bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4136694: Impact of left ventricular support devices on myocardial and pulmonary recovery in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation
Authors: Masaru Ishida , RYOMOTO MASAAKI , Funatsu Toshihiro
Published: November 2024

Background:
Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is used to treat cardiogenic shock. However, retrograde arterial perfusion from the femoral artery can increase left ventricular (LV) afterload, resulting in LV distention which may hamper myocardial recovery and worsen pulmonary congestion. An intra-aortic balloon pump (IABP) can mitigate LV afterload, and Impella (Abiomed, Danvers, MA) can directly unload LV pressure. This study aimed to evaluate the efficacy of LV support devices during VA-ECMO in patients with cardiogenic shock.

Methods:
We retrospectively collected data from 213 consecutive patients treated with VA-ECMO due to cariogenic shock at our institution between January 2013 and December 2023. Patients were categorized as either receiving VA-ECMO alone or VA-ECMO with an LV support device. The LV support device was characterized as VA-ECMO with IABP or Impella. Data were analyzed for mortality, weaning from VA-ECMO, and changes in pulmonary congestion using the congestion score index (CSI), which is a semi-quantitative approach to pulmonary congestion based on a 6-zone evaluation of chest radiography, scoring each zone from 0 (no congestion) to 3 (intense pulmonary edema).

Results:
In this study, 95 patients received VA-ECMO alone, whereas 118 patients received an LV support device (101 VA-ECMO with IABP and 17 VA-ECMO with Impella). LV support devices improved weaning from VA-ECMO (odds ratio, 3.09 [95% confidence interval (CI), 1.75–5.55]; p<0.0001) whereas there was no difference in IABP versus Impella cohorts. Compared with VA-ECMO alone, patients with VA-ECMO with an LV support device had better survival at 30 days (OR, 3.04 [95% CI, 1.73–5.43]; p<0.0001). The rate of survival to discharge was better in VA-ECMO with an LV support device versus VA-ECMO alone (hazard ratio, 2.51 [95% CI, 1.72–3.65]; p<0.0001). The evaluation of pulmonary congestion using the CSI revealed that congestion significantly improved in VA-ECMO with Impella (changes of CSI: 1.86 to 1.36) but not in VA-ECMO with IABP (1.80 to 1.96) and VA-ECMO alone (1.94 to 2.14).

Conclusion:
An LV support device may be associated with reduced mortality and increased success in weaning off VA-ECMO in patients with cardiogenic shock. Impella may be particularly effective in reducing pulmonary congestion.
Abstract 4136705: Complexity and Inconsistency of Echocardiogram Prices at Top-Rated Hospitals in the United States
Authors: Triana Austin , Van Horn R. , Alford Mason , Quintana Joseph , Van Horn R.
Published: November 2024

Background:
Recent U.S. policies require hospitals and health insurers to post payer-specific negotiated prices for services. Few studies, if any, have thoroughly investigated the accuracy of these payer-specific prices for individual hospitals.

Hypothesis:
Top-rated medical centers charge consistent prices for echocardiograms, which are reflected in price transparency files.

Aim:
To evaluate the concordance of prices of echocardiograms using three datasets: 1) hospital price transparency, 2) payer price transparency data, and 3) Electronic Remittance Advice (ERA) claims data, reflecting actual payments.

Methods:
We extracted prices for transthoracic echocardiograms (CPT 93306) at 22 top-rated hospitals by
US News&World Report
from 1/1/2022 to 12/31/2022. We used price transparency data aggregated by Turquoise Health and compared with ERA claims data. This analysis included 9,171 insurance claims, matched to either payer or hospital-reported prices. For each claim, concordance between datasets was determined by evaluating whether each claim payment fell within a $10 margin of a publicly reported payer-specific price.

Findings:
In the payer and hospital price transparency files, reported prices ranged from $1.3 to $34,424. In the ERA claims data, the median payment for the professional fee was $203 (Q1 = $116, Q3 = $245), and the median payment for the facility fee was $2682 (Q1 = 1829, Q3 = $4531). There was a ten-fold difference in median price between the cheapest and most expensive facility. Only 27.4% of claim payments had a concordant price in the payer price transparency dataset, and 11.9% in the hospital dataset.

Conclusion:
Deriving accurate price estimates for patients requires precise matching of the insurance plan, place of service, and fee type. This process highlights the complexity of insurance contracting, and it is not surprising that there is some disagreement in prices. Regardless, we are hopeful that highlighting variation and complexity in prices is a step towards a better system of healthcare payments in the United States.
Abstract 4136712: Fontan-specific morbidities impact on heart transplant outcomes: a multicenter study
Authors: Ybarra Aecha , Cousino Melissa , Blume Elizabeth , Bano Maria , Deshpande Shriprasad , O'Connor Matthew , Chen Sharon , Wright Lydia , Kindel Steven , Joong Anna , Ploutz Michelle , Feingold Brian , Mao Chad , Lorts Angela , Simpson Kathleen , Richmond Marc , Amdani Shahnawaz , Conway Jennifer , Bearl David , Friedland-Little Joshua , Batazzi Adriana , Reichle Garrett , Yu Sunkyung , Rosenthal David , Schumacher Kurt
Published: November 2024

Introduction:
Fontan circulatory failure (FCF) is associated with poor long-term survival. The impact of Fontan-specific morbidities on outcomes in those evaluated for heart transplant (HT) are not well understood.

Hypothesis:
FCF-specific morbidities, their degree of severity, and the accumulation of morbidities are associated with mortality in individuals undergoing HT.

Methods:
This 20 center, retrospective cohort study of individuals with FCF from 2008-2023 collected data on FCF-specific morbidities, waitlist (WL), and post-HT outcomes. Each unique FCF morbidity was defined with graded severities (absent, mild, moderate, severe, and life-threatening) via a prior effort. The primary outcome was survival from WL to 1-year post-HT. Appropriate 2-group statistics and multivariable logistic regression compared surviving with those who died. Receiver operating characteristic curve determined the most discriminating value of total cumulative morbidities on mortality.

Results:
Of the 340 patients included, 51(15%) died between WL and 1 year post-HT. On univariate analysis, 7 of 27 FCF morbidities were associated with the mortality (p < 0.2) including: anatomic Fontan pathway obstruction, clinical hypoxia, chronic pleural effusions, sleep apnea, portal variceal disease, acute kidney injury within 1 year prior to WL, and mental health disorders. On multivariable analysis, only clinical hypoxia and portal variceal disease emerged as independent risk factor for mortality (adjusted odds ratio [aOR]: 2.48, p = 0.03 and aOR 2.74 P=0.02 respectively). When assessing the impact of increasing severity of each morbidity, again worsening clinical hypoxia (aOR 1.42 increase with each increase in grade, p=0.01) and portal variceal disease (aOR 1.80 with each increase in grade, p=0.01) had differential effects on mortality. Risk of death increased with greater number of FCF morbidities. Having 2 or more of the 7 univariately significant morbidities was the value best discriminating survivors from those who died (Area under the curve 0.67; sensitivity 78%, negative predictive value 93%).

Conclusion:
Clinical hypoxia and portal variceal disease confer independent risk for non-survival in patients with Fontan from WL to 1 year after HT. Additionally, the magnitude of mortality risk for both hypoxia and varices worsens as disease severity worsens. Given the impact, consistent evaluation for these morbidities and timely referral for heart failure evaluation is warranted.
Abstract 4136741: Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Lipid Reduction: A Network Meta-Analysis
Authors: Shen Hua , Chai Meng , Zhou Yujie
Published: November 2024

Background:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offer additional lipid reduction beyond that achieved with statins. However, the optimal PCSK9 therapy for lowering lipid levels in patients with hypercholesterolemia and/or hyperlipidemia on background statin therapy remains unclear.

Methods:
PubMed and EMBASE databases were searched for RCTs assessing tafolecimab, evolocumab or alirocumab vs. placebo (administrated Q2W or Q4W, 12-week treatment) in patients with hypercholesterolemia and/or hyperlipidemia on medium-intensity statin up to March 28, 2024. The outcomes of interest were the percentage change in low-density lipoprotein cholesterol (LDL-C) or lipoprotein(a) from baseline to the 12th week. A frequentist random-effect network meta-analysis was applied to calculate MD and 95% CI using Stata 16.0 software.

Results:
A total of 4960 patients [PCSK9 inhibitors (n=3230), placebo (n=1730)] across 13 RCTs were included. At week 12, tafolecimab, evolocumab and alirocumab (either Q2W or Q4W) all induced significant reductions in LDL-C levels compared to placebo (
Figure
). The efficacy of evolocumab Q2W was significantly higher compared with alirocumab Q2W (MD=-18.67%, 95% Cl [-29.59%, -7.74%]), while similar LDL-C reduction was observed in tafolecimab Q2W vs. alirocumab Q2W and evolocumab Q2W vs. tafolecimab Q2W. Furthermore, tafolecimab Q4W and evolocumab Q4W were more effective in lowering LDL-C levels compared to alirocumab Q4W (tafolecimab vs. alirocumab: MD=-23.66%, 95% Cl [-32.58%, -14.74%]; evolocumab vs. alirocumab: MD=-25.84%, 95% Cl [-34.21%, -17.46%]), while there was no difference between evolocumab Q4W and tafolecimab Q4W. Lastly, the ranking of the effects for reducing lipoprotein(a) levels was as follows: tafolecimab > evolocumab> alirocumab (either Q2W or Q4W).

Conclusions:
In patients with hypercholesterolemia and/or hyperlipidemia treated with medium-intensity statins, tafolecimab and evolocumab (either Q2W or Q4W) might be preferred choices for lowering LDL-C. Additionally, tafolecimab (either Q2W or Q4W) appears to be the most effective agent for reducing lipoprotein(a) levels.
Abstract 4136784: Diagnostic significance and prognosis prediction of electrocardiogram plane QRS-T angle in patients with non-ST segment elevation acute coronary syndrome
Authors: Chen Yiming , Zhang Junyi , Zhou Yafeng
Published: November 2024

Objective:
For patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), the diagnostic efficacy of traditional ECG is not sensitive and specific. Plane QRS-T angle (PQRS-Ta) can be used as a supplement to the current diagnostic criteria of ECG.

Methods:
The patients with recurrent chest pain in our hospital were analyzed retrospectively, and the plane QRS-T angle of the patients was calculated. The main results were as follows: (1) the clinical indexes of the two groups were analyzed according to the angle of QRS-T. (2) all patients were divided into three groups according to the final diagnosis. The diagnostic efficacy of QRS-T angle combined with standard ECG diagnostic criteria was analyzed, and the incremental diagnostic value of the new standard relative to the original standard was calculated. (3) the patients were scored by Gensini, and the differences of plane QRS-T angle among patients with different scores were compared. (4) the frequency of MACE was recorded, and the prognostic effect of QRS-T angle on the study population was analyzed.

Results:
After analyzing the data, there was a difference in the value of plane QRS-T angle between NSTE-ACS population and non-ACS population (p < 0.001). It was found that every 1 °increase of plane QRS-T angle increased the risk of NSTE-ACS by 2.5% (χ 2, 27.59, P < 0.001). The diagnostic accuracy of AUC quantified plane QRS-T angle combined with standard ECG in the diagnosis of NSTE-ACS was 0.68 (CI [0.64 ~ 0.70]). Through the analysis of NRI and IDI index, the relative NRI of the new model to the original model is 6.67%, 95% CI is 3.91%, and the CI is 9.42% (P < 0.001). The IDI is 6.30%, the CI is 4.65%, and the CI is 7.95% (P < 0.001). The new model improves the prediction effect by 6%. When the QRS-T angle increased by 1 °, the Gensini score increased by 0.199 points (95% CIRV 0.149) (Fidel60.975 (P < 0.001). Comparing prognosis of the three groups, there was a statistical difference in the overall survival time among the three groups (χ 2 = 19.090 P < 0.001).

Conclusion:
Compared with the original standard, the new diagnostic standard can improve the diagnostic efficiency of ECG. QRS-T angle can predict the prognosis of patients with NSTE-ACS. The higher the value of QRS-T angle, the greater the probability of major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome.
Abstract 4136847: Administration of the Recombinant Activated Protein C Rescues the Cardiac Vulnerability to Ischemic Insults in Aging through Modulating Inflammatory Response during Ischemia and Reperfusion
Authors: Slotabec Lily , Rouhi Nadiyeh , Seale Blaise , Wang Hao , Filho Fernanda , Adenawoola Michael , Li Ji
Published: November 2024

Introduction:
Activated protein C (APC) is an endogenous vitamin-K-dependent serine protease and exhibits therapeutic potential for ischemic heart disease. The APC derivatives with anticoagulant and/or cytoprotective properties were produced through chemical engineering to characterize the functional domain of APC for limiting ischemia/reperfusion (I/R) injury.

Hypothesis:
The thromboinflammatory regulation by APC ameliorates ischemic insults caused by I/R through the receptor EPCR/PAR1.

Methods:
Young (3 months)/aged (24 months) wild type C57BL/6J mice and PAR1

R46Q/R46Q

(block cleavage by APC) knock in mutant (3 months, C57BL/6J) mice were subjected to ligation of left anterior descending coronary artery with 45 min of ischemia. 5 min prior to reperfusion, wild type APC, cytoprotective selective APC-2Cys, or anticoagulant selective APC-E170A (0.2 μg/kg i.v.) was administered followed by 24 hr of reperfusion. The left ventricles of hearts were used for immunoblotting and flow cytometry analysis.

Results:
APC and APC-2Cys but not APC-E170A reduced I/R-induced myocardial infarction. Echocardiography showed that APC and APC-2Cys but not APC-E170A can rescue systolic dysfunction by I/R in young/aged WT but not in PAR1

R46Q/R46Q

mice. Biochemical analysis showed that administration of APC and APC-2Cys inhibited activation of inflammation signaling c-Jun N-terminal protein kinase (JNK) and NF-κB by I/R and reduced mRNA levels of the proinflammatory cytokines TNFα and IL-6 in young/aged WT but not in PAR1

R46Q/R46Q

hearts. The plasma cytokine array demonstrated that APC and APC2-Cys reduced potency of pro-inflammatory cytokines and apoptotic signaling cytokines during I/R. Moreover, I/R-triggered inflammasome NLRP3 was reduced by APC and APC-2Cys in young/aged WT but not in PAR1

R46Q/R46Q

hearts. The flow cytometry showed that APC and APC-2Cys increased lymphocyte and decreased myeloid cell abundance and increased the recruitment of inflammation-mediating CD8a
+
T-cells during I/R in young/aged WT but not PAR1

R46Q/R46Q

hearts, indicating that the APC/EPCR/PAR1 axis mediates APC's immune regulation under I/R. Moreover, APC and APC-2Cys reduced I/R-triggered macrophage abundance in young/aged WT hearts, although the proportion of M1 and M2 macrophages was unchanged.

Conclusions:
The cytoprotective domain of APC is critical for its cardioprotection against ischemic insults. EPCR/PAR1 receptor complex mediates APC's immune regulation in aging during I/R conditions.
Abstract 4137045: Sustained Anti-Thrombotic Efficacy of CS585, a Novel Prostacyclin Receptor Agonist, Demonstrates Therapeutic Potential
Authors: Stanger Livia , Flores Mariane , Yalavarthi Pooja , Dahlof Bjorn , Holinstat Michael
Published: November 2024

The formation of occlusive thrombi resulting in myocardial infarction or stroke present a significant challenge for the healthcare community. Activation of the prostacyclin (IP) receptor has been shown to decrease platelet reactivity, however current IP agonists lack a sustained effect in the blood. We have developed CS585, an IP receptor agonist with sustained anti-thrombotic effects in the blood, which could represent a novel prevention strategy in targeting thrombosis. We sought to assess the anti-thrombotic efficacy and pharmacodynamic stability of IP agonists CS585, iloprost and selexipag, in both
ex vivo
and
in vivo
models.

We evaluated the timeframe of effect of CS585, iloprost, and selexipag in mice following a single IV dose. Inhibition of thrombus formation was measured
ex vivo
in whole blood under arterial shear rates.
In vivo
, CS585, iloprost, or selexipag, were administered prior to labeling of platelets and fibrin. Thrombus formation at the site of injury was measured using the cremaster arteriole injury thrombosis assay.

CS585 administered to mice prior to blood draw decreases platelet adhesion and blood clot formation under arterial shear conditions. These effects are observed up to 24 hours post-administration; however, the effects of iloprost and selexipag return to pre-treatment levels by 24 hours.
In vivo
, mice administered iloprost or selexipag demonstrated a decrease in platelet accumulation and fibrin formation, however the effects were abrogated post-administration by 10 minutes and 4 hours, respectively. Administration of CS585, however, demonstrated sustained inhibition of thrombus formation at the site of injury, with inhibitory effects observed at 18 hours post-administration.

We have used both
in vivo
and
ex vivo
models to demonstrate the anti-thrombotic efficacy of IP receptor agonists. Our results suggest that CS585, a novel IP receptor agonist, sustainably inhibits platelet activation and clot formation for extended periods, in contrast to existing alternatives. This demonstrates a significant improvement in the pharmacodynamic effects of IP receptor agonists in the blood, highlighting CS585 as a novel anti-platelet therapeutic with the potential to treat thrombotic diseases.
Abstract 4137113: The Effectiveness of Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Retrospective Analysis
Authors: Sani Maryam , Flynn James , Abdollahi Ashkan , Gilotra Nisha , Chrispin Jonathan
Published: November 2024

Background:
Cardiac sarcoidosis (CS) manifests in a wide range of clinical presentations, including conduction system abnormalities, ventricular arrhythmias, and systolic heart failure. Although cardiac resynchronization therapy (CRT) has shown efficacy in treating select nonischemic cardiomyopathy patients, its specific impact on CS patients remains less explored. This study aimed to evaluate the outcomes of CRT therapy in CS patients, focusing on implantable cardioverter defibrillator (ICD) therapies, heart failure (HF) hospitalizations and mortality.

Methods:
We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent device implantation (ICD or Permanent Pacemaker (PPM)) with or without CRT therapy at Johns Hopkins Hospital between 2004 and 2024. Baseline characteristics and echocardiographic parameters were assessed. Heart failure hospitalizations, the frequency of ATP (Anti-Tachycardia Pacing) or ICD shocks, and all-cause mortality were also evaluated as the outcomes.

Results:
The study included 212 patients (40.1% female, average age 52.8 ± 11.1 years). Eighty-five patients underwent CRT implantation (82 CRT-D and 3 CRT-P), whereas the rest received either an ICD or a PPM without CRT therapy. Most CRT devices (58.82%) were upgrades from an initial PPM or ICD. Over a follow-up of 6.15 ± 4.43 years, 27 (12.74%) patients were hospitalized for heart failure (HF), 86 (40.56%) experienced ATP or ICD shocks, and 17 (8.02%) died. The composite outcome was observed in 103 patients (48.5%), with no significant differences between CRT and non-CRT groups (
P
= .51). Survival analysis indicated significantly reduced freedom from HF hospitalizations in the CRT group compared to non-CRT group (
P
= .01). However, ATP/ICD shocks did not have a significant difference. CRT recipients showed an improvement in left ventricular ejection fraction (LVEF) from 35.3 ± 12.6% to 38.9 ± 13.6% at 6 months (
P
= .01). Non-recipients showed no significant change in LVEF (
P
= .43).

Conclusions:
Over an average six-year follow-up period, CRT upgrade does not appear to affect ATP/ICD shock and mortality in CS patients, although it is associated with significantly higher rates of heart failure (HF) hospitalizations compared to CS patients with an ICD or PPM alone. These findings underscore the complex response of CS patients to CRT, highlighting the need for further research to optimize treatment strategies within this subgroup.
Abstract 4137240: MHCII
hi
LYVE1
lo
CCR2
hi
Interstitial Macrophages Promote Medial Fibrosis in Pulmonary Arterioles and Contribute to Pulmonary Hypertension
Authors: Qiu Fan , Miao Hao-Ran , Hui Hong-Liang , Lin Yan-Gui , Li Hua-Ming , Li Dan , Luo Min , Ong Sang-Bing , Hu Xue-Fei , Jiang Bo , Zhang Yi-Qian
Published: November 2024

Background:
Pulmonary hypertension (PH) is a lethal disease characterized in part by progressive pulmonary arteriole (PA) remodeling. Excessive PA fibrosis and macrophage infiltration are often present in PH, but potential association is obscure. We invesitgated the link between interstitial macrophage (iMΦ) infiltration and PA fibrosis in PH and idiopathic pulmonary arterial hypertension (IPAH).

Methods:
Lung tissue samples from patients with IPAH (n=11) and experimental PH (sugen-5416 and hypoxia, hypoxia, or monocrotaline, n=5) animals (adult male and female SD rats) were obtained to analyze the extent of fibrosis in PA adventitia and media and their correlation to disease severity. Single-cell RNA sequencing, immunohistological analyses, iMΦs and PA smooth muscle cells (PASMCs) coculture, and transgenic animal experiments were used to investigate the cell heterogeneity and molecular mechanisms by which iMΦs promote PA medial fibrosis. Data in this study were analyzed with unpaired two-tailed t-tests with Welch’s correction, Kruskal-Wallis one-way ANOVA followed by Dunn’s test, RM ANOVA with Geisser-Greenhouse correction, or Pearson correlation test, and
p
< 0.05 was considered statistically significant.

Results:
We found that increased collagen deposition and fibrosis in the PA media were correlated with PH severity, and iMΦ medial infiltration may be involved in these pathological processes. Single-cell transcriptomics suggested that ligand-receptor associations between MHCII
hi
LYVE1
lo
CCR2
hi
iMΦ and fibroblast-like vascular SMC subclusters contributed to PA medial fibrosis. Mechanistically, MHCII
hi
LYVE1
lo
CCR2
hi
iMΦs regulated PASMC phenotypic transition and collagen production through the wingless member 11 (WNT11)/planar cell polarity (PCP) pathway. Deletion of iMΦ-enriched
Wnt11
in myeloid cells of PH rats (
Itgam
CreERT2
;
Wnt11
fl/fl
) normalized the fibrotic PASMC phenotype and decreased PA medial fibrosis, thereby protecting against PH. Moreover, myeloid-specific
C-C motif chemokine receptor 2
(
Ccr2
) deficiency (
Itgam
CreERT2
;
Ccr2
fl/fl
) in PH-PAs inhibited MHCII
hi
LYVE1
lo
CCR2
hi
iMΦ infiltration.

Conclusions:
PA medial fibrosis is a causative factor of PH, and the inhibition of MHCII
hi
LYVE1
lo
CCR2
hi
iMΦ pathogenicity or infiltration reverses PA medial fibrosis and thus alleviates PH.
Abstract 4137248: Mechanical chest compression increases intrathoracic bleeding complication in patients receiving extracorporeal cardiopulmonary resuscitation
Authors: Matsushima Yoshihisa , Shibata Tatsuhiro , Yamakawa Rei , Hayashida Miyu , Shibao Koudai , Yanai Toshiyuki , Homma Takehiro , Ishimatsu Takashi , Nohara Shoichiro , Otsuka Maki , Fukumoto Yoshihiro
Published: November 2024

Background:
Mechanical cardiopulmonary resuscitation (CPR) is widely used to ensure high-quality CPR while reducing the burden on the medical team; however, it carries the risk of intrathoracic bleeding complications. Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest also poses significant challenges due to major bleeding complications. To date, no studies have specifically investigated bleeding complications when mechanical CPR is combined with ECPR.

Aim:
To compare the risk of major intrathoracic bleeding between manual and mechanical CPR in ECPR patients.

Methods:
We retrospectively analyzed 85 patients (mean age 59.6 ± 13.3 years, 90.6% male) who underwent ECPR at our hospital between April 2017 and March 2024 after failure to achieve a return of spontaneous circulation for more than 15 minutes despite appropriate CPR. From April 2020 to June 2023, our emergency department actively used mechanical CPR devices. Patients were divided into manual and mechanical CPR groups. The primary outcome was major intrathoracic bleeding requiring transcatheter arterial embolization (TAE), and the association between mechanical CPR and the outcome was examined.

Results:
There were 40 patients in the manual CPR group and 45 in the mechanical CPR group. Age, sex, medical history, acute coronary syndrome, out-of-hospital cardiac arrest, presence of bystander CPR, initial rhythm, total cardiac arrest time, and CPR time did not differ between the two groups. Only BSA showed a significant difference (1.75 ± 0.17 vs 1.84 ± 0.17m
2
, p = 0.018). The primary outcome occurred in 1 case (2.5%) in the manual CPR group and 9 cases (20%) in the mechanical CPR group. Univariate analysis using Firth's penalized logistic regression showed that age, thoracic transverse diameter, and mechanical CPR were significantly associated with the primary outcome. After multivariate adjustment, the associations between the primary outcome and age (HR 1.09 [1.02-1.20], p = 0.013), mechanical CPR (HR 6.62 [1.25-68.60], p = 0.024), and the outcome remained significant.

Conclusions:
In ECPR patients, mechanical CPR is significantly associated with an increased risk of major intrathoracic bleeding requiring TAE compared to manual CPR.
Abstract 4137484: Clinical implications of combined midodrine and pulmonary vasodilator therapy in Portopulmonary Hypertension
Authors: Bergeron Nicholas , Reddy Yogesh , Cajigas Hector , Burger Charles , Cartin-Ceba Rodrigo , DuBrock Hilary , Keaveny Andrew , Krowka Michael , swanson karen , Vargas Hugo , Watt Kymberly
Published: November 2024

Introduction:
Portopulmonary hypertension (POPH) and associated pulmonary vascular resistance (PVR) elevation is seen in the context of underlying portal hypertension and liver disease. In the systemic circulation, liver cirrhosis can cause inappropriate splanchnic and systemic vasodilation with decreased systemic vascular resistance (SVR). Midodrine is used to maintain blood pressure in the setting of low SVR. Pulmonary vasodilators have systemic vasodilatory effects; the implications of combined midodrine and pulmonary vasodilator use in POPH are unanswered questions.

Hypothesis:
We hypothesized that SVR would decrease over time in patients with POPH started on pulmonary vasodilators, and that use of midodrine (as a surrogate for depressed SVR), may be associated with increased risk of mortality in patients with POPH starting pulmonary vasodilator therapy.

Methods:
Patients from the 3 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) diagnosed with POPH from 1988-2020 were included in the database. Patients met hemodynamic criteria for POPH via right heart catheterization (RHC). Hemodynamics were obtained from echocardiography and RHC at initial and subsequent visits. The hazard ratio for risk of death was estimated using Cox proportional hazards method. SVR was calculated using mean arterial pressure and cardiac output.

Results:
Analysis included 147 POPH patients, 34 (23%) on midodrine and 113 (77%) not requiring midodrine. There were 116 patients with longitudinal SVR data. The mean initial SVR was 1224 Dyne sec cm-5 and decreased 251 Dyne sec cm-5 [95% CI -337 to -165 251 Dyne sec cm-5, p<0.0001] with no difference between midodrine groups (p=0.57). Patients in the midodrine POPH group had an increased risk of mortality compared to those without midodrine use (HR 1.51, 95% CI: 1.02-2.21, p=0.0371).

Conclusions:
Patients with POPH starting pulmonary vasodilator have a reduction in SVR related to vasodilator therapy. Midodrine use with pulmonary vasodilator therapy is associated with increased mortality in the POPH population. Further study of the safety of combined midodrine and pulmonary vasodilator use in POPH is needed along with exploration of more selective pulmonary vasodilators.
Abstract 4137609: Lentiviral shRNA Library Screen Using Human Pluripotent Stem Cell-derived Cardiomyocytes Identified Mediators of Protection via MAP4K4 Inhibition against Doxorubicin-induced Cardiotoxicity
Authors: Qin Yue , Jablonska Zuzanna , Herbort-Brand Ursula , Yazdani Momina , Yi Ranney , Schneider Michael , Noseda Michela
Published: November 2024

Background:
Doxorubicin (Dox) is a common component in chemotherapy for a wide range of tumors, but the cardiotoxicity has restricted its use. There is an unmet need for novel therapeutics of Dox-induced cardiotoxicity (DIC). We previously identified the protein kinase MAP4K4 as a mediator of DIC. Notably, we showed that blocking MAP4K4 activity via DMX-5804 protected against Dox-induced cell death and dysfunction in human iPSCs derived cardiomyocytes (hiPSC-CMs). As a powerful tool to study the protective mechanism, pooled library screen performs high-throughput phenotypic examination, but its potential on hiPSC-CMs is poorly explored.

Hypothesis:
A pooled lentiviral shRNA library screen in hiPSC-CMs treated with Dox ± DMX-5804 could identify mediators of protection against DIC.

Methods:
To maximize the chances to uncover key factors mediating DMX-5804 protection, we performed a high-throughput loss-of-function screen. A pooled library of 1731 lentiviral shRNAs was generated. hiPSC-CMs were transduced, then treated with Dox ± DMX-5804. Cardiac troponin I ELISA was used to examine myocyte injury. Genomic DNA was isolated, followed by amplification and sequencing of the integrated shRNAs. Log2 fold change was calculated and transformed into Z score to identify significantly shifted shRNAs.

Results:
To build the shRNA library we included 1) genes identified via transcriptomic analysis of hiPSC-CMs treated with Dox ± DMX-5804; 2) genes in the MAP4K4 signaling cascade; 3) previously defined pro-death or pro-survival genes in DIC. To ensure single gene silenced per cell, we used a low MOI of 0.5. After transduction, cells were treated with Dox ± DMX-5804. Confirming the cardiotoxicity and protection, Dox induced a 2-fold increase of cardiac troponin I release and DMX-5804 significantly reversed it.

Next, we recovered and sequenced the integrated shRNAs, and quantified the frequency of each. We identified 146 significantly enriched or depleted shRNAs (|Z score| > 2). When comparing Dox treated group to vehicle or DMX-5804 protected group, shRNA enrichment indicates pro-death function of the targeted gene. Conversely, pro-survival genes can be inferred from shRNA depletion. Amongst the 5 most consistently targeted genes, we identified
SIRT6
and
GATA4
which are known pro-survival in DIC, suggesting the screen is potent to define key genes.

Conclusion:
We performed a proof-of-concept pooled library screen in human cardiomyocytes and identified mediators of protection against DIC.
Abstract 4137665: Getting to the Heart of Stroke
TM
: A Novel American Heart Association Initiative Which Increases Identification of Stroke Etiology and Evidence-Based Post-Stroke Evaluation by Strengthening Cardiology and Neurology Collaboration
Authors: Jauch Edward , Baird Ali , Witt John , Bailey Alison , Lakkireddy Dhanunjaya , Schneider Alexander , Stergar Lindsay , Orndorff Kevin , Harper Russell , Thomas Kathie , Beon Chandler , Manoukian Steven
Published: November 2024

Background:
Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggests that up to 40% of stroke patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, improved cardiology and neurology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrent stroke risk and improve outcomes.

Methods:
In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of Stroke
TM
(GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics and performance improvement feedback.

Results:
Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (58.06% vs. 48.63%), while decreasing cryptogenic stroke rates (31.01% vs. 34.89%) and lack of a documented stroke etiology (10.93% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p<0.0001). In addition, the use of evidence-based post-stroke diagnostic evaluation increased in GTTHOS centers, including intracranial vascular and carotid imaging, echocardiography, short-term and extended (surface, implantable) cardiac monitoring (Table).

Conclusion:
In this novel AHA GTTHOS initiative in patients with stroke, which includes improved cardiology and neurology collaboration, rates of identified stroke etiology increased, while cryptogenic stroke and lack of a documented stroke etiology decreased. Furthermore, evidence-based post-stroke diagnostic evaluation, including imaging, echocardiography and short- and long-term surface and implantable cardiac monitoring, increased. These findings may contribute to improved outcomes.
Abstract 4137689: Artificial Intelligence Assessment of Diastolic Dysfunction by Electrocardiogram: Outcomes in Cardiac Intensive Care Unit Patients
Authors: Hillerson Dustin , Jentzer Jacob , Lee Eunjung , Attia Zachi , Kane Garvan , Lopez-Jimenez Francisco , Noseworthy Peter , Friedman Paul , Oh Jae
Published: November 2024

Background:
Left ventricular diastolic dysfunction (LVDD) predicts mortality in cardiac intensive care unit (CICU) patients. A novel artificial intelligence enhanced electrocardiogram (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in the cardiac intensive care unit (CICU). We aim to assess if LVDD by AI-ECG is associated with in-hospital and one-year mortality in CICU patients.

Methods:
In this retrospective cohort study, we included consecutive unique adults admitted to the Mayo Clinic CICU from 2007 to 2018 with an admission AIECG, which AI assigned LVDD grade (0 to 3). Medial mitral E/e’ ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. AIECG and TTE assessment of LVDD were used to assign patients to four groups based on TTE as gold standard: true and false negative, and true and false positive. In-hospital mortality was evaluated using multivariable logistic regression. One-year survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional-hazards.

Results:
We included 11,868 patients (median age 69.5 years, 37.7% females); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grades were: grade 0 (normal), 33%; grade 1, 7%; grade 2, 39%; grade 3, 21%. In-hospital (adjusted OR) and one-year (adjusted HR) mortality increased in each higher AIECG LVDD grade (Figure A/B), before and after adjustment including TTE measurements. Patients with grade 2-3 LVDD by AIECG and medial mitral E/e’ ratio >15 by TTE (true positive) had the highest in-hospital (adjusted OR 2.5 [1.7-3.9]) and one-year (adjusted HR 1.9 [1.5-2.5]) mortality (Figure C/D), and mortality was elevated similarly in patients with either grade 2-3 LVDD by AIECG (false positive) or medial mitral E/e’ ratio >15 by TTE (false negative).

Conclusions:
The AIECG LVDD grade was strongly associated with in-hospital and one-year mortality in CICU patients, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures (true positive) were at highest risk.
Abstract 4137693: CC-Chemokine Receptor 2 Inhibition Prevents Monocyte/Macrophages Recruitment in Abdominal Aortic Aneurysms
Authors: Elizondo Benedetto Santiago , Zaghloul Mohamed , Arif Batool , Bredemeyer Andrea , Lavine Kory , Gropler Robert , Liu Yongjian , Zayed Mohamed
Published: November 2024

Intro:
Abdominal aortic aneurysm (AAA) is a prevalent condition in the elderly, with a significant risk of mortality if it ruptures. Despite this, there is currently no effective medical therapy to prevent AAA growth and rupture. The monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis appears to play a role in AAA development. We demonstrated the potential of CCR2 as a theranostic marker for predicting AAA rupture, along with the effectiveness of a CCR2 inhibitor (RS-504393) in mitigating rupture. We further hypothesized that CCR2 inhibition can impact monocytes/macrophages trafficking in aortic tissue.

Mehtods:
Sprague-Dawley rats (N=54) underwent intraluminal aortic exposure to porcine pancreatic elastase (PPE) to induce aneurysmal degeneration. To stimulate AAA rupture, rats also recieved β-aminopropionitrile (BAPN). After 3 days of PPE exposure, a group of rats with AAA were administered a CCR2 inhibitor (CCR2i) either daily until the end of the study (CCR2i Full), or discontinued at day 5 (CCR2i Short), while the remaining rats proceeded without intervention (Fig1A). Ultrasound (12MHz) was performed at 7&14 days to assess diameter, while another cohort of animals were euthanized at 6 days, prior to rupture, for single-cell RNA sequencing analysis. The relative content of inflammatory cells within the aortic tissue was analyzed.

Results:
Both CCR2i Short and CCR2i Full treated, exhibited a significant reduction in AAA diameter at day 7 and 14 compared to controls (p<0.05; Fig1B&C). Notably, rats treated with CCR2i Full did not experience any AAA ruptures, while controls had a 56% risk of rupture. In contrast, CCR2i Short delayed the occurrence of ruptures without reducing the rupture rate (p<0.01; Fig1D). Single-cell RNA seq analysis of aortic tissue revealed that CCR2 inhibition led to a decrease in the number of recruited monocytes/macrophages. Cell recruitment was also relative to the duration of CCR2i treatment (Fig1E-G).

Conclusions:
Our study findings highlight the impact of CCR2-targeting in reducing AAA growth and the risk of rupture. Interestingly, length of CCR2i was a crucial variable for AAA rupture prevention. Furthermore, treatment length impacted the relative recruitment of monocytes/macrophages to AAA tissue, highlighting the role these cells in AAA disease pathology. Future analysis of CCR2+ inflammatory cell subgroups may help elucidate how CCR2 mechanistically modulates AAA progression and rupture risk.
Abstract 4137869: Ross Procedure for Correction of Congenitally Unicuspid Aortic Valve: A Paradigm Shift?
Authors: Wahaj Ahmed , Maqsood Naima , Toyoda Yoshiya , Islam Sabrina
Published: November 2024

Case 1:
A 54-yr-old man reported exertional dyspnea for 3 months, with a systolic murmur on exam. TTE noted severe aortic stenosis, moderate insufficiency and possible bicuspid valve morphology. Coronary angiogram showed no obstructive disease. CT chest showed a 5-cm ascending aortic aneurysm. CT surgery evaluation was sought, and patient had a Ross procedure with aortic hemiarch repair. Intra-operative TEE confirmed a congenitally unicommissural, unicuspid aortic valve (UAV). A 7-month follow-up TTE showed a normal aortic and pulmonic prosthetic gradient.

Case 2:
A 46-yr-old lady reported progressive exercise intolerance, with a systolic murmur and faint S2 noted on exam. TTE showed severe aortic stenosis. MR angiogram showed a unicuspid valve and a mildly dilated aortic root. The patient was evaluated by CT surgery and underwent Ross procedure. TTE 4 years later showed a normal aortic and a moderately elevated pulmonic prosthetic gradient. Patient continues to exercise without limitations.

Discussion:
UAV is a rare entity with an incidence of 0.02%. It has a bimodal distribution, in infants and adults, with the unicommissural type more common in adults. Due to rapid progression of valvular disease, the mean age at diagnosis is 42 years. Concurrent aortic dilatation is present in 48% patients.

Management of UAV is a matter of ongoing investigation. Classically, young patients with aortic valve disease underwent mechanical AVR. Ross procedure was under-utilized due to concerns about the surgical complexity and potential need for re-operation of the aortic and pulmonic grafts. However, recent studies show promising results. Patients with UAV have lower reoperation rates after a Ross procedure compared to a repair alone. Furthermore, a Ross procedure confers mortality benefit over mechanical AVR with no significant difference in immediate perioperative complications and mortality, although, this needs further investigation in a UAV cohort. Our cases support the feasibility of a Ross procedure for UAV, in providing a durable solution while avoiding anticoagulation in young patients. As Ross procedure is performed in limited centers, patients with UAV should be referred to such centers for definitive management.
Abstract 4138007: Mechanisms of Mitral Regurgitation in Fabry Disease
Authors: Vecerova Alena , Linhart Ales
Published: November 2024

Introduction:
Fabry disease, caused by mutations in the gene encoding alpha-galactosidase A, results in the accumulation of globotriaosylceramide (Gb3), leading to systemic complications including cardiac involvement such as mitral regurgitation (MR).

The aim of this study is to investigate the association between MR severity and mitral leaflet morphology in Fabry disease patients. A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up.

Mitral leaflet morphology was categorized as normal, fibrodegenerative changes, or leaflet thickening. MR severity varied, with the primary cause being leaflet restriction. Additionally, left ventricular outflow tract obstruction (LVOTO) and annular dilatation were observed. The study suggests that MR in Fabry disease is primarily due to leaflet restriction, either through degenerative changes or leaflet thickening.

This study investigates the association between MR severity and mitral leaflet morphology in Fabry disease patients.

Methods:
A cohort of 38 symptomatic Fabry disease patients with moderate or significant MR was followed up. Echocardiographic assessments were conducted to determine MR severity and categorize mitral leaflet morphology. Statistical analyses were performed to evaluate associations between MR severity and leaflet morphology.

Echocardiographic assessments of the mitral valve were conducted using a Vivid E95 Cardiac Ultrasound and meticulously analyzed using the EchoPAC
TM
and TOMTEC Imaging Systems. A crucial aspect of the examination involved measuring all components of the mitral valve and determining the requisite angles to evaluate each mechanism thoroughly.

Results:
Most patients exhibited leaflet restriction as the primary cause of MR, with varying degrees of severity. Mitral leaflet morphology was categorized as normal in 15,8%, fibrodegenerative changes were in 31,5% and leaflet thickening in 52,7%.

In addition, outflow tract obstruction (LVOTO) was observed in 15,7% but without systolic anterior motion (SAM) and annular dilatation (dilatation of anteroposterior annulus more than 35 mm in systole) was present in 66%.

Conclusion:
The study suggests that MR in Fabry disease is primarily attributed to leaflet restriction, either due to degenerative changes or leaflet thickening. An additional, albeit not unexpected, finding not always considered is the presence of anteroposterior annular dilatation in some cases.
Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study
Authors: Dzaye Omar , Razavi Alexander C. , Dardari Zeina A. , Wang Frances M. , Honda Yasuyuki , Nasir Khurram , Coresh Josef , Howard-Claudio Candace M. , Jin Jin , Yu Bing , de Vries Paul S. , Wagenknecht Lynne , Folsom Aaron R. , Blankstein Ron , Kelly Tanika N. , Whelton Seamus P. , Mortensen Martin Bødtker , Wang Ziqiao , Chatterjee Nilanjan , Matsushita Kunihiro , Blaha Michael J.
Published: November 2024

BACKGROUND:

Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age.

METHODS:

There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987–1989) and CAC scans at visit 7 (2018–2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components.

RESULTS:

In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09–0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88–7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants.

CONCLUSIONS:

Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course.