bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142627: Cardiac Resident Macrophage Produces Collagen I and Contribute to Vascular Maturation After Myocardial Infarction
Authors: Jia Daile , Zhang Jinghong , SUN AIJUN , Ge Junbo
Published: November 2024

Background:
Cardiac resident macrophages engage in a wide array of functions such as endocytosis, angiogenesis, and regeneration and are essential to the maintenance of homeostasis in the steady heart. After myocardial infarction, cardiac resident macrophages are highly heterogenous with diverse functions and therapeutic potentials and primarily within the infarct border zone. Cardiac resident macrophages drive postinfarction remodeling by secreting proteins that impart signals to nearby cells expressing their cognate receptors. The full complexity of this intercellular cross-talk that shapes wound healing and functional adaptation after MI remains incompletely understood.

Methods:
Single-cell transcriptomes from human and mouse acute myocardial infarction documented CCR2
−
collagen I
+
macrophage expansion. Multiple transgenic mice such us Col1a1
F/F
; LysM
Cre
, and Col1a1
F/F
; Cx3cr1
CreER
were used to determine the functional significance of collagen I derived from macrophage in MI. Moreover, collagen I expression from macrophages was analyzed by immunohistochemistry and qPCR in the cardiac tissues of patients with ischemic cardiomyopathy and healthy controls.We generated a genetic lineage-tracing system that uses dual recombinases (Cre and Dre) to specifically track collagen I
+
macrophages in vivo.

Results:
Dual recombinases-mediated genetic system targeted CCR2
−
MHC-II
low
Col1a1
+
macrophages specifically and efficiently. Lineage tracing study revealed accumulation of CCR2
−
MHC-II
low
Col1a1
+
macrophages in the border zone after MI. Macrophage-specific deletion of
Col1a1
significantly reduced collagen I production in the border area and resulted in a considerable exacerbation in cardiac function, accompanied with impaired epicardial cell migration and new vessel formation. Collagen I derived from cardiac resident macrophage controls epicardial cell migration through the DDR1–NF-κB–MMP9/Efna1/Adgra2 axis.

Conclusions:
In this study, we deciphered how cardiac resident macrophage and epicardial cells cross-talk that shapes wound healing and functional adaptation after myocardial infarction.
Abstract 4142628: Machine learning models based on hyperspectral images accurately diagnose coronary artery disease
Authors: Li Zeyan , Yang Xiaomeng , Shi Xiaoyu , Yu Lilei
Published: November 2024

Background:
Hyperspectral imaging (HSI) can be used for high-precision classification, offering high spectral resolution, wide spectral coverage, and high data dimensionality. Patients with coronary artery disease (CAD) possess distinctive body surface image characteristics. However, value of HSI for the diagnosis of CAD remains unclear

Hypothesis
CAD patients exhibit characteristic spectral signatures on surface, which can be used for diagnostic identification of CAD.

Methods:
This is a cross-sectional observational study. Clinical baseline characteristics, results of coronary artery angiography (CAG) and tongue dorsum hyperspectral images (spectral range:688-951nm) were collected from the subjects. In this study, 3650 hyperspectral images were included. These images are divided into training sets(N=2555) and validation sets(N=1095). Machine learning algorithms were used to selection of features in hyperspectral images and construction of CAD diagnosis models (including Gaussian process (GP), random forest (RF), support vector machine (SVM), gradient boosting (GB), TheilSen etc). Model fusion was achieved by forward selection strategies to improve model performance. The screened features are further used to generate new clinical markers through band math. Predictive performance of the models was assessed based on the results from CAG.

Results:
The model performance was evaluated through area under receiver operating characteristics (AUROC), decision curve analysis (DCA), calibration curve, accuracy, precision, sensitivity, specificity, and F1 score. (1) The top 5 performance models were selected from 29 models, including GP, RF, SVM, GB, and TheilSen. The corresponding AUROC for top 5 models were 0.879, 0.827, 0.844, 0.854 and 0.783.(2) Based on forward selection strategy, GP, GB and SVM models were selected to develop fusion model (GP-GB-SVM model). Model performance of GP-GB-SVM model was upgraded and AUROC of GP-GB-SVM was 0.92. (3) The top 10 features were recognized from top 5 models. Combination of 10 features through band math generated new clinical marker (Hyper-CAD), which can effectively predict risk of CAD.

Conclusion:
The present study suggests that patients with CAD exhibit characteristic HSI alterations on the surface. Patients with CAD can be effectively diagnosed and identified based on these alterations.
Abstract 4142631: Trends in Heart Failure-Associated Mortality in Individuals with Diabetes Mellitus Type II
Authors: Nofal Abdullah , Rahman Sara , Khurram Maheen , Khaskheli Sarah Ashraf
Published: November 2024

Introduction:
Diabetes mellitus type II is among the nine leading causes of mortality. All-cause mortality hikes by folds in those affected. Heart failure (HF) is a common cause; however, patient demographics and other factors impact the trends. Identifying these can help direct relevant healthcare agendas.

Research Question:
What are the trends in HF-associated mortality in individuals with diabetes mellitus type II in the USA?

Goals:
Identifying trends stratified by age, gender, race, and geographical location in HF-associated mortality in diabetic individuals.

Methodology:
Crude mortality rate (CMR) and age-adjusted mortality rate (AAMR) per 100,000 population were extracted from the National Vital Statistics System from 1999 to 2020 using the CDC Wonder database, with diabetes mellitus type II as the underlying cause and heart failure as a contributing cause. Changes over time, as annual percentage change (APC), were analyzed with Joinpoint regression analysis.

Results:
The overall AAMR increased from 1999-2004 (APC: 6.054), followed by a decrease during 2004-2014 (APC: -0.139) and a final incline till 2020 (APC: 11.52). Older adults (aged 85+) had the highest CMR of 97.08. Men had a higher AAMR than women (5.61 versus 3.87). Ethnicity-wise, the highest AAMR was observed in Non-Hispanic (NH) American Indians or Alaska Natives (7.13), followed by the Hispanic or Latino (5.26), NH Black or African American (4.90), NH White (4.57), and NH Asian or Pacific Islander (3.20) populations. Among states, the lowest AAMR was observed in the District of Columbia (1.63) while the highest was in Oregon (8.51). Stratified by census regions, the highest mortality rate was in the Western region (AAMR: 5.81), followed by the Midwestern, Southern, and Northeastern regions; 5.50, 4.17, and 2.97, respectively.

Conclusions:
Our study found substantially rising trends in HF-related mortality in type II diabetics. In different strata, the highest rates were observed in individuals over 85 years, males, NH American Indian or Alaska Natives, and those residing in the Western region, especially Oregon. Such results call for directive policy introduction in relevant areas of healthcare that can help limit fatal outcomes.
Abstract 4142639: Assessing low-density lipoprotein cholesterol (LDL-C) equations in childhood for long-term risk of cardiovascular disease events: Superior performance of the Sampson equation
Authors: Meng Yaxing , Wu Feitong , Juonala Markus , Jacobs David , Bazzano Lydia , Daniels Stephen , Dwyer Terence , Kahonen Mika , Sinaiko Alan , Steinberger Julia , Urbina Elaine , Venn Alison , Viikari Jorma , Whitaker Kara , Woo Jessica , Raitakari Olli , Magnussen Costan
Published: November 2024

Background:
Low-density lipoprotein cholesterol (LDL-C) is the primary lipid factor for diagnosing and managing lipid disorders in children. Although multiple equations are available for estimating LDL-C, the best one for assessing long-term cardiovascular (CV) risk is unclear.

Hypothesis:
Childhood LDL-C levels estimated from different equations differently associates with adult CV events.

Aim:
To compare the prospective association of childhood LDL-C levels estimated by the Friedewald, Martin/Hopkins, Sampson, and DeLong equations with adult CV events.

Methods:
Data were from seven prospective cohorts in the US, Finland, and Australia within the International Childhood Cardiovascular Cohort Consortium. LDL-C levels were estimated using four equations: Friedewald, Martin/Hopkins, Sampson, and DeLong. Discordance was defined as differing LDL-C categorizations (acceptable <110 mg/dL versus elevated ≥110 mg/dL) between equations. CV events were adjudicated from medical records. Associations between discordance and incident CV events were estimated using proportional-hazards regression, adjusted for sex, childhood age, systolic blood pressure, and body mass index.

Results:
Over a mean follow-up of 35 years, 171 fatal CV events occurred among 22262 participants (49.4% male; 24.2% Black; mean age 11.9 years in childhood) and 376 fatal/nonfatal CV events among 11627 participants. Although LDL-C levels estimated by different equations were similarly associated with CV events, predictive utility varied with discordant classifications (discordance ranging from 1.2-4.7%). Children with acceptable LDL-C by the Friedewald equation but elevated by the Martin/Hopkins, Sampson, or DeLong equations had an increased risk for CV events compared to those with concordant LDL-C (Figure). Similarly, discordance between acceptable Martin/Hopkins LDL-C but elevated LDL-C by the Sampson or DeLong equations indicated an increased risk. Conversely, discordance between elevated DeLong LDL-C but acceptable Sampson LDL-C indicated a decreased risk.

Conclusions:
The Sampson equation provides the most accurate assessment of long-term CV risk—outperforming the underestimation by Friedewald and Martin/Hopkins and the overestimation by DeLong— suggesting its potential for estimating elevated childhood LDL-C and improving early risk stratification.
Abstract 4142656: The Lack of Sphingosine Kinase 1 in Smooth Muscle Cells Protects Mice Against Angiotensin II-Induced Hypertension
Authors: Jozefczuk Ewelina , Szczepaniak Piotr , Mikolajczyk Tomasz , Nosalski Ryszard , Urbanski Karol , Wojciechowska Emilia , Filip Grzegorz , Stefanska Monika , Blyszczuk Przemyslaw , Guzik Tomasz , Siedlinski Mateusz
Published: November 2024

Introduction:
The function of the cardiovascular system is regulated by sphingosine-1-phosphate (S1P) signaling. Vascular sphingosine kinase 1 (Sphk1), an S1P-producing enzyme, is upregulated in hypertension (HTN), and mice lacking
Sphk1
globally exhibit alleviated AngII-induced HTN. Identifying cellular mechanisms providing this protection remains challenging due to the pleiotropic action of S1P.

Aim:
To identify the contributions of
Sphk1
within endothelial cells (ECs) or vascular smooth muscle cells (SMCs) to the blood pressure-lowering effect of global
Sphk1
deletion in mice.

Methods:
Mice lacking
Sphk1
either in SMCs or ECs were generated using the Cre-loxP system. Male mice were infused with AngII (490 ng/min/kg for 14 days), using osmotic minipumps, to induce HTN. Systolic blood pressure (SBP) was monitored, and vascular structure and function were examined
ex vivo
using wire/pressure myography and histological analysis. To identify key mechanistic pathways, RNA Sequencing was performed in mouse aortas and mesenteric arteries, followed by Gene set enrichment analysis. The expression patterns of the identified genes were confirmed by RT-qPCR and Western Blotting in mouse arteries and human internal mammary arteries (IMAs).

Results:
The lack of
Sphk1
in SMC conferred significant protection against HTN (mean SBP±SD 132±14.6 mmHg vs. 168±14.3 mmHg as compared to WT
flox/flox
control, p<0.05, Fig. 1), while EC KO-
Sphk1
developed HTN to the same extent as WT
flox/flox
controls (mean SBP±SD: 166±22.8 mmHg vs. 171±27.7 mmHg respectively). Lower SBP in SMC KO-
Sphk1
in HTN was associated with a significantly reduced myogenic tone of mesenteric arteries and lower expression of Rock1/2. In spite of impaired HTN development, mesenteric arteries of AngII-infused SMC KO-
Sphk1
mice were significantly stiffer and showed impaired vasorelaxations compared to the control arteries of AngII-infused WT mice, which was associated with excessive fibronectin 1 deposition. Likewise, an inverse correlation between FN1 and SPHK1 protein expression was observed in human IMAs.

Conclusion:
Our findings indicate a prevailing role of SMC-derived
Sphk1
in the regulation of myogenic tone as an important molecular regulator of AngII-induced HTN.
Abstract 4142663: Mechanism of empagliflozin improves aortic pathological remodeling in TAAD mice based on NLRP3 inflammasome
Authors: Li Shen , Xu Danyan , Qin Huali
Published: November 2024

Background:
Thoracic aortic aneurism and dissection (TAAD) is a severe macrovascular disease that lead to aortic rupture and sudden death. To date, there are no effective clinical agents to prevent the formation or control the progression of TAAD.

Objectives:
Investigate the mechanism of empagliflozin improves aortic pathological remodeling in TAAD mice.

Methods:
Four-week-old male mice were given BAPN (β-aminopropionitrile monofumarate; 1 g/kg/d) in drinking water for 4 weeks for TAD modeling. RNA sequencing analysis was performed to recapitulate transcriptome profile changes.TRIM59 with USP7 and NLRP3 in VSMCs was tested by coimmunoprecipitation assay.

Results:
1. Compared with BAPN group or MFS group, the degree of elastic fiber rupture and collagen fiber deposition in TAAD mice with two kinds of NLRP3 knockout were significantly improved (all
P
<0.05). Transcriptional sequencing showed that the effect of NLRP3 knockout on the aorta of TAAD mice was mainly focused on extracellular matrix remodeling.

2. Empagliflozin was confirmed to significantly ameliorate pathological remodeling of aortic ECM in TAAD mice (all
P
<0.05). GO/KEGG enrichment analysis revealed that empagliflozin primarily impacts ECM structure and function, as well as inflammation-related signaling pathways. Compared with the vehicle group, BAPN group displayed increased mRNA and protein levels of NLRP3, while empagliflozin decreased NLRP3 protein levels. These findings suggest that empagliflozin may regulate the post-transcriptional level of NLRP3.

3. In vitro studies have shown that empagliflozin promotes the degradation of NLRP3 protein in a dose- and time-dependent manner. MG132 offset the effect of empagliflozin on NLRP3 degradation; coimmunoprecipitation assay confirmed that empagliflozin promotes the degradation of NLRP3 through the ubiquitin-proteasome system (all
P
<0.05). In addition, TRIM59 knockdown increased NLRP3 ubiquitination levels, whereas the presence of TRIM59 increased NLRP3 deubiquitination levels. Further through the Ubibrowser 2.0 website found that TRIM59 has a strong interaction with USP7. Finally, compared with DMSO group, the interaction between USP7 and NLPR3 was weakened and the ubiquitination level of NLRP3 was increased in the empagliflozin-treated group. Notably, overexpression of TRIM59 reversed this effects of empagliflozin.

Conclusion:
Empagliflozin reduces TRIM59 expression reduces the binding of USP7 to NLRP3 and promotes ubiquitination and degradation of NLRP3.
Abstract 4142669: Elevated remnant cholesterol, LDL cholesterol, and risk of peripheral artery disease: a Mendelian randomization study
Authors: Nilsson Wadstrom Benjamin , Borges Carolina , Wulff Anders , Smith George , Sanderson Eleanor , Nordestgaard Borge
Published: November 2024

Background:
Elevated remnant cholesterol and low-density lipoprotein (LDL) cholesterol both increase risk of coronary artery disease (CAD), but it is not known if the same is true for peripheral artery disease (PAD).

Hypothesis:
We tested the hypothesis that elevated remnant cholesterol and LDL cholesterol, each independent of the other, have causal effects on risk of PAD.

Methods:
We constructed genetic scores from variants near genes known to directly affect levels of remnant cholesterol and LDL cholesterol, identified through a genome-wide association study of individuals in the UK Biobank. We used univariable (remnant cholesterol and LDL cholesterol genetic scores separately) and multivariable (remnant cholesterol and LDL cholesterol genetic scores combined) Mendelian randomization to estimate the causal effects of higher remnant cholesterol and LDL cholesterol levels on odds ratios for PAD (N = 38,414 cases and 758,308 controls) and CAD (N = 221,445 cases and 770,615 controls).

Results:
Increments in remnant and LDL genetic scores corresponding to 1 mmol/L (39 mg/dL) higher remnant and LDL cholesterol, respectively, were associated with univariable odds ratios for PAD of 2.72 (95% confidence interval: 2.10-3.52) and 1.37 (1.25-1.51), respectively (Image 1); corresponding multivariable odds ratios were 2.16 (1.49-3.12) and 1.14 (1.00-1.30), respectively. For CAD, corresponding univariable odds ratios were 2.92 (2.34-3.64) and 1.67 (1.56-1.79), while multivariable odds ratios were 1.86 (1.39-2.47) and 1.44 (1.29-1.60), respectively.

Conclusions:
Elevated remnant cholesterol had a causal effect on risk of PAD even after accounting for elevated LDL cholesterol, whereas most of the causal effect from elevated LDL cholesterol on risk of PAD was dependent on simultaneously elevated remnant cholesterol. These results indicate that remnant cholesterol may be the major cholesterol fraction responsible for increased risk of PAD, which calls for clinical trials to test if remnant cholesterol-lowering therapy could prevent PAD.
Abstract 4142677: Impact of baseline tricuspid regurgitation on outcomes after transcatheter edge – to - edge repair in patients with mitral regurgitation
Authors: Cosyns Bernard , Motoc Andreea , Donal Erwan , Marut Benjamin , Galloo Xavier , LOCHY STIJN , Unger Philippe , aminian adel , Prihadi Edgard Alexander , Droogmans Steven
Published: November 2024

A moderate or severe tricuspid regurgitation (TR) is frequently associated with mitral regurgitation (MR) and may impact prognosis after mitral valve intervention. It is yet unclear whether both valves should be treated simultaneously, especially using a percutaneous approach. Therefore, we sought to determine the impact of TR on outcomes in patients with moderate-to-severe or severe MR treated by edge-to-edge repair (TEER).

Methods:
Consecutive patients undergoing transcatheter mitral valve edge - to edge repair for moderate or severe MR from 2 tertiary centers were retrospectively included in a registry. The primary endpoint was one-year primary composite of death and heart failure hospitalization (HFH) and with the separate endpoints as secondary endpoints.

268 patients (76.4 ± 9.0 years old, 61.9% males) were included in the study, divided into 2 groups by baseline TR severity: none/trace/mild TR (≤Mild TR) (n=144) and moderate/severe TR (≥Mod TR) (n= 124). Primary MR was present in 124 (46.3%) patients, 117 (43.7%) patients had a secondary MR and 27 (10.0%) patients had a mixed MR etiology. In the total population, 45 patients reached the primary endpoint: 26 patients died and 24 patients had a HFH during the follow - up period of 1 year. An associated ≥Mod TR was an independent predictor of the primary endpoint in the global study population (OR 3.737, CI 1.020 – 13.694, p = 0.047). Other independent predictors of the primary endpoint in the global population by multivariable logistic regression analysis were left ventricle ejection fraction (OR 0.951, CI 0.916 – 0.987, p =0.009) and glomerular filtration rate (OR 0.960, CI 0.933 – 0. 987, p =0.009). In the primary MR subgroup, 14 (11.2%) patients reached the primary endpoint. In this subgroup, a ≥Mod TR was present in 56 (45.2%) of the patients and it was significantly associated with a worse outcome by univariable logistic regression analysis (OR 5.296, CI 1.398 - 20.065, p=0.014). In the secondary MR group, 21 (17.9%) patients reached the primary endpoint. In this subgroup, an associated ≥Mod TR was present in 47 (40.2 %) of the patients. A ≥Mod TR was not significantly associated with the occurrence of the primary endpoint in the secondary MR subgroup analysis. In conclusion ≥Mod TR conveys a worse 1-year outcome after TEER for MR. TEER for primary MR is associated with a worse outcome when ≥Mod TR is present, suggesting that, in this subgroup, a concomitant TEER for the TR could improve prognosis.
Abstract 4142680: Functional Heterogeneity of Na
V
1.5 in Mouse Heart
Authors: Choi Bum-rak , Dierdorff Jason , Clark Colin , Bronk Peter , Solola Nussbaum Sade , Yoon Jin-Young , Choi Hannah , Mehdi Haider , Ahern Christopher , London Barry
Published: November 2024

Introduction:
The voltage-gated sodium channel Na
V
1.5 controls cardiac excitability. The mechanisms by which loss of function Na
V
1.5 mutations cause diverse pathogenic outcomes (Brugada syndrome, conduction disease, heart failure) are not fully resolved. The physiological significance of non-Na
V
1.5 Na
+
channels in the heart is also uncertain.

Methods:
We engineered knock-in mice in which Na
V
1.5 was modified to contain a high-affinity binding site for acylsulfonamide (GX) drugs, enabling a pharmacological strategy to drive nonconducting channel conformations. We used optical mapping (di-4 ANEPPS) of Langendorff-perfused WT (n=6) and homozygous GX/GX hearts (n=14) to investigate how selective Na
V
1.5 blockade influences action potential (AP) propagation and arrhythmogenesis.

Results:
In the absence of the GX drug (GX-674) in sinus rhythm, action potential duration (APD; 71±7 vs. 68±10 ms), APD dispersion (13±5 vs. 12±3 ms), AP upstroke rise time (6±1 vs. 6±1 ms) and longitudinal (CVL, 0.71±0.16 vs. 0.85±0.16 m/s) and transverse conduction velocity (CVT, 0.43±0.11 vs. 0.49±0.1 m/s) were not statistically different between GX/GX and WT hearts. GX-674 application (0 ~ 300 nM) during optical mapping with S1S2 pacing resulted in loss of excitability (50% loss at 10 nM in GX/GX ; 0% loss up to 300 nM in WT) associated with an increase of AP upstroke rise time (10±3 vs. 5.4±0.5 ms) and conduction slowing mainly along the longitudinal direction (CVL=0.49±0.22 vs. 0.85±0.24 m/s); APD remained relatively stable (85±15 vs. 76±11 ms). The AP upstroke in GX/GX hearts often exhibited 2 steps (Fig-A), leading to frequent premature beats, reentry, and non-sustained ventricular tachycardia (Fig-B,C). The loss of excitability was heterogeneous, with sensitivity to GX-674 being higher in the right versus left ventricle (16% vs. 50% at 10 nM), Purkinje fibers and AV node (100% AV block at 100 nM), and atrial tissue (100% excitable at 100 nM but complete loss at 300 nM).

Conclusion:
Regional heterogeneities in Na
V
1.5 function, along with Na
+
channels other than Na
V
1.5, may contribute to cardiac conduction and arrhythmias in the mouse heart.
Abstract 4142690: Yoga with Low-Exercise Movement is Beneficial for Improving Sleep Quality and Altering a Sedentary Lifestyle in Patients with Heart Failure
Authors: Chung Misook , Moser Debra
Published: November 2024

Introduction:
Given the well-documented benefits of yoga on the cardiovascular system and improvement of exercise tolerance and quality of life, the American Heart Association recently recommended yoga as a safe and well-tolerated adjunctive therapy for patients with heart failure (HF). However, most studies have focused on testing yoga with moderate levels of physical movement, leaving a gap in our understanding of the potential benefits of yoga with low levels of physical movement.

The specific aims of this pilot study were to explore the potential benefits of yoga with low levels of physical exercise movement, combined with longer deep breathing and meditation, on the psychological and physical health outcomes of patients with HF.

Methods:
Yoga was delivered using tele-health to patients with HF at home. Outpatients with HF (N=17) were randomly assigned to either the intervention (n=11) or the control (n=6) groups using a 2:1 ratio. The intervention group participated in twice-weekly live-streamed yoga sessions over a 12-week period led by nurse yoga instructors. Outcome measures included depressive symptoms (Patient Health Questionnaire-9), anxiety (Hospital Anxiety Index), sleep quality (Pittsburgh Sleep Quality Index), perceived control (Control Attitude Scale-Revised), sit-stand test, and length of activity measured with an ActiGraph watch worn for 7 days. Paired t-tests were conducted to examine the differences in outcomes over time.

Results:
For the intervention group, there was a significant improvement in global sleep quality (8.8 vs. 6.0, p= 0.4 respectively), with a significant increase in sleep duration (3.0 vs 0.6, P <.001). The sit-stand score also improved significantly (9.4 vs. 11.4, p =.048). Sedentary time, as measured by ActiGraph watch, decreased significantly by 10.06 hours over 7 days (5463 vs 4859 minutes, p= 0.17), and moderate activity time increased by 2.5 hours per week, though this was not statistically significant (P=0.126). Depressive symptoms (p= 0.073) and anxiety (p=0.065) decreased, and perceived control (p =.095) improved, but those were not statistically significant. The control group showed no changes in any measures.

Conclusion:
Yoga with a low level of physical movement demonstrated benefits for enhancing sleep quality and altering sedentary lifestyles in patients with HF, with several other potential advantages. Large randomized controlled trials are needed to confirm these findings.
Abstract 4142700: Inverse decremental conduction in the left bundle following cardiac surgery: potential clinical implications
Authors: Pacifici Stefano , Istvanic Filip , Zhang Yubin , Ceron Carlos , Olleik Farah , Liu Tong , Gao Chuanyu , Yan Gan-Xin
Published: November 2024

Background:
New onset left bundle branch block (LBBB) is the most common complication following transcatheter aortic valve replacement (TAVR), occurring in up to 35% of cases. Previous case studies have shown that in some patients with new onset LBBB, the QRS duration is positively correlated with the preceding RR interval. This unique phenomenon, known as inverse decremental conduction (IDC) or Yan conduction, prompted us to investigate its clinical features and implications.

Methods:
We reviewed 12-lead ECGs and available in-patient telemetry for patients with new onset LBBB within 14 days following any types of cardiac surgery from 2018 to 2023 at two medical centers. Patients with ≥3 different degrees of LBBB in response to different preceding RR on 12-lead ECGs or on telemetry were included in the analysis.

Results:
A total of 22 patients (19 males) with a mean age of 75±8 years were identified to exhibit varying degrees of LBBB, with QRS duration that was positively correlated to the preceding RR interval within a certain range of heart rates. Among these patients, 17 had undergone TAVR, while the remaining 5 underwent surgical aortic valve replacement (AVR) and/or mitral valve replacement. 13 of the 22 patients were in sinus rhythm with premature atrial beats or sinus arrhythmias, while the remaining 9 patients were in atrial fibrillation.
Figure 1
shows the typical manifestations of
IDC
in the left bundle on ECG in a patient post TAVR, with a positive correlation between QRS duration and the preceding RR (r = 0.87, p < 0.01).
IDC
in the left bundle in patients with new-onset LBBB occurred within three days following cardiac surgeries in 20 of the 22 patients, while the remaining 2 patients exhibited
IDC
in the left bundle > 7 days after the surgeries.
IDC
in the left bundle is a temporary phenomenon, commonly lasting <24 hours in most cases, and evolving into either a normal QRS or permanent LBBB. Interestingly, alternating LBBB occurred in 5 patients with
IDC
in the left bundle as shown in
Figure 2
.

Conclusion and Comment:
1) there is a positive correlation between the preceding RR interval and QRS duration, indicating IDC in left bundle, in the patients with new onset of LBBB following cardiac surgeries particularly AVR; 2) this unique phenomenon is often short-lived; 3) theoretically, IDC in left bundle can translate into PR interval changes consistent with IDC in patients with preexisting right bundle branch block, leading to paroxysmal AV block.
Abstract 4142716: Double Guiding Catheter Technique for Orbital Atherectomy in a Heavily Calcified Coronary Bifurcation Using Microcatheter Protection for Non-atherectomy Wire
Authors: Yinadsawaphan Thanaboon , Kulthamrongsri Narathorn , Baquero Giselle
Published: November 2024

Background:
Heavily calcified coronary bifurcation lesions present significant challenges during percutaneous coronary intervention, particularly during atherectomy due to the risk of side branch occlusion from plaque shift. We describe the "Double Guiding Catheter Technique" to minimize side branch closure and wire damage to non-atherectomy vessels during bifurcation orbital atherectomy (OA).

Case:
A 74-year-old male with a recent NSTEMI presented for elective coronary artery revascularization. A coronary angiogram revealed non-obstructive left coronary arteries and a dominant right coronary artery (RCA) with heavily calcified stenosis at the bifurcation of the right posterolateral (RPL) and right posterior descending (RPD) branches. After placing temporary transvenous pacing and inserting sheaths in the right radial and right femoral arteries, both the RPL and RPD were wired with coronary guidewires. Using a coronary microcatheter, the wire in RPL was replaced with a ViperWire guidewire for OA, while the microcatheter in RPD served as guidewire protection. OA of RPL was successfully performed with the Diamondback 360° OA system (Cardiovascular Systems Inc), followed by multiple dilatations with non-compliant balloons and placement of two drug-eluting stents in the distal RCA to RPL and RPD, achieving good angiographic and IVUS results.

Discussion:
The Double Guiding Catheter Technique has been described in a few case reports of heavily calcified left main coronary bifurcation atherectomy which is limited to relatively proximal lesions due to the need to pass a second wire to a non-atherectomy vessel outside a guide extension catheter for the main branch. This is the first reported case of OA using this technique in the right coronary artery and a relatively distal part of the coronary artery. The primary advantage of this technique is eliminating the need to withdraw one of the two wires, which can be challenging when recrossing the side branch. The microcatheter can safely protect the other branch wire during atherectomy.

Conclusion:
By maintaining both wires with a protective microcatheter, OA of coronary bifurcation stenosis can be successfully achieved, potentially reducing the risk of wire transection.
Abstract 4142721: Hyperspectral imaging is effective in diagnosing patients with ischemia with non-obstructive coronary artery
Authors: Xu Tianyou , Yu Lilei
Published: November 2024

Backround:
Patients with Ischemia with non-obstructive coronary artery (INOCA) have symptoms of chronic myocardial ischemia without comorbid obstructive coronary artery disease. As a result, they often fail to receive timely diagnosis and treatment, increasing the risk of poor prognosis. Hyperspectral imaging (HSI), developed on the basis of multispectral remote sensing, can provide information on the spatial distribution of various tissue structures, analyze the chemical composition and physical characteristics of different diseases.

Objective:
In this study, we attempted to analyze the functional status of peripheral microvessels by HSI and thus identify patients with INOCA.

Methods:
This study was an observational cross-sectional study. The study included 500 patients with chest pain who underwent coronary angiography from December 2023 to May 2024 at Renmin Hospital of Wuhan University. We acquire HSI of the patient's face, palms and ears prior to coronary angiography. Patients were divided into a control group, an INOCA group, and a coronary artery blockage group according to guideline diagnostic criteria.

Results:
1. The data model (Model 1) was built by deep learning the waveband and texture data of HSI, and it showed good sensitivity and specificity for recognizing INOCA patients;2. The image model (Model 2) is built after deep learning of HSI features, and it also has good sensitivity and specificity for the diagnosis of INOCA patients. The specificity of the image model is higher than the data model, but the sensitivity is slightly worse;3. We constructed the composite model (Model 3) by fusing the data model with the image model. Compared to the data model and image model, the composite model showed higher sensitivity and specificity in the identification of INOCA patients.

Conclusion:
The model constructed based on deep learning of peripheral microvascular HSI can diagnose INOCA patients with high sensitivity and specificity.
Abstract 4142740: O
2
-independent photodynamic neuroimmune modulation for prevention and treatment of malignant arrhythmia post myocardial infarction
Authors: Liu Hengyang , Lin Heng , Yu Lilei
Published: November 2024

Background:
Hyperactivation of the left stellate ganglion (LSG) is a key link in the occurrence of ventricular arrhythmias after myocardial infarction (MI). It is reported that neuroimmune interaction based on the depleting of macrophages modulated the overactive neural activity. However, exogenous macrophage scavengers, which is the common depletion strategy in animal models, are hardly capable of depleting the target cells selectively in certain tissues and transient control performance. Consequently, a degradable nanocomposite (PPSM@CS/DSS) were fabricatedto deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarction.

Hypothesis:
In this study, we constructed a degradable nanocomposite with dual functions of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, which isanticipated to deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarctionfor prevention and treatment of ventricular arrhythmias post MI.

Methods:
The prepared nanocomposite material, which is capable of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, was slowly microinjected into LSG of Beagle dogs. The effectiveness and safety of this method based on apoptosisof M1 macrophagesby oxidizing active species was explored and the mechanism of prevention as well as treatment of malignant arrhythmias were discussed. M1 macrophages were selectively apoptotic in the LSG after myocardial infarction under the irradiation of near infrared light.

Results:
PPSM@CS/DSS is a core-shell structure with a particle size of about 50nm. The PPSM@CS/DSS nanocomposites exhibits band adsorption between 200-900 nm with a pronounced peaks at 650 nm.Cell experiments showed that PPSM@CS/DS was targeted and mainly induced apoptosis of M1 macrophages under 650nm near-red light, but did not significantly increase apoptosis of neuronal cells. PPSM@CS/DSS significantly reduced LSG activity and the incidence of malignant arrhythmias after MI in Beagle dogs under the action of 650nm light.

Conclusion:
An innovative nanomaterial for regulating LSG through depletion M1 macrophages selectively in LSG is developed to prevent and treat malignant arrhythmias after myocardial infarction.The implementation of this work will provide a novel neural modulation strategy for preventing ventricular arrhythmias.
Abstract 4142748: Direct Oral Anticoagulants Versus Aspirin for Secondary Stroke Prevention in Patients with Embolic Stroke of Undetermined Source: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Authors: Talavera Juan Armando , Teixeira Larissa , Costa Thomaz , Navalha Denilsa , Gibicoski Tathiane , Fernandez Nicole , Armaganijan Luciana , Dagostin de Carvalho Guilherme
Published: November 2024

Background:
Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. The optimal treatment strategy for secondary prevention remains uncertain for patients with ESUS. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of direct oral anticoagulants (DOACs) versus aspirin therapy in patients with a history of ESUS.

Methods:
PubMed, Embase, Cochrane and Web of science databases were systematically searched for eligible trials until March 2024. The primary outcome of interest was recurrent stroke. Major bleeding and clinically relevant non-major bleeding (CRNMB) were assessed as safety outcomes. We pooled hazard rations (HRs) with 95% confidence intervals (CIs) for analysis.

Results:
Four RCTs comparing direct oral anticoagulants (DOACs) versus aspirin were included comprising 13,970 patients, of whom 6,989 (50%) were randomized to the DOACs group. The mean follow-up was 16 months. Compared to aspirin, DOACs did not reduce the incidence of recurrent stroke (HR: 0.95; 95% CI: 0.81-1.09; p=0.44), ischemic stroke (HR: 0.91; 95% CI: 0.79-1.06; p=0.23), all-cause mortality (HR: 1.11; 95% CI: 0.87-1.42; p=0.40), and major bleeding (HR: 1.56; 95% CI: 0.85%-2.86; p=0.15). However, patients in the DOACs group presented significantly higher incidence of CRNMB (HR: 1.54; 95% CI: 1.23-1.92; p=0.0002) when compared with the aspirin group.

Conclusion:
Compared with aspirin, DOACs use was associated with an elevated risk of CRNMB and did not demonstrate superior efficacy in preventing recurrent stroke among patients with ESUS.
Abstract 4142758: Circumferential Tethering Of Pacemaker Leads To Bone Is Associated With Costoclavicular Intervention During Lead Extraction
Authors: Wagner Ethan , Lewis Robert , Pokorney Sean , Hegland Donald , koweek lynne , Piccini Jonathan
Published: November 2024

Introduction/Background:
Binding sites in the costoclavicular space are commonly encountered during transvenous lead extraction. Severe adhesions may warrant use of more aggressive rotational cutting tools or surgical intervention.

Research Questions/Hypothesis:
It is not known whether pre-procedural CT can provide information about the likelihood that a patient will require costoclavicular intervention.

Goals/Aims:
The purpose of this study was to determine if there are pre-procedural CT findings associated with need for intervention in the costoclavicular space during lead extraction.

Methods/Approach:
In this retrospective, single-center, observational study, patients who underwent lead extraction between 2013 and 2024 and required use of stiffer rotational cutting tools (TightRail Sub-C) or surgical intervention in the costoclavicular space were included. Controls who did not require costoclavicular intervention and had at least one lead with dwell time >10 years were matched to cases based on age and sex. Pre-procedural CT was evaluated for patterns of lead tethering to bone and adjacent calcification. Data were analyzed with descriptive statistics.

Results/Data:
Overall, 56 patients were included (n=20 Sub-C only, n=8 surgical intervention, and n=28 matched controls). The mean patient age of interventional cases was 65.0 ± 14.7 years, 18% were female, and the mean lead age was 12.3 ± 6.2 years. Four major patterns were identified on imaging: fat plane between lead and bone preserved by ≥1 mm (Sub-C intervention rate 5/24 patients, surgical intervention rate 0/24); fat plane not preserved (<1 mm) and <180° tethering of lead to bone (Sub-C 9/19, surgical 2/19); fat plane preserved with adjacent calcifications (Sub-C 2/4, surgical 1/4); and circumferential (>180°) tethering of lead to bone (Sub-C 4/9, surgical 5/9).

Conclusions:
Tethering of at least one lead to bone >180° was associated with a 100% rate of costoclavicular intervention and the highest rate of surgical intervention (56%). Absence of any degree of bone tethering or adjacent calcifications was associated with a 0% rate of surgical intervention. CT may be useful in pre-procedural planning for adhesions in the costoclavicular space.
Abstract 4142820: Vessel-by-Vessel CT Calcium Scoring in Peripheral Artery Disease: Association with Patient-Level Factors
Authors: Rimmerman Eleanor , Musini Kumudha , Chou Ting-Heng , Trainer Jenna , Atway Said , Go Michael , Stacy Mitchel
Published: November 2024

Introduction:
Peripheral artery disease (PAD) is an atherosclerotic condition that promotes lower extremity arterial calcification, which can decrease skeletal muscle perfusion, limit revascularization options, contribute to worse revascularization outcomes, and increase risk of adverse events. Although vascular calcium scoring via computed tomography (CT) imaging has already gained attention for risk assessment in coronary artery disease (CAD), analytical methods for vessel-by-vessel CT calcium scoring in PAD remain underdeveloped and understudied. We hypothesized that CT imaging would allow for vessel-specific calcium scoring in PAD patients and elucidate the contributions of patient-level factors promoting vascular calcification.

Methods:
PAD patients (n=90) were prospectively enrolled and underwent non-contrast CT imaging of the legs (CT parameters: slice thickness 3.27 mm, 120 kVp, 85 mA). Five arteries of interest (femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, peroneal) were manually segmented using axial CT images along the length of the symptomatic limb. Calcium mass was quantified for each arterial segment using a CT image threshold of ≥130 Hounsfield units and mean calcium mass was calculated for each artery. T-tests were used to compare calcium values between patients with (n=62) and without diabetes mellitus (DM) (n=28). Multivariate linear regression was conducted to assess the role of patient-level factors on vessel-specific calcium burden.

Results:
Image analysis demonstrated that PAD patients with DM had significantly higher calcium burden compared to PAD patients without DM for 4 out of 5 peripheral arteries assessed (femoral-popliteal p=0.01, anterior tibial p=0.002, peroneal p=0.004, posterior tibial p=0.001). After adjusting for age, sex, and body mass index, multivariate analyses revealed that a history of CAD, dialysis dependence, and DM were significantly and positively associated with peripheral artery calcium burden.

Conclusions:
CT imaging allows for vessel-by-vessel calcium scoring in PAD and provides insight into the patient characteristics that may contribute to calcium burden. Future broader use of calcium scoring in PAD may allow for identification of ideal roadmaps for interventional planning, identify who is most susceptible to technical failure from interventions, and predict limb outcomes by providing quantitative data related to disease characteristics on a vessel- and lesion-specific basis.
Abstract 4142836: Association of Lipoprotein(a) with Cardiovascular Outcomes Across the Spectrum of HbA1c Levels
Authors: Alebna Pamela , Ambrosio Mathew , Akakpo Divine , Bolden Gabrielle , Razavi Alexander , Chew Nicholas , Hundley William , Salloum Fadi , Sperling Laurence , Shapiro Michael , Bhatia Harpreet , Mehta Anurag
Published: November 2024

Introduction:
Both Lipoprotein(a) [Lp(a)] and Hemoglobin A1c (HbA1c) are established independent predictors of major adverse cardiovascular events (MACE). Evidence suggests there is an inverse association between Lp(a) concentration and risk of T2DM. While prior studies have evaluated the effect of Lp(a) on DM incidence, the association of Lp(a) with MACE across the spectrum of HbA1c and a potential interaction between the two markers has not been evaluated. This study assessed the association between Lp(a) and cardiovascular outcomes across HbA1c levels.

Methods:
This analysis included 356,054 participants from the UK Biobank. Non-elevated and elevated Lp(a) levels were categorized as <125 nmol/L and
>
125 nmol/L, respectively. Participants with HbA1c levels below the 0 percentile (<4.3%) and above the 99.9th percentile (>9.0%) were excluded, totaling 2,342 individuals (less than 1% of the entire data). These values were excluded due to the poor performance of the spline model at the extremes. MACE was defined as a composite of myocardial infarction (MI), stroke, and cardiovascular death. The association of elevated Lp(a) with MACE was evaluated using a Cox proportional hazards regression model. A quadratic spline function of baseline HbA1c by Lp(a) was used to analyze the association of elevated vs. non-elevated measures of Lp(a) with MACE across a continuum of baseline HbA1c values. Secondary analyses were performed for the risk of MI, stroke, and heart failure.

Results:
There were 39,934 participants with Lp(a)
>
125 nmol/L (11.22%). The mean age was 56.5 years, 54.4% were women, and 94.2% were White. The mean HbA1c was 5.5% ± 0.6%. During a median follow-up of 14.3 years, there were 18,848 MACE (5.29%), including 10,826 MIs, 6,746 strokes, and 3,780 cardiovascular deaths. Elevated Lp(a) level (HR 1.20; 95% CI: 1.09 -1.32) and higher HbA1c (per 1% increase, HR 1.45; 95% CI: 1.38 -1.53) were independently associated with MACE. Across a continuum of HbA1c values, MACE was consistently higher and stable in participants with elevated Lp(a). (Figure). The interaction between Lp(a) and HbA1c in the quadratic spline model was not significant. A similar trend was observed for MI, stroke, and heart failure risk.

Conclusion:
Elevated Lp(a) and HbA1c are independently associated with MACE risk. HbA1c values do not modify the relationship of Lp(a) with MACE, suggesting that measurement of Lp(a) should be prioritized for individuals with and without DM