bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13982: Ischemic Heart Disease Burden in the United States: Prevalence, Mortality, and Regional Differences From 1990-2019
Authors: Abughazaleh Saeed , Obeidat Omar , Tarawneh Mohammad , Mkhaimer Yaman , Abdalla Khalid
Published: December 2023

Background:
Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality.

Aim:
To understand the burden of IHD, identify gender disparities and risk factors, explore the relationship between socioeconomic growth and IHD, and analyze risk factor distribution across states.

Method:
utilizing data from the GBD Study 2019. The study assessed the relationship between IHD and socioeconomic development using SDI and measured the overall impact of IHD using DALYs, considering premature death and disability. Data analysis involved comparing prevalence, mortality, SDI, DALYs, attributable burden, and risk estimation among states.

Results:
Between 1990 and 2019, there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states, and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend with a 37.1% decrease in ASPR from 1990. Metabolic risks were the leading contributors to the disease burden, accounting for 50% of cases, with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely, Minnesota had the lowest burden of IHD among all states.

Conclusion:
This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences.
Abstract 13989: Automated VT Localization System Based on Patient-Specific Integration of Two-Dimensional (2D) Intracardiac Echocardiography (ICE) and 3DElectroanatomic (EA) Mapping
Authors: Zhou Shijie , AbdelWahab Amir , Berger Ronald D , Tandri Harikrishna S , Chrispin Jonathan , Sapp John L
Published: December 2023

Introduction:
We have previously developed an intraprocedural automated localization system to identify VT-exit sites projected onto a patient-specific CT geometry using 12-lead ECGs. However, the accuracy of the system depends on a registered reconstruction of the cardiac surface.

Objective:
To assess the feasibility of using a registered integration of 2D ICE and 3D EA mapping to perform intraprocedural localization, while avoiding errors being introduced by registration of the CT geometry and EA map.

Methods:
Four patients with 7 VTs (5 LV VTs, 2 RV VTs) were enrolled. A 3D patient-specific shell of both ventricles that combines ICE and EA map was reconstructed during the ablation procedure. It was imported into the automated localization system post-procedure for offline analysis. The system was used to estimate the location of VT-exit sites on the reconstructed 3D geometry. Localization accuracy was quantified for the VT-exit sites by comparing the distance of the calculated site to the site of successful ablation or that of best pacing site match.

Results:
Five reentrant VT-exit sites were identified using activation and entrainment mapping, supplemented by pace-mapping at the scar margin; two focal VTs were identified by pace mapping. The proposed system achieved mean localization accuracy of 6.4 mm for 7 VTs.

Conclusions:
ICE and EA mapping can be successfully integrated for intraprocedural automated localization of ventricular activation in both ventricular chambers and may avoid registration errors of CT geometry integration.
Abstract 140: Near-Infrared Spectroscopy, Pupillometry and End-Tidal Co2 as Predictive Factors of Survival for Patients With Out-of-Hospital Cardiac Arrest
Authors: Segond Nicolas , Savary Dominique , Bouzat Pierre , Veloso Melanie , Turk Julien , Sanchez Caroline , Bosson Jean-Luc , Viglino Damien , Payen Jean-François , Debaty Guillaume
Published: December 2023

Background:
During out-of-hospital cardiac arrest (OHCA), early prognostication of patient’s outcomes at the early phase is difficult and based on a combination of factors. EtCO2 is one of the validated parameters associated with survival. Near-infrared spectroscopy (rSO2) and infrared automated pupillometry measurements could in addition be of value in the prehospital setting.

Hypothesis:
To assess the prognostic value of rSO2, pupillometry and EtCO
2
alone or in association with other prognostic factors for patients with OHCA.

Methods:
We conducted a prospective cohort analysis in 3 French prehospital intensive care units. Adult patients with a presumed medical OHCA were included. Measurements were made at medical team arrival every 5 minutes for 15 minutes by the ambulance driver in order to ensure blindness for the medical team. The primary outcome was the prognostic value of rSO2, pupillometry, bystander CPR and initial cardiac rhythm alone or in association for survival at hospital admission. The secondary outcome was the prognostic value of capnography (EtCO2) alone or in association with primary outcomes parameters for survival at hospital admission.

Results:
112 patients were included and analyzed. Bystander CPR was initiated for 72 (65.5%) patients, 19 (17.3%) survived to hospital admission. For survival at hospital admission, rSO2 alone had an AUC of 0.74 (IC95% 0.59-0.88) and the optimal threshold was 29% with a negative predictive value of 90.8% (IC95% 81-96.5). All patients with rSO2 ≥ 45% survived at hospital admission. Pupillometry alone had an AUC of 0.65 (IC95% 0.51-0.79) and no optimal threshold was found. The association of rSO2 and pupillometry adjusted on bystander CPR and initial rhythm provided an AUC of 0.77 (IC95% 0.61-0.92). EtCO2 alone had an AUC of 0.77 (IC 95% 0.64-0.89) and the optimal threshold was 25 mmHg with a negative predictive value of 97.7% (IC95% 87.7-99.9). In association, EtCO2 and rSO2 provided an AUC of 0.85 (IC 95% 0.73-0.96).

Conclusion:
During OHCA, near-infrared spectroscopy alone and in association with EtCO2 could be a major prognostic factor of survival at hospital admission. Pupillometry alone failed to be a prognostic factor of survival at hospital admission.
Abstract 14014: Inclusion of Chronic Kidney Disease Measures Improves Heart Failure Risk Prediction: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Koyawala Neel , Echouffo Justin B , Zhang Sui , NAMBI VIJAY , Grams Morgan , Matsushita Kuni , Blumenthal Roger S , Rangaswami Janani , Ballantyne Christie M , Coresh Josef , Ndumele Chiadi E
Published: December 2023

Introduction:
Although chronic kidney disease (CKD) is closely linked to hypertension and diabetes, and is an independent risk factor for heart failure (HF), most HF risk prediction algorithms do not include CKD measures as covariates.

Hypothesis:
We hypothesized that the addition of estimated glomerular function (eGFR), using creatinine (Cr) and cystatin C (CysC), and urine albumin to creatinine ratio (UACR) to the ARIC HF Risk Score will improve risk discrimination for HF.

Methods:
We performed a prospective analysis of participants at ARIC Visit 4 (1996-1998) to assess changes in risk prediction after incorporating CKD measures. eGFR was estimated by both Cr and by Cr-CysC using CKD-EPI 2021 race-free equations. Using eGFR and UACR, we categorized CKD into four risk progression levels per the Kidney Disease Improving Global Outcomes (KDIGO) heat map. We assessed changes in 10-year risk discrimination of the ARIC HF Risk Score with the addition of eGFR-Cr, eGFR-Cr-CysC, and with KDIGO CKD categories using eGFR-Cr+UACR and eGFR-Cr-CysC+UACR. Analyses were performed in the overall population and stratified by hypertension and diabetes.

Results:
Among 10,277 participants (mean age 63.2 years, 56% women, 21.4% Black, 15.5% diabetes, 40.8% hypertension), 845 people developed HF over 10 years. Risk discrimination progressively improved by adding eGFR-Cr, eGFR-Cr-CysC, and KDIGO categories with eGFR-Cr+UACR and eGFR-Cr-CysC+UACR to the ARIC HF Risk Score (C-statistic base model, 0.783 [95% CI, 0.768, 0.798] versus 0.796 [95% CI, 0.781, 0.810] with KIDIGO categories using eGFR-Cr-CysC+UACR). Greater improvements in risk discrimination were observed among those with diabetes and hypertension than in those without these conditions (Table).

Conclusion:
Incorporating eGFR and UACR in prediction algorithms improves HF risk discrimination and can help inform HF screening and prevention efforts, particularly among individuals with diabetes and hypertension.
Abstract 14029: Association Between Depressive Symptoms Severity and Physiological Age as Determined by Artificial Intelligence-ECG
Authors: Medina-Inojosa Betsy J , Medina-Inojosa Jose R , chen zhuo , Clark Matthew M , Rajai Nazanin , Lerman Amir , Attia Zachi , Friedman Paul , Lopez-Jimenez Francisco
Published: December 2023

Background:
Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used an artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) that has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG

Methods:
A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals age ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and filled the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors

Results:
Mean chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index.
Figure.
There is significant attenuation of the association once accounting for age, sex and CVD risk factors

Conclusions:
Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD
Abstract 14048: Stromal Cell-Derived Factor-1α-Encapsulated Nanoparticles Specifically Target the Ischemic Myocardium and Attenuate Myocardial Injury via Proangiogenic Effects
Authors: Yajima Shin , Manna Manoj K , Zhu Yuanjia , Elde Stefan , Mullis Danielle , Venkatesh Akshay , Ethiraj Sidarth , Ueyama Tsuyoshi , Wesley Brandon T , Ichimura Kenzo , Shudo Yasuhiro , Rajadas Jayakumar , Woo Y Joe J
Published: December 2023

Hypothesis:
Intravenously injected nanoparticles (NPs) containing stromal cell-derived factor-1α (SDF-1α) (SDF-NPs) could sustainably target the ischemia reperfusion (I/R)-injured myocardium and induce robust angiogenesis by increasing systemic EPC levels, thereby attenuating myocardial I/R injury.

Methods:
Male Wistar rats were subjected to myocardial I/R insult by ligating the left anterior descending artery for 30 min followed by reperfusion. At reperfusion, rats were randomized to receive intravenous injections of 5 mL/kg of phosphate-buffered saline (PBS), 6 μg/kg of NPs, SDF-1α, or SDF-NPs. One and 4 days after the treatments, SDF concentrations in the plasma and cardiac tissue, and the EPC population in the circulating blood were assessed. Therapeutic efficacy was investigated using histopathology and cardiac functional studies 4 weeks after the treatments.

Results:
Four days after the treatments, intravenously injected SDF-NPs circulated and accumulated selectively in the ischemic myocardium (Figure), with an SDF concentration roughly three times that of the other three treatments. SDF-NP-treated rats had more EPCs in the blood and preserved capillaries and arterioles in the ischemic border myocardium 4 weeks after treatment, which improved microvascular perfusion, reduced fibrosis, and preserved heart function. Of note, the hearts treated with SDF-NPs retained left ventricular function at 4 weeks compared to 1 day post-treatment, with an increase in the ejection fraction of 2.7±1.2%. The other three treatments decreased left ventricular function at 4 weeks (PBS: -7.8±1.2%, P<0.001; empty NPs: -3.9±1.3%, P=0.004; and SDF solution: -5.1±1.3%, P=0.001).

Conclusions:
Intravenous SDF-NPs selectively accumulate in ischemic cardiac tissue, protecting the myocardium from I/R injury via angiogenic effects along with EPC migration. This novel cardioprotective drug may be clinically translatable.
Abstract 14082: Evans Syndrome Post Transcatheter Aortic Valve Replacement: A Rare Presentation
Authors: Ren Jie , Lei KaChon , Aboaid Hazem , Varada Neilmegh , Gollard Russell , Ahsan Chowdhury
Published: December 2023

Description of Case:
Evans Syndrome is a rare hematologic condition. Here we present a patient who developed Evans Syndrome post TAVR. A 63-year-old male with history of HFrEF and aortic stenosis presented with 2-week history of worsening shortness of breath and bilateral lower extremity swelling. He was found to be in cardiogenic shock. TTE showed (LFLG) aortic stenosis (AS). Due to concomitant cardiogenic shock and tachyarrhythmias, we were unable to perform dobutamine stress echo. A cardiac CT was performed which revealed an aortic valve calcium score of 2761 (Figure 1). The diagnosis of severe AS was confirmed, and patient underwent TAVR. Postprocedural TTE showed significant improvement in EF. Patient’s complete blood count on admission was remarkable for Hgb of 12.5 g/dL and PLT of 148 k/mm
3
. Both Hgb and PLT began to drop significantly following TAVR. We ruled out vascular access site bleeding, mechanical complication from paravalvular leak, nutritional deficiencies, disseminated intravascular coagulation, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, myelodysplastic syndrome, HIV, hepatitis C. Autoimmune hemolytic anemia was identified given elevated lactate dehydrogenase, low haptoglobin, and positive IgG direct antiglobulin test. We started steroids and treat the case as Evans syndrome. PLT count improved from 67 to 117 k/mm
3
within 2 days of steroids initiation. The bone marrow biopsy was deferred to outpatient follow up given the response to steroids. Patient was discharged on oral prednisone. Three-month follow up showed Hgb and PLT with normal limits.

Discussion:
Anemia and thrombocytopenia are common complications post TAVR. Both anemia and thrombocytopenia are suggested to be excellent markers for clinical outcomes, morbidity and mortality after TAVR. It is crucial to keep a broad differential for post TAVR anemia and thrombocytopenia. Less common causes should be evaluated and addressed to improve prognosis.
Abstract 14112: Reproductive Risk Factors and Pulmonary Arterial Hypertension in Women
Authors: Badlam Jessica , Badesch David , Benza raymond , Callas Peter , Chung Wendy , Elliott Greg , Farber Hap , Frost Adaani , Nichols Bill , Pauciulo Michael , Poms Abby , Stapleton Renee , Yu Chang , Austin Eric D ,   United States Pulmonary Hypertension Scientific Registry (USPHSR) Investigators
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating disease that affects women more often than men. The female predominance has increased over time; recent U.S. cohorts demonstrate a female:male ratio of nearly 4:1. The role of women-specific risk, such as reproductive exposures, is poorly understood in the pathophysiology of PAH.

Hypothesis/Goals:
We hypothesize that reproductive exposures influence the development and/or severity of PAH in women. We sought to investigate the role of reproductive factors and contribution of exogenous estrogen exposures to PAH onset and severity.

Methods:
Using reproductive history/exposure questionnaires from 390 women with PAH, enrolled in both the PAH Biobank and United States Pulmonary Hypertension Scientific Registry, we conducted linear regression analyses to assess the association between individual disease severity variables, as well as REVEAL Lite 2.0 scores, and patient reported reproductive variables as the predictors (Table 1). We adjusted for potential confounders including age, race, BMI, and PAH sub-group (idiopathic, heritable, or associated).

Results:
We found that younger menopause age, less than or equal to 40 years old, associates with a lower cardiac index (CI) at diagnosis [β -0.57, p 0.02]. The association persisted when controlling for use of hormone replacement therapy (HRT). There was a trend toward lower CI in those with menopause age of 41 to 50 years old, but not statistically significant [p 0.10]. Ever use of HRT was associated with a higher pulmonary vascular resistance [β 1.6, p 0.05] and lower CI [β -0.28, p 0.01] at diagnosis.

Conclusion:
Premature menopause (age less than 40 years) and ever use of HRT associate with worse hemodynamics at diagnosis in women with PAH, including lower cardiac index. Further investigations into reproductive exposures may offer an opportunity for more comprehensive risk factor screening and modification by physicians treating PAH patients.
Abstract 14127: Differential Stroke Volume Between Left and Right Ventricles as Predictor of Clinical Outcomes: The MESA Study
Authors: Abdollahi Ashkan , Kato Yoko , Bakhshi Hooman , Varadarajan Vinithra , Chehab Omar , Zeitoun Ralph , Ostovaneh Mohammad R , Wu Collin , Bertoni Alain G , Shah Sanjiv J , Ambale Venkatesh Bharath , Bluemke David A , Lima Joao AC
Published: December 2023

Background:
Valvular heart diseases and intra-cardiac shunts associated with congenital heart disease can cause persistent disruption in the balance between left (LV) and right (RV) ventricular stroke volumes (SV). However, the prognostic value of such imbalances has not been established among asymptomatic individuals in the general population.

Methods:
4,058 participants from multi-ethnic study of atherosclerosis who had a cardiac MRI at cohort inception were included in this study. ΔSV was calculated as LVSV-RVSV, and participants were classified as: Balanced ΔSV: -30 mL ≤ ΔSV ≤ 30 mL; Negative ΔSV: ΔSV < -30 mL; and Positive ΔSV: ΔSV > 30 mL. Multivariable Cox proportional hazard regression models were applied to compute hazard ratios for the association between ΔSV and mortality, heart failure (HF), and atrial fibrillation (AF).

Results:
The average age of participants was 61±10 years, with women making up 52% of the cohort. Participants were followed for a median of 17 years (IQR, 16.9-17.1) for AF, and 18.4 years (IQR, 18.3-18.5) for other outcomes. At baseline 1.2% of participants (n=47) had ΔSV > 30 mL, 2% (n=80) had ΔSV < -30 mL, and 96.8% (n=3931) had ΔSV between -30 and 30 mL. During follow up, 1,006 participants died, 235 incurred HF, and 764 developed AF. After adjusting for demographics and baseline cardiovascular risk factors, ΔSV > 30 mL was associated with increased mortality (HR 1.73; 95% CI 1.12-2.67; p=0.01), HF (HR 2.40; 95% CI 1.11-5.20; p=0.02), and AF (HR 1.89; 95% CI 1.16-3.08; p=0.01). These relationships were independent of LV and RV function at baseline. ΔSV < -30 mL solely linked to HF (HR 2.09, 95%CI 1.09-3.99; p=0.02) and lost significance after adjusting for baseline LV function.

Conclusions:
In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, LVSV exceeding RVSV by at least 30 mL was independently associated with lower long-term survival and greater risk of HF and AF.
Abstract 14149: Neighborhood Income and Heart Failure Outcomes: A Nationwide Retrospective Cohort Analysis
Authors: Kotta Prasanti Alekhya , nambi vijay , Misra Arunima , Fedson Savitri , Virani Salim S , Abramov Dmitry , Minhas Abdul Mannan Khan
Published: December 2023

Introduction:
The association between socioeconomic status (SES) and heart failure (HF) outcomes is not well understood.

Methods:
We conducted a retrospective analysis of adult HF hospitalizations from the United States National Inpatient Sample (NIS) between 2016 - 2020. Quartile classification of the median household income of the zip code of the patient’s residence provided by NIS was used. Multivariable logistic regression, adjusting for multiple variables (Table 1), was performed.

Results:
From lowest to highest income quartile, mean age and proportion of White race increased; proportion of females, Black, and Hispanic race decreased (Table 1). Higher income quartiles had a higher proportion of Medicare and private payors, lower income quartiles had higher proportion of Medicaid. Higher income quartiles received a greater proportion of care in urban teaching hospitals, lower income quartiles received more care in rural hospitals.The prevalence of obesity, pulmonary disease, diabetes, and substance use decreased; prevalence of atrial fibrillation, valvular disease, and ischemic heart disease increased in higher income quartiles. Compared with lowest income, highest income residents had higher rates of pressor use (odds ratio [OR] 1.32, 95% CI 1.2 - 1.5, P < 0.001), mechanical circulatory support (OR 1.5, 95% CI 1.4 - 1.7, P < 0.001), cardiogenic shock (OR 1.18, 95% CI 1.11 - 1.25, P < 0.001), and cost ($16163 vs $12555). There was a decreasing, but statistically insignificant, difference in in-hospital mortality (OR 0.98, 95% CI 0.94 - 1.02, P = 0.35), and cardiac arrest (OR 0.95, 95% CI 0.9 - 1, P = 0.07); with no difference in disposition to care facility (OR 1.01, 95% CI 0.99 - 1.03, P = 0.216) in highest compared to lowest income quartiles.

Conclusions:
We found differences in demographic and clinical outcomes across income quartiles, which could be suggestive of different factors contributing to HF development, its trajectory, and management based on SES.
Abstract 14180: A Case of Symptomatic Thoracic Aortic Aneurysm After Recent Fluoroquinolone Use
Authors: Farooqui Naba , Inglis Sara , Lopez-Jimenez Francisco
Published: December 2023

Background:
Thoracic aortic aneurysms (TAAs) can be found in 1-2/1000 individuals in the general population and are commonly associated with genetic disorders of connective tissue and bicuspid aortic valve (BAV). Larger size, distal aneurysms, high DBP and presence of BAV are some factors that can accelerate aneurysm growth.

Case:
A 37-year-old male without a history of recent trauma or stimulant use presented to the emergency room with 2 days of chest tightness. He had acute worsening overnight and awoke with chest pain, discomfort in the suprasternal notch and between the shoulder blades. He had no other medical history, however, was treated with a 10-day course of Ciprofloxacin for epididymitis 3 weeks prior. On presentation, the patient had active pleuritic chest pain, tachycardia and tachypnea with no abnormalities on cardiac auscultation. EKG showed sinus tachycardia, PVCs, and nonspecific ST elevations in leads II, III and aVF with normal troponins and chest X-ray. CT chest angiogram revealed a 60 mm ascending aortic aneurysm (
Fig. 1a
). Doming of the right cusp of the aortic valve in the parasternal view (
Fig. 1b
) raised suspicion for BAV which was confirmed with the classic fish mouth appearance on the TEE (
Fig. 1c
). The patient underwent successful aortic repair with graft placement. First degree relatives were offered screening for BAV. Ciprofloxacin was replaced with Sulfamethoxazole-Trimethoprim for treating his residual epididymal infection.

Discussion:
TAA rupture is associated with a >90% mortality rate. It is important to be aware of echocardiographic features of BAV as this can predispose to accelerated aneurysm growth. Additionally, fluoroquinolones (FQs) are a commonly prescribed class of antibiotics that may affect the structural integrity of the aorta, associated with aneurysm enlargement and rupture. This case offers an important example to highlight why the FDA recommends against the use of FQs in patients with known TAA or risk factors for it.
Abstract 14199: Whole Blood RNAseq Reveals a Pro-Inflammatory Signature in Patients With Coronary Microvascular Dysfunction and Ischemia With Non-Obstructive Coronary Arteries
Authors: Smilowitz Nathaniel R , Schlamp Florencia , Hausvater Anais , Joa Amanda , Serrano-Gomez Claudia , Farid Ayman , Hochman Judith , Barrett Tessa A , Reynolds Harmony , Berger Jeffrey
Published: December 2023

Background:
Coronary microvascular dysfunction (CMD) is a key mediator of ischemia with non-obstructive coronary arteries (INOCA), but pathogenic mechanisms remain unknown. Whole blood gene expression profiling is an unbiased method to investigate molecular and cellular pathways associated with disease. We analyzed whole blood expression profiles in patients with and without CMD to provide insights into INOCA mechanisms.

Methods:
Women with ischemic symptoms or myocardial ischemia on stress testing with <50% stenosis in all major epicardial coronary arteries were enrolled. Coronary flow reserve (CFR) was measured invasively by thermodilution and CMD was defined as a CFR <2.5. Whole blood RNA was collected at the time of coronary angiography and sequenced. Age adjusted differential expression analyses were performed with DESeq2 to identify differentially expressed transcripts in patients with and without CMD, and by CFR as a continuous function. Canonical pathways were obtained with Ingenuity Pathway Analysis (IPA). Nominal P-values <0.05 were used to identify relevant genes and pathways.

Results:
We enrolled 28 women with INOCA (mean age 60 ± 8.4 years, 82% white, 32% Hispanic/Latino ethnicity), among whom 7 had CMD; 1,450 transcripts were differentially expressed when stratified by CMD status (
Panels A and B
). When CFR (median 3.2 [IQR 2.5-4.2]) was evaluated as a continuous variable, IPA revealed lower CFR was associated with upregulated inflammatory pathways including neutrophil extracellular trap signaling, macrophage activation, interferon, IL-8, and IL-6 signaling, Fcγ receptor-mediated phagocytosis, and pathways related to reactive oxygen species production
(Panel C)
.

Conclusion:
Among women with INOCA undergoing invasive testing, pro-inflammatory signaling pathways were upregulated in those with versus without CMD. Additional investigation is warranted to explore inflammation in CMD to identify possible treatment targets.
Abstract 14201: Double the Trouble: Extremely Rare Incidental Finding of a Double Interatrial Septum With Atrial Septal Aneurysm and Coexisting Patent Foramen Ovale
Authors: Bharani Vishnu , Tang Kevin , Krishnam Kavin , Urgun Deniz , Naqvi Ali
Published: December 2023

Case:
A 59-year-old female with a past medical history of hypothyroidism and IgG deficiency presents to cardiology clinic due to palpitations and premature ventricular complexes (PVCs) noted at a recent urgent care visit. In-office vitals, physical exam, labs, and EKG were unremarkable. Ambulatory cardiac monitoring showed predominantly sinus rhythm with a PVC burden of 1.4%. Echocardiogram revealed an extremely rare structural anomaly – a double interatrial septum (DIAS) with atrial septal aneurysm.

Cardiac MRI (cMRI) further confirmed the presence of a DIAS enclosing an interatrial space, along with blood flow within the interatrial space and a discontinuity in the anterior right lateral atrial septum suggestive of a patent foramen ovale (PFO). There was no evidence of thrombus within the interatrial or intracardiac spaces. Mild right atrial enlargement was seen. The patient was initiated on aspirin for cardioembolic stroke prophylaxis.

Discussion:
DIAS is a highly rare congenital cardiac anomaly with limited number of cases in literature. It has been described as a midline third atrium resulting in a “tri-atrial heart”. As of 2018, less than 20 cases have been cited. DIAS is characterized by two parallel interatrial septa along with a clear echo lucent midline space that expands in systole and collapses in diastole. This case is unique as it is one of the few to include additional characterization with cMRI.

Patients with DIAS are usually asymptomatic but can experience cardioembolic events as the interatrial space is at risk for thrombus formation. Communication across the DIAS makes these events more likely. Unlike with atrial fibrillation/flutter, no current criteria for anticoagulation (AC) initiation exists for DIAS given the scarcity of cases. While some sources advocate for use of anti-platelet agents, others have indicated a preference for oral AC.

Our patient had an interatrial space and a PFO but lacked communication across the DIAS, had low bleeding risk, and no other classic risk factors of Virchow’s triad. We determined her risk for thrombus formation to be relatively low, and thus initiated her on aspirin over oral AC. Percutaneous closure of the interatrial space was deferred as it has been dismissed as a viable treatment option in the literature.
Abstract 14216: Acute Heart Failure and Mitral Stenosis in a Patient With Spindle Cell Sarcoma of the Mitral Valve
Authors: Ormachea Kori , Cranston Ariana , Khadilkar Arjun , Quintero Bisono Janina , George Bistees
Published: December 2023

A 27-year-old male with no past medical history presented with a productive cough, intermittent hemoptysis, dyspnea, orthopnea, and lower extremity edema. He underwent an echocardiogram that was significant for a large 6.2 cm x 3.5 cm left atrial mass moving into the left ventricle across the mitral valve concerning for a myxoma. Other pertinent findings were an ejection fraction of 50-55%, severe mitral stenosis with a mean mitral valve gradient of 23, severely reduced right heart function, and severe tricuspid regurgitation. Cardiovascular surgery was consulted for evaluation of atrial mass. He underwent left atrial mass resection. The left atrial mass was attached to the mitral valve, so the mitral valve was repaired with Onyx mechanical valve. After the surgery, there was a significant improvement in right heart function, mitral valve gradient, and velocities were within the expected range. Pathology from atrial mass back with high-grade spindle cell sarcoma so Oncology was consulted. Further studies were negative for metastatic spread. He was started on adjuvant chemotherapy and currently, he is undergoing his fourth cycle. Follow-up TEE six months later noted a left atrial mass located in or where the left atrial appendage should be approximately that was 2.5cm x 1.5cm concerning for recurrence of his sarcoma.

This case demonstrates a rare primary cardiac tumor, spindle cell sarcoma, which is generally aggressive and therefore has a poor prognosis. The clinical symptoms are more related to the location of the sarcoma than the histopathology. Depending on location, cardiac sarcomas generally present with heart failure as in this patient. About 25% of cardiac tumors are malignant with the majority of those being sarcomas. Initial evaluation of primary cardiac sarcomas should include echocardiography. The primary treatment is surgical resection of the mass with adjuvant chemotherapy, however, there is a high rate of recurrence and metastatic spread.
Abstract 14280: Real-World Study of Fondaparinux in Chinese Non-ST-Segment Elevation Acute Coronary Syndrome Patients: REFOCAS
Authors: Chen Yundai , li dandan , Tuo Xiaodan , Yu Yani
Published: December 2023

Introduction:
In NSTE-ACS patients, fondaparinux appears to have superior benefits than LWMH, however its application in patients with different risk stratification is still not obvious.

Hypothesis:
The use of fondaparinux or LMWH has an impact on prognosis in NSTE-ACS patients with different ischemic and bleeding risks.

Methods:
A multicenter, prospective, open-label, real-world study was conducted in 8066 adult patients with non-emergency PCI at 89 hospitals from July 2019 to July 2021. Patients received fondaparinux (2.5 mg/d) or LMWH (1 mg/kg, twice/day) , they were followed-up within 6-month. The GRACE and CRUSADE scores were used to stratify the included patients. The primary outcome was the incidence of NACCE (all-cause death, reinfarction, nonfatal stroke, or BARC≥type 2 bleeding) at 30 days, and secondary endpoints included BARC≥type 2 bleeding or MACE during hospitalization, 30 days, and six months.

Results:
In total, 5430 patients received fondaparinux treatment and 2636 received LMWH treatment, with 4976 and 2477 completed the trial respectively. The primary outcome occurred in 136 patients (2.7%) receiving fondaparinux and in 110 patients (4.4%) in LMWH [HR=0.608(0.471,0.785), p<0.001]. The rate of BARC≥2 bleeding at 30-day was significantly lower in the fondaparinux group compared with the LMWH group[68(1.4%) vs. 66(2.6%), HR=0.509(0.361,0.716), P<0.001]. Reduction in rate of NACCE and BARC ≥ type 2 bleeding were still observed during hospitalization and at six-month follow-up in fondaparinux group. In low bleeding risk individuals (CRUSADE score≤40), fondaparinux reduced the rate of BARC≥2 bleeding at 30-day by 0.9% compared with LMWH, which decreased by 3.1% in high bleeding risk individuals(CRUSADE score>40). Among patients with low ischemic risk (GRACE score≤140 ), fondaparinux significantly reduced the incidence of NACCE, MACE, and BARC ≥ 2 bleeding at each follow-up visits.

Conclusions:
In Chinese patients with NSTE-ACS, fondaparinux reduced the incidence of the composite endpoint event of bleeding and ischemia of 30 days compared with LMWH. Meanwhile, fondaparinux exhibited better safety in patients with high bleeding risk, and in the low ischemic risk group, the overall efficacy and safety were also better than LMWH.
Abstract 14291: Novel 4D Procrustes Motion Analysis Applied to CMR Links
LMNA
Mutation Severity With Myocardial Dynamics
Authors: Topriceanu Constantin-Cristian , Al-Farih Mashael , Joy George , Chan Fiona , Webber Matthew , Ilie-Ablachim Denis C. , Shiwani Hunain , Pettit Stephen , O'Brien Ben , Choapde Sandesh , Hingorani Aaron , Hughes Alun , Mohiddin Saidi , Savvatis Konstantinos , Moody William E , Steeds Richard P , Moon James C , Puddu Paolo Emilio , Barison Andrea , Piras Paolo , Captur Gabriella
Published: December 2023

Introduction:
Procrustes motion analysis (PMA) is a novel method to extract microstructural tensor data from CMR cines.

Aim:
To illustrate its usefulness in phenotyping patients with confirmed pathogenic lamin (
LMNA
) mutations (
LMNA+).

Methods:
This n=187 prospective multi-centre CMR study (NCT03860454) recruited
LMNA+
(n=67), participants with dilated cardiomyopathy carrying wild-type
LMNA
gene (DCMwt; n=73) and healthy volunteers (HV, n=47). Left ventricular (LV) cines were analyzed using 3D feature tracking. Generalized procrustes analysis was used to calculate the radial, circumferential, and longitudinal strains. To explore differences in myocardial dynamics between these groups, PMA was employed to derive the procrustes trajectory size at 16 homologous time points of the cardiac cycle in comparison to a common diastolic reference point.

Results:
Compared to HV,
LMNA+
had worse radial and circumferential strain values (
Fig. 1
). Compared to DCMwt,
LMNA
+ had better strain profiles after adjusting for late gadolinium enhancement.
LMNA+
truncating variant carriers had a smaller procrustes trajectory size during diastole compared to splice and missense variant carriers (i.e., reduced myocardial dynamics according to the PMA) (
Fig. 2A
). Similarly,
LMNA+
who had a mutation upstream of nuclear localization signal (worse mutation) had lower myocardial dynamics compared to those who had a downstream mutation (
Fig. 2B
).

Conclusion:
Detailed information on myocardial deformation patterns between diastole and systole can be inferred using PMA applied to CMR cines. Procrustes trajectory size may be a novel marker of myocardial dynamics linked to mutation severity.
Abstract 14308: Perioperative Cyclohexanone Exposure During Neonatal Congenital Heart Surgery Potentiates Brain Injury
Authors: Gupta Ria , Kuiper Jordan , Buckley Jessie , Russell Mark , Ellis Greg , Graham Eric M , Stengelin Martin , Graham David , Everett Allen D
Published: December 2023

Introduction:
Neurodevelopmental delay is hallmark for children with congenital heart defects. Risk factors include industrial contaminants in medical devices, such as cyclohexanone.

Hypothesis:
To evaluate associations between perioperative cyclohexanone and cyclohexanone metabolites with perioperative biomarkers of brain injury.

Methods:
From 75 neonates who underwent congenital heart surgery involving cardiopulmonary bypass (CPB), we assayed perioperative serum samples (preoperation, post-CPB, 24 hours postoperation) for cyclohexanone, two cyclohexanone metabolites (trans-1,2- and trans-1,4-cyclohexanediol), and biomarkers of brain injury: glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), and Tau. We calculated the molar sum of cyclohexanone metabolites (Σmetabolites), and at each timepoint we used quantile regression to evaluate differences in median brain injury biomarker concentrations (pg/mL) per doubling in concentration of cyclohexanone or Σmetabolites (ng/mL). We adjusted associations for cyclohexanone assay batch, postnatal age at surgery (days), weight at surgery (kg), The Society of Thoracic Surgeons and The European Association for Cardio-Thoracic Surgery (STAT) mortality risk category, and total duration of CPB (min).

Results:
In adjusted analyses, a doubling in preoperation cyclohexanone concentration was associated with a 19 pg/mL (95% CI: 3, 35) greater median Tau concentration. Similarly, a doubling in post CPB cyclohexanone was associated with an 88 pg/mL (95% CI: 20, 156) greater median concentration of Tau and 137 pg/mL (95% CI: 54, 220) greater median concentration of NF-L. Associations with Σmetabolites were generally null, though a doubling in post-CPB concentration was associated with a 34.7 pg/mL (95% CI: -0.8, 70) greater NF-L and 54.1 pg/mL (95% CI: 15, 94) greater Tau concentration. Associations with GFAP at all timepoints were null.

Conclusions:
Perioperative cyclohexanone exposure is associated with worse neurodevelopmental outcomes and in this study, cyclohexanone levels were associated with NF-L and Tau which are measures of axonal damage. Interventions to reduce cyclohexanone exposure may improve long term neurodevelopment.
Abstract 14314: Streamlining Cardiovascular Assessment Through Expert Intervention: Reduction in Superfluous Troponin I Testing Requests
Authors: Fernandes Ariana E , Diniz Raissa , Strunz Celia , Nairo Sumita , Antonangelo Leila , Calderaro Daniela , Cardozo Francisco , Fornari Luciana S , Gualandro Danielle M , Caramelli Bruno
Published: December 2023

Introduction:
Cardiac troponin (cTn) measurements play a pivotal role in diagnosing and managing myocardial infarction (MI). Nonetheless, to prevent unnecessary expenditure, it is essential to optimize the usage of cTn testing. The AHA guidelines underscore the importance of minimizing low-value care, considering the widespread prevalence and substantial expenses related to cardiovascular disease. Hence, our study hypothesis is that expert-recommended cTn testing could effectively decrease unnecessary testing requests.

Aims:
This study aims to contrast the frequency of normal and of serial cTn I test results within a General University Hospital (GUH) setting and a specialized Cardiology University Hospital (CUH).

Methods:
Our cross-sectional study encompassed all cTn I tests performed at both GUH and CUH between November 2022 and March 2023. We excluded patients receiving postoperative care following invasive cardiac procedures and those engaged in research protocols. We categorized the study population by sex and age (<60 or ≥60 years), as well as by whether the cTn I test was serially conducted (≥2 times within 24 hours). A serial cTn I test, as recommended by the 4th Universal definition of MI to detect any rise and/or fall, was considered a correct request. We utilized the chi-square test for categorical variables and the Mann-Whitney test for continuous data, setting a 5% significance level. Normal reference levels were <16 and <34 ng/L for women and men, respectively.

Results:
The study incorporated a total of 5,360 tests performed in GUH, with 46.2% on women and 60.9% on individuals aged ≥60 years. In CUH, 8,487 tests were conducted, with 42.0% on women and 53.8% on individuals aged ≥60 years. GUH displayed a higher proportion of normal cTn I test results compared to CUH (70% versus 45%, p < 0.0001) and a lower percentage of serial cTn I tests (40.3% versus 53.4%, p < 0.0001). Moreover, GUH demonstrated a lower median troponin value of 8 (2.5-33.8) versus 37 (7-455) in CUH, p < 0.0001.

Conclusions:
The increased prevalence of normal cTn I results and the lower frequency of serial cTn I tests in GUH indicate potential economic inefficiencies related to excessive cTn I testing requests. Expert intervention could help in avoiding unnecessary cTnI test requests.
Abstract 14319: Riociguat in Pulmonary Arterial Hypertension: Application of the 4-strata COMPERA 2.0 Risk Assessment Tool in the PATENT Studies
Authors: Rosenkranz Stephan , Hoeper Marius , Badesch David , Humbert Marc , Langleben David , McConnell John W , Rahner Claudia , Ghofrani Ardeschir H
Published: December 2023

Background:
The 2022 ESC/ERS treatment guidelines for pulmonary arterial hypertension (PAH) recommend using a four-strata risk assessment strategy at follow-up. COMPERA 2.0 is a refined four-strata risk assessment tool that subdivides patients at intermediate risk of mortality at 1 year into intermediate-low and intermediate-high risk groups for a more granular approach to risk prediction.

Aim:
This post-hoc analysis applied COMPERA 2.0 to the PATENT studies of riociguat in patients with PAH.

Methods:
COMPERA 2.0 was applied to patients who were pretreated with PAH therapy at PATENT-1 entry. Patients with missing data for COMPERA 2.0 variables were excluded. In PATENT-1, risk strata were assessed at baseline and Week 12; and 6-minute walking distance (6MWD) at Week 12 was analyzed by risk strata at baseline. All pretreated patients entering the PATENT-2 open-label extension were included in Kaplan-Meier analyses to assess association of risk strata at PATENT-1 baseline and Week 12 with clinical worsening and survival.

Results:
At PATENT-1 baseline (riociguat 2.5 mg n=102, placebo n=49), more patients were at intermediate-low risk than intermediate-high risk (Figure 1). At PATENT-1 Week 12, a higher proportion of patients were at low risk with riociguat vs placebo (Figure 1). At PATENT-1 Week 12, the following mean [SD] changes in 6MWD were seen in patients at intermediate-low risk (riociguat 24 m [57 m], placebo 10 m [60 m]) and intermediate-high risk (riociguat 34 m [56 m], placebo –2 m [70 m]) by COMPERA 2.0 at baseline. COMPERA 2.0 assessed at PATENT-1 baseline and Week 12 was able to discriminate between risk strata for clinical worsening and survival in PATENT-2 (n=167, log-rank tests: p≤0.001 for all analyses).

Conclusion:
This analysis confirmed the risk-reduction benefits of riociguat in patients with PAH and validated the utility of COMPERA 2.0 in the long-term risk assessment of patients from a clinical trial population.
Abstract 14337: Identification of New Clinical Phenotypes of Sudden Cardiac Death Using Artificial Intelligence
Authors: Jabre Patricia , Youssfi Younes , Bougouin Wulfran , BEGANTON Frankie , Chopin Nicolas , Jouven Xavier
Published: December 2023

Introduction:
Current classifications of Sudden Cardiac Death (SCD) are based on cardiovascular (CV) conditions and risk factors, and frequently fail to explain numerous SCD cases. Hypothesis: a data-driven machine learning approach could identify new clinical phenotypes of SCD in the general population, using a wide range of CV and non-CV variables.

Methods:
All case of SCD over 18y that occurred between 2011-15 in Paris and suburbs were included in the Paris Sudden Death Expertise Center. Data from the French National Health Insurance database that occurred up to 10y before SCD were collected (drugs, examinations,diagnosis). We performed a non-supervised statistical approach to identify relevant clinical phenotypes of SCD, using clustering and dimension reduction methods. A validation was performed between 2016-20.

Results:
12,651 SCD subjects were included. Mean age was 68y, and 61% were men. The clustering analysis identified 8 distinct clusters of SCD, with homogeneous characteristics. 3 clusters were already well known: a group mainly composed of aged women (3,307, 38% men, 81y), one with mainly CV diseases (3,638, 74% men, 74y) and one of young subjects with very few comorbidities (2,645, 65%men, 54 y). 4 non-CV clusters were identified: a group with psychiatric and/or neurologic disorders (862), a group with chronic or acute pulmonary diseases (688) and a group with malignant neoplasms of different sites and related drugs (518), and a group with kidney diseases (279). The last group was composed of subjects with characteristics related to social deprivation (alcohol related disorder, hepatitis, HIV, etc) (252).The same 8 clusters were identified in the validation cohort (11,485).

Conclusions:
By extending far beyond CV pathology, our approach provides for the first time a global picture of SCD, revealing the involvement of extra CV medical fields that might eventually lead to discover new pathways and help identifying high risk subjects.
Abstract 14353: Deficiency of Protein Kinase Cδ Revamps Atherosclerotic Plaque Complexity by Halting Inflammasome Activation and Intensifying Mitochondrial Function
Authors: Lien Chih-Feng , LIN CHIN , Lin Chin-Sheng
Published: December 2023

Introduction:
Plaque complexities substantially contribute to acute coronary syndrome. Inflammation and cell death in macrophages play a vital role in the formation of vulnerable plaques. Previous study had shown that protein kinase Cδ (PKCδ) is involved in the initiation and progression of atherosclerosis. However, the role of PKCδ on plaque stability remains unclear.

Hypothesis:
PKCδ regulates macrophage inflammation and cell death, leading to the formation of vulnerable plaques.

Methods:
The PKC family gene expressions in human atheroma plaques and nearby macroscopically intact tissues were analyzed from the gene expression omnibus data sets GSE43292. Two main mice models, including

Ldlr
-/-
/ PKCδ
-/-

mice and

Ldlr
-/-

mice lethally irradiated and bone marrow transplanted (BMT) with either

PKCδ
-/-

or wild type (WT), were applied to evaluate the impact of macrophages PKCδ on atherosclerosis. Blood, aorta, and aortic sinus were collected. The effects and underlying molecular mechanisms of PKCδ on inflammasome activation, pyroptosis, and mitochondrial function were explored using bone marrow-derived macrophage (BMDM) from

PKCδ
-/-

and WT mice.

Results:
The gene expression of PKCδ significantly increases in human atheroma plaques, which is correlated with the expression of NLRP3 inflammasome. The deletion of PKCδ reduces plasma lipid profile and atherosclerosis in

Ldlr
-/-

mice. Moreover, the deletion of PKCδ attenuates necrotic core formation, in both double knockout and BMT models. The RNA-seq analysis revealed that pyroptosis and mitochondrial oxidative phosphorylation (OXPHOS) are the potential mechanisms in PKCδ-regulated atherosclerosis. Additionally, knockout of PKCδ reduces expressions of LPS/IFNγ-induced TNFα, IL-6, and NLRP3 inflammasome in BMDM. Finally, the deficiency of PKCδ increases mitochondrial OXPHOS in BMDM, suggesting a potential role for PKCδ in the regulation of cellular metabolism and inflammation.

Conclusions:
Our findings indicate a crucial role for PKCδ in the development of complex atherosclerotic plaques, as it promotes inflammation, pyroptosis, and mitochondrial dysfunction. Targeting PKCδ could potentially be a therapeutic strategy for the treatment of atherosclerosis.