bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146232: Kidney Transplant Outcomes From Deceased Donors Who suffered Acute Kidney Injury: Systematic Review and Meta-Analysis
Authors: Queiroz Ivo , Tavares Arthur , Barbosa Lucas , Mesquita Cynthia , Leandro Giovanna , Fukunaga Christian , Pimentel Tulio , Monteiro Arthur , Defante Maria Luiza Rodrigues , Antunes Vanio do Livramento Junior
Published: November 2024

Background:
Kidney transplant is the most common transplanted organ in the world. However, the efficacy of transplants from deceased donors with acute kidney injury (AKI) before transplantation is a matter of debate. For this reason, we performed a meta-analysis to assess the outcomes of kidney transplants from deceased donors with AKI when compared to non-AKI deceased donors.

Methods:
We systematically searched MedLine, Embase, and Cochrane databases for studies comparing kidney transplants from deceased donors with AKI compared to those without AKI. The endpoints were Acute Rejection (AR), Delayed Graft Function (DGF), and Graft Failure (GF). We calculated event prevalence with risk ratios for binary outcomes, along with 95% confidence intervals (CI). Statistical analysis was performed using R version 4.3.2. A random-effects model was used for all outcomes, and heterogeneity was assessed with Cochrane's Q and I2 statistics.

Results:
We included 10 retrospective cohort studies, that comprised 68,619 patients, where 33,623 (49%) were females after we disposed of major overlapping populations. We found that the overall risk of AR, DGF, and GF to be respectively (RR 0.93; 95% CI: 0.88 to 0.98; p<0.01; Figure 1), (RR 1.36; 95% CI: 0.98 to 1.90; p=0.07; Figure 2) and (RR 0.93; 95% CI: 0.84 to 1.03; p=0.16; Figure 3). The subgroup of stage 3 AKI showed an increase in the risk of DGF (RR 1.68; 95% CI: 1.28 to 2.19; p<0.01; Figure 2) for these donors.

Conclusion:
In our Meta-analysis, we found that there’s no difference in the outcomes between AKI and non-AKI deceased donors. However, there is an increase in the risk of DGF in organs from deceased donors with stage 3 AKI. More studies are warranted to assess these results.
Abstract 4146242: Superiority of Ultrahigh-Resolution Photon-Counting Computed Tomography in Follow-up In-Stent Restenosis
Authors: Nguyen Duc Chinh , Tran Cuong , Ngo Minh Tuan , Bui Bich , Nguyen Duong Quoc Anh , Dang Hoang Tuyen , Ngo Khiem , Vu Loc , Ho Dung , Nguyen Thach
Published: November 2024

Background:
In 2021, the Food and Drug Administration approved the first Photon Counting Computed Tomography (PCCT) system, marking an extraordinary milestone in medical imaging. This advanced technology offers significant advantages in cardiac imaging, particularly in detecting severe calcification lesions and in-stent restenosis (ISR). Subsequently, in October 2023, our hospital became the first to implement a PCCT system. Leveraging the benefits of PCCT, we conducted a study to investigate ISR in patients who had undergone stenting over the course of a year.

Methods:
From October 2023 to January 2024, all high-risk stented patients, including those with multiple stents, bifurcation lesions, chronic total occlusions, and severe calcification lesions, were included in the study. The PCCT system (tube voltage 120 kV, collimation 120 x 0.2 mm, 50-70 ml Iohexol 300 mg/ml) was utilized to detect ISR. Intra-stent lesions with more than 50% narrowing were classified as ISR. Additionally, the quality of the PCCT images was assessed by two radiology experts using a five-point scale, where 1 indicated excellent quality (absence of artifacts) and 5 indicated non-diagnostic quality (severe artifacts).

Results:
Eighty patients (77.5% male) met the inclusion criteria, with a mean age of 64.7 ± 10.9 years. Among these patients, 56 had stents in the Left Anterior Descending (LAD) artery, while 27 and 34 had stents in the Left Circumflex Artery (LCx) and Right Coronary Artery (RCA), respectively. In total, 25 patients (31.2%) were identified with ISR. Specifically, ISR was most prevalent in the LCx at 25.9% (7/27), followed by the LAD at 21.4% (12/56), and the RCA at 17.7% (6/34). Nine patients underwent repeat percutaneous coronary intervention (PCI). The overall image quality was rated as excellent, with a median score of 1.5 [IQR, 1-2]. Additionally, 40 patients (50%) had a calcium score over 400.

Conclusion:
These findings represent the first results obtained using PCCT at our hospital. The results indicated a relatively high rate of ISR, particularly among high-risk patients. Given the excellent image quality, PCCT is a promising technique for the follow-up of patients post-PCI.
Abstract 4146244: Late Gadolinium Enhancement-Derived Heart Digital Twins Non-Invasively Predict Ventricular Tachycardia Risk in Duchenne Muscular Dystrophy
Authors: Tso Justin , Prakosa Adityo , Zhang Kelly , Kholmovski Eugene , Vasquez Nestor , Yanek Lisa , Beckman Brian , Bibat Genila , Yep Mary , Dellefave-Castillo Lisa , Villa Chet , Kertesz Naomi , McNally Elizabeth , Wagner Kathryn , Calkins Hugh , Leung Doris , Cripe Linda , Barth Andreas , Trayanova Natalia
Published: November 2024

Introduction:
Patients with Duchenne muscular dystrophy (DMD) universally develop dilated cardiomyopathy. Characteristic left ventricular (LV) fibrosis and decreased LV systolic function can increase the likelihood of fatal ventricular arrhythmias (VA). However, the benefits of ICD therapy in DMD remain uncertain, and there are no established VA risk stratification methods to guide clinical decision making. Here, we developed a digital twin approach that uses standard-of-care late-gadolinium enhanced cardiac magnetic resonance (LGE CMR) imaging alone to non-invasively screen for VA risk in DMD.

Methods:
Thirty-nine DMD patients from three centers with LGE CMR and Ziopatch monitoring were included, with fast nonsustained VT (NSVT; >170 BPM) as the primary clinical outcome (positive control). From short-axis 2D LGE CMR, we constructed 3D computational models of the LV with patient-specific fibrosis distribution (Fig A). These models were separated into positive and negative groups by performing unsupervised clustering on regional substrate percentages (Fig B). DMD-specific EP properties were then assigned to the 3D models, and a rapid pacing protocol was used to assess in silico VT inducibility (Fig C). Patients were predicted to have VA if they tested positive with both clustering and simulation methods. Tests were performed blinded to clinical outcome, cohort positivity rate, and covariates such as ejection fraction.

Results:
Five patients were observed to have fast NSVT. Our approach achieved 80% (4/5) sensitivity, 79.4% (27/34) specificity, and 79.5% (31/39) accuracy in predicting these events. The sole false negative patient had lower LGE CMR resolution relative to the rest of the cohort (p < 0.01). While extensive LGE was present in all patients, the positive cluster showed higher inferolateral, apical, and total fibrosis burden (p < 0.01) compared to the negative cluster. Without using simulation, specificity and accuracy decreased to 58.8% and 64.1%.

Conclusion:
LGE-derived digital twin models show strong potential for screening for VA risk in DMD patients. Future application of these models may help define optimal indications for ICD implantation in DMD.
Abstract 4146267: Causal Relationship of Obesity with Chronic Kidney Disease and Diabetic Nephropathy: A Meta-Analysis of Mendelian Randomization Studies
Authors: Doshi Kesha , Doshi Preet , Pasnoor Diksha Sanjana , Brereton Brian , Mettela Sambasiva Rao , Konakanchi Vijaya Rupa , KALAPALA CHAITANYA , Cheruvu Naga Pratyusha , Prajapati Kesar , Desai Rupak
Published: November 2024

Background:
Despite there being a significant association between obesity and chronic kidney disease (CKD) there is a paucity of evidence on the causal role of obesity in the development of CKD. Hence, this meta-analysis aims to elucidate a causal relationship between body mass index (BMI) and the risks of CKD and diabetic nephropathy (DN) using Mendelian randomization studies.

Method:
We searched PubMed/Medline and Google Scholar for the Mendelian Randomization studies evaluating the association of BMI with the occurrence of CKD/renal failure and DN until May 2024. The inverse-variance weighted method was employed for the meta-analysis. The random effects models and I2 statistics were used for pooled odds ratio (OR) and heterogeneity assessment. Leave-one-out sensitivity analyses were also performed to assess the robustness of the findings

Result:
Our search rendered a total of 81 studies which were screened thoroughly. From those, 8 studies, all with a unique instrumental variable database were selected. Out of these 6 studies consisted of cases from European Ancestry and remaining 2 from east asian ancestry. According to our meta-analysis, increased genetically predicted BMI was significantly associated with increased risk of CKD (OR 1.40, 95 % CI: 1.26-1.55, I2= 66.74 %, P < 0.02) and DN (OR 2.00, 95 % CI: 1.15-3.50, I2= 87.15 %, P<0.01). In addition, leave-one-out sensitivity analysis showed that the effect size did not change substantially by removal of any particular study in MR studies.

Conclusion:
The meta-analysis provides robust evidence supporting a causal relationship between higher BMI and increased risks of CKD and DN. These findings underscore the importance of managing BMI as a modifiable risk factor to mitigate the risk of developing CKD and DN. Further studies should explore the underlying mechanisms and evaluate the impact of BMI management on the progression of CKD and DN.
Abstract 4146282: Safety and efficacy of the bioactive titanium-nitric-oxide coated stent in contrast to everolimus-eluting stents (EES) among patients diagnosed with ACS: An updated meta-analysis.
Authors: Abdelaziz Ahmed , Desouki Mariam , Ramadan Shrouk , Elaraby Ahmed , Mohamed Ahmed , Afify Raneem , Nasr Ahmed , Ali Ahmed Hamdy G. , Arian Roua , Banour Sandi , Abdelazeem Basel
Published: November 2024

Introduction:
Drug-eluting stents (DES) have effectively decreased the incidence of restenosis; however, recent investigations raised the potential for late stent thrombosis (LST). Bioactive stent (BAS) coated with titanium-nitride-oxide has demonstrated favourable outcomes with conflicting results in individuals with acute coronary syndromes. We aimed to outline the comparison of BAS and EES among patients diagnosed with acute coronary syndrome (ACS).

Methods:
We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until February 2024. We included randomised controlled trials (RCTs) and observational studies comparing bioactive titanium-nitric-oxide coated stent stents versus EES stents. The primary outcome was MACE, while secondary outcomes were MI, Cardiac death, All-Cause Death, definite stent thrombosis, and Minimal lumen diameter. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data.

Results:
Seven RCTs involving 3101 patients were included in the analysis. BAS coated was associated with a reduction in definite stent thrombosis (OR= 0.35, 95% CI [ 0.16 to 0.77], P=0.009), MI (OR= 0.47, 95% CI [ 0.34 to 0.64], P=<0.001), and minimal lumen diameter (MD= -0.22, 95% CI [ -0.35 to -0.10], P=0.0004). However, there was no significant difference in terms of MACE, all-cause mortality, or cardiac mortality between the two studied approaches.

Conclusion:
BAS showed a reduction in definite stent thrombosis, MI, and minimal lumen diameter, with no significant difference in other reported outcomes. This opens the door for large-volume RCTs to validate the current findings.
Abstract 4146283: Infrequent Cognitive Assessments in CABG Trials (from 2005-2023) Highlight Need for Improved Strategies for Cognitive Screening post-coronary bypass grafting (CABG) surgery
Authors: Srivatsa Shantanu , Sujanthan Sajeevan , Ninode Rivera Stephanie , Masterson Creber Ruth , Swartz Richard
Published: November 2024

Objective:
The incidence of cognitive decline following coronary artery bypass grafting (CABG) is well-documented, significantly impacting patient morbidity, mortality, and quality of life. We conducted a systematic review that examines cognitive outcomes in CABG randomized controlled trials (RCTs) to identify which cognitive assessments were used, their administration frequency, attrition rates, and their effectiveness in detecting perioperative cognitive changes in control groups.

Methods:
We conducted a search of MEDLINE, EMBASE, Cochrane Library, and PsycINFO for CABG RCTs that included cognitive assessments, from January 2005 to December 2023. Descriptive statistics were used to summarize the frequency, domains, and attrition rates of each cognitive task. For tasks assessed both pre- and post-operatively in at least three RCTs, control group scores and standard deviations were reported.

Results:
Out of 3337 screened studies, 2163 were CABG RCTs, and only 69 (3.2%) included cognitive evaluations (Figure 1). These trials involved 15,839 subjects (79% male, mean age 64.4, median follow-up time 90 days) and used 145 unique cognitive tasks. The Trailmaking Test Part B (40/69; 58.0%) and Part A (38/69; 55.0%) were the most frequently used. Only 7 tasks had means and standard deviations reported before and after surgery in more than three RCTs, and none detected significant pre- to post-operative changes. Attrition rates averaged 19.3%, with a wide range from 0% to 62%. Figure 2 demonstrates the decline in cognitive assessments in CABG trials over the years, with a sharp decline after 2014. Trials that assessed cogntion after 2014 tended to favor screening tasks (MMSE/MoCA) alone.

Conclusion:
Cognitive assessments are infrequent in CABG trials, and existing tests fail to consistently detect cognitive changes. To effectively evaluate and address cognitive impact after CABG, new assessment strategies that are resilient to attrition and practical for use in diverse trial settings are needed.
Abstract 4146286: Embolization of an Amplatzer Amulet Through a MitraClip Causing Torsades and LVOT Obstruction: A Case Report
Authors: Davis Clayton , Giacomino Bria
Published: November 2024

Introduction:
The morphology and blood stasis of the left atrial appendage (LAA) in tandem with disorganized conduction in atrial fibrillation (AF) creates favorable conditions for thrombus formation. Left atrial appendage occlusion (LAAO) devices have become increasingly utilized for stroke prevention in select patients with AF who have contraindications to oral anticoagulation (OAC). We present a unique case of an embolized Amplatzer Amulet LAAO device through a MitraClip into the LV causing polymorphic VT and obstructive shock.

Case Presentation:
An 80-year-old man with AF and mitral valve prolapse status post MitraClip presented to the hospital for difficulty breathing and palpitations two days after implantation of a 31mm Amplatzer Amulet LAAO device. Notably, he underwent failed attempt at Watchman LAAO implantation due to peridevice leak one year prior. On arrival, he was hypotensive with numerous episodes of polymorphic VT, requiring cardioversion, vasopressors, and mechanical ventilation. TTE located the Amulet within the LV outflow tract (LVOT) creating LVOT obstruction and revealed single-leaflet attachment of the MitraClip. He was evaluated for device retrieval and mechanical support but was deemed not a surgical candidate due to severe thrombocytopenia and guarded prognosis. Despite ongoing resuscitative efforts, the patient became increasingly unstable and died in the cardiac ICU.

Discussion:
In patients who are unable to tolerate OAC, occlusion of the LAA for stroke prevention has garnered growing interest; however, these devices are not without complication and do not guarantee full occlusion of the LAA. Despite our patient’s history of failing Watchman deployment, he was discharged on the same day after implant of the Amulet device without post-procedure TTE. We postulate that the Amulet device dislodged shortly after deployment and was held within the left atrium by the MitraClip until detachment, allowing for device embolization and severe MR. To our knowledge this is the first documented instance of Amulet device migration into the LV in a patient with a MitraClip. This case highlights the need for heightened post-procedure monitoring, surveillance, and imaging in select patients.
Abstract 4146347: Oxidative Stress Lipids Associate with Mood Disturbance Symptoms and Quality of Life in Acute Ischemic Stroke Patients
Authors: Martha Sarah , Pen Alice , McGuire Laura , Alaraj Ali , Testai Fernando , Thompson Hilaire
Published: November 2024

Background:
Acute ischemic stroke (AIS) is a leading cause of mortality and disability globally, disproportionately affecting Black and Latinx populations who experience increased morbidity and mortality compared to their white counterparts. At one month, roughly 50% of AIS survivors experience mood disturbances (e.g., anger, irritability, and aggression) and exhibit a lower health-related quality of life (HRQOL) compared to pre-AIS levels. Downstream biomarkers of mitochondrial dysfunction such as oxidative stress may be important pathophysiological mechanisms underlying mood disturbance symptoms, stroke severity, and long-term functional recovery.

Purpose:
To examine associations among early and late peripheral plasma lipid levels, mood disturbance symptoms (e.g., anger, irritability), and HRQOL outcome over 3 months (baseline/study day 5, and months 1, 3) in persons following AIS.

Methods:
The pilot study is a non-probability, convenience sample of adult subjects (> 18 years of age) with a diagnosis of AIS. Lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS) of untargeted lipids. The Agilent 6545 LC/Q-TOF platform was used to determine the absolute concentration of lipid species from peripheral plasma samples collected days 1, 3, 5 and months 1 and 3 post-AIS. General linear mixed models were used to test the predictive association of lipidomic biomarker mean value of peripheral plasma lipid levels and symptoms and outcomes over time (baseline and months 1 and 3).

Results:
We analyzed 82 subjects (age = 64 ± 12.1, 52% male, 78% Black, and 94% with hypertension). Elevated oxidative stress biomarkers (e.g., lipoxygenases, arachidonic acid, glycosylphosphatidylinositol) were associated with higher severity of anger and irritability symptoms, and a poorer HRQOL from baseline to 1- and 3-months post-AIS (p=0.04).

Conclusion:
An untargeted LC-MS lipidomics approach was used to identify lipids following AIS. Because oxidative stress plays a key regulatory role in complex downstream cellular function, these findings may be of great significance in understanding AIS pathophysiology that has the potential to inform personalized preventive strategies.
Abstract 4146386: The Effect of Pioglitazone on Rate of Atrial Fibrillation in Patients with Diabetes Mellitus and Stable Coronary Artery Disease
Authors: Abraham Andrew , Noureldine Hussein , Alqudah Qusai , Mojadeddi Sanaullah , tong ann
Published: November 2024

Introduction:
Atrial fibrillation (AF) and coronary artery disease (CAD) has a strong association. Diabetes Mellitus (DM) is also a known risk factor for the development of AF and the severity of DM is almost directly correlated with worsening AF burden. Thiazolidinediones (TZDs) are a treatment option in DM that have been found to decrease risk of developing AF in certain populations.

Hypothesis:
We hypothesized that the use of pioglitazone in patients with DM and stable CAD decreases the odds of developing AF and development of rapid ventricular response (RVR) in patients with AF.

Methods:
We identified adult patients presenting to any Hospital Corporation of America (HCA) facility within the North Florida division with a diagnosis of Type II DM and stable CAD between 01/01/2021 and 12/31/2022 (N=38,151). A cohort of patients with documented pioglitazone usage (N=1,055) compared AF rates against those with no documented pioglitazone usage using a Chi-Square Test of Proportions. We also examined a cohort of patients with documented pioglitazone usage (N=197) who had diagnosed AF with RVR against those no documented pioglitazone usage using a Chi-Square Test of Proportions. In addition, multiple covariates that contribute to the development of AF and AF with RVR were evaluated using Logistic Regression with Firth’s Penalized Likelihood.

Results:
We find evidence that pioglitazone usage is associated with 0.846 lower odds of developing AF (95% CI 0.719-0.991, p<0.038). However, within patients with established AF, pioglitazone use is not associated with decreased odds of developing RVR. Odds of AF and AF with RVR increase if the patient is diagnosed with chronic kidney disease, obstructive sleep apnea, cirrhosis, and alcohol use disorders, regardless of pioglitazone usage.

Conclusion:
Based on the results of this study, use of pioglitazone was associated with decreased odds of developing atrial fibrillation. However, when we control for various factors, we do not see a difference in rates of developing RVR in patients with AF taking pioglitazone versus those not taking pioglitazone. Further research is needed to establish if there is a synergistic role to other anti-diabetic medications that lower risk of AF.
Abstract 4146391: Multinational Validation of Fully Automated Diagnostic Reports using Artificial Intelligence-enabled Application for ECG Images
Authors: Khunte Akshay , Sangha Veer , Oikonomou Evangelos , Dhingra Lovedeep , Aminorroaya Arya , Coppi Andreas , Vasisht Shankar Sumukh , Mortazavi Bobak , Bhatt Deepak , Krumholz Harlan , Nadkarni Girish , Vaid Akhil , Khera Rohan
Published: November 2024

Background:
Accurate ECG interpretation is critical for triaging, diagnosis, and managing patients with cardiovascular conditions. Current computerized methods have limited accuracy and are often proprietary algorithms based on raw signal data. We sought to evaluate ECG-GPT, a novel vision-text transformer model capable of generating free-text diagnosis statements from images of ECGs.

Methods:
ECG-GPT was developed with 3 million ECGs at Yale and validated in 2 large and geographically distinct populations: (1) 1.4 million ECG images with diagnosis statements from Mount Sinai Health System (MSHS), NY, and (2) 45,389 ECG images with 6 diagnostic labels from UK Biobank (UKB). We employed 2 metrics: (A) a rule-based approach to evaluate diagnostic accuracy for 19 rhythm and conduction disorders on MSHS ECGs and 6 key conditions on UKB ECGs, and (B) semantic similarity (similar meaning) using a fine-tuned DistilBERT model. Using semantic similarity methods, we assessed the quality of generated text across the full range of ECG diagnoses by computing similarity both for all model-generated and reference statements and for subsets specific to ECGs flagged for each of the 19 extracted conditions. To establish baseline similarities, we also computed semantic similarities between random combinations of model-generated and reference statements within each of these sets.

Results:
The model performed well across multiple key labels, spanning rhythm and conduction disorders, including an AUROC of 0.92 for atrial fibrillation, 0.95 for left bundle branch block, and 0.90 for atrioventricular block (Table A). More importantly, in addition to the labels, ECG-GPT identified the full context of the diagnosis statements with allied conditions. It had a median pairwise cosine similarity of 0.86 (IQR 0.78-0.94), significantly greater than the median baseline similarity of 0.73 (IQR 0.66-0.79, p<0.001) (Table B). This separation between median pairwise and baseline similarity remained consistent across all 19 condition-specific subsets. Results were comparable in the UKB dataset, with AUROCs of 0.95, 0.92, and 0.95 for AF, ST, and SB, and AUROCs of 0.99, 0.99, and 0.95 for LBBB, RBBB, and AVb (Table C).

Conclusion:
Our model represents a scalable and accessible strategy for generating accurate, expert-level reports from photos of ECGs, validated across large, multinational datasets using both individual diagnostic labels and the comprehensiveness of the diagnostic statement.
Abstract 4146398: Single-Nucleus Transcriptome Profiling Identifies Phenotypic Shift in Pulmonary Vascular Endothelial Subpopulations in Pulmonary Arterial Hypertension
Authors: Dai Jingbo
Published: November 2024

Rationale:
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive rise in pulmonary vascular resistance and occlusive vascular remodeling, leading to right heart failure and premature death. Endothelial cell (EC) damage and dysfunction is a key feature of pulmonary vascular remodeling and PAH. However, the understanding of how different EC subpopulations contribute to this process is limited.

Methods:
We utilized single-nucleus RNA sequencing (snRNAseq) to provide transcriptome insights into cellular composition changes within idiopathic PAH (IPAH) and donor lungs. Principal component analysis (PCA) for dimensional reduction was performed based on the variable genes previously identified and cells are clustered using uniform manifold approximation and projection for dimensions reduction (UMAP) algorithm. Differentially expressed gene (DEG) analysis and cell pseudotime trajectory analysis were performed to identify biological pathway changes and differentiation states of EC subpopulations.

Results:
Our data revealed 4 distinct EC subsets in human lungs: general capillary EC (gCap), alveolar specific capillary EC (aCap), pulmonary venous EC (PVEC), and pulmonary arterial EC (PAEC). The EC proportion in the whole lung diminished markedly in IPAH patients. Differentially expressed gene (DEG) analysis led to identification of IPAH-related biological process in different EC subsets including aberrant vasoconstriction and cell autophagy in PAEC. The function of aCap in IPAH lungs was skewed from a pro-gas/substance exchange to a pro-inflammation state. Transcriptionally distinct gCap subpopulations were enriched in specific biological processes and could be distinguished into 3 major clusters: angiogenic gCap, inflammatory gCap, and quiescent gCap. Moreover, we identified a skewed cellular distribution from the angiogenic gCap to inflammatory gCap in IPAH lungs.

Conclusions:
The current study complements efforts to establish a lung cellular atlas and provides a blueprint of molecular/cellular changes associated with EC dysfunction in IPAH at single-nucleus level. EC dysfunction in the pathogenesis of IPAH is centered on EC phenotypic shift and skewed intercellular signaling pattern. Thus, targeting the genes that underlying the EC identity shift and dedifferentiation process may serve as a novel therapeutic strategy to reverse pulmonary vascular remodeling in PAH.
Abstract 4146421: Efficacy of Atrial Shunt Devices in Heart Failure with Preserved Ejection Fraction: A Systematic review and Meta-analysis of randomized trials.
Authors: Prata Alonzo , Katsuyama Eric , Scardini Pedro Gabriel , Coan Ana Carolina , Fukunaga Christian , Fernandes Julia , Falco Neto Wilson , Petri Santos Pinheiro Rafael , Andrade Naieli , Gioli-Pereira Luciana
Published: November 2024

Background:
The potential benefit of an iatrogenic interatrial shunt in heart failure (HF) is based on observations wherein decompression of the pressure-overloaded left atrium appears beneficial. Consequently, devices designed to mimic this effect have been developed. However, their effectiveness remains controversial.

Methods:
We searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) comparing the use of atrial shunt devices (ASD) versus standard therapy in patients with heart failure with preserved ejection fraction (HFpEF). The outcomes of interest were: (1) quality of life assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and (2) HF events after ASD intervention. Heterogeneity was examined with I2 statistics. Statistical analysis was performed using R Studio 4.3.2.

Results:
A total of 3 RCTs were included, encompassing 966 patients, of whom 479 (49.5%) were in the ASD group. Most of the participants were female (53%), had a three or higher NYHA class(92%), with a mean age of 72.5 years and a mean follow-up of 1.2 years. In the pooled analysis, there was no difference between groups in improvement of KCCQ (MD 0.65; 95% CI −2.22,3.52; p=0.66;I2=0%; Fig 1) and HF events (RR 1.06; 95% CI 0.81,1.39; p=0.68;I2=0%; Fig 2).

Conclusion:
In this meta-analysis of patients with HFpEF, ASD therapy was not associated with improvements in quality of life and HF events.
Abstract 4146447: Deficiency of Mitochondrial Serine Hydroxymethyltransferase Impairs Endothelial Cell Phenotype and Function
Authors: Geng Xiaoxiao , Wei Yuhua , Zhang Jianyi , Ye Lei
Published: November 2024

Introduction:
Our previous study showed that endothelial cells (ECs), differentiated from human induced pluripotent stem cells (hiPSCs) derived from patients with type 2 diabetes (dia-hiPSCs), displayed impaired phenotypes and function, including lower intracellular glycine content, increased senescence and inflammation, and impaired mitochondrial function. Furthermore, of the four molecules that regulate glycine homeostasis (glycine transporter 1 and 2 and the cytoplasmic and mitochondrial serine hydroxymethyltransferases [cSHMT and mSHMT, respectively]), only mSHMT was downregulated in dia-hiPSCs derived ECs (dia-hiPSC-ECs). Thus, we aim to determine whether deficiency of mSHMT protein expression will impair EC phenotype and function due to increased oxidative stress.

Methods:
hiPSCs reprogrammed from the cells of healthy human subjects (nor-hiPSCs) were differentiated into ECs (nor-hiPSC-ECs), and transduced with adenoviral vectors carrying shRNA targeting mSHMT (Ad-shRNA/mSHMT) or Scramble (Ad-Scramble) for 48 hours, and cultured in endothelial growth medium for 14 days. Intracellular glycine content and ROS were measured by liquid chromatography and MitoSOX, respectively, cell senescence was assessed by β-galactosidase staining, mitochondrial membrane potential was visualized using JC-1 dye, and expression of intercellular adhesion molecule-1
(ICAM-1, an indicator of inflammation) protein was evaluated via Western blot.

Results:
Ad-shRNA/mSHMT starting 25 infectious unit/EC dramatically inhibited mSHMT protein expression, which was accompanied with significantly reduced glycine content in nor-hiPSC-ECs. Compared to Ad-scramble transduced nor-hiPSC-ECs, down-regulation of mSHMT, caused by Ad-shRNA-mSHMT, resulted in significant increase of senescence (increased abundance of β-gal and P53 expression) and inflammation (increased ICAM-1 protein expression), and significant decline in mitochondrial membrane potential (reduced red fluorescence intensity) in nor-hiPSC-ECs. Although low intracellular cellular glycine level can lead to oxidative stress as it is required for glutathione synthesis, increased oxidative stress, by MitoSOX labeling, was not found in nor-hiPSC-ECs with mSHMT knockdown.

Conclusion:
Deficiency of mSHMT impairs nor-hiPSC-EC phenotype and function, which is independent of oxidative stress.
Abstract 4146453: Efficacy of Bilateral Cardiac Sympathetic Denervation in Treating Different Etiologies of Nonischemic Cardiomyopathy: A Subset Analysis
Authors: Ghazal Rachad , Chelikam Nikhila , Katapadi Aashish , Ahmed Adnan , Bawa Danish , Darden Douglas , Gopinathannair Rakesh , Pothineni Naga Venkata , Kabra Rajesh , romeya ahmed , Atkins Donita , Lakkireddy Dhanunjaya
Published: November 2024

Background:
Bilateral cardiac sympathetic denervation (BCSD) has shown promise in treating patients with nonischemic cardiomyopathy (NICM) suffering from refractory multifocal premature ventricular contractions (PVCs) and ventricular tachycardia (VT). Despite its growing use, the effectiveness of BCSD across different NICM etiologies has not been extensively studied.

Research Question:
How effective is BCSD across a variety of NICM etiologies?

Goals:
To evaluate the effectiveness of BCSD on left ventricular ejection fraction (LVEF) and PVC burden in patients with NICM.

Methods:
We conducted a subset analysis on a previous retrospective, observational study of NICM patients who underwent BCSD. Eight NICM etiologies were assessed.

Results:
43 NICM patients underwent BCSD (mean age 52.3±14.7 years; 30% females). Overall, LVEF significantly improved (38.7±7.9% to 46.2±9.6%,
p
<0.001), and PVC burden (PVCb) significantly decreased (23.7±9.9% to 1.3±1%,
p
<0.001). A similar phenomenon was seen in idiopathic/dilated cardiomyopathy (CM) (LVEF: +8.7%,
p
<0.001; PVCb: -20.6%,
p
<0.001), post-viral CM (LVEF: +4.8%,
p
=0.2; PVCb: -24.2%,
p
<0.001), familial CM (LVEF: +10%; PVCb: +23.3%), giant cell CM (LVEF: +10%; PVCb: + 30.5%), and arrhythmogenic right ventricular CM (LVEF: +12.5%, p=0.09; PVCb -30.6%,
p
=0.001). Catecholaminergic polymorphic VT had a non-significant increase in LVEF (+5%, p=0.5) but a significant decrease in PVCb (-21.8%, p=0.02), whereas sarcoidosis had the opposite effect with significant increase in LVEF (LVEF: +13.4%, p=0.3) but non-significant decrease in PVCb (-16.1%, p=0.02). Lastly, hypertrophic CM remained unchanged in LVEF (30%) but PVCb decreased (-8%).

Conclusion:
BCSD demonstrates efficacy in improving LVEF and reducing PVCb across almost all NICM with refractory VT. However, a case-by-case evaluation is still needed for its use.
Abstract 4146454: Managing Depression in Rural Depressed Cardiac Patients in the Face of Perceived Depression Stigma: A Randomized Controlled Trial of Two Types of Online Cognitive Behavioral Therapy
Authors: Moser Debra , Wu Jia-Rong , Latimer Abigail , Kang JungHee , Lin Chin-Yen , Chung Misook
Published: November 2024

Introduction:
Rural areas experience marked disparities in cardiac and mental health and access to health care. Rural cardiac patients with depressive symptoms (DS) do not receive needed therapy because of lack of mental health providers, worries about stigma, and difficulty accessing mental health care. Cognitive behavioral therapy (CBT) reduces DS in cardiac patients, but in its traditional form (in-person meetings) is inaccessible to most rural patients. Wireless internet technology has the potential to make CBT more accessible.

Hypothesis:
Our aim was to determine whether patient perceptions of stigma would moderate the impact on DS of two types of remote-delivery CBT: 1) real-time, face-to-face, video-conferenced CBT with a therapist (vcCBT); and 2) self-administered internet-based CBT without a therapist (iCBT). We hypothesized that patients with high perceptions of stigma would have a better response to iCBT than vcCBT, but that both would be effective in patients with lower perceptions of stigma.

Methods:
In this randomized controlled trial (N = 303, mean age 58 ± 12 years, 49% women) rural cardiac patients who had at least mild-moderate DS underwent 6-8 weeks of CBT delivered as either vcCBT or iCBT. DS were measured using the Patient Health Questionnare-9. Stigma was measured using the Depression Stigma Scale. Data were collected at baseline, 3, 6 and 12 months. Data were analyzed using mixed models for repeated measures.

Results:
Patients in the vcCBT compared to the iCBT group had similar levels of DS at baseline (11.2±5 vs 11.3±5, p=0.45; respectively). Patients with higher levels of perceived stigma had worse DS compared to those with lower levels of stigma (10.6±5 vs 11.9±5, p=0.018; respectively). Both intervention groups experienced statistically and clinically significant improvements in DS (Figure), with DS decreasing from moderate levels to non-depressed at 3 months (p<0.001), which was maintained at 12 months. Perceived stigma did not moderate the impact of the intervention, rather, patients with higher levels of perceived stigma demonstrated a lesser response to either intervention.

Conclusion:
Both types of intervention were effective at managing DS, however, contrary to our hypothesis, high levels of stigma alone rendered patients less responsive to either intervention. Nonetheless, all patients regardless of intervention type of level of stigma experienced meaningful reductions in DS.
Abstract 4146456: Biased Activation of RXFP1 signaling via ML290 Attenuates Experimental Pulmonary Hypertension
Authors: Sangam Shreya , Triantafyllou Georgios , Pham Uyen , Troncone Luca , Yung Lai-Ming , Chundi Anand , Darbha Srikrishna , Gipson Gregory , Rajesh Shreyas , Brackin Riley , Zeghibe Ana , Shin Elizabeth , Agoulnik Irina , Marugan Juan , Agoulnik Alexander , Rajagopal Sudarshan , Yu Paul
Published: November 2024

Background:
Dysregulated smooth muscle cell (SMC) hypertrophy and proliferation contribute to vascular remodeling in pulmonary arterial hypertension (PAH). Relaxin-2 (RLN2), a peptide hormone known to exert potent vasodilator, anti-fibrotic, anti-apoptotic, and anti-inflammatory effects in diverse myogenic lineages, signals via G-protein coupled receptor (GPCR) Relaxin Family Peptide Receptor 1 (RXFP1). Therapeutic use of RLN2 has been limited by its short half-life and need for parenteral administration. ML290, an orally bioavailable small molecule allosteric agonist of human RXFP1, exhibits properties of biased GPCR signaling compared to RLN2.

Hypothesis:
Biased modulation of relaxin-RXFP1 signaling via ML290 attenuates experimental PH.

Methods and Results:
RXFP1 expression was upregulated in the smooth muscle layer of lung sections from patients with PAH compared to controls. In human pulmonary artery SMCs (HPASMCs), RLN2 (100 ng/mL) and ML290 (10 mM) inhibited TGFβ-SMAD2/3 signaling, and inhibited myofibrogenic differentiation of HPASMCs, blocking TGFβ-mediated expression of αSMA, Calponin, Caldesmon, fibronectin and type 1 Collagen. Both RLN2 and ML290 inhibited serum-induced and PDGF-BB-induced migration of HPASMCs. TRUPATH BRET assays performed in HEK cells revealed ML290 to be less potent in activating Gαi3, GαoB, and GαS than RLN2, and that ML290 elicted partial cAMP and cGMP responses. In contrast to RLN2, ML290 did not recruit β-arrestin 1 and had diminished activation of β-arrestin 2. Continuous infusion of RLN2 did not improve experimental PH in several rodent models. In contrast, ML290 (10 mg/kg daily oral gavage) attenuated right ventricular systolic pressure, RV hypertrophy and muscularization in humanized
RXFP1
knock-in (
hRXFP1
KI/KI
) mice exposed to Sugen-hypoxia (SuHx). but not in WT or
Rxfp1
-/-
mice, demonstrating specificity for human RXFP1.

Conclusions:
ML290 exhibits biased GPCR-mediated signaling of RXFP1 in comparison to the native ligand RLN2. ML290 potently inhibits TGFb-mediated plasticity of vascular SMCs, and demonstrates efficacy in experimental PH in RXFP1 KI mice. The efficacy of ML290 in contrast to RLN2 in experimental PH may be related to its biased signaling, pharmacokinetics, or pharmacodynamics.
Abstract 4146466: Targeting Gut Microbiota-Derived Kynurenine to Predict and Protect the Remodeling of the Pressure Overloaded Young Heart
Authors: He Xiaomin
Published: November 2024

Background:
Without timely intervention, pressure-overloading left ventricular (poLV) remodeling may become progressive and readily degenerate into heart failure. The relative risk is especially high in children with congenital heart disease who are awaiting surgical correction.

Aims:
The aims of this study were to identify a plasma metabolite that is clinically and mechanically linked to poLV remodeling and heart failure in children and investigate a safe, efficacious treatment that blocks its action.

Methods:
We used multi-omics including untargeted metabolomics on the plasma of poLV children and neonatal ascending aorta constriction (nAAC) mice, whole-transcriptome resequencing and single-nucleus RNA sequencing of mouse and human LV samples, and metagenomics analysis of mouse gut microbiota to disclose the gut microbiota-kynurenine (Kyn)-remodeling axis. Aryl hydrocarbon receptor (AHR) knockout mice and germ-free (GF) mice as well as fecal microbiota transplantation were used to clarify its mechanism.

Results:
Abnormally elevated plasma kynurenine (Kyn) was detected in both the patient cohort and the mouse model. Plasma Kyn levels were clinically associated with the cardiac functions and the degree of remodeling. Excessive Kyn induced the hypertrophy and fibrosis phenotypes both in vitro and in vivo, which was blocked by AHR inhibitors and by AHR knockout, respectively. It was demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by promoting AHR nuclear translocation, initiating ADAMTS2 transcription which accelerates hypertrophy, and inducing FN1 and COL1A1 which exacerbate fibrosis. There were significant alterations in the gut microbiota of nAAC mice.Transplantation of nAAC mouse feces to GF mice augmented their Kyn level, indicating the existence of a gut microbiota-Kyn relationship. Oral probiotic supplementation reconstructed the gut microbiota in the nAAC mice, modulated the Kyn-AHR axis, and alleviated poLV remodeling.

Conclusions:
Plasma Kyn levels were strongly correlated with cardiac remodeling and function in pediatric patients and mice with poLV. Kyn is a pathological signal from an altered gut microbiota to activates AHR and its gene targets in poLV remodeling heart, promoting hypertrophy and fibrosis in respective cells. Oral probiotics reshaped the gut microbiota, lowered Kyn levels, and showed great potential at delaying cardiac remodeling and preventing heart failure.
Abstract 4146476: Clinical and CT morphological features versus CT texture analysis in identification of primary pulmonary artery sarcoma and central pulmonary embolism
Authors: Wang Jingxi , Liu Chenyue
Published: November 2024

Research Queation:
To evaluate clinical and CT morphological features versus CT texture analysis in differentiating primary pulmonary artery sarcoma (PAS) and central pulmonary embolism (PE).

Methods:
23 pathology-proven primary PAS patients and 54 pathology-proven central PE patients from September 2013 to September 2023 were continuously enrolled. Clinical features and qualitative CT pulmonary artery (CTPA) morphological features were retrospectively collected. The chi-square tests or Mann–Whitney U test was applied to find the significant features. Then the discriminative features were identified by univariate logistic analysis. The CTPA texture features were extracted using a radiomics software (Radiomics, Syngo.Via FRONTIER, version 1.4.0; Siemens). Minimum redundancy and maximum relevance (MRMR) method was used to select significant texture features. A clinical model and a texture model for distinguishing primary PAS from central PE were built using multivariate logistic regression. The performance of two models was assessed using the area under the curve (AUC).

Results:
10 from 1226 texture features selected by MRMR showed good performance in discriminating between the two groups (AUC > 0.80), of which 5 were chosen to build the texture model using multivariate logistic regression. These features were wavelet_LLL_glrlm_ShortRunHighGrayLevelEmphasis, wavelet_LHH_glszm_LargeAreaEmphasis, exponential_glszm_GrayLevelNonUniformity, original_glcm_Imc1 and wavelet_HLH_firstorder_Mean, respectively. Univariate logistic analysis was used to find 18 discriminative (p < 0.05) features, of which 4 were selected to build the clinical model using multivariate logistic regression. These features were lower limb edema, involvement of main pulmonary artery, involvement of pulmonary valve or right ventricular outflow tract and expansive growth in peripheral pulmonary artery. We evaluated these two prediction models based on CT textural features and clinical plus qualitative CTPA morphological features. These two models both showed high predictive accuracy. AUC of CT textural features model and clinical plus qualitative CTPA morphological features model were 0.97 (0.90 - 0.99) and 0.93 (0.85 - 0.98) respectively (p=0.36).

Conclusion:
We found very effective clinical and CTPA morphological features for the differential diagnosis of PAS and central PE, while CT texture analysis can additionally provide accurate, objective and quantitative diagnostic information.
Abstract 4146491: Impact of marathon running on cholesterol transfer to high-density lipoprotein in individuals with and without dyslipidemia.
Authors: Pimentel Colognese Thaiz Carolina , Freitas Fatima , RACHED FABIANA HANNA , Serrano Carlos , Kontush Anatol , Maranhao Raul , Senger Pedro , Vanalli Baroni Roberta , Lima Eduardo , Tavoni Thauany
Published: November 2024

Introduction:
Exercise training is known to improve cardiovascular risk, to increase HDL cholesterol (HDL-C) levels and HDL functionality, by improvement of cholesterol uptake by HDL, and decreases the potential atherosclerotic of low-density lipoprotein (LDL) particles. Marathon running is presumed to have the same effects, however health benefits of high volume running in dyslipidemic marathon runners are unknown.

Aims:
Using marathon runners as models for intense exercise training, this study aimed to evaluate differences in HDL composition, function and vascular reactivity between marathons runners with and without dyslipidemia, comparing with sedentary controls.

Methods:
20 marathon runners with and 13 without dyslipidemia, 17 sedentary individuals with and 12 without dyslipidemia were enrolled. In all individuals, plasma lipids and apolipoproteins (apo) were measured by commercial kits and HDL size by laser light scattering method. Paraoxonase 1 (PON1) activity using commercial kits and vascular reactivity were evaluated. Lipid transfer was performed by incubating plasma with a lipid donor nanoemulsion containing radioactively labeled non-esterified cholesterol (NEC) and esterified cholesterol (EC), followed by chemical precipitation and radioactive count. We also performed an assay that analyses the cholesterol transfer to HDL from TGRL upon lipolysis.

Results:
All individuals were male, with no age difference between groups (42 to 47 years). Marathon runners without dyslipidemia were thinner than the other groups. While HDL-C concentrations and apo A1 levels were higher in runners, LDL-C and apo B levels were higher in dyslipidemic groups. Regarding PON1 and vascular reactivity, no statistical differences were observed. We observed greater transfer of EC and NEC in the marathon runners compared to sedentary individuals (p 0.015), with no difference between marathon runners with and without dyslipidemia. Important correlations were observed between Apo A1 and all transfers: both NEC and EC, and also cholesterol transfer to HDL from triglyceride-rich lipoprotein (TGRL) upon lipolysis (p < 0.001, <0.001 and 0.011, respectively). Additionally, we observed correlation between ApoA1 and vascular reactivity (p=0.032).

Conclusion:
Marathon runners have higher levels of HDL-C and apo A1. They have a better ability to cholesterol transfer to HDL and this functionality remains despite being dyslipidemic, with increased levels of LDL-c and apo B.