bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16783: Discovery and Characterization of Transient Endothelial Stem-Like Cells Responsible for Rapid Lung Microvascular Regeneration Post Endothelial Ablation
Authors: Safaie Qamsari Elmira , Cober Nicholas D , Soares Godoy Rafael , Wang Liyuan , Schlosser Ken , Stewart Duncan
Published: December 2023

Background:
Single-cell RNA sequencing (scRNA-seq) has revealed two main types of alveolar capillary endothelial cells (ECs): aCap ECs (or aerocytes) express typical aCap markers, including apelin, whereas general (gCap) ECs express apelin receptor,
Aplnr
/APJ. Aerocytes constitute the air-blood barrier and are incapable of proliferation, unlike smaller gCap ECs that can proliferate.

Hypothesis:
After lung microvascular injury, gCap ECs give rise to stem-like ECs that can regenerate depleted lung EC populations, including highly specialized aerocytes.
Approach:
scRNA-seq was used to study depletion and regeneration of lung EC populations after intratracheal instillation of diphtheria toxin (DT) in transgenic mice harboring an EC-targeted human DT receptor.

Results:
DT resulted in ~80% loss of lung microvascular EC populations including aerocytes, associated with severe acute lung injury (ALI), and there was full spontaneous recovery by day 7. Interestingly, a novel EC population appeared at day 3 post injury in a transitional gCap EC cluster characterized by paradoxical expression of ‘aCap’ marker, apelin, together with endothelial progenitor/stem cell markers,
Cd34
and endothelial protein C receptor (
Procr
/EPCR). These ‘transient endothelial stem-like cells’ (TESCs) transitioned to highly proliferative progenitor-like
FoxM1
+ cells ultimately repopulating all depleted EC populations by day 7. Using flow cytometry of lung cells harvested at 3 days post DT instillation, TESCs were identified by unique co-expression of CD34 and EPCR (Figure), thereby allowing isolation and culture in vitro for further characterization of their proliferation and differentiation potential.

Conclusions:
Lung microvascular repair is orchestrated by the emergence of stem-like, gCap ECs (TESCs), transiently expressing aCap/aerocyte marker, apelin, together with
Procr
/EPCR, which have the capacity to regenerate lung microvasculature rapidly and efficiently.
Abstract 16797: The Role of Adiposity on Microvascular Dysfunction and Arterial Stiffness in Patients With New Onset Breast Cancer
Authors: Bajaj Pratima , Looney Jacob , Blackburn Marsha , Crandall Reva , thomas jeffrey , Mukundi Tiffany , Simon Abigayle , Guha Avirup , Weintraub Neal L , Raval Priyanka , Ciuro Jordan , Harris Ryan A
Published: December 2023

INTRODUCTION:
Increased adiposity is a risk factor for both cardiovascular disease (CVD) and cancer. Microvascular endothelial dysfunction and arterial stiffness are independent risk factors for CVD and can accelerate vascular aging. Whether or not adiposity plays a role in vascular aging over time in patients with new-onset breast cancer (BC) has yet to be elucidated.

Hypothesis:
Adiposity impacts microvascular dysfunction and arterial stiffness differently in women undergoing therapy for recent BC diagnoses.

Methods:
Two lean (L; BMI < 25 kg/m
2
) and four overweight and obese (Ow/Ob; BMI > 25 kg/m
2
) women diagnosed with BC within the last 3 months participated in the study. Using laser Doppler imaging, microvascular endothelial function was assessed with three protocols: 1) cutaneous post-occlusion reactive hyperemia (PORH), 2) local thermal heating (LTH), and 3) iontophoresis of acetylcholine. Arterial stiffness was assessed using pulse wave velocity (PWV) and pulse wave analysis (PWA). Assessments were made at baseline and at 3 and 6 months following enrollment. Data are reported as means ± SE.

Results:
No differences in age, height, blood pressure, or total cholesterol (all
p
>0.05) were observed between L and Ow/Ob groups. Microvascular function and arterial stiffness were similar at baseline between groups. There was a greater decrease in LTH responses from baseline to 6 months post-baseline in Ow/Ob women (Δ-48±4 PU;
p
=0.001) compared to L women (Δ-16±13 PU;
p
=0.125). Similar responses in both groups were noted for PORH (
p
=0.886) and iontophoresis (
p
=0.784). PWV was similar from baseline to 6 months post-baseline in both groups; however, the PWA tended to increase over time in Ow/Ob women (Δ2.5±4.7) and decrease in L women (Δ-3.0±5.0).

CONCLUSION:
Ow/Ob women have a greater rate of decline in LTH responses compared with L women, whereas similar responses between L and OW/OB women were observed over time for PORH and iontophoresis. In addition, central aortic stiffness increased in Ow/Ob women and decreased in L women, while no change in PWV was observed. These findings suggest that adiposity may impact vascular beds differently over time following the initial diagnosis of breast cancer.
Abstract 16806: Transcatheter Edge-to-Edge Repair Lessens Atrial Fibrillation Burden by Ameliorating Left Atrial Strain in Moderate-to-Severe Mitral Regurgitation Patients
Authors: Romano Letizia R , Curcio Antonio , Scalzi Giuseppe , Malizia Biagio , Augusto Florinda M , Bartone Anna , Aquila Iolanda , Polimeni Alberto , Santarpia Giuseppe , Indolfi Ciro
Published: December 2023

Introduction:
trans-catheter edge-to-edge repair (TEER) represents a therapeutic possibility in patients with moderate-severe mitral regurgitation (MR) considered at high surgical risk. Only in recent years, it has been realized that left atrial (LA) function plays a prognostic role in these patients.

Hypothesis:
since atrial fibrillation (AF) depends in part on LA geometry, we considered that two-dimensional speckle-tracking-echocardiography analysis could predict AF burden.

Aim:
we therefore evaluated the AF occurrence long term after TEER.

Methods:
one hundred nine patients treated by TEER between February ‘15 and April ’22 underwent reservoir (R_s), conduct (D_s), and contractile (C_s) evaluations strains before and 1,6,12 months after TEER. Cardiac rhythm was monitored through 24 hours Holter-ECG or previously implanted cardiac devices, when available. Statistical analysis was performed with SPSS. Comparisons were carried out by ANOVA and MANOVA.

Results:
to the permanent AF group (n=35), no paroxysmal (N=15), nor persistent (N=8) case was added during follow-up after TEER. Among the sinus rhythm (N=51) group, one episode of atrial tachyarrhythmia was found at device interrogation and one patient developed paroxysmal AF (2/51; 3,9%). Significant improvements in total cohort were observed at 12 months follow-up for R_s (from 10,77±5,74% to 16,28±6,93%; p<0,0001), D_s (from -6,72±4,44% to -9,73±4,48%; p=0,0003) and C_s (from -5,21±5,11% to 7,72±5,4%; p=0,0184) compared to baseline. AF burden in paroxysmal AF (baseline: 9,2±4,7 hours, follow-up: 5,8±4,2 hours; p<0,001) was significantly reduced as well as ventricular rate (baseline 88±14 bpm; 12 months 76±13 bpm; p<0,001) in permanent AF group.

Conclusions:
MR reduction following TEER dictates positive LA remodelling and significant improvement of LA strain. Overall, the impact on LA geometry contributed to lessen incidence and burden of AF.
Abstract 16809: Deep-Learning-Based Assessment of Left Atrial Volume in Coronary Calcium CT: Association With NT-proBNP and Clinical Outcomes
Authors: Kay Fernando , Simek Shawn , Abbara Suhny , Ayers Colby , Garg Sonia , Pandey Ambarish , Khera Amit , Drazner Mark H , Rohatgi Anand , Budoff Matthew J , de Lemos James A , Peshock Ronald M , Joshi Parag H
Published: December 2023

Introduction:
Artificial Intelligence (AI) promises to extract imaging biomarkers for cardio-cerebrovascular (CV) risk prediction, though validation is still lacking. Recognizing the importance of left atrial pathology on CV events, we developed an AI algorithm to measure left atrial volume (LAvol) from CAC-CT. Its correlation with MRI, biomarkers, and CV incidents was then tested in the Dallas Heart Study 2 (DHS).

Hypothesis:
LAvol will be associated with elevations in baseline NT-proBNP levels and incident CV events.

Methods:
We trained a 3D U-Net model for cardiac chamber segmentation on CAC-CT, assessing congruity with manual segmentation via the Dice score. Normalized left atrial volume (LAvol/BSA) from 3D segmentations was compared to MRI using ICC, and its associations with baseline NT-proBNP and incident Afib, TIA, and stroke were evaluated with logistic regression and Cox models.

Results:
Cardiac segmentation showed an excellent Dice score of 0.93 ± 0.01. Moderate correlation was observed between CAC-CT estimates of LAvol/BSA and MRI (ICC 0.57, 95% CI 0.52-0.62). Our study, excluding those with prior events, comprised 1852 participants (mean age 50, 41% male, 46% black, 15% Hispanic). Upon multivariable adjustment (detailed in the table), LAvol/BSA was linked with elevated NT-proBNP (≥ 100 pg/mL) (OR 1.9, 95% CI 1.6-2.2 per 1SD LAvol/BSA). Over a 12.5-year follow-up, CAC-CT-derived LAvol/BSA showed association with a composite of Afib, TIA, and stroke (55 events) (HR 1.4, 95% CI 1.1 - 1.8), and Afib (HR 1.7, 95% CI 1.2 - 2.3), post-adjustment. No significant association was found with TIA (HR 1.2, 95% CI 0.6 - 2.1) or stroke (HR 1.3, 95% CI 0.9 - 1.8). Among 749 subjects, MRI-derived LAvol/BSA correlated with NT-proBNP (OR 1.7, 95% CI 1.44 - 2.10) but not with other clinical outcomes.

Conclusions:
Given associations with NT-proBNP levels and incident CV events, AI-measured LAvol from CAC-CT promises to improve risk prediction.
Abstract 16819: Activation of Mitochondrial Calpain 1 Contributes to Complex I Damage During ER Stress
Authors: Chen Qun , Li Ling , Thompson Jeremy , Ying Hu , Willard Belinda , Lesnefsky Edward J
Published: December 2023

Introduction:
ER (Endoplasmic reticulum) stress is increased in failing hearts. The increased ER stress impairs complex I in cardiac mitochondria (MITO). Calpain 1 (CPN1) and calpain 2 (CPN2) are calcium-dependent cysteine proteases located in cytosol and MITO (mCPN1 and mCPN2). Activation of mCPN1 contributes to complex I damage during ischemia-reperfusion (IR) and aging. Activation of the mCPN2 causes complex I damage following IR. However. the role of mCPN1 and mCPN2 activation in ER stress-mediated complex I damage remains unclear.

Hypothesis:
ER stress leads to complex I damage by activating mCPN1 and mCPN2.

Methods:
Wild type (WT) and conditional cardiomyocyte specific calpain 4 (CPN4) knockout (KO) mice were used. CPN4 is a small regulatory subunit of CPN1 and 2, and KO of CPN4 eliminates CPN1 and CPN2 activities. Tunicamycin (TUNI, 0.4 mg/kg) was used to induce ER stress in both WT and KO mice through one time IP injection. DMSO was used as vehicle treatment. Mice were sacrificed for cardiac mitochondrial isolation after 72 hours of vehicle or TUNI treatment.

Results:
ER stress was increased in both WT and KO mice, as shown by increased BIP in TUNI-treated mice (Figure, Panel A). Compared to vehicle, the rate of oxidative phosphorylation (OXPHOS) was decreased in TUNI-treated WT when glutamate + malate was used as complex I substrate (Panel B). In contrast, TUNI treatment did not alter OXPHOS with complex I substrate in KO (Panel B). Direct measurement of complex I activity showed that TUNI treatment only decreased complex I in MITO from WT but not from KO (Panel C). Proteomic study showed that the contents of complex I subunits including NDUFV2 and ND5 were decreased in WT but not in KO mice (Panel D); confirmed by western blotting (data not shown). These results indicate that activation of mCPN1 and mCPN2 contributes to the degradation of complex I subunits during ER stress.

Conclusion:
Induction of acute ER stress using TUNI damages complex I by activating mCPN1 and mCPN2.
Abstract 16840: A Novel Long-Acting CRF2 Receptor Agonist COR-1167 Improves Cardiac and Renal Function on Top of Furosemide in a Sheep Model of Pacing Induced Heart Failure
Authors: Kowala Mark C , Rademaker Miriam T , Scott Nicola J , Charles Chris J , Lawson Francesca C , Ozoux Marie-Laure , Janiak Philip
Published: December 2023

Urocortin-2 (UCN-2), a member of the corticotrophin releasing factor family, has cardiovascular protective effects mediated via activation of CRF2 receptors. Exploratory studies in ovine heart failure (HF) and in HF patients demonstrated that acute intravenous (IV) infusion of UCN-2 (1-4hrs), on top of standard of care, temporarily improved cardiac function. However, the short t
1/2
of recombinant UCN-2 (~15 min) limits its therapeutic utility. A stable CRF2 peptide agonist was developed, named COR-1167, that is potent and selective for CRF2 versus CRF1 receptors and it was tested chronically in vivo. Adult female sheep were anesthetized, and instrumented with 7F His bundle electrodes, arterial, venous and Swan-Ganz catheters, pressure transducers, and flow probes. After recovery, HF was induced by rapid cardiac pacing that was maintained during the study. COR-1167 (5 μg/kg/day SC) in combination with furosemide (0.35 mg/kg/day IV) versus furosemide alone was administered for 5 days and cardiorenal parameters were constantly monitored in conscious sheep. Furosemide had no effect on cardiac function while it increased urine Na
+
, when compared to pre-treatment measurements. Compared to furosemide, COR-1167 plus furosemide significantly enhanced cardiac and renal function parameters (Table).

Mean
+
SEM for Days 1-5 (CV, biomarker and renal parameters), F (n=5-7), F + COR-1167 (n=6-7), Repeated Measures ANOVA; *BW Day 0 minus Day 5 = BW change, Unpaired t test. COR-1167 cardiorenal benefits occurred within 2 hours of the first dose and were sustained, without changing SBP. It increased natriuresis and decreased net fluid balance (water intake minus urine volume) and BW (reflecting a reduction in congestion). In conclusion, chronic CRF2 receptor activation by COR-1167 significantly improved both cardiac and renal function on top of furosemide in ovine HF and potentially is a unique therapy for HF patients.
Abstract 16848: Reduced Survival of Patients Treated With Leadless Right Ventricular Pacemakers
Authors: Wong Anne J , Hauser Robert G , Kapphahn-Bergs Melanie J , Casey Susan A , Witt Dawn R , Walser-Kuntz Evan T , Sengupta Jay D
Published: December 2023

Introduction:
Leadless right ventricular pacemakers (LVP) are particularly valuable for patients who lack venous access for transvenous pacing (TVP) or who are at risk for pocket complications including infection, erosion, or hematoma. Since such patients constitute a unique population, we sought to compare their 2-year survival (SURV) to that of patients paced with traditional TVP or conduction system pacemakers (CSP).

Hypothesis:
The SURV of patients treated with a LVP for reasons related to venous access or potential pocket complications is different from the SURV of TVP or CSP patients.

Methods:
We calculated the weighted and unweighted Kaplan-Meier SURV of patients implanted with a LVP, TVP, or CSP at our institution. The Piccini risk score variables (age, BMI, gender, heart failure, CAD, prior MI, pulmonary hypertension, COPD, atrial fibrillation, prior cardiac intervention, and chronic kidney disease) were used to weight patients via the generalized linear model method, which successfully reduced comorbidity variability between the LVP, TVP, and CSP groups. All analyses were conducted in R 4.2.3.

Results:
The weighted and unweighted SURV of 335 patients who were implanted with a LVP (n=196), CSP (n=89), or traditional TVP (n=50) are shown in the graph. Despite weighting patients using the Piccini risk score, LVP SURV was significantly lower than that of patients paced with TVP or CSP pacemakers (p<0.01). The SURV of CSP and TVP patients were similar (p=0.51).

Conclusions:
For unclear reasons, the near-term prognosis of these LVP patients appears to be considerably less favorable than those receiving TVP or CSP pacemakers. Importantly, while further study is needed, this finding should be considered when evaluating the survival of leadless pacemaker populations.
Abstract 16850: Suicide Left Ventricle After Transcatheter Aortic Valve Replacement. A Systematic Review
Authors: Barzallo Diego , Torrado Juan F , Benites Moya Cesar J , Kharawala Amrin , Sturla Matteo , Echarte Morales Julio , Scotti Andrea , Terre Juan , wiley jose , Goldberg Ythan
Published: December 2023

Introduction:
Suicide left ventricle (LV) is an infrequent but severe complication of transcatheter aortic valve replacement (TAVR) that is poorly defined. It is generally referred to as hemodynamic collapse following valve deployment due to acute LV dynamic obstruction. Understanding this complication is essential for its prompt diagnosis and treatment.

Methods:
We conducted a systematic literature review for studies describing suicide LV (i.e., severe hypotension causing hemodynamic collapse and/or end-organ failure in the setting of a new or worsened dynamic intraventricular gradient after TAVR). Two authors reviewed each study for eligibility, and a third author resolved disagreements.

Results:
Of 506 studies, 27 publications were considered for the final analysis. Most patients that met the inclusion criteria of suicide LV were women (96%), demonstrating a small ventricle (70%), a hypertrophic septum (81%), and hyperdynamic contractility (50%) on pre-TAVR echocardiographic assessment. An intraventricular gradient pre-TAVR was found in half of the cases. Suicide LV manifested as severe hypotension occurred most often immediately after valve deployment. The LV outflow tract was the most common site of obstruction (85%) (i.e., LVOTO), compared to midventricular obstruction (MVO). Advanced therapies were required in nearly 70% of the cases. The most common advanced therapies were alcohol septal ablation and ventricular pacing.

Conclusions:
LV suicide after TAVR occurred almost invariably in women. The use of echocardiography before TAVR may be essential to anticipate this complication. Although previous studies report MVO being a more common site of dynamic intraventricular gradient after TAVR, LVOTO appears to carry the highest risk of suicide LV. Further research is required to predict better the risk of suicide LV to improve the ability to perform a bailout strategy in patients with hemodynamic collapse refractory to medical therapy.
Abstract 16861: Early Sedation With Dexmedetomidine in Patients With Acute Myocardial Infarction Who Require Mechanical Ventilation
Authors: Schenck Christopher S , Singh Avinainder , Banna Soumya , Garimella Sanjana , Thomas Alexander W , Heck Cory , Ludmir Jonathan , Ali Tariq , Dudzinski David M , Miller Elliott
Published: December 2023

Background:
Patients with acute myocardial infarction (AMI) who require mechanical ventilation (MV) are a critically ill population which require sedatives and analgesia for comfort. However, clinical trials, including those for dexmedetomidine, exclude or poorly represent patients with AMI.

Research Question:
Is early sedation with dexmedetomidine associated with lower hospital mortality compared to usual-care sedation in patients with AMI who require MV?

Methods:
We utilized the Vizient® Clinical Data Base to identify patients aged ≥18 years who were admitted between 2015 and 2019 with a primary diagnosis of AMI and required MV within 7 days of admission. Patients were assigned to the early dexmedetomidine group if they received dexmedetomidine on the first day of MV; the remaining patients were assigned to the usual care group. Inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk differences between groups.

Results:
Of the 21,303 patients included in the study, 1,620 (7.6%) received early dexmedetomidine (
Table
). Patients who received early dexmedetomidine were younger (66 vs 67 years) and less likely to be female (29.3% vs 33.8%) (both,
P
<0.05). Median ventilator days for early dexmedetomidine vs usual care was 4 and 3 days, respectively (
P
<0.001). Patients who received early dexmedetomidine had lower hospital mortality compared to usual care (33.0% vs 46.0%,
P
<0.001) despite higher prevalence of cardiogenic shock. After IPTW, the early dexmedetomidine group had a 16.2% (95% confidence interval [CI]: 13.6%-18.7%) lower mortality. The early dexmedetomidine group had more ventilator-free days (13.6 vs 9.7,
P
<0.001), which persisted after IPTW (mean difference: +4.9 days, 95% CI: 4.2-5.5 days).

Conclusion:
Early sedation with dexmedetomidine may be associated with lower mortality compared to usual care in patients with AMI who require MV. A randomized controlled trial of sedative agents in this population is warranted.
Abstract 16888: Reduced Diastolic Myocardial Strain From Interstitial Fibrosis Dissociates the Myocardial Transcriptional Response to Transient Increases in Left Ventricular End-Diastolic Filling Pressure (LVEDP)
Authors: Graser Luke , Weil Brian R , Young Rebeccah , Canty John M
Published: December 2023

Objective:
Brief repetitive pressure overload (RPO) in swine leads to interstitial fibrosis and reduced diastolic left ventricular (LV) compliance in the absence of LV hypertrophy. The present study determined whether LV compliance influences the transcriptional response to elevated LVEDP.

Methods:
Brief pressure overload was produced with phenylephrine (1-2 hours) to elevate LVEDP from 11.4±1.2 mmHg to 30.3±2.4 mmHg in normal hearts (n=6) and from 12.3±0.9 mmHg to 30.0±1.6 mmHg after 2 weeks of daily RPO (n=8). Interstitial fibrosis was quantified using picrosirius red staining. Whole tissue RNA-seq was performed on RNA isolated from LV samples collected 24 hours after increased LVEDP in each group vs. unstressed controls (n=10). Transcripts were mapped to Ensembl Sscrofa 11.1 gene index, aligned with Salmon, and mapped to human homologs using Biomart. Differential expression analysis was performed with DESeq2 package and gene ontology was performed using DAVID. Genes were considered differentially expressed (DEG) if the absolute value of log2fc was > 0.477 (∼33% change) and a p < 0.05.

Results:
Chronic RPO increased interstitial fibrosis (12.9±1.8% vs. 6.5±1.5% in normals; p<0.05) and markedly reduced diastolic circumferential strain (1.5±2.7% vs. 20.3±4.4% in normals; p<0.05). Stretch activated genes ANP and BNP were significantly upregulated with increased LVEDP in normal hearts (fc 35.8 and 14.3; both p<9x10
–
9
), but not in hearts after RPO (fc 1.4 and 1.8; both p-ns). Among the 15,133 total genes expressed, increased LVEDP induced 3,534 DEGs in normal hearts. Top gene ontology enriched pathways included ECM, cytoskeleton, cell junction, and microtubules. In contrast, there was a marked reduction in DEGs (117) observed when LVEDP was elevated in the stiff LV after RPO.

Conclusions:
Elevated LVEDP in the normal heart leads to many DEGs including the ECM and cytoskeleton proteins involved in reducing LV compliance. In contrast, after RPO and the development of interstitial fibrosis, there is a marked attenuation of the transcriptional response to increased LVEDP. These data support the notion that myocardial strain rather than pressure is the primary physiological determinant of the transcriptional response to pressure overload.
Abstract 16898: Myocardial Recovery Associated Gene Cdcp1 Expression Attenuates Cardiac Fibrosis in a Pressure Over-Load Mouse Model
Authors: Wang Min , Vyas Hridyanshu , Roos Carolyn , Huang Runqing , Liu Duan , Sahni Jyotan , McNamara Dennis M , Barlera Simona , Pileggi Silvana , Mestroni Luisa , Merlo Marco , Sinagra Gianfranco , Pinet Florence , Chaloupka Anna , Krejci Jan , de GROOTE Pascal , Weinshilboum Richard , Miller Jordan D , Pereira Naveen L
Published: December 2023

Background:
We have previously demonstrated by performing a genome-wide association study that a genetic locus resulting in ↓CDCP1 expression was associated with myocardial recovery in patients with dilated cardiomyopathy (DCM). We have subsequently shown that ↓CDCP1 decreases human cardiac fibroblast proliferation
in vitro
, however, its potential role in modulating cardiac fibrosis and function
in vivo
is unknown.

Methods:
A
Cdcp1
knock-out (KO) mouse was generated on FVB/NJ background. Angiotensin II/Phenylephrine (AngII/PE) or saline was infused by an osmotic pump into mice (
Cdcp1
KO n=20; wild type/wt n=18) for 4 weeks. Echocardiography was performed at 0 and 4 weeks. Picrosirius red (PSR) staining was performed on cross-sectional heart tissue to identify cardiac fibrosis, which was quantified, using ImageJ software, as a percentage of left ventricular (LV) area stained by PSR.

Results:
LV mass index (LVMI) significantly increased in AngII/PE wt mice as compared to saline wt (figure a. 3.65±0.15 mg/g
vs
3.05±0.17mg/g, p=0.01), however, AngII/PE
Cdcp1
KO mice had significantly decreased LVMI as compared to AngII/PE wt mice (figure a. 3.17±0.09 mg/g vs 3.65±0.15 mg/g, p=0.01). In addition, fractional shortening trended higher in AngII/PE
Cdcp1
KO mice as compared to AngII/PE wt mice (figure b. 50.36±2.06%
vs
45.48±1.43%, p=0.07). Extent of cardiac fibrosis was significantly higher in AngII/PE wt mice as compared to saline wt (figure c. 15.79±0.49%
vs
7.93±0.39%, p<0.0001), however AngII/PE
Cdcp1
KO mice had significantly reduced cardiac fibrosis as compared to AngII/PE wt mice (figure c. 9.41±0.43%, p<0.0001).

Conclusions:
CDCP1 KO significantly reduces pressure over-load induced LV hypertrophy and cardiac fibrosis. Its role as a novel therapeutic target in attenuating fibrosis and improving cardiac function in DCM needs to be further explored.
Abstract 16967: Effect of Catheter Ablation of Persistent Atrial Fibrillation on Surface Atrial ECG Dominant Frequency
Authors: Zaatari Ghaith , Bohorquez Jorge , McDermott Laura , Mitrani Raul , Blandon Catherine , velasquez alex , Lambrakos Litsa , Goldberger Jeffrey J
Published: December 2023

Background:
There are no standard techniques to track effects of catheter ablation (CA) of persistent atrial fibrillation (PeAF). The Atrial ECG (A-ECG) derived from the standard ECG provides the atrial dominant frequency (DF), an estimation of atrial rate.

Research Question:
Does CA for PeAF diminish A-ECG DF?

Aims:
To evaluate change in A-ECG peak DF pre- and post-CA.

Methods:
We obtained 1-minute epochs of surface ECG pre- and post-CA in 32 patients (age 63±9 years; 71% males) undergoing CA for PeAF. A-ECG was derived by QRST subtraction and independent component analysis filtering, and divided into overlapping10-second windows, each subjected to Fast Fourier Transform. DF was calculated for each lead as the average DF for all 10-sec segments. Peak A-ECG DF was assessed by regional lead group and among all leads. 10 patients were excluded for significant artifact. Of the 22 analyzed patients, all had pulmonary vein isolation and 3 had posterior wall isolation. Two-year outcomes were available in 20 patients (13 were free from recurrent AF).

Results:
The figure shows the change in the time-frequency plot (left panel) of DF for one subject and the shift in the spectra (right panel) with CA. A-ECG peak DF was significantly lower post- versus pre-CA: 5.96±0.63 vs 6.16±0.64 Hz, p=0.0009. By lead group, peak DFs were all lower post CA - Anterior (V1-3): 5.94±0.62 vs 6.13±0.64 Hz, p=0.0015; Inferior (II, III, aVF): 5.82±0.63 vs 6.01±0.66 Hz, p=0.0040; Lateral (I, aVL, V5-6): 5.82±0.64 vs 5.99±0.63 Hz, p=0.0015. In this small cohort, there was no significant difference in change of peak DF in those free from AF versus with recurrent AF (-2.4±4.3% vs -4.6±3.7%, p=0.26).

Conclusion:
The A-ECG provides physiologic information of activation rate in PeAF, but despite current, advanced signal processing techniques is analyzable in only 69% of patients. CA results in a significant reduction in DF. Clinical implications of these CA induced changes require further study.
Abstract 16984: A Wearable Device Reproducibly Identifies Premature Ventricular Contractions and Tachyarrhythmias in Heart Failure Patients
Authors: Romano Letizia R , Curcio Antonio , Scalzi Giuseppe , Festa Miriam , Malizia Biagio , Panarello Alessandra , Bartone Anna , Serafino Sergio , Passafaro Francesco , Indolfi Ciro
Published: December 2023

Introduction:
occurrence of ventricular arrhythmias (VAs) has a dramatic impact on prognosis of patients with heart failure (HF).

Hypothesis:
wearable devices, including smartwatch (SW), might provide real-time informations in patients at risk of VAs.

Aims:
we therefore evaluated if SW detection of QRS interval width and voltage could reproducibly detect VAs and/or premature ventricular contractions (PVCs) in HF patients.

Methods:
HF patients (N=100) underwent continuous electrocardiographic (ECG) recordings through telemetry and SW during hospital admission. Left ventricular ejection fraction (EF) and laboratory pro-BNP levels assessments were obtained as well. Correlation of the ECG results was addressed using Pearson’s analysis for normally distributed data and Spearman’s analysis for non-parametric data. Bland-Altman was used for reliability between telemetry and SW ECG measurements.

Results:
mean EF was 45.92±12.12%; mean pro-BNP was 2826±5823 pg/mL. Using the SW and the ECG data, QRS width and voltage correlation coefficients were 0.990 (p<0.001) and 0.974 (p<0.001), respectively. Concordance was found between the two assessments for QRS width (bias, 0.20; SD 3.0; lower limit, –5.68; upper limit, 6.08), and voltage (bias, -0.029; SD, 0.611; lower limit, –1.227; upper limit, 1.169). Moreover, we found correlation coefficients of 0.964 (p<0.001) and 0.970 (p<0.001), respectively, for PVCs width and PVCs voltage using SW and telemetry or other ECG report. Similarly, both techniques showed positive concordance for PVCs width (bias, 0.368; SD, 2.65; lower limit, -4.83; upper limit, 5.56) and PVCs voltage (bias, 0.54; SD, 1.25; lower limit, -1.91; and upper limit, 2.996). Remarkably, VAs identification by the SW was reproducible and standardized.

Conclusions:
continuous monitoring through SW might be considered in HF patients upon discharge.
Abstract 16985: Spatial Accuracy of Non-Invasive Activation Mapping Modalities for Complex Ventricular Arrhythmias: A Direct Comparison of Electromechanical Wave Imaging (EWI) Using High Frame Rate Transthoracic Echocardiography and Electrocardiographic Imaging (ECGi) With Cardiac CT
Authors: Tonko Johanna , Tourni Melina , Konofagou Elisa , Lambiase Pier
Published: December 2023

Background:
Non-invasive identification of the site of origin (SOO) of ventricular arrhythmias is vital in informing ablation strategy. ECGi is an established method to generate 3D activation maps with a multielectrode vest combined with cardiac CT. EWI is an emerging echocardiography based modality that provides a low cost & non-ionizing mapping alternative.

Hypothesis:
EWI more precisely localises SOO of Complex Ventricular Ectopy (VEs) & intramural location than commercial ECGi.

Aim:
Compare spatial accuracy of EWI and ECGi to estimate SOO and validate against contact mapping.

Methods:
VE-ablation patients underwent preprocedural EWI & ECGi to estimate SOO on the AHA segment-model. A commercial ECGi system with cardiac CT was used for reconstruction of epicardial VE activation maps. EWI was performed using a research ultrasound acquiring B-mode and high frame rate (2000fps) images with simultaneous ECG. Local electromechanical activation was defined as time-point of the downward zero-crossing on the incremental axial strain curve (250 strain curves/view) and displayed on 3D rendered maps. The site of earliest activation & successful VE ablation was defined as ground truth for VE SOO.

Results:
10 patients were enrolled: 50% male, age 40.8 +/- 18.1 years, LV EF 41+/-15%, 50% with scar on MRI. CT ECGi correctly identified the VE AHA segment in 8/10 (80%) cases (misclassified 2 papillary muscle (PM) VEs) but did not afford transmural localization. After excluding 1 patient with insufficient VE’s for EWI, EWI correctly identified the VE-SOO segment in 8/9 (88%) cases locating 2 subepicardial, 2 septal intramural & 3 VEs at the base or intramural segment adjacent to a PM. It misclassified 1 PM VE.

Conclusion

Both EWI & ECGI identified the VE-SOO segment in at least 80% of cases irrespective of presence of scar. EWI also correctly determined the transmural VE origin which cannot be located using commercial ECGI. This has important implications in planning ablation procedures.
Abstract 16989: Clonal Hematopoiesis of Indeterminate Potential Status is Associated With Left Main Artery Stenosis
Authors: Heimlich Brett , Raddatz Michael , Wells John , Vlasschaert Caitlyn , Olson Sydney , Threadcraft Marcus , Foster Kristoff , Boateng Emmanuel , Su Yan Ru , Barker Colin , Bick Alexander G
Published: December 2023

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) occurs secondary to acquired mutations in bone marrow progenitor cells. CHIP confers a twofold risk of atherosclerotic cardiovascular disease (ASCVD). The two most common CHIP mutations are ten eleven translocase 2 (TET2) and DNA methyltransferase 3A (DNMT3A). However, there is limited data on specific cardiovascular phenotypes in this population.

Methods:
We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to assign CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and coronary angiography.

Results:
We sequenced 1,469 patients, and 1,149 had complete angiographic data. Of these, 214 (18.6%) had CHIP mutations with a variant allele frequency of >2%. CHIP patients were significantly older (68 vs. 59 years, p = 7.7 x 10-16). CHIP carrier status was significantly correlated with any stenosis and degree of stenosis in the left main (LM) coronary artery (OR 1.87 [1.28-2.74]; P = 0.0013 and OR 2.12 [1.42-3.15]; P = 2.2 x 10-4). This association was stronger among patients with TET2 CHIP, both for any LM stenosis (OR 2.98 [1.48 - 5.96]; P = 0.0021) and the degree of LM stenosis (OR 3.52 [1.78 - 6.95]; P = 2.9 x 10-4) (Fig. 1). TET2 CHIP was also correlated with obstructive (>70%) stenosis in any vessel (OR 2.28 [1.15 - 4.52]; P = 0.019), and the number of obstructive stenoses across coronary vessels (OR 1.83 [1.04 - 3.23]; P = 0.037).

Conclusions:
This is the first description of a specific atherosclerotic phenotype in CHIP and serves as a basis for understanding enhanced morbidity and mortality in CHIP. Our findings reveal a population enriched for CHIP carriers in the catheterization laboratory, an important observation for future studies focused on secondary prevention in CHIP-related ASCVD.
Abstract 16990: Empagliflozin Therapy is Associated With Improved Left Ventricular Diastolic Function in Patients With Transthyretin Amyloid Cardiomyopathy
Authors: Zemljic Gregor , Frljak Sabina , Poglajen Gregor , Zorz Neza , Cerar Andraz , Okrajsek Renata , Vrtovec Bojan
Published: December 2023

Introduction:
Although SGLT-2 inhibitors demonstrated beneficial clinical effects in patients with heart failure with preserved ejection fraction, their role in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains undefined.

Hypothesis:
We investigated the effects of empagliflozin on myocardial function in patients with ATTR-CM.

Methods:
In a prospective single-center non-randomized cohort study we enrolled 15 consecutive patients with ATT-CM receiving tafamidis 61 mg qd and standard heart failure therapy for at least six months prior to enrolment. At the time of inclusion, all patients started receiving empagliflozin 10 mg qd. Biochemical and echocardiographic parameters were evaluated at baseline and again at 6-months.

Results:
At the time of inclusion, the average age of patients was 74.8±5.7 years, 14 (93%) were male, and 14 (93%) had NYHA class II symptoms; 10 (67%) patients were receiving ARNI/ACEI/ARB, 5 (33%) were treated with beta blockers, and 3 (20%) were receiving mineralocorticoid receptor antagonists. At 6-months follow-up we found no change in NT-proBNP levels (1694±1237 ng/L at baseline vs. 1549±1203 ng/L at follow up; P=0.78), hs-Troponin I levels (33±19 ng/L vs. 39±26 ng/L; P=0.50), or eGFR (65.9±14.4 mL/min vs. 64.9±14.8 mL/min; P=0.87). Furthermore, we observed no changes in LVEDV (84±19 mL vs. 88±17 mL; P=0.61), LVEF (57±8% vs. 57±7%; P=0.94), LV mass (265±74 g vs. 279±88 g; P=0.67), or RVIDd (39±8 mm vs. 36±7 mm; P=0.39). However, at 6 months we found a significant decrease in E/e’ (19.2±5.1 vs. 14.9±5.4; P=0.05). When stratifying patients according to the baseline E/e’ value we found a significant improvement of right ventricular FAC (44.1±6.2% vs. 31.9±8.9%; P=0.04) and TR pressure gradient (26.0±5.7 mmHg vs. 39.7±5.2 mmHg; P=0.04) in patients with E/e’ below median compared to patients with E/e’ above median value.

Conclusion:
In patients with ATTR-CM, empagliflozin therapy appears to reduce left ventricular filling pressures and may be associated with improved right ventricular systolic function in a subset of this patient population.
Abstract 16992: Superior Vena Cava Syndrome in a Patient With Metastatic Primary Cardiac Diffuse Large B-cell Lymphoma - Case Report
Authors: Magdon Dorota , Galazka Patrycja , Allaqaband Suhail Q
Published: December 2023

Introduction:
Primary cardiac tumors are uncommon, with an estimated incidence of 0.02%. Primary cardiac lymphomas (PCL), a subtype of non-Hodgkin lymphoma, account for about 10% of malignant and 1% of all primary cardiac tumors. Diffuse large B-cell lymphomas (DLBCLs) emerge as the predominant histological subtype within PCL cases.

Case presentation:
54-year-old White male with no medical history presented with a few weeks of exertional dyspnea, nonproductive cough, and neck fullness. Exam was notable for tachycardia, jugular venous distension, bilateral upper extremity edema, and distended chest wall vasculature. Labs showed elevation of alkaline phosphatase and CRP. CT of the chest showed a right atrial mass extending into and obstructing the superior vena cava (SVC) and mediastinal lymphadenopathy (Panel A & B). Coronary CTA performed a few years earlier showed normal interatrial septum (Panel C) and coronary arteries. Transthoracic echo (TTE) confirmed a 7.6 x 5.0cm mass visualized in the interatrial septum extending to both atria. Cardiac MRI redemonstrated a large cardiac mass with malignant features suggestive of cardiac lymphoma vs angiosarcoma (Panel D-F). PET-CT showed enhanced fluorodeoxyglucose (FDG) uptake within cardiac mass, mediastinal, and intraabdominal lymph nodes (Panel G). Lymph node biopsy confirmed DLBCL. Patient underwent three cycles of EPOCH (etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) chemotherapy with excellent response. TTE following cycle 2 demonstrated decreased tumor size, and PET-CT after cycle 3 confirmed complete resolution of lymphadenopathy and minimal residual intracardiac FDG uptake.

Conclusion:
SVC syndrome can be a rare presentation of PCL. Multimodality imaging is important in cardiac mass characterization, diagnosis, treatment planning, and follow-up. Timely diagnosis and initiation of chemotherapy results in improved outcomes.
Abstract 170: Late CCL23 Response is Associated With Poor Outcomes After Cardiac Arrest
Authors: Ryzhov Sergey V , deKay Joanne T , Chepurko Elena , Chepurko Vadim , Knudsen Lacey , Lord Christine , Searight Meghan , Tsibulnikov Sergey , Robich Michael P , Sawyer Douglas B , Gagnon David , May Teresa , Riker Richard , Seder David B.
Published: December 2023

Introduction:
Chemokines mediate the entrance and migration of leukocytes to inflamed tissue areas, contributing to the intensity of local inflammation. We found a high level of circulating chemokines, CCL2, CCL4, and CCL23, in patients resuscitated after cardiac arrest (CA).

Hypothesis:
The level of circulating chemokines is associated with systemic immune cell response, neurologic injury, and outcome after cardiac arrest.

Goal:
To characterize temporal chemokine and immune cell responses to cardiac arrest.

Methods:
A total of 42 patients after CA and 22 control subjects who underwent coronary artery bypass grafting (CABG) were enrolled. ELISA was used to determine chemokines in plasma at 6 hr, 24 hr, 48 hr, and 72 hr after CA and in CABG patients pre-operatively. Flow cytometry was used to determine subpopulations of immune cells. We measured changes in chemokines over time and the association of chemokine levels with outcome, markers of inflammation, and brain injury. A mouse model of CA was employed to assess the activation of human neutrophils locally in brain tissue.

Results:
Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a late elevation in CCL23 at 48 hours after resuscitation. A higher level of CCL23 was associated with a worse cerebral performance category score (r
s
=0.3, p=0.042) and higher mortality (r
s
=0.3, p=0.039). Positive correlations were found between CCL23 and an increased number of neutrophils, cellular mediators of inflammation, and levels of neuron-specific enolase. To study the potential role of neutrophil activation locally in injured brain tissue, we injected human post-CA neutrophils into the bloodstream of successfully resuscitated mice and measured the CCL23 in human neutrophils in mouse blood and brain 24 hours after resuscitation. An increased level of CCL23 production was found in mouse brain neutrophils compared to those in the peripheral circulation.

Conclusion:
It is well known that an early intense inflammatory response is associated with poor outcomes after CA. Our new data indicate that late activation of neutrophils in brain tissue may represent an additional mechanism contributing to ongoing brain tissue injury via the production of CCL23 after cardiac arrest.
Abstract 17000: Adipokines and Subclinical Myocardial Injury Following Bariatric Surgery
Authors: Wallace Amelia S , Ozkan Bige , Aryee Ebenezer K , Echouffo Justin B , Gerstenblith Gary , Blumenthal Roger S , ballantyne Christie , Selvin Elizabeth , Coresh Josef , Ndumele Chiadi E
Published: December 2023

Background:
Bariatric surgery results in marked weight loss and has many cardiometabolic benefits. Adipokines, proteins secreted by adipose tissue with diverse metabolic effects, are affected by bariatric surgery. Whether favorable changes in adipokines after bariatric surgery are associated with improvements in cardiac biomarkers is unknown.

Methods:
We studied 294 bariatric surgery patients and 294 controls matched on age, sex, BMI, and diabetes in the Geisinger Obesity Registry. We measured serum markers of subclinical cardiac injury (high-sensitivity cardiac troponin I [hs-cTnI]), cardiac fibrosis (galectin-3), and adipokines (adiponectin, leptin, resistin, visfatin) prior to surgery and 6-18 months post-surgery in bariatric surgery patients and at similar intervals in controls. We used linear regression to evaluate the associations of changes in log-transformed adipokines with changes in log-transformed hs-cTnI and galectin-3.

Results:
Participants (mean age 45; 83% female; 97% White; mean BMI 47 kg/m
2
) undergoing bariatric surgery lost 38.5 kg and matched controls gained 0.4 kg on average. Leptin, resistin, visfatin, hs-cTnI and galectin-3 decreased while adiponectin increased in bariatric surgery participants. There were no significant changes in any biomarkers in control participants. Increasing adiponectin and decreasing leptin were associated with decreases in hs-cTnI, but these associations were attenuated by adjustment for weight loss (
Table
). Decreasing resistin was linked to decreasing hs-cTnI and galectin-3, and decreasing visfatin with decreasing galectin-3, independent of weight loss.

Conclusion:
Bariatric surgery induced weight loss results in favorable changes in adipokines, which are associated with reversal of subclinical myocardial injury, and to a lesser degree, with decreasing myocardial fibrosis. Associations for some adipokines were weight loss-dependent, while others were independent of weight loss.
Abstract 17003: Associations of SGLT2 Inhibitor-Related Plasma Proteins With Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Buckley Leo , Lamberson Victoria , Dorbala Pranav , Yu Bing , Claggett Brian , Coresh Josef , Grams Morgan , Tang Weihong , Ballantyne Christie M , Hoogeveen Ron C , Lennep Brandon , Bancks Michael , Chang Patricia , Shah Amil M
Published: December 2023

Introduction:
The mechanisms by which SGLT2 inhibitors reduce heart failure (HF) hospitalization is unclear. Data from EMPEROR-Reduced and two pilot clinical trials identified 288 plasma proteins modifiable by SGLT2 inhibitors.

Methods:
Among participants in the community-based ARIC study who were free of HF and had aptamer-based proteomic measurements (SomaLogic, Boulder, CO) at Visit 2 (mid-life, n=10,983; 1991-1993) and Visit 5 (late-life, n=4,321; 2011-2013), we studied the association of these 288 SGLT2 inhibitor-related proteins with incident HF after Visit 2 (1149 incident HF events) and Visit 5 (453 events) using multivariable Cox proportional hazards regression models, cardiometabolic traits using multivariable linear regression and Mendelian randomization to assess for potential causal effects.

Results:
The mean age was at 57±6 at Visit 2 and 76±5 at Visit 5 and 55% were women. Of 288 plasma proteins reported to be modulated by SGLT2 inhibition, 39 associated with incident HF after both Visit 2 and Visit 5: 24 with HFpEF [LVEF>50%], 2 with HFrEF, and 8 with both (
Figure
). These proteins also associated with plasma glucose levels, hematocrit and urine albumin-to-creatinine ratio and were enriched with immune signaling pathways and the fatty acid binding pathway. Two sample Mendelian randomization suggested causal effects of higher IGFBP1, lower CHRDL1 and higher B2M on higher incident HF risk (P<0.05).

Conclusions:
Proteins impacted by SGLT2 inhibition and associated with risk of HF suggest glucose metabolism, erythropoiesis and kidney damage as potential contributors to the effect of SGLT2 inhibitors on HF outcomes.