tbuckley/cabot-search huggingface dataset:
Abstract 4137155: Relationship between Subclinical Myocardial Injury and Global Cognitive Performance: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Shubham Tomar, Karita Lidani, Aline Moraes, Shi Huang, Khurram Nasir, Michael Blaha, Susan Heckbert, Timothy Hughes, Christopher deFilippi, Yader Sandoval, Allan Jaffe, Andrew DeFilippis
Journal: Circulation (2024)

Background: With demographic trends transitioning towards older adults, dementia and cognitive impairment are predicted to increase dramatically. We aim to elucidate the relationship between subclinical myocardial injury, as indicated by asymptomatic increased levels of high-sensitivity cardiac Troponin (hs-cTnT), and cognitive performance. Methods: We studied MESA participants from Exam 1 (2000-02) to Exam 6 (2016-18), categorizing them based on baseline hs-cTnT at Exam 1. Cognitive decline was defined as a decrease of ≥5 units in CASI between Exam 5&amp;6. We used Pearson correlation and linear regression to analyze the association of hs-cTnT levels with CASI scores, and logistic regression to examine the association with cognitive decline. We also explored the relationship between different hs-cTnT categories and cognitive measures. Models were adjusted for demographics, lifestyle, APOE status, comorbidities, and medication use ( Figure ). Results: 4445 participants had both baseline hs-cTnT and valid Exam 5 CASI scores while only 1776 participants had valid Exam 6 CASI scores. Cohort was predominantly female (53%), mean age of 60 years, and 27% had at least one APOE e4 allele. Median hs-cTnT was 6.32 ng/L, and median CASI scores were 89 at Exam 5 and 91.5 at Exam 6. We found a negative correlation between the log-hs-cTnT at Exam 1 and Exam 5 with CASI scores at Exam 5. An increase of one unit in log-hs-cTnT level was associated with a decrease of 0.67 (CI -1.17, -0.17) in CASI and corresponded to higher odds (OR: 1.44; CI 1.05-1.95) of cognitive decline, after adjusting for covariates. When comparing various categories of hs-cTnT with category 1, we observe that the odd of cognitive decline increases as the category increases. However, this trend does not hold for category 5 with significantly lower sample size ( Figure ). Conclusion: Our findings indicate an inverse relationship between hs-cTnT and cognitive function years later, which is significantly attenuated by known risk factors for cognitive decline. Further research is needed to determine hs-cTnT as a predictor of future global cognitive functions.
Abstract 4137165: Changes in Contrast Volume among Patients Undergoing Percutaneous Coronary Intervention: a Report from NCDR CathPCI registry
Authors: Nobuhiro Ikemura, Paul Chan, David Cohen, kevin kennedy, Anezi Uzendu, Shun Kohsaka, John Spertus
Journal: Circulation (2024)

Background: Acute kidney injury (AKI) is the most common complication after percutaneous coronary intervention (PCI) and can be mitigated by using less iodinated contrast. The National Cardiovascular Data Registry (NCDR) supports quality improvement initiatives by providing quarterly, risk-adjusted, institutional AKI rates. However, it remains uncertain whether these efforts have reduced procedural contrast volume, particularly in high-risk patients. Aims: Examine temporal trends in contrast volume during PCI across different pre-procedural AKI risk strata. Methods: Within the NCDR CathPCI Registry, we identified PCIs performed between April 1, 2018, and December 31, 2022, and examined changes in mean contrast volume over time across different pre-procedural AKI risk strata defined by the validated NCDR AKI risk model. A multivariable hierarchical model, with the physician as a random effect, was constructed to assess the trend in contrast volume use over time. Results: Among 3,126,559 patients undergoing PCI (mean age = 66.8 ± 11.7 years, 69.4% men, and 39.9% elective procedures), contrast volume declined from a mean of 168.1±77.6 ml in Q2 2018 to 149.8±71.2 ml in Q4 2022 ( p &lt; 0.001 for trend) with the trend being consistent across AKI risk strata ( Figure ). After adjusting for patient and pre-procedural characteristics, the contrast volume declined by 18.9 ml (95%CI 19.1 to 18.6, P &lt;0.001) between 2018 and 2022. Despite marked physician variability in mean contrast use, the lowest mean contrast doses were observed in patients at greatest AKI risk (&gt;15%). Conclusions: PCI contrast administration has declined over time, and the average exposure was lowest in patients at highest risk for AKI, suggesting improved efforts to reduce AKI over time.
Abstract 4137186: No Room for Chronotropic Incompetence in Living Fontan Patients: Enhanced Heart Rate Increase in Response to Exercise to Compensate Low Stroke Volume Reserve
Authors: Takeshi Tsuda, Daphney Kernizan
Journal: Circulation (2024)

Background: Fontan patients reveal decreased peak exercise performance in combination with low peak heart rate (HR), which is frequently interpreted as chronological incompetence. This is counterproductive as HR increase has to be enhanced to compensate limited stroke volume increase in Fontan physiology. Methods: Cardiopulmonary exercise testing (CPET) data in asymptomatic Fontan patients and age-matched control subjects were retrospectively studied. Peak and submaximal CPET parameters were obtained by cycle ergometer. Chronotropic capacity was assessed by peak HR/peak [WR/kg] and submaximal slope of HR/[work rate (WR)/kg] (ΔHR/Δ[WR/kg]) for males and females, separately. Results: Table 1 presents CPET data of Fontan patients (51) and controls (65). Fontan patients showed significantly lower peak HR, peak WR, peak oxygen consumption (VO2)/kg, %predicted maximum VO2, and peak oxygen pulse (pOP)/kg than controls in both sexes whereas peak HR/peak [WR/kg] was significantly higher in Fontan patients, indicating higher HR at the maximum effort in Fontan patients than in controls. Fontan patients showed higher ΔHR/Δ[WR/kg], a marker for HR-dependency, and lower Δ[VO2/kg]/ΔHR, a surrogate of stroke volume, suggesting higher HR was compensating lower stroke volume during submaximal phase of exercise in Fontan patients. Figure 1 demonstrates a linear relationship between ΔHR/ΔWR and peak HR/peak WR in both sexes. Male Fontan patients revealed a comparable trend with controls, whereas female Fontan patients showed higher HR increase at the peak exercise effort than controls with the same ΔHR/ΔWR, suggesting more limited stroke volume reserve than male Fontan patients. Conclusions: Fontan patients showed higher HR-response to exercise than controls in both sexes due to limitation in stroke volume increase. Our data indicate that lower peak HR in Fontan patients results from early exhaustion due to limited stroke volume reserve rather than primary chronotropic incompetence.
Abstract 4137103: Myofibril Mechanics and Transcriptomic Profiling Confirm Distinct Phenotype of <i>TNNI3-</i> Cardiomyopathy Mouse Model
Authors: Elizabeth Silver, Betul Gunes, Axel Fenwick, Anthony Cammarato, Eric Adler, Paul Bushway
Journal: Circulation (2024)

Introduction: Cardiac troponin I (cTnI, TNNI3 gene) is a highly conserved subunit of the sarcomere that inhibits contraction by preventing actin-myosin interaction. Pathogenic TNNI3 variants can cause both hypertrophic and restrictive cardiomyopathies but lack targeted therapies. We identified a family with restrictive cardiomyopathy carrying a cTnI variant at amino acid 157 (A157V). Using CRISPR-Cas9, we generated a knock-in mouse model reflecting this mutation (A158V in mouse). Our previous studies showed that homozygous A158V mice had impaired cardiac relaxation on invasive hemodynamics but normal lifespan, no echocardiographic changes, and no fibrosis. Hypothesis: Myofibril mechanics and transcriptomic studies will better discriminate TNNI3 A158V mice from WT than previous phenotyping studies. Methods: Heart tissue was obtained from wild-type (WT) and homozygous A158V mice at 9-10 months. Myofibrils were isolated from heart tissues and mechanical measurements were completed using the fast solution switching method. RNA was extracted for bulk RNA sequencing. Results: Isolated myofibril studies showed significant prolongation of the linear relaxation phase in A158V mice versus controls (p=0.02) but no significant differences in active tension. Unsupervised clustering of bulk RNA samples separated A158V samples from controls, with 44% transcriptional variation derived from genotype. Cardiac changes in the A158V model were confirmed by significant depletion of pathways involved in structural components of the contractile apparatus, including contractile fiber, sarcomere, and I-Band. On an individual gene level, A158V mutated mice displayed higher expression of cardiac remodeling genes such as Timp1 , Postn , and Tnc . Conclusion: The TNNI3 A158V variant consistently produces impaired relaxation with myofibril studies showing prolonged linear relaxation phase. Transcriptomic studies highlight distinct clustering of TNNI3 A158V mice from WT, with prominent depletion in contractile apparatus pathways. Our findings suggest traditional methods to characterize mouse models may fail to capture disease phenotype in cardiomyopathies; however, myofibril studies and transcriptomic profiling may reveal earlier phenotypic changes.
Abstract 4137191: Association of Cost-Related Medication Non-Adherence with Food Insecurity in U.S. Adults with Atherosclerotic Cardiovascular Disease
Authors: Alexander Ambrosini, Sridhar Mangalesh, Emily Fishman, Kamil Faridi, Michael Nanna
Journal: Circulation (2024)

Background: The association of cost-related medication non-adherence (CRN) with food insecurity (FI) is not well described in those with atherosclerotic cardiovascular disease (ASCVD). Research Questions: Is FI associated with CRN in those with ASCVD, and does enrollment in the Supplemental Nutrition Assistance Program (SNAP) modify this effect? Methods: Data from the National Health Interview Survey (NHIS) 2011-2018 cycles were analyzed. A total of 22,304 adults (weighted: 17.7 million) with ASCVD and available food security, medication adherence and linked mortality data from the National Death Index were included. FI was defined as 3 or more affirmative responses to the USDA food security survey. CRN was identified by an affirmative response to delayed prescription filling, took less medication, or skipped medication doses to save money in the past 12 months. Analyses accounted for the complex survey design to obtain nationally representative estimates. Survey-weighted logistic regression was used to determine predictors of CRN, and Cox regression was used for mortality analyses. Results: Among adults with ASCVD, 13.3% (95% CI 12.7-13.9%; 2.34 million) reported CRN, 15.0% (95% CI 14.3-15.7%; 2.65 million) reported FI, and 5.7% (95% CI 5.3-6.2%; 1.01 million) reported both concomitantly. Those reporting CRN were more likely to be younger, female, non-white, without health insurance, below the federal poverty limit, have lower educational attainment, more comorbidities, and report FI. FI and SNAP enrollment were significantly associated with CRN after multivariable adjustment (adjusted odds ratio [aOR] 4.35 [95% CI 3.74-5.05] and 1.28 [95% CI 1.06-1.55], respectively). A significant interaction was observed between FI and SNAP enrollment (Pint = 0.001), and FI was associated with lower odds of CRN among the SNAP-enrolled versus unenrolled (aOR 2.50 [95% CI 1.98-3.14] vs 5.74 [95% CI 4.82-6.85]) (Figure 1). CRN and food security were not significant predictors of all-cause or cardiovascular mortality in the fully adjusted models. Conclusion: Among adults with ASCVD, FI and SNAP enrollment independently predict CRN. Among adults with ASCVD and FI, more than one third reported CRN and those without SNAP had more than twice the odds of CRN. Greater SNAP enrollment may improve medication adherence in those with ASCVD and FI.
Abstract 4137267: A novel reproducible low-cost model of acute myocardial infarction in swine
Authors: Yichen Li, Zilong Zheng, Weijie Tang, Wangping Chen, Jinfu Yang, Chengming Fan
Journal: Circulation (2024)

Background: Traditional open- and closed-chest methods for inducing acute myocardial infarction (AMI) in pigs typically require extensive and expensive instrumentation, including ventilators and inhalation anesthesia. This study aims to evaluate a reproducible and low-cost model for AMI in pigs using lower hemisternotomy. Methods: Twenty Yorkshire swine (15-20 kg, 45-50 days of age) underwent permanent ligation of the roots of the first and second diagonal branches of the left anterior descending coronary artery. The procedure was performed under intramuscular anesthesia (1ml 0.5mg/kg Zoletil™ and 2ml 10mg/kg xylazine hydrochloride) with spontaneous respiration. Cardiac function was assessed via echocardiography and cardiac PET/MRI scans at 1 and 4 weeks post-MI. Heart tissue was collected for pathological analysis to evaluate the establishment of the AMI model. Results: All animals exhibited ECG changes, including premature ventricular complexes and ST-segment elevation immediately after ligation. No ventricular tachycardia and fibrillation was observed during the operation. No animals (0%) died during infarct creation. The "Skin-to-Skin" procedure time was 18±3.3 minutes. this procedure produced an infarction that occupies ~10% of the left ventricular mass accompanied with the decrease of LV heart function and LV anterior wall thickness 4 weeks post-MI. Conclusions: This novel low-cost technique provides reproducible acute coronary artery occlusion at a selected location with subsequent AMI. It avoids ventilation, inhalation anesthesia, major surgery and does not require expensive instrumentation for intracoronary intervention.
Abstract 4137064: High Incidence of Adverse Neonatal Outcomes of Pregnancy in Women with Congenital Heart Disease
Authors: Lindsay Edwards, Sarah Goldstein, Ester Nilles, Karen Chiswell, Alfred DOttavio, Matthew Reeder, Jill Glidewell, Kathleen Wood, Neeta Sethi, Cheryl Raskind-Hood, Wendy Book, Marcia Feldkamp, Jennifer Li, Lorenzo Botto
Journal: Circulation (2024)

Background: Neonates born to women with congenital heart disease (CHD) are at high risk for adverse outcomes. We sought to describe these outcomes and maternal/pregnancy risk factors. Methods: We analyzed linked clinical, administrative, and birth certificate data in 3 geographic areas in Georgia, North Carolina and Utah from 2011 through 2014. Birth certificates provided neonatal, maternal and pregnancy characteristics. Maternal CHD was identified from linked clinical and administrative data and categorized as severe , shunt , valve , or shunt+valve . Neonatal outcomes of interest included preterm delivery (&lt;37 wk), low birth weight (&lt;2500 g) (LBW), small for gestational age (SGA), neonatal intensive care unit admission (NICU), a composite “any poor outcome” (one or more of preterm, SGA, or NICU), and CHD. Neonatal outcomes were summarized using descriptive statistics. Differences by maternal CHD severity were assessed using Kruskal-Wallis and Chi-square tests for continuous and categorical variables, respectively. Association of maternal/pregnancy characteristics and neonatal outcomes were assessed using generalized estimating equations with logit link function clustered on mother and adjusted for mother’s age, birth year, and state. Results: We identified 2,422 liveborn neonates (median gestational age 38 wks, weight 3155 g) born to 1,987 women with CHD (34% severe , 32% non-White, median age 28yrs). Overall, 19% were preterm, 18% LBW and 14% SGA; 25% required NICU and 40% experienced the composite adverse outcome (preterm, SGA, and/or NICU). CHD was present in 4.2%. Infants born to mothers with severe CHD (vs. combined non-severe) were more likely to have an adverse composite outcome [aOR 2.1 (1.7, 2.5)] and CHD [aOR 17.1 (9.3, 31.5)]. Black race [vs. White, aOR 1.8 (1.4, 2.3)], pregestational diabetes (DM) [vs. no, aOR 2.5 (1.3, 5.0)], gestational hypertension (GHTN) [vs. no, aOR 2.1 (1.5, 3.1)], prior preterm birth [vs. no, aOR 2.0 (1.3, 3.1)] and multiples [vs. singleton, aOR 6.7 (3.8, 11.6)] were associated with increased risk of composite adverse outcome. Conclusions: Forty percent of neonates born to women with CHD experienced an adverse neonatal outcome. Risk increased with maternal CHD severity, Black race, GHTN, DM, prior preterm birth, and multiple pregnancy. These findings highlight the need for heightened awareness and surveillance of these risk factors and expert preconception and pregnancy counseling for woman with CHD.
Abstract 4136758: Apabetalone: evaluating cardiovascular and safety outcomes in meta-analysis
Authors: Lokman Hekim Tanriverdi, Muhammed Melih Dogan, Ibadete Bytyci, PEter Penson, Peter Toth, Maciej Banach
Journal: Circulation (2024)

Background: Epigenetic mechanisms play a pivotal role in the transcriptional programs associated with cardiovascular disease (CVD). Apabetalone, an orally available inhibitor of BET proteins that serve as key epigenetic readers, and modulating gene expression - holds promise as a therapeutic intervention in CVD management. Understanding its efficacy and tolerability is crucial for delineating its potential impact on disease progression and patient outcomes. Purpose: This systematic review and meta-analysis aimed to assess the impact of apabetalone in patients with cardiovascular disease. Methods: The meta-analysis was registered with PROSPERO (CRD42023423298). Databases searched included Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science. Three unique RCTs with total of 2897 patients were included, with trial durations ranging from 12 to 124 weeks. Primary outcomes assessed were all-cause mortality and non-fatal myocardial infarction (MI). Data analysis was performed using the inverse variance common effect model. Subgroup analyses were conducted based on the presence of atherosclerotic cardiovascular disease (ASCVD) or its increased risk. Results: Among the primary outcomes, no significant effects of apabetalone were observed on all-cause mortality (RR 0.88, 95% CI 0.63 to 1.23) or non-fatal MI (RR 0.83, 95% CI 0.62 to 1.11). Apabetalone demonstrated favorable effects on increasing Apo A1 (SMD 0.20, 95% CI 0.04 to 0.35) and HDL (SMD 0.29, 95% CI 0.09 to 0.49). However, no significant effects were observed for changes in Apo B, LDL, non-HDL, total cholesterol. Subgroup analysis did not reveal any significant differences in outcomes. Significant effects were noted in secondary outcomes. Apabetalone showed a significant increase in adverse events (AEs) leading to withdrawal (RR 1.61, 95% CI 1.21 to 2.15) and ALT and AST increases greater than three times the normal value (RR 4.50, 95% CI 2.73 to 7.41). Conclusion: Our meta-analysis highlights the significant impact of apabetalone on certain lipid parameters and adverse events. However, it did not demonstrate significant effects on all-cause mortality or non-fatal MI. Further well-designed and reported RCTs were warranted to elucidate the clinical implications of apabetalone in selected group of patients that might benefit the most from apabetalone that may also improve cardiovascular disease management.
Abstract 4136861: Title: Protein interaction profiling of the Kv11.1 potassium channel reveals new therapeutic targets for Long QT Syndrome
Authors: Christian Egly, Lea Barny, TRI DO, Lars Plate, Bjorn Knollmann
Journal: Circulation (2024)

Background: The voltage-gated potassium ion channel K V 11.1 plays a crucial role in cardiac repolarization. Genetic variants in K V 11.1 lead to Long QT Syndrome (LQTS), a condition associated with fatal arrhythmias. Approximately 90% of missense variants linked to LQTS cause intracellular protein transport (trafficking) dysfunction. Some K V 11.1 channel blockers act as chemical chaperones (e.g., E-4031) and increase K V 11.1 channel trafficking. However, these drugs cannot be used in LQTS patients. The underlying mechanisms, such as the protein networks involved in folding and quality control for K V 11.1 channel trafficking remain largely unexplored. Methods: We used affinity-purification (e.g., coimmunoprecipitation) coupled with mass spectrometry to quantify protein interaction changes in human embryonic kidney cells expressing wild-type K V 11.1 or two trafficking-deficient channel variants in the presence or absence of chemical chaperone E-4031. After co-immunoprecipitations and protein digestions, peptides were identified using multiplexed mass spectrometry. Results: We identified 572 protein interactions enriched in K V 11.1-expressing cells. We used bioinformatic analysis to make a cellular model showcasing likely K V 11.1 protein interactions localization from early biogenesis and transcription to plasma membrane expression (Figure 1). We revealed proteins responsible for protein folding, translation, proteasomal degradation, and others with most protein interactions significantly elevated in the genetic variants compared to wild-type (Figure 2). Upon 24-hour treatment with E-4031, some of these interactions were reduced towards wild-type and indicated potential molecular targets for therapeutic intervention (Figure 3). Conclusions: We report the discovery of novel K V 11.1 protein-protein interactions that could be therapeutically targeted to improve K V 11.1 trafficking and treat Long QT Syndrome.
Abstract 4137188: Racial and Ethnic Disparities in Catheter Ablation for Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Sheikh Moinul, Manuel Urina-Jassir, Joan Rodriguez-Taveras, Matthew Yuyun
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is the most prevalent arrhythmia globally, with an escalating incidence in the United States. It is known that racial and ethnic disparities exist in the management of AF. Although current guidelines recommend catheter ablation (CA) as one of the most effective rhythm control strategies, recent data suggest that minority populations, including Black, Hispanic, and Asian individuals with AF, are less likely to undergo CA, and aggregate data are lacking in this area. Aims/Hypothesis: To determine differences in CA rates and the likelihood of undergoing CA for AF in racial/ethnic minority populations compared to Caucasians. We hypothesized that minorities are less likely to undergo CA for AF than their non-minority counterparts. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library, based on an a priori registered protocol (PROSPERO Registration CRD42024496174), from January 1st, 2010, to January 2nd, 2024, was conducted to identify studies with ≥ 500 participants assessing CA use in AF in at least two racial/ethnic groups. Data were combined using a random-effects model meta-analysis. Results: A total of 431 non-duplicate records were identified. After independent screening based on inclusion/exclusion criteria, 19 studies comprising 12,598,109 patients were included. Among them, 9,577,652 (76.0%) were White, 789,954 (6.3%) were Black, 476,216 (3.8%) were Hispanic, 113,005 (0.9%) were Asian, while 1,641,282 (13.0%) were classified as other or were missing race/ethnicity data. The proportion of White subjects who underwent CA for AF was 4% (95% CI 3-5%). In contrast, the proportion of Black, Hispanic, and Asian individuals with AF who underwent CA was 2% (95% CI 1-3%), respectively, for each group. Pooled odds ratios (OR) of having CA for AF compared to Whites were 0.68 (95% CI 0.56 - 0.83), 0.72 (95% CI 0.63 - 0.82), 0.64 (95% CI 0.48 - 0.86) for Blacks, Hispanics, and Asians, respectively. Conclusions: The use of CA among the total AF population was low across all ethnic groups. Moreover, racial/ethnic minority groups were significantly less likely to undergo CA compared to White patients.