bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13870: Association of Gait Speed and Cardiac Rehabilitation With Death and Disability Following Acute Myocardial Infarction
Authors: Flint Kelsey M , Kennedy Kevin , Arnold Suzanne V , Spertus John A , Dodson John A , Cresci Sharon , Alexander Karen P
Published: April 2024

Background:
Slow gait speed is associated with worse outcomes in older patients after acute myocardial infarction (AMI). Cardiac rehabilitation (CR) may improve outcomes in these patients, however participation in CR may be challenging in older patients with limited mobility. We assessed for an association between gait speed and CR participation, and examined whether CR modifies the association between slow gait speed (<0.8m/sec) and 1-year outcomes.

Methods:
Among patients ≥ 65 years old enrolled in TRIUMPH (24-site US AMI registry) assessed with a 5-meter walk test at 1-month after AMI, we measured CR participation in patients with slow and normal gait speed. CR participation was self-reported 1 month after AMI. The association between slow gait speed and CR participation with death or disability (i.e., ADL loss) was assessed with multivariable logistic regression. We also measured the interaction between slow gait speed and CR participation with the outcomes.

Results:
Among 329 older patients, 177 (54%) had slow gait speed 1 month after AMI. 48 (27%) patients with slow gait speed participated in CR, whereas 62 (40%) patients with normal gait speed participated in CR (p=0.012). Patients with slow gait speed who did not participate in CR were most likely to experience death or disability at 1 year following AMI (43%), while similar outcomes were noted for slow gait speed/CR group (24%) and normal gait speed/no CR group (24%), with best outcomes in the normal gait speed/CR group (9%). In a multivariable model (Figure), lack of CR and slow gait speed were independently associated with death or loss of ADL at 1 year after adjustment for GRACE score and cognitive impairment. There was no interaction between gait speed, CR participation and 1-year mortality or disability (p interaction=0.67).

Conclusions:
Less CR participation is notable among older patients with slow gait speed; however, CR participation is associated with improved outcomes after AMI, regardless of gait speed.
Abstract 13891: Prognostic Value of Simple Risk Index at Discharge in Patients Admitted for Acute Decompensated Heart Failure With Reduced or Preserved Left Ventricular Ejection Fraction
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ozaki Tatsuhisa , Seo Masahiro , Sato Yoshihiro , Ikeda Iyo , Fukuhara Eiji , Abe Makoto , Nakamura Jun , Fukunami Masatake
Published: April 2024

Backgrounds:
Increased heart rate (HR) and low systolic blood pressure (SBP) are associated with adverse clinical outcomes in patients (pts) admitted for acute decompensated heart failure (ADHF). It has been reported that simple risk index (SRI) based on easily assessed clinical characteristics (age, HR, and SBP) is useful for the prediction of short-term mortality in pts with acute myocardial infarction. However, there is no information available on the prognostic significance of pre-discharge SRI in pts admitted for ADHF relating to reduce or preserved left ventricular ejection fraction (HFrEF or HFpEF).

Methods and Results:
We studied 303 consecutive ADHF pts discharged with survival (HFrEF(LVEF<50%);n=163, HFpEF(LVEF≥50%);n=140), and obtained clinical characteristics, conventional hemodynamic parameters and laboratory data. SRI was calculated as (HRх[age/10]
2
)/SBP. During a follow up period of 4.2±3.3 yrs, 96 pts had all-cause death. In HFrEF group, at multivariate Cox analysis, SRI at the discharge (adjusted hazard ratio:1.055[95%CI 1.029 to 1.081], p<0.0001) was significantly associated with total mortality, independently of prior heart failure hospitalization, and serum sodium and albumin levels after adjustment for anemia and renal function. The mortality risk significantly increased by SRI tertiles (lowest tertile [<26.3]: 19%, middle tertile [26.3-36.3]: 38% and highest tertile [>36.3]: 54%, p=0.0001). In HFpEF group, SRI at the discharge (adjusted hazard ratio:1.065[95%CI 1.022 to 1.109], p=0.0026) was also significantly associated with total mortality, independently of anemia and serum sodium level after adjustment for renal function. Pts with highest and middle SRI tertile had a increased risk of total mortality than those with lowest tertile (30% vs 28% vs 13%, p=0.002, respectively).

Conclusion:
SRI at the discharge would provide the long-term prognostic information in ADHF pts, regardless of HFrEF or HFpEF.
Abstract 13941: CT-derived Skeletal Muscle Index: A Novel Predictor of Frailty and Hospital Length of Stay After Transcatheter Aortic Valve Replacement
Authors: Dahya Vishal , Batchelor Wayne , Xiao Jingjie , Prado Carla , McGee Dan , Silva Aline , Burroughs Penny , Noel Thomas , Hurt Julian , Mohamed Shafi
Published: April 2024

Introduction:
We determined the prevalence of sarcopenia in patients undergoing transcatheter aortic valve replacement (TAVR) and whether skeletal muscle mass measured from preoperative computed tomography (CT) images provides value in predicting post-operative length of stay.
Background:
There is limited data on the use of body composition as a frailty measure in TAVR patients and no studies have determined if this measure predicts length of stay.

Methods:
We studied 104 consecutive patients who underwent TAVR at Tallahassee Memorial Hospital from 2012 to 2016. Patient demographics, frailty measures (hand grip, albumin, and 5m walk test), clinical comorbidities and echocardiographic data were recorded. Skeletal muscle index (SMI) [skeletal muscle mass cross-sectional area/height
2
] was measured from CT images using Slice-O-Matic software (Tomovision, Montreal, Quebec, Canada) (Figure 1). Clinical outcomes were assessed and multivariate methods used to determine predictors of LOS.

Results:
Sarcopenia was prevalent in men (83%) and women (56%). Only SMI and mitral regurgitation showed a univariate relationship with LOS, while none of the established frailty measures predicted LOS. SMI was correlated with age, gender, BMI, handgrip strength, previous PCI and previous CABG. A multivariate model including age, gender, major complications, BMI, SMI, mitral regurgitation, grip strength and walk test showed only SMI, MR, and major complications as independent predictors of LOS. For every 8.6 cm
2
/m
2
increase in SMI, there was a 1 day reduction in LOS.

Conclusions:
SMI, a measure of sarcopenia readily determined from pre-TAVR CT scans, independently predicts TAVR LOS better than standard frailty testing. Further evaluation of SMI as a frailty measure after TAVR is warranted.
Abstract 13992: The Clinical Significance of Diastolic Late Mitral Annular Velocity in Heart Failure With Preserved Left Ventricular Ejection Fraction
Authors: Oike Fumi , Yamamoto Eiichiro , Tokitsu Takanori , Hirata Yoshihiro , Yamamura Satoru , Izumiya Yasuhiro , Kaikita Koichi , Hokimoto Seiji
Published: April 2024

Background:
Left atrial (LA) structure are altered in the majority of HF with preserved LVEF (HFpEF) patients. Because diastolic late mitral annular velocity (a’) measured by transthoracic echocardiography (TTE) is reported to represent the severity of LA remodeling, we investigated clinical significance of a’ in HFpEF.

Methods:
We enrolled 422 consecutive HFpEF patients (sinus rhythm [SR]: n=337 [79.9%], atrial fibrillation [AF] rhythm: n=85 [20.1%]), admitted to Kumamoto University Hospital from 2006 to 2013, and performed TTE at stable condition after optimal therapy for HF. In patients with SR at the time of TTE, a’ values as an average of tissue Doppler velocities measured at septal and lateral mitral annuli. All HFpEF patients were followed until occurrence of cardiovascular events.

Results:
In HFpEF patients with SR, a’ had a weak but significant negative correlations with B-type natriuretic peptide (BNP) (r=0.22, p<0.001), LA volume (r=0.28, p<0.001), the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e’) (r=0.24, p<0.001) and LV mass index (LVMI) (r=0.35, p<0.001). In multivariate logistic-regression analysis, E/e’ and LVMI were significantly and independently associated with decreased a’ (both, p<0.05). HFpEF patients with low-a’ (<8; median value of a’) had significantly higher BNP (p=0.01) and prevalence of hypertension (p<0.01), and lower prevalence of coronary artery disease (p=0.01) than those with high-a’ (≧8). In Kaplan-Meier analysis, HFpEF patients with AF had a significant higher risk of all cardiovascular and HF-related events than those with SR (both, log-lank test, p<0.01). Furthermore, HFpEF patients with low-a’ had a significant higher risk of cardiovascular events and HF-related events (both, log-lank test, p<0.01) than those with high-a’, and was prognostically equivalent to those with AF. Multivariate-Cox-hazard analysis identified that low-a’ as an independent predictor of both cardiovascular (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.76-0.99, p=0.04) and HF-related events (HR: 0.71, 95%CI: 0.57-0.88, p=0.002).

Conclusion:
Estimation of a’ value is a non-invasive and useful method for risk stratification in patients with HFpEF.
Abstract 16620: Left Ventricular Ejection Time is an Independent Predictor of Cardiovascular Morbidity and Mortality Following Acute Coronary Syndrome
Authors: Alhakak Alia Saed , Skaarup Kristoffer G , Iversen Allan , Brainin Philip , Jørgensen Peter G , Jensen Jan S , Biering-Sørensen Tor
Published: April 2024

Background:
Color Tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to obtain the cardiac time intervals including the left ventricular ejection time (LVET). The aim of this study was to investigate whether the LVET can be used to predict cardiovascular morbidity and mortality following acute coronary syndrome (ACS).

Methods:
We retrospectively studied 390 patients with ACS (mean age 64 ±12 years, men 74%, STEMI 81%, mean LVEF 41±11%, mean LVET 256±35ms) who underwent echocardiography, following percutaneous coronary intervention. The LVET was measured. The primary endpoint was major adverse cardiac events (MACE) and consisted of heart failure, myocardial infarction and cardiovascular death. The secondary endpoint was all-cause mortality. Patients with prevalent HF were excluded.

Results:
During a median follow-up of 3 years, 180 patients (46%) reached the composite endpoint MACE, and 77 (20%) suffered from all-cause mortality. LVET was significantly associated with risk of MACE (HR 1.13; 95% CI (1.08-1.18), p<0.001) with a 13% increase in risk per 10ms decrease in LVET (figure ). The association remained significant after adjusting for age, sex, hypertension, diabetes, body mass index, previous ischemic heart disease, STEMI, multivessel culprit lesions, left ventricular ejection fraction, left ventricular mass index, E/e’, E/A and deceleration time (HR 1.10; 95% CI (1.03-1.17), p=0.002 per 10ms decrease). Additionally, the LVET predicted all-cause mortality and the association remained significant even after multivariable adjustment (HR 1.11; 95% CI (1.01-1.21), p=0.032 per 10ms decrease).

Conclusion:
In patients with ACS the LVET provides novel and independent prognostic information on the risk of cardiovascular morbidity and mortality.
Abstract 16628: Improvement of LV-Strain in HFrEF-Patients at 12 Months Follow-Up Using the Revivent
TM
System (Bioventrix) Compared to Patients Treated by OMT- Results From a CMR-Multi-Center-Trial
Authors: Lapinskas Tomas , Klein Christoph , Pedrizzetti Gianni , Stoiber Lukas , Hennig Felix , Knosalla Christoph , Schmitz Christoph , Schickling David , Annest Lon , Kelle Sebastian
Published: April 2024

Introduction:
After an acute coronary syndrome many patients with ischemic cardiomyopathy (ICM) suffer from heart failure with reduced ejection fraction (HFrEF). Beside surgical ventricular reconstruction (SVR) by open-chest-surgery as an option to improve myocardial function by restoring the shape and size of the heart in HFrEF patients, first results demonstrated a significant reduction of LV volumes and LVEF using the Revivent TC
TM
System compared to optimal medical therapy (OMT) in patients with aneurysms in the anterior region of the LV.

Objectives:
To assess the impact of the Revivent TC™ system (Bioventrix Inc.) as a Less Invasive Ventricular Enhancement (LIVE™) technique to improve systolic and diastolic LV-function in patients with HFrEF compared to treatment of patients with OMT.

Methods:
We analyzed data from 10 patients and 10 controls with ICM and LVEF ≤ 45% from a multi-center-trial as well as 12 healthy subjects. In total, 10 patients underwent LV reduction with the new LIVE™ technique. The control group patients received OMT only (natural course of disease). Global longitudinal strain (GLS) as advanced, quantitative CMR measurement has been performed both at baseline and 12 months to quantitatively assess LV function. In addition, hemodynamic forces (HF) as an equivalent to intraventricular pressure gradients derived from CMR-data have been evaluated.

Results:
After 12 months follow-up, LVEF improved after using the Revivent
TM
System (27.8 ± 10.6 % vs. 31.5 ± 10.9 %), but not in controls (31.8 ± 8.2 % vs 31.3 ± 6.7 %). Minimal invasive treated patients showed a significant reduction in HF (33.6 ± 9.4 vs. 28.5 ± 10.5, p=0.04) and improved GLS (-9.4 ± 3.5 % vs. -11.4 ± 4.7 %; p=0.08). No change was observed in controls (31.5 ± 7.3 vs. 31.9 ± 6.9, p=0.37 and -12.8 ± 2.8 % vs. -12.6 ± 2.1 %; p=0.38) (see Figure).

Conclusion:
We demonstrate an improvement of LV strain and hemodynamic forces 12 months after using the Revivent TC
TM
System in HFrEF-patients compared to OMT. The impact on outcome and exercise capacity of HFrEF-patients has to be proven in larger trials with longer follow-up.
Abstract 16644: Independent Predictors of 30-Day Readmission After Acute Myocardial Infarction at a Large, Inner City Medical Center
Authors: Bennet Catherine , Fashanu Oluwaseun , Marvel Francoise , Leung Curtis , Deutschendorf Amy , Brotman Daniel , Gerstenblith Gary , Berkowitz Scott , Chandra-Strobos Nisha , Martin Seth
Published: April 2024

Background:
Acute myocardial infarction (AMI) accounts for one of the most common reasons for cardiovascular disease admission in the United States. Despite modern therapeutics, 15-20% of index admissions for AMI result in unplanned readmission within 30 days of discharge. In tailoring efforts to decrease AMI 30 day readmissions we sought to identify independent predictors for readmission.

Methods:
All 1771 patient discharges from Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center in fiscal years 2016 and 2017 with a primary discharge diagnosis of AMI were included. The age, sex, race, insurance status, aggregated AHRQ comorbidity count, concomitant diagnosis of specific comorbidities, discharging hospital, discharging service, destination at discharge, diagnosis (NSTEMI vs. STEMI), procedures during index admission and length of index admission for each discharge were recorded and odds ratios with 95% confidence intervals for 30 day readmission to a Maryland hospital were calculated. If a patient was readmitted to a Hopkins hospital the reason for readmission was recorded.

Results:
Of the 1771 patient discharges over the study period, 273 were excluded because the patient was not eligible for readmission in CMS reporting algorithms (i.e. same or next day transfer, death), had a planned readmission, or was <18 years old. Of the remaining 1498 discharges, 264 (17.6%) were readmitted within 30 days. In a multivariable model, major independent predictors of 30 day readmission risk were high comorbidity burden (OR for 4-5 vs. 0-1 comorbidities: 3.27, 95% CI 1.55 - 6.88; OR for > 5 vs. 0-1 comorbidities: 6.86, 95% CI 3.2 -14.71) and leaving the hospital AMA (OR 3.77, 95% CI 1.63-8.72). In a separate model considering specific comorbidities, a concomitant diagnosis of CHF (OR 1.94, 95% CI 1.4-2.67), renal failure (OR 1.76, 95% CI 1.27-2.45), or depression (OR 1.61, 95% CI 1.12-2.33) were independent predictors of readmission risk. Of patients whose readmission diagnoses were known (n=143), the majority (n=75, 52.4%) were readmitted with cardiac diagnoses. The most prevalent cardiac readmission diagnoses were CHF (n=28), NSTEMI (n=25), and chest pain (n=15).

Conclusions:
In our large, inner city hospital system, patients with a greater number of comorbidities, in particular CHF, renal failure, or depression, were at significantly greater risk for 30 day readmission after AMI. Identifying high risk patient characteristics is an important first step in designing tailored, system-wide initiatives to reduce AMI readmissions.
Abstract 16647: Loss of Reversibility in Flow-Induced Pulmonary Arterial Hypertension is Associated With a Senescent Vascular Phenotype and Can Be Rescued by Targeted Senolysis
Authors: van der Feen Diederik , Jorna Lysanne M , Moonen Jan Renier , Chappell James , Vallania Francesco , Donato Michele , Demaria Marco , de Boer Rudolf A , Rabinovitch Marlene , Berger Rolf M , Bartelds Beatrijs
Published: April 2024

Introduction:
Patients with congenital heart disease (CHD) are at risk of developing progressive pulmonary arterial hypertension (PAH). Timely hemodynamic unloading (HU) by surgical shunt correction usually reverses the arteriopathy, but the timepoint when or reason why PAH becomes irreversible remains elusive.

Methods:
PAH was created in syngeneic rats by monocrotalin (MCT) injection and an aorto-caval shunt. For HU at different PAH stages, the left donor lung with PAH was transplanted into healthy recipients at t14/t21/t28. Recipients were sacrificed 21days after transplantation.

Results:
MCT+Shunt induced medial neomuscularization from t14, and neointimal lesions from t21, causing arteriolar occlusion and PAH. HU normalized the vascular morphology in all t14 rats and in 7/10 t21 rats, whereas no reversal or progressive occlusion occurred in 3/10 t21 and all t28 rats. RNA-sequencing revealed that activated pro-proliferative/regenerative, pro-apoptotic and DNA-repair pathways were associated with reversal after HU. This was confirmed immunohistochemically by increased vascular-specific Ki67, Caspase3 and Rad51 protein expression. In contrast, irreversibility was associated with deactivation of latter pathways and activated pro-survival, pro-senescence and pro-inflammatory pathways, as confirmed by increased Survivin, p16
ink4A
, p21
cip1
, TNFα, IL6 and MMP2. These findings were also confirmed in human PAH-CHD explant tissue. Finally, we report that the senolytic BCL2 antagonist ABT263 selectively targets rat endothelial cells made senescent by irradiation. Moreover, low-dose ABT263 treatment from t25 to t32 in MCT+Shunt rats significantly improved pulmonary hemodynamics and relieved PAH symptoms.

Conclusions:
Similar to clinical observations in PAH-CHD, this study showed that HU reverses PAH only in an early stage, and describes a zone of no return. We characterized the mechanistic basis for (loss of) reversibility, showing a distinct switch from increased proliferation/regeneration, apoptosis and DNA-repair, to a growth arrested, apoptosis-resistant and intrinsically pro-inflammatory phenotype, suggesting a role for senescence. Reversal of this phenotype by targeted senolysis also reversed PAH beyond the zone of no return.
Abstract 16777: Augmentation of Spinal Cord Pre-Collateralization to Prevent Paraplegia After Aortic Surgery
Authors: Eldeiry Mohamed , Kohtz Patrick , Halpern Allison , Cleveland Joseph C , Fullerton David , Reece T. B , Aftab Muhammad
Published: April 2024

Introduction:
Spinal cord ischemia from complex aortic surgery can lead to paraplegia. Spinal cord is supplied by a rich collateral network of segmental arteries. Emerging data demonstrate that patients with staged aortic repairs suffer fewer spinal cord injuries than those with a single operation.

Hypothesis:
Paraplegia can be induced in a swine model by ligation of segmental spinal arteries. Induction of spinal cord pre-collateralization by staging the spinal segmental arterial coverage can minimize the risk of paraplegia.

Methods:
Twenty-four female Yorkshire pigs (50-70kg) underwent abdominal exposure of the aorta. Lumbar aortic group underwent ligation of the lumbar segmental arteries (5-7) and median sacral trunk. Thoracic aortic coverage consisted of stent graft placement from the left subclavian to celiac artery. Full coverage un-staged group underwent a simultaneous lumbar and thoracic coverage. Similar procedure was performed one week apart in staged full coverage group. Fluorescent microspheres were injected to evaluate regional spinal cord flow distribution. Protein expression in the spinal cord was analyzed using Western Blot.

Results:
Reproducible paresis was demonstrated in full coverage animals. This was associated with decreased viable spinal cord neurons. In the staged full coverage, complete motor recovery occurred within 24h of the second stage. Neurologic recovery was associated with higher levels of Neuropilin-1. Regional blood flow was quantified by microsphere density in various segments of spinal cord using laser confocal microscopy.

Conclusions:
A reproducible model of spinal cord injury can be carried out in swine by disrupting spinal cord segmental blood flow. This injury can be ameliorated by partial or staged coverage of the segmental arteries. Induction of regional spinal cord pre-collateralization can be demonstrated using fluorescent microspheres. This may be dependent on Neuropilin-1 expression in the tissue.
Abstract 16812: Clinical Use of Rate Adaptive Pacing With a Leadless Pacemaker: Results From the Micra Transcatheter Pacing System Post-Approval Registry
Authors: Birgersdotter-Green Ulrika , Roberts Paul R , Piccini Jonathan P , Soejima Kyoko , Stromberg Kurt D , Eakley Alyssa K , El-Chami Mikhael F
Published: April 2024

Introduction:
The Micra transcatheter pacemaker has similar functionality and features to existing transvenous VVIR systems despite its small size and intracardiac location. Rate adaptive pacing with Micra is achieved via a programmable 3-axis accelerometer that detects activity in the presence of cardiac motion and has demonstrated to be proportional to workload in the investigational trial. In this analysis, we report the clinical usage of rate adaptive pacing in the Micra Post-Approval Registry (PAR).

Methods:
The Micra PAR is a prospective, non-randomized, multi-center registry evaluating safety performance of Micra in real-world clinical practice following commercial release. All patients intended to be implanted with a Micra were eligible for enrollment. Micra PAR patients with device data available from an interrogation at least 30-days post-implant were included in this analysis. The clinical usage of VVIR vs. VVI pacing modes was summarized based upon last device interrogation.

Results:
Among the 713 patients included in this analysis from 117 centers, average age was 75.4 ± 14.4 years and 60.0% were male. Overall 45.3% had rate adaptive pacing enabled. Of 457 patients with a primary pacing indication of bradyarrhythmia with AF, 58.0% were programmed VVIR (figure). The pacing indication distribution for the VVIR patient group was: 82% bradycardia with AF, 4% sinus node dysfunction, 8% AV block, 4% syncope, and 1% other. Among patients with a primary indication of syncope or sinus node dysfunction, the majority were programmed VVI (83.9% and 79.1%, respectively). Of patients with <10% pacing, 2.5% were programmed VVIR vs. 97.5% VVI. Of those with >90% pacing, 88.8% were VVIR vs. 11.2% VVI.

Conclusions:
In real-world clinical practice, VVIR was programmed in <50% of Micra patients. Patient groups with the highest utilization of VVIR mode include those with >90% ventricular pacing and those with a primary pacing indication of bradyarrhythmia with AF.
Abstract 16819: Circulating Growth Factors and Cardiac Remodeling in the Community: The Framingham Heart Study
Authors: Castro-Diehl Cecilia , Song Rebecca J , Xanthakis Vanessa , Sawyer Douglas B , Cheng Susan , Vasan Ramachandran S
Published: April 2024

Cardiac and vascular growth factors may influence myocardial and vascular remodeling through their pro- and anti-angiogenic effects. We hypothesized that higher circulating concentrations of growth factors will be associated with cardiac remodeling patterns consistent with their known biological effects.

We related circulating concentrations of vascular endothelial growth factor (VEGF), VEGF-1, angiopoietin 2 (Ang2), Hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, growth differentiation factor-15 (GDF-15), to echocardiographic (echo) indices of cardiac remodeling in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following echo measures (dependent variables): left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), left atrial ejection fraction (LAEF), and aortic root diameter (AoR) using generalized linear models to account for relatedness. We also related circulating NTProBNP and Troponin (TnI) to echo measures (as positive controls). In multivariable-adjusted analyses blood GDF-15 levels were associated with higher values of LVMi. TnI concentrations were negatively associated with LVEF. IGF-1 and Ang2 concentrations were positively and negatively associated with GLS, respectively. Lower IGFBP-3 concentrations and higher NT-ProBNP concentrations were associated with lower LAEF. Higher VEGF-1, Ang2 and NT-Pro-BNP levels were associated with smaller AoR (Figure).

In our large community-based cross-sectional study, we observed patterns of associations between several circulating vascular growth factors and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional findings are warranted to replicate our findings and assess their prognostic significance
Abstract 16886: Caspase-4/11 Mediates Intima Formation by Increasing Inflammation and Smooth Muscle Cell Migration and Proliferation
Authors: Yu Ze , Zhu Guofu , Jiang Dongyang , Liu Hao , Fan Linlin , Li Xiankai , Zhang Dekui , Xu Yawei , Ge Junbo , Luo Hong , Pang Jinjiang
Published: April 2024

Introduction:
Intima formation after vessel injury occurs via vascular smooth muscle cell(VSMC) proliferation, migration, dedifferentiation and inflammatory response. Recently, it was demonstrated that caspase-4 (Casp4, human)/caspase11(Casp11, mouse) increases the synthesis and release of inflammatory factors in macrophages, indicating a potential role of Casp4/Casp11 in intima formation. However, to date, the biological role of Casp4/Casp11 in vivo has not been investigated. Therefore, we hypothesize that Casp4/Casp11 deficiency will inhibit intima formation.

Method and Results:
We measured Casp4 expression and location by immunohistochemistry (IHC) staining in human coronary artery intima lesions from coronary artery disease patients. Surprisingly, we found Casp4 expression was remarkably increased in smooth muscle cells (SMC) and macrophages. We observed similar phenomena of Casp11 expression and location in intima of complete carotid ligation mouse model. These findings imply an important role of Casp4/11 in SMC function. Thus, we performed complete carotid ligation on Casp11 wild type (WT) and knockout (KO) mice.Morphometric analysis demonstrated that Casp11 depletion robustly attenuated intima area and intima/media ratio (I/M) compared with WT mice . Inflammation was quantified by CD45 IHC staining . SMC proliferation was detected by PCNA staining and there was a marked decrease of PCNA positive SMCs. In vitro, Casp4 expression was time- and dose-dependently increased by platelet-derived growth factor(PDGF), angiotensin II(AngII) and TNF-α in human coronary artery SMCs(HCASMCs). Depletion of Casp4 by siRNA decreased expression of cytokines, e.g. IL-1α, IL-1β, IL-6, as well as protein expression of adhesion factors (VCAM-1, ICAM-1, MCP-1) induced by PDGF, AngII or TNF-α. Moreover, HCASMC proliferation stimulated by PDGF was measured by EdU cell proliferation assay and was inhibited by 65% after knockdown of Casp4. Wound scratch assay demonstrated impaired HCASMC migration in Casp4 depleted cells. However, Casp4 has no effects on HCASMCs dedifferentiation. Mechanistically, Casp4 knockdown significantly inhibited NF-κB signaling.

Conclusions:
Casp4/11 promotes intima formation by increasing SMC proliferation, migration and inflammation through NF κB signaling. Specific inhibition of the Casp4/11 will provide novel therapeutic strategy for vascular remodeling related diseases.
Abstract 16917: Shear Stress Regulates Blood-Brain Barrier Integrity Through the CD44 Receptor
Authors: Galie Peter
Published: April 2024

Rationale:
The “no-reflow” period that follows a stroke is characterized by reduced blood flow and an increase in blood-brain barrier (BBB) permeability, which exacerbates injury to the surrounding tissue.

Objective:
Here, we evaluate the hypothesis that reduced shear stress on the endothelium contributes to BBB breakdown through attenuation of a cd44-mediated signaling mechanism.

Methods and Results:
Our studies rely on a three-dimensional
in vitro
model of a cerebral arteriole that mimics specific aspects of the
in vivo
BBB, including an endothelium featuring tight junctions, a robust basement membrane, and interaction with astrocytic endfeet. The
in vitro
vessels are patterned inside a collagen/hyaluronan (HA) composite scaffold within a microfluidic device that allows for the application of controlled levels of shear stress to the endothelium. Perfusion with culture medium exerting a shear stress of at least 0.07 Pa for a period of four days establishes vessel permeability on par with
in vivo
vasculature, as determined by dextran exclusion experiments and transendothelial electrical resistance (TEER) using impedance spectroscopy. Ceasing the fluid flow resulted in a significant increase in the permeability of the
in vitro
vessels within two hours (Figure 1A). Removal of HA from the scaffold prevents the formation of tight junctions, suggesting that a cell surface receptor specific for HA could be responsible for the mechanotransduction of fluid shear stress. Knockout of the cd44 receptor using CRISPR-Cas9 negated flow-mediated barrier formation, as shown by reduced tight junction formation in Figure 1B. Quantification of vessel permeability demonstrated that cd44 knockout had a significant affect on barrier function (Figure 1C).

Conclusions:
Our
in vitro
model demonstrates the importance of shear stress for maintaining the BBB. Moreover, our findings indicate that the cd44 receptor is a crucial component of the mechanosensing complex that mediates the endothelial response to shear stress.

Figure 1: A) Vessel permeability following cessation of fluid flow. B) 180-um diameter cd44 KO endothelial channel (green: actin, red: zonula-occludin 1, blue: nuclei). C) the effect of HA and cd44 knockout on vessel permeability.
Abstract 16919: Third Grade Academic Performance and Episodes of Care Among Children With Congenital Heart Defects
Authors: Watkins Stephanie E , Kemper Alex R , D’Ottavio Alfred , Wiedemeier Manuela , Meyer Robert , Greene Nathaniel , Hoffman Timothy M , Sang Charlie , Paolillo Joseph , Walsh Michael J , Li Jennifer S
Published: April 2024

Introduction:
Children with Congenital Heart Defects (CHD) may be at risk for poor academic performance in elementary school. Cumulative episodes of care among children with CHD may impact neurocognitive outcomes. We examined the association between the number of episodes of care and third-grade academic performance among children with CHD.

Methods:
We identified children with CHD from electronic medical records between 1/1/2008 and 12/31/2013 among five North Carolina (NC) tertiary care centers. We classified children by CHD type (severe disease, shunt lesion, valve disease, other) and matched subjects to the NC Department of Public Instruction educational records. We calculated the number of episodes of care by adding inpatient and outpatient visits from the EMR in the follow up period prior to administering the EOG. We estimated the odds of failing third-grade reading or math end of grade (EOG) tests among children with CHD who had episodes of care >50
th
percentile compared to children ≤50
th
percentile using logistic regression controlling for maternal education, race/ethnicity, and gestational age. We also estimated the average change in the developmental scale score using linear regression for the same comparison group. The inability to demonstrate proficiency in NC grade level standards was considered a failing score.

Results:
A total of 425 children with CHD had third-grade EOG scores. Of these, 57% were male and 45% of children had a severe CHD, 30% had a shunt lesion, and 21% had valve disease. The median number of episodes of care was 4 (range: 1-60). Children with number of visits above the 50
th
percentile (>4 visits) had 2.09 (95% CI: 1.04,4.21) greater odds of failing the math EOG compared to children at or below the 50
th
percentile (1-4 visits). The third- grade math developmental scale score declined by 1.54 points (p<0.008) for every 10 episodes of care. There was no statistically significant effect of episodes of care on third grade reading performance.

Conclusions:
Children with CHD in NC with number of episodes of care above the 50
th
percentile, may be at risk for delays in third-grade academic performance. Additional services may be required to improve academic success in this population.
Abstract 16935: Severity of Congenital Heart Disease, Not Risk of Acute Coronary Syndrome,Drives Extent of Ischemic Evaluation for Chest Pain in the Emergency Department
Authors: Gales Jordan , Krasuski Richard , Awerbach Jordan
Published: April 2024

Introduction:
Population growth and increasing complexity of disease among adults with congenital heart disease (ACHD) has led to an increased burden on U.S. emergency services. Assessment of chest pain (CP) within this population poses a challenge to emergency department (ED) providers; and as this population ages, their cardiovascular risk profile continues to change. There is a paucity of literature describing appropriate assessment of CP among ACHD patients within the ED setting.

Hypothesis:
Despite very low probabilities for acute coronary syndrome (ACS), ACHD patients are likely to undergo extensive evaluations for CP within the ED, possibly correlating with ACHD complexity.

Methods:
Retrospective review of ED visits for primary complaint of acute CP among ACHD patients aged 18-50 years (n=182) presenting to a single tertiary center between 1/1/1998 and 4/1/2018. CP quality was classified according to Diamond-Forrester criteria and severity of ACHD according to the Bethesda Classification.

Results:
The mean age of the cohort was 32.8±8.7 years, 88 were women, 102 were Caucasian, 74 had simple CHD, 58 had moderate severity CHD, and 50 had high complexity CHD. Although 94.5% of patients were identified as having a low 30-day risk of major adverse cardiovascular events according to Heart Score, 86.3% had ≥1 set cardiac biomarkers drawn. Only 6 patients (3%) had an initial ECG with changes concerning for possible ischemia. 3 patients (2%) had troponin levels above the upper limit of normal and only 1 case required urgent catheterization. Among ACHD complexity groupings (simple, moderate severity, and high complexity), there were no differences seen with regard to, gender, frequency of ECG changes suggesting ischemia, chest pain quality or coronary disease risk factors (hypertension, hypercholesterolemia, diabetes, smoking, BMI or predefined cardiovascular disease). Despite this fact, complexity of ACHD was associated with increased ED length of stay (p=0.02), likelihood of an urgent echocardiogram being performed (p<0.001), ordering of cardiology consultation (p <0.001) and hospital admission (p =0.009), without concurrent increase in 30-day overall mortality.

Conclusion:
ACHD patients undergo extensive evaluation for ACS despite having low pre-test probability, with complexity of underlying congenital disease correlating with increased ED resource utilization despite similar clinical outcomes.
Abstract 16953: Prospective Negative Microvolt T-Wave Alternans Testing is a Marker for Lower Risk of Cardiovascular Death and Appropriate Shock Therapy
Authors: Biton Yitschak , Baman Jayson R , Mansour Moussa , Heist E K , Ruskin Jeremy N , Costantini Ottorino , Danilowicz-Szymanowicz Ludmila , Salerno-Uriarte Jorge A , Caravati Fabrizio , Pedretti Robert , Molon Giulio , Calo Leonardo , Ikeda Takanori , Erciyes Demet , Zecchin Massimo , Piancastelli Maurizio , Maury Philippe , Marangoni Daniele , Merchant Faisal , Armoundas Antonis
Published: April 2024

Introduction:
Microvolt T-wave alternans (MTWA) refers to a pattern of beat-to-beat oscillations in T-wave morphology.

Hypothesis:
We hypothesized that patients with negative MTWA testing were at decreased risk for cardiovascular death and appropriate shock therapy.

Methods:
We studied 913 patients from a prospective international registry from Europe, Asia and USA (9 centers total). All recruited patients qualified for primary prevention of sudden cardiac death with ICD or CRT-D. Beta-blockers were discontinued prior to MTWA testing. We used best-subsets analysis of our study population to identify predictors of all-cause mortality. Ten clinical and demographic variables were included in the analysis. We then used these predictors to evaluate the predictive capacity of MTWA in a multivariate model.

Results:
The mean follow-up was 4.0 ± 3.0 years, mean age was 69.5 ± 12.5 years, 84% were male, and 63% had ischemic cardiomyopathy. 52% and 11% of patients received ICD and CRT-D, respectively. LVEF <25% (HR 2.17, p<0.001), NYHA class>II (HR 1.75, p=0.01) and use of diuretics (HR 2.64, p<0.001) were significantly associated with all-cause mortality in a multivariate model. Using this multivariate model, a negative MTWA outcome was not associated with all-cause mortality (HR 0.95, p=0.80), however a negative MTWA outcome was associated with the risk of cardiovascular death (HR 0.40, p=0.01) and the combined endpoint of cardiovascular death and ICD-rendered shock therapy (HR 0.28, p<0.001). This was consistent in both ischemic and nonischemic cardiomyopathy (p value for interaction=0.999).

Conclusions:
These findings suggest that non-negative MTWA testing is indicative of an underlying arrhythmogenic substrate, manifested as cardiovascular death and appropriate shock therapy. MTWA testing can provide further information for patient selection for ICD placement.
Figure 1
. Kaplan-Meier Curve demonstrating the time-dependent endpoint of cardiovascular death. The follow-up time displayed on this graph is measured in days.
Abstract 11902: Evaluating Right Ventricular Pacing Burden Leading to Pacing Induced Cardiomyopathy
Authors: mahajan pranav , Aedma Surya , Jose Jemin , Sathe Sanjivani , Naik Anant , Garg Anuj , Kocheril Abraham G
Published: April 2024

Introduction:
Pacing induced cardiomyopathy (PICM) is defined as a drop in left ventricular ejection fraction (LVEF) due to high amount of right ventricular (RV) pacing. Although PICM occurs with chronic, and occasionally, acute high burden RV pacing, the minimum burden of RV pacing inducing PICM is not widely established.

Hypothesis:
Based on multiple cases at our hospital, we hypothesize that >40% RV pacing would induce PICM.

Methods:
A single center retrospective analysis was done on patients undergoing permanent pacemaker (PPM) placement between January 2019 and April 2020 at our hospital. Data for 88 patients was collected and analyzed using paired student’s t test, comparing mean LVEF in the two groups.

Results:
Out of 88 patients, 6 patients with cardiac ischemia and 9 patients with biventricular PPM were excluded. 40 out of the remaining 73 (54.8%) patients had >40% RV pacing, out of which 36 patients had pre-PPM and post-PPM implantation echocardiograms and were included in the final analysis. 33 patients (45.2%) had <40% RV pacing, out of which 30 patients had pre-PPM and post-PPM implantation echocardiograms and were included in the final analysis. Median duration of pacing at the time of analysis was 418 days. There was a statistically significant decrease in LVEF in patients with >40% RV pacing [pre-PPM LVEF= 55.4861%, post-PPM LVEF= 51.5972%, mean difference between post-PPM and pre-PPM LVEF= -3.8889% (p=0.032)], but not in patients with <40% pacing [pre-PPM LVEF= 57.1167%, post-PPM LVEF= 57.4833%, mean difference= 0.3666% (p=0.810)] (Image 1; ns: not significant).

Conclusion:
Our findings showed a statistically significant decrease in LVEF for patients with >40% RV pacing, but not for patients with <40% RV pacing, suggesting that 40% RV pacing is the likely threshold for producing LV systolic dysfunction and cardiomyopathy. Although this difference is statistically significant, clinical significance of this difference varies case-by-case.
Abstract 11910: Prevalence and Variation in Malnutrition in Non-Obstructive Coronary Artery Disease
Authors: Schwartz Brandon H , Torosyan Nare , Chen Billy , Ebinger Joseph E , Gransar Heidi , Berman Daniel , Bairey Merz C N
Published: April 2024

Introduction:
Prior work demonstrates up to 50% of patients with acute coronary syndrome are malnourished, as evaluated by the Controlling Nutritional Status (CONUT) score. We investigated the prevalence of malnutrition in stable nonobstructive coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA).

Methods:
In a single-center, retrospective cohort, we examined the electronic health records of 429 patients with normal coronary arteries (NCA) without evidence of atherosclerosis on CCTA (n=144), nonobstructive CAD (<70% stenosis) by CCTA (n=143), or ICA (n=142) on clinically ordered studies for chest pain or exertional dyspnea. CONUT scores, an aggregate of albumin, lymphocyte count, and total cholesterol, were calculated at time of CCTA or ICA in patients with available lab values. Patients within each group were stratified by severity of malnutrition defined as none (0-1), mild (2-4), moderate (5-7), or severe (8-12). Diabetic patients were excluded. Number of risk factors including history of hypertension, hyperlipidemia, or smoking were compared.

Results:
Among all patients with complete data (n=332), 33% overall had malnutrition, including 31% with mild, 2% with moderate, and none with severe malnutrition. In patients with NCA, 24% had malnutrition, compared to 31% in nonobstructive CAD by CCTA and 45% in ICA. There was a direct positive relationship between malnutrition presence and severity with age, cardiac risk factors and the presence of nonobstructive CAD (
Table
).

Conclusions:
Malnutrition is present in over one-third of stable patients with no obstructive CAD and directly associated with age, risk factor burden, and nonobstructive CAD. Future prospective studies are needed to understand whether malnutrition directly contributes to development of CAD or if age and cardiac risk factors associated with CAD lead to progression of malnutrition, or both.
Abstract 11913: Mortality Along the Rheumatic Heart Disease Cascade of Care in Uganda
Authors: Chang Andrew Y , Barry Michele , Bendavid Eran , Watkins David , Beaton Andrea Z , Lwabi Peter , Ssinabulya Isaac , Longenecker Chris , Okello Emmy
Published: April 2024

Introduction:
Rheumatic heart disease (RHD) predominantly affects people living in low- and middle-income countries but receives little attention in relation to many infectious diseases. The Cascade of Care model, a tool developed for the public health response to HIV, has improved the care of HIV patients worldwide and has recently been adapted for RHD. The utility of these metrics would be improved if epidemiological evidence existed to confirm that clinical outcomes are linked to progression through the steps of the RHD cascade.

Objective:
We described the all-cause mortality of people living with RHD who were (1) retained in care, (2) appropriately prescribed prophylactic benzathine benzylpenicillin G (BPG), and (3) optimally adherent to BPG.

Methods:
We performed a retrospective cohort study using participant data between June 2009 and May 2018 in the Uganda National RHD Registry. Assigning subjects diagnosed with clinical RHD but not retained in clinical care to the reference group, hazard ratios for all-cause mortality risk were calculated for those who were retained in care (received at least annual follow-up), prescribed BPG, and optimally adherent to BPG (received ≥80% of indicated doses), using three multivariable Cox-proportional hazards models adjusted for age, sex, and heart failure history (chosen
a priori
as variables reported to most impact mortality). Survival was visualized with Kaplan-Meier curves.

Results:
Of 1568 subjects diagnosed with clinical RHD, only 357 (23%) were retained in care, 337 (21%) were prescribed penicillin, and 311 (20%) were optimally adherent over the study period. There were 46 deaths in the retained group (289 in those not retained) and 35 deaths among optimally adherent subjects (300 in those not optimally adherent). There was a trend towards a mortality benefit among individuals retained in care (HR 0.76, 95% CI 0.55-1.05), with a statistically significant difference in mortality risk among those retained in care and optimally adherent to penicillin compared to those not retained in care (HR 0.67, 95% CI 0.47-0.96).

Conclusion:
Our study is the first to assess mortality along the RHD Cascade of Care, providing preliminary evidence to support utilizing these metrics to improve RHD outcomes in Sub-Saharan Africa.
Abstract 11916: Patterns of Care and Outcomes of Lower Extremity Peripheral Endovascular Intervention in Peripheral Artery Disease: Insights From National Ambulatory Surgery Sample
Authors: Chaturvedi Abhishek , Gertz Zachary , Lawson Barbara D , Gupta Rahul , Milioglou Ioannis , Sung Jonathan G , Desai Nihar R , Vetrovec George W , Kochar Ajar , Guha Avirup
Published: April 2024

Introduction:
Over the past 2 decades, the use of peripheral endovascular intervention (PVI) has surpassed surgical revascularization as the primary treatment modality for patients with symptomatic peripheral artery disease (PAD) refractory to non-invasive interventions.

Hypothesis:
To examine the patterns of care and associated outcomes in patients with PAD undergoing ambulatory lower extremity PVI (LE-PVI) in the United States (US).

Methods:
Records for patients with PAD who underwent LE-PVI between 01/01/2016 and 12/31/2017 were identified using appropriate CPT codes in the National Ambulatory Surgery Sample, the largest ambulatory surgery database in the US. Patient demographics, comorbidities, socioeconomic status, hospital characteristics, periprocedural mortality and complications were computed using Stata 15.0.

Results:
Total 266,574 (weighted) LE-PVI encounters were identified during the study period. The cohort had a mean age of 68.9 years and 40.5% were female (Table 1). Most common comorbidities were hypertension (54.3%), ischemic heart disease (IHD) (36.3%) and diabetes (24.6%). Periprocedural mortality (PM) was 0.02%, mean charges per encounter were $56,500, and 97.6% patients were discharged home. Complication rate was low (3.3%) including distal emboli (1.8%), dissection (0.4%), periprocedural bleeding (0.3%) and acute kidney injury (0.3%). On multivariable analysis, age [OR(CI), p = 1.02 (1.003 to 1.04), 0.02], Midwest region [OR(CI), p = 1.9 (1.2 to 3.2), 0.01], Southern region [OR(CI), p = 2.2 (1.3 to 3.7), 0.002], IHD [OR(CI), p = 1.6 (1.2 to 2.2), 0.002], arrhythmia [OR(CI), p = 2.4 (1.7 to 3.4), <0.001], valvular disease [OR(CI), p = 1.5 (1.01 to 2.3), 0.045], and coagulopathy [OR(CI), p = 2.6 (1.1 to 5.9), 0.03] were associated with higher odds of PM.

Conclusion:
Our nationally representative study demonstrates the overall safety of ambulatory LE-PVI in a real-world setting with low periprocedural complications and mortality.