tbuckley/cabot-search huggingface dataset:
Abstract 4140246: AI and Quantum Sensors: Realization of a Safe and Effective Unshielded Bedside Magnetocardiogram to Detect Ischemia in the Emergency Room
Authors: Geoffrey Iwata, Kirstin Aschbacher, Sajiny John, Simon Tam, Kit Yee Au-Yeung, Johanna Contreras, Deepak Bhatt, Jeffrey Bander
Journal: Circulation (2024)

Introduction: Magnetocardiography (MCG) has potential to significantly improve cardiac disease diagnosis, but adoption in clinical practice is hindered by high cost and large footprints of traditional systems. Hence, we developed a bedside, non-contact MCG system that utilizes quantum magnetometers and AI methods to extract validated cardiac biomarkers, while rejecting ambient magnetic interference. Goal: To investigate the safety and efficacy of the bedside MCG device in identifying non-ST-segment elevation myocardial infarction (N-STEMI) among patients from an urban emergency department. Methods: The MCG system is a custom prototype with 26 optically pumped magnetometers - quantum sensors that measure cardiac magnetic fields with picoTesla sensitivity. We recruited a diverse sample of 78 adult patients (72 with analyzable data) presenting to the ED with chest pain symptoms suggestive of ACS who were not experiencing STEMI (mean age=56 years; 64% male; 11% Asian, 28% Black, 7% American Indian/Alaska Native, 44% White, 1% Native Hawaiian/Pacific Islander, 9% other/unknown; 6 technically unusable recordings, 8%). A 5-minute MCG was recorded within 2 hours of an initial 12-lead ECG. Signal processing and AI algorithms were used to remove ambient interference and recover cardiac signal. Literature-based MCG markers were inputted to a classification and regression tree (CART) model to classify patients as NSTEMI ACS rule-in or rule-out. Results: The CART model successfully discriminated clinically determined ACS rule-in patients (n=7) from rule-outs (n=65) with sensitivity=86% and specificity=92%. The most predictive MCG markers were the field pattern angle difference between R- and T-wave maximum, the power ratio between the R- and T-waves, and the field maximum to minimum ratio. No adverse events were reported. Conclusions: MCG is a promising, non-contact diagnostic tool for emergency physicians diagnosing suspected ACS cases. This pilot study shows that a bedside, quantum-sensing MCG that utilizes AI has the potential to provide safe and accurate diagnostic results, and it is feasible to integrate the device into the ED workflow.
Abstract 4139703: Developing normal values for pulse wave velocity in healthy young people
Authors: Vimarsha Kodithuwakku, Monique Breslin, Jeanne Hersant, Rosa Bruno, Pierre Boutouyrie, Elaine Urbina, Seana Gall, Rachel Climie
Journal: Circulation (2024)

Background: A high prevalence of cardiovascular disease (CVD) globally prompts the necessity of a surrogate marker to identify CVD development at the subclinical stage. Observation of early alterations to the vasculature has proven to be beneficial in identifying adults who have an increased risk of CVD. Hence, utilizing vascular ageing as an effective, non-invasive, subclinical marker in assessing cardiovascular risk in young people could be promising for the reduction of CVD incidence. Pulse wave velocity (PWV) is a marker of vascular ageing, and even though the importance of PWV in cardiovascular health assessment in adults has been established, to use it routinely to evaluate young people at risk, normal values need to be determined. The Youth Vascular Consortium (YVC) is an international collaborative that was established to comprehensively investigate vascular ageing with a range of measures among young people. This study aimed to develop normal values for PWV measured by commonly used devices among healthy young people using data from the YVC. Methods: This retrospective study included data on demographics, anthropometric, biochemical and vascular ageing measures collected from participants aged 1 to 40 years. Generalised additive models were used to derive percentile curves for the PWV data by age. Observed and predicted percentiles at years of age were reported by sex, geographical region and device. Results: The YVC collected data on 36,973 participants from 24 countries across five different regions. Of these, 19,018 participants (mean age = 17 years, 51% female, 71% European) were classified as healthy based on their systolic and diastolic blood pressure, serum glucose, serum cholesterol and body mass index. Six devices were used to measure PWV (30% SphygmoCor). Device-specific percentile curves for PWV against age were constructed and an increasing trend in PWV was identified with age for both males and females. Conclusion: This study provided normal values for PWV measured with six different devices for young people as age and sex-specific percentile curves. These curves may be applied clinically to identify young people with impaired vascular ageing and thus, those who may be at risk of overt CVD.
Abstract 4139757: COVID-19-Related Changes in Dalily Life, Concerns, and Their Associations with Sleep Disturbances
Authors: Sung-il Cho, Young-Mee Kim
Journal: Circulation (2024)

Background: The COVID-19 pandemic has significantly exacerbated sleep problems. Pandemic-related lockdowns and drastic changes in daily life have disrupted sleep patterns, resulting in a marked increase in sleep disturbances. Research questions: This study aims to investigate the primary factors contributing to the increase in sleep disturbances during the COVID-19 pandemic in Korea. By utilizing nationally representative data encompassing various variables, this study seeks to identify COVID-19-related factors associated with sleep disturbances during the pandemic. Method: We analyzed data from the nationally representative Korea Community Health Survey conducted in 2020, including 216,809 adults. Changes in daily life due to COVID-19 were assessed by asking participants to score their current situation compared to their pre-pandemic situation, ranging from 100 (no change) to 0 (complete cessation of daily activities). COVID-19 concerns were assessed with five questions: 1) fear of contracting the virus; 2) fear of mortality if infected; 3) fear of blame from others; 4) concerns about the health of vulnerable family members; and 5) concerns about economic impacts. Sleep disturbances were defined as sleeping 5 hours or less per night on average. Logistic regression analyses with a complex sample design were performed to examine the relationship between COVID-19-related factors and sleep disturbances, adjusting for socioeconomic and health-related variables. Results: A high level of lifestyle changes due to COVID-19 (OR = 1.15, 95% CI = 1.11–1.19) and high COVID-19 concerns (OR = 1.04, 95% CI = 1.01–1.08) were associated with an increased likelihood of sleep disturbances. Conversely, resting during COVID-19 symptoms (OR = 0.81, 95% CI = 0.76–0.87), having support during quarantine (OR = 0.93, 95% CI = 0.89–0.97), and trust in the government and neighbors (OR = 0.92, 95% CI = 0.89–0.96) were associated with a decreased likelihood of sleep disturbances. Conclusion: These findings suggest that sleep disturbances during the COVID-19 pandemic were mediated by lifestyle disruptions and high levels of concern. Social support and trust mitigated the impact of COVID-19-related risk factors. As part of preparedness, improving the environment to facilitate adequate rest during illness, ensuring strong social support, and fostering high levels of trust in the government and neighbors may be important to protect sleep health during future public health emergencies.
Abstract 4139723: Safety and Efficacy of Antisense Oligonucleotides On Triglyceride and Apolipoprotein C-III Levels in Hypertriglyceridemia; A Network Meta-Analysis Of Randomized Controlled Trials
Authors: Kerollos Abdelsayed, Abdelrahman Mahmoud, Qasi Najah, Ahmed Almahdy Mohamed, Anas Abdulkader, Karim Ali, Shehroze Tabassum, Mohamed Abouzid, Sandi Banour, Basel Abdelazeem
Journal: Circulation (2024)

Background: Hypertriglyceridemia is an independent risk factor for cardiovascular diseases. Apolipoprotein C-III (APOC3) inhibition through the antisense oligonucleotides volanesorsen, olezarsen, and plozasiran, reduced triglycerides in the previous trials. However, the safety and efficacy of the three medications have not been compared yet. Methods: A network meta-analysis was performed to compare multiple doses of the three medications to each other through the placebo. Nine randomized controlled trials (RCTs) were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane. The mean difference (MD) and 95% confidence interval (CI) were used for continuous outcomes. The risk ratio (RR) and 95% CI were used for dichotomous outcomes. Results: A total of 782 patients were included. Volanesorsen 300 mg once weekly showed the most significant reduction in triglyceride levels (MD = -90.98%, 95% CI: [-109.2%; -72.8%]; p&lt;0.01 ). Only plozasiran once monthly, regardless of the dose, showed a non-significant reduction in triglycerides, which should be taken with caution as the data were derived from a phase 1 trial with a small sample size. All the regimens significantly reduced APOC3 levels compared to placebo with plozasiran 100 mg and 50 mg once monthly and volanesorsen 300 mg once weekly, showing the most significant reduction (MD range: -92.8% to -88.4%; p&lt;0.01 ). Plozasiran regimens, especially the 25 mg, 50 mg, and 10 mg once monthly dosages, respectively, reduced total cholesterol levels the most compared to placebo (MD range: -30.6% to -23.5%; p&lt;0.01 ). Only volanesorsen, regardless of the dose, did not significantly reduce total cholesterol compared to placebo. None of the treatments showed a statistically significant difference in the adverse events rate compared to placebo. Conclusion: APOC3 antisense oligonucleotide inhibitors effectively reduced triglyceride, APOC3, and total cholesterol levels in hypertriglyceridemia, with an acceptable safety profile. However, due to the relatively small sample size, the results should be interpreted with caution. Further research is needed to confirm the beneficial effects of APOC3 inhibitors and provide strong evidence on the effects of each medication regimen.
Abstract 4139715: The impact of CSL112 and atorvastatin on lipid core stiffness in murine atherosclerotic plaques
Authors: Alireza Rezvani Sharif, Avinash Ashok, Anna Watson, Elena Velkoska, Brandon Greene, Yung-Chih Chen, Ineke Muir, Karlheinz Peter, Raymond Dagastine, Bronwyn Kingwell
Journal: Circulation (2024)

Background: Plaque structural stress (PSS) is the stress within the body of atherosclerotic plaques, resulting from the dilation and stretching of vessels due to arterial pressure. Plaque rupture often occurs at sites of elevated PSS, especially when the stress level exceeds the mechanical strength of the plaque. Notably, a significant difference in stiffness between the softer lipid core and the stiffer fibrous cap significantly increases PSS. By increasing the elastic modulus (a measure of material stiffness) of lipid cores and thus reducing the stiffness disparity between plaque components, it may be possible to transition vulnerable plaques from a state of instability to stability. Hypothesis: Both CSL112, a human plasma-derived apolipoprotein A-I formulation that enhances reverse cholesterol transport, and atorvastatin increase the stiffness of plaque lipid cores. Methods: Rupture-prone atherosclerotic plaques were induced in 47 ApoE knockout male mice using a carotid tandem stenosis model after a 7-week high-fat diet. After surgery, mice were treated with either CSL112 (100 mg/kg) intravenously twice weekly (n=15), saline intravenously (n=15), or atorvastatin (10 mg/kg) daily by gavage for 5 weeks (n=17). All animals were euthanized at 20 weeks of age. Multiple sections from the first proximal segment of the right common carotid artery were extracted for stiffness measurements and adjacent tissues were sliced for histological examination to identify lipid cores. Using atomic force microscopy, nano-indentation tests were conducted on the lipid-rich regions of plaque samples, and the elastic moduli were determined by fitting the Hertzian contact model to the force-indentation data. Measurements were conducted in a blinded manner with respect to treatment groups. Results: The CSL112 group had the highest lipid stiffness, with a mean elastic modulus of 5.27 kPa (95% CI [4.74, 5.80]), followed by the atorvastatin group at 3.02 kPa (95% CI [2.51, 3.53]), and the saline group at 2.11 kPa (95% CI [1.54, 2.68]). Statistical analysis indicated that CSL112 significantly increased the elastic modulus of lipid cores compared to both atorvastatin and saline (p &lt;0.001), while lipid stiffness was also significantly higher in the atorvastatin group compared to saline (p = 0.039). Conclusion: The increase in lipid pool stiffness within atherosclerotic plaques treated with CSL112 and atorvastatin may reduce the level of PSS and enhance plaque structural stability.
Abstract 4140247: Place and Race in Cardiovascular Outcomes among Prostate Cancer Patients in Georgia: a 20-year Geospatial Analysis
Authors: Priyanshu Nain, Neel Kulkarni, Manali Rupji, Harikrishnan Hyma Kunhiraman, Biplab Datta, Vraj Patel, Stephanie Jiang, Nickolas Stabellini, Neal Weintraub, Anant Mandawat, Stephanie Cantu, kevin ward, Jeffrey Switchenko, Sagar Patel, Avirup Guha
Journal: Circulation (2024)

Background: Men with prostate cancer (PC) frequently die of cardiovascular disease (CVD). Rurality has shown to increase adverse outcomes in PC men. 26% of Georgians live outside Urban centers and 120/159 counties of Georgia (GA) are considered rural. Aim: To identify CVD mortality (CVDm) risk factors in GA public health districts (PHD) and map the racial differences in CVDm across PHDs. Methods: Men ≥ 18 years with PC (2004–2018) were identified using GA Cancer Registry, with mortality data from state vital statistics and National Death Index. CVDm was identified by ICD-10 codes. A multivariable Fine and Gray model identified CVDm risk factors. Adjusted competing risk analysis included factors like PHD, race, age, T-stage, hormone therapy, and Gleason Score. Race specific 5-year CVDm rates per 100000 were calculated by multiplying county-specific standardized mortality ratios (SMRs) by the crude race-specific mortality rates of CVD and then aggregating these into PHDs. The ratio of Black vs White CVDm was calculated for each of GA's 18 PHD and mapped using R. Results: Of 51,262 men with PC (median age 63), 36.2% were Black, predominantly from greater Atlanta area (36%) and ~17% received hormone therapy. CVDm was noted in 4.1% of cohort. The PC cohort risk factors for CVDm are presented in Table 1. Men with stage T2-3 PC had a lower risk of CVDm vs stage T1 PC (aHR 0.52, CI 0.36-0.75; aHR 0.47, CI 0.31 – 0.71). CVDm was significantly higher in northwest (aHR 1.72), west central (aHR 1.85), coastal (aHR 1.92), and southeast (aHR 1.90) GA vs. greater Atlanta area. CVDm was significantly higher in Black men (aHR 1.47). High Gleason scores significantly correlated with CVDm (aHR 1.48), though hormone therapy use showed no statistical difference (P=0.124) Figure 1 shows the mapped relative racial disparity. Overall, the highest Black vs. White CVDm differences were noted in Northeast, LaGrange, and Southwest GA as well as Dekalb County in Atlanta (1.81 - 3.63). Conclusion: In GA, there are significant geographic and racial differences in CVDm in men with PC. Determining the reasons (i.e., insufficient access to care, inadequate CVD risk prevention) is needed to establish healthcare equity for all men with PC in GA.
Abstract 4140304: Protein Arginin Deiminase 4 Deficiency Prevents Streptozotocin-induced Diabetic Cardiomyopathy and Heart Failure with Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation
Authors: Nicolas Schommer, Casey Sheehy, Stijn Van Bruggen, Pierre-André Jarrot, William Chan, Dirk Westermann, Denisa Wagner, Lukas Heger
Journal: Circulation (2024)

Background: Heart failure (HF) is a complication of Type 1 diabetes mellitus (T1D) causing high mortality. In T1D activated neutrophils overproduce peptidyl arginine deiminase 4 (PAD4). Aim: Evaluate the role of PAD4 in the pathobiology of HF development in T1D. Methods: T1D was induced in PAD4 -/- and wild type (WT) mice by i.p. injection of 55 mg/kg of Streptozotocin for 5 days. Echocardiography, lung wet-to-dry ratio and exercise intolerance were performed after 8 weeks to evaluate cardiac structural and functional changes. Cardiac collagen content was assessed by picrosirius green staining, levels of neutrophil extracellular traps (NETs) by co-location of Ly6G + , and H3Cit + signal in tissue and inflammasome activation by protein aggregates of the inflammasome adaptor ASC in neutrophils determined by immunofluorescence. Results: PAD4 deficiency did not affect onset or severity of T1D. T1D WT but not T1D PAD4 -/- mice showed a significantly increased proportion of ASC speck + neutrophils (13.8± 4% vs. 3.3±3.1%; n=5; p=0.007). This resulted in elevated IL-1β levels both in plasma (21.7±7pg/ml vs. 11.4±1pg/ml; n=8; p=0.001) and cardiac tissue (0.08±0.002pg/ml vs. 0.06±0.001pg/ml; n=8/6, p=0.001) of T1D-WT mice. T1D-PAD4 -/- mice showed reduced cardiac damage (Troponin I: 58±11pg/mL vs. 91.3±37pg/mL; n=12; p=0.005), collagen deposition (1.2±0.5% vs. 3.3±1.3%; n=6; p=0.008) and tissue levels of transforming growth factor-β (0.23±0.03 vs. 0.33±0.04 ng/L). Echocardiography demonstrated preservation of both systolic (Ejection fraction: 63.8±5.4 vs. 43.7±11.4 %; n=8; p=0.001) and diastolic (E/E’: -19.6±4 vs. -29.9±9; n=10; p=0.004) function with PAD4 deletion and reduced clinical HF parameters (Lung wet/dry ratio: 4.1±0.5 vs. 5.9±0.9; n=8; p=0.001; time to fatigue: 28.1±10min. vs. 7.6±4 min.;n=10,p=&lt;0.0001). Flow cytometry analysis showed significantly reduced levels of infiltrating neutrophils (42±2% vs. 52± 3% Ly6G + of CD11b + CD45 + events; n=8, p=0.02) in the myocardium and histological analysis showed significantly reduced cardiac NET deposition in T1D- PAD4 -/- mice (1.1±0.4% vs. 10.2±2.2% H3Cit + of LV section; n=5, p=0.008). Conclusion: We show, that T1D primes neutrophils for NLRP3 Inflammasome assembly and IL-1β release in a PAD4 dependent manner. Increased cardiac neutrophil infiltration, inflammasome assembly and NET deposition drive profibrotic cardiac remodeling and HF in T1D. Our data suggest PAD4 as a promising target for primary cardiac prevention in T1D.
Abstract 4139769: Fluoxetine, a Novel Therapeutic Strategy for Early Repolarization Syndrome Caused by a <i>KCND3</i> Gain-of-Function Variant
Authors: Tserenlkham Byambajav, Koichiro Takayama, Dimitar Zankov, Minoru Horie, Seiko Ohno
Journal: Circulation (2024)

Introduction: Kv4.3 encoded by KCND3 is an α-subunit of the I to channel and is highly expressed in both brain and heart. Several KCND3 variants have been shown to be related to inherited arrhythmias and neurological disorders. We have reported a gain-of-function (GOF) KCND3 variant, p.G306A, which was identified in a young patient with early repolarization syndrome (ERS) and refractory epilepsy (RE). The variant increased peak current densities and slowed inactivation of I to . Micromolar quinidine inhibited increased I to and accelerated its delayed inactivation. In addition, administration of quinidine to our patient prevented his lethal arrhythmia and epileptic attack. Thus, the suppression of increased I to can be an effective treatment for ERS and RE. However, it remains unknown if other medicine except for quinidine is effective to suppress the GOF effect on I to . Hypothesis: Selective serotonin reuptake inhibitor, fluoxetine which has inhibitory effect for I to normalizes the GOF effect caused by KCND3 variants. Aims: To utilize the fluoxetine for the treatment of ERS and RE, we aimed to elucidate the pharmacological effect of fluoxetine on Kv4.3-G306A comparing those to Kv4.3-wild type (WT). Methods: Plasmids with Kv4.3 WT or G306A were transiently transfected to Chinese Hamster Ovary cells with KChIP2, and reconstituted I to was measured using whole-cell patch-clamp method at 37 0 C degrees. Fluoxetine loading at 1-100 µM was applied externally. Results: The peak current densities of I to at +50 mV were 135.7±19.8 for WT and 321.0±116.7 pA/pF for G306A, and they were decreased to 101.1±20.9 and 199.6±63.6 pA/pF by application of 20 µM fluoxetine (Figure A and B). Fluoxetine inhibited I to peak current with IC 50 of 41.6±7.1 µM for WT and 83.7±16.7 µM for G306A. Although the inactivation in G306A was significantly slower than WT, they were almost normalized after 20 µM fluoxetine application (Figure A and Table). The inhibition effect of fluoxetine was concentration dependent for both peak current densities and inactivation time constants. Conclusion: Fluoxetine rescued the GOF effect on I to reconstituted by KCND3 G306A variant, suggesting that fluoxetine could be an effective therapeutic for ERS and RE.
Abstract 4139722: Association between Age at Menarche and Age at Onset of Angina Pectoris: An Analysis of NHANES Data from 2017-2020
Authors: Prachawanee Nuchpramool, Narathorn Kulthamrongsri, Nisha Wanichwecharungruang, Napat Suriyathumrongkul, Thanaboon Yinadsawaphan, Phuuwadith Wattanachayakul, Chutawat KOOKANOK, Sakditad Saowapa, Tatchaya Kanthajan, Vitchapong Prasitsumrit, Kritpong Kulthamrongsri, Ben Thiravetyan, Thanathip Suenghataiphorn, Chalothorn Wannaphut, Thitiphan Srikulmontri, Ekamol Tantisattamo
Journal: Circulation (2024)

Background: There is suspicion that estrogen may protect against atherosclerosis. Women who experience menarche earlier, and thus have earlier estrogen exposure, might develop atherosclerosis later. The relationship between menarche age and the onset of angina pectoris, a symptom of coronary artery disease, remains unknown. Goal: This study aims to find the correlation between menarche age and the onset age of angina pectoris, and the association between early menarche (onset of menarche ≤ 10 y/o) and early onset of angina pectoris (onset of angina pectoris ≤ 40 y/o). Methods: A cross-sectional study using a population from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The question collects self-reported data on onset of menarche and onset of angina pectoris. The relationship between menarche age and age in onset of angina pectoris was analyzed by linear and logistic regression analysis. Multivariate analysis adjusted for race, age, body mass index (BMI), smoking , diabetes mellitus (DM), hypertension, and dyslipidemia status. Results: Among 4,816 females who reported their menarche age, 88(1.8 %) have had an angina pectoris. The study involved 82 females who reported both the age of menarche and the age of onset of angina pectoris. The mean ± SD of the age at menarche and the age at onset of angina pectoris was 12.53 ± 1.79 y/o and 51.66 ± 15.16 y/o, respectively. The study found a significant association between the menarche age and the age at onset of angina pectoris. After adjusting for confounders, we found that every 1-year increase in the age of menarche will delay the onset of angina pectoris by 1.43 years, with a 95% CI of 0.01 to 2.86.(Table 1A,Graph 1A-1B) We also found that early menarche has a significantly increased risk 2.8 times (95%CI: 1.3, 6.2) of early onset of angina pectoris.After adjusting for confounders, the association became even stronger. The odds ratio (OR) increased to 3.3 (95%CI: 1.4, 8.0), indicating that women with early menarche were 3.3 times more likely to experience early angina pectoris compared to those with later menarche.(Table 2A) Conclusion: In contrast to our hypothesis, age at menarche is positively associated with onset of angina pectoris. The earlier onset of menarche is linked to the earlier onset of angina pectoris. We suspected that factors beyond estrogen levels may contribute to this unexpected finding. Additional studies are needed to examine the cause of this correlation.