tbuckley/cabot-search huggingface dataset:
Abstract 4147292: An ECG-based Heart Failure Screening Tool for People with Sickle Cell Disease
Authors: Ibrahim Karabayir, Robert Davis, Lokesh Chinthala, Parul Rai, Dan McGuir, Jane Silva Hankins, Oguz Akbilgic
Journal: Circulation (2024)

Background: Tissue hypoxia and chronic anemia associated with sickle cell disease (SCD) leads to structural and physiological alterations in the heart. Early detection of heart failure (HF) in patients with SCD can assist with timely interventions, but current methods (e.g., echocardiogram and heart MRI) are not easily accessible in resource-deprived settings. The integration of artificial intelligence (AI)-powered tools utilizing low-cost ECG data to increase the power to detect more patients eligible for early treatment, thus improving patient outcomes, and needs to be validated. Hypothesis: We hypothesize that ECG-AI models developed to detect incident HF in the general population can detect HF in SCD patients. Methods/Approach: We previously developed an ECG-AI model employing convolutional neural networks to classify patients with HF using a large ECG-repository at Wake Forest Baptist Health (WFBH). This model was developed using 1,078,198 digital ECGs from 165,243 patients, 73% White, 19% Black, and 52% female individuals, with a mean age (SD) of 58 (15) years. The hold-out AUC of this previous model in distinguishing ECGs of HF patients from controls was 0.87. In this study, we externally validated this ECG-AI model using SCD patients’ data from the University of Tennessee Health Science Center (UTHSC). Additionally, a logistic regression (LR) model was constructed in the UTHSC cohort by incorporating other simple demographic variables with the outcome of ECG-AI model. Results/Data: The UTHSC external validation cohort included data from 2,107 SCD patients (188 HF and 1,919 SCD patients with no HF), 98% were Black, 72% were female, with a mean age of 39 (14) years. Despite demographic differences between the validation (more Blacks) and derivation cohorts (lower age), our ECG-AI model accurately identified HF with an AUC of 0.80 (0.77-0.82) in the UTHSC SCD cohort. When incorporating ECG-AI outcome (an ECG-based risk value between 0 and 1), age, sex, and race in a LR model, the AUC significantly improved (DeLong Test, p&lt;0.01) to 0.84 (0.82-0.87) with a sensitivity of 0.76 (0.73-0.79) and specificity of 0.76 (0.74-0.79). Conclusion: The ECG-AI model can detect HF in SCD patients from ECG data alone with moderately high accuracy. The accuracy improves with incorporation of simple demographic data. Future studies will incorporate other clinical risk factors of HF and sickle cell genotype data for further improved accuracy allowing its use for surveillance.
Abstract 4147724: Effect of Nicorandil Therapy on Infarct Size in ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta Analysis of Randomized Controlled Trials
Authors: Malik Saad Hayat, Obaid Ur Rehman, Ahmed Chaudhary, Muhammad Talha Shaukat, Muhammad Mukarram Shoaib, Rayyan Naseer, Wania Rehman, Hadia Ahmad, Muhammad Mohtasham Shoaib, Aqeeb Ur Rehman, Aleenah Mohsin, Muhammad Ahmad Qureshi
Journal: Circulation (2024)

Background: ST-Elevation Myocardial Infarction (STEMI) has a huge clinical burden globally. Pre-administration of Nicorandil before primary percutaneous coronary intervention for STEMI has demonstrated efficacy in enhancing microvascular recovery and reducing reperfusion injury in RCTs. Consequently, Nicorandil exhibits potential in providing considerable cardioprotective advantage in STEMI patients. Aims: Nicorandil therapy is being extensively investigated as a treatment for reperfusion injury associated with primary percutaneous coronary intervention. This meta-analysis evaluates various studies to determine the cardioprotective effects of nicorandil, with particular emphasis on its influence on infarct size. Methods: MEDLINE (via PubMed), Scopus, Cochrane Library, and Google Scholar were systematically searched for relevant studies. Primary endpoint was infarct size. Left Ventricular End Diastolic volume, Left Ventricular End Systolic Volume, Left Ventricular Ejection Fraction (LVEF), Major Adverse Cardiovascular Events (MACE), and rehospitalizations were analysed as secondary end points. Review Manager 5.4 was used to pool mean differences (MD) and Risk Ratios (RR) along with their 95% Confidence Intervals (CI). Results: 3 RCTs including a total of 438 patients were included in our review. Compared with placebo, nicorandil therapy significantly reduced infarct size with a pooled MD of -3.20 (95% CI -5.25 to -1.14). There was also significant reduction in Left Ventricular End Systolic Volume (MD= -5.63; 95% CI -11.22 to -0.05) and a nonsignificant reduction in Left Ventricular End Diastolic Volume (MD= -6.37; 95% CI -12.74 to 0.01). Nicorandil therapy caused a nonsignificant decrease in MACE (RR=0.74; 95% CI 0.37 to 1.46) and readmission rate (RR=0.73; 95% CI 0.30 to 1.77) compared to placebo. It also caused a significant increase in the Left Ventricular Ejection Fraction (LVEF) with a pooled MD of 2.53 (95% CI 0.53-4.54). Conclusion: Pre-treatment with Nicorandil in STEMI patients being treated with primary percutaneous coronary intervention is associated with significant improvement in infarct size and cardiac systolic function.
Abstract 4146923: Self-reported Race, Genomic Ancestry and Hypertension in Hispanic/Latino adults: The Hispanic Community Health Study/Study of Latinos (HCSH/SOL)
Authors: Raul Montanez Valverde, Vivian Kim, Priscilla Duran Luciano, Yawen Yuan, Tamar Sofer, robert kaplan, Sharon Browning, Linda Gallo, Gregory Talavera, Krista Perreira, Martha Daviglus, Sylvia Rosas, Maria Llabre, Tali Elfassy, Xihao Li, Carmen Isasi, Carlos Rodriguez
Journal: Circulation (2024)

Introduction: Among non-Hispanics, hypertension (HTN) disparities by self-reported race exist. Hispanics/Latinos (H/L) are an admixed population of African (AA), European (EA) and Amerindian (AI) continental genetic ancestry (GA). Few studies have explored self-reported race and HTN among H/L. We assessed, among H/L, the associations of self-reported race with GA, and self-reported race and GA with HTN. Methods: Data was obtained from the HCHS/SOL, a population-based cohort of United States (US) H/L. We included mutually unrelated subjects ≥18 years old with genotyping data. Proportions and quintiles of GA were computed with the ADMIXTURE software. HTN was defined as systolic blood pressure (SBP) &gt;130mmHg, diastolic BP (DBP) &gt;80mmHg or on antihypertensive medication. Self-reported race categories were based on the Federal Directive 15. Sampling weights were utilized. Results: We report 9,592 subjects, 49.6% female, mean age 42.9 ±0.28 years. Over half of all H/L self-reported race as Unknown, Declined or Some Other Race (UNK), which did not vary per background group except for H/L of Cuban descent. Among those who self-reported race as Black, White and Native American (NA), the majority were of Dominican, Cuban and Mexican descent, respectively. H/L who self-reported race as Black and White had the greatest proportion of AA and EA ancestry, respectively. H/L who self-reported race as NA or UNK had a predominant mix of EA and AI ancestry. The highest HTN prevalence was seen in H/L who self-reported Black race, as well the ones in the highest EA and AA quintile. H/L in the highest AI quintile had the lowest HTN prevalence along with lower mean SBP and DBP, compared to those in the lower AI quintiles. Conclusions: The majority of H/L did not identify their race suggesting that the concept of race does not resonate since the social context of race in Latin America may not be equivalent to the US. H/L self-reporting race as Black and White, had predominantly AA and EA ancestry, respectively. H/L self-reporting race as Black or in the highest AA quantile had the highest HTN prevalence, similar to what has been reported in non-Hispanic Blacks, whereas H/L in the highest AI quantile had a more favorable HTN profile.
Abstract 4147134: Statin Use and Its Association with Lower LDL Levels in STEMI and NSTEMI Patients at the Time of MI
Authors: Farima Kahe, Jad Lawand, Kaveh Momenzadeh
Journal: Circulation (2024)

Introduction: Elevated LDL cholesterol is linked to microvascular injury and adverse cardiac events in STEMI patients. Statins, or HMG CoA reductase inhibitors, lower LDL levels and reduce cardiovascular risk. This study examines the impact of prior statin use on LDL levels at the time of MI, focusing on NSTEMI and STEMI patients. We hypothesize that patients on statins before an MI will have lower LDL levels and a reduced likelihood of elevated LDL (≥100 mg/dL) compared to those not on statins. Methods: We utilized TriNetX, a comprehensive database of de-identified electronic medical records aggregated from 64 healthcare organizations in the US Collaborative network. The study included patients who sustained either STEMI or NSTEMI for the first time and had a documented LDL cholesterol measurement on or within 24 hours of their MI. Patients were stratified based on whether they had received HMG CoA reductase inhibitor medications at least one month before their MI. The primary outcome was the incidence of LDL levels equal to or greater than 100 mg/dL at the time of the MI. Results: A total of 345,934 patients were included, divided into four cohorts based on their diagnosis (NSTEMI or STEMI) and statin treatment status. The analysis revealed that statin-treated patients had significantly lower LDL levels at the time of MI compared to untreated patients. For STEMI, the treated group had an average LDL level of 87.8 ± 42 mg/dL versus 103 ± 41.2 mg/dL for the untreated group (P&lt;0.0001). For NSTEMI, the treated group had an average LDL level of 84.3 ± 41.5 mg/dL versus 97.6 ± 41 mg/dL for the untreated group (P&lt;0.0001). After propensity matching, the risk of elevated LDL levels was significantly lower in statin-treated patients, with a risk difference of -14.6% and an odds ratio (OR) of 0.54 for STEMI, and a risk difference of -12.8% and an OR of 0.55 for NSTEMI (P&lt;0.0001 for both). Conclusion: This study confirms that proactive statin use is associated with lower LDL cholesterol levels at the time of MI in both NSTEMI and STEMI patients. The significant differences observed between treated and untreated groups highlight the importance of statin therapy in managing patients at risk of myocardial infarction. The marked reduction in LDL cholesterol levels among treated patients suggests that statins could be a critical factor in mitigating the severity of an MI by effectively controlling cholesterol levels.
Abstract 4147664: Retrieval-Augmented Generation for Extracting CHADS-VASc and HAS-BLED Risk Factors from Unstructured Clinical Notes in Patients with Atrial Fibrillation
Authors: Philip Adejumo, Phyllis Thangaraj, Sumukh Vasisht Shankar, Rohan Khera
Journal: Circulation (2024)

Background: Assessment of stroke and bleeding risk in patients with atrial fibrillation (AF) is crucial for guiding anticoagulation therapy. CHADS-VASc and HAS-BLED are widely used scores for defining these risks, but current assessments rely on manual calculation by clinicians or approximations from structured EHR data elements. Unstructured clinical notes contain rich information that could enhance risk assessment. We developed and validated a Retrieval-Augmented Generation (RAG) approach to extract CHADS-VASc and HAS-BLED risk factors from unstructured notes in patients with AF. Methods: We employed a RAG architecture paired with the large language model, Llama3, to extract features relevant to CHADS-VASc and HAS-BLED scores from unstructured notes. The model was deployed on a random set of 1,00 clinical notes (416 AF patients) from Yale New Haven Hospital. To establish a gold standard, 2 clinicians manually reviewed and labeled CHADS-VASc and HAS-BLED risk factors in a random subset of 200 notes. The CHADS-VASc and HAS-BLED scores were calculated for each patient using structured data alone and by incorporating risk factors identified with RAG. We assessed performance across risk factors using macro-averaged area under the receiver operating characteristic (AUROC). Results: The RAG model demonstrated robust performance in extracting risk factors from clinical notes. In the 1000 clinical notes, RAG identified several risk factors more frequently than structured elements, including hypertension (59.7% vs 46.6%), stroke (19.2% vs 12.7%), vascular disease (35.6% vs 27.2%), diabetes (33.9% vs 27.8%), medication usage predisposing to bleeding (29.1% vs 20.9%), and alcohol use (14.4% vs 8.9%). The RAG approach achieved an accuracy of 91% and macro-AUROC of 0.88, significantly outperforming structured data (accuracy 78%, macro-AUROC 0.76) in 200 expert annotated notes. Incorporating risk factors identified by RAG increased both CHADS-VASc and HAS-BLED scores compared with using structured data, with the mean CHADS-VASc score increasing from 3.3 ± 1.9 using structured data to 4.2 ± 2.1 with RAG. Similarly, the mean HAS-BLED score increased from 2.2 ± 1.3 to 2.7 ± 1.5. Conclusion: An LLM-optimized RAG can accurately extract CHADS-VASc and HAS-BLED risk factors from unstructured clinical notes in AF patients. This approach can enable computable risk assessment and guide appropriate anticoagulation therapy.
Abstract 4147229: Guideline-directed medical therapy improves cell viability in an iPSC-derived cardiomyocyte hypoxia injury model
Authors: Jiwen Li, Gentaro Ikeda, Eileen Tzng, Hiroyuki Inoue, Mariko Koike-Ieki, Phillip Yang
Journal: Circulation (2024)

Introduction: Beta blockers, renin-angiotensin-aldosterone antagonists, and mineralocorticoid antagonists are mainstays of current guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction. They have been shown to reduce morbidity and mortality in heart failure patients, reverse remodeling, and improve left ventricular ejection fraction (LVEF) in landmark human clinical trials. GDMT has been hypothesized to interact and have protective effects in bioenergetics in cardiac injury by reducing cardiac workload and energy demand. We have previously used a human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCM) injury model to provide an in vitro validation of bioenergetics through measurement of cell viability and proliferation, intracellular measurement of ATP, contractility, and respiratory function. The application of GDMT in this in vitro model has not been previously assessed. Methods: Highly pure iCMs were differentiated from a healthy, human monoclonal iPSC line using CHIR99021 followed by C59 to modulate Wnt pathway activity. Upon spontaneous contractility, iCMs were replated for purification. Prior to hypoxia exposure, iCMs were treated with either 5uM metoprolol, 5uM losartan, 5uM spironolactone, or a control for 24 hours. To mimic in vivo ischemia, iCM are placed in a glucose deprived media (GDM) in a hypoxia inductor chamber with &lt;1% oxygen-containing mixed gas in a 37°C incubator for 18 hours. A second iCM group is similarly treated in GDM for 18 hours in a normoxic setting. Cell viability and proliferation was then studied using MTT assay. Results: The metoprolol, losartan, and spironolactone treatment groups significantly improved cell viability after hypoxic injury when compared to the control treatment groups. Metoprolol treatment had the highest cell viability after hypoxic injury (46%), followed by spironolactone (23%) and losartan (22%), compared to control (13%). In the normoxic group, metoprolol, losartan, and spironolactone treatment showed no significant difference in viability compared to the control group. Conclusion: iPSC-derived iCMs treated with GDMT improved cell viability after hypoxic injury. The iPSC hypoxia-injury model appears to be a promising in vitro platform for studying the effects of GDMT on cellular bioenergetics.
Abstract 4147779: Dynamin-Related Protein (DRP1) during Myocardial Ischemia-Reperfusion Injury: Culprit or innocent bystander?
Authors: andrew kulek, Karin Przyklenk
Journal: Circulation (2024)

Background: Dynamin-related protein (DRP1) is hailed as the “master regulator” of mitochondrial morphosis events and is understood to orchestrate fission and membrane permeabilization: events largely regarded as the apoptotic “point of no return”. Historically, DRP1 has been targeted through genetic downregulation and small-molecule inhibition, thereby mitigating apoptosis and lethal ischemia-reperfusion (IR). Aim: Our goal was to establish whether knockdown of cellular DRP1 has a protective effect in HL1 cardiomyocytes subjected to lethal IR. Methods and Results: To test this hypothesis, HL1 cells were transfected with siRNA against DRP1 (DRP1 KD group), scrambled siRNA, or vehicle and subjected to a standard IR insult or a time-matched normoxic period. Transfection with DRP1 siRNA achieved ~80% reduction in cellular DRP1. Transfected HL1 cells and matched controls underwent IR and viability analysis with the MTT assay. Our data show that in normoxic controls, DRP1 knockdown was associated with ~35% reduction in viability (Figure). In the IR group, IR produced a ~55% reduction in viability. However, contrary to our hypothesis, DRP1 knockdown modestly exacerbated rather than attenuated - cell death (Figure). To provide a mechanistic explanation for these findings, immunoblotting for markers of mitochondrial injury (i.e., cytochrome c, cleaved caspase 3, cleaved OPA1) were assessed following DRP1 knockdown. Knockdown of DRP1 associated with increases in cytosolic cytochrome c, cleaved caspase 3 and processing of OPA1. Conclusion: Prior studies have reported cardioprotection when DRP1 is either silenced or inhibited. Our data; however, suggests that DRP1 knockdown may promote mitochondrial injury pathways and worsen viability.
Abstract 4147325: Electronic Health Alerts to Improve Mortality and Medication Adherence in Heart Failure Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ubaid Khan, Arej Iltaf, Ahmed Mazen Amin, Mohammed Ayyad, Muhammad Imran, chet ranabhat, Mohamed Abuelazm
Journal: Circulation (2024)

Background: Heart failure (HF) patients are frequently re-hospitalized shortly after discharge. Telemonitoring and electronic health alert follow-up may reduce the mortality and hospitalization in HF patients following discharge. Methodology: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Web of Science, Scopus, Embase, and CENTRAL until May 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using RevMan v 5.4. Results: We included seven RCTs with a total of 6,820 patients. The patients who received electronic alerts were at lower risk of all-cause mortality than those who received usual care [RR: 0.64 with 95% CI (0.45, 0.92, P = 0.01). However, there was no difference in all-cause hospitalization [RR: 0.66 with 95% CI (0.22, 1.98), P = 0.46) between the two groups. Additionally, electronic alert led to a significant increase in the addition of mineralocorticoid antagonist (MRA) in treatment compared to usual care [RR: 1.77 with 95% CI (1.48, 2.11), P &lt; 0.00001) but there was no difference in addition of all class guidelines directed medical therapy (GDMT) [RR: 1.23 with 95% CI (1.00, 1.52), P = 0.05) between the two groups. Conclusion: An electronic health alert was associated with a significant reduction in all-cause mortality and the addition of MRA. Still, there was no difference in all-cause hospitalization and the addition of all-class GDMT.
Abstract 4147009: Advocacy in Cardiology: Healthcare lobbying and campaign finance activities of major cardiovascular professional societies, 2003 to 2023
Authors: Prem Patel, Michael Milks, Andrew Miller, Laxmi Mehta
Journal: Circulation (2024)

Introduction: Political advocacy is crucial for combating health inequities, improving population health, increasing funding of cardiovascular research, and promoting clinician wellbeing. The political activities of major cardiovascular organizations have not previously been characterized. Methods: Lobbying expenditures for six major cardiovascular professional societies were queried from OpenSecrets. Campaign finance data for three cardiovascular political action committees (PACs), ACC’s HeartPAC, SCAI-PAC, and STS-PAC, were obtained directly from the Federal Election Commission. Descriptive statistics of each organization’s lobbying expenditures and PAC donations from members were compared to other medical specialties. Data were aggregated per year to assess trends between 2003-2023. Results: From 2003-2023, the ACC and AHA spent $34,130,110 and $14,285,652 on lobbying, respectively. Other societies reported less robust and consistent lobbying expenditure over the study period: American Society of Echocardiography ($2,080,000), Heart Rhythm Society ($1,450,918), American Society of Nuclear Cardiology ($759,000), and Heart Failure Society of America ($140,000). Annually, the ACC and AHA spent more on lobbying compared to all other societies combined ($2,526,767 vs. $224,000). Temporal analysis revealed a meaningful increase for ACC, from $80,068 in 2003 to $1,890,000 by 2023 and a numerical decrease for AHA, from $570,000 in 2003 to $550,000 by 2023. Notably the American Society of Nuclear Cardiology and American Society of Echocardiography showed increases in annual lobbying expenditure over the study period ($10,000 to $90,000 and $40,000 to $200,000). HeartPAC and SCAI-PAC collected 19,326 donations from 2003-2023. HeartPAC received $7,015,821 from 6266 donors (median, $250) and SCAI PAC received $358,643 from 256 donors (median, $500). STS-PAC received $3,160,192 from 2231 donors (median, $500). Most donations to HeartPAC and SCAI-PAC came from cardiologists (95.5%), followed by administrators (1.0%) and executives (1.0%), and 2870 donations (14.9%) came from university-affiliated individuals. Conclusion: The ACC and AHA remain key stakeholders in cardiovascular lobbying efforts. Several other medical specialties raise &gt;two-fold greater PAC contributions compared to cardiovascular medicine. With the rising importance of advocacy to affect issues facing clinicians, enhancing cardiovascular society engagement would be an important political strategy.