bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis
Authors: Awoyemi Toluwalase , Tolu-Akinnawo Oluwaremilekun , Anuforo Anderson , Alagbo Habib , Ezekwueme Francis , Daniel Emmanuel , Barriga Guzman Rocio , Teeri Samira
Published: November 2024

Background:
Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients.

Methods:
This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted.

Results:
Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p<0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p<0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort.

Conclusion:
The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.
Abstract 4134655: Clinical Outcomes of Patients with Alcoholic Cirrhosis and Acute STEMI Undergoing PCI
Authors: Alwarawrah Zaid , Alziadin Nmair , alhalaseh saleh , Odac Barbara , El Sharu Husam , Al Omar
Published: November 2024

Original research:

Background:
The objective is to evaluate the outcomes of percutaneous coronary intervention (PCI) in patients with alcoholic cirrhosis presenting with ST-segment elevation myocardial infarction (STEMI).

Methods:
We analyzed data from the National Inpatient Sample (NIS) for the years 2016-2020. Our cohort included patients admitted with STEMI and a secondary diagnosis of alcoholic cirrhosis, excluding those under 18 or those not receiving PCI. Propensity score matching using a kernel method was applied to adjust for 22 variables, including patient demographics, hospital characteristics, and comorbid conditions.

Results:
Among 119,799 patients, 98 had alcoholic cirrhosis. These patients exhibited higher mortality (18% vs. 5%) and longer hospital stays (5.4 days vs. 3.6 days). They also had increased risks of acute blood loss anemia (13% vs. 3.5%) and gastrointestinal bleeding (18% vs. 2%). Additionally, acute kidney injury was more prevalent in the cirrhosis group (25.5% vs. 14%). Although heart failure exacerbation and cardiac arrhythmias were more common, these were not statistically significant (Table 1).

Conclusion:
Our study indicates a significantly higher mortality rate among patients with alcoholic cirrhosis undergoing PCI for STEMI. These patients are also at increased risk of postoperative bleeding due to compromised liver function and hemostatic abnormalities, as reflected by higher incidences of acute blood loss anemia and gastrointestinal bleeding. Additionally, there is an elevated risk of acute kidney injury post-PCI, highlighting the need for renal-protective strategies. These findings stress the necessity for specialized care, vigilant monitoring, and tailored protocols to address the unique challenges faced by this population, aiming to reduce morbidity and mortality.
Abstract 4134687: Takotsubo Cardiomyopathy Complicating Stroke
Authors: Jang Seon Ho , Sposato Luciano , Choi Yun-Hee , Geressu Amir , Mamas Mamas , Bagur Rodrigo
Published: November 2024

Background:
There have been studies suggesting Takotsubo cardiomyopathy (TCM) as a potential complication following cerebrovascular accident (CVA), but the association, contributing factors, and prognosis significance have not been well-characterized.

Aims:
1) To assess the incidence, factors and prognosis associated with TCM-complicated CVA, and 2) to determine the 30-day unplanned readmission rates for TCM after discharge for CVA and the associated factors.

Methods:
The U.S. Nationwide Readmission Database was queried using ICD-codes to gather information on discharges with primary diagnosis of CVA between January 2010 and November 2020. Incidence and factors associated with TCM-complicated CVA and 30-day readmissions with primary diagnosis of TCM were assessed.

Results:
Of 3,696,202 patients hospitalized with primary diagnosis of CVA, 5,526 (0.15%) individuals developed TCM during the admission. Patients with TCM were more likely to be women (80% vs. 52%, P<0.001), present with hemorrhagic (as opposed to ischemic stroke, P<0.001), and have a higher comorbidity burden, adverse events, and longer hospital stay. Mortality rate was significantly higher among those with TCM vs no-TCM (20% vs. 6.4%, P<0.001). Of 3,690,676 patients who were discharged without experiencing TCM during index admission for CVA, 255,947 (6.9%) patients had unplanned readmissions within 30 days of discharge, and 250 (0.1%) of these were with a primary diagnosis of TCM. These individuals with TCM were more likely to be women (78% vs. 51%, P<0.001), had a higher comorbidity burden, and experienced higher mortality rate during readmission compared to those without TCM (12% vs. 5.7%, P=0.009).

Conclusions:
Although rare, a TCM-complicated CVA can be highly fatal. Female sex, presentation with hemorrhagic stroke and pre-existing health conditions were strong factors associated with TCM-complicated CVA. Readmission for TCM after discharge for CVA is also uncommon but carries a significantly elevated risk of mortality. Our study presents an opportunity to improve processes and clinical outcomes by monitoring and recognizing TCM post-CVA, both during and after hospitalization.
Abstract 4134729: Quantitative, time-efficient viability cardiac magnetic resonance with delayed-phase dynamic contrast enhancement model: a pilot study in dogs with myocardial infarction
Authors: Huang Li-Ting , Yang Hsin-jung , Zhang Xinheng , Li Xinqi , Malagi Archana , Huang Yuheng , Guan Xingmin , Ho Hao , Kwan Alan , Wei Janet , Bi Xiaoming , Christodoulou Anthony , Li Debiao , Han Hui , Dharmakumar Rohan
Published: November 2024

Introduction:
Late gadolinium enhancement (LGE) is the gold standard for myocardial viability imaging, recommended by all major cardiology societies. In this study, we aimed to develop a time-efficient viability imaging technique utilizing a dynamic contrast enhancement(dDCE) model to shorten the LGE wait time, provide quantitative measures of the contrast washout procedure, and potentially enable a fast and quantitative mean for scar imaging.

Methods:
A canine study(n=10) was conducted on reperfused myocardial infarction(MI). A dDCE model using dynamic post-contrast T1 maps was adopted to depict the contrast washout process. dDCE maps were reconstructed using the whole dataset(dDCE
30min
) and a 5-minute subset of the T1 maps(dDCE
5min
). To test the dDCE models for shortening the LGE wait time, LGE
dDCE
images were synthesized using the dDCE
5min
maps and compared to the clinical LGE images. Remote and MI dDCE parameters on dDCE
30min
and dDCE
5min
maps were compared to test the model's ability to extract physiological features.

Results:
dDCE
30min
and dDCE
5min
map showed a good visuospatial difference between remote and MI(Fig. 1A) and no quantitative difference (Fig.1B). v
e
and PS showed a significant elevation in MI than in remote (61.12±13.65% vs 13.43±5.00%,
P
=0.018; 44.62±21.40mL/g/min vs 0.42±0.55mL/g/min,
P
=0.018, respectively). v
p
and F
p
were significantly decreased in MI than in remote (4.17±2.06% vs 10.85±3.77%,
P
=0.02; 1.11±0.32mL/g/min vs 1.51±0.42mL/g/min,
P
=0.04, respectively). Representative LGE and LGE
dDCE
images showed high agreement in the presence of MI (Fig. 2A). Bland-Altman analysis showed good agreement between LGE and LGE
dDCE
images for the measurement of infarct area (bias, -1.74 ± 6.60 %, Fig. 2B) and transmuraltiy (bias, 1.86 ± 2.73 %, Fig. 2C). The simple liner regression showed strong correlations between LGE and LGE
dDCE
images for the infarct area (R
2
, 0.95; slope, 0.93,
P
<0.01; Fig. 2D) and transmurality (R
2
, 0.97; slope, 0.93,
P
<0.01; Fig. 2E). ROC analysis showed that the AUC was 0.97 (95% CI: 0.94 to 1.00) (Fig. 2F). Increased lesion-blood pool contrast by 10 folds on dDCE images improved subendocardial MI detection (Fig.3).

Conclusions:
The developed dDCE model provides comparable viability assessment ability to the standard LGE images without the prolonged wait time and reflects MI pathophysiological changes. It shows the potential for a rapid and quantitative myocardial viability imaging protocol using cardiac magnetic resonance.
Abstract 4134796: Safety of over 1000 consecutive, selected low risk patients with accelerated discharge from a chest pain unit with early generation cardiac troponin use, no cardiac functional or anatomic testing and no clinical risk scores
Authors: Al Chalaby Shahad
Published: November 2024

Introduction:
Over 6 million patients (pts) present to US emergency departments annually with chest pain (CP), of which the majority are found to have no serious disease. Evaluation of these pts results in substantial costs for unnecessary hospitalization and extensive testing. We evaluated the utility of early discharge of selected low-risk (LR) CP pts from a chest pain unit (CPU) in which no predischarge testing or risk scores were used.

Methods:
This retrospective study analyzed 1,037 consecutive LR CP pts from a prospectively recorded database. LR was based on normal examination, stable hemodynamics, normal electrocardiograms (ECG), and negative cardiac troponin I, without pre-discharge functional or anatomic cardiac testing or risk scores. We assessed demographics, comorbidities, medications, and major cardiac events at 30 d and 6 mos post-discharge.

Results:
The study group of 1037 pts comprised 26% of the 4010 pts admitted to the CPU during the study interval from May 2005 to March 2015. Mean patient age was 55 yrs, 56% (n=575) were women, and comorbid conditions were frequent: hypertension (64.1%), dyslipidemia (46.1%), diabetes (25.7%), documented coronary artery disease (19.3%), previous revascularization (20.6%), previous myocardial infarction (10.1%). Length of stay (LOS) in the CPU to discharge was 10.4 hrs. Women received more discharge cardiac medications than men: antiplatelet agents, statins, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers, and nitrates (p=0.0002 - 0.04).

Follow-up (F/U) at 30 d was 91% (n=948) complete and revealed 0.3% (n=3) cardiac deaths, 0.6% (n=6) acute coronary syndromes (ACS), and 6.2% (n= 64) receiving revascularization. F/U at 6 mos was 90% (n=936) complete and total cumulative cardiac deaths were 0.9% (n=9), 0.7% (n=7) ACS and 6.3% (n=65) revascularization.

Discussion:
Cardiac events at both 30 d and 6 mos were very low and did not differ in men and women (P=0.8). LOS in CPU was minimized and patient safety was maintained. These selected LR pts remained at reduced risk for cardiac events despite a high rate of comorbidities. Early discharge of selected LR CP pts based on history, examination, ECG, and biomarker evaluation was safe and effective.

Conclusion:
This approach in selected LR pts has the potential to reduce unnecessary diagnostic testing and CPU LOS. This strategy could lead to substantial savings in healthcare costs without compromising patient safety.
Abstract 4134845: Primary Percutaneous Coronary Intervention versus Thrombolytic Therapy Outside Cardiology Reference Center for Acute Myocardial Infarction: A Meta-Analysis of Randomized Control Trials
Authors: Alves Filho Francisco Willamy , Alves Lima Nágila , Lopes Monte Neto Vicente , Tomaz Wellington
Published: November 2024

Introduction:
Fibrinolysis is the treatment of choice for patients with ST-elevation acute myocardial infarction (STEMI) who cannot reach door-to-balloon time for primary reperfusion therapy (PCI) 1. This therapy is widely used in some countries in Europe and Brazil2. However, these patients who undergo thrombolysis have a higher mortality rate compared to patients who undergo primary PCI3. The objective of the study is to evaluate the outcomes of mortality, reinfarction and stroke in patients with STEMI who underwent thrombolysis outside referral centers (community hospitals and inside ambulances) versus patients who underwent primary PCI.

Methods:
We performed a systematically review and meta-analysis of randomized control trials (RTCs) comparing of pre-hospital thrombolysis (PHT) with primary coronary intervention (PCI). PubMed, Embase and Cochrane databases were searched from April 2024 with the following search terms: ‘STEMI’, ‘myocardial infarction’[Mesh],’pre hospital’,’thrombolysis’,PHT, ‘thrombolytic therapy’. We used random-effects model to estimate the Risk Ration (RR) with 95% CI. Heterogeneity was examined with I2 statistics. We also performed leave-one-out sensitivity analyses and used Review Manager 5.4 for statistical analysis. The study was registered on PROSPERO: CRD42024547309.

Results:
A total of 1890 patients from 3 studies RTCs were included. Pre-hospital thrombolysis was used to treat STEMI in 940 patients (49%). Follow-up time varied from 4.6 to 5 years. The average age was 60.3 years. The anterior infarction on the ECG was similar between groups: average 43% (PHT) and 41.6% (PCI). Pre-hospital thrombolysis was associated with a higher risk of reinfarction ( RR 2.33; 95% CI 1.30-4.16; p=0.004; I2=0%) and composite outcomes of stroke, mortality and reinfarction(RR 1.67; 95% CI 1.25-2.23; p=0.0005; I2=0%). No significant differences were found between treatment groups regarding mortality (RR 1.23; 95% CI 0.70-2.18; p=0.47; I2=42%) and stroke (RR 3.82; 95% CI 0.54-27.23; p=0.18; I2=38%).

Conclusion:
This study suggests that pre-hospital thrombolysis is associated with a higher risk of reinfarction. More randomized studies on patients treated in a pre-hospital environment are needed to better investigate this question.
Abstract 4134900: Cellular Crosstalk in Endocardial Fibroelastosis: NRG Signaling Dysregulation Contributes to Fibrosis and Myocardial Dysfunction in Hypoplastic Left Heart Complex
Authors: Diaz-Gil Daniel , Morton Sarah , Brown Kemar , Wei Eric , Saraci Kerstin , von Piechowski Magnus , Emani Sitaram , Del Nido Pedro , Seidman Jonathan , Seidman Christine , Friehs Ingeborg
Published: November 2024

Background:
Endocardial fibroelastosis (EFE) is marked by a thickened fibro-elastic layer derived by endothelial-to-mesenchymal transition (EndMT), leading to restrictive myocardial function and poor cardiac growth, complicating biventricular repair in hypoplastic left heart complex (HLHC) patients. Neuregulin (NRG) signaling, crucial in EndMT and myocardial development, is implicated in various cardiomyopathies and heart failure, and its dysregulation may drive EFE pathogenesis.

Hypothesis:
NRG signaling dysregulation influences the cellular and molecular mechanisms of EFE.

Methods:
Single nucleus RNA sequencing (snRNA-seq) was conducted on human left ventricular (LV) tissue resected from 7 EFE patients (0.4-15 years) and 4 non-congenital heart disease (CHD) postmortem human controls (0.02-16 years). Differential gene expression was analyzed using the Wilcoxon Rank Sum test. We used CellChat, a computational tool for analyzing intercellular communication networks, to identify signaling changes via quantitative contrasts and joint manifold learning.

Results:
We identified 11 cell types in 64,963 nuclei. In EFE samples compared to non-CHD samples, NRG1-expressing fibroblasts increased from 3.4% to 21.2% (P<0.0001), and NRG2-expressing cardiomyocytes from 11.9% to 45.9% (P<0.001). CellChat analysis revealed a denser NRG signaling network in EFE, with enhanced interactions among cardiomyocytes, endocardial cells, fibroblasts, mast cells, and smooth muscle cells (Fig. 1A-B). Cardiomyocytes emerged as significant senders of NRG signaling in EFE, while endocardial cells, though still key senders, showed reduced influence. Fibroblasts became strong mediators, receivers, and influencers, smooth muscle cells emerged as prominent receivers, and mast cells gained roles as mediators and influencers (Fig. 1 C-D). These changes indicate a complex NRG signaling network in EFE, highlighting altered cellular interactions driving disease progression.

Conclusion:
Dysregulated NRG signaling in EFE contributes to pathological cellular crosstalk, fibrosis, and myocardial dysfunction, potentially hindering successful biventricular repair in HLHC patients. Targeting NRG pathways could represent a novel therapeutic approach. These findings offer promising implications for affected patients, potentially improving outcomes. Future research should explore additional molecular pathways involved in EFE and assess the therapeutic efficacy of targeting NRG signaling.
Abstract 4134922: Trends in Coronary Artery Disease-Related Mortality in Adults with Hyperlipidemia in the United States: A CDC WONDER Database Analysis
Authors: Naveed Muhammad Abdullah , Ali Ahila , Neppala Sivaram , Omer Rehan Muhammad , Azeem Bazil , Iqbal Rabia , Chigurupati Himaja Dutt , Sattar Yasar , Paul Timir
Published: November 2024

Background:
Coronary artery disease (CAD), related to high blood lipid levels, is a significant contributor to adult mortality in the United States. This study examines the patterns of CAD-related deaths associated with high lipid levels in adults aged 25 and above, with a specific focus on variations related to geography, gender, and race/ethnicity from 1999 to 2020.

Methods:
This study employed a comprehensive retrospective analysis using death certificate data from the CDC WONDER database, covering 21 years from 1999 to 2020. We calculated age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) per 100,000 persons, categorized by year, gender, race/ethnicity, and geographic regions. This approach ensured a robust and reliable analysis of the trends in CAD-related deaths associated with high lipid levels.

Results:
Between 1999 and 2020, CAD in individuals with high levels of lipids resulted in 407,667 deaths among adults aged 25 and above in the United States. The majority of these deaths occurred in medical facilities (40.1%) and at home (37.3%). The AAMR for CAD in individuals with high lipid levels increased from 4.1 in 1999 to 12.1 in 2020, showing an AAPC of 4.44 (95% CI: 3.69 to 5.48, p < 0.000001). Men had a higher AAMR (12.4) than women (5.6), and both sexes experienced significant increases over time. Disparities in AAMRs by race/ethnicity revealed the highest rates among Whites (8.9), followed by American Indians/Alaska Natives (8.6), Blacks (7.3), Hispanics (6.5), and Asians/Pacific Islanders (5.9). The most significant increase was observed in Blacks (AAPC: 5.07, p < 0.000001). This detailed breakdown of the disparities in CAD mortality rates among different racial and ethnic groups provides a clear picture of the health inequalities that need to be addressed.

Conclusion:
This study emphasizes the discrepancies in CAD mortality related to high lipid levels among adults in the United States based on race, gender, and geographic location. The consistent rise in AAMRs between 1999 and 2020 emphasizes the necessity for specific public health interventions to tackle these increasing inequalities.
Abstract 4134935: Impact of COVID-19 on Cardiology Fellows and Faculty in the United States: Two Years Later
Authors: Chitsazan Mandana , Hu Jiun-Ruey , Pires Jacqueline , Obradovic Aleksandar , Gulati Martha , Clark Katherine , Z Ali Yehia , Altin Elissa , Kwan Jennifer
Published: November 2024

Introduction:
Recent data demonstrated that the COVID-19 pandemic adversely affected cardiovascular fellows in training (cFIT) and faculty in terms of educational disruption and search for job prospects, respectively. However, less is known about the pandemic's effect on cFIT and faculty in terms of general well-being, shifts in personal and professional priorities, quantitative measures of stress levels, and research productivity.

Methods:
A national survey targeting cFIT and faculty was developed to assess the effect of the pandemic two years later on these parameters. Fifty-four participants, including 21 cFIT and 33 faculty, responded to the survey. The survey was distributed between October 2021 and May 2022 to program directors of ACGME-accredited general cardiology fellowship programs in the United States.

Results:
30% of cFITs perceived impaired clinical training during the pandemic; 36% of fellows experienced a decline in their clinical skills in the cardiac catheterization lab, while 27% experienced a decrease in their echocardiographic skills. Additionally, a significant percentage of cFIT reported negative interference in their competencies in nuclear cardiology (27%) and electrophysiology (12%). Most participants (76%), including faculty and fellows, reported several health issues such as sleep problems, low energy, changes in appetite, difficulty concentrating, and restlessness due to the pandemic. 43% of the faculty and 61% of cFIT reported high rates of impaired short-term productivity (Figure).

Conclusion:
In this national survey, we found that two years after the onset of the COVID-19 pandemic, cardiology fellows and faculty continued to experience significant concerns for decreased hands-on training and diminished research productivity. While faculty were not distressed regarding decreased clinical competencies, concerns about short-term and long-term research productivity persisted. Faculty and fellows all experienced increased stress levels and impaired productivity. Although limited by a small sample size, which can introduce bias, these results signal the importance of performing a follow-up study on the impact of COVID-19 on wellness as well as the impact on career.
Abstract 4134949: Effect of anakinra in patients with ST-elevation myocardial infarction according to the renal function
Authors: Golino Michele , Del Buono Marco Giuseppe , Damonte Juan Ignacio , chiabrando juan guido , Denicolai Martin , Corna Giuliana , Moroni Francesco , Thomas Georgia , Trankle Cory , Buckley Leo , Wohlford George , Turlington Jeremy , MARKLEY ROSHANAK , Van Tassell Benjamin , Abbate Antonio
Published: November 2024

Introduction:
Interleukin(IL)-1 blockade with anakinra dampens the inflammatory response and prevents heart failure (HF) events in patients with ST-elevation myocardial infarction (STEMI). The efficacy of anakinra according to the baseline renal function in STEMI has not been addressed.

Hypothesis:
The efficacy of anakinra is independent of the baseline renal function.

Aim:
To determine the effect of anakinra according to the baseline renal function in patients with STEMI.

Methods:
We pooled patients with STEMI from 3 double-blind randomized clinical trials. Patients with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m2 were excluded. We divided the cohort based on the median baseline eGFR using the modified 2021 CKD-EPI equation (≥ or < 86 mL/min/1.73m2). We analyzed the area-under-the-curve for C-reactive protein (AUC-CRP) at 14 days, and the incidence of the composite outcome of all-cause death or new-onset HF at 1 year using the Log-rank test. We also evaluated the creatinine changes at 48-72 hours after percutaneous coronary intervention (PCI).

Results:
We analyzed 139 patients, 110 (79%) males, 52 (37%) Black or African-American, with a median age of 56 [49–63] years. The AUC-CRP at 14 days was significantly higher in patients receiving placebo vs. anakinra both in those with eGFR <86 mL/min/1.73m2 (250.5[131.4-512.0] vs. 66.4[42.3-126.5] mg●day/L, p<0.001) and those with eGFR ≥86 mL/min/1.73m2 (214.2[113.6-303.4] vs. 86.4[35.9-194.3] mg●day/L, p<0.01). Anakinra significantly reduced the composite outcome of all-cause death or new-onset HF in patients with baseline eGFR <86 mL/min/1.73m2 (4/41 [9.8%] vs. 9/27 [33.3%], Log-rank p=0.024) as well as in patients with baseline eGFR ≥86 mL/min/1.73m2 (3/43 [6.9%] vs. 7/28 [25%], Log-rank p=0.038)(p=0.97 for interaction)(Figure). No differences in creatinine changes 48-72 hours after PCI were observed (0.01 [-0.10 to 0.15] mg/dL in anakinra vs. 0.01[-0.08 to 0.14] mg/dL in placebo; p=0.80).

Conclusion:
In a cohort of patients with STEMI and mainly preserved or mildly reduced renal function, IL-1 blockade with anakinra blunts the acute inflammatory response and prevents all-cause death or new-onset HF at 1 year independent of baseline renal function.
Abstract 4134975: ROS-Traf6-Yap Promotes the Development of Cardiac Hypertrophy
Authors: Li Yuting , Zhou Xiaoxia
Published: November 2024

Introduction:
Heart failure (HF) is caused by structural and functional abnormalities of the heart and is associated with high morbidity and mortality. Pathological myocardial hypertrophy accounts for a significant portion heart failure. The Yap protein was found to be responsive to mechanotransduction signals and can limit organ size by inducing cell cycle arrest during development. In the heart, pathological activation of Yap has been shown to drive cardiac hypertrophy, but regenerative activation of Yap can promote myocardial cell-cycle re-entry. However, how Yap is pathologically activated in the beating cardiomyocyte remains elusive.

Hypothesis:
ROS-Traf6 promotes the development of cardiac hypertrophy by activating Yap in a non-canonical fashion.

Methods:
Traf6 protein levels in heart failure patients biopsies as well as in various murine failing hearts were examined by immunofluorescence. Molecular interrogation of ROS-Traf6-Yap signaling axis was performed in primary neonatal rat cardiomyocytes (NRCM) and human induced pluripotent stem cell derived cardiomyocytes. Yap protein stability and activation by Traf6 was examined by immunoprecipitation, CHX induction, and point mutation. Myocardial specific Traf6 knockout and Yap mutant animals were used to evaluate Traf6-Yap signaling
in vivo
.

Results:
We found that Traf6 expression was significantly elevated in multiple heart failure models. Using the transverse aortic constriction (TAC)-induced cardiac hypertrophy model, pressure overload increased ROS levels which activated Traf6. Traf6 overexpression induced myocardial hypertrophy while knockdown blocked myocardial hypertrophy in Ang II treated NRCMs. Mechanistically, Traf6 binds to and ubiquitinates Yap-K234 – this promotes Yap protein stability and nuclear translocation evidenced by increase in phosphorylated Yap. Myocardial Traf6 deficiency prevents TAC-induced cardiac hypertrophy. Moreover, overexpression of Yap-K237 mutant did not restore TAC-induced cardiac hypertrophy in myocardial Yap deficient mice.

Conclusions:
Our results demonstrate that non-canonical Yap activation is responsible for pressure overload induced cardiac hypertrophy. Targeting of the newly identified ROS-Traf6-Yap signaling axis may provide a new approach to prevent pathogenic cardiac hypertrophy.
Abstract 4135061: Myocardial work in different patients with electrical dysynchrony due to left bundle branch block
Authors: Rimskaya Elena , Svetlana Dobrovolskaya , Kukharchuk Elizaveta , kashtanova Svetlana , Mironova Nataliia , Komlev Alexey , Imaev Timur , Tarasovskiy Gennadiy , Saidova Marina , Golitsyn Sergey
Published: November 2024

Left bundle branch block (LBBB) in patients with dilated cardiomyopathy (DCM) is defined by huge wasted work and decreased myocardial constructive work. The aim of this study is to assess the myocardial work in patients in LBBB and other clinical situations.

Materials and methods:
The echocardiographic study was performed in 25 patients with LBBB and DCM (LBBB-DCM); 20 patients with DCM and narrow QRS complex (nonLBBB-DCM group); 15 patients with LBBB developed after transcatheter aortic valve implantation (TAVI group); 12 patients with idiopathic LBBB, normal systolic LV function and excluded cardiovascular pathology (LBBB group); 27 patients with right ventricular pacing due to atrioventricular block of high grade (RVP group) and 20 healthy volunteers (HV group). In all of them global longitudinal strain (GLS) and myocardial work parameters including global constructive work (GCW), global wasted work (GWW), global work index (GWI) and global work efficiency (GWE) were assessed. In all patients the segments with maximum and minimum GWI value were determined.

Results:
GLS, GWI and GCW values were comparable in LBBB and RVP groups, whereas in TAVI and in both DCM groups they was significantly lower than in HV (p = 0.049, 0.006, 0.025; p < 0,001 respectively, (Fig.1A,B,C)). Patients from LBBB, TAVI, RVP and LBBB-DCM groups were characterized by increased amount of GWW (261 [203.5; 291.5], 273 [184.8; 385,3] and 237 [149.5; 445.3] vs 108 [74.3; 137.3] mmHg%, p = 0.033, 0.006, < 0.001, < 0.001 respectively). GWW value in LBBB-DCM group was the highest (346.5 [255.5; 437.8] mmHg% (Fig.1D). There was moderate strength of relation between GWW and QRS duration (ρ=0.456, p<0.001). A huge amount of wasted work affected the GWE value and led to its considerable reduction in LBBB, TAVI, RVP and LBBB-DCM groups compared to HV (p = 0.033, 0.007, 0.023, < 0,001, respectively, Fig.1E). The zone of maximum GWI localized in posterolateral wall, the zone of minimum GWI was in interventricular septum in most LBBB patients (Fig.1F). At the same time, these zones turned out to be very variable in RVP group.

Conclusion:
Although all patients with LBBB pattern of electrical activation are characterized by significant amount of wasted work, its contribution to global myocardial work manifested only in DCM patients. Wasted work doesn’t lead to reduced constructive work in patients with idiopathic LBBB and RVP and normal systolic function probably due to compensatory mechanisms.
Abstract 4135080: Relation of focal and diffuse myocardial fibrosis to left bundle branch block in patients with dilated cardiomyopathy and structurally normal heart
Authors: Rimskaya Elena , Aparina Olga , Stukalova Olga , Kormilitsyn Semen , Mironova Nataliia , Chumachenko Petr , Ternovoy Sergey , Golitsyn Sergey
Published: November 2024

The role of fibrosis in etiology of left bundle branch block (LBBB) in still not defined. The aim of this study was to assess the relation of focal and diffuse LV fibrosis to LBBB in patients with dilated cardiomyopathy (DCM) and in patients with structurally normal heart.

Materials and methods:
60 DCM with LBBB (DCM-LBBB group, 46.7% male, mean age 57[50;63] years), 50 non-LBBB DCM (78% male, mean age 43[32.3;54] years), 15 patients (53.3% male, mean age 39[28;50] years) with LBBB and no signs of structural heart disease and 10 healthy volunteers (HV) were included in the study. Endomyocardial biopsy (EMB) was performed in 15(24,6%) LBBB-DCM and 16(32%) non-LBBB DCM patients and allowed the quantification of collagen volume fraction (CVF, Fig.1A-D). All patients and HV underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) analysis. Obtained LGE LV images were post-proceed for core scar (CS) and gray zone (GZ) calculation and 3D reconstruction. Diffuse LV interstitial fibrosis was estimated on all LGE-CMR images with the novel introduced marker - diffuse intensity ratio (DIR).

Results:
DIR was validated on EMB samples: the percentage of CVF (8.2[4.6;10.8]%) correlated with the DIR value (0.71 ± 0.13) in the same segment (r=0.66, p<0.001, Fig.1E-F). The value of CVF (Fig1A-D) and LGE presence in the septum in both DCM groups (Fig2) was comparable (8.2[4.6; 10.3] versus 7.6[6.1;15.3]%, p=0.82 and 19 (31.7%) versus 17 (34%) patients in non-LBBB DCM group respectively, p=0.8) Moreover, the presence of LGE and midwall fibrosis in septum was not related to the QRS duration (p=0.93 and 0.59). In non-LBBB DCM patients the percentage of CS was significantly higher (4.0[1.55; 11.68]% versus 1.4[0.05;8.5]% in LBBB-DCM patients, p=0.047), whereas percentage of GZ and total fibrosis in both DCM groups was comparable (Fig.3A,B). DIR value was higher in patients with idiopathic LBBB than in HV (0.54±0.09 versus 0.34±0.1, p<0.001) while the percentage of GZ and CS was extremely low and did not differ from its amount in HV (Fig.3C,D).

Conclusion:
Neither focal (including midwall striae) nor interstitial fibrosis is associated with LBBB in patients with DCM. Diffuse inflammation in LBBB-DCM patients may contribute to the progression of systolic dysfunction but is not the reason for LBBB. The increased value of interstitial fibrosis in patients with LBBB may reflect latent diffuse process in myocardium inexorably leading to DCM development.
Abstract 4135092: Prolonged Procedure Time and Its Association with Peri-Procedural Complications in Endovascular Therapy for Symptomatic Lower Extremity Arterial Disease
Authors: Toyoshima Taku , Iida Osamu , Higuchi Yoshiharu
Published: November 2024

Background:
Prolonged operative times in surgical procedures have been significantly associated with an increased risk of complications. However, the impact of prolonged procedure time of peri-procedural complications in patients undergoing endovascular therapy (EVT) for symptomatic lower extremity arterial disease (LEAD) has not been systematically evaluated.

Aims:
To determine the association between prolonged procedure time and peri-procedural complications in patients undergoing EVT for symptomatic LEAD.

Methods:
Data from a nationwide EVT registry in Japan (J-EVT) between 2021 and 2022 were analyzed. The outcome measure was peri-procedural complications defined as a composite of perioperative death, major bleeding, contrast nephropathy, myocardial infarction, ischemic stroke, and major amputation. Procedure time was categorized into four clinically relevant groups (≤59, 60–119, 120–179, and ≥180 minutes). The logistic regression model was developed to investigate the risk of peri-procedural complications across subgroups of procedure time with the shortest subgroup (≤59 minutes) set as the reference category.

Results:
A total of 47,301 patients (average age: 75±9 years, male: 69.0%, chronic limb-threatening ischemia [CLTI]: 51.0%) undergoing EVT for symptomatic LEAD were analyzed. Notable comorbidities included diabetes mellitus at 60.6% and dialysis at 29.9%, respectively. A history of coronary artery disease was noted in 40.7% of the participants. The median procedure time (interquartile range) was 110 (74–161) minutes. A total of 431 patients (0.9%) experienced perioperative complications. The perioperative complications included 48 deaths, 277 cases of major bleeding, 28 cases of contrast nephropathy, 10 myocardial infarctions, 16 ischemic strokes and 72 major amputations. After adjusting for patient and limb characteristics, and hospital and operator volumes, the odds ratios for perioperative complications were 1.21 (P=0.45) for 60–119 minutes, 2.36 (P=0.001) for 120–179 minutes, and 5.31 (P<0.001) for ≥180 minutes with the shortest subgroup (<59 min) set as the reference.

Conclusions:
Prolonged procedure time of EVT for symptomatic LEAD was significantly associated with an increased risk of perioperative complications.
Abstract 4135113: Referral to a Heart Failure Clinic Substantially Increases the Use of Angiotensin Receptor Neprilysin Inhibitor (ARNi) and Sodium-glucose cotransporter-2 Inhibitor (SGLT2i) in Heart Failure Patients.
Authors: Baksh Gladys , Ali Omaima , Haydo Michele , Velasco Claudia Mae , Reesor Heather
Published: November 2024

Introduction:
Addressing access to life-saving therapy is crucial in influencing health outcomes. The stark reality of limited access to pharmacological therapy for heart failure with reduced ejection fraction (HFrEF), particularly novel drugs such as angiotensin receptor neprilysin inhibitors (ARNi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for patients with heart failure (HF), underscores the challenges we face.

Hypothesis:
We analyze the impact of referring patients diagnosed with HF to our HF clinic by evaluating access to the 4 pillars of HFrEF, emphasizing cost-prohibiting pharmacological therapy, and assessing the efficacy of these medications when applied.

Methods:
This study compared 314 patients who live in counties within and outside the Penn State Health System. The data collected included healthcare insurance coverage, HF etiology, comorbidities, onset, initial and within six months post titration of guideline-directed medical therapy (GDMT) echocardiogram, and medication dose.

Results:
Among patients referred to our HF clinic, 184 live in counties within, and 130 live outside the Penn State Health System. The average age was 64, 69.4% were male, and a significant number of patients had HFrEF (92.7%). The prevailing comorbidities between the 2 groups were hypertension, hyperlipidemia, and diabetes. Upon completion, there was a significant increase in ARNi (83.1%) and SGLT2i (65.3%) use in both groups. They both (within vs. outside) reached almost similar percentages of triple therapy (77.9% vs. 79.2%; p-value=0.78), except for quadruple therapy (36.4% vs. 44.6%; p-value=0.16) and maximum tolerated dose (83.3% vs. 75%; p-value=0.11). The overall mean ejection fraction (EF) in both groups demonstrated significant improvement from pre-EF (30.5%) to post-EF (45.9%).

Conclusion:
Despite their location, patients referred to the HF clinic experienced intensified use of cost-prohibiting medications such as ARNi and SGLT2i, compared to the current gap in GDMT use. After optimizing GDMT, both groups had markedly improved EF. These findings suggest that referral to a HF clinic is a promising strategy for addressing the use of life-saving therapy and potentially reducing adverse health outcomes.
Abstract 4135252: Associations between Group 2 Pulmonary Hypertension and 30-Day Readmissions Following Acute Myocardial Infarction Hospitalizations.
Authors: abdallah nadhem , Mohamoud Abdilahi , Abdallah Meriam
Published: November 2024

Background:
Pulmonary hypertension (PH) is a major contributor to cardiovascular disease-related morbidity and mortality. Despite this, little is known regarding the outcomes of 30-day re-admissions following Acute Myocardial Infarction (AMI) in the context of group 2 PH.

Hypothesis:
Group 2 PH is associated with a higher likelihood of 30-day readmissions in patients presenting with AMI.

Goal:
To assess the relationship between group 2 PH and adverse hospitalization outcomes in cases of AMI.

Methods:
We queried the 2016-2020 Nationwide Readmission Database (NRD) and identified AMI as the primary diagnosis. We compared in-hospital outcomes based on the presence versus absence of Group 2 PH. The primary outcome was 30-day readmissions. Secondary outcomes included the odds of in-patient mortality, mechanical ventilation use, vasopressor use, and mechanical circulatory support (MCS) use. Multivariable regression models were used to adjust for confounders.

Results:
Among 182,308 AMI hospitalizations, 364 (0.2%) had a secondary diagnosis of Group 2 PH. Group 2 PH was associated with a higher likelihood of re-admission within 30 days (adjusted OR [aOR] 1.21, 95% CI 1.07–1.36, p=0.002). Additionally among patients presenting with AMI, group 2 PH was associated with higher odds of in-patient mortality (aOR 2.64, 95% CI 1.52–4.58, p=0.001), mechanical ventilation use (aOR 2.07, 95% CI 1.19–3.6, p=0.010), vasopressor use (aOR 5.4, 95% CI 2.7-10.9, p<0.001) and MCS use (aOR 2.39, 95% CI 1.46-3.91, p<0.001) during index hospitalization compared to the patients without group 2 PH.

Conclusion:
Patients with Group 2 PH admitted for AMI had higher odds of 30-day readmissions and both fatal and non-fatal adverse outcomes compared to patients without PH. Further studies are needed to confirm these findings and develop strategies to improve outcomes for this high-risk population.
Abstract 4135270: Clinical and Procedural Outcomes after Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Shoaib Aqsa , Khan Ayesha Ali , Khan Muhammad , Khan Iqra , Arif Muhammad Hammad , Afzal Ahson , Mohiuddin Neha , Siddiqi Tariq Jamal
Published: November 2024

Introduction:
A growing body of evidence from randomized controlled trials (RCTs) has demonstrated the superiority of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) irrespective of surgical risk in patients with severe aortic stenosis (SAS). Given the rise in TAVR procedures, analyzing trends in outcomes over time is critical to aid clinical decision-making. Hence, we pooled RCT data for a robust assessment of clinical and procedural outcomes in SAS patients undergoing TAVR and SAVR.

Methods:
PUBMED and SCOPUS were queried until April 2024. Trials were classified into high and low-risk groups based on surgical risk. The outcomes were analyzed at 30 days (short-term), 1 year (mid-term), and 5 years (long-term). Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).

Results:
10 RCTs with a total of 10,252 patients were included. There was no significant association between TAVR and SAVR in reducing all-cause mortality at 30 days (RR: 0.84 [0.64, 1.10]; Figure 1a). While TAVR was associated with a significantly lower all-cause mortality at 1 year (RR: 0.82 [0.68-0.97]; Figure 1b), it was linked with a significantly higher all-cause mortality at 5 years (RR: 1.14 [1.07-1.21]; Figure 1c). Myocardial infarction and stroke were similar in both groups up to 5 years. TAVR was associated with a lower risk of acute kidney injury for up to 1 year and atrial fibrillation for up to 5 years but a higher risk of new permanent pacemaker implantation and aortic valve re-intervention for up to 5 years. In low-risk patients, TAVR showed no significant differences from SAVR for all-cause mortality at 30 days and 5 years, but it was significant at 1 year. In high-surgical-risk patients, all-cause mortality was comparable between TAVR AND SAVR at 30 days and 1 year, with a higher rate observed with TAVR at 5 years.

Conclusion:
Compared with SAVR, TAVR was superior in reducing all-cause mortality at 1 year in low-risk patients and inferior in reducing all-cause mortality at 5 years in high-risk patients. A thorough evaluation of anatomical, clinical, and procedural factors is crucial to tailor the optimal intervention for each patient.
Abstract 4135273: Frailty increases the risk of in-hospital mortality and post-procedural complications in patients undergoing Cardiac Implantable Electronic Devices placement
Authors: Quevedo Ramirez Andres , Malkani Sharan , Aryal Badri , Jha Vivek
Published: November 2024

Background:
Heart failure with reduced ejection fraction (HFrEF) often necessitates the use of cardiac implantable electronic devices (CIED) such as cardiac resynchronization therapy defibrillators (CRT-D) or implantable cardioverter-defibrillators (ICD). These devices are proven to reduce mortality, prevent hospitalizations, and improve symptoms and quality of life. Frailty, characterized by an age-associated decline in physiological reserve, significantly impacts outcomes in these patients. This study uses the Hospital Frailty Risk Score (HFRS) to assess the effect of frailty on mortality and post-procedural complications in HFrEF patients undergoing CIED implantation.

Hypothesis:
Frail patients with HFrEF have worse in-hospital outcomes after CIED placement

Methods:
We conducted a retrospective cohort study using the 2020 National Inpatient Sample database from the Healthcare Utilization Project. Our population included patients aged 18 years or older with HFrEF who underwent CRT-D or ICD placement, identified using ICD-10 procedure codes. The primary risk factor was frailty, classified by an HFRS score of ≥5 (frail) or <5 (not frail). The primary outcome was in-hospital mortality, and the secondary outcome was the composite of post-procedural complications. Multivariate regression analysis was used to estimate the odds ratio.

Results:
Out of 24,809 patients who underwent ICD or CRT-D placement, 48.8% were frail. Non-Frail patients had lower mean age compared to Frail patients (66.2 vs 67.3 years old, p=0.003). In-hospital mortality was 1.1%, and 7% experienced post-procedural complications. In-hospital mortality was higher in frail patients compared to non-frail patients (2% vs 0.3%, p<0.001). In the multivariate analysis, frail patients had higher odds of in-hospital mortality compared to the non-frail group subset (OR=5.97; 95% CI: 2.77-12.88, p<0.001). Additionally, frailty was associated with higher odds of post-procedural complications (OR=1.28; 95% CI: 1.01-1.63, p<0.001), increased length of stay (5 vs 11.6 days, p<0.001), and total hospital charges (215,668 vs 324,474 , p<0.001).

Conclusion:
Frailty significantly increases the risk of in-hospital mortality and post-procedural complications in HFrEF patients. This highlights the importance of considering frailty as part of a pre-procedural risk stratification assessment and tailoring management strategies to improve outcomes for these high-risk patients.
Abstract 4135301: Cardiac specific gene therapy to treat diabetic heart failure with preserved ejection fraction
Authors: Guo Yugene , Liu Hong , Kang Gyeoung-Jin , Liu Man , Butler Jonah , Dudley Samuel
Published: November 2024

Background:
We have previously demonstrated that diabetes mellitus (DM) causes cardiac inflammation leading to heart failure with preserved ejection fraction (HFpEF). Arachidonate 5-lipoxygenase (5-LOX), encoded by the ALOX5 gene, is an enzyme that is highly expressed in leukocytes. 5-LOX synthesizes specialized pro-resolving mediators (SPMs) including Resolvin D1 (RvD1), which reduce inflammation.

Hypothesis:
We hypothesize that cardiac-specific ALOX5 upregulation could prevent diabetes-associated HFpEF without inducing systemic immunosuppression.

Methods:
DM was induced by feeding mice with a high fat diet (HFD, 60% fat by kcal) starting from 6 weeks of age for 22-24 weeks. At 24 weeks of age, DM mice were treated with RvD1, by intraperitoneal injection at 100 ng/mouse for 2 weeks. To specifically upregulate 5-LOX in the heart, another cohort of DM mice were injected with either AAV9-plain or AAV9-
ALOX5
viral vectors under the control of the α-myosin heavy chain (MHC) at 22 weeks old. At 28 weeks, we performed echocardiographic measurement of diastolic function and heart extraction.

Results:
HFD-induced DM mice showed lower cardiac 5-LOX expression (0.72 ± 0.05 a.u. vs. 1.09 ± 0.12, p < 0.05) and RvD1 levels (1 ± 0.08 vs. 1.9 ± 0.14 fold change over DM mice, p<0.0001) than the mice with normal diet. RvD1 treatment significantly improved DM-associated diastolic function (19.7 ± 1.4 a.u. vs. 22.9 ± 0.4, p<0.05). With cardiac specific upregulation of 5-LOX, cardiac 5-LOX expression (0.89 ± 0.06 vs. 0.70 ± 0.04 a.u., p<0.05) and RvD1 levels were increased (2.1 ± 0.3 a.u. vs. 1.2 ± 0.2, normalized to AAV9-plain, p<0.05). AAV9-
ALOX5
also reduced NLRP3 inflammasome activity (0.80 ± 0.02 a.u. vs. 0.90 ± 0.02, p<0.01) and improved DM-associated diastolic dysfunction (17.0 ± 1.2 a.u. vs. 20.5 ± 1.0, p<0.05) without affecting glucose metabolism and obesity in DM mice. Moreover, no alterations of cardiac macrophage infiltration, inflammatory IL1β signaling, or macrophage phenotype were observed in response to cardiac-specific ALOX5 upregulation.

Conclusion:
In conclusion, both direct RvD1 treatment and cardiac-specific gene therapy to enhance resolution of inflammation in cardiomyocytes reversed DM-associated HFpEF. Gene therapy avoided off-target immunosuppression. Therefore, AAV-directed cardiac ALOX5 upregulation represents a novel cardiac-specific gene therapy for HFpEF that avoids systemic immunosuppression.