OH/C10:2-DC, C12:1-OH, C12-OH/C10-DC, C14, C16:3-OH/C14:3-DC) independent of sex, diastolic blood pressure, smoking history, and body habitus. Compared to men of similar age, women had superior LVGLS (-21.9±2.6 vs -20.1±2.8%, adj. p=0.024) in tandem with smaller ventricles and less hypertrophy despite similar adjusted LVEF. Higher anaplerotic (methionine, arginine) and proteogenic (phenylalanine, tyrosine) amino acids (AA), together with lower acylcarnitines, distinguished women with better over poorer LVGLS while no AA differences were observed among men. During follow-up, poorer baseline LVGLS was associated with incident composite mortality and hospitalizations (OR=1.12 95%CI 1.01-1.24, p=0.026 adj. p=0.049). Conclusion: Preserved ventricular systolic function among older women was linked to superior LVGLS and favorable remodeling than men. Better LVGLS was accompanied by biomarkers of better mitochondrial oxidation, anaplerosis, and proteogenesis, suggesting enhanced myocardial fuel energetics and biosynthesis with better strain. LVGLS represents a promising quantifiable marker of early systolic aging among older adults without CVD linked to prospective clinical outcomes. Biological insights into the aging-adaptive mechanisms of strain conservation may reveal targets in preventing aging susceptibilities to myocardial dysfunction.
Abstract 4137339: Application of PLGA-PEG-PLGA Thermosensitive Hydrogel Loaded with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Ginsenoside Rb3 in the Treatment of Acute Myocardial Infarction
Authors: Kun Xiang, Zilong Zheng, Yichen Li, Weijie Tang, Wangping Chen, Jinfu Yang, Chengming Fan
Journal: Circulation (2024)

Background: Ginsenoside Rb3 (GSRb3) is a traditional Chinese medicine monomer. We aim to investigate the effects of GSRb3 on the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the reparative effects of PLGA-PEG-PLGA thermosensitive hydrogel loaded with hiPSC-CMs and GSRb3 (NP GSRb3 @Gel+iCM) on myocardial infarction (MI). Methods: 1. Western Blot, RT-qPCR, cell immunofluorescence staining, and CCK-8 assays were employed to assess the proliferative effects of different concentrations of GSRb3 on neonatal mouse primary cardiomyocytes (NCMs) and hiPSC-CMs. 2. Transcriptomic gene sequencing technology was utilized to investigate the mRNA expression changes of hiPSC-CMs induced by GSRb3; The NP GSRb3 @Gel+iCM was injected into the left ventricular myocardium of the MI mice; the same volume injections of hiPSC-CMs (iCM group) and PLGA-PEG-PLGA thermosensitive hydrogel loaded with GSRb3 (NP GSRb3 @Gel group) served as control; Additionally, MI model group without additional treatment and sham group were established. 3. At 4 weeks post-MI, echocardiography, Sirius Red/Fast Green staining and immunofluorescence staining were utilized to evaluate the heart function, infarction size and survival rate of transplanted hiPSC-CMs. Results: GSRb3 inhibit the apoptosis of NCMs while promote proliferation of NCMs and hiPSC-CMs significantly. After 4 weeks of treatment, the engraftment rate of hiPSC-CMs in NP GSRb3 @Gel+iCM group (36.7%) was 4.8 times that of iCM group (7.7%); Compared to the MI group, NP GSRb3 @Gel group and iCM group, NP GSRb3 @Gel+iCM group showed significant improvement in cardiac function; The myocardial repair effect in NP GSRb3 @Gel+iCM group was significantly superior to NP GSRb3 @Gel group and iCM group, with a 47% reduction in infarct size compared to MI group, and further reduction in left ventricular anterior wall thickness compared to NP GSRb3 @Gel group and iCM group. Conclusion: GSRb3 promotes the proliferation of hiPSC-CMs both in vitro and in vivo. NP GSRb3 @Gel+iCM significantly increase the engraftment of hiPSC-CMs, promote angiogenesis, reduce infarction size, inhibit left ventricular remodeling and improve cardiac function.
Abstract 4137804: Associations between falls and other serious adverse events and antihypertensive medication in individuals with dementia: An observational cohort study
Authors: Takeshi Fujiwara, Constantinos Koshiaris, Ting Cai, Ariel Wang, Joseph Lee, Sarah Lay-Flurrie, Amitava Banerjee, Andrew Clegg, Rupert Payne, Subhashisa Swain, Margaret Ogden, Satoshi Hoshide, Kazuomi Kario, Richard Hobbs, Richard McManus, James Sheppard
Journal: Circulation (2024)

Background: The balance of benefits and risks associated with lowering blood pressure levels in individuals with dementia remains controversial with a lack of evidence for possible harms associated with antihypertensive treatment (AHT). Objectives: We examined the association between AHT and serious adverse events (SAEs) in individuals with dementia compared to those without. Methods: This was a retrospective analysis using nationally representative, UK general practice population between 1998 and 2018, using data from electronic health records (Clinical Practice Research Datalink, GOLD). Individuals included were age ≥40 years and not previously prescribed AHT. Diagnosis of dementia was based on standardised clinical codes. The primary outcome was the first hospitalisation or death from a fall within 10 years of the follow-up period. Secondary outcomes were first hospitalisation or death from hypotension, syncope, and fracture. Cox regression analyses, adjusted for propensity score were used to assess the risk of SAEs. Results: In a population of 1,219,732 individuals, 23,510 had dementia. Antihypertensive medications were newly prescribed in 4,062/23,510 (17.3%) individuals with dementia and 142,385/1,196,222 (11.9%) individuals without dementia in the 12 months exposure period. In individuals with dementia, AHTs were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08, 1.22), hypotension (aHR 1.51, 95%CI 1.29, 1.78), syncope (aHR 1.34, 95%CI 1.11, 1.61), but not fracture (aHR 1.05, 95%CI 0.96, 1.15). In individuals without dementia, the association between AHT and SAEs was similar, with an increased risk of hospitalisation or death from falls (aHR 1.07, 95%CI 1.05, 1.10). However, absolute risk of falls with AHT per 10,000 individuals per year was significantly higher in individuals with dementia (47, 95%CI 26, 70) compared to those without (14, 95%CI 10, 18). The absolute risks of hypotension and syncope with AHT were also higher in the individuals with dementia compared to those without. Conclusions: AHT was associated with increased risk of SAEs in individuals with and without dementia, however, the absolute risk of harm from falls was more than double in individuals with dementia. Clinicians, patients, and their carers should consider these risks before starting new antihypertensive medications, particularly in the context of dementia, although they remain small.
Abstract 4137833: The plasma cell-free transcriptome non-invasively profiles the immune response and myocardial damage in immune checkpoint inhibitor-induced myocarditis.
Authors: Alireza Raissadati, Xuanyu Zhou, Harrison Chou, Yuhsin Huang, Arturo Hernandez, Sharon Loa, Anne Xu, Yin Sun, Han Zhu, Sean Wu
Journal: Circulation (2024)

Introduction: Immune checkpoint inhibitor-induced myocarditis (ICI-m) is a severe complication of cancer immunotherapy, marked by cardiac inflammation. Despite its high mortality rate, diagnosing ICI-m remains challenging due to the lack of sensitive and non-invasive diagnostic modalities. Plasma cell-free mRNA (cf-mRNA) has recently been highlighted as a promising tool for non-invasive tissue profiling. Hypothesis: The plasma cf-mRNA profile contains disease-specific immune and tissue transcriptomic signatures of ICI-m that can be leveraged for disease-specific precision diagnostics. Aims: To establish and validate a novel cf-mRNA bench and bioinformatic pipeline for noninvasive profiling of the immune and tissue landscape of patients with ICI-m. Methods: We isolated, DNase-treated, and sequenced bulk cfRNA from frozen plasma of patients with ICI-treated cancer patients with no autoimmunity (group A, n=5), extracardiac autoimmunity (group B, n=7), and ICI-m with or without extracardiac autoimmunity (group C, n=10). Publicly available healthy control cfRNA was downloaded (n=30) as external controls. We used cell type-specific gene panels curated from single-cell RNA-sequencing datasets of circulating immune cells and cardiac cells for cellular deconvolution of the cf-mRNA. Signature scores of the sum of the counts of each cell type-specific gene were used to compare cell type contributions between patient groups. Results: Cancer and inflammatory gene pathways were significantly enriched in the cf-mRNA of all ICI-treated cancer patients. Cardiac pathways and conduction genes were significantly enriched in group C vs. A and B patients. Signature scores of Temra CD8+ T cells and cardiomyocytes, and gene expression of CCL5 and MYH6 were elevated in group C patients. Our custom ICI-m classifier containing 3 cardiac- and 3 immune cell-specific genes differentiated group C from A (AUC 0.903, 95% CI 0.858-0.903) and B patients (AUC 0.983, 95% CI 0.970-0.983) effectively, outperforming a diagnostic classifier obtained from unsupervised feature selection from all differentially expressed genes. Conclusions: Using our novel plasma cf-mRNA platform, we developed a diagnostic classifier that captures the disease-specific immune and tissue transcriptomic signatures of ICI-m, highlighting the advantages of this disease-specific approach over conventional biomarker discovery, and demonstrating the broader implications of the platform for the field of precision diagnostics.
Abstract 4134949: Effect of anakinra in patients with ST-elevation myocardial infarction according to the renal function
Authors: Michele Golino, Marco Giuseppe Del Buono, Juan Ignacio Damonte, juan guido chiabrando, Martin Denicolai, Giuliana Corna, Francesco Moroni, Georgia Thomas, Cory Trankle, Leo Buckley, George Wohlford, Jeremy Turlington, ROSHANAK MARKLEY, Benjamin Van Tassell, Antonio Abbate
Journal: Circulation (2024)

Introduction: Interleukin(IL)-1 blockade with anakinra dampens the inflammatory response and prevents heart failure (HF) events in patients with ST-elevation myocardial infarction (STEMI). The efficacy of anakinra according to the baseline renal function in STEMI has not been addressed. Hypothesis: The efficacy of anakinra is independent of the baseline renal function. Aim: To determine the effect of anakinra according to the baseline renal function in patients with STEMI. Methods: We pooled patients with STEMI from 3 double-blind randomized clinical trials. Patients with estimated glomerular filtration rate (eGFR) &lt;15 mL/min/1.73m2 were excluded. We divided the cohort based on the median baseline eGFR using the modified 2021 CKD-EPI equation (≥ or &lt; 86 mL/min/1.73m2). We analyzed the area-under-the-curve for C-reactive protein (AUC-CRP) at 14 days, and the incidence of the composite outcome of all-cause death or new-onset HF at 1 year using the Log-rank test. We also evaluated the creatinine changes at 48-72 hours after percutaneous coronary intervention (PCI). Results: We analyzed 139 patients, 110 (79%) males, 52 (37%) Black or African-American, with a median age of 56 [49–63] years. The AUC-CRP at 14 days was significantly higher in patients receiving placebo vs. anakinra both in those with eGFR &lt;86 mL/min/1.73m2 (250.5[131.4-512.0] vs. 66.4[42.3-126.5] mg●day/L, p&lt;0.001) and those with eGFR ≥86 mL/min/1.73m2 (214.2[113.6-303.4] vs. 86.4[35.9-194.3] mg●day/L, p&lt;0.01). Anakinra significantly reduced the composite outcome of all-cause death or new-onset HF in patients with baseline eGFR &lt;86 mL/min/1.73m2 (4/41 [9.8%] vs. 9/27 [33.3%], Log-rank p=0.024) as well as in patients with baseline eGFR ≥86 mL/min/1.73m2 (3/43 [6.9%] vs. 7/28 [25%], Log-rank p=0.038)(p=0.97 for interaction)(Figure). No differences in creatinine changes 48-72 hours after PCI were observed (0.01 [-0.10 to 0.15] mg/dL in anakinra vs. 0.01[-0.08 to 0.14] mg/dL in placebo; p=0.80). Conclusion: In a cohort of patients with STEMI and mainly preserved or mildly reduced renal function, IL-1 blockade with anakinra blunts the acute inflammatory response and prevents all-cause death or new-onset HF at 1 year independent of baseline renal function.
Abstract 4134744: Trends and Disparities in Mortality Among Patients with Hypertensive Heart Disease and Congestive Heart Failure in the United States from 1999 to 2020
Authors: Aman Goyal, Humza Saeed, Surabhi Maheshwari, Abdullah ., Hritvik Jain, Urooj Shamim, Kamna Bansal
Journal: Circulation (2024)

Background: Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases. Methods: This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status. Results: Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1). Conclusions: Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.
Abstract 4134622: Hyperglycemia Induces Heterotaxy Syndrome by Lowering Intracellular pH
Authors: Ryohei Matsuoka, Keiko Kitajima, Shouichi Ohga, Chikara Meno
Journal: Circulation (2024)

Background: Pregestational diabetes is an established risk factor for congenital heart disease (CHD), including heterotaxy syndrome, which results from abnormal left-right (L-R) axis. However, the specific mechanism by which hyperglycemia disturbs the L-R axis still remains unsolved. In addition, it is unknown how a variety of heterotaxy is provoked by pregestational diabetes. Methods: We conducted whole-mount in situ hybridization, reporter analysis and RNA-seq in mouse embryos of streptozotocin-induced diabetic dams and Wnt3a –/– embryos. Additionally, the effect of high-glucose conditions on intracellular pH (pH i ) was investigated. We also examined the influence of maternal vitamin A intake on L-R axis formation in embryos of diabetic dams. Results: We observed various patterns of Pitx2 expression in embryos of diabetic dams, indicating disrupted L-R axis. The initial step of L-R axis formation was impaired, with Nodal expression, which induces Nodal - Pitx2 cascade in the lateral plate mesoderm, being regressed in the node. Consistent with the resemblance to the phenotype of Wnt3a –/– embryos, canonical Wnt signaling was downregulated in embryos of diabetic dams. As the RNA-seq analysis suggested dysregulation of glycolysis, we assessed pH i to find that hyperglycemia lowers pH i in the primitive streak, leading to the regression of Nodal expression in the node. Furthermore, maternal vitamin A intake was found to increase the incidence and diversity of L-R axis defects, likely as a result of dysregulation of retinoic acid metabolism apparent in embryos of diabetic dams and Wnt3a –/– embryos. Conclusions: Hyperglycemia downregulates canonical Wnt signaling by lowering pH i , which not only impairs L-R axis formation but also dysregulates retinoid metabolism. Consequently, embryos of diabetic dams become vulnerable to fluctuation of maternal vitamin A intake, resulting in diverse L-R axis defects. These findings provide insights into the etiology of CHD and suggest the importance of diet for prevention of heterotaxy during diabetic pregnancy.
Abstract 4134729: Quantitative, time-efficient viability cardiac magnetic resonance with delayed-phase dynamic contrast enhancement model: a pilot study in dogs with myocardial infarction
Authors: Li-Ting Huang, Hsin-jung Yang, Xinheng Zhang, Xinqi Li, Archana Malagi, Yuheng Huang, Xingmin Guan, Hao Ho, Alan Kwan, Janet Wei, Xiaoming Bi, Anthony Christodoulou, Debiao Li, Hui Han, Rohan Dharmakumar
Journal: Circulation (2024)

Introduction: Late gadolinium enhancement (LGE) is the gold standard for myocardial viability imaging, recommended by all major cardiology societies. In this study, we aimed to develop a time-efficient viability imaging technique utilizing a dynamic contrast enhancement(dDCE) model to shorten the LGE wait time, provide quantitative measures of the contrast washout procedure, and potentially enable a fast and quantitative mean for scar imaging. Methods: A canine study(n=10) was conducted on reperfused myocardial infarction(MI). A dDCE model using dynamic post-contrast T1 maps was adopted to depict the contrast washout process. dDCE maps were reconstructed using the whole dataset(dDCE 30min ) and a 5-minute subset of the T1 maps(dDCE 5min ). To test the dDCE models for shortening the LGE wait time, LGE dDCE images were synthesized using the dDCE 5min maps and compared to the clinical LGE images. Remote and MI dDCE parameters on dDCE 30min and dDCE 5min maps were compared to test the model's ability to extract physiological features. Results: dDCE 30min and dDCE 5min map showed a good visuospatial difference between remote and MI(Fig. 1A) and no quantitative difference (Fig.1B). v e and PS showed a significant elevation in MI than in remote (61.12±13.65% vs 13.43±5.00%, P =0.018; 44.62±21.40mL/g/min vs 0.42±0.55mL/g/min, P =0.018, respectively). v p and F p were significantly decreased in MI than in remote (4.17±2.06% vs 10.85±3.77%, P =0.02; 1.11±0.32mL/g/min vs 1.51±0.42mL/g/min, P =0.04, respectively). Representative LGE and LGE dDCE images showed high agreement in the presence of MI (Fig. 2A). Bland-Altman analysis showed good agreement between LGE and LGE dDCE images for the measurement of infarct area (bias, -1.74 ± 6.60 %, Fig. 2B) and transmuraltiy (bias, 1.86 ± 2.73 %, Fig. 2C). The simple liner regression showed strong correlations between LGE and LGE dDCE images for the infarct area (R 2 , 0.95; slope, 0.93, P &lt;0.01; Fig. 2D) and transmurality (R 2 , 0.97; slope, 0.93, P &lt;0.01; Fig. 2E). ROC analysis showed that the AUC was 0.97 (95% CI: 0.94 to 1.00) (Fig. 2F). Increased lesion-blood pool contrast by 10 folds on dDCE images improved subendocardial MI detection (Fig.3). Conclusions: The developed dDCE model provides comparable viability assessment ability to the standard LGE images without the prolonged wait time and reflects MI pathophysiological changes. It shows the potential for a rapid and quantitative myocardial viability imaging protocol using cardiac magnetic resonance.
Abstract 4137928: Race-Dependent Association of Inflammation and Cholesterol with Cardiovascular Mortality in US Population
Authors: Pengfei Li, Yiwen Zhang, Hongwei Ji
Journal: Circulation (2024)

Background: Inflammation and cholesterol jointly contribute to cardiovascular disease and mortality. The relative contributions of inflammation and cholesterol to the risk of future cardiovascular events might shift according to pre-existing traits of each individual. Whether the association of inflammation and cholesterol with cardiovascular mortality differ by race remains unclear. Method: We sampled 12,726 participants from NHAENS III who were categorized as non-Hispanic White, non-Hispanic Black or Mexican Americans. In all race groups, we used the Cox proportional hazard regression model to relate log-transformed CRP and LDL-C levels to CVD deaths. All models simultaneously included CRP and LDL-C, and were adjusted for age, current smoking, hypertension, diabetes mellitus, body mass index, lipid-lowering medications, total cholesterol and family income. Results: 12,726 participants (53.4% female, mean age 46.8 ± 19.7 years) including 5648 non-Hispanic White (44.4%), 3484 non-Hispanic Black (27.4%) and 3594 Mexican-American (28.2%) were followed up for a median 26.3 years , and 1905 cardiovascular deaths were documented. After adjusting for cardiometabolic risk factors, per 1 SD increase in log-transformed CRP was associated with 14% (HR 1.14 [95% CI, 1.08-1.21], P &lt; 0.001) and 13% (HR 1.13 [95% CI, 1.04-1.23], P = 0.001) higher risk of CVD mortality in non-Hispanic White and non-Hispanic Black respectively, while the association was neutral in Mexican American. Notably, per 1 SD increase in LDL-C was not associated with CVD mortality in all race groups (P &gt; 0.05 for all). Conclusion: After a follow up of median 26.3 years, we found that, in non-Hispanic White and Black individuals, but not in Mexican American, inflammatory was a stronger predictor of cardiovascular mortality, compared to cholesterol.