bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4147446: Safety and Outcomes of Leadless Pacemaker Retrieval in the United States
Authors: Abe Temidayo , Udongwo Ndausung , Fatuyi Michael
Published: November 2024

Introduction:
While the utilization of leadless pacemakers is growing, the safety of device retrieval remains an important question that has yet to be addressed.

Methods:
Using the State Inpatient Database (2016 to 2021), we identified 426 cases of leadless pacemaker (Medtronic MICRA) revision or replacement using ICD-10-PCS codes 02WA3NZ and 02PA3NZ. In-hospital mortality and procedure-related complications, including vascular or access site injuries, pericardial and myocardial injuries, bleeding, and emergent open-heart surgery, were examined. Additionally, healthcare resource utilization and post-discharge outcomes were assessed.

Results:
The mean age of the patients was 69 ± 14 years. Most procedures (77%) were performed electively at large urban teaching hospitals. Device malfunction was a secondary diagnosis in 10% of cases, and infection occurred in 14%. The in-hospital mortality rate was 7.4%, with 29% experiencing procedure-related complications, primarily post-procedural bleeding (64%) and pericardial injury (23%). These complication rates remained unchanged throughout the study period and were more likely to occur in patients with a high comorbidity burden and those undergoing non-elective procedures. The mean length of stay was 12.1 days, and the inflation-adjusted cost was approximately $76,432. The 30-day all-cause readmission rate was 14%.

Conclusion:
Leadless pacemaker retrieval presents significant risks, with complication rates remaining unchanged over the past five years. Prior to retrieval, careful evaluation is essential, and retrieval protocols should be optimized.
Abstract 4147560: Interoperable and Scalable Electronic Clinical Quality Measurement for Appropriate Use of Anticoagulation for Atrial Fibrillation in a Multicenter Health System
Authors: Thangaraj Phyllis , Dhingra Lovedeep , Khera Rohan
Published: November 2024

Background:
Anticoagulation (AC) in patients with atrial fibrillation (AF) at high risk for stroke is strongly recommended in guidelines, but tracking the optimal use of AC at scale and across hospital systems is challenging due to the need to examine both thrombotic and bleeding risks that often factor in clinical decisions. We propose a novel electronic clinical quality measure (eCQM) based on a computable phenotyping algorithm developed for and applied to a common data model (CDM) to enable at-scale assessments of CHA
2
DS
2
VASc and HAS-BLED to patients with AF in a multi-hospital health system.

Methods:
In patients with AF, we extracted CHA
2
DS
2
VASc and HAS-BLED scores by mapping individual components to standardized concepts from the Observational Medical Outcomes Partnership CDM concept set building tool, ATLAS. Clinician experts pursued manual curation of applicable concepts spanning demographics, conditions, laboratory values, medications, procedures, and vital signs, based on either the presence/absence of conditions in the patient EHR, or the given threshold of lab values or vital signs. We then assessed patients’ AC status across stroke and bleeding risk ranges [A].

Results:
Across 5 hospitals and clinic sites, there were 64,632 patients with AF, mean age 74 (SD 14) with 27,846 (43%) female, and 4,060 (8%) Black who interacted with the health system within the past year. The mean CHA
2
DS
2
VASc score was 4.5 (SD 2.0) and HAS-BLED was 3.0 (SD 1.5). For those on AC, the mean CHA
2
DS
2
VASc score was 4.8 (SD 2.0) versus 3.8 (SD 2.1) for those not on AC [B], while the mean HAS-BLED score for those on AC was 3.2 (SD 1.5) vs 2.7 (SD 1.5) for those not on AC [C]. By score, 92% had a stroke risk of 2% or greater, and 66% of these patients were on AC, with a mean HAS-BLED score of 3.2 (SD 1.5). The most common contributors to a HAS-BLED score of 2 or greater were medication exposure predisposing to bleeding (90%), age greater than 65 (85%), prior bleeding event (47%), and uncontrolled hypertension (46%). Across hospital sites, the proportion of patients with AF with a CHA
2
DS
2
VASc score of 2 or more and HAS-BLED score of 4 or less not on AC varied from 58% (Greenwich Hospital) to 72% (Bridgeport Hospital) [D].

Conclusion:
We demonstrate the ability of a scalable EHR-native eCQM that accounts for thrombotic and bleeding risk at scale to monitor the quality of care, with gaps in care noted in a large diverse health system.
Abstract 4147574: Prevalence of albuminuria in US adults: 2017-2020
Authors: Kibbi Ramzi , Huang Xiaoning , Seegmiller Laura , OBrien Matthew , Khan Sadiya , Shah Nilay
Published: November 2024

Introduction:
Chronic kidney disease (CKD) is a major source of morbidity and mortality yet is underdiagnosed. Screening for CKD can include measurement of urinary albumin-to-creatinine ratio (UACR). However, the yield of elevated UACR to diagnose CKD in the US population with cardiometabolic comorbidities is not known.

Objective:
We sought to investigate the prevalence of elevated UACR among high-risk populations to explore the public health benefits of UACR screening within those populations.

Methods:
This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2017 to March 2020. We included adults aged 20 years and older with available data on UACR. Elevated UACR was defined as ≥30 mg/g and was evaluated overall and among adults with a diagnosis of hypertension or diabetes, defined as self-reported diagnosis or use of medication. Elevated UACR was also evaluated across various weight statuses, including obesity (BMI ≥ 30). All analyses accounted for the NHANES complex sampling design. Chi-square analysis evaluated for differences in proportion with elevated UACR among participants with and without cardiometabolic risk factors.

Results:
Among 8,644 participants representing 240,823,181 US adults, mean (standard deviation) age was 48 (18) years. Participants were 16% Hispanic, 11% non-Hispanic Black, and 63% non-Hispanic White. There was a high prevalence of obesity (41%), hypertension (32%), and diabetes (11%). In the overall sample, approximately 10% had elevated UACR. The prevalence of elevated UACR was higher in those with obesity (12%), hypertension (18%), and diabetes (31%). Chi-square analysis showed that the proportion of participants with elevated UACR was higher among adults with cardiometabolic risk factors (p<0.001).

Conclusions:
A substantial proportion of US adults have elevated UACR, especially among those with cardiometabolic comorbidities, such as hypertension and diabetes. Future research should evaluate the cost-effectiveness of screening for CKD with UACR.
Abstract 4147579: Nationwide trends in Major Adverse Cardiac and Cardiovascular Events and ALL-cause Mortality in Cardiovascular-Kidney-Metabolic Syndrome Among Geriatric Patients.
Authors: Prajapati Kesar , Doshi Kesha , Doshi Preet , Pasnoor Diksha Sanjana , Brereton Brian , Mettela Sambasiva Rao , KALAPALA CHAITANYA , Cheruvu Naga Pratyusha , Desai Rupak
Published: November 2024

Background:
The American Heart Association (AHA) has acknowledged the interconnection of obesity, type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) as a complex health disorder named Cardiovascular-Kidney-Metabolic (CKM) syndrome. Patients with CKM progress to major adverse cardiac and cerebrovascular Events (MACCE). The aim of the study is to analyse nationwide trends in MACE and all causes. mortality among patients aged 65 years and older with CKM syndrome.

Methods:
Using a National Inpatient Sample (2016–2020) geriatric admissions among patients admitted with CKD and at least One cardiometabolic risk factor (HTN, DM, HLD, and obesity) were selected using ICD-10. codes. Patients were classified into MACCE+ve cohorts if they had acute myocardial infarction, cardiac arrest or acute ischaemic stroke present otherwise into MACCE-ve. Trends, Demographics, comorbidities, and all-cause mortality were analysed between the two cohorts.

Results:
In our NIS study, the MACCE+ve and -ve cohorts had median ages of 78 (72–85) and 78 (72–85). years with 55.9% and 51.1% males and 44.1%. and 48.9% females, respectively. over a period of 5 years (2016–2020) in patients with CKM syndrome hospitalisation has increased with MACCE (from 10.4% to 12.7%) with an increase in hospital mortality (4.6% to 6%) (ptrend<0.001). In our analysis, patients with CKM admitted to MACCE had statistically significant all-cause mortality (15.3% vs. 3.4%), total length of stay (5 vs. 4), and hospital cost ($66,824 vs. $43,727) compared to MACCE-ve cohorts (p-value < 0.001).

Conclusion:
Our analysis suggests alarmingly rising trends in MACCE in CKM syndrome, which significantly impacts in-hospital outcomes. We need to conduct more studies to enhance our comprehension of managing CKM syndrome.
Abstract 4147741: The Effect of Anemia on the Mechanisms of Exercise Intolerance in Adults with HFpEF
Authors: Manferdelli Giorgio , Wakeham Denis , Leahy Michael , Skow Rachel , Kissel Claire , Brazile Tiffany , MacNamara James , Fadel Paul , Haykowsky Mark , Levine Benjamin , Sarma Satyam , Hearon Christopher
Published: November 2024

Introduction:
Anemia (males: [Hb] <13.5 g/dL, females: <12 g/dL) is common in heart failure with preserved ejection fraction (HFpEF) and associated with exercise intolerance. The hemodynamic effect of anemia and the mechanism by which anemia impairs exercise capacity in patients with HFpEF are unclear. We investigated the effects of anemia on exercise hemodynamics and oxygen transport and utilization (VO
2
) during a cardiopulmonary exercise test (CPET) and single leg knee extension exercise (SLKE) in patients with HFpEF.

Methods:
Patients with HFpEF (n=57) classified as non-anemic (n=33, 67% female, age: 70±7 y, BMI: 39.3±5.8 kg/m
2
, [Hb]: 13.7±1.5 g/dL) or anemic (63% female, age: 71±7 y, BMI: 34.7±5.9 kg/m
2
, [Hb]: 11.2±0.9 g/dL) completed CPET on a seated upright cycle ergometer. A subgroup (n=20 non-anemic; 14 anemic) also completed SLKE to exhaustion. During CPET we measured VO
2
(indirect calorimetry), arterio-venous O
2
difference (Δa-vO
2
; arterial and right heart catheters) and cardiac output (Qc; Direct Fick). During SLKE we measured femoral artery blood flow (LBF; Doppler ultrasound), Δa-vO
2
(pulse oximetry and femoral venous catheter) and leg VO
2
. We also measured total hemoglobin mass (tHbmass; carbon monoxide rebreathing) and plasma volume. Data were compared via independent samples t-tests.

Results:
The anemic group had lower relative tHbmass (g/kg lean mass; Figure 1A) compared to non-anemic, with no difference in plasma volume (Figure 1B). Peak VO
2
during CPET was similar between groups (non-anemic: 1.32±0.39 vs anemic: 1.24±0.44 L/min,
P
=0.269), but the anemic group had a higher Q
c
-VO
2
slope (Figure 1C&D) and a lower Δa-vO
2
(non-anemic: 12.6±1.8; anemic: 10.7±1.4 mL/dL,
P
<0.001). During SLKE, no difference was detected in peak leg VO
2
, LBF, Δa-vO
2
, or diffusive capacity (all,
P
>0.175); however, the anemic group had a significantly greater LBF-VO
2
slope (Figure 1D).

Conclusion:
Patients with HFpEF and anemia present with a hyperdynamic circulation during exercise despite similar peak VO
2
to non-anemic peers. [Hb] modifies the coupling of oxygen delivery and demand and may be a key mechanism responsible for hyperdynamic circulatory responses to exercise in patients with HFpEF and anemia.
Abstract 4147796: Cardiovascular Manifestations of Amphetamine Misuse: A Pooled Analysis
Authors: Sarfraz Zouina , Jain Lakshit , Shahzad Anum , Sabzwari Syed Rafay Ali
Published: November 2024

Background:
In the United States, the misuse of stimulants such as the amphetamines Adderall and Ritalin is rising. Recent data indicates that annually, about 5.1 million Americans aged 12 and older misuse these prescription medications. The literature on the cardiovascular effects of such misuse, including acute myocardial infarction (MI), cardiac arrhythmias, and catecholamine toxicity, remains limited. This first-ever pooled analysis aims to document and report the cardiovascular manifestations associated with amphetamine misuse.

Methods:
This study was reported in adherence to PRISMA Statement 2020 guidelines. An exhaustive literature search was conducted without language or date restrictions up to June 8th, 2024, using PubMed/Medline, Scopus, Cochrane, and Web of Science, in addition to manual hand searching following an umbrella framework. This strategy yielded 621 potential studies, with 42 undergoing full-text review. Seventeen studies met the inclusion criteria, pooling a total of 433,392 patients. SPSS V26 (IBM) was used to compute pooled counts.

Results:
The median age was 30 years (IQR: 11.5). Males constituted 293,798 (67.75%) and females 140,594 (32.25%). Intravenous administration was reported in 2,586 (0.60%) of cases, and oral administration in 6 (0.0014%). The mean dosage of amphetamine was 186.25 mg. The median duration of exposure was 9 years (IQR: 7.75). Hypertension was present in 218,435 (50.7%), smoking in 169,720 (39.4%), and diabetes mellitus in 112,767 (26.2%). Recreational use was reported in 431,825 (99.77%) of cases. Chronic or long-term use was seen in 2,020 (0.47%) and daily use in 32 (0.0074%). Atherosclerotic cardiovascular disease was reported in 135,703 (31.51%), ischemic heart disease in 110,823 (25.72%), and MI in 68,443 (15.89%). Clinical diagnosis methods confirmed 430,763 (99.39%) of cases. Medication management was used in 32 (0.0074%) of cases. Continued medical therapy was needed in 30 (0.007%) of cases. Mortality was reported in 499 (0.115%) of cases.

Conclusion:
This pooled analysis highlights the significant cardiovascular risks associated with amphetamine misuse, particularly hypertension, smoking, and diabetes. There is an urgent need for coordinated psychiatric-cardiological interventions, focusing on early detection, comprehensive addiction therapy, and managing cardiovascular health to improve patient outcomes.
Abstract 4147865: Single Nucleus Transcriptomics Supports a Role for CCNA2-Induced Human Adult Cardiomyocyte Cytokinesis
Authors: BOUHAMIDA Esmaa , Vadakke-Madathil Sangeetha , Mathiyalangan Prabhu , Ranjan Amaresh , Sherman Cherrie , Miller Paul , Ghetti Andre , Abi Najah , Chaudhry Hina
Published: November 2024

Background:
Cyclin A2 (CCNA2) is a hallmark cell cycle regulator typically silenced in postnatal mammalian cardiomyocytes (CMs). We previously demonstrated successful myocardial regeneration in infarcted porcine hearts, showing a 55% increase in new CMs and significantly enhanced cardiac function following CCNA2 gene therapy.

Hypothesis:
We hypothesize that CCNA2 gene delivery can induce cytokinesis in isolated adult human CMs.

Methods and Results:
We designed a human gene therapy vector featuring a replication-deficient, E1/E3-deleted human adenovirus five encoding human CCNA2 driven by the cardiac Troponin T promoter (Ad5-cTnT-hCCNA2, vector lacking CCN2 control). We utilized time-lapse microscopic live imaging of cultured adult human CMs isolated from a 55-year-old male, 41-year-old female, and 21-year-old male. We quantified cytokinesis events in human adult CMs compared to controls and observed a significant increase in cytokinesis rate in the aging heart, particularly in the 55-year-old male (17.52 + 1.72 vs. 8.33 + 2.25, p=0.003) and the 41-year-old female (9.27 + 2.22 vs. 2.5 + 1.16, p=0.005). No significant difference was observed in the 21-year-old male (3.63 + 1.77 vs. 3.00 + 1.52, p=0.789). We measured the calcium flux in transfected CMs compared to controls after cell division under pacing conditions (0.5 Hz and 1 Hz current) and detected sarcomere structures using fluorescence microscopy. Approximately 4-5% of Ad5-cTnT-hCCNA2 transfected adult human CMs exhibited active Ca
2+
mobilization. We now report that CCNA2 can induce complete cytokinesis in in adult human CMs, preservation of sarcomere integrity in the resultant daughter cells.To understand further CCNA2 signaling pathways involved in CM cytokinesis, we conducted single nucleus transcriptomics analysis in hearts isolated from adult transgenic mice that constitutively express CCNA2 in CM (Tg) and non-transgenic mice (nTg). We identified a subpopulation of CMs enriched with cytokinesis (
Aurkb, Anln, Sept7,
and
Rho
), proliferative (
Mki67
and
Kif23
), and reprogramming (
Pou5f1, Klf4, Gata4, Myc,
and
Sox2
) genes in Tg mice compared to nTg mice. Bulk RNA sequencing of human adult and fetal hearts unveiled key reprogramming genes involved in CCNA2-induced cytokinesis.

Conclusion:
Our findings highlight promising mechanisms for the clinical development of cardiac regenerative therapy through strategic manipulation of the CM cell cycle.
Abstract 4147884: Transitions Across Stages of Cardiovascular-Kidney-Metabolic Syndrome and Related Implications for Cardiovascular Disease Risk: the ARIC Study
Authors: Ozkan Bige , Zhang Sui , Nambi Vijay , Rangaswami Janani , Echouffo Justin , Blumenthal Roger , Ballantyne Christie , Khan Sadiya , Coresh Josef , Ndumele Chiadi
Published: November 2024

Background:
Higher stages of Cardiovascular-Kidney-Metabolic (CKM) Syndrome are associated with greater cardiovascular disease (CVD) risk. However, the rates of CKM stage progression over time and its impact on CVD outcomes are currently unknown.

Methods:
We evaluated 8,367 ARIC Visit 4 (1996-98) participants without CVD at Visit 1 (1987-89), with available data to define CKM stage at Visits 1 and 4. We categorized based on CKM Stages at Visits 1 and 4, defined as: Stage 0, no CKM risk factors; Stage 1, excess/dysfunctional adiposity; Stage 2, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, or diabetes) and/or moderate- to high-risk chronic kidney disease (CKD, per KDIGO classification); Stage 3, ≥20% predicted CVD risk per PREVENT calculator or very high-risk CKD; and Stage 4, clinical CVD. For those in CKM stages 0-3 at Visit 1, we quantified transitions in CKM stages by Visit 4, as well as incidence rates of atherosclerotic CVD (ASCVD), heart failure (HF), total CVD (ASCVD + HF), and CVD mortality over 10 years according to CKM stage progression. We evaluated rates of first CVD events for those in Stages 0 to 3 by Visit 4, and of first recurrent CVD events for those in Stage 4 by Visit 4.

Results:
The mean age was 55 years at Visit 1, with 52% female, and 21% Black adults. Most participants progressed to a higher CKM stage by Visit 4 (~9-year interval): 77% of those in Stage 0 at Visit 1, 73% of Stage 1, 42% of Stage 2, and 75% of Stage 3 (Figure). Within each CKM stage at Visit 1, progression to higher CKM stages by Visit 4 was associated with a higher incidence of CVD events (Table), with higher risk for those at a higher CKM stage at Visit 1. The transition from Stage 2 to 3 was associated with the highest rate (per 1000 person-years) of first CVD events (49.8, versus 20.0 for remaining in stage 2), while the transition from stage 3 to 4 was associated with the highest rate of recurrent CVD events (151.1). Similar patterns were seen for ASCVD, HF and CVD mortality.

Conclusion:
Most middle-aged adults transition to a higher stage of CKM Syndrome over a decade, which is linked to greater CVD risk. Preventing the progression of CKM Syndrome may help to mitigate CVD risk.
Abstract 4147894: Epicardial vs endocardial ablation for ventricular tachycardia: Patient Characteristics, Procedural Factors, and Outcomes
Authors: Poddar Aastha , Futela Pragyat , Woelber Tiffany , Kowlgi Gurukripa , Heybati Kiyan , Prasitlumkum Narut , Amin Hina , Deshmukh Abhishek
Published: November 2024

Background:
Patients undergoing epicardial access for ventricular tachycardia (VT) have a higher rate of complications and VT recurrence post-procedure. Data regarding electrophysiological factors driving the outcomes are scant.

Objective:
To compare the factors and outcomes associated with epicardial vs endocardial VT ablation.

Methods:
A single-center, retrospective study of patients undergoing catheter ablation for scar-related VT was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes.

Results:
Our cohort of 554 patients had 89 (16.1%) epicardial and 465 (83.9%) endocardial VT ablations. Patients undergoing epicardial ablation had a greater frequency of NICM, and more patients had undergone sympathetic modulation for VT (p < 0.05) but had lesser frequency of valve surgery, and CABG. Epicardial ablation was associated with greater use of both short-term (<3 months) and long-term (>6 months) anti-arrhythmic drugs (AAD) (p<0.01). Epicardial access was obtained by micropuncture or needle-in-needle technique for 22.5% (n=20) of patients. Except for more use of general anesthesia and the lesser usage of drugs for VT induction during epicardial procedures, there were no significant differences. Epicardial ablation had a higher risk of acute complications (<30 days) after the procedure (driven by pericarditis) (25% vs 7.8%, p<0.01). On survival analysis, epicardial access was associated with an increase in VT recurrence and repeat ablation (p<0.01) during a mean follow-up of 1072 days. On multivariate analysis, after adjusting for age, sex and comorbidities, epicardial access was an independent predictor of VT recurrence or repeat ablation [aHR 1.61 (CI: 1.18- 2.2)]

Conclusion:
Patients undergoing epicardial ablations with fewer comorbidities demonstrated increased AAD usage prior to and after the procedure, and a higher risk of acute complications after the procedure. Epicardial access was an independent predictor of VT recurrence or repeat ablation.
Abstract 4147905: A Machine Learning Readmission Risk Prediction Model for Cardiac Disease
Authors: Bailey Angela , Wang Wei , Shannon Clarence , Huling Jared , Tignanelli Christopher
Published: November 2024

Introduction:
Circulatory disease ranks ninth highest amongst all-cause US readmissions, and despite an increase in quality improvement initiatives, emergency department visits have increased. Diagnosis specific cardiac machine learning readmission risk prediction models have been created, and at least one general readmission risk model has demonstrated a 25% relative readmission rate reduction in a focused setting.

Hypothesis/Aims:
The objective of this study was to create a high performing 30-day hospital readmission/emergency department (ED) visit or death risk prediction model. We hypothesized that the model would perform equitably and with high accuracy.

Methods:
The model was derived from a cohort of acute, cardiac inpatient admissions during 2010-2023 within ten integrated Midwestern hospitals. Encounters in which patients died or were discharged to hospice were excluded. A total of 1,498 clinical and non-clinical predictors were included in three machine learning models. Primary composite outcome was 30-day hospital readmission/ED visit or death.

Results:
The primary outcome rate was 23.8% and ED visit rate was 7.7% amongst 73,926 encounters spanning 49,144 patients. Heart failure, dysrhythmias, and acute myocardial infarction were the most common readmission diagnoses. XGBoost had the overall highest performance (AUROC of 0.691 and PR-AUC of 0.4158). At a precision of 0.5, XGBoost demonstrated a net benefit relative to current practice. Top predictors include the LACE index and total hospitalized days in the past year. The DeLong test yielded a significant difference in model performance between men and women.

Conclusions:
We successfully built a 30-day cardiac readmission/ED visit or death risk prediction model that demonstrated a net benefit relative to current practice. The difference in model performance could be driven by gender gaps in cardiac disease recognition, presentation, and treatment. Future directions include external model validation.
Abstract 4148010: Evaluation of Echocardiography and Biomarkers for Prognostication of RV Failure in COVID-19 Patients Undergoing Extracorporeal Membrane Oxygenation (ECMO)
Authors: Potarazu Deepika , Zhao Qiong , desai mehul
Published: November 2024

Background:
Severe COVID-19 infection has been associated with acute respiratory distress syndrome (ARDS) and right ventricular (RV) dysfunction. In this study, we report associations between echocardiographic findings and laboratory markers that portend RV failure in patients with ARDS secondary to COVID-19 infection on ECMO.

Methods:
A single-center study was conducted in the cardiovascular ICU of our institute. A retrospective chart review was performed on 41 patients with COVID-19 on ECMO between March and October 2020. Twenty-two patients had transthoracic echocardiograms (TTE) completed while on ECMO (VV-ECMO = 19, VA-ECMO = 3). Echocardiograms (echo) were obtained pre-cannulation, during ECMO, and post-ECMO decannulation. RV parameters analyzed included tricuspid annular plane systolic excursion (TAPSE), basal diastolic RV diameter, right ventricular fractional area of change (RV FAC), and S’. Laboratory values including BNP, CRP, D-dimer, ferritin, fibrinogen, lactate and troponin were analyzed for correlation with echo findings.

Results:
TAPSE was significantly lower in deceased patients (1.9± 0.4cm vs 1.3±0.6 cm, P< 0.05). RV FAC and S’ were also lower in the deceased group. TAPSE while on ECMO showed a positive association with peak D-dimer levels in survivors and a negative association in deceased patients. Peri-ECMO fibrinogen and CRP levels were negatively associated with TAPSE in survivors while fibrinogen showed positive association in deceased patients. LDH peak, fibrinogen initial and lactate peak were higher in the deceased[ZQ1] group. There is a trend of increased RV basal diameter in the deceased group (3.9±0.9 vs 4.2±0.9 cm). Last troponin levels were negatively associated with basal diastolic RV diameter while on ECMO in deceased patients.

Conclusion:
Preservation of RV longitudinal contractility, as reflected by TAPSE, may play an important role in the survival of COVID-19 patients on ECMO. Laboratory markers such as LDH, D-dimer, fibrinogen and lactate may have prognostic value in predicting RV failure. Further studies are required to determine if early initiation of therapies to improve RV systolic function in COVID-19 ECMO patients with ARDS improves outcomes.
Abstract 4148121: Identification of Acute Air Pollution Induced Altered Metabolomic Pathways that May Lead to CAD and AMI: the BioHEART-CT Study
Authors: Fathieh Sina , Gray Michael Patrick , Tang Owen , Astell-Burt Thomas , Grieve Stuart , Figtree Gemma
Published: November 2024

Background:
Outdoor air pollution, a persistent threat since the Industrial Revolution, continues to pose a global challenge with severe implications for public health. Despite advancements, air quality issues —particularly particulate matter —are associated with diseases like coronary artery disease (CAD) and stroke. The unknown pathophysiology that links air pollution to cardiovascular diseases is a pressing issue that demands immediate attention. Understanding these mechanisms is critical for effective prevention and treatment.

Methods:
The BioHEART-CT Discovery cohort included 1,002 adults referred for elective CTCA (2015-2020). Blood (20-30 ml) was collected at the time of CTCA, processed, stored at -80°C, and analysed using Agilent 1260 LC and QTRAP 5500 MS. Maximum daily PM2.5 was measured using home postcodes and publicly available land-based monitors. After normalisation, PCA and PLS-DA were employed to reduce dimensionality and identify significant variables, followed by pathway analysis of significant metabolites using metabolite set enrichment analysis.

Results:
Using the threshold of PM
2.5
≥12 μg/m
3
to categorise patients into high vs low-exposure, low-exposure subjects formed a distinct cluster from high-exposure subjects. PLS-DA clustering with ten-fold cross-validation identified key metabolites with high VIP scores: transHYP, betaine, and alanine. Metabolite set enrichment analysis revealed significant pathways: Glycine, Serine, and Threonine metabolism, and Arginine and Proline metabolism (p<0.001, FDR <0.05) (Figure 1).

Conclusion:
Our study's most significant finding—the enriched metabolic set of glycine, serine, and threonine metabolism, along with arginine and proline metabolism—has been implicated in the development of CAD in previous studies. These findings can potentially inform preventive and treatment strategies, making a real difference in the lives of those affected by air pollution-related cardiovascular diseases.
Abstract Or103: Thematic analysis of cardiac arrest survivor-caregiver dyads’ psychosocial intervention needs
Authors: Presciutti Alexander , Siry-Bove Bonnie , Parker Robert , Wu Ona , Elmer Jonathan , Donnino Michael , Perman Sarah , Vranceanu Ana-maria
Published: November 2024

Background:
Emotional distress in cardiac arrest survivors and their caregivers (dyads) is prevalent, persistent, and undermines clinical and quality of life outcomes. To date, there is an absence of interventions that address early distress to prevent chronicity.

Aim:
To inform psychosocial intervention content for new cardiac arrest survivor-caregiver dyads.

Methods:
Between September 2023 and March 2024, we conducted semi-structured interviews with consecutively admitted cardiac arrest survivor-caregiver dyads from Massachusetts General Hospital early after the survivor’s cardiac arrest (i.e., during the survivor’s index hospitalization or within 1 week of discharge). We audio recorded interviews, transcribed them verbatim, and conducted hybrid deductive-inductive thematic analysis of the transcripts. At least one member of the dyad must have screened positive for emotional distress (i.e.,
>
8 on either subscale of the Hospital Anxiety and Depression Scale). The survivor must have demonstrated sufficient cognitive status for meaningful participation (i.e.,
>
4 on the Short Form Mini Mental State Exam). We prespecified 4 supraordinate domains of inquiry: 1) stressors and psychosocial treatment needs, 2) coping methods, 3) reactions to preliminary content that we presented during the interview, and 4) barriers and facilitators to participation in psychosocial interventions early after cardiac arrest.

Results:
Dyads (
N
=13; survivors: female 31%, non-Hispanic White 69%, out-of-hospital cardiac arrest 62%; caregivers: female 77%, non-Hispanic White 62%, spouse/romantic partner 77%) overwhelmingly reported a need for anticipatory guidance and coping skills to address uncertainty, trauma, existential distress, and post-arrest sequelae (Domain 1). To cope (Domain 2), dyads reported utilizing social support, distraction, mind-body techniques, gratitude, and meaning and purpose. After we previewed preliminary content (Domain 3), dyads recommended we prioritize anticipatory guidance and family distress throughout. Regarding barriers and facilitators (Domain 4), dyads suggested interventions be low burden and begin after medical stabilization.

Conclusions:
Early after cardiac arrest, distressed survivor-caregivers dyads recommend that psychosocial interventions include anticipatory guidance, coping skills training, be low-burden, and begin after medical stabilization. Our findings can inform various early psychosocial intervention approaches for survivors and caregivers.
Abstract Sa305: Association Between Area of Maximal Compression During CPR Determined by Transesophageal Echocardiography, ETCO2, and Return of Spontaneous Circulation: An International Multicenter Study
Authors: Teran Felipe , Owyang Clark , Wray Trenton , Lessard Justine , Bedard Michel William , Hipskind John , Salinas Pedro , Dieiev Vladyslav , Nogueira Jonathan , Doynow Daniel , de villa Eleonora , Woo Michael , Thavanathan Rajiv , Burns Katharine , Prager Ross , Arntfield Robert , Myslik Frank , Robinson Evan , Haines Lawrence , Buchanan Brian , Jafry Zan , Sands Nathaniel , Kaviyarasu Aarthi , Abella Benjamin
Published: November 2024

Background:
TEE is increasingly recognized as a valuable imaging modality during cardiac arrest (CA) resuscitation, particularly for assessing the area of maximal compression (AMC) during CPR. Small single center studies have shown that compression of the left ventricular outflow tract or the aortic root (AMC-LVOT/Ao) is common during CPR, and that when CPR is performed with the AMC over the LV, this results in higher ETCO2, and ROSC. This study aimed to investigate the AMC and its relationship to ETCO2, and ROSC, hypothesizing that patients experiencing AMC-LVOT/Ao have lower ETCO2 and are less likely to achieve ROSC.

Methods:
A prospective, multicenter cohort study of patients with out-of-hospital and in-hospital CA (OHCA/IHCA) in whom TEE was performed during CPR comparing AMC over the LV (AMC-LV) vs AMC-LVOT/Ao. The study was conducted through the Resuscitative TEE Collaborative Registry, an ongoing multicenter research network involving 37 hospitals (NCT04972526). Collected data included patient and procedure characteristics, hemodynamics, and outcomes according to Utstein-style guidelines. Primary outcome was ROSC, and the secondary outcome was ETCO2 at the time of AMC determination. We performed univariate analysis and multivariate regression evaluating variables known to impact resuscitation outcomes.

Results:
271 patients including 205 OHCA and 66 IHCA were included. Only 133 (49%) of the total cohort had AMC-LV, with AMC-LVOT/Ao in 47% of OHCA and 42.1% of IHCA. There was no significant difference in the location of the AMC when analyzed by demographic characteristics, height, weight, or comorbidities between patients who received manual vs mechanical CPR. In OHCA, there was no difference in ROSC between AMC-LV and AMC-LVOT/Ao, however the group of patients with AMC-LVOT/Ao had on average 10 units lower ETCO2 compared to AMC-LV (Beta -10; 95% CI -19 - 1.5; p = 0.023). In IHCA, after controlling for factors known to impact outcomes, patients with AMC-LVOT/Ao had significantly lower probability of ROSC (OR 0.25, 95% CI 0.06-0.88; p=0.038).

Conclusion:
Obstruction of the LVOT/Ao during CPR is a common finding in CA patients evaluated with TEE. This multicenter study extends previous animal and smaller clinical studies suggesting the mechanistic association between the AMC during CPR, with ETCO2 and ROSC, and the potential of TEE-guided resuscitation to improve the effectiveness of CPR.
Abstract Sa802: Why Physicians Use Sodium Bicarbonate During Cardiac Arrest: A Mixed Methods Survey of Adult and Pediatric Clinicians
Authors: Ross Catherine , Sorcher Jill , Gardner Ryan , Pannu Ameeka , Kleinman Monica , Donnino Michael , Sullivan Amy , Hayes Margaret
Published: November 2024

Background:
Despite national recommendations against the routine use of sodium bicarbonate (SB) during cardiac arrest, SB is used in about 50% of both pediatric and adult IHCA, making it the second most used drug, after epinephrine.

Aims:
To explore clinician practices and beliefs surrounding intra-arrest SB administration.

Hypothesis:
We hypothesized that SB use would vary by specialty, and that indications for intra-arrest SB
not
endorsed by AHA guidelines would be common.

Methods:
We performed a mixed methods electronic survey amongst adult and pediatric intensive care unit (ICU), emergency medicine (EM) and anesthesia attendings at two local institutions in Boston, MA from October 3
rd
to December 15
th
, 2023. Likert scale responses for likelihood of giving SB in 2 cardiac arrest scenarios were compared using a Chi-squared test. These responses were dichotomized to reflect those who would “probably” or “definitely” give SB versus those who would not, and respondent characteristics were compared. For the open-ended items, we performed qualitative thematic analysis.

Results:
Of 356 physicians invited, 224 (63%) responded. The likelihood of giving SB in Scenario 1 (10-minute asystolic arrest) and Scenario 2 (20-minute asystolic arrest) differed (Figure 1), with 54/224 (24%) respondents indicating they would give SB in Scenario 1 and 110 (49%) for Scenario 2. Additionally, likelihood of giving SB in Scenario 1 varied based on practice location (p = 0.025) with the lowest rates in pediatric and adult EM (8% and 10%, respectively) and the highest amongst those in adult ICUs (38%). These differences persisted for Scenario 2 (p = 0.001). SB use in Scenario 1 also decreased with increasing years of experience (p = 0.032). The most reported indications for SB were: hyperkalemia (78%); metabolic acidosis (76%) with a median reported threshold pH of 7.1 (IQR: 7, 7.2); tricyclic anti-depressant overdose (71%); and arrest duration (64%) with a median reported threshold of 15 minutes (IQR: 10, 20). In the qualitative analysis, additional themes emerged for reasons respondents give SB, including specific diagnoses, arrest rhythms, team dynamics and beliefs about the physiological effects of SB.

Conclusions:
Physicians reported significant practice variations surrounding cardiac arrest management with SB, including several indications for SB which are not supported by national cardiac arrest guidelines.
Abstract Sa804: Brain-Directed Management of Venoarterial Extracorporeal Membrane Oxygenation in a Pediatric Swine Model
Authors: Ko Tiffany , Terakawa Katsunari , Smood Benjamin , Slovis Julia , Menezes Forti Rodrigo , Melchior Richard , Sueishi Takayuki , Chalifoux Nolan , Ranieri Nicolina , Seeney Alyssa , Krishna Akshatha , Goto Rika , Lewis Alistair , Hurlock April , Lin Yuxi , Hwang Misun , Senthil Kumaran , Aronowitz Danielle , Spelde Audrey , Morgan Ryan , Mavroudis Constantine , Baker Wesley , Kilbaugh Todd
Published: November 2024

Introduction:
We present a novel demonstration of brain-directed management of venoarterial extracorporeal membrane oxygenation (ECMO) using real-time feedback from non-invasive neurometabolic optical monitoring (NOM) of the cerebral oxygen extraction fraction (OEF) in pediatric swine. In our prior work, OEF>0.82 was associated with hypoxic-ischemic brain injury during ECMO. Maintaining OEF below this threshold may prevent injury.

Hypothesis:
Cerebral OEF levels of 0.8, 0.7, and 0.6 will be achieved during 7 h of brain-directed ECMO after prolonged cardiac arrest.

Methods:
Continuous cerebral OEF was acquired in a pediatric swine model (
sus scrofa
, 8-12 kg) of ECMO-assisted cardiopulmonary resuscitation (CPR) using NOM on the left forehead. Animals had 8 min of ventricular fibrillation followed by 30 min of low-flow ECMO (20 ml/kg/min) with epinephrine (0.02 mg/kg) boluses every 4 min to simulate prolonged CPR. Then, ECMO flow rate was increased to 70-100 ml/kg/min to reflect clinical return of circulation. After 1 h, animals were randomized to a cerebral OEF target of 0.8 (n=11), 0.7 (n=12), or 0.6 (n=12) and brain-directed ECMO management was performed for 7 h; OEF was re-assessed every 5 min. If the OEF target was not achieved (±0.05 of target), first, ECMO flow rate was adjusted between 50-120 ml/kg/min, second, arterial blood pressure (ABP) was modulated using vasoactive infusions. Blood gas, hematocrit, anticoagulation, and anesthesia were otherwise standardized across all subjects. Mitochondrial respirometry assessed maximal oxidative phosphorylation of cortical tissue following ECMO as a metric of brain health which we have shown to correlate with neurologic outcomes across injury models. Associations with mean cerebral OEF, ECMO pump flow, and ABP were examined by linear regression.

Results:
Brain-directed ECMO achieved and maintained respective OEF targets for 79% [57, 93] of the 7 h period (median [IQR] across animals). 71% (n=25/35) of animals achieved their target within 1 h of initiating brain-directed management. OEF, but not pump flow or ABP, was significantly correlated with maximal oxidative phosphorylation (p=0.005).

Conclusion:
Our results demonstrate the efficacy and precision of real-time modulation of cerebral OEF during ECMO based on neurophysiologic feedback from the individual patient. The association of OEF with brain health suggests that brain-directed management may provide new opportunities to mitigate neurological injury.
Abstract Sa807: Spread of Chest Compression-Only CPR During the COVID-19 Pandemic Increased Pediatric Out-of-Hospital Cardiac Arrest Mortality: A Nationwide, Retrospective, Observational Study
Authors: Obara Takafumi , Naito Hiromichi , Matsumoto Naomi , Tsukahara Kohei , Nojima Tsuyoshi , Hongo Takashi , Yumoto Tetsuya , Yorifuji Takashi , Nakao Atsunori
Published: November 2024

Background:
Despite the lack of evidence supporting the use of chest compression-only cardiopulmonary resuscitation (CO-CPR) emphasizing the importance of rescue breathing for pediatric out-of-hospital cardiac arrest (OHCA), prehospital CO-CPR is increasing. The COVID-19 pandemic may have led more bystanders to perform CO-CPR, even for pediatric OHCA. However, studies on the dissemination of CO-CPR and outcomes in pediatric OHCA are limited.

Hypothesis:
Spread of CO-CPR led to increased mortality in pediatric OHCA.

Aims:
Investigate the mortality of nationwide pediatric OHCA patients with the dissemination of CO-CPR pre- and post-COVID-19.

Methods:
We conducted a retrospective study using a Utstein-Style population cohort database (Japanese National Registry). Pediatric OHCA patients (≤17 years old) with bystander resuscitation attempts registered between the pre-COVID-19 era (2017-2019) and the post-COVID-19 era (2020-2021) were included. The primary outcome was 30-day mortality after OHCA. The secondary outcome was 30-day poor neurological outcomes, defined as Cerebral Performance Category scores of 3, 4, or 5. We used Poisson regression with robust variance to estimate adjusted risk ratio (aRR) with 95% confidence interval (CI) and the population attributable fraction (PAF, %) with a focus on the post-COVID-19 period.

Results:
A total of 3,352 pediatric OHCA, 2,023 pre-COVID-19, and 1,329 post-COVID-19 patients received bystander CPR and were registered in the database. CO-CPR was more common than CPR with rescue breathing (RB-CPR) during the pre- and post-COVID-19 periods [pre-COVID-19: 1,356 (67.0%) vs. 667 (33.0%), post-COVID-19: 1,048 (78.9%) vs. 281 (21.1%)]. Comparison of CO-CPR vs. RB-CPR showed increased 30-day mortality in both periods [pre-COVID-19: 1,081/1,356 (79.7%) vs. 420/667 (63.0%), post-COVID-19: 841/1,048 (80.2%) vs. 181/281 (64.4%)]. In the overall cohort, mortality increased with CO-CPR (aRR: 1.16, 95% CI: 1.09-1.23, PAF:1.60%). Due to the increased number of patients receiving CO-CPR, we estimated 21.2 excess deaths over the two-year post-COVID-19 period. Similar results were observed for poor neurological outcome (aRR: 1.10, 95% CI: 1.05-1.16, PAF: 1.10%, excess poor outcome: 14.6]).

Conclusion:
With the spread of CO-CPR for pediatric OHCA, an estimated 10.6 excess deaths per year attributed to CO-CPR may have occurred in the post-COVID-19 period compared to the pre-COVID-19 period in Japan.
Abstract Sa906: Topological Distribution of
KCNH2
Variants and Genotype-Phenotype Relationship in Patients with Long QT Syndrome
Authors: Hong Kui , Liu Hongyu , Jiang zh , Shen Yang , Su Yuhao , Shao Ying
Published: November 2024

Aims:
The aim of this study was to investigate the topological distribution of single nucleotide variants (SNVs) in
KCNH2
in patients with long QT syndrome (LQTS) and to explore the relationships between genotypes and phenotypes.

Methods:
Information on
KCNH2
variants in LQTS patients was retrospectively obtained from the HGMD, ClinVar and PubMed databases through October 2022. SNV pathogenicity was classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Unpaired t tests and Fisher's exact tests were used to analyze the SNV distributions across structural and functional domains, and their correlations with clinical phenotypes.

Results:
A total of 2826 variants were obtained; 2152 were SNVs, 1328 of which were non-synonymous SNVs (nsSNVs) associated with LQTS. Enrichment analysis revealed that 602 pathogenic (P) and likely pathogenic (LP) nsSNVs were significantly enriched in the Cyto2, S5, S6, H5, and Extra3. In addition, 759 nsSNVs were enriched in the Per-Arnt-Sim (PAS) and selectivity filter (SF) functional domain. The P and LP nsSNVs remained enriched in the PAS, SF, and cyclic nucleotide binding domain (cNBD). Clinical data showed that patients with nsSNVs located at S5-H5-S6, PAS and SF regions were associated with increased risk of life-threatening cardiac events, including Torsade de Pointes and sudden cardiac death, and were predominantly female. Furthermore, nsSNVs enriched in N-terminus region, S5-H5-S6 region and PAS domain were associated with an increased risk of syncope.

Conclusion:
The
KCNH2
nsSNVs located at the S5-H5-S6 region, and the PAS and SF domains are associated with increased risk of life-threatening cardiac events.
Abstract Sa909: The Importance of Extended-hours Patient Recruitment in Cardiac Arrest Trials
Authors: Lee John , Vine Jacob , Meier Max , Berkovitz Alan , Balaji Lakshman , Grossestreuer Anne , Moskowitz Ari , Berg Katherine , Donnino Michael
Published: November 2024

Introduction:
Patient recruitment is a critical factor in running successful and timely clinical studies. This is particularly crucial in cardiac arrest research where the timing of presentation of study participants is unpredictable and interventions are often time-sensitive. Previous studies have identified adequate staffing as one of the most important enablers of successful recruitment. However, studies have also shown that recruitment outside of business hours is less common even at major academic centers.

Hypothesis:
We hypothesize that a substantial portion of potential study participants present outside of business hours and therefore providing coverage only during business hours results in missing a large number of potential study participants.

Aims:
The objective of this study was to analyze the timing of all patient enrollments from our previous cardiac arrest trials to identify patterns and assess the impact of providing 24/7 coverage on participant recruitment.

Methods:
We reviewed the patient enrollment time data for two cardiac arrest trials performed by our group (NCT02974257 and NCT03450707). We quantified the number of enrollments during business hours (9 AM - 5 PM) vs. outside of business hours and analyzed the frequency of enrollment by day of the week and time of day.

Results:
There were 112 patients enrolled between 2016 and 2022 across the two trials. A total of 80 patients (71.4%) were enrolled outside of business hours (Fig. 1). 75% of patients were enrolled during weekdays and 25% during weekends. By day of the week, enrollments occurred most frequently on Friday (20, 17.9%) and least on Monday (12, 10.7%) and Sunday (12, 10.7%) (Fig. 2A). By time of day, enrollments occurred most frequently during 2 - 4 PM and 6 - 8 PM (15, 13.4%) and least frequently during 4 - 6 AM and 8 - 10 AM (2, 1.8%) (Fig. 2B). Recruiting only during business hours would have resulted in additional 18 and 11 years to complete each study (Fig. 3).

Conclusion:
In our two most recent cardiac arrest trials, 75% of enrollment occurred outside of business hours. Limiting recruitment to only business hours would have resulted in a prohibitively longer time to complete the studies. This analysis provides a strong motivation and rationale for extending research staffing coverage beyond business hours.