bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13104: Prognostic Value of a Progressive Decrease in Apoj-Glyc Levels in Patients Attending A&E Departments With Suspected Acute Coronary Syndrome or Angina-Like Pain
Authors: Kaski Juan-Carlos C , Cubedo Judit , Lluch Nuria , Lopez-sendon Jose L , Gorog Diana , Antorrena Isabel , Avanzas Pablo , Herrero Puente Pablo , Sionis Alessandro , Gonzalez-Juanatey Jose R , Iñiguez Andrés , Cordero Alberto , Ako Emmanuel , Fernandez-Aviles Francisco , Atienza Felipe , Recio-Mayoral Alejandro , Badimon Lina
Published: June 2023

Introduction:
Reduced serum levels of glycosylated apolipoprotein J (ApoJ-Glyc) have been proposed as a marker for the early detection of myocardial ischemia with a potential prognostic value.

Objective:
The EDICA clinical trial assessed the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischemia in patients attending the A&E department with chest pain suggestive of acute coronary syndrome (ACS) and investigated -as a secondary pilot objective- its prognostic value.

Methods:
EDICA -a multi-centre, international, diagnostic study (NCT04119882) assessed 404 patients. Based on clinical variables and diagnostic tests, 291 patients were considered to have had a “non-ischemic” event and 113 an “ischemic” event. Blood samples were obtained for the assessment of high-sensitivity troponin and ApoJ-Glyc at admission and at 1h and 3h thereafter. GRACE Risk Score was calculated in all ischemic patients. Patients were followed up for 6 months after presentation and the occurrence of MACE (cardiac death, recovered cardiac arrest, re-infarction, cardiac failure, new admission for ACS after discharge, or unplanned revascularization for cardiac ischemia after discharge) was recorded. ApoJ-Glyc serum levels were analyzed with a novel ELISA targeting a specific glycosylated variant of ApoJ (ApoJ-GlycA2).

Results:
Among the patients in the ischemic group, 8.8% had MACE at 6-months and these showed a 26% mean reduction in ApoJ-GlycA2 levels 3h post-admission compared with levels at presentation. This reduction was not observed in patients without MACE. Patients in the highest GRACE Risk Score tertile (>118 points) showed a progressive decrease in ApoJ-GlycA2 levels after presentation compared with patients in the lower risk tertiles (mean decrease: 41% at 1h, P=0.01 and 35% at 3h, P=0.02 when compared with admission levels).

Conclusions:
A progressive decrease in ApoJ-Glyc levels after A&E admission appears to not only identify patients with ischemic events but also those at higher risk of suffering serious recurrent cardiovascular events at 6-months’ follow-up. Further studies in larger cohorts of patients are warranted to validate the potential role of ApoJ-Glyc in risk stratification in the context of cardiac ischemic events.
Abstract 13105: The Effect of Mechanical Stress on Cardiac Fibroblasts in Pulmonary Arterial Hypertension
Authors: Bekedam Fjodor T , Smit Marisa C , Vonk Noordegraaf Anton , Bogaard Harm J , Goumans Marie Jose , De Man Frances S , Llucia-Valldeperas Aida
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop an
in vitro
model of the failing right ventricle, for which cardiac fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC).

Methods:
Confluent iPSC were induced to differentiate by adding 12 μM CHIR99021 for 24h to RPMI supplemented with B27 without insulin. Next, cells recovered for 24 h in RPMI supplemented with B27 without insulin, followed by stimulation with 75 ng/ml FGF2 up to day 20. Finally, the differentiated cells were reseeded and submitted to 10% cyclic stretch at 1 Hz for 4 days using the Flexcell FX-6000 system. Control and PAH cFBs were characterized at gene and protein levels.

Results:
The differentiated cells had a spindle morphology typical of FBs. Furthermore, the presence of cardiac (
GATA4, TCF21
) and fibroblast (
VIM, PDGFRα, COL1A1
) markers at gene and protein levels confirmed the cFB identity. Comparable expression of fibroblast related genes was observed in PAH cFBs as well as controls. Over 4 weeks of culture, iPSC-cFBs increasingly expressed markers of activated FBs (
ACTA2
and
POSTN)
over time, similar to in vitro adult cFBs. When exposed to mechanical stretch, cell aligned to the stretch direction. Surprisingly, no increase in gene expression of extracellular matrix (
COL1A1, COL3A1
) or activated fibroblasts (
ACTA2, POSTN
) markers was observed
.
Interestingly, under static and stretch conditions expression of these genes was increased in PAH cFBs compared to healthy cells.

Conclusion:
The cellular morphology after differentiation as well as the gene and protein analyses indicate that cFBs were successfully generated. Furthermore, cyclic stretch induced alignment of the cells but was not sufficient to stimulate fibroblast activation in either PAH or healthy cFBs.
Abstract 13139: Explainable Machine Learning Model for Prediction of Cardiovascular Disease With Routinely Collected Clinical Data Combined With Publicly Available Data on Environmental Risk Factors
Authors: Kim Kyuwoong , Oh Sanghyun , Hong Yoo S. , Lee Jihwan
Published: June 2023

Introduction:
Little is known about the performance benefit of combining these data with publicly available environmental risk factors for CVD prediction models.

Hypothesis:
We aimed to test whether routinely collected clinical data (age, sex, systolic blood pressure, total cholesterol, cigarette smoking) in combination with data on environmental risk factors could improve the performance of CVD prediction using an explainable machine learning (ML) technique.

Methods:
We identified individuals without previous history of CVD from the National Health Insurance Service, 2002-2015 in the Republic of Korea, linked to publicly available data on annual average of fine particulate matter (PM
10
) exposure and urban green space coverage according to the administrative code for residence in each individual. Random forest (RF) model and SHapley Additive exPlanations (SHAP) value were used for prediction for newly diagnosed CVD and explanation for contribution of each component to the model output, respectively. Performance of the prediction models were evaluated using area under the curve (AUC).

Results:
Among 151,936 individuals included, there were 2,837 subsequent CVD events. The AUCs for the RF model with the clinical data only and the model with environmental risk factors (high annual average PM
10
and low UGS coverage) in addition to the clinical data were 0.731 and 0.733, respectively. The SHAP values showed that adding these environmental risk factors did not have significant impact on the model output (SHAP summary plot). However, the clinical data comprised of traditional CVD risk factors had notable contribution to the performance of prediction model.

Conclusions:
This study showed that adding publicly available data on environmental risk factors to the routinely collected clinical data had only marginal improvement in the prediction of CVD outcomes.
Abstract 13150: Risk Factors Associated With Major Adverse Cardiovascular Events Following First-Ever Ischemic Stroke: An Observational Study Using Linked Data From an Australian Stroke Registry
Authors: Dharan Ajay S , Dalli Lachlan L , Kilkenny Monique F , Olaiya Muideen T , Cadilhac Dominique A , Nedkoff Lee , Kim Joosup , Andrew Nadine E , Sundararajan Vijaya , Kuhn Lisa ,   on behalf of the Stroke123 Investigators
Published: June 2023

Introduction:
Survivors of stroke are at increased risk of experiencing subsequent major adverse cardiovascular events (MACE). We aimed to determine the incidence of MACE within two years following first-ever ischemic stroke and identify associated factors.

Methods:
Patient-level data from the Australian Stroke Clinical Registry (2009-2013) were linked with emergency department and hospital admission data. Patient comorbidities were identified in the emergency and admissions data using published algorithms. Adults with no prior history of acute cardiovascular events were followed for two years post-discharge, or until first occurrence of MACE, whichever occurred earlier. Multivariable competing risks regression, accounting for deaths due to non-cardiovascular causes, was used to determine factors associated with MACE post-stroke.

Results:
Among 5,994 patients with first-ever ischemic stroke (median age 73 years, 45% female), 17% were admitted for MACE (129/100,000 person-years). MACE incidence was greatest in the first year following stroke (157/100,000 person-years). Compared to participants aged ≥65 years, the median time to first MACE was 37 days earlier for those aged <65 years. As there was a significant interaction (p<0.05) between age and other factors in predicting MACE incidence, subsequent analyses were stratified by age group. Being discharged to inpatient rehabilitation (sub-distribution hazard ratio [SHR]: 0.63; 95% Confidence Interval (CI): 0.44-0.90) was associated with reduced risk of MACE in patients aged <65 years only. Whereas, in those aged ≥65 years, MACE was associated with being female (SHR: 1.04; 95% CI: 1.03-1.05), initial stroke severity (SHR: 1.33; 95% CI: 1.15-1.54), smoking (SHR: 1.41; 95% CI: 1.14-1.71), and atrial fibrillation (SHR: 1.31; 95% CI: 1.14-1.51). Being treated in a large hospital (>300 beds) was associated with a lower risk of MACE in those aged <65 (SHR: 0.68; 95% CI: 0.44-0.90) and ≥65 years (SHR: 0.74; 95% CI: 0.62-0.87).

Conclusion:
MACE presentations are common within two-years of stroke, with most events occurring in the first year. We have identified factors (e.g., use of rehabilitation among younger patients) to consider when designing interventions to prevent MACE after stroke.
Abstract 13169: Cardiac Arrest and Severe Arterial Vasospasm in a 37-Year-Old Woman With Recent Covid Infection
Authors: Dow Sam , Lee Christopher , Myerson Merle
Published: June 2023

CASE:
A 37-year-old woman with history of smoking, hypertension and mild COVID-19 diagnosed 40 days prior with intermittent chest pain since then presented to the emergency department (ED) via EMS for an out-of-hospital ventricular fibrillation cardiac arrest. She was resuscitated at home with a downtime of 15 minutes. Her initial ED EKG was normal and she was admitted to the cardiac ICU. Shortly after admission she developed a junctional rhythm with ST elevation in lead II followed by polymorphic ventricular tachycardia which degenerated into ventricular defibrillation. She received 3 shocks with subsequent resuscitation. She was started on an amiodarone drip and underwent coronary angiography. With right femoral artery engagement she was noted to have severe vasospasm. An initial angiogram of the left coronary system showed mild coronary disease, subsequent injection showed diffuse vasospasm in the entire left coronary system. Telemetry showed diffuse ST elevations and QT widening with injections followed by ventricular fibrillation treated with 8 counter-shocks and the addition of lidocaine. An intra-aortic balloon pump was placed prior to transfer back to the ICU. She was initially treated with nicardipine and transitioned to amlodipine for treatment of vasospasm. Rheumatologic work-up was unremarkable and she underwent placement of an ICD for secondary prevention. A Coronary CT was performed in follow-up showing only minimal luminal irregularities with no RCA disease.

DISCUSSION:
COVID-19 has been linked to many cardiovascular abnormalities including diffuse vasospasm with acute infection. This is the first case describing diffuse vasospasm in a person who is in the post-COVID period which is defined as greater than 4 weeks after diagnosis. This case provides information on severe arterial vasospasm seen in the time period after acute COVID infection indicating that follow up after COVID for any cardiovascular abnormalities is needed.
Abstract 13181: Accurate, Non-Invasive Monitoring of VO2 Max Using Wearable ECG Technology
Authors: Lilburn Mark , Deery Adrian , McKenna Stacey , Fitzpatrick Matthew , Easlea Holly , Funston Rebecca , Condon Adrian
Published: June 2023

Introduction:
Maximal aerobic capacity (VO2 max) corresponds to the maximum volume of oxygen the body can utilize during high-intensity exercise and is widely regarded as the criterion measurement for cardiorespiratory fitness (CRF). In addition to its use as a metric to evaluate aerobic endurance, VO2 max has been identified as a significant and independent risk factor for all-cause and disease-specific mortality. The integration of VO2 max functionality into wearable devices allows CRF to be unobtrusively monitored, providing an important insight into clinical health.

Methods:
ECG data acquired on the non-invasive HeartKey
®
Chest Module throughout a multi-stage, high-intensity exercise protocol was used by the HeartKey VO2 Max algorithm to generate a VO2 max rate. The algorithm’s performance was evaluated against data simultaneously collected on gold standard CRF equipment using indirect calorimetry (Korr
®
CardioCoach). Participants (N=45) of varying ages and physical fitness were recruited to ensure a wide range of CRF levels were represented.

Results:
A strong correlational relationship (
R=
0.9) was observed between the HeartKey VO2 max values and those generated on the criterion device. HeartKey VO2 Max algorithm demonstrated high accuracy, with a mean absolute percentage error of ~6% over the 45 subjects. The mean absolute error for the HeartKey algorithm was 3.1 ml/min/kg, with a root mean square error value of 3.9 ml/min/kg.

Conclusions:
HeartKey generated highly accurate and reliable VO2 max metrics from ECG data collected on a non-obstructive, non-invasive, dry electrode wearable device, with a performance comparable to that of a gold standard indirect calorimetry device. This study highlights the opportunity to make CRF monitoring accessible in everyday scenarios by using wearable ECG devices functionalized with accurate VO2 max capability, which is convenient, cost-effective, and highly scalable.
Abstract 13194: Towards Understanding the Pathogenesis of Covid-19: Acute and Long-Term Mouse Models
Authors: Wang Chenxiao , Chen Zheng , currey joshua M , Blair Robert V , Maness Nicholas J , Rappaport Jay , Pociask Derek , Kolls Jay , Qin Xuebin
Published: June 2023

SARS-CoV2 (CoV2) infection causes both acute and long-term health effects via damaging multiple organs including lung. The endothelial dysfunction associated with the infection may contribute to pathogenesis of acute COVID-19 and long COVID. However, the mechanisms underlying the endothelial dysfunction remain elusive. Development of mouse models for these diseases will help us better dissect these mechanisms and facilitate the development of therapeutics for treatment of the disease. Previously, we developed an acute COVID model by infecting human ACE2 transgenic (K18) mice with a lethal CoV2 dose. K18 mice developed severe COVID-19, including progressive body weight loss and fatality at days 7 post infection (DPI), severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. We detected CoV2 in capillary endothelial cells, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs in this model. These results indicate that CoV2 infection and infection-mediated immune activation caused endothelial dysfunction, which contributes to the pathogenesis of severe COVID-19. To further develop a model for long COVID, we infected K18 mice with sub lethal CoV2 dose, monitored the body weight and survival rate and characterized the lung and brain histological changes at 21 and 45 DPI. The infected mice progressively lost body weights from 5 to 7 DPI and started to rebound from 8 DPI and then returned to baseline at 13 DPI. Mice had extensive patchy inflammation in the lungs associated with collagen deposition and smooth muscle action expression. We also found moderate levels of total viral RNA in the lung but not brain while viral subgenomic RNA (a correlate of viral replication) was undetectable in lung or brain by qRT-PCR assay. Fluorescence staining showed co-localization of CoV2 spike protein and CD206 in lungs, suggesting macrophage engulfment CoV2 at late time points. Together, we have successfully established long-term COVID mouse models, which will be useful tools for further defining the role of endothelial dysfunction in pathogeneses of CoV2-related acute and long COVID.
Abstract 13200: Loss of Cardiomyocyte β2 Spectrin Promotes Cardiac Dyad Dysfunction and Accelerated Heart Failure
Authors: Scott Shane S , Schwendeman Ethan J , Matzko Anna , Derbala Mohamed H , Pietrzak Maciej , xu Xianyao , Tonniges Jeffrey R , Biesiadecki Brandon J , Mohler Peter J , Hund Thomas J , Smith Sakima A
Published: June 2023

Background:
The cardiac dyad and associated calcium (Ca
2+
) release units (CRUs) are integral for cardiac excitation-contraction (E-C) coupling. The cardiac dyad is a multicomponent complex composed of the transverse-tubules, junctional sarcoplasmic reticulum (jSR), and CRU-associated proteins. Proper E-C coupling requires Ca
2+
influx via long-lasting-L-type Ca
2+
channels (Cav1.2), which triggers Ca
2+
release from adjacent ryanodine receptor 2 (RyR2) located in jSR. βII-spectrin loss alters RyR2 localization, but its contribution to cardiac dyad organization and E-C coupling remains unclear.

Hypothesis:
We hypothesized that βII-spectrin is required for cardiac dyad organization and proper cardiomyocyte calcium signaling.

Methods:
Cardiomyocyte-specific βII-spectrin knockout (βII-cKO) and control mice (βII-flox) were generated and harvested for immunoblotting, qRT-PCR, and imaging by transmission electron microscopy (TEM). Mice hearts were also interrogated by echocardiography following transaortic constriction.

Results:
Cardiac dyad structure and CRU components are significantly altered in βII-cKO hearts. Ultrastructural analysis of βII-cKOhearts by TEM showed fragmented cardiac dyads, dilated jSR and reduced jSR contact with T-tubules. Quantitative RT-PCR showed increased expression of calsequestrin 1 and 2, decreased phospholambam,
Ncx
and
Cacna1c
(major Cav1.2 subunit), while
Ryr2
,
Jph2
,
Serca2a
are unchanged. Protein expression of NCX was decreased, while expression of CAV1.2, RYR2, CASQ2, and SERCA2A remained unchanged. Furthermore, pressure-induced overload of βII-cKO hearts promoted accelerated heart failure (HF).

Conclusions:
This is the first demonstration that the βII-spectrin cytoskeletal protein is critically important for maintaining the structural integrity of the cardiac dyad. βII-spectrin loss and the resulting alterations in CRU structure, genes, and protein composition promoting accelerated HF.
Abstract 13215: Accuracy of Visual Qualitative Estimates of CAC Incidentally Found on Chest CT Compared With Formal CAC Scoring
Authors: Raygor Viraj , Joshi Parag H , Canan Arzu , Abbara Suhny , Assadourian Joanna N , Khera Amit , Peterson Eric D , Navar Ann M
Published: June 2023

Introduction:
While coronary artery calcium (CAC) scoring improves CVD risk assessment, it remains underutilized and is often not covered by insurance. Coronary calcium can be detected on chest CT scans performed for other indications and may allow identification of higher-risk people without a dedicated CAC scan. However, qualitative CAC scoring on non-gated chest CT scans is not widely validated.

Methods:
Since 2016, radiologists at two large health systems in Dallas (an academic medical system and a large safety net hospital) have routinely documented the presence and severity of CAC (none, mild, moderate, large) on all chest CT scans. We identified all adults who underwent both dedicated CAC scanning and a separate chest CT scan within 6 months. We compared qualitative visual CAC by CT scan versus a CAC score from a dedicated, gated coronary CT scan.

Results:
From 2016-2021, 891 patients (mean age 60 ± 12y, 43% male, 61% White, 35% Black, 24% Hispanic) underwent both a CT scan and a CAC score. Of these, 424 had no CAC, 268 small, 137 moderate, and 62 large CAC on CT scan. Qualitative CAC estimate from non-gated CT scans were highly correlated with formal CAC scores (Kendalls tau-b=0.75, p<0.0001, figure). To detect CAC (score >0), qualitative assessment on CT had a sensitivity of 82%, specificity of 95%, positive predictive value (PPV) of 97%, and negative predictive value (NPV) of 77%. Only 6% with small, 1% with moderate, and 0% with large CAC on CT had a CAC score = 0. For detection of CAC ≥ 100, moderate to large CAC on CT had a sensitivity of 62%, specificity of 96%, PPV of 89%, and NPV of 84%.

Discussion:
At two different hospitals serving a diverse population, visual estimates of CAC on routine CT scans were strongly correlated with formal CAC scores from dedicated, gated CT scans. Incidental identification of CAC on routine CT scans should prompt more aggressive cardiovascular risk reduction, particularly when moderate to large CAC burden is seen.
Abstract 13220: Real-World Analysis of the Electrical Performance and Projected Longevity of Leadless Ventricular Pacemakers
Authors: El-Chami Mikhael F , Ibrahim Rand , Stromberg Kurt , Fagan Dedra H , Piccini Jonathan P
Published: June 2023

Introduction:
The Micra™ VR leadless pacemaker has demonstrated a high implant success rate and a low rate of complications in both investigational and real-world settings. Although the manufacturer’s product performance reporting suggests a high device survival rate, projected longevity based upon real-world usage has not been assessed.

Objective:
To summarize device electricals and battery longevity in Micra VR leadless pacemakers in nationwide practice.

Methods:
A retrospective analysis was performed using Micra VR remote transmissions from the CareLink de-identified database queried on 1 June 2022. A patient’s last transmission ≥ 30 days post-implant was used for analysis. Pacing percentage, electrical performance, and battery longevity were summarized. To standardize the analysis, projected battery longevity was computed by adding the number of years between implant and the device’s last transmission and the projected battery life remaining at last transmission based on device use conditions.

Results:
Transmissions from 26,698 patients qualified for analysis. Median time from implant to final transmission was 19.8 months (range 1-96.7). Mean pacing capture threshold (PCT) was 0.61 ± 0.50 V (standardized to 0.24 ms) with 92.1% of patients having a PCT ≤1.0 V. Mean pacing impedance and sensing amplitude were 567 ± 118 ohms and 13.7 ± 6.3 mV. Median pacing percentage was 82.3% (IQR: 25.7% - 98.6%) with 43.9% of patients paced >90%. Median projected battery longevity for the overall cohort was 13.7 years (IQR: 12.4 - 15.3 years) with 91.9% of devices exceeding 10 years (Figure). Among patients with >90% pacing burden (N=11,717), median projected battery longevity was 12.6 years (IQR: 11.6-13.4) with 87.2% of devices exceeding 10 years.

Conclusions:
Real-world performance of the Micra VR leadless pacemaker demonstrates favorable pacing parameters with 92.1% of patients having pacing thresholds of ≤1.0 V and a median projected battery longevity of 13.7 years.
Abstract 13226: Low-Carbohydrate Diets and Risk of Type 2 Diabetes in U.S. Men and Women
Authors: Wang Yeli , Hu Yang , Wan Yi , Rimm Eric B , Hu Frank B , Sun Qi
Published: June 2023

Introduction:
Evidence regarding associations between overall low-carbohydrate diets (LCDs) and the risk of developing type 2 diabetes (T2D) remains to be mixed. In the current analysis, we aimed to prospectively assess associations of various LCDs that emphasize different quality of protein, fat, and carbohydrate with T2D risk in U.S. men and women.

Methods:
A prospective cohort study was conducted in 203,541 men and women participating in the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, and cancer at baseline and were followed for up to >30 years. Five LCD scores based on sources of protein, fat, and carbohydrate differentiated by their qualities were derived every four years based on dietary assessments by a validated food frequency questionnaire.

Results:
During 5,095,048 person-years of follow-up, 19,675 T2D cases were documented. In the multivariable model, a higher overall LCD score was associated with higher T2D risk in a dose-response manner: the hazard ratio (HR) comparing highest vs. lowest quintile was 1.28 (95% confidence interval: 1.22-1.34;
P
-trend <0.001). A vegetable-based LCD score that emphasizes vegetable protein and fat intake was associated with 6% lower T2D risk (0.94 [0.90-0.98;
P
-trend =0.003]), and a healthy LCD score that further de-emphasizes refined carbohydrate intake was associated with 15% lower T2D risk (0.85 [0.81-0.89;
P
-trend <0.001]). In contrast, LCD scores emphasizing high animal protein and fat intake were associated with higher T2D risk. The HRs (95% CIs) comparing extreme quintiles were 1.35 (1.29-1.42;
P
-trend <0.001) for an overall animal-based LCD score and 1.39 (1.32-1.46;
P
-trend <0.001) when such a score that further de-emphasizes whole grain intake.

Conclusions:
LCDs were not beneficial for the primary prevention of T2D unless they emphasize the quality of the macronutrient compositions.
Abstract 13237: Single Cell Transcriptomes Reveal Novel Macrophage and Endothelial Subtypes in Pulmonary Hypertension
Authors: Li Bolun , Xing Yanjiang , Zhou Yitian , Xiao Xingqi , Shu Ting , Song Xiaomin , Zhao Hongmei , Pang Junling , Yang Peiran , Yu Paul B , Wang Jing , Wang Chen
Published: June 2023

Introduction:
Animal models are widely used to study pulmonary hypertension and test experimental therapies. The detailed cellular phenotypes of these diverse models, and their relationship to human disease remain unclear.

Hypothesis:
This study aimed to assess several commonly used models and their correlations with human disease at single-cell resolution.

Methods:
Single-cell RNA sequencing was performed on lung tissues from mice exposed to chronic hypoxia or SU5416 with hypoxia, rats exposed to monocrotaline, and control animals. Immunofluorescence was used to validate the findings in animal and patient tissues.

Results:
Perturbed cell populations in diseased rats and mice were similar to those in patients, with macrophages and endothelial cells being primarily affected. A novel DHCR24
high
macrophage population harboring tissue remodeling and pro-inflammatory features were consistently increased across rodent models, and whose phenotypic modulation corresponded with disease progression. Functionally diverse endothelial subtypes were found, including a novel ETB
+
endothelial population with potentially protective functions. These endothelial subtypes exhibited key motifs of pulmonary hypertension, including enhanced apoptosis, dysregulated angiogenesis, proliferation, and reactive oxygen species-mediated stress. These macrophage and endothelial subtypes exhibited dysregulation of numerous genes targeted by approved PAH drugs. Changes in these cell populations were confirmed by animal and patient lung histology. Potential intercellular interactions between macrophage and endothelial subtypes, via ANGPTL4, CXCL12, or SEMA3 signaling, and autocrine endothelial signaling were predicted to occur.

Conclusions:
We established a comprehensive single-cell atlas of the mainstream rodent pulmonary hypertension models, and highlighted potential functional roles of novel macrophage and endothelial subpopulations.
Abstract 13273: Real-World Efficacy of Tafamidis in Patients With Transthyretin Amyloidosis and Heart Failure
Authors: Ghoneem Ahmed , Bhatti Ammar W , Mitchell Joshua D , Liu Jennifer , Zhang Kathleen , Trachtenberg Barry , Wechalekar Ashtoush , Cheng Richard , Baron Suzanne J , Nohria Anju , Lenihan Daniel , Dani Sourbha , Ganatra Sarju
Published: June 2023

Background:
Tafamidis was associated with reduction in cardiovascular hospitalizations and all-cause mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the ATTR-ACT trial. However, real-world data on the efficacy of tafamidis are limited.

Methods:
We conducted a retrospective, observational cohort study using the TriNetX research network, a multicenter federated research network with data pooled from electronic health records. Patients with wild-type TTR amyloidosis and heart failure (HF) were identified based on ICD-10 codes on or before May 15, 2021. The study cohort was then divided into two groups based on treatment with tafamidis. Propensity score matching (PSM) was performed to balance the confounders. Rates of heart failure exacerbations (HFE) and all-cause mortality at 12 months were compared between the two cohorts.

Results:
We identified 1362 patients with wild-type ATTR amyloidosis with HF (tafamidis group =553, non-tafamidis group =809). After PSM, there were 421 patients in each group (mean age: 76 years, Female 14%, White race 64%). During the 12-month follow-up period, 38 (9.0%) patients experienced HFE in the tafamidis group compared to 58 (13.8%) patients in the non-tafamidis group (OR 0.62; CI0.40-0.95, p=0.030). Patients treated with tafamidis had lower all-cause mortality compared to the non-tafamidis group (10.7% vs. 16.4%; OR 0.61, CI 0.40-0.91, p=0.016). The treated cohort had a higher probability of event-free survival for HFE (HR 0.61; 95% CI 0.40-0.92, Log-Rank p= 0.018) and all-cause mortality (HR 0.619; 95% CI 0.425, 0.901, Log-Rank p= 0.011).

Conclusion:
This real-world analysis confirms that tafamidis use is associated with reduced HF exacerbations and all-cause mortality in patients with wild-type TTR amyloidosis and HF. Longer term follow-up is needed to better understand the utility of tafamadis given the increasing recognition of ATTR-CM and its high cost.
Abstract 13281: In vivo Reprogramming of Mouse Fibroblasts Into Cardiac Progenitor Cells for Myocardial Infarction Treatment
Authors: Liang Jialiang , Wang Yi-gang
Published: June 2023

Introduction:
Our previous study demonstrated that fibroblasts can be reprogrammed into induced cardiovascular progenitor cells (iCPCs) by a CRISPR activation approach. However, it is still unknown whether in vivo iCPC reprogramming can be achieved by direct activation of endogenous genes.

Hypothesis:
Direct activation of endogenous loci by using CRISPR tools targeting genomic DNA can fulfill in vivo iCPC reprogramming to repair infarcted hearts.

Methods:
A new fibroblast-specific CRISPRa model (Col1a2-cre/ERT;CAG-cas9) was generated. SgRNAs targeting the core promoter region of
Gata4, Isl1, Nkx2-5, Baf60c,
or
Tbx5
were locally introduced through an AAV system in MI mice that were created by permanent LAD ligation. Heart function was measured by echocardiography and tissue sections were harvested for immunostaining. Cardiovascular cells derived from iCPCs were determined by immunostaining, ex vivo characterization, and electrophysiological assay.

Results:
The CRISPR system was activated in ~50% of fibroblasts after tamoxifen induction. The lineage conversion into iCPCs was identified by the Nkx2.5-eGFP reporter. eGFP+ cells were expressing proliferative markers (Ki67 and Pcna) and aggregated into spheres during suspension culture after sorting. Progenitor markers (Flk1, Ssea1, and Pdgf-α) were co-expressed in eGPF+ cells. The ejection fraction and scar formation of infarcted hearts were improved after injection of sgRNA-AAVs for 4 weeks. The engrafted iCPCs were identified by the lineage-tracing reporter and differentiated into cTnT+ cardiomyocytes, α-SMA+ smooth muscle cells, or CD31+ endothelial cells in infarcted hearts.

Conclusions:
Activation of endogenous loci enables in vivo iCPC reprogramming for cardiac regenerative medicine.
Abstract 13297: Higher Maternal Serum Ferritin in the Third Trimester is Associated With Reduced Endothelial Function in the Preadolescent Child
Authors: Boehme Cleighton , Moran Martha , Do Victor , Lasso-Mendez Juliana , Bell Rhonda C , Bourque Stephane L , Fruitman Deborah S , Cooke Christy-Lynn , Hornberger Lisa K
Published: June 2023

Introduction:
Elevated iron status in pregnancy has been implicated in gestational diabetes (GDM) development and in cardiovascular (CV) disease progression in adults. Animal models, however, have suggested maternal iron deficiency anemia may increase the offspring’s risk of CV disease. Whether maternal iron levels impact the CV health of the child in humans is unknown. This study investigated the relationship between maternal iron markers and the child’s CV health.

Methods:
This is a nested observational study tied to the Alberta Pregnancy Outcomes and Nutrition (APrON) Study. Children of mothers with and without GDM but otherwise uncomplicated pregnancies were prospectively recruited. Maternal serum ferritin, total iron binding capacity, and hemoglobin in the 2
nd
and 3
rd
trimesters were obtained. CV outcomes included: left ventricular mass Z-score, reactive hyperemia index score (lnRHI, EndoPAT), Doppler-based aortic and peripheral arterial pulse wave velocity, and carotid intima-media thickness. Univariate and multiple linear regression models, including maternal GDM as a covariate, were built to explore relationships between maternal iron markers and the child’s CV health.

Results:
Fifty-two children, 40 (77%) female, were assessed at a mean age of 10.9±0.7 years. Maternal serum ferritin in the 2
nd
(median (IQR): 38.8 (39.2) ng/mL; B=-0.0039, p=0.01) and 3
rd
trimesters (13.7 (9.0); B=-0.011, p=0.008) inversely related to the child’s lnRHI in univariate analyses, whereas no other relationships were observed between maternal iron markers and the child’s CV health. While the effect of 2
nd
trimester serum ferritin was attenuated in a multiple linear model adjusting for maternal GDM, another model demonstrated a persistent relationship of 3
rd
trimester serum ferritin with lnRHI (B=-0.028, p=0.007), not impacted by maternal GDM (B=-0.37, p=0.11) or their interaction term (B=0.020, p=0.07).

Conclusions:
High maternal serum ferritin in the 3
rd
trimester may be associated with reduced endothelial function of the child. If validated, further work is needed to understand pathogenic mechanisms, and the impact of supplementation guidelines in pregnancy.
Abstract 13298: Racial and Ethnic Variation in ECMO Use, Failure to Rescue, & Mortality in Pediatric Cardiac ICU Patients: A Multicenter Cohort Study From the Pediatric Cardiac Critical Care Consortium Registry
Authors: Brunetti Marissa A , Griffis Heather M , Obyrne Michael L , Glatz Andrew C , HUANG JING , Chan Titus , Schumacher Kurt , Bailly David , Domnina Yuliya , Lasa Javier J , Moga Michael-Alice , Zaccagni Hayden , Simsic Janet M , Gaynor James W
Published: June 2023

Introduction:
Previous studies have reported racial disparities in ECMO use. Using a clinical registry, we sought to determine if there was racial & ethnic variation in ECMO use &, if so, whether outcomes were mediated by differences in ECMO use.

Methods:
Multicenter, retrospective cohort study of the Pediatric Cardiac Critical Care Consortium (PC
4
) clinical registry. Racial/ethnic categories included White, Black, Hispanic, Asian, & other race (Native American, Pacific Islander, & mixed race). Analyses were stratified by hospitalization type (medical vs. surgical). Multivariable logistic regression models adjusted for measurable confounders & evaluated the association between race/ethnicity with ECMO use, failure to rescue (FTR), & mortality. Analyses of outcomes were adjusted for ECMO use. Secondary analyses explored interactions between race/ethnicity, insurance, & socioeconomic status with ECMO use & outcomes.

Results:
From 8/1/14-1/31/19, 50,552 hospitalizations from 34 hospitals were studied. Across all hospitalizations, 2.9% (n=1467) included ECMO. In both surgical & medical hospitalizations, Black race & Hispanic ethnicity were associated with severity of illness proxies. In medical hospitalizations, race & ethnicity were not associated with the likelihood of ECMO use. In medical hospitalizations, other race had higher adjusted odds of FTR (aOR 1.69 95% CI 1.06-2.70 p=0.03) & higher adjusted odds of mortality (aOR 1.61 95% CI 1.22-2.12 p=0.001). For surgical hospitalizations, Black (aOR 1.24 95% CI 1.02-1.50 p=0.03) & other race (aOR 1.50 95% CI 1.17-1.93 p=0.001) were associated with higher adjusted odds of ECMO use compared to Whites. No significant differences were found in FTR for surgical hospitalizations but hospitalizations of Hispanics had higher adjusted odds of mortality (aOR 1.31 95% CI 1.03-1.68 p=0.03). No significant interactions were demonstrated between race/ethnicity & indicators of SES with ECMO use or outcomes.

Conclusions:
Black & other race were associated with increased likelihood of ECMO during surgical hospitalizations. There were racial/ethnic disparities in outcomes not explained by differences in ECMO use. Efforts to mitigate these important disparities should include other aspects of care.
Abstract 13303: Influence of ARNI on Cardiac Autonomic Nervous System
Authors: Boehmer Andreas A , Schubert Tim , von Stuelpnagel Lukas , Bauer Axel , Dobre Bianca , Kaess Bernhard M , Ehrlich Joachim R
Published: June 2023

Background

Mortality in heart failure with reduced ejection fraction (HFrEF) is associated with imbalance of cardiac autonomic nervous system (CANS). Sacubitril/ Valsartan (ARNI) reduces risk of death and HFrEF hospitalization. Whether ARNI exerts effects on CANS has not been studied. Accordingly, we prospectively compared heart rate variability (HRV) as a noninvasive measure of CANS before and after initiation of ARNI therapy.

Methods:
The study was as a single-arm prospective interventional study. Patients with HFrEF underwent echocardiography and standardized 30-minute 12-lead Holter ECG recording before and 3 months after initiation of ARNI therapy. Study endpoints were changes in HRV parameters (standard deviation of normal-to-normal intervals (SDNN), mean square of differences between consecutive R-R intervals (RMSSD), periodic repolarization dynamics (PRD) and deceleration capacity (DC) as well as left ventricular ejection fraction (LVEF) and heart rate (HR).

Results:
Between June 2021 and March 2022 we recruited 63 consecutive patients. At follow-up 48 (76.2%) patients were still on ARNI and therefore analyzed. Mean age was 65±13 years, 88% were male. All patients received identical beta-blockers dosage at baseline and follow-up. Heart rate was reduced by ~12% (P=0.005). SDNN increased by ~42% (P<0.001), RMSSD by ~55% (P<0.001) and ~DC by 370% (P<0.001). No change in PRD was observed (P=0.13). These results were accompanied by increased LVEF (28±6% vs. 38±10%, P<0.001) and reduced plasma nt-proBNP levels (5083±790 pg/ml vs. 1838±621 pg/ml, P=0.002). NYHA class improved from III to II.

Conclusion

Significant increase of parasympathetic CANS tone was observed after initiation of ARNI therapy as evidenced by decreased HR, increased DC, SDNN and RMSSD. Part of the beneficial effects of ARNI might be related to the accentuation of parasympathetic CANS modulating mortality risk and risk for HFrEF hospitalizations.
Abstract 13365: Real World Clinical Outcomes Associated With Controlled versus Uncontrolled Blood Pressure in Patients With Apparent Treatment Resistant Hypertension
Authors: Bakris George , Singhal Mukul , Chen Cindy , Campbell Alicia , Haskell Lloyd , Ashton Veronica
Published: June 2023

AHA estimated 10.3 million US adults with apparent treatment resistant hypertension (aTRH) in 2018; limited data exist regarding clinical outcomes for these patients. This retrospective cohort study assessed risk of major adverse cardiac events (MACE: stroke, myocardial infarction, heart failure hospitalization) and end stage renal disease (ESRD) among aTRH patients, comparing those with controlled blood pressure (CBP; SBP/DBP <130/80 mm Hg) vs uncontrolled blood pressure (UBP; ≥130/80 mm Hg), using linked IQVIA Ambulatory EMR- US and IQVIA PharMetrics® Plus claims data. Patients taking ≥3 antihypertensive (anti-HTN) classes within 30 days (index regimen) between 1/1/2015 and 6/30/2021, having ≥2 BP values post-index regimen (2
nd
BP date = index date) with ≥12 months pre-index enrollment (baseline) were included. Unbalanced covariates were adjusted in the multivariable model. Cohorts consisted of 11,427 CBP and 22,333 UBP patients: mean (SD) age 62 (13) vs 60 (12) years, female (48% vs 46%), African-American (8% vs 12%), mean (SD) baseline SBP/DBP 118 (8)/70 (6) vs 141 (14)/82 (9) mm Hg, mean (SD) BMI 32 (8) vs 34 (10) kg/m
2
, respectively. The index regimen consisted of 3, 4, or ≥5 anti-HTN classes in 82% vs 79%, 15% vs 18%, and 2% vs 3% of CBP vs UBP patients, respectively (all p<0.001). Frequently observed baseline comorbidities in CBP vs UBP patients included hyperlipidemia (79% vs 76%), mild to moderate diabetes (43% vs 42%), chronic pulmonary disease (31% vs 25%), and congestive heart failure (27% vs 16%). Mean (SD) follow-up time was 2.7 (2.1) years for both cohorts. Patients with UBP were at 8% and 53% increased risk of developing MACE and ESRD, respectively, MACE risk was mainly driven by a 31% increased risk of stroke (figure). Despite being treated with 3+ anti-HTN classes, 66% of aTRH patients had UBP and demonstrated increased risk of MACE and ESRD compared to CBP patients. Development of future innovative treatment approaches can add value in the management of aTRH.
Abstract 13438: Resource Utilization and Outcome Trends of Intravascular Physiologic Testing During Percutaneous Coronary Intervention - United States National Inpatient Database Analysis 2014 Through 2019
Authors: Almani Muhammad Usman , Qudrat Ullah Muhammad , Usman Muhammad , Matute-Martinez Carlos , Yousuf Muhammad , Vij Aviral
Published: June 2023

Introduction:
Physiologic assessment of intermediate coronary stenosis has shown superiority in guiding decision making when compared to angiographic assessment alone. Many recent trials have shown improved outcomes using resting or hyperemic indices for severity assessment. In this study, we aimed to analyze the trends of intravascular physiologic testing during percutaneous coronary intervention (PCI), adjusted in-hospital mortality, adjusted in-hospital stay and adjusted hospital cost.

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2014 through 2019 Database. The NIS was searched for PCI with and without intravascular physiologic testing in adult patients (age ≥18) using ICD 9 and 10 codes. Outcomes of interest were utilization rates of intravascular physiologic testing during PCI, trend of adjusted in-hospital mortality, adjusted mean LOS and adjusted mean hospital cost. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis.

Results:
Of 2,871,865 PCIs in 2014 through 2019, 118,795 (4.1%) were coupled with intravascular physiologic testing. The use of intravascular physiologic testing during PCI steadily increased from 2.8% in 2014 to 5.0% in 2019 (trend p <0.001). The adjusted in-hospital mortality for PCI with physiologic testing did not show any significant statistical linear trend through the years (0.8% in 2014 vs. 0.9% in 2019, trend p=0.123). The mean adjusted LOS remained the same (3 days, trend p=0.530), whereas, mean adjusted hospital cost showed a linear trend of higher hospital cost (24033$ in 2014 vs. 25434$ in 2019, trend p=0.014).

Conclusions:
There is a rise in use of coronary intravascular physiologic testing during PCI. No statistically significant linear trend was observed in terms of in-hospital mortality or LOS for PCI with intravascular physiologic testing, however, over the years the mean hospital cost is on the rise.
Abstract 13454: Utilization Rate and Outcome Trends for Watchman Procedure - Nationwide Analysis
Authors: Qudrat Ullah Muhammad , Almani Muhammad Usman , Usman Muhammad , Vij Aviral
Published: June 2023

Introduction:
Left atrial appendage closure is increasingly offered to patients with atrial fibrillation who are poor candidates for long-term anticoagulation. We set out to determine the utilization rates and adjusted outcome trends for the WATCHMAN procedure.

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2015 through 2019 Database. The NIS was searched for atrial appendage closure in adult patients (age ≥ 18) using ICD 9 and 10 codes. Outcomes of interest were utilization rates of WATCHMAN procedure through time, trends of adjusted mean length of stay (LOS), and adjusted mean cost. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis.

Results:
There were 63,190 WATCHMAN procedures performed from 2015 through 2019. The mean patient age was 76 years, and 58% were males. The utilization rates of the WATCHMAN procedure steadily increased from 1800 in 2015 to 26,915 in 2019 (the rise was steeper for females than males and for Caucasians than African Americans). The adjusted mean LOS decreased from 3.4 days to 1.4 days, trend p<0.001. No statistically significant linear trend was observed in terms of adjusted mean hospital cost (32784$ in 2014 vs. 27385$ in 2019, trend p=0.071).

Conclusions:
There has been a steady rise in the use of WATCHMAN procedure in the United States, more so in females than males and in Caucasians than African Americans. Over the years, there has been a decrease in LOS for WATCHMAN hospitalizations, however, the hospital cost remained unchanged.
Abstract 13455: Clinical Outcomes of Intravascular Ultrasound During Percutaneous Coronary Intervention- United States Nation-Wide Analysis 2014 Through 2019
Authors: Usman Muhammad , Almani Muhammad Usman , Qudrat Ullah Muhammad , Yousuf Muhammad , Vij Aviral
Published: June 2023

Introduction:
Intravascular Ultrasound (IVUS) is a catheter-based real-time imaging procedure that assists in both diagnosis and treatment during Percutaneous Coronary Intervention (PCI). Over the years, IVUS-guided PCI have become more popular. In this study, we aimed to analyze the trends of use of IVUS-guided PCI, adjusted in-hospital mortality, hospital length of stay (LOS) and inpatient cost over the years.

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2014 through 2019 Database. The NIS was searched for PCI with and without IVUS in adult patients (age
≥
18) using ICD 9 and 10 codes. Outcomes of interest were utilization rates of IVUS during PCI, trend of adjusted in-hospital mortality, adjusted mean LOS and adjusted mean cost. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis.

Results:
Of 2,871,865 PCIs in 2014 through 2019, 201,075 (7.0%) were coupled with IVUS. The use of IVUS during PCI steadily increased from 6.2% in 2014 to 9.3% in 2019 (trend p<0.001). The adjusted in-hospital mortality and inpatient LOS for PCI with IVUS showed statistically insignificant trend of higher mortality (1.3% in 2014 vs. 1.6% in 2019, trend p=0.053) and shorter LOS (3.2 days in 2014 vs. 3.0 days in 2019, trend p=0.148). The mean adjusted cost steadily increased over the years for patients undergoing PCI with IVUS (24236$ in 2014 vs. 28700$ in 2019, trend p=0.012).

Conclusions:
There is a steady rise in use of IVUS during PCI. There is a steady hike in hospital costs for PCI with IVUS hospitalizations however in-hospital mortality and LOS remain the same.