tbuckley/cabot-search huggingface dataset:
Abstract 18860: Molecular Pathways Altered in Pediatric Dilated Cardiomyopathy Hearts Are Dependent on Disease Etiology
Authors: Zoe N Leroux, Anis Karimpour-Fard, Bonnie Neltner, Matthew Taylor, Matthew Stone, Brian L Stauffer, Shelley D Miyamoto, Carmen Sucharov
Journal: Circulation (2023)

Introduction: Dilated cardiomyopathy presents a significant clinical burden in pediatric patients due to limited effective treatment options. This study hypothesizes molecular alterations in the heart of pediatric dilated cardiomyopathy (DCM) patients are dependent on specific etiologies. By understanding the molecular mechanisms underlying different etiologies, we aim to enhance diagnostics and guide future targeted therapies. An advanced understanding of the molecular mechanisms of DCM holds potential to transform pediatric cardiovascular care. Methods: RNA was extracted from the IRB approved University of Colorado's pediatric cardiac tissue bank. Samples included non-failing (NF), idiopathic dilated cardiomyopathy (IDCM), myocarditis, and left-ventricle non-compaction (LVNC) hearts. RNA-seq was performed using the Illumina HiSeq 4000 platform, and aligned using the TOPmed RNA-seq pipeline. Statistical analysis between NF and each etiology was performed to identify fold changes and q-values. Gene expression analysis was further examined using Ingenuity Pathway Analysis (Qiagen). Results: Demographics of patient samples were as follows: NF (N=23, % male=61%, Median age=13.65 years, Interquartile range (IQR)=8.6), IDCM (N=20, % male=55%, Median age=9.83 years, IQR=8.98), myocarditis (N=4, % male=75%, Median age=0.35 years, IQR=0.1), LVNC (N=3, % male=33.3%, Median age=0.27 years, IQR= Undetermined). Comparisons between NF versus IDCM, NF versus myocarditis, and NF versus LVNC hearts revealed noteworthy differences in gene expression patterns. Pathways associated with IDCM related to inflammation and immune response trends, whereas DNA repair and cellular damage were strongly associated with myocarditis. Lastly, analysis of LVNC hearts suggest pathways associated with ischemic remodeling. Conclusions: In conclusion, our study provides insights into gene expression patterns associated with different etiologies of DCM in pediatric patients. Distinct patterns were observed between non-failing and IDCM, myocarditis, or LVNC hearts. These findings have implications for improving diagnostics and guiding targeted therapies in pediatric DCM management.
Abstract 17910: Is Implantation of a Larger Edwards Sapien Transcatheter Pulmonary Valve Associated With Early Valve Failure? A Different Type of Patient-Prosthesis Mismatch
Authors: Andrew Headrick, Dana Boucek, Nancy Freestone, Matthew Boucek, Zhining Ou, Robert Gray, Bryan Jepson, Mikayla Gallenberger, Edem Binka, Mary H Martin
Journal: Circulation (2023)

Introduction: Transcatheter pulmonary valve replacement (TPVR) is an alternative option to address failing native and bioprosthetic pulmonary valves (BPV). TPVR has expanded to implantation in native right ventricular outflow tracts (nRVOT) and progressively smaller patients. We aim to define the relationship between valve-to-patient size ratio and early development of pulmonary insufficiency (PI). Methods: This single-center retrospective cohort study identified patients who underwent TPVR with a Sapien valve between 2014 and 2021. We collected demographic, anatomic, and pre- and post-TPVR echo data. Echo data were collected at four post-TPVR time points: prior to discharge, short-term (1-9 months), mid-term (9-18 months), and most recent study. The primary outcome was development of moderate or severe PI by mid-term follow-up. Valve size-to-body surface area (BSA) ratio was evaluated for correlation with the development of moderate or severe PI. Results: The cohort consisted of 187 patients; 79 (42.2%) underwent TPVR within the nRVOT (Table). Compared to patients with TPVR in a conduit or BPV, patients with a nRVOT were younger, had lower weight, and lower BSA. Moderate or severe PI post-TPVR was more common in patients in the nRVOT group (P-value &lt; 0.001), occurring in 9 (11.5%) by mid-term follow-up, compared to 2 (1.9%) in a conduit or BPV. In the subset of patients with TPVR within the nRVOT, the development of moderate or severe PI was associated with a larger valve size-BSA ratio (OR=1.13, 95% CI: 1.03, 1.26, P-value=0.012). Conclusions: Development of moderate or severe PI following TPVR with a Sapien valve was rare in this cohort. Patients receiving a Sapien TPVR within the nRVOT with a large valve size-to-BSA ratio were more likely to develop early PI. The increased risk of early valve failure in these patients should inform counseling regarding expected longevity of the valve and may guide valve choice as more transcatheter valve options become available.
Abstract 13244: Real World Evaluation of an Artificial Intelligence Enabled Digital Stethoscope for Detecting Undiagnosed Valvular Heart Disease in Primary Care
Authors: Moshe A Rancier, Igor Israel, Vimalson Monickam, John Prince, Ben Verschoore, Caroline Currie
Journal: Circulation (2023)

Background: Clinically significant valvular heart disease (VHD) affects 1 in 10 adults over 65. Cardiac auscultation, the current point of care clinical standard, has shown a 44% sensitivity for detecting VHD, leaving most patients undiagnosed. A deep learning based artificial intelligence (AI) platform that detects cardiac murmurs associated with clinically significant VHD (moderate severity or higher, confirmed by echocardiogram) was used to assess its real-time impact on the point of care. Hypothesis: Use of AI during point of care auscultation may lead to higher discovery rates and earlier diagnosis of VHD compared to conventional practice. Aim: Evaluate real world performance of AI vs. primary care physician (PCP) auscultation in identifying previously undiagnosed VHD. Methods: This blinded, prospective study enrolled 369 patients aged 50 and older without a prior VHD diagnosis or history of murmur from three different primary care clinics. Four-point cardiac auscultation was performed on each patient by (1) PCP with a standard stethoscope, and (2) coordinator with an Eko digital stethoscope to collect phonocardiogram (PCG) data for analysis by the AI. Each patient received an echocardiogram to confirm whether clinically significant VHD was present, and their PCG recordings were reviewed by an outside expert panel to confirm whether audible murmurs were present. PCP and expert panel were blinded to AI and echocardiogram results. Performance metrics were calculated for both PCP auscultation and the AI in detecting audible VHD. Results: The AI showed over twofold improvement in sensitivity vs. PCP auscultation for detecting audible VHD (94.1% vs. 41.2%) with limited impact on specificity (84.5% vs. 95.5%). The AI identified 22 patients with moderate-or-greater VHD who were previously undiagnosed, while PCPs identified eight previously undiagnosed patients with VHD. Conclusion: When applied in a primary care setting, a digital stethoscope with structural murmur detection AI showed meaningful impact on new discovery of VHD as compared to conventional practice. These results suggest that AI-powered auscultation at the point of care may significantly increase earlier VHD discovery, facilitate appropriate patient care, and improve outcomes.
Abstract 15804: Intervention to Improve Self-management of Blood Pressure for Low-Income Black Patients With Severe Hypertension
Authors: Anna Tharakan, Holly Biola, Jada Allen, Devan Desai, Megan Gaines, Rohan Gupta, Camryn Johnson, Jennifer Nguyen, Ashna Sai, David Surzykiewicz, Aiyana Villanueva, Vivien Wambugu, Velda Wang, Elliot Yoon, Bradi B Granger
Journal: Circulation (2023)

Background Hypertension is a leading cause of preventable mortality and morbidity and is disproportionately represented among minority populations. Despite proven interventions outlined in practice guidelines, only 48% of patients who are diagnosed with hypertension have their condition controlled. In a southeastern US county, the prevalence of hypertension is 42%, with a strong association with race, suggesting opportunities to intervene at a neighborhood level to reduce hypertension disparities and improve overall population health. Aims To improve access to care through targeted opportunities for self-management of blood pressure (BP). Methods: This quality initiative used a pre-post evaluation design. We identified Black low-income patients with uncontrolled hypertension (SBP &gt; 160 mmHg and/or DBP &gt; 100 mmHg) from a local federally qualified health center (FQHC). Trained student ambassadors provided telephone outreach, BP cuffs, and goal setting on AHA Essential 8 for 4 months. Follow-up occurred at 7 months. Results: Among Black participants (n=345), average age was 55.4 years (SD 8.7), and a majority were male (n=173, 50.1%) and uninsured (n=159, 46.1%). Engagement in calls occurred for 67.8% (n=234) of the cohort; cuff distribution was 22.9% (n=79); and AHA Essential 8 goal setting occurred for 64 patients. BP improved for 40% of the cohort (mean pre: 168/98 mmHg, mean post: 150/89 mmHg; p &lt;0.0001). Of the cohort reached, 33% expressed social needs such as food insecurity, housing, and medication costs. Conclusion Findings suggest that telephone outreach with student ambassadors successfully improves patient engagement and reduces blood pressure, on average.
Abstract 14640: Community Socioeconomic Distress is Associated With Poor Access to Heart Failure Clinical Trials in the United States
Authors: Anirudha S Chandrabhatla, Taylor M Horgan, Adishesh K Narahari, Kenan W Yount, Nicholas R Teman, John A Kern, Sula Mazimba, JAMES D BERGIN, Leora Yarboro
Journal: Circulation (2023)

Introduction: Clinical trials have historically lacked representation from minorities and individuals from lower socioeconomic backgrounds. Little is known about the role geographic access plays in recruiting diverse populations for clinical trials. Objectives: Given disparities in clinical trial enrollment, we sought to analyze how access to heart failure trials varies across demographic groups. Methods: We queried clinicaltrials.gov for trials classified under “heart failure” that are recruiting and enrolling adult patients. Trial site addresses were obtained using Google Maps. We calculated drive times from each US census tract to the closest trial site using ArcGIS Pro v3.1. Demographic information and urban / rural statuses for census tracts were obtained from the US Census Bureau. Distressed Community Index (DCI) scores (0 = no distress, 100 = severe distress) based on metrics including education level, poverty, and unemployment were collected. Data were analyzed using Python v3.8. Results: We identified 954 heart failure trials with 644 unique sites in the US. About 54% of the rural population lives more than 30 minutes from a trial site compared to 22% of the urban population (OR 0.23; p &lt; 0.001). Analysis of DCI scores covering 328 million people revealed that drive times increase with higher socioeconomic distress ( p &lt; 0.001; Figure). In both urban and rural settings, median drive times for individuals in the top 10% of distressed communities (56 min urban and 79 rural) are more than three times those of individuals in the lowest 10% of distressed communities (18 min urban and 23 rural). A larger proportion of non-white minorities live less than 30 minutes from a trial site compared to the white population (77% vs. 60%; OR 2.23; p &lt; 0.001). Conclusions: Increased socioeconomic distress is associated with worse access to heart failure trial sites for both urban and rural populations. Geographic barriers should be addressed to improve diversity in trials.
Abstract 17336: A Hepato-Cardiac FGF21 Signaling Axis Promotes Cardiac Hypertrophy
Authors: Sobuj Mia, Rafailia Sidiropoulou, Matthew Hoffman, Eftychia Markopoulou, Konstantinos Fragkiadakis, Georgios Siokatas, Veera Ganesh Yerra, Craig H Selzman, Stavros Drakos, Dipayan Chaudhuri, Jeff Molkentin, Maria Marketou, Konstantinos Drosatos
Journal: Circulation (2023)

FGF21 is expressed mainly in the liver and other organs, including the heart. The role of FGF21 is controversial, with potential benefits for obesity and certain heart conditions, but also associations with heart failure and increased mortality. We found higher serum FGF21 levels (2.5-fold) in left ventricular hypertrophy patients (N=31) compared to those without hypertrophy (N=45). Similarly, mice subjected to Transverse Aortic Constriction (TAC) had elevated plasma FGF21 levels and hepatic expression. Surprisingly, a time course experiment showed that liver FGF21 production peaked 3 days post-TAC (prior to the onset of hypertrophy), while an unexpected increase of cardiac FGF21 expression was observed 2 weeks post-TAC, coinciding with hypertrophy and dysfunction. FGF21 expression in skeletal muscle did not change. As in mice, hypertensive individuals (N=6) showed a 14-fold increase in cardiac FGF21 mRNA levels compared to normotensive (N=6). To delineate the role of hepatic and cardiac FGF21 in hypertrophy, TAC was performed on mice with hepatocyte- (HEP-FGF21-KO) or cardiomyocyte-specific (CM-FGF21-KO) FGF21 ablation. Both HEP-FGF21-KO and CM-FGF21-KO mice were protected from hypertrophy, pro-hypertrophic signaling, fibrosis, and cardiac dysfunction. Notably, hepatocyte FGF21 deletion prevented cardiac FGF21 upregulation with TAC, suggesting control of CM FGF21 expression by liver-derived FGF21 and highlighting the role of CM FGF21 in driving cardiac hypertrophy. This was confirmed by treatment of AC16 human cardiomyocytes with recombinant FGF21 that increased endogenous FGF21 expression and cell size. RNAseq analysis revealed attenuation of cardiac fibrosis- and hypertrophy-related transcriptome in both HEP-FGF21-KO and CM-FGF21-KO mice. To explore if FGF21 increase is a cause and not a consequence of cardiac hypertrophy, we developed anti-sense oligonucleotides against FGF21 and administered them in C57BL/6 mice with TAC. ASO-FGF21 treatment attenuated cardiac hypertrophy and fibrosis and improved cardiac function. Thus, FGF21 emerges as a therapeutic target for pathological cardiac hypertrophy.
Abstract 14525: Mapping Disparities in Use of Guideline-Directed Medical Therapies for Heart Failure Patients With Reduced Ejection Fraction
Authors: Rishi Desai, Danielle Stonely, naira ikram, Raisa Levin, Ankeet Bhatt, Muthiah Vaduganathan
Journal: Circulation (2023)

Introduction: Current guidelines recommend simultaneous or rapid sequence initiation of multidrug guideline-directed medical therapy (GDMT) classes for heart failure with reduced ejection fraction (HFrEF). Despite this, well documented gaps in implementation exist; however, little is known regarding geographic disparities at the county level. Methods: A cohort study was conducted using Medicare claims (2013-2019). Patients from the study cohort were assigned to counties based on their residential ZIP codes. County level triple therapy use- defined as simultaneous prescription fills for beta blockers, renin-angiotensin system inhibitors (RASi), and mineralocorticoid receptor antagonists (MRAs), within 90 days of a medical encounter where HF was recorded- were calculated as %s. Features of counties including area-level indicators of poverty, employment, and educational attainment and aggregated patient-level sociodemographic and medical history variables were compared by quintiles of triple therapy use. Results: 304,857 patients from 2,600 counties were included. The median (interquartile range [IQR]) for three drug therapy use was 14.3% (10.3%-18.8%) across included counties with a wide variation (range: 0% to 54.5%). Counties in the lowest quintile of triple therapy use were concentrated in the South. Compared to counties in the highest use quintile, counties in lowest triple therapy use quintile had worse area-level indicators of socioeconomic status and were more frequently rural. Among patient-level sociodemographic factors, counties in lowest quintile had higher proportion of Blacks and patients with low-income subsidy. Conclusion and Relevance: Simultaneous use of three GDMT classes was infrequent in patients with HFrEF and a marked variation across counties was observed correlating with indicators of socioeconomic disadvantage. Addressing implementation gaps in GDMT use is a pressing need that requires urgent attention.
Abstract 14746: Association of Left Atrial Late Gadolinium Enhancement With Electrogram Abnormalities, Tissue Impedance, and Proximity to the Aorta
Authors: MirMilad Khoshknab, Tarek Zghaib, Lingyu Xu, Erica Zado, David J Callans, Francis Marchlinski, Yuchi Han, Timothy Markman, Benoit Desjardins, Saman Nazarian
Journal: Circulation (2023)

Introduction: Left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) predominates near the aorta(AO); however, LGE does not equate fibrosis and may be artifactual or indicate expanded interstituim. Hypothesis: We sought to examine the association of LA LGE with proximity to the descending and ascending AO and use regional impedance and voltage measurements to dissect the mechanism of LGE . Methods: The retrospective cohort included consecutive patients who underwent pre-procedural CMR and atrial fibrillation (AF) ablation between January 2016 - 2021. The association of voltage amplitude, impedance, and image intensity ratio (IIR) at each electroanatomic map point with distance from the nearest AO point was examined after adjustment for age, sex, AF type, AO stenosis, LA volume, and AO diameter. Results: Included 63 patients (age 65.5±8.8 years, 33% female). Among 42 ablation naive patients, distance from AO was unassociated with bipolar and unipolar voltage amplitudes, but associated with impedance (+0.04 ohm/mm, P=0.011) and IIR (-0.03 /mm, P&lt;0.001). Among 21 patients with prior ablation, distance from AO was unassociated with IIR, but associated with bipolar (+0.01 mV/mm, P&lt;0.001) and unipolar (+0.01 mV/mm, P=0.001) voltage amplitudes and impedance (+0.03 ohm/mm, P=0.025). Conclusions: Given lower impedance but normal voltage, de novo peri-AO LA-LGE likely signifies expanded interstitium, rather than fibrosis or fat infiltration. Following ablation, peri-AO voltage and impedance are both decreased compared to other LA regions, suggesting that peri-AO lesion delivery is more effective, likely due to lower impedance at baseline.
Abstract 126: Does a Difference in Bystander Cardiopulmonary Resuscitation Initiation and Continuation Exist Due to Patient Sex After Accounting for the Bystander-Patient Relationship?
Authors: Emogene S Aldridge, Stephen Ball, Janet Bray, Nirukshi Perera, Austin Whiteside, Judith C Finn
Journal: Circulation (2023)

Introduction/Background: Differences in bystander cardiopulmonary resuscitation (B-CPR) provision based on the patient’s sex have been reported extensively, with equivocal results. Research question: Do differences in B-CPR according to the patient’s sex exist after adjusting for the bystander-patient relationship? Aim: To explore sex differences in B-CPR initiation and continuation for out-of-hospital cardiac arrest (OHCA) patients while accounting for the bystander-patient relationship. Methods: We analysed consecutive paramedic-confirmed OHCA emergency calls, from 1 January to 30 April 2021, in Western Australia. Calls included were non-traumatic, non- emergency medical service (EMS)-witnessed OHCA, where the bystander was with the patient and CPR was not already in progress. Calls were reviewed in full, and patient and bystander characteristics were coded. Bystander relationship was categorised as either related to the patient or unrelated. We performed a logistic regression of B-CPR initiation by sex, adjusting for patient age (&lt;65 and ≥65) and location (private and public), and bystander-patient relationship. Results: Of the 295 calls included, 203 (69%) of the patients were male, and 164 (56%) were over 65 years of age. Two thirds of the bystanders (65%) were related to the patient. The majority of OHCAs were in private locations (84%). Bystander CPR was initiated in 205 (69%) calls, 69% (139 out of 201) in male patients and 70% (66 out of 94) in female patients (p=0.85). There was no difference in CPR initiation between male and female patients, unadjusted (odds ratio, OR=0.95, 95% confidence interval, 95% CI = 0.56-1.62), or when adjusted for bystander-patient relationship, location, and patient age (OR=0.92, 95% CI=0.53-1.59). Of those who started CPR (205), 175 (85%) bystanders continued performing CPR till EMS arrived. Male OHCA patients were less likely to have CPR continue to EMS arrival than female OHCA patients (OR=0.46, 95% CI=0.16-1.29). Conclusion: There was no effect of patient sex on bystander CPR, both before and after accounting for bystander-patient relationship. Bystanders were more likely to continue performing CPR on female OHCA patients.
Abstract 14596: Differences in Healthcare Resource Utilization Among Patients Receiving Comprehensive Guideline-Directed Medical Therapy by Prior History of Worsening Heart Failure Events
Authors: Catelyn R Coyle, Boshu Ru, Andrew P Ambrosy, Ciaran J McMullan, Andra S Stevenson, Lei Ai, Lori D Bash, Hanna K Gaggin
Journal: Circulation (2023)

Background: Heart failure (HF) is a leading cause of hospitalizations in the US. While Guideline-Directed Medical Therapy (GDMT) improves outcomes in patients with heart failure with reduced ejection (HFrEF), healthcare resource utilization (HCRU) among patients with worsening heart failure (WHF) has not been well characterized. Aim: We compare HCRU by history of WHF at initiation of “2022 GDMT” (i.e., ARNi+β-blocker+MRA+SGLT2i). Methods: Patients with HFrEF who had concurrent exposure for ARNi, SGLT2i, β-blocker, and MRA between Jan 2020-Jun 2022 were identified using Optum’s deidentified Clinformatics® Data Mart Database. HCRU (i.e., all-cause hospitalizations [ACH] and HF hospitalizations [HFH]) was compared by history of WHF (i.e., HFH or IV diuretic administration) in the prior 12 months. Cox proportional hazard and negative binomial regressions estimated factors independently associated with risk of first and recurrent hospitalizations and their durations, respectively. Results: The analytical cohort included 3,881 HFrEF patients receiving 2022 GDMT, 1,835 (47%) with a prior history of WHF. Patients with and without a history of WHF had similar sociodemographic characteristics. The median (IQR) follow-up time was 352 (244, 544) days for the cohort. Patients with WHF were hospitalized sooner, more frequently, and for a longer duration of time ( Table ) compared to those without. After adjusting for sociodemographic characteristics, WHF was independently associated with longer length of stay of ACH (coefficient, 95% CI: 1.91, 1.59-2.31) and HFH (2.13, 1.74-2.61) and almost three times the risk of first and recurrent ACH (HR, 95% CI: 2.93, 2.64-3.26) and HFH (2.93, 2.61-3.29). Conclusion: Prior history of WHF was associated with clinically meaningful and statistically significant worse HCRU, despite first-line “2022 GDMT”. Additional care strategies and novel therapies are required to further decrease residual risk among these patients.