tbuckley/cabot-search huggingface dataset:
Abstract 14286: Rapid Involution of a Bioprosthetic Transcatheter Aortic Valve Replacement Presenting as Late Bioprosthetic Stenosis
Authors: Shiv Dixit, Jamshid Shirani, Patrick Field
Journal: Circulation (2023)

A 65 year old male with a bioprosthetic 29 mm Edwards Sapien Ultra S3 TAVR implant for symptomatic severe aortic stenosis presented for evaluation after a 30-day transthoracic echocardiogram demonstrated bioprosthetic valve stenosis. Following TAVR deployment, TEE showed normal bioprosthetic valve function without evidence of significant paravalvular regurgitation. There were no procedural complications. Echocardiogram performed 1-day post-implantation demonstrated expected transvalvular gradients and valve area. The patient reported immediate symptomatic improvement following TAVR. At 30 days post-implant, TTE demonstrated a peak velocity of 3.37 m/s, mean gradient of 29 mmHg, dimensionless index of 0.29, and effective valve orifice area of 0.9 cm2. This was associated with a progressive decline in exercise capacity. At 57 days post-implant, TEE showed tissue growth of the aortic root anterior to the valve stent, causing deformation and under-expansion of the valve architecture from a circular to an ovoid shape. Notably, the bioprosthetic leaflets did not appear thickened or calcified, but exhibited restricted motion as a result of the abnormal valve architecture. Peak velocity had further increased to 4.6 m/s, with a mean gradient of 57 mmHg, dimensionless index of 0.21, and calculated effective orifice area of 0.52 cm2. Bioprosthetic aortic valve valve stenosis is an expected complication of valve replacement, though typically characterized by progressive leaflet calcification and pannus formation over several years or by valve thrombosis. Here, we present a rare case of rapidly progressive bioprosthetic TAVR stenosis identified at 30 days post-implantation after normal morphology and gradients on immediate and 1-day imaging. Stenosis was characterized by a process of tissue growth anterior to the stent with involution and underexpansion of the stent architecture and morphologically normal leaflet tissue.
Abstract 11749: Identifying Infants With Long QT Syndrome Type 1: Looking Beyond the QTc
Authors: Robert Przybylski, Robyn Hylind, Jennifer Noon, Elizabeth S Dewitt, Vassilios J Bezzerides, Dominic J Abrams, Judy Ashouri
Journal: Circulation (2023)

Background: Abnormal repolarization in long QT syndrome type 1 (LQT1) is characterized by QT prolongation and abnormal T-waves. In the absence of familial disease, LQT1 is easily missed in infants as the QTc is often normal, exposing children to life-threatening arrhythmia. Hypothesis: T-wave morphology metrics are superior to QTc for diagnosis of LQT1. Aim: Compare quantifiable aspects of T-wave morphology and QTc to differentiate infants with and without LQT1. Methods: Infants aged 0.5-6 months with a pathogenic/likely pathogenic KCNQ1 variant were compared to age/sex-matched controls in a 1:2 ratio. Measurements were made in leads II/V5. T-wave morphology was assessed by J-point to T-wave peak (J-Tp) and Tp to T-wave end (Tp-Te). Bazett’s formula was used to correct for heart rate and Te defined using the tangent method. Results: We identified 34 LQT1 infants and 68 controls. The median (IQR) QTc was 457 (430-476) ms for LQT1 cases and 402 (392-420) ms for controls (p&lt;0.001). The 98%tile QTc for controls was 448 ms and 13/34 (38%) LQT1 cases were below this value. In lead II, LQT1 cases had a significantly longer rate corrected J-Tp compared to controls, 294 (272-312) ms v. 222 (211-234) ms (p &lt;0.001) and shorter Tp-Te, 71 (60-80) ms v. 85 (75-95) ms (p&lt;0.001). The J-Tp/Tp-Te ratio was 0.25 in LQT1 cases and 0.39 in controls (p&lt;0.001). Findings were similar in V5. V5 rate corrected J-Tp best discriminated between LQT1 cases and controls (ROC AUC 0.99, optimal cut point ≥256ms) and outperformed QTc (AUC 0.92). This remained true in those with QTc &lt;98%tile (AUC 0.98). Measurements in a subset of 30 infants made by 3 ECG readers showed superior reliability for J-Tp in leads II and V5 (ICC coefficient 0.92) compared to QTc (0.88). Conclusions: Nearly 40% of infants with LQT1 have a normal a QTc, yet a significantly abnormal and quantifiable T-wave morphology. J-Tp and Tp-Te are reliable and reproducible measurements and should be included in the assessment of potential infantile LQT1.
Abstract 13805: Associations of Subclavian Artery Calcification With Future Cardiovascular Events and Death: The Multi-Ethnic Study of Atherosclerosis
Authors: Daniel A Duprez, David R Jacobs, Michael R Daniels, Leah Andrews, Lyndia Brumbach, Julie Denenberg, Kelly Watanabe, Germaine Cornelissen Guillaume, Michael H Criqui, Moyses Szklo, Matthew A Allison
Journal: Circulation (2023)

Introduction: Atherosclerosis affects the upper limbs and may be a marker of diffuse atherosclerosis and increased risk for cardiovascular events. Hypothesis: Subclavian artery calcification (SAC) and thoracic aorta calcification (TAC) obtained by chest CT provide additional information about future CV events and death beyond coronary artery calcification (CAC) and CV risk factors. Methods: Chest CT scans of MESA participants (N = 2519) at exam 5 (2016-18) were interrogated for the presence and extent of SAC, TAC, and CAC. Proportional hazards regression was conducted for associations with incident total CVD events (n = 209), adjusted for age, race/ethnicity, and sex, then SAC, TAC, and CAC adjusted for demographics and each other, and finally adding adjustment for CV risk factors. Results: The mean age of the sample was 68.3±9.2 years; 48% were male, 27% Black, 13% Chinese, 22% Hispanic, 38% White. The prevalence of any calcification was 62% for SAC, while being 60 and 69% for TAC and CAC, respectively. Among those with any calcification, N and median Agatston score were SAC: 1704, 76; TAC: 1655, 152; CAC 1896, 135. CAC predicted future events in all models (Table). After adjustment for demographics, the ln(Agatston score +1) in each calcified vascular bed predicted future CVD. Mean±SD of the predictors were ln(SAC+1): 2.4±2.4, ln(TAC+1) 2.7±2.9 and ln(CAC+1) 3.1±2.6. SAC, but not TAC, was still predictive after mutual adjustment. SAC was marginally predictive (HR: 1.08, p = 0.06) when CV risk factors were also included in the model. Conclusions: Calcification was common in all 3 vascular beds, but there is no evidence that predictions using SAC and TAC are independent of CAC. We speculate that although the tendency to calcify is similar across vascular beds, CAC is most relevant for incident CVD.
Abstract 14388: Meta-Analysis of Randomized Controlled Trials Comparing Immediate vs Staged Complete Revascularization in Patients With Acute Coronary Syndrome
Authors: Sahib Singh, Udaya Tantry, Kevin Bliden, Aakash Garg, Paul Gurbel
Journal: Circulation (2023)

Introduction: Complete revascularization with percutaneous coronary intervention (PCI) has been shown to improve clinical outcomes in patients with acute coronary syndromes (ACS) and multivessel disease (MVD). In order to address the conflicting results reported with respect to the timing, we aimed to perform a meta-analysis of the available randomized controlled trials (RCTs). Methods: Online databases were searched for RCTs comparing immediate to staged complete PCI in patients presenting with ACS. The primary outcomes of interest were major adverse cardiovascular events (MACE), all cause death, myocardial infarction (MI), cardiovascular death, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), cerebrovascular events and bleeding at the longest available follow up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. Results: Three RCTs with a total of 2,261 patients, with 1,131 in the immediate PCI group and 1,130 in the staged PCI group were included. The mean age was 67 years, 79% of patients were men and the mean duration of follow up was 1 year. The immediate PCI group compared to staged complete PCI was associated with a significant reduction in MI (RR 0.50, 95% CI 0.31-0.83, p = 0.007) (Figure 1) and TVR (RR 0.58, 95% CI 0.41-0.80, p = 0.001). There were similar risks of cardiovascular death (RR 1.15, 95% CI 0.55-2.42, p = 0.71), TLR (RR 0.88, 95% CI 0.17-4.65, p = 0.88), cerebrovascular events (RR 0.87, 95% CI 0.41-1.82, p = 0.71), all-cause death (RR 1.30, 95% CI 0.48-3.50, p = 0.61), MACE (RR 0.70, 95% CI 0.48-1.02, p = 0.06), stent thrombosis (RR 0.89, 95% CI 0.36-2.22, p = 0.81) and bleeding (RR 0.65, 95% CI 0.18-2.41, p = 0.52) between the two groups. Conclusions: Complete PCI of the culprit and non-culprit vessels during the index procedure (immediate) significantly reduces the risk of MI and TVR when compared with staged PCI.
Abstract 13387: Transradial Intervention in Dialysis Patients Undergoing Percutaneous Coronary Intervention: A Japanese Nationwide Registry Study
Authors: Toshiki Kuno, Kyohei Yamaji, Tadao Aikawa, Mitsuaki Sawano, Tomo Ando, Yohei Numasawa, Hideki Wada, Tetsuya Amano, Ken Kozuma, Shun Kohsaka
Journal: Circulation (2023)

Introduction: Transradial intervention (TRI) for percutaneous coronary intervention (PCI) is used to reduce periprocedural complications. However, its effectiveness and safety for patients on dialysis are not well established. Hence, we aimed to investigate the association of TRI with in-hospital complications in dialysis patients undergoing PCI. Hypothesis: TRI reduces periprocedural complications for dialysis patients undergoing PCI. Methods: We included 52,639 patients on dialysis who underwent PCI using Japanese nationwide PCI registry data (2019-2021). Patients were categorized based on access site: TRI, transfemoral intervention (TFI), or other access site. Periprocedural access site bleeding complication requiring transfusion was the primary outcome and in-hospital death and other periprocedural complications were the secondary outcomes. Matched weighted analysis was performed for TRI and TFI. Results: Here, 8,267 (15.7%) underwent TRI, 36,195 (60.2%) underwent TFI, and 8,177 (15.5%) underwent PCI from other access sites. Patients who received TRI were older and had lower rates of comorbidities than those who received TFI. Access site bleeding rate and in-hospital death were significantly lower in the TRI group (0.1% versus 0.7%, P&lt;0.001; 1.8% versus 3.2%, P&lt;0.001, respectively). After adjustment, TRI was associated with a lower risk of access site bleeding (odds ratio [OR] [95% confidence interval (CI)]: 0.19 [0.099-0.38]; P &lt;0.001) and in-hospital death (OR [95% CI]: 0.79 [0.65-0.96]; P=0.02). Other periprocedural complications between TRI and TFI were not significantly different. Conclusions: In patients undergoing dialysis and PCI, TRI had a lower risk of access site bleeding and in-hospital death than TFI. This suggests that TRI may be safer for this patient population. Further investigation is necessary to promote the widespread utilization of TRI for patients on dialysis.
Abstract 15922: Integrative Analysis of Extracellular Vesicles in Heart Transplant Rejection: From Biomarker Discovery to Novel Immune Mechanisms
Authors: Monique S Bagwell, Mohsin Abbas, Dhivya V Meenakshi Siddhartha, Ryan Mahlberg, Mary Nagel, Tyra A Witt, Paul Stalboerger, Humberto De Vitto, Atta Behfar
Journal: Circulation (2023)

Introduction: At the forefront of post-heart transplant care is early detection of transplant rejection. However, the current gold standard for detecting acute cellular transplant rejection is recurrent invasive endomyocardial biopsies (EMB). We aimed at developing a non-invasive biomarker for acute cellular heart transplant rejection (ACR) using a plasma extracellular vesicle (EV) platform. Methods: Peripheral and coronary sinus plasma samples were prospectively collected from 183 (31.7% female) patients from 2020 to 2023 during routine surveillance EMB. A discovery cohort comprised five patients who displayed ISHLT 0-1R biopsy followed by an ISHLT 2R grade rejection event. Plasma EVs were isolated from the baseline (0-1R) and rejection (2R) time points. Subsequently, integrative analysis of plasma EV proteomic, miRNomic, and metabolomics was performed pairwise with the samples. Results: The study collected 943 sample time points from 183 patients. Of these sample collections, 43 (4.5%) cases were 2R rejections. Our proteomic analysis of the plasma EVs identified 28 proteins found explicitly during a grade 2R rejection and 87 differentially expressed proteins during a 2R rejection event. An Ingenuity Pathway Analysis (IPA) analysis of the upregulated proteins highlighted EVs mediated mTOR signaling and antigen presentation as central to rejection events. Although all patients in the discovery cohort were negative for antibody-mediated rejection (AMR), the proteomic findings also revealed increased B-cell receptor signaling, implying a mechanistic intersection of ACR and AMR. Conclusions: A distinct set of proteins were found in plasma EVs during ACR events, providing potentially specific and sensitive biomarkers to reduce the need for EMB that could be exploited for ACR diagnosis. The proteins identified formed an immune signaling network that suggests a novel role for EVs in ACR pathogenesis.
Abstract 15096: miR-132 Inhibition Shows Anti-Hypertrophic Effects in Preclinical Heart Failure Models and in Exploratory Pharmacodynamic Parameters of a First-in-Human Phase 1b Clinical Trial
Authors: Sandor Batkai, Celina Genschel, Janika Viereck, Steffen Rump, Wilfried Hauke, Mariann Gyongyosi, Denise Traxler, Rabea Hinkel, Christian Kupatt, Arthur A Levin, Thomas Thum
Journal: Circulation (2023)

Introduction: Cardiac expression levels of miR-132 are elevated in patients with heart failure (HF) and have been associated and provoke pathological cardiac hypertrophy. To inhibit these cardiac remodeling processes and restore normal cardiac function, we developed the synthetic antisense oligonucleotide inhibitor CDR132L targeting miR-132. Anti-hypertrophic effects of miR-132 inhibition have been shown previously in cell culture models and a mouse model of pressure overload-induced HF. Methods and Results: MiR-132 inhibition with CDR132L was now tested in a mouse model of pressure overload induced HF induced by transverse aortic constriction (TAC) and in three different porcine HF models to further confirm the translatability of therapeutic effects. The first pig model was an early post-myocardial infarction (MI). Pigs were treated with CDR132L by intravenous (IV) or intracoronary (IC) infusion on day 3 and day 28 and analyzed on day 56 post-MI. As a second model, chronic post-MI HF pigs received monthly IV treatments over 3 or 5 months starting from month 1 post-MI. Third, percutaneous aortic constriction was induced in pigs by reduction stent implantation and CDR132L was administered IC on day 0 and day 28 followed by analysis on day 56. Hypertrophy was determined by cell size measurements in wheat germ agglutinin (WGA) stained cardiac sections and was significantly decreased between 15% and 29% in CDR132L-treated groups with sufficient dose levels compared to placebo-treatment independent from the large animal model and dosing regimen. Furthermore, TAC mice treated with CDR132L showed a significant decrease in left ventricular mass by 14 % compared to placebo. In line with these data, the cardiac remodeling marker lipocalin-2 (NGAL) was reduced in plasma of chronic HF patients assessed in a first-in-human phase 1b clinical to test safety, efficacy, and also exploratory pharmacodynamics of CDR132L (NCT04045405). Conclusions: Our results confirm beneficial effects of CDR132L treatment on pathological cardiac remodeling in HF.
Abstract 14105: Impact of Aortic Atheromatous Plaques Identified by Aortic Angioscopy on Five-Year Clinical Events: Novel Evaluation by Non-Obstructive General Angioscopy Registry
Authors: Keisuke Kojima, Sei Komatsu, Tsunekazu Kakuta, Junichi Yoshida, Daisuke Fukamachi, Hiroyuki HIKITA, Hiroyuki Fujii, Shigeki Kimura, Masayoshi Matsuura, Hideo Kawakami, Kazuoki Dai, Yoshiharu Higuchi, Yasunori Ueda, Shichiro Abe, Itaru Takamisawa, Akira Sato, Hiroaki Watabe, Satoru Takahashi, Eisuke Usui, Masanori Asakura, Chikao Yutani, Yasuo Okumura, Atsushi Hirayama, Kazuhisa Kodama
Journal: Circulation (2023)

Introduction: Non-obstructive general angioscopy (NOGA) has become a novel method of evaluating atheromatous plaques of the aortic intimal wall. Aortic atheromatous plaques are potentially related to future cardiovascular events, but these associations remain undetermined regarding long-term follow-up. Methods: We conducted a multicenter, observational, prospective registry of consecutive 577 patients with confirmed or suspected coronary artery disease underwent NOGA at 13 centers in Japan and counted atheromatous plaques from aortic cusp to terminal aorta with intra-aortic scan of NOGA. All patients were divided into three groups based on the tertile of the number of aortic atheromatous plaques. The relationships between aortic atheromatous plaques and clinical events after five-year follow-up were evaluated. Results: The median number of aortic atheromatous plaques was 6 [IQR: 3-12]. The mean follow-up duration was 1860 ± 860 days. At five-year follow-up, the incidence of major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, cerebral infarction, or peripheral artery disease) was significantly higher in the higher tertile group (lower tertile 7.4% vs. middle 13.2% vs. higher 20.7%, p&lt;0.001, respectively). Kaplan-Meier analysis demonstrated a significantly higher probability of MACE in higher tertile group of all (log-rank test: p &lt; 0.001). Conclusions: Aortic atheromatous plaques identified by NOGA could be vulnerable, and thus were strongly associated with clinical events during five-year follow-up.
Abstract 18645: Phenylacetylglutamine Causes a Pathologic Hyperinflammatory State and Enhances Atherosclerosis Through the ß2-Adrenergic Receptor in Diabetes
Authors: lu huang, Jinyan Zhang
Journal: Circulation (2023)

Background: Type 2 diabetes (T2DM) affects billions of patients and has a pathophysiologically important inflammatory component. Macrophage plasticity in diabetes is impaired, and remains in a persistent proinflammatory state; yet currently, the cause of the inflammatory state is unknown. Phenylacetylglutamine (PAGln) is an amino acid metabolism end product that rises in T2DM patients and is associated with incident major adverse cardiovascular events. However, the role of PAGln in the inflammatory component of T2DM remains unknown. Purpose: Here, we aim to identify blood-based systemic factors for pathologic inflammation status and risk of atherosclerosis as they are highly reproducible at low cost and search for effective and safe agents to attenuate diabetic inflammatory complications. Methods: In vivo, phenylacetylglutamine was dissolved in normal saline and injected in mice daily (ip). The levels of PAGln were analyzed by liquid chromatography-mass spectrometry. The effect of PAGln on atherosclerosis progression was analyzed by Ldlr-/- mice, followed by a Western diet feeding for 12 weeks. In vitro, primary mice bone marrow-derived macrophages (BMDMs) and haematopoietic stem cells (HSCs) were treated with phenylacetylglutamine (100 uM) for the indicated time. Results: In vivo, increased immune cells and inflammatory macrophages were detected in PAGln-treated mice blood, spleens, bone marrow, and arteries. In vitro, PAGln leads to macrophage M1 polarization. The result of bone marrow transplantation on Ldlr-/- mice further confirmed the effect of PAGln on the central immune system of mice. Besides, the negative effects of PAGln could be rescued by ß-blockers. Conclusion: Our study unravels a novel mechanism by which PAGln accelerates atherosclerosis progression and causes pathologic inflammation by activating the ß2-adrenergic receptor. The negative effect of PAGln could be rescued by carvedilol (ß blocker). Thus, our recognition of chronic inflammation in diabetes needs to be revised, and understanding these mechanisms can inform alternative treatment strategies and refine atherosclerosis repair therapies for diabetic patients.
Abstract 16325: Racial and Ethnic Differences in the Age of Onset of Type II Diabetes Among United States Adults: A Cross-Sectional Analysis
Authors: Shreya Srivastava, Aayush Visaria, Payal Dave, Ranita Sharma
Journal: Circulation (2023)

Background Several studies have examined racial/ethnic differences in Type II Diabetes (T2D) incidence and prevalence in the United States and have found significantly increased risk of T2D in African American, Asian, and Hispanic populations. However, it is still unknown whether age of onset of T2D is different across racial/ethnic groups, specifically that of Asian Indians, a group known to have a high incidence of T2D and cardiovascular disease risk. Methods: We used the National Health Interview Surveys (NHIS) from 1999-2019 to identify participants with self-reported T2D diagnosed after the age of 18. Multivariable linear regression was conducted to identify differences in age of onset of diabetes by race/ethnicity. Covariates of interest included sex, insurance status, education, alcohol use, smoking history, physical activity, BMI, coronary heart disease, hypertension, COPD, liver disease and kidney disease. Sample weighting and survey analysis was conducted per NHIS guidelines to generate nationally representative estimates. Results: A total of 53,613 individuals (representative of 36,543,628, 1% Asian Indian, 65% non-Hispanic White (NHW), 16% non-Hispanic Black (NHB), 14% Hispanic, 1.3% Native American, 0.53% Chinese with mean age 62 years [SD, 14]) were included. Asian Indians, after adjusting for covariates of interest, had an estimated age of onset of 3.83 years earlier than NHW (p-value &lt;0.001). Additionally, Asian Indians had an earlier age of onset compared to NHB, Hispanic, Native American and Chinese groups (age of onset 2.95 years earlier, 3.14 years earlier, 3.76 years earlier, and 3.31 years later compared to NHW, respectively). ( Figure 1) . Conclusions: Among the study population, Asian Indians had an earlier predicted onset of diabetes, ranging from 0.69 to 6.96 years younger, compared to NHW, NHB, Native American, Hispanic, and Chinese populations. This may suggest utility in a younger screening age for higher risk groups.