bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4136413: AV Junctional Ablation in the Era of Conduction System Pacing: Just Rate Control or also Rhythm Control?
Authors: Mencer Nicholas , Patel Ritesh , Brunetti Ryan , Mumtaz Mishal , Khan Shoaib , Einhorn Nathan , Herweg Bengt
Published: November 2024

Background:
Rate and rhythm controlling therapy in patients with atrial fibrillation (AF) are theoretical concepts, however, in clinical practice there is a substantial overlap between these strategies. AV junctional (AVJ) ablation is the ultimate form of rate control; however, it may result in rhythm control as well.

Hypothesis:
We hypothesize that individuals that underwent AVJ ablation for AF have a decrease in their AF burden after the procedure.

Goals:
The purpose of our study was to determine the outcome of AVJ ablation in patients with AF, in respect to atrial rhythm and AV synchrony.

Methods:
Retrospective review of AF patients that underwent AVJ ablation with prior or de novo conduction system pacing (CSP) lead. Included were only patients with a cardiac monitor/device allowing assessment of AF burden prior to AVJ ablation.

Results:
Thirty-six patients were identified, age 74±5 years, 14 male (39%), 15 paroxysmal AF (42%), 10 persistent AF (28%), 11 longstanding persistent AF (31%). 25/33 patients (76%) had a history of AF ablation. All patients underwent implantation of, or had a prior, CSP lead [His bundle pacing n=11 (31%), LBBAP n=25 (69%)]. The heart rate decreased from 89±28 bpm pre procedure to 78±7 bpm post-AVJ ablation, p=0.01. The spontaneously conducted QRS complex prior to AVJ ablation was 116±34 ms and the QRS during CSP after AVJ ablation was 129±25 ms, p=0.02. In the entire population, AVJ ablation resulted in a reduction of AF burden from 69±40% to 48±49%, p=0.005. Of those with persistent and longstanding persistent atrial fibrillation, 5/21 patients (24%) restored normal sinus rhythm without other intervention following AVJ ablation. Of those patients that spontaneous restored normal sinus rhythm, 3/5 had prior ablations (60%). During a follow-up of 703±524 days, LV EF improved from 42±16% to 47±13%, p=0.01
.

Conclusion:
Although AVJ ablation is the ultimate form of rate controlling therapy, in the era of CSP it may also result in better rhythm control in a substantial number of patients. Therefore, implantation of an atrial lead and avoidance of placing the CSP lead in the atrial channel may be advisable to assure AV synchrony.
Abstract 4136462: Provider understanding of Coronary Artery Calcium Scoring (CAC) testing in Atherosclerotic CArdiovascular Disease risk stratification and Racial Disparities Study (CAC-CARD) to reduce healthcare disparities
Authors: Daga Pawan , Devanand Dakshinkumaar , Umer Muhammad , Sagheer Usman , Menon Tushar , Singh Gurnoor , Kalra Dinesh
Published: November 2024

Background:
Coronary Artery Calcium (CAC) scoring is critical in assessing Atherosclerotic Cardiovascular Disease (ASCVD) risk. Despite its utility, many primary care physicians lack confidence and familiarity with its application. Significant racial disparities in CAC scoring utilization have been observed, potentially affecting patient outcomes.

Hypothesis:
We hypothesized that a short targeted educational intervention would enhance physicians' confidence, knowledge, and utilization of CAC scoring and awareness of racial disparities.

Methods:
A pre- and post-intervention study (Image 1) was conducted among 39 physicians at the University of Louisville. The intervention included a 20-minute educational session on CAC scoring and racial disparities. A video summarizing the ACC2018 guidelines for prevention and cholesterol treatment was provided. A summary of key points for clinical practice was given. The ASCVD plus calculator app was provided. Data were collected using a structured questionnaire before and after the intervention. Viewing time and engagement were recorded. Descriptive and inferential statistics analyzed the data.

Results:
The average correct physician responses increased from a mean of 59.5% pre-intervention to 92.0% post-intervention. Post-intervention, the number of physicians who felt confident or very confident in CAC testing increased from 17.9% to 94.8%. Additionally, 33 out of 39 physicians (84.6%) reported likely to use CAC testing more frequently. Correct responses on racial disparities improved from 59% pre-intervention to 92.0% post-intervention. (Image 2). The average viewing time was 28 minutes. Time spent on the questionnaires was 14 min pre and 12 min post.

Conclusion:
Our targeted educational intervention significantly enhanced physicians' knowledge and confidence in CAC scoring for ASCVD risk assessment and raised awareness about racial disparities, promoting more equitable practices.
Abstract 4136565: Atrial Fibrillation Linked to Right Ventricular Dysfunction in Patients with Acute Pulmonary Embolism
Authors: Mallery Quinn , Gupta Riya , Clarke Jacob , Greathouse Frances , Choi Myoung Hyun , Koura Simran , Bruno Elizabeth , Arora Punit , Malas Waddah , Shah Parth , Sutherland David , Kumar Amudha , Wroblewski Igor , Darki Amir
Published: November 2024

Background:
Atrial fibrillation (AF), both new-onset and preexisting, is linked to increased mortality in acute pulmonary embolism (APE). The causal pathway for this association, whether through increased right ventricular dysfunction (RVD) is less well understood.

Hypothesis:
AF independently predicts RVD in APE patients, affecting mortality and clinical outcomes.

Goals:
Examine the relationship between AF and RVD to understand its impact on APE survival.

Guide further research into optimal APE therapeutic strategies, focusing on early rhythm control.

Methods:
We conducted a retrospective, multi-center cohort study using data from our Pulmonary Embolism Response Team (PERT) registry. Inclusion criteria included PERT activation and adults over 18. Exclusions were for missing transthoracic echocardiogram (TTE) within 3 days or incomplete TTE data. Patients were categorized by AF status, with RVD assessed by TTE markers. Analysis involved logistic regression and Cox proportional hazards models.

Results:
Among 535 APE patients, 15% had AF. These patients showed higher unadjusted RVD rates (56% vs. 39%, p=0.006) and significant differences in TTE parameters: TAPSE (1.72 vs. 1.89 cm, p=0.007), S` (11.5 vs. 13.4 cm/s, p=0.0002), and RVOT VTI (13 vs. 14 cm, p=0.019). Adjusted analyses confirmed AF's significant association with RVD (OR 2.32, CI 1.3-4.1), inpatient mortality (OR 4.9, CI 1.5-17, p=0.0106), acute renal failure (OR 2.2, CI 1.2-4.1, p=0.0102), and one-year mortality (HR 1.9, CI 1.06-3.44, p=0.03).

Conclusions:
AF significantly influences mortality in APE, partly through increased RVD. These findings underline the need for further studies to confirm these relationships and enhance treatment strategies.
Abstract 4136592: Comparative performance of PREVENT and Pooled Cohort Equations to predict cardiovascular disease in multisite healthcare populations
Authors: Cho So Mi , Levin Michael , Chen Robert , Judy Renae , Postupaka Darina , Viscosi Victoria , Fahed Akl , Honigberg Michael , Hornsby Whitney , Damrauer Scott , Do Ron , Natarajan Pradeep
Published: November 2024

Introduction:
The American Heart Association’s race-agnostic Predicting Risk of cardiovascular EVENTs (PREVENT) framework has emerged to better capture multilevel determinants of health in contemporary population. Whether PREVENT better predicts incident atherosclerotic cardiovascular disease (ASCVD) than the preceding Pooled Cohort Equations (PCE) is unknown in healthcare populations. We evaluated calibration and discrimination of the two equations across three major U.S. healthcare networks.

Methods:
We retrospectively evaluated electronic health records of 209,879 individuals (Mass General Brigham [MGB]: 118,801; Mount Sinai Healthcare System: 38,834; Penn Medicine: 52,424) aged 40-79 years and without prior ASCVD between 2010-2012. Calibration was assessed using discordance ratio between 10-year observed and predicted risk. Discrimination was evaluated by Harrell’s C-index.

Results:
Based on PREVENT, the mean [SD] estimated 10-year ASCVD risk ranged from 5.5 [4.7] % in MGB (mean age 56y, 42% female), 6.6 [5.6]% in Mount Sinai (59y, 54% female), and 6.4 [5.2]% in Penn (60y, 55% female). PREVENT substantially underestimated empirical 10-year ASCVD incidence in MGB (16.9%) and Mount Sinai (10.9%), whereas it closely mirrored the observed rate in Penn (5.5%). Both PCE and PREVENT had comparable discrimination C-index [95% CI] across MGB (0.69 [0.69-0.70] vs. 0.69 [0.68-0.69]), Mount Sinai (0.72 [0.71-0.73] vs. 0.70 [0.70-0.71]), and Penn (0.68 [0.67-0.69] vs. 0.67 [0.66-0.68]). Nevertheless, compared to PREVENT, PCE demonstrated better overall calibration in MGB (-70% vs. -42%) and Mount Sinai (-36% vs. +5%), whereas largely overestimated risk in Penn (+3% vs +94%). Calibration varied across demographics with PREVENT consistently underestimating risk in Hispanics, Asians, Black and African Americans across all sites, whereas PCE largely overestimated risk for White or multiracial Penn healthcare patients.

Conclusions:
The race-agnostic PREVENT model discriminated ASCVD incidence comparably or better than the race-informed PCE across three geographically distinct academic health systems in the Northeast. However, calibration metrics between the two models varied widely across health systems and demographics.
Abstract 4136597: Atherosclerotic plaque healing as a marker of plaque vulnerability: Insight from intracoronary polarization-sensitive optical frequency domain imaging
Authors: FUJISAWA NAOKI , Otsuka Kenichiro , Villiger Martin , Jones Georgia , Sugioka Kazuya , Yamaura Hiroki , Okamoto Akihiro , Yamaguchi Tomohiro , Kagawa Shunsuke , Shimada Takenobu , Shibata Atsushi , Ito Asahiro , Yamazaki Takanori , Bouma Brett , Fukuda Daiju
Published: November 2024

Background:
Collagen is the major extracellular matrix that imparts mechanical strength to fibrous caps covering fibroatheromas. Intracoronary polarimetry with polarization-sensitive (PS) optical frequency domain imaging (OFDI) measures polarization properties, such as birefringence and depolarization (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, while depolarization is increased by the presence of macrophages and lipid/necrotic cores.

Purpose:
This study aimed to investigate polarimetric signatures of coronary lesions with healed coronary plaques (HCP) in patients with ACS and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions.

Methods:
We conducted a single center prospective registry of intracoronary PS-OFDI imaging in patients with coronary artery disease (n = 50). A total of 862 OFDI frames selected from culprit or target lesions were analyzed. Coronary plaque phenotypes were assessed using conventional OFDI imaging. HCP was defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components on intensity images. Birefringence and depolarization of the newer intima was measured in cross-sectional images. Birefringence and depolarization of ACS- and CCS-lesions were compared using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate the diagnostic performance of polarimetric signatures for identifying ACS-lesions.

Results:
Compared to CCS-lesions, ACS-lesions featured significantly higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025).

Conclusions:
Intracoronary polarimetry provides quantitative assessment of plaque composition in patients. Further research is warranted to investigate whether birefringence can serve as a marker of healing failure following plaque rupture and erosion.
Abstract 4136600: Hypertensive disorders of pregnancy and the risk of Dementia, Alzheimer’s disease, and Vascular Dementia. A Systematic review and Meta-analysis of 25,03,538 women participants.
Authors: Jaiswal Vikash , Shrestha Abhigan , Hanif Muhammad , Danisha FNU , Borra Vamsikalyan , Ang Song Peng , Chia Jia Ee , Gupta Ira , Wajid Zarghoona , Ariff Madiha , Sarfraz Zouina , Nasir Yusra , Daguipa Christine Dawn
Published: November 2024

Background:
Hypertensive disorders of pregnancy (HDP) are associated with maternal adverse cardiovascular outcomes. However, their association with maternal Dementia and Alzheimer’s disease is not well established with limited and conflicting results to date.

Objective:
We sought to evaluate the association between HDP and risk of incidence of Dementia, and Alzheimer’s disease.

Methods:
We performed a systematic review and meta-analysis of available literature that enrolled women with HDP and women without HDP groups. PubMed, Embase and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were pooled using a random-effect model.

Results:
A total of 8 studies with 2503538 patients (1,51,905 in women with HDP and 23,51,633 in the women without HDP group) were included. Pooled analysis shows that HDP women were having 37% higher risk of dementia (aHR, 1.37(95%CI: 1.27-1.46), P<0.001, I2=0%) when compared with women without HDP. Further pooled analysis showed that women with HDP were having 28% higher risk of Alzheimer’s disease (aHR, 1.28(95%CI: 1.56), P<0.001, I2=53.98%), and 2-fold higher risk of vascular dementia (aHR, 2.49(95%CI: 1.29-3.68), P<0.001, I2=71.51%) when compared with women without HDP.

Conclusion:
Women with HDP were at higher risk of developing Dementia, and Alzheimer's disease in future.
Abstract 4136605: Effect Of A Bone Morphogenetic Protein Receptor Type 2 Mutation On The Cardiomyocyte Response To Pressure Overload
Authors: Llucia-Valldeperas Aida , Van Wezenbeek Jessie , Smal rowan , Bekedam Fjodor , Vonk Noordegraaf Anton , Bogaard Harm , De Man Frances
Published: November 2024

Introduction:
A mutation in the Bone Morphogenetic Protein Receptor Type 2 (
BMPR2
) gene is in 70% of hereditary pulmonary arterial hypertension (hPAH) patients the causative mutation of the disease. Previous work demonstrated that right ventricular function is more impaired in hPAH patients with a BMPR2 mutation. However, the underlying mechanism remains elusive. Moreover, natriuretic peptides, such as N-terminal Brain Natriuretic Peptides (NTproBNP) and Mid Regional proAtrial Natriuretic Peptides (MRproANP), are secreted from cardiomyocytes upon stretch as adaptation to increased pressure overload. We hypothesize that the
BMPR2
mutation impairs the response to increased pressure overload. For this purpose, we make use of ventricular induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of hPAH patients carrying a
BMPR2
mutation and their isogenic controls in which the mutation was corrected.

Aim:
To study the effect of a
BMPR2
mutation on the response to pressure overload
in vitro
.

Methods:
iPSCs from 2 hPAH patients and its isogenic controls were used. iPSCs were differentiated into ventricular iPSC-CMs and stretched 10% equiaxially for 24h at 1Hz on the Flexcell FX-6000 system. Natriuretic peptides gene expressions were quantified via RT-PCR. NTproBNP and MRproANP release were measured on cell supernatants throughout specific immunoassays. Normality of the data was checked, and statistics were performed accordingly.

Results:
No differences were observed on natriuretic peptides gene expression on static and stretched iPSC-CMs. There is a clear correlation between NTproBNP and MRproANP release (R
2
=0.83, p<0.0001, Figure 1A). Interestingly, hPAH iPSC-CMs showed higher baseline values for NTproBNP release compared to isogenic iPSC-CMs (p<0.01, Figure 1B). Furthermore, stretching resulted in increased NTproBNP and MRproANP secretion in both hPAH and isogenic iPSC-CMs (Figure 1B-C).

Conclusions:
Secretion of NTproBNP and MRproANP was closely correlated in iPSC-CMs. iPSC-CMs of hPAH patients with a
BMPR2
mutation showed higher baseline values of NTproBNP. Increased secretion of NTproBNP and MRproANP upon mechanical stimulation was similar between hPAH and isogenic iPSC-CMs. Experiments in atrial iPSC-CMs are currently ongoing to test potential differences in natriuretic peptide secretion between ventricular and atrial cardiomyocytes as the right atrium is also under stretch in PAH.
Abstract 4136700: Sodium-Potassium Pump: Newly O-GlcNAc Protein Offering Potential Benefits in Hemorrhagic Shock situation
Authors: Vergnaud Amandine , Dupas Thomas , Aillerie Virginie , Persello Antoine , Erraud Angelique , Girardeau Aurore , Oliveira Mendes Barbara , Montnach Jerome , De Waard Michel , Rozec Betrand , Lauzier Benjamin
Published: November 2024

Hemorrhagic shock(HS) results from significant blood loss, leading to insufficient oxygen delivery, which causes metabolic changes and multi-organ dysfunction.The HS-related acute kidney injury developed by the patient are mainly due to alteration in Na/K ATPase.In previous O-GlcNAcylomic studies, we identified the Na/K ATPase as potentially O-GlcNAcylated.O-GlcNAcylation, a post-translational modification, plays a role in various cellular processes, such as cell survival and stress response.O-GlcNAcylation may have beneficial effect in shock situations.

The objective of this study is to ascertain whether Na/K ATPase is O-GlcNAcylated and to elucidate its potential role during HS.

Hemorrhagic shock was induced by an exsanguination of rats.They were then randomly treated or not with an O-GlcNAcase inhibitor, the NButGT(10mg/kg), to increase O-GlcNAc level.Blood pressure and heart rate were monitored throughout the experiment.Blood samples were collected for complete blood analysis, including biochemistry and gas measurements. kidneys were immediately frozen for histological and biochemical studies.To study the O-GlcNAcylation of Na/K ATPase an immunoprecipitation and Wheat Germ Agglutinin(WGA) based lectin affinity gel electrophoresis were used. HEK cells were treated with or without NButGT(100µM,6 hours) and/or ouabain(Na/K ATPase inhibitor) and a colorimetric kit was assessed to study O-GlcNAcylation impact on Na/K ATPase activity.

O-GlcNAc levels increased by 2 folds in heart and kidney due to the NButGT treatment(p<0.05).Mean arterial pressure(MAP,p<0.01) and bicarbonate(p<0.01) are restored in treated group as kalemia(Sham:4.2 ± 0.1;HS:4.7±0.1;NButGT:4.3 ±0.1;mmol/L;p<0.05) and natremia(Sham:141.5±0.4;HS:139.8±0.5;NButGT:141.9 ±0.4; mmol/L;p<0.01).The study of the O-GlcNAcylation of the Na/K ATPase validated its O-GlcNAcylation.Histological analysis of the kidney showed that HS decreased Na/K ATPase expression, but treatment restored it(Sham:15.1±1.1;HS:10.3±0.6;NButGT:13.78±1.1;%area;p<0.05). An acute increase in O-GlcNAc levels through NButGT enhances Na/K ATPase activity.

Increased O-GlcNAcylation during hemorrhagic shock restored MAP and reduced indicators of metabolic acidosis.Treatment with NButGT restored natremia and kalemia.This effect is linked to an increase in the expression and activity of Na/K ATPase.Our study is the first to confirm that Na/K ATPase is regulated by O-GlcNAcylation, particularly in terms of its localization and stability.
Abstract 4136745: How do sleep quality and heart failure symptoms impact functional status among patients with heart failure?
Authors: Wu Jia-Rong , Lin Chin-Yen , Biddle Martha , Kang JungHee , Latimer Abigail , Cha Geunyeong , Thapa Ashmita , Lennie Terry , Moser Debra
Published: November 2024

Background:
Patients with heart failure (HF) frequently experience poor sleep quality and multiple HF symptoms, both of which are linked to diminished functional status. Poor sleep quality can manifest as prolonged latency, short duration, low efficiency, or difficulty staying asleep. HF symptoms encompass different dimensions: presence, frequency, severity, and distress of HF symptoms. Different dimensions of sleep quality and HF symptoms may uniquely influence functional status, necessitating tailored interventions, yet how individual dimensions of sleep quality and HF symptoms impact functional status remains unexplored.

Research Question:
how do individual dimensions of sleep quality and HF symptoms impact functional status in patients with HF?

Methods:
We studied 197 adults with HF (male: 66%, age: 62±11 yrs). The Pittsburgh Sleep Quality Index was used to assess seven dimensions of sleep quality: subjective sleep quality, latency, duration, efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. Four dimensions (i.e., presence, frequency, severity, distress) of 7 HF symptoms (e.g., shortness of breath, fatigue, swelling) were assessed using the Symptom Status Questionnaire-HF. Functional status was measured using the Duke Activity Status Index. Correlations and two multiple linear regression models (1
st
model: 7 dimensions of sleep quality on functional status, and 2
nd
model: 4 dimensions of HF symptoms on functional status) were conducted for data analysis.

Results:
Worse subjective sleep quality, longer latency, more sleep disturbances, use of sleeping medications, and higher levels of daytime dysfunction were correlated with poor functional status. All four dimensions of HF symptoms were negatively correlated with functional status. In the 1
st
multiple linear regression model, more sleep disturbances (B=-3.91,
p
=.006) and higher daytime dysfunction (B=-5.70,
p
<.001) were predictive of poor functional status (model R
2
=0.23,
p
<.001). In the 2
nd
multiple linear regression model, only higher frequency of HF symptoms (B=-.70,
p
=.022) predicted poor functional status (model R
2
=0.34,
p
<.001).

Conclusion:
Increased sleep disturbances, daytime dysfunction, and frequency of HF symptoms were associated with poorer functional status in patients with HF. These findings underscore the importance of developing tailored interventions to address individual sleep problems and HF symptoms to improve functional status.
Abstract 4136762: Association Between Circadian Rest/Activity Rhythms and Incident Dementia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wang Wendy , Wanigatunga Amal , Etzkorn Lacey , Rabinowitz Jill , Palta Priya , Pike James , Dougherty Ryan , Zipunnikov Vadim , Marino Francesca , Crainiceanu Ciprian , Spira Adam , Schrack Jennifer , Chen Lin
Published: November 2024

Introduction:
Alterations in circadian rest/activity rhythms (RARs) are common among older adults. RARs can be derived from accelerometry data and are routinely used as proxy measures. Evidence suggests that altered (e.g., fragmented, delayed) RARs may be risk factors for dementia. However, results have been mixed. Using data from the ARIC Study, a community-based cohort, we assessed the association between RARs and incident dementia.

Methods:
ARIC participants without dementia who wore the Zio XT ECG Patch in 2016-17 for
>
3 days were included. RARs were obtained from an accelerometer within the Zio XT ECG Patch and measures of interdaily stability (IS; consistency), intradaily variability (IV; fragmentation), and relative amplitude (RA; strength) were derived. Dementia cases were identified through 2020 using in-person and phone-based cognitive assessments, hospitalization discharge codes, or death certificates. Cox proportional hazards models were used.

Results:
Of the 2,183 participants (mean [SD] age 79 [4.5] years, 58% female, 24% identified as Black), 176 (8%) developed dementia. Median follow-up time was 3 years and mean Zio XT ECG Patch wear time was 12 days. After multivariable adjustment, lower RA and higher IV were associated with incident dementia (HRs [95% CIs] per 1-SD increment: 0.65 [0.56-0.76], 1.19 [1.02-1.38]). No significant association between IS and dementia was noted; however, there was an interaction by race (p=0.03). Stratified results were not significant, but effect estimates were in opposite directions: (HRs [95% CIs] per 1-SD increment in IS: 0.78 [0.59-1.02] in Black participants and 1.17 [0.96-1.41] in white participants, respectively). No interactions by sex or APOEε4 were noted (p>0.10).

Conclusion:
In this community-based cohort of older adults, weaker circadian rhythm strength and fragmentation were associated with dementia risk. The association between IS and dementia may differ by race; however, this needs to be further examined in future research. Overall, measures of circadian RARs may be risk factors for dementia. Additional research is warranted to determine whether they can be novel targets for dementia prevention.
Abstract 4136786: Prediabetes increases platelet activation and thrombotic susceptibility via mitochondrial oxidants
Authors: Ahmed Azaj , jensen melissa , Geasland Katharine , Swamy Jagadish , Spitz Douglas , Abel E. Dale , Jalal Diana , Dayal Sanjana
Published: November 2024

Recent studies suggest that prediabetes is not only a prelude to diabetes, but also is an independent risk factor for cardiovascular thrombotic events in young and aged people. However, the mechanisms that may promote platelet activation and thrombosis during prediabetes have not been studied. We hypothesized that in prediabetes, dysregulation of electron transfer and accumulation of mitochondrial oxidants promotes platelet activation and thrombosis, and that aging exacerbates the phenotype. We recruited young (18-50 year) and middle-aged (51-64 year) Veterans with prediabetes and age- and BMI- matched healthy Veterans. Compared to healthy cohort, platelets from prediabetes exhibited enhanced agonist induced platelet activation, mitochondrial oxidants, membrane potential and thrombus formation
ex vivo
in both young and middle-aged cohorts to a similar extent. Preincubation of platelets with either a mitochondria targetable superoxide dismutase (SOD) mimetic or MitoQ (transfers electrons from Complex I/II to complex III to lower superoxide generation within mitochondria), rescued the prothrombotic phenotype. We confirmed these platelet phenotypes in C57BL6/J mice fed high fat (HF) diet for 2 weeks (model of early diabetes). Importantly, HF-fed mice showed increased susceptibility to carotid artery and pulmonary thrombosis
in vivo
. Pharmacological treatment of HF-fed mice with SOD-mimetic or MitoQ, or genetic overexpression of catalase within mitochondria, rescued the prothrombotic state. This is the first report showing platelet hyperactivity and enhanced thrombotic susceptibility in prediabetes. Further, our findings suggest that enhanced mitochondrial oxidants due to the premature electron escape contribute to the phenotype. Our data imply a therapeutic potential of SOD-mimetic and MitoQ in lowering thrombotic burden in prediabetes.
Abstract 4136813: Redox Serum Proteomics Of Left Ventricular Assist Device Unloaded Human Heart
Authors: Halawa Sarah , Marin-Vicente Consuelo , Ibrahim Ayman M. , Wagdy Dr. Kerolos , Soliman Saifullah , Samy Besra , Selwanos Peter , khedr hadeer , MOSTAFA MOSTAFA SABER , Samaan Kerollos , Calvo Enrique , El Bayoumy Youssef M. , Ellithy Amany , Torres Miguel , Vazquez Jesus , Aguib Yasmine , Yacoub Magdi
Published: November 2024

Heart failure (HF) is a global epidemic claiming millions of lives worldwide. Unloading the heart of end-stage HF patients via left ventricular assist devices (LVADs) is used not only as a bridge to transplantation but also as a bridge to recovery in certain selected patients. To date, assessment of patients’ recovery from HF is based on clinical and symptomatic evaluation. The use of non-invasive biomarkers that monitor the remodeling/reverse remodeling associated with HF progression/recovery is still lacking. In this study we applied mass spectrometry-based quantitative redox proteomics to identify serum biomarkers to monitor both the progression of HF and its recovery after LVAD treatment. A fingerprint of reversed behavior at the protein and at the oxidized Cys peptide level has been discovered when comparing HF and LVAD patients. HDL proteins related to lipid metabolism were decreased in HF samples and increased in LVAD patients. In addition, a number of inflammatory proteins showed a decrease in LVAD samples and an increase in HF samples. In particular APOA4, C7, F2 or SAA2 discriminated between HF and LVAD patients. A pool of peptides containing specific oxidized Cys residues showed an inverse relationship in HF as opposed to LVAD samples. Oxidized Cys-containing peptides derived from Albumin, IGK and IGG1 discriminated HF from LVAD samples. Discriminatory sensitivity and specificity were enhanced by using a combination of the proteins APOA4, C7, F2 and the above-mentioned peptide derived from Albumin. Responders and non-responders could also be separated by proteins such as APOA4, and Cys-oxidized peptides, such as the ones derived from Albumin or IGK mentioned above. This is the first study to apply redox proteomics to explore the protein profile of the LVAD unloaded human heart. These data suggest that HDL plays an important role in LVAD recovery and that a specific group of peptides is associated with the recovery process; the mechanisms involved need further study. Our data could have important implications to the management of patients in the LVAD recovery program and could serve to identify new therapeutic targets.
Abstract 4137009: Treating Elderly Cardiogenic Shock Patients with a Microaxial Flow Pump; Is It DANGERous?
Authors: Klein Anika , Beske Rasmus , Hassager Christian , Jensen Lisette Okkels , Eiskjaer Hans , Mangner Norman , Polzin Amin , Schulze Christian , Skurk Carsten , Nordbeck Peter , Clemmensen Peter , Panoulas Vasileios , Zimmer Sebastian , Schaefer Andreas , Engstrom Thomas , Holmvang Lene , Junker Anders , Schmidt henrik , Terkelsen Christian , Moller Jacob
Published: November 2024

Background:
The Danish German Cardiogenic Shock trial (DanGer Shock) recently showed a reduction in all-cause mortality when treating selected patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock with a microaxial flow pump (mAFP). Whether there is an age-related differential survival benefit is unknown.

Objective:
To assess the influence of age on 180-day all-cause mortality in patients with STEMI and cardiogenic shock randomized in DanGer Shock.

Methods:
In DanGer Shock (an open-label, international, multicenter trial), 355 adult patients (aged ≥18 years with no upper age limit) with STEMI and cardiogenic shock were included and randomized to a mAFP (Impella CP) plus standard care or standard care alone. Patients were stratified in quartiles according to age, and logistic regression analyses were used to assess mortality according to age quartiles, and to evaluate whether age modified the treatment effect of the mAFP.

Results:
From lowest to highest quartile, patients’ ages ranged from 31-59, 60-69, 70-76, and 77-92, respectively. There were no differences in blood pressure, lactate level, left ventricular ejection fraction and shock severity across age groups. However, the proportion of females (41%) and the prevalence of hypertension (64%) was higher in patients aged ≥77 years (highest quartile), while more patients aged <60 years (lowest quartile) had been resuscitated before randomization.

Mortality increased incrementally from the lowest quartile to the highest (31% vs. 47% vs. 61% vs. 73%, p
log-rank
<0.001), with an adjusted odds ratio for death at 180 days of 5.50 (95%CI 2.65-11.8, p<0.001) in the highest quartile compared to the lowest.

Patients in the three lower quartiles had a lower absolute mortality at 180 days if randomized to the mAFP group, whereas patients in the highest quartile had a higher mortality if randomized to the mAFP group, p=0.028 for interaction, Figure.

Conclusion:
In patients with STEMI-related cardiogenic shock, the overall mortality increased with advancing age, and treatment benefit of the mAFP appeared to diminish in the eldest patients. (DanGer Shock, NCT01633502)
Abstract 4137019: Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Tanashat Mohammad , Shaaban Abdelgalil Mahmoud , Abuelazm Mohamed , Manasrah AlMothana , Abouzid Mohamed , Abu El Haija Mohanned , El Khatib Suhaib , Abu-Laila Mutaz , Ayyad Mohammed
Published: November 2024

Background:
Despite the effectiveness of drug-eluting stents (DES) in preventing restenosis, many patients still experience DES restenosis. Neointimal hyperplasia and neoatherosclerosis can develop within these stents, leading to recurrent coronary syndromes.

Hypothesis:
Repeated stenting with DES is limited by additional metal layers, the need for prolonged dual antiplatelet therapy, and heightened risks of stent thrombosis. Locally acting drugs with sustained efficacy may prevent this progression. Paclitaxel delivery via contrast medium or drug-coated balloon catheters could exert antiproliferative effects, reducing neointimal proliferation.

Aims:
To synthesize existing evidence on the efficacy and safety of Paclitaxel-Coated Balloons versus Uncoated Balloons in coronary in-stent restenosis.

Methods:
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched five electronic databases (PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science) to identify eligible studies reported up to March 23, 2024. Using R version 4.4.0, we reported outcomes as risk ratios (RRs) or mean differences (MD) and confidence intervals (CIs). This review has been registered and published in PROSPERO (CRD42024527412).

Results:
The meta-analysis included a total of six trials with 1,541 patients. PCB significantly reduced the incidence of myocardial infarction (RR 0.65, 95% CI [0.42, 1.00], p = 0.052), stent thrombosis (RR 0.26, 95% CI 0.08, to 0.83], p = 0.023), major adverse cardiac events (RR 0.32, 95% CI 0.25, to 0.42], P < 0.001), target lesion revascularization (RR 0.34, 95% CI [0.14, 0.84], p < 0.001). No significant differences were observed between PCB and UCB regarding cardiac-related mortality, target vessel revascularization, percutaneous coronary intervention, all-cause death, Q wave and non-Q wave myocardial infarction, coronary artery bypass grafting, and target vessel failure.

Conclusion:
PCB for ISR significantly reduced the incidence of myocardial infarction, MACE, and stent thrombosis compared to UCB.
Abstract 4137053: Association of Childhood Opportunity Index and No Show Rates in a Pediatric Cardiology Clinic.
Authors: Elliott Pietro , Ather Mishaal , Lynch Miranda , Guglielmo Kimberly , Chowdhury Devyani
Published: November 2024

Introduction:
Childhood Opportunity Index (COI) measures access to quality education, safe housing, and healthcare based on zip codes. These scores can influence patient behaviors, such as no-shows (NS), which can affect resource utilization and health outcomes.

Objective:
To quantify the correlation between COI and NS through odds ratio (OR) in a pediatric cardiology clinic.

Methods:
Patient data was collected from a single, independent pediatric cardiology practice for all visits between 2019 to 2021. COI was categorized into 3 subdomains; education, health and environment, social and economic according to zipcode from Diversitydatakids. The COI was split into low (<40), moderate (40-60U), and high (>60U). Additional variables included age, insurance type, lead time (time from scheduling to appointment date), and telehealth status. Multiple logistic mixed-effect models, both unadjusted (single predictor) and adjusted (multiple predictors), were used to obtain OR for NS.

Results:
There were 11,474 total encounters. 92% were completed appointments and 8% were NS. Unadjusted model showed statistical significance (p<.05) with increased odds of NS for low COI education, low COI social and economic, and low COI, compared to high COI as the reference category (Table 1). Adjusted model 2 showed similar significant results for the low COI overall category, while for adjusted models 1 and 3, none of the COI categories were statistically significant. In all 4 models, OR for all age categories, all lead times, and public and mixed insurance types were significant.

Conclusion:
The unadjusted and adjusted model 2 showed that patients with lower COIs were more likely to NS. Public insurance and longer lead times were indicators of NS while higher ages were indicators for completed appointments. Therefore, efforts need to be made to identify vulnerable patients; younger patients, and those with lower COIs and public insurance; and address barriers such as arranging transport and sending reminders that can help decrease NS. Interestingly, the NS rate was lower than the national average. Future research is needed to assess the impact of NS on patient outcomes.
Abstract 4137064: High Incidence of Adverse Neonatal Outcomes of Pregnancy in Women with Congenital Heart Disease
Authors: Edwards Lindsay , Goldstein Sarah , Nilles Ester , Chiswell Karen , DOttavio Alfred , Reeder Matthew , Glidewell Jill , Wood Kathleen , Sethi Neeta , Raskind-Hood Cheryl , Book Wendy , Feldkamp Marcia , Li Jennifer , Botto Lorenzo
Published: November 2024

Background:
Neonates born to women with congenital heart disease (CHD) are at high risk for adverse outcomes. We sought to describe these outcomes and maternal/pregnancy risk factors.

Methods:
We analyzed linked clinical, administrative, and birth certificate data in 3 geographic areas in Georgia, North Carolina and Utah from 2011 through 2014. Birth certificates provided neonatal, maternal and pregnancy characteristics. Maternal CHD was identified from linked clinical and administrative data and categorized as
severe
,
shunt
,
valve
, or
shunt+valve
. Neonatal outcomes of interest included preterm delivery (<37 wk), low birth weight (<2500 g) (LBW), small for gestational age (SGA), neonatal intensive care unit admission (NICU), a composite “any poor outcome” (one or more of preterm, SGA, or NICU), and CHD. Neonatal outcomes were summarized using descriptive statistics. Differences by maternal CHD severity were assessed using Kruskal-Wallis and Chi-square tests for continuous and categorical variables, respectively. Association of maternal/pregnancy characteristics and neonatal outcomes were assessed using generalized estimating equations with logit link function clustered on mother and adjusted for mother’s age, birth year, and state.

Results:
We identified 2,422 liveborn neonates (median gestational age 38 wks, weight 3155 g) born to 1,987 women with CHD (34%
severe
, 32% non-White, median age 28yrs). Overall, 19% were preterm, 18% LBW and 14% SGA; 25% required NICU and 40% experienced the composite adverse outcome (preterm, SGA, and/or NICU). CHD was present in 4.2%. Infants born to mothers with
severe
CHD (vs. combined non-severe) were more likely to have an adverse composite outcome [aOR 2.1 (1.7, 2.5)] and CHD [aOR 17.1 (9.3, 31.5)]. Black race [vs. White, aOR 1.8 (1.4, 2.3)], pregestational diabetes (DM) [vs. no, aOR 2.5 (1.3, 5.0)], gestational hypertension (GHTN) [vs. no, aOR 2.1 (1.5, 3.1)], prior preterm birth [vs. no, aOR 2.0 (1.3, 3.1)] and multiples [vs. singleton, aOR 6.7 (3.8, 11.6)] were associated with increased risk of composite adverse outcome.

Conclusions:
Forty percent of neonates born to women with CHD experienced an adverse neonatal outcome. Risk increased with maternal CHD severity, Black race, GHTN, DM, prior preterm birth, and multiple pregnancy. These findings highlight the need for heightened awareness and surveillance of these risk factors and expert preconception and pregnancy counseling for woman with CHD.
Abstract 4137107: The Impact of Race in the Evaluation Process for Advanced Heart Failure Therapies
Authors: Sherwood Dalton , Saleem Khoula , Wills Courtney , Byku Mirnela , Watkins Randall , Li Quefeng , Chang Patricia
Published: November 2024

Introduction:
Racial and socioeconomic disparities in heart failure therapy and heart transplantation have been well described. Potential racial disparities during the evaluation process for advanced heart failure (AHF) therapies is not well understood. We examined whether there were differences by race in the evaluation process for heart transplantation or left ventricular assist device (LVAD) implantation.

Methods:
Adult patients who underwent heart transplant or LVAD evaluation between May 1, 2014 – Dec 31, 2022 at the University of North Carolina Medical Center were included. Logistic regression models assessed whether approval for heart transplant listing or LVAD implantation differed by race. The multivariate model adjusted for demographic and clinical characteristics, LVEF, RV function, and substance use. Secondary outcomes assessed included the time between critical points in the evaluation process: first clinical encounter with an AHF specialist, evaluation initiation, and final decision.

Results:
The study cohort included 611 patients (304 non-Hispanic Black patients, 307 non-Hispanic White patients). Black patients were younger than White patients (52.4 vs. 60.7 years), less male-predominant (65.5% vs. 81.4%), with less ischemic cardiomyopathy (16.8% vs. 58.3%, all p<0.05). There was no significant difference in approval for advanced therapies between Black and White patients (unadjusted OR [95% CI]: 1.24 [0.90-1.72]; adjusted OR 0.98 [0.64-1.48]). Male sex was associated with a higher likelihood of approval for AHF therapies (adjusted OR 1.55 [1.02-2.36]). Age (OR 0.98 [0.96-0.99]) and creatinine (OR 0.66 [0.53-0.82]) were associated with a lower likelihood of approval for AHF therapies. Black patients had a significantly longer time interval from the first AHF specialist encounter to the initiation of evaluation for AHF therapies (median 45.5 vs. 14 days, p <0.01), and from the initiation of the evaluation process to the final decision (25.5 vs. 14 days, p <0.01).

Conclusions:
Male patients had a greater approval rate for advanced heart failure therapies. Black and white patients did not have significantly different approval rates for LVAD implantation or listing for heart transplantation. However, the evaluation process was longer for black patients. Further work is needed to investigate which factors contribute to these racial and sex differences in the evaluation and approval process for advanced heart failure therapies.
Abstract 4137204: Classifying Left Ventricular Hypertrophy from ECG in Overall Population and Bundle Branch Blocks: Machine Learning Models are Superior to Published ECG Criteria
Authors: DeBauge Ashley , Harvey Christopher , Gupta Amulya , Noheria Amit
Published: November 2024

Background:
Published ECG criteria for left ventricular hypertrophy (LVH) have low diagnostic yield, esp. with right/left bundle branch block (RBBB/LBBB). Machine learning (ML) may improve LVH classification.

Hypothesis:
ML performs better than published LVH criteria to classify LVH from ECG in overall population, and subgroups of RBBB/LBBB.

Methods:
In addition to standard ECG features like rates, intervals, axis etc., R, S and overall QRS amplitudes, and voltage-time-integrals were extracted from standard 12 leads and reconstructed vectorcardiographic X, Y, Z lead representative beats. Further, a variational autoencoder was used to extract latent encodings from the representative beats. ML algorithms (logistic regression, random forest, light gradient boosted machine, multilayered perceptron, residual network, and convolutional neural network) were trained to predict LVH (LV mass index women >95, men >115 g/m
2
) from ECG features on a training set of adult ECGs and echocardiogram within 45 days of each other (general population N=240,476, RBBB n=22,110, LBBB n=12,563). We obtained ROC AUCs in a separate validation set for LVH classification by (a) individual ECG variables, (b) published LVH criteria and (c) ML models.

Results:
As shown in
Tables 1-2
and
Figure 1
, for LVH classification among the validation sets, AUCs were highest for ML models, intermediate for univariable models and least for published criteria (best ML model vs. best criteria: general population women 0.77 vs. 0.63, men 0.78 vs. 0.63; RBBB women 0.70 vs. 0.57, men 0.77 vs. 0.57; LBBB women 0.71 vs. 0.55, men 0.72 vs. 0.54).

Conclusions:
ML models perform better than published LVH criteria at classifying LVH from ECG in overall population, RBBB and LBBB.
Abstract 4137267: A novel reproducible low-cost model of acute myocardial infarction in swine
Authors: Li Yichen , Zheng Zilong , Tang Weijie , Chen Wangping , Yang Jinfu , Fan Chengming
Published: November 2024

Background:
Traditional open- and closed-chest methods for inducing acute myocardial infarction (AMI) in pigs typically require extensive and expensive instrumentation, including ventilators and inhalation anesthesia. This study aims to evaluate a reproducible and low-cost model for AMI in pigs using lower hemisternotomy.

Methods:
Twenty Yorkshire swine (15-20 kg, 45-50 days of age) underwent permanent ligation of the roots of the first and second diagonal branches of the left anterior descending coronary artery. The procedure was performed under intramuscular anesthesia (1ml 0.5mg/kg Zoletil™ and 2ml 10mg/kg xylazine hydrochloride) with spontaneous respiration. Cardiac function was assessed via echocardiography and cardiac PET/MRI scans at 1 and 4 weeks post-MI. Heart tissue was collected for pathological analysis to evaluate the establishment of the AMI model.

Results:
All animals exhibited ECG changes, including premature ventricular complexes and ST-segment elevation immediately after ligation. No ventricular tachycardia and fibrillation was observed during the operation. No animals (0%) died during infarct creation. The "Skin-to-Skin" procedure time was 18±3.3 minutes. this procedure produced an infarction that occupies ~10% of the left ventricular mass accompanied with the decrease of LV heart function and LV anterior wall thickness 4 weeks post-MI.

Conclusions:
This novel low-cost technique provides reproducible acute coronary artery occlusion at a selected location with subsequent AMI. It avoids ventilation, inhalation anesthesia, major surgery and does not require expensive instrumentation for intracoronary intervention.