bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14532: The Off-Hour Effect on Clinical Outcomes of ST-Segment Elevation Myocardial Infarction Complicated by Cardiogenic Shock Patients Treated With Impella: Insight From Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD)
Authors: Suzuki Takahiro , Asano Taku , Yoneoka Daisuke , Kijima Yasufumi , Mizuno Atsushi ,   and the J-PVAD Investigators
Published: December 2023

Introduction:
The off-hours effect is a contentious issue in that patients admitted on weekends or nighttime have worse outcomes than on weekday daytime. The off-hours effect in patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMI-CS) treated with Impella has not been fully evaluated. Hypothesis: The off-hours admission is associated with longer door-to-unload (DTU) time, door-to-balloon (DTB) time, and higher mortality in this population.

Methods:
We used the Japanese large-scale registry data for Percutaneous Ventricular Assist Device (J-PVAD), which registered all consecutive patients treated with Impella from December 2019 to July 2022. We compared the effects of on-hours and off-hours admissions on DTU time, DTB time, and 30-day mortality. We defined “on-hours” as between 8:00 and 19:59 on weekdays and the other time as “off-hours”. A multiple linear regression model was used to reveal the independent factors of prolonged DTU and DTB times. The Cox proportional hazards model was applied to calculate adjusted hazard ratios [aHR] for 30-day mortality, controlling for conventional cardiac risk factors.

Results:
Of 2,453 patients, 775 (32%) (mean age 68 years, 628 (81%) male) STEMI-CS patients treated with Impella were included. Among them, 401 (39%) were admitted during off-hours. We observed 155 deaths (49%) among patients admitted off-hours and 134 deaths (36%) among patients admitted on-hours during the follow-up period (median: 23 days). The DTU and DTB times were significantly longer in patients admitted off-hours than in patients admitted on-hours (91 (IQR 74-164) vs. 74 (62-151) minutes, p<0.001; 104 (77-134) vs. 89 (61-122), p<0.001, respectively). The linear regression model showed that the off-hours admission was associated with longer DTU time (β=14.3 minutes, 95% CI 4.8-23.8, p=0.003) and DTB time (15.4, 5.0-25.7, p=0.004). The Cox proportional hazards model showed that off-hours admission was associated with a higher risk of 30-day mortality than on-hours admission (aHR=1.42, 95% CI: 1.03-1.96, p=0.03).

Conclusion:
Our findings implied that the off-hours effect existed in DTU time, DTB time, and 30-day mortality among STEMI-CS patients treated with Impella.
Abstract 14654: Contemporary Gender Differences in Clinical Outcomes of Patients With Takotsubo Cardiomyopathy - A United States National Inpatient Sample Database Analysis
Authors: Almani Muhammad U , Khan Rasha , Qudrat Ullah Muhammad , Fatima Anum , Suarez Audry Chacin , bonita Raphael , Bozorgnia Behnam
Published: December 2023

Introduction:
Takotsubo cardiomyopathy (TCM) is classically more prevalent in females, however whether gender differences exist in clinical outcomes of patients with TCM need further clarification. Given the lower prevalence of TCM in males, limitations of previous research included small sample size and demographic disproportion between groups. The purpose of our study is to analyze gender differences in clinical outcomes of TCM hospitalizations using national inpatient sample (NIS).

Methods:
We searched the 2020 NIS for TCM hospitalizations using ICD 10 code I51.81. Multivariable logistic regression model adjusted for patient and hospital level confounders was used to compare the clinical outcomes between genders.

Results:
We identified 41,290 TCM hospitalizations in 2020. Of these 19.9% were males (mean age = 63 years, mean charlson comorbidity index = 3.2) and 80.1% were females (mean age = 68 years, mean charlson comorbidity index = 2.7). Females had a lower risk of inpatient mortality (OR: 0.49, 95% CI 0.41-0.58, p < 0.001), cardiac arrest (OR: 0.58, 95% CI 0.43-0.79, p = 0.001) and cardiogenic shock (OR: 0.67, 95% CI 0.55-0.82, p < 0.001). There was no gender difference in the use of intra-aortic balloon pump (IABP), Impella assist system, or extra-corporeal membrane oxygenation (ECMO)
Figure 1.

Conclusion:
Our findings indicate that despite a higher prevalence of TCM in females, clinical outcomes were worse in males. In our analysis, there was no gender difference in the use of IABP, Impella or ECMO. Future research is needed to better understand clinical predictors of adverse cardiac events in male patients hospitalized with TCM to improve outcomes.
Abstract 14872: A Nationwide Telehealth Heart Failure Program: Can Remote Patient Monitoring and Guideline Directed Treatment Protocols Benefit HFpEF Management?
Authors: Feldman David I , Repnikov Dmitri , Campbell Marcus L , Babikian Sarine , Sanchez Diana , Sharma Ashwyn , Curnow Randall , Feldman Theodore , Fudim Marat
Published: December 2023

Introduction:
Heart failure (HF) patients experience unnecessary morbidity and mortality due to inadequate use and dose of GDMT. While RPM has proven to help HFrEF patients achieve higher rates of GDMT, its value in optimizing comorbidities and GDMT in HFpEF patients is less clear.

Hypothesis:
A team of multi-disciplinary HF clinicians can leverage RPM and guideline directed treatment protocols to bridge the gaps in HFpEF management.

Methods:
Cadence enrolled Medicare patients with HFpEF across 11 states into a virtual HF program from December 2021 to April 2023. Eligible patients had either an ICD-10 code for diastolic HF, diastolic dysfunction on TTE, or an EF>50% and a prior HFH or active treatment for HF by their clinician. Patients were given a cellular enabled BP cuff and weight scale to measure vitals. Coupling a technology enabled vitals and symptoms tracker with a guideline directed clinical protocol algorithm, symptom, vital and medication optimization was achieved.

Results:
Two-hundred fifteen patients (mean (SD) values: age 76 (9); white 64%, women 49%; BP 141/79 (9/6) mmHg; EF 60% (0.1)) were followed for a mean of 223 (82) days. Comorbidities, including DM (41%), AF (53%) and HTN (92%), were highly prevalent. There was a statistically significant reduction in BP and weight, but not heart rate (BP: -11/6 mmHg, Wt -4 lbs; p<0.001). Patient engagement information, including number of vitals recorded, clinical visits and phone calls completed, and high acuity clinical alerts resolved, is depicted in Figure 1A. There was a 286% and 71% increase in percentage of patients on a SGLT2i and MRA, respectively, at follow-up compared to baseline (SGLT2i: 15 (7%) vs. 44 (20%); p<0.001, MRA: 30 (14%) vs. 50 (24%); p<0.05). Additional changes in use and dose of GDMT are shown in Figure 1B.

Conclusion:
A telehealth HF program that utilizes RPM and technology enabled treatment protocols can meaningfully improve HF-specific vitals and rates of GDMT in patients with HFpEF.
Abstract 14883: Low Dose Intravenous AAV9 Mediated Transduction of cBIN1 Lasts at Least Six Months in Minipig Hearts
Authors: Wang Claire , Li Jing , Balmaceda Pia , Shaw Robin M
Published: December 2023

Introduction:
Heart failure (HF) is a highly morbid disease with few treatment options that are designed to benefit heart muscle. In individual cardiomyocytes, HF is associated with disrupted t-tubule microdomains, limiting organization of the calcium handling machinery and cardiac function. Microdomain disruption is caused by reduced transcription of cardiac bridging integrator 1 (cBIN1), which can be restored by gene therapy to rescue HF. In a minipig model of non-ischemic HF, we found low dose intravenous delivery of cBIN1 gene therapy is efficacious for at least 6 months. However, it is not known how long the exogenous cBIN1 transgene persists in minipig hearts.

Hypothesis:
AAV9-cBIN1 transduction in minipig hearts can last for months

Methods:
8-10 months old Yucatan minipigs with tachycardia-induced HF received a dose of PBS or AAV9-CMV-cBIN1-V5 (6x10
11
vg/kg,
i.v.
). Weekly blood work was obtained to evaluate liver and renal function. Animals were terminated 6 months after injection and tissue samples were obtained from heart and other organs for histopathology and gene expression analysis. rtPCR was used to quantify exogenous mouse cBIN1-V5 gene using a probe detecting V5 and endogenous cBIN1 using a probe specific for porcine cBIN1 gene.

Results:
Throughout the 6-month period, no organ dysfunction was noted by blood test, or with histopathology at 6 months. At 6 months, ΔΔCt results of
V5/HPRT1
indicate that AAV9 effectively transduces cBIN1-V5 (24.1 ± 5.4 fold above PBS) in hearts without detectible transduction elsewhere (Figure 1). ΔCt results of
V5/cBIN1
(porcine) indicate that exogenous cBIN1-V5 expresses at 20.9 ± 1.8 % of endogenous cBIN1 gene in minipig hearts which is the level of cBIN1 overexpression needed to restore cardiac function.

Conclusions:
A single low dose intravenous therapy of AAV9-cBIN1 can reach efficacious levels for at least 6 months in minipig hearts without transduction in other organs.
Abstract 15085: Analysis of the Composite of Death and Stroke at Follow-Up Among Risk Profiles in Trials Comparing Transcatheter and Surgical Aortic Valve Implantation. A Systematic Review and Meta-Analysis
Authors: Barili Fabio , Anselmi Amedeo , Brophy Jay , Boden William E , De Caterina Raffaele S , Dayan Victor , Roda Jorge R , Sousa-Uva Miguel , ALMEIDA RUI M , Tomasi Jacques , Verhoye Jean-Philippe , Musumeci Francesco , Mandrola John M , Kaul Sanjay , Parolari Alessandro ,   INTEGRITTY
Published: December 2023

Introduction:
To compare the effectiveness of transcatheter vs surgical aortic valve implantation on mid-term composite of death for any cause or stroke within high, intermediate and low-risk profiles.

Methods:
We performed a systematic review of the literature between 2007 and 2023 including randomized controlled trials comparing a composite of all-cause mortality or stroke of transcatheter vs surgical aortic valve replacement. Hazard ratios (HRs) and restricted mean survival time (RMST) differences within high, intermediate and low-risk profiles were estimated by reconstructing time-to-event data from Kaplan-Meier curves.

Results:
Seven trials were included (8418 participants). The incidence of composite endpoint increases concordantly with higher risk profiles for both treatments. A time variant effect unites all the risk profiles with transcathteter superior to surgery early and a trend toward HR reversal after 24 months, also supported by an cumulative additional time-to-event of 0.57 months at 3 years driven by high risk (95%CI 0.19 - 0.9) that is reabsorbed at 60 months, The benefit of transcatheter approach increased over time till 5 years in high risk, while intermediate and low risk showed a similar quadratic association (a parameter -0.0004, 95%CI -0.0008 - 0, p-value 0.05; b parameter 0.029, 95%CI 0.012 - 0.046, p-value 0.001), with a smaller increase of the transcatheter that is reabsorbed after a nadir at 36 months.

Conclusions:
There is a different trend of benefit of transcatheter approach within risks. TAVI maintains a benefit over surgery at 5-years in high risk, while its advantage is smaller and runs out at 5 years in the low-mid risk groups.
Abstract 15266: Inhibiting Endothelial Mammalian Sterile 20-Like Kinase 1 Attenuates Acute Lung Injury in Mice
Authors: Tongmuang Nopprarat ,   Jianxin Sun's lab - Cntr for Translational Medicine
Published: December 2023

Introduction:
Lung endothelium plays a pivotal role in the orchestration of inflammatory and injury responses to acute pulmonary insults. Mammalian sterile 20-like kinase 1 (Mst1), a mammalian homolog of Hippo, is a serine/threonine kinase that is ubiquitously expressed in many tissues and has been shown to play an important role in the regulation of complex biological processes, such as apoptosis, oncogenesis and organ growth. While Mst1 is highly expressed in the lung, its role in the endothelial response to pulmonary insults is largely unknown.

Hypothesis:
Mst1 regulates inflammatory responses in acute lung injury.

Methods:
Mst1 activity was assessed in lung endothelium by western blot and immunofluorescent staining. EC activation was measured by nuclear factor kappa B (NF-κB) dependent luciferase assay and the electrophoresis mobility shift assay. Mst1 knockout mice and pharmacological inhibitor were employed to assess the effects of Mst1 on homeostatic and lipopolysaccharide (LPS)-induced endothelial inflammation.

Results:
In this study, we found that Mst1 activation, as determined by Mst1 phosphorylation and nuclear translocation, was significantly increased in lung ECs after exposure to tumor necrosis factor-alpha (TNF-α) and in lungs of LPS-instilled mice as compared to the vehicle control. Overexpression of either full length Mst1 or its kinase domain promoted NF-κB activation by approximately 6.5-fold and 8-fold, respectively, whereas overexpression of the dominant negative forms of Mst1 attenuated endothelial inflammatory responses to both TNF-α and interleukin-1β stimulation. Consistent with these observations, endothelial specific deletion of Mst1 markedly attenuated LPS-induced acute lung injury in mice. Furthermore, we found that treatment of wild-type mice with Mst1 specific pharmacological inhibitor significantly prevented LPS-induced lung injury.

Conclusion:
Our findings identified Mst1 kinase as a key regulator in promoting lung EC activation and vascular inflammation, and suggest that therapeutic strategies aimed at inhibiting Mst1 activation might be effective for preventing inflammatory vascular diseases of the lung.
Abstract 15326: A Wearable Accelerometry and AI Framework for Phenotyping Step-Count Trajectories in Older Adults Undergoing Cardiac Rehabilitation
Authors: Barua Souptik , Tellez Kelly , Meng Yuchen , Johanek Camila , Pena Stephanie , Adhikari Samrachana , Schoenthaler Antoinette , Dodson John A
Published: December 2023

Background:
Wearable accelerometers, which record daily physical activity (PA) patterns over time, are a common component of mobile health-enabled cardiac rehabilitation (mHealth-CR). Artificial intelligence (AI) algorithms may be able to identify personalized insights of PA patterns to optimize mHealth-CR adherence.

Methods:
We used data from the RESILIENT trial, an ongoing randomized clinical trial of mHealth-CR in patients aged ≥65 years with ischemic heart disease. All participants in the intervention arm received Fitbit devices for activity tracking. We analyzed Fitbit step-count data collected over 3 months in these individuals using an AI framework based on functional principal component analysis (FPCA) and k-means clustering to identify distinct step count-based PA phenotypes. We then also computed adherence to using the Fitbit over time and clustered resultant adherence trajectories to identify distinct adherence patterns within the participant cohort.

Results:
We analyzed data from the first 75 intervention arm participants in RESILIENT (mean age 72 years, 19% female, 32% non-White). Using our AI framework, we identified four PA phenotypes based on their step count trends over 3 months:
Unchanged
(n=32),
Steady Increase
(n=14),
Increase then Decrease
(n=13), and
Decrease and Increase
(n=14) (
Figure 1A
). Two participants’ step count trajectories were not classifiable within this framework. We also examined changes in adherence to Fitbit use over 3 months based on a minimum step count cutoff for nonadherence (<128 steps). Applying our AI framework, we identified four adherence phenotypes:
Constantly adherent
(n=39)
, Mostly adherent
(n=13)
, Moderately adherent
(n=14)
, and Mildly adherent
(n=9) ((
Figure 1B
)).

Conclusions:
Wearable accelerometry combined with AI can provide novel insights into PA patterns during CR, which may help inform personalized PA regimens that can maximize adherence to mHealth-CR.
Abstract 15710: Sex-Specific High-Sensitivity Cardiac Troponin Thresholds for Rule-Out of Non-ST-Elevation Myocardial Infarction
Authors: Restan Ingar Ziad , Steiro Ole-Thomas , Tjora Hilde L , Langoergen Joerund , Omland Torbjorn , Collinson Paul O , Bjoerneklett Rune , Vikenes Kjell , Steinsvik Trude , Skadberg Oyvind , Mjelva Oeistein R , Larsen Alf Inge , Bonarjee Vernon V , Aakre Kristin Moberg M
Published: December 2023

Introduction:
The use of sex-specific cut-offs is recommended when high-sensitivity cardiac troponins (hs-cTn) are used for diagnosing acute myocardial infarction (MI). In this prospective, multi-centre study we evaluated the prognostic performance of sex-specific cut-offs for predicting low risk of MI in the Emergency Department (ED).

Methods:
1895 patients (45% female) from two Norwegian centres where evaluated for potential non-ST-elevation myocardial infarction (NSTEMI). Cardiac troponins were tested with hs-cTnT (Roche) and hs-cTnI (Abbott and Siemens). Sex-specific differences in performance for a single-sample NSTEMI rule-out were investigated.

Results:
NSTEMI was diagnosed in 98 women (11.5%), 135 men (12.9%). Baseline hs-cTn concentrations were consistently lower in women compared to men, though not significantly so in the NSTEMI subgroup (Table 1). ROC curves showed consistent, though non-significantly, smaller AUCs for women compared to men with all three assays (Figure 1). Cut-offs for single sample rule-out aiming at >97% or >99% sensitivity for NSTEMI were evaluated. Women had consistently lower cut-off levels compared with men, with significantly lower (p < 0.001) Youden index for all three assays at >99% sensitivity and for the hs-cTnI assays at >97% sensitivity (Table 2).

Conclusions:
Sex-specific cut-offs for single sample rule-out should be considered in accelerated diagnostic protocols for evaluation of NSTEMI.
Abstract 15889: An Artificial Intelligence-Derived Pediatric Pulmonary Hypertension Risk Prediction Model From the Pediatric Pulmonary Hypertension Network (PPHNet) Registry
Authors: Griffiths Megan , Manlhiot Cedric , Chinni Bhargava K , Sleeper Lynn A , Abman Steven , Rosenzweig Erika , Romer Lewis H , Mullen Mary P , Lin Shili , Benza raymond , Everett Allen D ,   PPHNet Investigators
Published: December 2023

Introduction:
Risk prediction is fundamental to guiding pulmonary hypertension (PH) treatment and is a key part of PH guideline based care. Data-driven risk prediction in pediatric PH has been lacking, relying instead on expert opinion.

Objective:
Use the multi-center Pediatric Pulmonary Hypertension Network (PPHNet) registry to develop a pediatric PH risk model.

Methods:
Pediatric PH patients (WSPH 1/3) enrolled in the PPHNet were used in this study and randomly split into train (80%) and test cohorts (20%). 176 variables were suitable for analysis including demographics, imaging, hemodynamics, functional/exercise testing, laboratory values, symptoms, and comorbidities. Boruta feature selection with random forest classifier identified variables that predicted the composite outcome of time to death, transplant or reverse Potts shunt.
2
The prediction model was built using an extreme gradient boost classifier with parameter tuning using Bayesian optimization. Model performance was quantified using confusion matrices, calculated sensitivity, specificity, AUC-ROC, and calibration slope.

Results:
A total of 1232 patients (985 Train, 247 test) were appropriate for inclusion; 134 patients (10.9%) met the composite outcome) with follow-up to 4 years from diagnosis. 37 variables were isolated for the prediction model. The Model performed strongly in the test cohort with an AUROC of 87% (Figure 1A), sensitivity of 85%, and specificity of 77%. Predicted probabilities were stratified into 3 major risk groups based on 1-year risk of event (Figure 1B; low <5%, medium 10-15%, high >15%) with good agreement between predicted and observed outcomes.

Conclusions:
Using the multicenter PPHNet cohort, we developed a well calibrated 1-year risk prediction model for pediatric groups 1 and 3 PH. This model is uniquely trained on incident and prevalent pediatric patients and could enable accurate identification of high-risk patients in need of aggressive therapy.
Abstract 16342: Age- and Sex-Differences in Accuracy of ICD-10 Codes for Identifying Adults With Pulmonary Embolism: PE-EHR+ Study
Authors: Mahajan Shiwani , Lo Ying-Chih , Bejjani Antoine , Khairani Candrika D , Jimenez David , Barco Stefano , Caraballo Cesar , Secemsky Eric A , Klok Erik , Hunsaker Andetta , Aghayev Ayaz , Muriel Alfonso , Hussain Mohamad A , Appah-Sampong Abena , MOJIBIAN HAMID , Lu Yuan , Lin Zhenqiu , Aneja Sanjay , Khera Rohan , Goldhaber Samuel , Zhou Li , Monreal Manuel , Piazza Gregory , Krumholz Harlan M , Bikdeli Behnood ,   PE-EHR+
Published: December 2023

Background
Age and sex-differences exist in presentation of adults with pulmonary embolism (PE). However, it remains unclear if these differences influence the accuracy of International Classification of Diseases, Tenth Revision (ICD-10) codes used for identification of PE.

Methods:
Using multicenter data from Mass General-Brigham Health System (2016-2021), patients were randomly selected from 3 groups: 578 patients with Principal Discharge codes for PE, 578 with Secondary Discharge codes for PE, and 578 without codes for PE. The reference standard for identification of PE was manual chart review by 2 independent physicians. Sensitivity, specificity, and positive and negative predictive values were determined by age (<65 vs ≥65 years) and sex (female vs male). Weighted estimates were obtained by using the total number of hospitalizations.

Results:
Among 1712 patients included in final analyses, 896 (52.3%) were female and 775 (45.3%) were ≥65 years. Use of Principal-or-Secondary ICD-10 codes had a similar sensitivity by sex (99.5% vs 100% among females vs males) and age (99.8% among both groups) in the study sample. The weighted sensitivity among females was 72.8% (vs 100% for males) and 80.4% among patients ≥65 years (vs 85.2% for <65 years). In the weighted cohort, the positive predictive value was 78.2% among females (vs 80.3% for males) and 78.3% among those ≥65 years (vs 80.0% for <65 years) (Table). Age and sex-differences in the diagnostic accuracy were similarly observed in analyses restricted to Principal, or to Secondary codes.

Conclusions:
Principal-or-Secondary ICD-10 codes had lower sensitivity and positive predictive value among females and older adults, though the sex-differences in sensitivity may be influenced by limited number of false negatives in this study. Additionally, Secondary codes had higher false positives among older adults. These findings may have important implications for identification of patients with PE using ICD-10 codes.
Abstract 16401: Optimizing ChatGPT to Detect VT Recurrence From Complex Medical Notes
Authors: Feng Ruibin , Brennan Kelly A , Azizi Zahra , Goyal Jatin , Pedron Maxime , Chang Hui Ju , Ganesan Prasanth , Ruiperez-Campillo Samuel , Deb Brototo , Clopton Paul L , Baykaner Tina , Rogers Albert J , Narayan Sanjiv M
Published: December 2023

Introduction:
Large language models (LLMs), such as ChatGPT, have remarkable ability to interpret natural language using text questions (prompts) applied to gigabytes of data in the world wide web. However, the performance of ChatGPT is less impressive when addressing nuanced questions from finite repositories of lengthy, unstructured clinical notes (Fig A).

Hypothesis:
The performance of ChatGPT to identify sustained ventricular tachycardia (VT) or fibrillation after ablation from free-text medical notes is improved by optimizing the question and adding in-context sample notes with correct responses (‘prompt engineering’).

Methods:
We curated a dataset of N = 125 patients with implantable defibrillators (32.0% female, LVEF 48.9±13.9%, 61.7±14.0 years), split into development (N = 75) and testing (N = 50) sets of 307 and 337 notes, with 256.8±95.1 and 289.8±103 words, respectively. Notes were deidentified. Gold standard labels for recurrent VT (Yes, No, Unknown) were provided by experts. We applied GPT-3.5 to the test set (N=337 notes), using 1 of 3 prompts (“Does the patient have sustained VT or VF after ablation” or 2 others), systematically adding 1-5 “training” examples, and repeating experiments 10 times (51,561 inquiries).

Results:
At baseline, GPT achieved an F1 score of 38.6%±19.4% (mean across 3 prompts; Fig B). Increasing the number of examples progressively improved mean accuracy and reduced variance. The optimal result was the illustrated prompt plus 5 in-context examples, with an F1 score of 84.6%±6.4% (p<0.05).

Conclusions:
ChatGPT can accurately identify VT recurrence from small numbers of complex medical notes with optimal prompt engineering. Future studies should define optimal context for different medical questions and domains. These findings pave the way for automated analysis of large medical repositories to broadly improve decision making.
Abstract 16503: C-X-C Motif Chemokine Ligand 12 is a Primary Determinant of Coronary Artery Dominance
Authors: Rios Pam , Zanetti Daniela , Hilliard Austin , Naftaly Jeffrey , Prabala Pratima , Kho Pik Fang ,   VA Million Veteran Program, Chang Kyong-Mi , Plomondon Meg E , Waldo Stephen , Tsao Philip S , CLARKE Shoa L , Horse Kristy , Assimes Themistocles L
Published: December 2023

Introduction:
Left coronary dominance is associated with worse clinical outcomes in the setting of coronary artery disease (CAD). Little is known about the determinants of dominance, including whether it is solidified in utero or sometime after birth.

Hypothesis:
Investigating the genetic determinants of dominance will identify new arteriogenesis pathways targetable for enhancing coronary artery growth and collateralization in humans.

Methods:
We conducted a stratified multi-population genome-wide association study of dominance using REGENIE and TopMed-imputed genotypes available in 43813 White, 9532 Black, and 3550 Hispanic participants of the Million Veteran Program (MVP) who had undergone a cardiac catheterization. We modelled left and co-dominant combined vs. right, as well as left vs. right dominance, adjusting for sex and 10 genetic principal components. We also explored whether dominance and CAD were genetically correlated using LD score regression. Lastly, we sought to validate compelling population genetic signals in mice using whole organ imaging of the heart, which allows for the quantification of coronary anatomy and variation.

Results:
Thirteen loci reached genome wide significance (GWS). The most intriguing was a top hit located downstream of C-X-C Motif Chemokine Ligand 12 (CXCL12) which, remarkably, reached GWS in both White and Black Veterans. While the CXCL12 signal robustly colocalized with the signal in this region for CAD (COLOC PPH4: 87.1%), the genome wide genetic correlation of dominance with CAD was otherwise modest in both MVP (rg=-0.18, p=0.007) and CardiogramplusC4D (rg=-0.16, p=0.018). To gain evidence for causality, we modeled dominance in Cxcl12-deficient mice (n=64 wildtype; n=62 heterozygous). Murine coronary arteries develop in a field of Cxcl12 expression and choose right or left dominance during embryogenesis, a time when we found human dominance to also be evident. Reminiscent of our human GWAS, dominance was skewed away from the common phenotype in Cxcl12 heterozygous mice (p=0.038).

Conclusions:
CXCL12 is a primary determinant of coronary artery dominance in humans and mice. The modest negative genetic correlation between CAD and dominance supports a developmental component to CAD susceptibility.
Abstract 16521: Using Electronic Health Record Data to Identify and Prioritize Patients With Heart Failure With Reduced Ejection Fraction for a Remote Medication Optimization Program
Authors: Unlu Ozan , Blood Alexander J , Ostrominski John W , Nichols Hunter J , Subramaniam Samantha , Gabovitch Daniel , Chasse Jacqueline , Cannon Christopher P , Desai Akshay S , Scirica Benjamin , Wagholikar Kavishwar
Published: December 2023

Introduction:
Remote medication management programs (RMMP) might be effective in optimizing guideline directed medical therapy (GDMT) for HFrEF. Identification of patients that can be safely managed remotely and prioritization of those with the highest need for medication optimization is crucial, especially in the setting of constrained resources.

Methods:
We analyzed records from our institutional enterprise data warehouse to identify patients with HFrEF in whom GDMT can be safely optimized by an RMMP within the Mass General Brigham health system between May 2021 and May 2023. After identifying a population with HFrEF, we excluded patients with contraindications to GDMT and with higher risk of adverse medication reactions. Next, we identified active and past medications by using medication discontinuation data (Figure). We performed chart review on a random sample of 100 patients to validate our analysis.

Results:
We have identified 1771 patients with HFrEF who are actively receiving care and are eligible for remote medication optimization. Only 7% (129/1771) of patients were prescribed all four GDMT, however in 4% (78/1771) at least one of these prescriptions was discontinued. Of all patients, 45% (801/1771) had stopped at least one GDMT, including 50% of SGLT2i, 30% of MRA, and 46% of ARNI. Patients who were never prescribed GDMT were identified as top priority for the RMMP.

Conclusion:
EHR data can effectively identify and prioritize HFrEF patients for medication optimization. Similar to prior HFrEF registries, our study showed poor utilization of GDMT. However, it also revealed a significant number of patients who had their GDMT prescriptions discontinued. Investigating the reasons for discontinuations may elucidate barriers to GDMT optimization. This study can be expanded to patients with HFpEF and HFmEF, and refined further by using natural language processing, machine learning, and by incorporating data for medication refill, claims, and dosages.
Abstract 16530: Impact of Hyperuricemia on 5-year Clinical Outcomes in Patients With Critical Limb Ischemia Underwent Percutaneous Transluminal Angioplasty
Authors: An Seong Joon , Ahn Woo Jin , Choi Byoung Geol , Rha Seung-Woon , Choi Se Yeon , Byun Jae Kyeong K , Cha Jinah , Hyun Sujin , Park Soohyung , Kang Dong Oh O , Park Eun Jin J , Choi Cheol Ung
Published: December 2023

Background:
A growing evidence on the correlation between hyperuricemia and cardiovascular disease (CVD) has been previously reported. However, there have been limited data on the impact of hyperuricemia on long-term clinical outcomes in patients with critical limb ischemia (CLI) who underwent percutaneous transluminal angioplasty (PTA).

Methods:
A total, 425 peripheral artery disease (PAD) patients who underwent PTA for CLI were enrolled. The patients were divided into the hyperuricemia group (n=101) and the normal group (n=324). The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was a major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders.

Results:

After IPTW matching analysis, compared to the normal group, the hyperuricemia group was associated with a higher incidence of MACCE (20.7% vs. 13.6%, hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.15 - 2.38, p=0.006) including non-cardiac death (11.7% vs. 6.3%, HR: 1.95, 95% CI: 1.19 - 3.19, p=0.006) and MALE (47.7% vs. 36.0%, HR: 1.62, 95% CI: 1.23-2.13, p=0.001) including non-target extremity revascularization (TER) (15.0% vs. 6.8%, HR: 2.42, 95% CI: 1.52-3.84, P<0.001).

Conclusions:

In the present study, hyperuricemia was associated with worse clinical outcomes in patients with CLI following PTA during 5-year clinical follow-up. Efficacy of controlling hyperuricemia in improving clinical outcomes should be evaluated in the further studies.
Abstract 16653: Assessment of Price Variation for TAVR and SAVR Procedures Across US Hospitals
Authors: Sharma Pranav , Wei Chen , Paranjpe Ishan , Heidenreich Paul A , Schulman Kevin , Sandhu Alexander T
Published: December 2023

Introduction
Transcatheter Aortic Valve Replacement (TAVR) has become a mainstay of aortic stenosis treatment, alongside Surgical Aortic Valve Replacement (SAVR). Despite their widespread use, little is known about their commercial cost burden as this data was confidential prior to the 2021 Federal Price Transparency Final Rule. Using newly available pricing data, we aimed to compare hospital variation in TAVR and SAVR prices and describe factors predictive of prices.

Methods
Prices for DRG 267 (TAVR) and 220 (SAVR) were extracted from the Turquoise Health database and linked to hospital characteristics using Medicare IDs. Price variation within and across hospitals was assessed by calculating the ratio between the 90th and 10th percentile commercial or hospital rates, respectively. The Kruskal-Wallis test was used to test for associations between price and categorical factors.

Results
1116 hospitals reported prices for TAVR and 1215 hospitals reported prices for SAVR. Commercial prices for TAVR ($70,482) and SAVR ($66,629) were 1.83 and 1.77x the Medicare price. Within hospitals, the 90th percentile payer-negotiated TAVR price was 1.80x the 10th percentile price, while across hospitals, the 90th percentile hospital by median commercial price was 3.40x the 10th percentile price. This was similar for SAVR. Several factors were associated with higher prices, including major teaching status (TAVR $17,736 and SAVR $19,057 vs non-teaching). For-profit status and investor-ownership were associated with lower prices. While higher hospital-wide readmission rates and higher hospital ratings were associated with higher prices, there was no significant association with hospital-wide mortality.

Conclusion
This analysis demonstrates substantial markups for TAVR and SAVR commercial prices and significant variation both within and between hospitals associated with teaching status, hospital ratings, and readmissions but not hospital mortality.
Abstract 16657: Prognostic Comparison Between Computer Modelling-Derived versus Conventional H2FPEF Scores
Authors: Konje Swiri , Omar Alaa M , Munoz Alba , Kim Ga Hee , Elias Joseph , Mahtani Arun , Gandhi Kruti , Moras Errol C , Perez Lizardo Christopher , Argulian Edgar
Published: December 2023

Introduction:
H2FPEF score of 0-1 and ≥6 indicate low and high risks of HFpEF, while scores of 2-5 may require additional testing. We compared the prognostic abilities of unsupervised cluster modeling (USCM) and the conventional H2FPEF score.

Methods:
Respectively, 532 patients with suspected heart failure (HF) symptoms were included (69±6 years, 57% females, EF: 61±5%, all>50%). H2FPEF score was calculated as recommended: BMI (>30: 2 points), atrial fibrillation (3 points), and 1 point each for age>60, ≥2 hypertension drugs, E/e' ratio >9, and pulmonary systolic pressure >35 mmHg. Using these variables, a 2-step USCM was done and compared to the H2FPEF score for death and cardiac hospitalization.

Results:
The mean H2FPEF score was 3.2±1.5. During a median follow-up of 3.8 years, 13 patients died, 66 hospitalized (35 HF and 51 non-HF causes), and 76 had the composite outcome. H2FPEF scores of 0-1 and ≥6 had the lowest and highest frequencies of individual and combined outcomes, respectively, while scores of 2-5 was intermediate (Figure 1A). Compared to scores of 0-1, scores of 2-5 (HR: 11, 95% CI: 1.5-78) and ≥6 (HR: 29, 95% CI: 4-219) had a higher risk of outcomes. USCM (Figure 1B) identified three clusters with varying risks: (low: 145 patients, intermediate: 333 patients, and high: 54 patients) (Figure 1C). The mean H2FPEF scores differed significantly between clusters (1±0, 3.3±1.1, 6.6±1, p<0.001). Compared to the low-risk cluster, the intermediate-risk (HR: 3.4, 95% CI: 1.5-8), and high-risk clusters (HR: 7.3, 95% CI: 3-18) had a higher risk of outcomes. Clusters significantly reclassified H2FPEF scores (Figure 1D), particularly those with scores of 2-5 (23% reclassified as low risk, 7% as high risk). Among the reclassified patients with H2FPEF scores of 2-5, there was significant discrimination in outcomes (p=0.02, Figure 1A).

Conclusions:
Machine learning techniques, can enhance the prognostic accuracy of the H2PEF score, particularly for intermediate scores.
Abstract 16660: Precision Diagnosis of Hypertrophic Cardiomyopathy: A New Definition of Inappropriate Hypertrophy
Authors: Shiwani Hunain , Davies Rhodri , Topriceanu Constantin-Cristian , Owens Anjali T , Raman Betty , Ditaranto Raffaello , Augusto Joao , Torlasco Camilla , Webber Matthew , Dowsing Benjamin , Hughes Rebecca , Miranda Inês , Witschey Walter , Thompson Elizabeth , Castelletti Silvia , Crotti Lia , Lovato Luigi , Ponziani Alberto , Moschonas Konstantinos , Joy George , Pierce Iain , Kellman Peter , Hughes Alun , Biagini Elena , Mohiddin Saidi , Lopes Luis , Ferrari Victor , Litt Harold , Captur Gabriella , Moon James
Published: December 2023

Introduction:
The definition of hypertrophic cardiomyopathy (HCM), unaltered for 50 years, requires unexplained left ventricular hypertrophy with a maximum wall thickness (MWT) ≥15mm in probands. However, this doesn’t consider age, sex and body-size which is inadequate for a precision therapy era.

Aim:
To develop a personalised definition of inappropriate hypertrophy using cardiac MRI and evaluate potential care implications.

Methods:
Healthy reference cardiac MRIs from the Framingham Heart Study, UK Biobank, and multiple healthy volunteer studies were analysed by a validated AI algorithm. Generalized additive mixed models accounting for age, sex, and body surface area (BSA) established a personalized hypertrophy threshold for MWT (>95% prediction interval) and conditional Z-scores. We assessed the discordance in HCM diagnosis between a “≥15mm” and “personalized hypertrophy” threshold applied to the UK Biobank and clinical HCM cohorts.

Results:
In healthy subjects (n=5,255), 36% of MWT variation was explained by age, sex and BSA. In the UK Biobank (n=44,690), using ≥15mm, there is a substantial sex skew; 8% of males and 1% of females are classified as hypertrophic. With a personalized threshold, this reduces to 3% of males and 2% of females classified as hypertrophic. 17% of subjects have a predicted hypertrophy threshold of 15mm (with 46% predicted ≤ 14mm, 37% predicted ≥16mm). In clinical HCM cohorts (n=1,854) across 5 centres in 4 countries (UK, USA, Italy, Portugal), females had thinner hearts (17.7 vs 19.1mm; p<0.001) but more relative hypertrophy evidenced by greater deviation (Z-scores) from their predicted MWT (5.4 vs 5.1; p=0.05).

Conclusion:
We propose a new, personalised definition for hypertrophy that mitigates for significant age, sex and BSA confounding inherent in a 15mm cut point. We have identified potential for under/over diagnosis in a population cohort and suboptimal risk stratification in smaller, younger and/or female HCM patients.
Abstract 16662: Factors Associated With Repeated Emergency Department Visits Among Symptomatic Patients With Heart Failure
Authors: Lee Solim , Han Soonbo
Published: December 2023

Heart failure (HF) is a prevalent cause of emergency department (ED) visits among adults. However, there is limited understanding of the characteristics of patients with HF who frequently utilize the ED for symptom management.

Aim:
To describe factors associated with ED revisits among symptomatic patients with chronic HF.

Methods:
We identified 1,472,083 adults (age ≥ 18 years) with HF who had no history of left ventricular assist device or heart transplantation between January 2010 and March 2020 from the TriNetX Research Network, which included 47 US healthcare organizations. In this retrospective observational study, 24,070 patients presenting with dyspnea and receiving intravenous (IV) Furosemide at the ED were followed up for 1 year from the index ED visit. ED revisits related to the treatment of dyspnea with IV diuretics were tracked. Factors associated with these ED revisits were identified using multivariate Cox regression analysis.

Results:
A total of 3,574 ED revisits were observed from 2,559 patients (10.6% of the sample, mean age 63 years, 51% men, 39% White, 62% Non-Hispanic). The ED revisit rates were 52, 96, 125, and 148 visits per 1,000 persons within 1, 3, 6, and 12 months, respectively. The median time to the first ED revisit for symptom management with IV diuretics was 65 days (range 2-364 days). In the Cox model, younger patients (< 65 years) had a higher risk of ED revisits compared to older patients (HR 1.65, 95% CI 1.50-1.82, p<0.001). Men had a higher risk of ED revisits compared to women (HR 1.12, 95% CI 1.02-1.23, p=0.02). Black patients had a higher risk of ED revisits compared to other races (HR 1.36, 95% CI 1.20-1.53, p<0.001). Patients with HFrEF (e.g., ICD-10 I50.2) had a higher risk of ED revisits compared to those with congestive HF (e.g., ICD-10 I50 without HF type information) (HR 1.25, 95% CI 1.12-1.40, p < 0.001). Patients diagnosed with HF more than 1 year prior to the index ED visit had a higher risk of ED revisits compared to those diagnosed within 1 year (HR 1.31, 95% CI 1.19-1.44, p < 0.001).

Conclusions:
Younger age, male gender, Black race, HFrEF classification, and longer duration of HF were associated with ED revisits among symptomatic adults with HF. To reduce repeated ED visits, targeted interventions for high-risk patients are essential.
Abstract 16676: Risk Assesment of Sudden Cardiac Death With RR Interval Fluctuations
Authors: Rasanen Esa , Pukkila Teemu , Molkkari Matti , Nikus Kjell , Lyytikainen Leo-Pekka , Lehtimaki Terho , Viik Jari , Kahonen Mika , Hernesniemi Jussi
Published: December 2023

Introduction:
Changes in conventional measures for short-term heart rate variability (HRV) have been associated with heart failure, coronary artery disease and even sudden cardiac death (SCD). However, the predictive value of HRV in clinical settings has been limited. Secondly, the current HRV methods have not discriminated SCDs from other causes of death, which would be relevant for proper prevention and treatment. In this study we utilize novel time series analysis methods for RR intervals in ultra-short-term measurements to distinguish SCD from other causes of death.

Methods:
We apply second-order detrended fluctuation analysis (DFA) with maximally overlapping windows to assess the correlations in RR intervals as a function of the scale, i.e., the range of consecutive RR intervals in one-minute resting ECG. The analysis is based on the baseline ECG recordings from the prospective FINCAVAS study of cardiac patients with a median follow-up time of 8.3 years, during which 378 deaths were recorded including 76 SCDs in the total population of 2794 subjects.

Results:
Our DFA method can discriminate between incident SCD cases and patients dying to other causes. The discrimination is maximized on scale 9, with an univariate hazard ratio of 0.71 and 95% confidence intervals (CI) (0.55-0.91). Excluding other cardiac deaths from the control group we are left with 279 deaths resulting to univariate hazard ratio of 0.62 (0.47-0.82 CI) on scale 8.

Conclusions:
The ability to distinguish SCD from other causes of death shows that the scale-dependent DFA method is a superior alternative to the conventional HRV methods. The utilization of one-minute RR interval measurements for risk assessment provides new non-invasive tools for clinical inspections, as well as promising prospects to health monitoring with wearable devices.
Abstract 16709: Metabolic Clusters and Their Association With Progression of Coronary Artery Calcification (From the ELSA-Brasil)
Authors: Cesena Fernando Y , Generoso Giuliano , Bittencourt Marcio , Pereira Alexandre , Santos Raul D , Lotufo Paulo A , Bensenor Isabela M
Published: December 2023

Introduction:
Metabolic risk factors for CVD tend to cluster. However, the association between metabolic clusters considering lipoprotein subclasses and subclinical atherosclerosis is not well understood. This study aimed to characterize metabolic clusters and determine their association with CAC progression.

Methods:
We included individuals with available lipid profiles assessed by NMR spectroscopy and excluded those taking lipid-lowering medications. Hierarchical clustering was performed using BMI, fasting glycemia, HbA1c, HOMA-IR, LDL-c, HDL-c, TG, and subclasses of LDLs, HDLs, and TG-rich lipoproteins (TRLs). CAC was evaluated in a subset of participants with two cardiac CT measurements and no prior history of ASCVD. The association between clusters and CAC progression (evaluated by the Berry method) was assessed using logistic regression.

Results:
The study included 4328 participants (55% females, mean age 50.6 ± 8.7 years), among whom 4 metabolic clusters were identified (Table). HOMA-IR, BMI, glycemia, HbA1c, TG, and hsCRP increased from Cluster 1 to Cluster 4. Compared to Cluster 1, Clusters 3 and 4 were significantly associated with CAC progression (OR 1.59 [95% CI 1.21; 2.09], p <0.001 and OR 2.79 [95% CI 1.43; 5.45], p=0.003, respectively). The Figure demonstrates that individuals with lower calculated CVD risk but more pronounced metabolic abnormalities may have a probability of CAC progression as high as those with higher calculated CVD risk but fewer metabolic alterations.

Conclusions:
Metabolic clustering around insulin resistance can help identify individuals at higher risk of CAC progression, regardless of calculated CVD risk and baseline CAC.
Abstract 16713: Pre-Clinical 30-day Survival Results of the BiVACOR TAH
Authors: Gluck Trenton , Timms Daniel L , Elgalad Abdelmotagaly , Shafii Alexis , Freundt Miriam , Dowling Robert , Cohn William E , Frazier O Howard
Published: December 2023

Introduction:
The BiVACOR Total Artificial Heart (TAH) replaces the failing heart with a durable and physiologically adaptive pump, which combines magnetic levitation and rotary blood pump technology. The pump has large clearances to minimize shear stress, generates pulse pressure via cyclic changes in pump speed, and modulates total outflow based on physiological conditions. A single rotor design enables a small pump size.
Aim:
Primary endpoint was survival at 30 days with normal end-organ function and absence of device related thromboembolism at necropsy.

Methods:
Five calves (82 - 108 kg) were implanted with the BiVACOR TAH and underwent continuous hemodynamic monitoring for 30 days. The pumps ability to generate a pulse pressure, balance outflow to the systemic and pulmonary circulations and to increase outflow in response to increased physical activity was assessed. Hemocompatibility and end-organ function were routinely monitored. Necropsy was performed on day 30 to evaluate for evidence of thromboembolism and end organ damage. Explanted pumps were examined.

Results:
All five calves survived to 30 days with normal end-organ function. Stable hemodynamics were achieved with normal pressures in the aorta and left and right atrium (MAP 111 ± 6 mmHg, CVP 12 ± 5 mmHg, LAP of 20 +/- 5 mmHg). Average estimated pump output was 12 ± 2 L/min with average pulse pressure of 30 mmHg. Pump output increased during changes in daily physiological condition (10 to 14 L/min). No device-related thromboembolism or other end organ pathologies were detected at necropsy. All explanted pumps were free of internal pump thrombus. Hemocompatibility was demonstrated (pfHb 4.34 ± 0.74 mg/dL). Bypass time decreased by 34 minutes over the entire study cohort.

Conclusion:
The BiVACOR TAH demonstrates normal hemodynamics including left/right balance. Pump design allows for a normal pulse pressure, increased pump output in response to exercise, and excellent hemocompatibility without device-related thromboembolism. Operative time markedly improves with surgeon experience. The small pump size may expand the use of TAH to smaller patients. This device may address the need for select patients with advanced heart failure who require biventricular support.