tbuckley/cabot-search huggingface dataset:
Abstract 4140257: <i>CDCP1</i> ’s Role in Cardiac Fibrosis: Unveiling Potential Mechanisms in a Pressure Over-Load Mouse Model
Authors: Li Wang, Min Wang, Hridyanshu Vyas, Carolyn Roos, Runqing Huang, Duan Liu, Rachad Ghazal, Laura Lambert, Richard Weinshilboum, Jordan Miller, Naveen Pereira
Journal: Circulation (2024)

Background: CDCP1 has been associated with reverse remodeling in human dilated cardiomyopathy (DCM) mediating its effect by reducing cardiac fibrosis which has been demonstrated in-vitro using human cardiac fibroblasts (CF) and in-vivo histologically in mice. However, the role of and the molecular mechanisms by which CDCP1 attenuates cardiac fibrosis in-vivo is unknown. Methods: To characterize the transcriptomic profiles of CDCP1 in cardiac fibrosis, Cdcp1 KO FVB/NJ mice were generated, and implanted with osmotic minipumps containing angiotensin II and phenylephrine (Ang II/PE) or saline at age of 10 weeks. There were 4 experimental groups (6 mice each), Saline_WT, Saline_KO, AngII/PE_WT, and AngII/PE_KO. After 4 weeks of AngII/PE induction, mice were euthanized, RNA was extracted from their heart tissue followed by RNA-seq to explore transcriptomic profiles. Fibrosis was histologically determined using picosirius (PSR) staining and was quantified by percentage of fibrosis area. Results: Histological analysis demonstrated that Cdcp1 KO attenuated severe cardiac fibrosis by 32.7% determined by quantification of percentage of fibrosis area. When comparing the transcriptome-wide gene expression in WT mice hearts from Saline to AngII/PE induction, a total of 316 differentially expressed genes (DEGs) were identified ( Fig. 1A ). Expression of Nppb (encodes ProBNP), a marker for heart failure, was significantly upregulated. The most significantly upregulated DEG after AngII/PE induction was Crlf1 ( Fig. 1A ), a gene predominantly expressed in CF, consistent with previous findings. We next compared transcriptomic profiles of AngII/PE induction WT and Cdcp1 KO mice hearts, to explore the role of CDCP1 in cardiac fibrosis. A total of 163 DEGs were identified ( Fig. 1B ). Notably, Cdcp1 -mediated DEGs enriched GO Pathways associated with extracellular matrix organization (Biological Process) and collagen-containing extracellular matrix (Cellular Component) ( Figs. 1C, 1D ), pivotal processes in cardiac fibrosis. In addition, Cdcp1 KO resulted in several “top” DEGs (including Rnase1, Ccl7, Ccl12 Il21r , and Il6 ) which have known function in inflammation, suggesting that CDCP1 might attenuate cardiac fibrosis through immune regulation . Conclusion: Our findings underscore the pivotal role of CDCP1 in modulating cardiac fibrosis in-vivo, potentially through immune regulation. Targeting CDCP1 may offer promising therapeutic avenues for mitigating myocardial fibrosis.
Abstract 4140513: Temporal Trends in Cardiovascular Risk Factors and Cardiovascular Disease Among Subgroups of Asian Americans in the United States
Authors: Xiaoyue Liu
Journal: Circulation (2024)

Aims: Asian Americans experience disproportionate burdens of cardiovascular risk factors and cardiovascular disease (CVD). However, the trends in cardiovascular risks in adults from different Asian ethnic backgrounds remain understudied. Therefore, we examined the temporal trends in cardiovascular conditions among Chinese, Filipino, and Asian Indian adults living in the U.S. Methods: We conducted a cross-sectional analysis using the 2004-2018 National Health Interview Survey. Age-standardized prevalence rates were calculated for eight conditions, including hypertension, type 2 diabetes, alcohol use, smoking, physical inactivity, overweight/obesity, short sleep (&lt; 7 hours), and CVD (defined as having coronary heart disease, heart attack, or stroke). Average annual percent change (AAPC) was employed to summarize and compare the trend of each outcome of interest over 15 years. Results: The sample consisted of 14,073 Asian adults, with 13% aged 65 years or older and 53% female. Of the sample, Filipino adults had the highest prevalence rates for most conditions, except for physical inactivity and overweight/obesity. Over 15 years, Chinese adults showed a 2% annual increase in short sleep ( p = 0.010). Asian Indian adults exhibited uptrends in overweight/obesity (AAPC: 1.1%, p &lt; 0.001) and alcohol use (AAPC: 2.3%, p &lt; 0.001), but downtrends in smoking (AAPC: -4.8%, p = 0.005) and physical inactivity (AAPC: -0.8%, p &lt; 0.001). Filipino adults demonstrated similar trends in the prevalence of alcohol use and smoking, with AAPCs at 1.6% ( p = 0.001) and -3.1% ( p = 0.001), respectively. No significant trends were found for other cardiovascular conditions in all three groups. Discussion: Our study assessed temporal trends in CVD and its risk factors among the three largest Asian ethnic groups in the U.S. The findings showed that Asian Americans from different ethnic backgrounds face varying disparities in cardiovascular health. Public health strategies should be customized to effectively address specific cardiovascular risks for each Asian subgroup.
Abstract 4140079: Inhibition of AT1R Attenuates AML and Prevents Chemotherapy-induced Cardiotoxicity
Authors: Yi Pan, Chen Wang, Wenxuan Zhou, Xiaduo Meng, Yao Shi, Zhenguo Liu, Yasir Muhammad, Richard Hammer, De Pei Li, Xunlei Kang
Journal: Circulation (2024)

Introduction: Patients with acute myeloid leukemia (AML) frequently develop significant cardiac toxicity when receiving chemotherapy with poor prognosis, but the mechanisms remain largely unknown. Our in silico analysis revealed that angiotensin II receptor type 1 (AT1R) is abundantly expressed in AML and significantly increased in the blood of AML patients. It is known that AT1R is associated with the pathogenesis of cardiomyopathy. Hypothesis: We hypothesize that inhibiting AT1R can simultaneously suppress AML development and reduce chemotherapy-induced cardiotoxicity. Methods and Results: Inhibition of AT1R inhibition using specific AT1R inhibitor or AT1R knockout (KO) substantially reduced AML stemness and boosted chemotherapy efficacy for AML. Mechanistically, AT1R regulates γ-secretase activity, which is responsible for Notch1 transcription factor activation. AT1R KO effectively reduced the expressions of Notch1 downstream genes responsible for AML stemness, cell cycle,and proliferation. When Notch1 was re-introduced into AT1R KO AML cells, the expressions of these Notch1 downstream genes were rescued. Additionally, chromatin structure omics (HiC) and epigenetic omics (CUT&amp;RUN)analysis revealed that 3D-chromatin structural and epigenetic alteration of multiple genes were associated with chemotherapy resistance. In fact, human AML patient derived xenograft model showedAT1R inhibition simultaneously boosted chemotherapy for AML while reducingchemotherapy-induced cardiotoxicity. Further mechanistic study demonstrated that the expression of angiotensin-converting enzyme was significantly increased in the cellsurface of AML with increased blood Ang II level in a mouse model, thus, may contributing to chemotherapy-induced cardiac toxicity. Conclusions: Together, these data demonstrated that AT1R-mediated signaling plays a key role in AML development and chemotherapy-induced cardiotoxicity. These findings indicate that the high incidence of cardiomyopathy in AML was increased AT1R-mediated signaling and targeting AT1R signaling could be a novel strategy for simultaneously suppressingleukemia, boosting chemotherapy efficacy, and preventing chemotherapy-inducedcardiotoxicity.
Abstract 4140203: Prognosis of Cardiovascular Magnetic Resonance Myocardial Characterization Among Individuals with Undifferentiated Non-ischemic Cardiomyopathy
Authors: Lu Zhang, Mawra Jha, Ujwala Shenoy, Warren Manning, Connie Tsao
Journal: Circulation (2024)

Background: Contrast cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method to characterize the left ventricular (LV) myocardium, yet its role in heart failure (HF) prediction in undifferentiated non-ischemic cardiomyopathy (uNICM, without etiology) is unclear. Aim: To evaluate CMR myocardial tissue characteristics [late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume (ECV)] in HF diagnosis and prognosis among patients with uNICM. Methods: From 3583 consecutive patients referred for clinical CMR at our center (2019-2023), we identified patients with uNICM, with or without HF, based upon presence of: elevated T1 or ECV, non-ischemic LGE (e.g., mid-wall, subepicardial, transmural in patchy or non-coronary distribution), global LV dysfunction, and/or conclusion of uNICM. Individuals without HF were assessed for incident HF by physician medical record review. Multivariable (MV) regression models were used to assess the association between T1, ECV, and LGE with prevalent and incident HF. Results: Among 782 patients with uNICM, 379 had all CMR variables of LV structure and function (59±15 y; 36% F, 48% prevalent HF). Patients with HF had less favorable LV function and structure: ejection fraction (37 vs. 50%), mass index (71 vs. 64 g/m 2 ), end-diastolic volume index (121 vs 100 ml/m 2 ), T1 (1287 vs 1259 ms), and ECV (34 vs 31%), all p&lt;0.001, except LGE (51 vs 59%, p = 0.150). In MV models, elevated T1 and ECV, but not LGE, were associated with prevalent HF ( Table ). In patients without prevalent HF (n=196), 33% patients developed HF over a median follow-up of 13 (IQR: 3-23) months. Elevated ECV conferred a &gt;2-fold risk for incident HF (HR 2.77, 95%CI:1.36-5.66, p=0.005) in MV models ( Table , Fig ). Conclusion: Elevated ECV, possibly indicating diffuse fibrosis, is associated with both prevalent and incident HF in patients with uNICM referral for CMR. Larger studies may allow study of the prognosis of these measures in other hard outcomes.
Abstract 4140042: Impact of Inflammatory and Insulin Resistance Biomarkers on Long-Term Risks in Coronary Heart Disease Patients with Cardiovascular-Kidney-Metabolic Syndrome
Authors: Kexin Zhang, Jiawen Li, Yulong Li, Kailun Yan, Xueyan Zhao
Journal: Circulation (2024)

Background: Abundant evidence has suggested that individuals with poor Cardiovascular-kidney-metabolic (CKM) health are at a heightened risk of adverse cardiovascular events. In patients with coronary heart disease, a considerable proportion has concurrent CKM, which warrants further attention. Purpose: This study aimed to evaluate the prognostic significance of inflammatory and non-insulin-based insulin resistance biomarkers in patients with confirmed CHD and CKM syndrome. Methods: Among 10724 consecutive patients admitted to our center for CHD in 2013, 9716 patients who met the diagnostic criteria for CKM syndrome were included in this study. The endpoint was the major cardiac and cerebrovascular event (MACCE). The optimal cut-offs of the indicators were determined by the receiver operating characteristic analysis. Results: During a median follow-up of 5.05 years, 2019 cases of MACCEs were observed. At baseline, the mean age of the overall cohort was 58.4 ± 10.3 years, and 7467 (76.9%) patients were male. Multivariable Cox regression analysis revealed that elevation of any inflammatory biomarkers levels [including white blood cells, neutrophils, monocytes, platelets, neutrophil-to-platelet ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory response index, systemic inflammatory index, pan-immune-inflammation value (PIV) and high-sensitivity C-reactive protein] was significantly associated with an increased risk of 5-year MACCE (all P &lt;0.05), while PIV demonstrated the relatively strongest association [hazard ratio (HR) 1.274, 95% Confidence Interval (CI) 1.161-1.397; P &lt;0.001]. However, among the indicators of insulin resistance [including the triglyceride and glucose (TyG) index, TyG-body mass index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and metabolic score for insulin resistance], only TG/HDL-C remained significant after adjusting for confounding factors, with a HR of 1.147 (95% CI 1.027-1.280; P&lt;0.05). Conclusions: This current study reveals that, multiple inflammatory biomarkers and TG/HDL-C have predictive significance for the long-term prognosis of CHD patients with CKM syndrome, suggesting the potential application of these indicators in the assessment among the high-risk population. Further investigation is warranted to determine whether targeted treatment of these biomarkers would be of benefit.
Abstract 4140466: Time Interval from Right Atrium to Coronary Sinus Predicts Atrial Fibrillation Recurrence After Catheter Ablation
Authors: Daiki Yamashita, Naoki Fujimoto, Shinya Sugiura, Yoshihiko Kagawa, Satoshi Fujita, Kaoru Dohi
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) recurrence after catheter ablation may occur in patients with atrial remodeling progression. Atrial conduction time has been proposed as a marker of atrial remodeling. This study aimed to investigate whether atrial conduction time, measured during an electrophysiological study, is related to AF recurrence. Methods: Overall, 441 patients with AF (mean age, 67 years; female, 144 years; paroxysmal AF (PAF)/non-PAF, 233/208) who underwent initial radiofrequency catheter ablation at Mie University Hospital between January 2018 and December 2022 were enrolled. We measured the interval from the earliest potential in the right atrium (RA) to the latest potential in the coronary sinus (CS) (RA-CS interval time) using a BeeAT catheter during sinus rhythm after ablation (Figure 1). The primary endpoint was the recurrence of AF or other atrial tachycardia lasting &gt; 30 s from 3 months to 1 year postoperatively. Results: During the 1-year follow-up, AF recurrence was observed in 44 patients. Patients were categorized into two groups according to AF recurrence. RA-CS interval times were significantly prolonged in the recurrence group (122.5±17.7 vs. 98.5±17.7 ms, p&lt;0.001). In Cox regression analysis, after adjustment for confounders, RA-CS interval time was an independent factor associated with AF recurrence (Hazard ratio 1.05; 95% CI 1.03–1.07, p&lt;0.001). The cut-off value of the RA-CS interval time using the ROC curve was 111 ms (Figure 2, AUC 0.845, 95% CI 0.785–0.905). Patients with RA-CS interval time ≥111 msec had a significantly higher recurrence rate rather than &lt;111 ms (Figure 3). Conclusions: The RA-CS interval was an independent predictor of AF recurrence in the first year after catheter ablation.
Abstract 4140053: Effect of Sacubitril/Valsartan in Patients with Concomitant Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease on Hemodialysis
Authors: Yuran Ahn, Mi-Hyang Jung, Jong-Chan Youn, Dong-Hyuk Cho, Jimi Choi, Byung-Su Yoo
Journal: Circulation (2024)

Aims: This study aimed to explore the comparative effectiveness of sacubitril/valsartan (SV) to renin-angiotensin system (RAS) blockade in patients with concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) on hemodialysis. Method: We enrolled patients with HFrEF and ESRD on hemodialysis using data from the Korean National Health Insurance Service data (2017–2021) covering the entire national population. A total of 2,248 patients with HFrEF who received SV were compared with 2,528 patients with HFrEF who received RAS blockade by inverse probability treatment weights. The primary endpoint was a 2-year composite outcome of all-cause mortality or any hospitalization. Differential effects according to medication adherence were also analyzed using proportion of days covered (PDC). Results: SV reduced the risk of the primary outcome compared to the RAS blockade group (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.75–0.96, P = 0.009). SV significantly reduced all-cause mortality (HR 0.74; 95% CI 0.59-0.93, P = 0.008) and any hospitalization (HR 0.85; 95% CI 0.75-0.95, P = 0.007). In the group with a PDC ≥80%, SV reduced the risk of all-cause, cardiovascular mortality and any hospitalization than RAS blockade (all-cause mortality, HR 0.61; 95% CI 0.46–0.80; P &lt;0.001, cardiovascular mortality, HR 0.59; 95% CI 0.43-0.82, P = 0.001, any hospitalization, HR 0.80; 95% CI 0.80-0.94, P = 0.007). Conclusions: In a real-world population with concomitant HFrEF and ESRD on hemodialysis, SV significantly reduced the risk of all-cause mortality and any hospitalization compared to the RAS blockade. These benefits were more definite in a subpopulation with a PDC ≥ 80%, suggesting the importance of medication adherence in improving cardiovascular outcomes.
Abstract 4139907: Evaluating the Associations Between Medications and Cusp Fusion Patterns on Aortic Growth in Children with Bicuspid Aortic Valve
Authors: Joseph Burns, Sara Stephens, William Kyle, Yu Cai, Shaine Morris
Journal: Circulation (2024)

Background: Children with bicuspid aortic valve (BAV) often have progressive aortic dilation, conferring an increased risk of dissection in adulthood. Data describing medication use in aortic dilation in children with BAV are limited. This study aims to evaluate longitudinal trends of aortic growth, comparing those on angiotensin receptor blockers (ARBs) or beta-blockers (BBs) to no medical therapy. Methods: This retrospective cohort included subjects with BAV with first echo &lt;18 years from 2010-2023 with &gt; 1 echocardiogram with root or ascending z-score &gt; 3.5 and &gt; 2 available echocardiograms. The primary exposure was medication status, stratified as none, ARB, or BB. Outcomes evaluated were trends in 1) ascending aortic (AscAo) z-score and 2) aortic root z-scores over time using multivariable mixed-effects linear regression to account for changing medication regimens over time. Results: In total, 115 patients (76% male) were included; 61 patients (53%) were treated at some point during the period of interest (17% ever on ARBs, 27% on BBs, and 9% on dual therapy). Regarding clinical features, for AscAo z-scores, only lower baseline AscAo z-score was associated with higher rate of growth; sex and cusp fusion type were not. On multivariable analyses controlling for baseline z-score, AscAo z-score decreased in patients on BBs relative to those not on medication (relative difference -0.1 + 0.03 z/year, p:&lt;0.0001, Figure). For root z-score, lower baseline z-score was again associated with faster growth. Right-left fusion was also associated with increased change in root z-score compared to unicuspid valves (relative change +0.09, p=0.027 respectively); sex was not associated. In multivariable analysis controlling for baseline root z-score BBs and cusp fusion type, there was no difference in root-z-score change by medication (Figure). Conclusions: In this cohort of children with BAV and aortic dilation with z-score &gt; 3.5, BB use was associated with a reduction in the ascending aorta z-score relative to patients not on medications. To date this is the largest study comparing change in aortic dimensions by medication class in children with BAV.
Abstract 4140591: Impact of Mitral Annular Calcification on Cardiovascular Outcomes in Patients with Diastolic Heart Failure
Authors: Evan Isaacs, Abiodun Idowu, Gregg Pressman
Journal: Circulation (2024)

Background: Mitral annular calcification (MAC) may be a marker of biological age; its impact on outcomes in patients with heart failure with preserved ejection fraction remains unclear. Methods: A retrospective propensity-matched cohort analysis of patients ages &gt; 18 years hospitalized with diastolic heart failure with and without MAC in the TriNetX database. Cohorts were balanced on socio-demographics, and medications (anticoagulants, antiplatelet, beta-blockers, diuretics, anti-arrhythmic, lipid-lowering agents, and SGLT2i). Patients with rheumatic valve disease were excluded. Adjusted odds ratios (aOR) were calculated for outcomes and Kaplan-Meier survival analysis curves with log-rank tests over five-year follow-up were analyzed using R software. Results: There were 11384 participants matched to each cohort; the average age at diagnosis was 72.5 + 11.6 years, 76.2% were Caucasian, and 56.9% were female. Left ventricular ejection fractions were similar in both MAC (58.3 + 11.9) vs non-MAC (58.2 + 12.6). Median follow-up was 423 days (MAC group) and 575 days (non-MAC group). All-cause hospitalization (HR: 2.31, 95%CI: 2.04 – 2.62, p&lt;0.001), heart failure hospitalization (HR: 2.22, 95%CI: 1.92 – 2.55, p&lt;0.001), acute myocardial infarction (HR: 2.06, 95%CI: 1.79 – 2.35, p&lt;0.001), unstable angina (HR: 2.28, 95%CI: 1.72-3.04, p&lt;0.001), and stroke (HR: 1.70, 95%CI: 1.45 – 2.00, p&lt;0.001) were all higher in MAC patients than non-MAC patients (table 1). Conclusion: Among patients hospitalized with ‘diastolic heart failure’ MAC is associated with worse cardiovascular outcomes.
Abstract 4139891: Endothelial Cell-Related Proteins in Plasma Predict Major Adverse Cardiovascular Events and Worsening Heart Failure in Patients with Hypertrophic Cardiomyopathy
Authors: Shogo Tamura, Keitaro Akita, Michael Fifer, Albree Tower Rader, Mathew Maurer, Muredach Reilly, Yuichi Shimada
Journal: Circulation (2024)

Introduction: Hypertrophic cardiomyopathy (HCM) often causes major adverse cardiovascular events (MACE) and worsening heart failure (WHF). Endothelial cell (EC) dysfunction is known to occur in patients with HCM. However, the prognostic value of proteins related to EC function in HCM is unknown. The present study aimed to test the hypothesis that the levels of plasma proteins related to EC function predict future MACE and WHF in patients with HCM. Methods: In this multicenter prospective cohort study of patients with HCM, we measured plasma levels of 90 proteins related to EC function upon enrollment. The primary outcome measure was MACE, defined as the composite of sudden cardiac death, death due to HF, heart transplant, HF hospitalization, any increase of New York Heart Association (NYHA) class, new-onset atrial fibrillation, and stroke. The secondary outcome measure was WHF, defined as increase in NYHA class or HF hospitalization. We developed EC protein-based LASSO classification models to predict MACE or WHF using data from one institution (training set). We tested the predictive ability in independent samples from the other institution (test set) and performed time-to-event analyses. Results: The study included 722 patients (n=458 in the training set and n=264 in the test set). During the median follow-up period of 3.3 years, the outcome event of MACE occurred in 192 (27%) patients and WHF in 139 (19%) patients. The area under the receiver-operating-characteristics curve to predict MACE was 0.71 (95% confidence interval [CI] 0.64-0.77. Figure 1a ) and that for WHF was 0.69 (95% CI 0.61-0.77. Figure 1b ). When we divided the test set into high- and low-risk groups according to the predicted probabilities derived from the training set, log-rank tests and Cox proportional hazards models revealed that the high-risk groups had significantly higher risks of developing MACE and WHF (log-rank P&lt;0.001, HR 2.45 [95% CI 1.47-4.10], P=0.0006. Figure 2 ) and WHF (log-rank P&lt;0.001, HR 2.62 [95% CI 1.52-4.54], P=0.0006. Figure 3 ) compared with the low-risk groups. Conclusions: The present multicenter prospective study demonstrated that plasma proteins related to EC function predict MACE and WHF in patients with HCM. These EC-related proteins have a potential to become novel biomarkers for risk stratification in HCM to improve current prediction models.