bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12634: The Association of 24-hour Holter-Derived Heart Rate Variability With Incident Heart Failure in the Cardiovascular Health Study
Authors: Patel Vaiibhav N , Pierce Brian , Bodapati Rohan , Brown David L , Ives Diane , Stein Phyllis K
Published: April 2024

Background:
Abnormal heart rate variability (HRV) has been used to predict multiple adverse cardiovascular outcomes but not the development of congestive heart failure (CHF). We hypothesized that the addition of Holter-based HRV parameters to an existing CHF clinical risk model would improve its ability to identify older adults at an increased risk of CHF in the Cardiovascular Health Study (CHS).

Methods:
The Health ABC Heart Failure (Health ABC) score is a clinically based CHF prediction tool that has been validated in the CHS. Asymptomatic CHS participants with interpretable 24-hour baseline Holter recordings were included (N=1,401). Holter-based HRV measures and premature ventricular contraction (PVC) counts were compared between participants with (N=260) and without (N=1,141) incident CHF on follow up. Significantly different parameters between groups were added to the components of the Health ABC score using stepwise Cox regression.

Results:
Participants who developed CHF were more likely to be older, male, and have left ventricular hypertrophy (LVH) and coronary artery disease (CAD). They were also more likely to have a higher body mass index, baseline heart rate, systolic blood pressure, fasting glucose and creatinine. The final prediction model included all components of the Health ABC score (age, creatinine, albumin, heart rate, systolic blood pressure, fasting glucose, LVH, smoking and CAD), ln (PVCs+1) (Hazard Ratio [HR]=1.12; 95% CI, 1.06-1.19; p<0.001) and the following HRV measures: abnormal heart rate turbulence onset (HR=1.52; 95% CI, 1.11-2.08; p=0.009), decreased short-term fractal scaling exponent (HR=0.27; 95% CI, 0.14-0.53; p<0.001), increased ln (very low frequency power) (HR=1.27; 95% CI, 1.01-1.60; p=0.039) and decreased coefficient of variance of NN intervals (HR=0.94; 95% CI, 0.90-0.99; p=0.01). The C-statistic for the final model was significantly improved over the Health ABC model alone (0.77 vs. 0.73, p=0.0002).

Conclusion:
Abnormal HRV parameters were significant and independent predictors of incident CHF in asymptomatic, older adults. When combined with increased PVCs, these measures improved the predictive power of the Health ABC score in identifying CHS participants at an increased risk of developing CHF.
Abstract 12691: The Biological Clock Regulates Cellular Iron Homeostasis
Authors: Yar Sumeyye , Bien Peek Clara , Jiang Xinghang , Wilsbacher Lisa , Ardehali Hossein
Published: April 2024

Introduction:
Iron is an essential metal for various cellular processes including mitochondrial respiration, DNA synthesis and protein synthesis. Low iron stores can disrupt any of these processes, while excess free iron increases oxidative stress. It is thus crucial to regulate iron levels to meet cellular needs while preventing excess iron accumulation. Previously it was reported that human serum iron levels show diurnal variations. However, the underlying mechanism by which iron homeostasis shows rhythmic variations and whether circadian iron regulation also exists at cellular level is unknown. Since the main function of the biological clock is to synchronize cellular demands with environmental signals such as nutrition, we hypothesize that the biological clock regulates cellular iron homeostasis to protect cells from oxidative damage.

Results:
Assessment of iron levels in various tissues in mice revealed that hepatic iron levels display 24-hour diurnal variations with peaks by the onset of the active period. Furthermore, disruption of the biological clock by the deletion of circadian transcriptional activator Bmal1 caused an increase in hepatic iron levels, which was associated with a decrease in serum iron. To investigate the underlying mechanism of the clock-mediated regulation of cellular iron, we next measured the mRNA levels of iron homeostasis genes in the liver of Bmall
-/-
and WT mice. Our results indicated that among all proteins involved in iron homeostasis, the levels of the iron exporter, ferroportin-1 (FPN1) was significantly decreased in Bmal
-/-
mice. Since Bmal1 deletion is associated with an increase in cellular iron, the reduced levels of FPN1 suggests that decreased iron export through FPN1 might be the mechanism for iron accumulation in Bmal
-/-
livers. Bmal1 deletion was also associated with decreased levels of iron importer protein transferrin-1, consistent with a cellular signature of iron overload. Finally, mRNA expression of FPN1 and TfR1 also displayed diurnal variations.

Conclusions:
Our data establish a link between the biological clock and cellular iron homeostasis pathways in mammals. Our data also suggests that FPN1 and TfR1 expression might be controlled by the clock machinery.
Abstract 12707: HIV Infection and Heart Failure Outcomes in Women
Authors: Janjua Sumbal A , Triant Virginia A , Szilveszter Balint , Addison Daniel , Regan Susan , Staziaki Pedro , Shah Ravi V , Steven Grinspoon K , Hoffmann Udo , Zanni Markella V , Neilan Tomas G
Published: April 2024

Introduction:
Women with HIV have an increased risk of incident heart failure (HF). Whether HF outcomes differ by HIV status in women has not been established.

Methods:
We performed a US health care system-based cohort study analyzing data from 1388 HIV-infected women initially matched 1:10 on age, race/ethnicity with uninfected women. The presence of HF was ascertained by ICD-9-CM codes and adjudicated by physicians blinded to HIV status. After adjudication, cohorts were re-matched 1:3 so that age, race/ethnicity would be similar in the final cohort. The primary outcome was incident HF hospitalization rate. Secondary outcomes included HF hospitalization length of stay, all cause and cardiovascular mortality.

Results:
The final HF cohort consisted of 34 HIV-infected and 102 uninfected women (mean age 59 years). There were no significant differences in the LVEF (54±15 vs. 52±14%, HIV+ vs. HIV-, p=0.48) or prevalence of HFrEF (EF<50%) (29 vs. 35%, HIV+ vs. HIV-, p=0.67). HIV-infected women with HF had more cocaine use (23 vs. 6%, p=0.006), lower BMI (28±5 vs. 33±8 kg/m
2
, p=0.002), increased QRS (113±19 vs. 97±20 msec, p <0.0001) and higher PASP (49±10 vs. 35±10 mmHg, p<0.0001). Over a median follow-up of 5 years (IQR 4.0-7.5), HIV-infected women with HF had 2.5 times the rate of incident HF hospitalization, adjusted for age, HTN, DM, sleep apnea, CAD, ACE I/ARB and LVEF (HR: 2.5 (1.54-4.29), p<0.0001) (Figure). HIV-infected women with HF also had an increased HF hospitalization length of stay (8 vs. 5 days, p<0.001), and higher all-cause (53 vs. 21%, p<0.001) and cardiovascular mortality (83 vs. 33%, p<0.006). In sub-group analysis, HIV-infected women with HFrEF had lower use of guideline-recommended HF therapy (40 vs. 83%, p=0.01).

Conclusions:
As compared with matched uninfected women with HF, HIV-infected women with HF had a lower use of HF therapies, increased HF hospitalization rate, HF hospitalization length of stay, and all-cause and cardiovascular mortality.
Abstract 12740: Clinical Impact of the Residual Syntax Score in Acute Coronary Syndrome Patients
Authors: Hiramori Seiichi , Hyodo Makoto , Soga Yoshimitsu , Shirai Shinichi , Ando Kenji
Published: April 2024

Introduction:
Some studies have shown prognostic value of the residual Syntax score (rSS) in patients with multivessel coronary artery disease. However, it remains unclear that how much impact the rSS has on clinical outcomes in ACS patients.

Hypothesis:
A reduction of rSS may relate to the improvement of clinical outcomes in ACS patients.

Methods:
This study was an observational study examining consecutive ACS patients from January 2009 to December 2014 at our institution. Study population included 2025 ACS cases. The rSS was derived from post primary and primarily scheduled PCI angiography. Patients were dichotomized into low (<8) and high rSS (≥8) groups and outcomes were compared between groups. The primary outcome of net adverse cardiovascular events (NACE) consisted of a composite of all-cause mortality, non-fatal MI, and any revascularization at 1 year.

Results:
The mean rSS was 5.1 (±6.6). The incidence of NACE at 1 year was significantly higher in high rSS group than low rSS group (48.7% versus 26.5%, p<.0001). The incidence of all-cause death (17.4% versus 6.5%, p<.0001) and any revascularization (36.4% versus 21.1%, p<.0001) were also higher in high rSS group. On the other hands, there was no significantly difference between two groups in non-fatal MI (1.9% versus 1.8%, p=.88). After adjustment for confounders, a high rSS was also an independent predictor of the primary outcome with a hazard ratio of 1.94 (95% confidential interval [CI], 1.58-2.39; p<.0001).

Conclusions:
Our study suggests that high residual Syntax score (≧8) is significantly associated with poor clinical outcomes.
Abstract 12796: Plaque Surface Irregularity and Calcification Length Within Carotid Plaque Predict Secondary Events in Patients With Coronary Artery Disease
Authors: Nonin Shinichi , Iwata Shinichi , Sugioka Kenichi , Kawai Yu , Fujita Suwako , Ishikawa Sera , Norioka Naoki , Ito Asahiro , Nakagawa Masashi , Yoshiyama Minoru
Published: April 2024

Introduction:
Although comprehensive risk factor modification is recommended, a uniform management strategy does not necessarily prevent secondary events in patients with coronary artery disease (CAD). Therefore, identification of high-risk patients who may benefit from more intensive interventions may improve prognosis. Carotid ultrasound can reliably identify systemic atherosclerosis, and carotid plaque and intima-media thickness (IMT) are known independent risk factors for CAD. However, it is unclear whether findings on carotid ultrasound can improve prediction of secondary CAD events.

Methods:
The study population comprised 146 consecutive patients with CAD (mean age, 66 ± 9 years; 126 with angina pectoris, 20 with myocardial infarction). IMT, plaque score, plaque area, plaque surface irregularity, and calcification length (calculated by summing the calcified lesions within each plaque accompanied by acoustic shadow) were measured at baseline. Patients were followed for 10 years to ascertain secondary CAD events.

Results:
Of 146 patients, secondary CAD events occurred in 63 after a median follow-up of 10 years. In univariate analysis, calcification length (P < 0.05) and plaque surface irregularity (P < 0.01) were associated with secondary CAD events, whereas IMT, plaque score, and plaque area were not. Multiple regression analysis demonstrated that calcification length (odds ratio, 1.06; P < 0.05) and plaque surface irregularity (odds ratio, 3.85; P < 0.01) remained independently associated with secondary CAD events after adjustment for age, sex, diabetes mellitus, dyslipidemia, hypertension, chronic kidney disease, and smoking. Moreover, when patients were divided into 4 groups according to calcification length and presence or absence of plaque surface irregularity, the group with longer calcification and plaque surface irregularity had greater risk of secondary CAD events (relative risk, 3.82; P < 0.05).

Conclusions:
These findings suggest that the combination of calcification length and plaque surface irregularity has additional value beyond traditional risk classification. Intensive intervention for these high-risk patients may avoid or delay progression of atherosclerosis towards secondary CAD events.
Abstract 12854: Parenchymal Lung Injuries Related to Standard Cardiopulmonary Resuscitation
Authors: Cha Kyoung-Chul , Hwang Sung Oh , Kim Hyung Il , Kim Oh Hyun , Cha Yong Sung , Kim Hyun , Lee Kang Hyun
Published: April 2024

Purpose:
Little is known about parenchymal lung injuries after external chest compressions during cardiopulmonary resuscitation (CPR). We analysed chest CT scan to evaluate parenchymal lung injury and its clinical significance in patients who received standard CPR and were resuscitated from cardiac arrest.

Materials and Methods:
We enrolled non-traumatic out-of-hospital cardiac arrest patients older than 18 years old who had been admitted to the ED in cardiac arrest and successfully resuscitated after CPR. Chest CT was obtained immediately after return of spontaneous circulation (ROSC). To allocate the area of lung contusion, we divided both hemithoraces into upper, middle, and lower parts longitudinally and each part was subdivided into 4 regions (anteromedial, anterolateral, posteromedial, and posterolateral) except the lower part of the left lung. Finally, both lungs were divided into 23 regions. To stratify the severity of lung contusion, each region was scored depending on the area of lung contusion (ALC) with 1 = ALC<1/3 of a region, 2 = 1/3≤ALC<2/3 of a region and 3=ALC≥2/3 of a region. Oxygenation index (OI: PaO
2
/FiO
2
) was measured at the time of ROSC, 24hr, 48hr, 72hr, and 1 week after cardiac arrest. Acute lung injury (ALI) was defined as OI below 300.

Results:
Ninety-one patients were enrolled. Lung contusion was developed in 37 patients (40.7%) and median lung contusion score was 15 (0-15). Lung contusion was not associated with hospital mortality (p=0.318), development of ALI (p=0.515), or the length of ICU stay (p=0.203). The OI at the time of ROSC was lower in patients with lung contusion score > 23 than in patients with lung contusion score≤23 (164±93 vs. 278±122, p=0.008). However, the OI at 24hrs, 72hrs, and 1 week after ROSC was not different between patients with lung contusion score > 23 and patients with lung contusion score≤23 (p=0.240, 0.698, 0.446, and 0.168, respectively)

Conclusion:
Extensive lung contusion is associated with a lower oxygenation index at the time of ROSC, but did not affect the resuscitation outcome.
Abstract 12945: A Novel Index for Quantification of Interventricular Septal Flattening in Pediatric Patients With Right Ventricular Hypertension
Authors: Averin Konstantin , Michelfelder Erik , Urbinelli Lindsay , Hirsch Russel
Published: April 2024

Introduction:
Systolic flattening of the inter-ventricular septum (IVS) is a marker of elevated right ventricular pressure (RVp). It can be non-invasively quantified by a left ventricular eccentricity index (LVEI), RV to left ventricular (LV) ratio and a novel index - the systolic flattening angle (SFA). Data evaluating the relationship between these indices and invasive RVp in pediatrics are limited.

Methods:
Patients referred for right and left heart cardiac catheterizations (CC) were enrolled and underwent echocardiograms after induction of anesthesia. The SFA, RV:LV ratio and LVEI were measured in end-systole. Peak systolic RVp and aortic pressure (pAo) were measured simultaneously during CC. The likelihood of SFA to predict an RVp:pAo ratio of > 0.5 was assessed using receiver-operator curve (ROC) analysis. Bland-Altman plots were used to assess inter-observer agreement.

Results:
Forty-one unique subjects were enrolled [56% female, median age 2.7 years (0.7, 7.1) and median weight 12.1kg (6.0, 22.3)]. The median mid-ventricular (MV), apical, and sub-costal LVEI was 1.18 (0.9, 1.7), 1.18 (1.0, 1.7), and 1.13 (1.0, 1.5), respectively. The mean SFA was 8.5±9.6°, the median RV:LV ratio was 0.71 (0.46, 1.23), and the mean RVp:pAo ratio was 0.68 ± 0.5. There was a significant negative correlation (r = -0.75, p <0.001) between SFA and RVp:pAo ratio and a modest correlation with other non-invasive indices (Figure). ROC analysis demonstrated an area under the curve = 0.90 for prediction of RVp:pAo > 0.50 by SFA. An SFA < 10.6 had a sensitivity of 88% and specificity of 79% in predicting RVp:pAo > 0.50. SFA was modestly reproducible with a Bland-Altman plot demonstrating a bias of 4.14 and limits of agreement of -7.8 and 16.1.

Conclusions:
SFA has the best correlation with RVp:pAO, good sensitivity and specificity, but relatively high inter-observer variability. Taken together, these non-invasive measures may help minimize the need for invasive assessment of RVp.
Abstract 12968: Early AV Conduction Recovery After Pacemaker Placement for High-Degree AV Block Secondary to Transcatheter Aortic Valve Replacement
Authors: Raelson Colin A , Gabriels James , Ruan Jonathan , Ip James E , Thomas George , Liu Christopher F , Cheung Jim W , Lerman Bruce B , Patel Apoor , Markowitz Steven M
Published: April 2024

Introduction:
Recovery of conduction has been demonstrated in >50% of patients who receive pacemakers (PPMs) for high-degree atrioventricular block (HDAVB) after trans-catheter aortic valve replacement (TAVR). Little information is available about the time course of conduction recovery in these patients, and there is little comparative data regarding resolution of AV block after balloon-expandable compared to self-expanding valves.

Methods:
A retrospective review was performed of patients who underwent TAVR with balloon and self-expanding valves and required PPMs for HDAVB at 2 institutions. Serial PPM interrogations were analyzed to detect recovery of AV conduction. Analysis was performed to identify predictors and timing of conduction recovery.

Results:
Of a total population of 578 patients, 54 (9.3%) received PPMs for HDAVB. In multivariate analysis, predictors of HDAVB requiring a PPM included right bundle branch block (OR 5.99 [3.08 -11.6]), atrial fibrillation (OR 1.87 [1.02-3.45]), and self-expanding valves (OR 3.45 [1.85-6.43]). Of the 54 patients who received PPMs, 38 had follow-up sufficient to evaluate AV conduction recovery. Of these, 23 (61%) showed recovery of AV nodal conduction; 20 had already recovered by their first interrogation a median of 22 days (IQR 14-31) post PPM placement (figure). There were no statistically significant predictors of AV nodal conduction recovery, including type of valve implanted. For those who recovered conduction, 9/23 (39%) had ventricular pacing >50% of the time on their final interrogation, of whom 5 had programmed AV intervals <200 msec.

Conclusions:
A majority of patients who receive PPMs for HDAVB after TAVR recover AV conduction during follow-up, and in most patients conduction recovery occurs within weeks. These findings imply that longer observation periods may be appropriate after TAVR before PPM implantation, and programming that minimizes ventricular pacing may be beneficial.
Abstract 12977: Neladenoson, a Partial Adenosine A1-receptor Agonist, Improves Mitochondrial Function in Left Ventricular Cardiomyocytes Isolated From Dogs With Chronic Heart Failure
Authors: Sabbah Hani N , Gupta Ramesh C , Singh-Gupta Vinita , Zhang Kefei , Xu Jiang , Albrecht-Küpper Barbara
Published: April 2024

Background:
Mitochondria (MITO) of failing cardiomyocytes (CMs) manifest structural and functional abnormalities characterized by hyperplasia, reduced organelle size and reduced respiration. These abnormalities lead to reduced rate of ATP synthesis and excess production of reactive oxygen species. We previously showed that chronic therapy with a partial adenosine A1-receptor agonist (pA1RA) improves LV function and normalizes tissue levels of MITO uncoupling proteins 2 and 3 in dogs with heart failure (HF).

Hypothesis:
Neladenoson, a new pA1RA, improves MITO function in freshly isolated CMs from dogs with chronic HF.

Methods:
CMs were isolated from LV of 7 microembolization-induced HF dogs (LV ejection fraction <30%) and from 6 normal (NL) dogs using a collagenase-based enzymatic process that yielded ~70% rod-shaped CMs that excluded trypan blue. Equal aliquotes of CMs were incubated in 0 (vehicle), 3, 10, and 30 nM concentration of Neladenoson for one hour at 37°C. MITO ADP-stimulated state-3 respiration, maximum rate of ATP synthesis and complex-IV activity (COX-IV) were measured at end of incubation. Respiration was measured with a Strathkelvin respirometer and COX-IV activity was measured polarographically and both expressed as nAtom Oxygen/min/mg protein. Rate of ATP synthesis was measured using the bioluminescent ApoSENSOR assay and quantified in RFU/μg protein.

Results:
Data are shown in the table. Increasing concentration of Neladenoson had no effect on measures of MITO function in CMs from NL dogs. In CMs from HF dogs, depressed levels of MITO respiration, ATP synthesis and COX-IV increased significantly and in a dose-dependent manner after exposure to Neladenoson.

Conclusions:
Neladenoson has beneficial effects on MITO function in CMs from HF dogs. Furthermore, the improvement in MITO function after treatment with Neladenoson can occur early after initiation of therapy (within one hour) and is dose-dependent up to concentrations of 30 nM.
Abstract 13024:
Cardiopulmonary Best Abstract Award
: A Disintegrin and Metalloproteinase With Thrombospondin Motifs 8 Downregulates AMP-activated Protein Kinase and Promotes Matrix Metalloproteinases Activation and Pulmonary Hypertension
Authors: Omura Junichi , Satoh Kimio , Kikuchi Nobuhiro , Satoh Taijyu , Kurosawa Ryo , Nogi Masamichi , Sunamura Shinichiro , Ohtsuki Tomohiro , Kozu Katsuya , Numano Kazuhiko , Sugimura Koichiro , Tatebe Shunsuke , Aoki Tatsuo , Suzuki Kota , Yaoita Nobuhiro , Shimokawa Hiroaki
Published: April 2024

Background:
Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries (PA) and excessive proliferation of PA smooth muscle cells (PASMCs). ADAMTS8, a member of the disintegrin and metalloproteinase, is a secreted extracellular enzyme that is specifically expressed in lung tissue.

Methods and Results:
To explore a novel therapeutic target of PAH, we performed microarray analysis of PASMCs from patients with PAH (PAH-PASMCs) and found a significant up-regulation of ADAMTS8 in PAH-PASMCs compared with controls (>5-fold, P<0.01). Protein levels of ADAMTS8 were significantly increased in PAH-PASMCs compared with controls (>1.3-fold, P<0.05, n=5 each). Indeed, immunoreactivity of ADAMTS8 was enhanced in the thickened medial layer of PA in PAH patients (n=2-3). Additionally, hypoxia increased protein level of ADAMTS8 in mouse lung homogenates compared with controls (P<0.05, n=6-10 each). Human recombinant ADAMTS8 (hrADAMTS8, 25 ng/mL) suppressed AMP-activated protein kinase (AMPK) signaling, activated matrix metalloproteinases (MMPs), and promoted PASMC proliferation (all P<0.05). In contrast, ADAMTS8 siRNA reduced PASMC proliferation (P<0.05). PASMC-specific ADAMTS8

-/-

mice exposed to hypoxia (10% O
2
, 4 weeks) showed significantly reduced RV systolic pressure (33.5±0.3 vs. 38.9±0.4 mmHg), RV hypertrophy (0.26±0.06 vs. 0.33±0.09), and PA remodeling compared with controls (all P<0.05, n=9 each). In situ zymography with DQ gelatin showed reduced MMP activities in PA in ADAMTS8
-/-
compared with controls (P<0.05). Primary cultured PASMCs from ADAMTS8

-/-

mice showed AMPK activation, reduced migration and proliferation compared with controls (P<0.05, n=6 each). Importantly, hrADAMTS8 treatment suppressed VEGFA-induced AMPK activation and VEGF receptor-2 phosphorylation in PA endothelial cells (P<0.05, n=6 each). Consistently, PAEC-specific AMPK

-/-

mice exposed to hypoxia showed significantly increased RV systolic pressure (39.3±1.0 vs. 33.1±0.9 mmHg), RV hypertrophy, and PA remodeling compared with controls (all P<0.05).

Conclusions:
ADAMTS8 downregulates AMPK in PA endothelial cells and induces MMP activation and PASMCs proliferation, thus promoting the development of PH.
Abstract 13033: Abnormal P-Wave Axis is Associated With an Increased Risk of Sudden Cardiac Death: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Maheshwari Ankit , Norby Faye L , O’Neal Wesley T , Adabag Selcuck , Alonso Alvaro , Soliman Elsayed Z , Chen Lin Y
Published: April 2024

Introduction:
Abnormal P-wave axis (aPWA) has been linked to all-cause mortality and incident atrial fibrillation (AF). The relationship between aPWA and sudden cardiac death (SCD), however, has not been defined.

Hypothesis:
We hypothesized that aPWA is independently associated with SCD and tested our hypothesis in the ARIC study, a community-based prospective cohort study.

Methods:
We included 15,381 participants (age 54.2 ± 5.7 years, 55% women, 26.4% blacks) who attended the baseline visit (1987-89) and with complete ECG data. aPWA was defined as any value outside 0-75 degrees using 12-lead ECGs obtained during the baseline exam. SCD was physician-adjudicated and defined as a sudden, pulseless condition in a previously stable individual without evidence of a non-cardiac cause of death. Cox regression was used to compute hazard ratios and 95% confidence intervals for the association of aPWA with SCD.

Results:
At baseline, there were 1,275 participants with aPWA. During a mean follow-up of 13.1 years (1987-2001), 272 SCDs were identified from coronary heart disease deaths. aPWA was associated with a 1.49-fold (95% CI, 1.03-2.15) increased risk of SCD independent of traditional SCD risk factors. However, after adjustment for time-dependent AF, the association of aPWA with SCD was attenuated (Table).

Conclusions:
aPWA is associated with an increased risk of SCD in the general population. This association, however, is likely mediated by AF; the latter we recently reported to be a risk factor for SCD.

aPWA is associated with an increased risk of SCD in the general population. This association, however, is likely mediated by AF; the latter we recently reported to be a risk factor for SCD.
Abstract 13037: Self-Care Questionnaire Detects More Brain Injury in Comparison to Cognitive Screener in Heart Failure
Authors: Woo Mary A , Roy Bhaswati , Fonarow Gregg C , Kumar Rajesh
Published: April 2024

Introduction:
Heart failure (HF) patients often have poor self-care (SC) and cognitive deficits. Both factors are closely related and require brain control of important skill sets. However, it is unclear if SC or cognition are linked to injury in different brain regions or if SC vs. cognition evaluation differs in the detection of brain damage amounts.

Hypothesis:
To determine if a measure of SC or cognition detects more brain injury in HF.

Methods:
Brain diffusion Tensor Imaging (DTI) data were collected from 10 HF (age 56.8±8.1 years; 8 male; LVEF 26.4±11.9% NYHA class II/III) using a 3 Tesla MRI scanner, Self-care was examined with the Self-Care of Heart Failure Inventory (SCHFI), and cognition with the Montreal Cognitive Assessment (MoCA) test. Using DTI data, mean diffusivity (MD; higher values=brain injury) maps were used to examine associations between SCHFI (maintenance and confidence subscales) and MoCA in HF subjects using partial correlation procedures (covariates: age and gender; uncorrected threshold p<0.005).

Results:
Significant negative correlations between MD and confidence scores emerged in the prefrontal cortex. hippocampus, amygdala, anterior and posterior cingulate, anterior corpus callosum, mid and posterior thalamus, posterior insula, putamen, inferior temporal lobe, and cerebral vermis, and between MD and maintenance scores in the right putamen, external and internal capsule, and right inferior temporal lobe (Figure). Significant negative correlations were observed between MD and MoCA scores in the prefrontal cortex, occipital cortex, cerebellum, and mid-inferior temporal lobe (Figure).

Conclusions:
HF subjects show more wide-spread and significant correlations between regional MD values/brain injury and SCHFI scores compared to MoCA values. The findings suggest that damage in cognitive and decision-making control sites better correlate with SCHFI over MoCA scores.
Abstract 13106: Over Expression of Glyoxalase 1 Prevents Chronic Hyperglycemia Induced Explant Derived Cardiac Stem Cell Dysfunction
Authors: Villanueva Melanie , Davis Darryl R
Published: April 2024

Diabetes increases the risk of heart disease and worsens clinical outcomes after myocardial infarction. Given that hyperglycemia promotes the generation of toxic methylglyoxal, the influence of the key detoxification enzyme glyoxalase 1 (Glo1) on chronic hyperglycemia induced explant-derived cardiac stem cell (EDC) dysfunction was investigated.

Methods/Results:
Sixteen-week old wild type (WT, n=22) or constitutive Glo1 overexpressing (Glo1TG, n=12) mice were studied 2 months after treatment with streptozotocin or vehicle (2.0±0.1 fold increase in glycated hemoglobin, p=0.001 vs vehicle treated mice). Hyperglycemia reduced overall culture yields (86±3% fewer EDCs cultured, p=0.0009) and prolonged population doubling time (30±4% slower growth, p=0.04) while increasing the cellular content of reactive dicarbonyls (27±3% more reactive oxygen species, p=0.0006) within EDCs cultured from WT mice. These intrinsic cell changes reduced the angiogenic potential (74±2% less total endothelial tubule formation, p=0.001) and production of pro-healing exosomes (43±6% fewer exosomes secreted, p=0.04) by hyperglycemic EDCs while promoting EDC senescence (98±28% more senescent EDCs, p=0.03). As compared to transplant of normoglycemic WT EDCs, hyperglycemia reduced the EDC-mediated increases in echocardiographic ejection fraction and dP/dTmax in infarcted normoglycemic WT mice 3 weeks after intra-myocardial injection by 37±8% (p=0.0001) and 25±1% (p=0.001), respectively. In contrast to EDCs cultured from WT hyperglycemic donors, EDCs cultured from Glo1TG mice: 1) decreased the reactive oxygen species content by 46±2% (p=0.0001), 2) increased cell culture yields by 2.2±0.2 fold (p=0.0004) and 3) boosted echocardiographic left ventricular ejection fraction by 27±7% (p=0.0001) while increasing dP/dTmax by 21±4% (p=0.007).

Conclusions:
Chronic hyperglycemia decreases the regenerative performance of EDCs. Over-expression of Glo1 reduces dicarbonyl stress and prevents chronic hyperglycemia-induced EDC dysfunction.
Abstract 13110: Pediatric Heart Transplantation in Pre-Sensitized Recipients: A Current Perspective
Authors: Das Bibhuti , Pruitt Elizabeth , Molina Kimberly , Ravekes William , Auerbach Scott , Savage Andrew , Knox Leah , Kirklin James , Naftel David , Hsu Daphne
Published: April 2024

Introduction:
Anti-HLA antibodies (Ab) are increasingly prevalent in pediatric patients (pts) awaiting heart transplant (HT) and may result in a significant delay in time to HT because of the need to wait for a negative prospective donor HLA crossmatch (XM).

Methods:
Data from pts in the Pediatric HT Study transplanted between 2010-2014 were analyzed to determine the association of pre-HT percent reactive anti-HLA Ab (PRA) detected by flow cytometry with retrospective donor XM results and outcomes after HT. Sensitization was defined as a PRA >20%.

Results:
HT was performed in 1,596 pts, 1,459 had a PRA calculated and 1,419 had XM results available. Sensitization was present in 32% of pts; 25% were sensitized against Class I and 20% were sensitized against Class II Ab (p<0.01). Sensitization was more common in pts with congenital heart disease (CHD) compared to cardiomyopathy (CM), 28% vs. 15%, respectively, p<0.01). Sensitization was similar between pts with and without ventricular assist device support, 20% vs. 25%, respectively, p=0.07. The level of sensitization was significantly associated with a +XM (p<0.01, Table). Sensitized pts who had a +XM were at higher risk for rejection than those who had a - XM and those who were not sensitized (p<0.01, Figure). There was no difference in post-HT survival between sensitized and nonsensitized pts, p=0.11, or those with and without a +XM, p=0.06.

Conclusions:
In the current era, 32% of pediatric HT pts are sensitized, with a higher incidence seen in pts with CHD compared to those with CM. Although, increasing PRA levels were associated with a higher likelihood of a positive retrospective XM, 68% of pts with a pre-HT PRA >50% had a negative XM. XM was positive in 9% of pts with a PRA between 1-20%. Sensitized pts with a positive XM had a higher incidence of rejection than all other pts. Better methods of identifying pts at risk for a positive XM are needed to refine the indications for a prospective XM in pediatric pts listed for HT.
Abstract 13125: FOXO1/Notch Signaling Modulates Ambient Ultrafine Particle Exposure-Impaired Vascular Development
Authors: Baek Kyung In , Beebe Tyler , Ma Zhao , Gau Jon , Saffari Arian , Sioutas Constantinos , Li Rongsong , Hsiai Tzung
Published: April 2024

Introduction:
Exposure to ultrafine particles (UFP,
d
< 0.1 μm), redox-active components of particular matter (PM
2.5
), promotes vascular inflammatory responses. Notch signaling in endothelial cells (EC) promotes differentiation and proliferation of vasculature. FOXO1, the dominant isoform of the forkhead box O subfamily (FOXO) in EC, interacts with Notch signaling via enhancing co-repressor clearance and assembly of activation complex during induction of Notch signaling. Whether a FOXO1/Notch signaling axis modulates UFP- impaired vascular development remains elusive.

Hypothesis:
We hypothesized that UFP impairs vascular repair by attenuating Notch signaling via inhibition on FOXO1.

Methods and Results:
Transgenic
Tg(fli1:gfp)
zebrafish at 3 days post fertilization (dpf) developed vascular regeneration at 3 days post amputation (dpa) of the tail, whereas exposure to UFP or treatment with ADAM10 inhibitor (inhibit Notch receptor activation to generate Notch intracellular cytoplasmic domain [NICD]) resulted in disrupted intersegmental vessels (ISV) and impaired tail regeneration (
P
< 0.05, n=20). Notch signaling was evidently visualized in the region of tail injury in the Notch responsive reporter fish
Tg(tp1:gfp)
crossed with
Tg( flk1:mCherry)
line at 3 dpa. UFP, ADAM10 inhibitor, and FOXO1 morpholino oligonucleotides (MO) micro-injection attenuated Notch activities at 3 dpa, respectively. NICD mRNA rescue partially restored Notch activity and vascular regeneration at 3 dpa, whereas combination of both NICD and FOXO1 mRNA rescue fully restored Notch activity and tail regeneration. As a corollary, UFP exposure induced a dose-dependent reduction in Notch reporter activity and FOXO1 mRNA expression in human aortic endothelial cells (HAEC). FOXO1 mRNA rescue restored Notch activity and Notch related gene expressions, including Dll4 and HES1(
P
< 0.05, n=3) in fish exposed to UFP.

Conclusions:
UFP impairs vascular regeneration via Notch signaling. Notch/FOXO1 cooperation is implicated in promoting vascular development.
Abstract 13140: Effectiveness of Rivaroxaban among Patients Diagnosed With Pulmonary Embolism
Authors: Wang Li , Baser Onur , Wells Phil , Peacock W. F , Coleman Craig , Fermann Gregory J , Schein Jeff , Crivera Concetta
Published: April 2024

Introduction:
Rivaroxaban is a fixed-dose anticoagulant that facilitates earlier hospital discharge, potentially reducing patient exposure to hospital-acquired complications (HAC). Due to the recent introduction of rivaroxaban and limited evidence on its impact in real world settings, we compared the effectiveness of rivaroxaban vs. standard of care (SOC) among pulmonary embolism (PE) patients in the Veterans Health Administration.

Methods:
Adult patients with continuous enrollment for ≥12 months before and 3 months after an inpatient diagnosis of PE between 10/1/11 and 6/30/15, and a prescription claim for an anticoagulant during the index hospitalization were included. SOC drugs were low molecular weight heparin, unfractionated heparin, and warfarin. Propensity score matching (PSM) compared PE-related outcomes (recurrent venous thromboembolism (VTE), major bleeding and death), HAC, healthcare utilization, and costs among patients receiving SOC and rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HAC.

Results:
Among 6,746 PE patients, 208 received rivaroxaban and 4,641 received SOC during the index hospitalization. Most (95%) were male; 22% were African American. After 1:3 PSM, there were 203 rivaroxaban and 609 SOC patients. Mean length of stay (LOS) was 6.3 days for rivaroxaban and 10.4 days for SOC (p=0.0402). In the 90-day post-discharge period, rivaroxaban users (vs. SOC) had similar rates of PE-related outcomes (recurrent VTE: 3.0% vs. 5.3%, p=0.1793, major bleeding: 2.0% vs. 2.6%, p=0.6011, death: 2.5% vs. 4.1%, p=0.2828), fewer HAC (10.3% vs. 15.9%, p=0.0506), and fewer bacterial pneumonias (10.3% vs. 17.2%, p=0.0188). Rivaroxaban users had better net clinical benefit (82.8% vs. 71.1%, p=0.0010). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs. 19.9, p=0.0005), similar rehospitalization rates (0.18 vs. 0.26, p=0.0836), lower inpatient costs ($3,501 vs. $6,189, p<0.0001), and lower total costs ($10,545 vs. $14,192, p=0.0002). When the sample was limited to low-risk PE patients, we found similar patterns.

Conclusions:
PE patients prescribed rivaroxaban had similar PE-related outcomes but shorter LOS, fewer HACs, and lower total costs than patients on SOC.
Abstract 13158: Hospitalization for De Novo versus Worsening Chronic Heart Failure: Insights From the ASCEND-HF Trial
Authors: Greene Stephen J , Hernandez Adrian F , Dunning Allison , Ambrosy Andrew P , Armstrong Paul W , Butler Javed , Cerbin Lukasz , Coles Adrian , Ezekowitz Justin A , Metra Marco , Starling Randall C , Teerlink John R , Voors Adriaan A , O’Connor Christopher M , Mentz Robert J
Published: April 2024

Introduction:
Heart failure (HF) is a heterogeneous syndrome and individual patient survival varies widely. It is unclear how hospitalized acute HF (AHF) patients who are long-term chronic HF survivors differ from those with more recent HF diagnoses.

Methods:
The ASCEND-HF trial randomized 7,141 hospitalized AHF patients with reduced or preserved ejection fraction (EF) to nesiritide or placebo in addition to standard care. The present analysis compared patients by duration of HF diagnosis prior to index hospitalization using pre-specified cutpoints (0-1 month [i.e. “
de novo
”], >1-12 months, >12-60 months, >60 months).

Results:
Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (
de novo
, N=1536; >1-12 months, N=1020; >12-60 months, N=1653; >60 months, N=1532). Mean age ranged from 64-66 years and mean EF from 29-32% across all HF duration groups. Compared to patients with longer HF duration,
de novo
patients were more likely to have non-ischemic HF etiology, fewer comorbidities, lower natriuretic peptide levels, and better baseline functional status (all P-value <0.01). After adjustment, compared to
de novo
patients, longer HF duration was associated with more persistent dyspnea at 24 hours and increased 180-day mortality
(Table).
The influence of HF duration on mortality did not differ by age, gender, race, etiology of HF, or EF (all P-value for interaction ≥0.05).

Conclusion:
In this large AHF trial cohort, patient profile differed by duration of the HF diagnosis.
De novo
HF diagnosis was independently associated with greater early dyspnea relief and improved post-discharge survival compared to those with chronic HF diagnoses.
Abstract 13165: Comparison of Strut Coverage at 2 Weeks After Second and Third Generation DES Implantation in Patients With STEMI
Authors: Shimoda Masahiro , Ando Hirohiko , Suzuki Akihiro , Sakurai Shinichiro , Kurita Akiyoshi , Waseda Katsuhisa , Takashima Hiroaki , Amano Tetsuya
Published: April 2024

Background:
Third generation drug-eluting stent (DES) is characterized by thinner strut and abluminal coating with bioabsorbable polymer, and in vitro studies has demonstrated earlier endothelialization than previous generation of DES. However, whether this holds true also in human coronary is unknown.

Objective:
Using optical coherence tomography (OCT), we compared strut coverage between 2
nd
generation DES (XIENCE) and 3
rd
generation DES (SYNERGY) at 2 weeks after stent implantation for ST-segment elevation myocardial infarction (STEMI).

Methods:
Twenty-four patients with STEMI who were underwent primary percutaneous coronary intervention with XIENCE (n=14) or SYNERGY (n=10) were enrolled in this study. Angiographic and OCT were conducted at just after and 2 weeks after stent implantation. Two independent analysts who were blind to the clinical and stent information analyzed all images.

Results:
A total of 4362 struts were analyzed in this OCT study. There was no difference between XIENCE and SYNERGY in percentage of malapposed struts (5.38% vs. 4.78%, p=0.81), percentage of residual thrombus (57.1% vs. 40.0%, p=0.43) and maximal thrombus area (0.20mm
2
vs. 0.15mm
2
, p=0.61).

Percentage of strut coverage was significantly higher in SYNERGY than XIENCE (42.9% vs. 22.8%, p=0.0007).

Conclusion:
At 2 weeks after stent implantation for STEMI lesions, increased strut coverage was observed in SYNERGY than XIENCE, suggesting earlier vascular healing after SYNERGY implantation.
Abstract 13219: Adult Mammalian Hearts Restore Intrinsic Regenerative Capacity Through Signal Transducer and Activation of Transcription 3 in the Resolution Phase of Myocarditis
Authors: Miyawaki Akimitsu , Obana Masanori , Mitsuhara Yusuke , Orimoto Aya , Nakayasu Yusuke , Yamashita Tomomi , Fukada So-ichiro , Maeda Makiko , Sakata Yasushi , Nakayama Hiroyuki , Fujio Yasushi
Published: April 2024

Background and Aims:
It is widely accepted that mammalian cardiomyocytes can hardly proliferate in response to injury, which limits regeneration of the heart. On the contrary, spontaneous recovery in cardiac function is frequently observed in clinical settings of myocarditis. Therefore, we investigated the molecular mechanisms underlying the recovery from myocarditis with regard to cardiomyocyte proliferation using an experimental autoimmune myocarditis (EAM) model.

Methods and Results:
EAM was induced by immunizing 8 week old male BALB/c mice with α-myosin heavy chain twice. Three weeks after the first immunization (EAM3w), cardiac tissue was severely disrupted by infiltration of inflammatory cells, and substantial loss of cardiomyocytes was observed. However, cardiomyocytes displayed proliferative signature as demonstrated by increased expression of proliferative markers, i.e., Ki-67 and Aurora B, and BrdU incorporation at EAM3w, leading to dramatic tissue restoration at EAM5w. Consistently, the number of cardiomyocytes in the inflamed area was significantly increased at EAM5w compared to EAM3w. Additionally, we employed genetic cell fate mapping methods to trace pre-existing cardiomyocytes with YFP expression and found that pre-existing cardiomyocytes, rather than precursors/stem cells, were the source of proliferating cardiomyocytes at EAM3w. Immunoblot analyses for isolated cardiomyocytes demonstrated that signal transducer and activation of transcription 3 (STAT3), but not Akt or ERK, signaling was robustly activated in the inflamed heart, in consistence with upregulation of various IL-6 family cytokines. Conditional ablation of STAT3 in cardiomyocytes significantly suppressed cardiomyocyte proliferation at EAM3w without preventing the resolution of inflammation, resulting in impaired tissue restoration and cardiac dysfunction at EAM5w.

Conclusions:
Adult mammalian hearts restored intrinsic regenerative capacity in response to myocardial inflammation. STAT3 plays a critical role in cardiomyocyte proliferation in the recovery process from inflammation-induced cardiac damage.
Abstract 13221: Efficacy and Safety of Therapeutic Angiogenesis by Basic Fibroblast Growth Factor With Atelocollagen Solution in Patients With Critical Limb Ischemia
Authors: Ohno Kazunori , Kojima Shinsuke , Ariyoshi Makoto , Kaimoto Satoshi , Uchihashi Motoki , Kaneda Hideaki , Kagimura Tatsuo , Fukushima Masanori , Matoba Satoaki
Published: April 2024

Objectives:
To evaluate efficacy and safety of a treatment comprising basic fibroblast growth factor (bFGF) with atelocollagen solution in patients with critical limb ischemia (CLI) due to peripheral artery disease (PAD) or Burger’s disease (TAO).

Methods:
Human recombinant bFGF (200μg) with 4.8 mL of 3% atelocollagen solution was prepared and injected into forty administration sites in the gastrocnemius muscle of the ischemic leg. The primary endpoint was the safety of the treatment, as evaluated by adverse events. The secondary endpoint was the efficacy of the treatment, as defined by improvements in Fontaine stage, the Rutherford category, rest pain, 6-minute walking distance, ankle brachial pressure index (ABPI), ulcerous/necrotic lesions, and cyanosis 2, 4, 8, 12, 24, and 48 weeks after the treatment from baseline values.

Results:
10 CLI subjects received the treatment between November 2009 and November 2011. No serious procedure-related adverse events were observed during the follow-up. Within 48 weeks, the Fontaine stage improved in 4 subjects and was stable in 6 other subjects. The rest pain scale improved in 9 subjects while pain disappeared in 7 subjects. The maximum 6-minute walking distance increased in 7 subjects while 2 regained the ability to walk.

Conclusions:
The results of the present study demonstrated that angiogenic therapy using bFGF with atelocollagen solution was safe and feasible in patients with CLI.
Abstract 13289: Reduction in Extracellular Volume Fraction After Mitral Valve Repair of Chronic Mitral Regurgitation: A Cardiac MRI Pilot Study
Authors: Yang Eric Y , Ghosn Mohamad , Khan Mohammad A , Gramze Nickalaus L , Avenatti Eleonora , Brunner Gerd , Nabi Faisal , Little Stephen H , Nambi Vijay , Ballantyne Christie M , Lawrie Gerald M , Zoghbi William A , Shah Dipan J
Published: April 2024

Background:
Global extracellular volume fraction (ECV) assessed with cardiac magnetic resonance (CMR) has been shown to be elevated in patients with chronic mitral regurgitation compared with healthy controls. Limited work has been published on ECV changes following reduction in chronic volume overload with mitral valve intervention. We examined changes in ECV in patients with chronic mitral valve regurgitation after surgical mitral valve repair (SMVR).

Methods:
All patients underwent CMR studies before and after SMVR. CMR studies were performed with cine, phase contrast, T1 maps, and late gadolinium enhancement (LGE) imaging. Mid, short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. ECV was derived from T1 maps using area-weighted averages of only segments where LGE was absent, by a reader blinded to study date, clinical history and valve status.

Results:
Fifteen patients underwent SMVR a median of 1.4 (interquartile range [IQR] 0.8, 2.3) months after an initial CMR study (Table). Repeat CMR was performed a median 12.4 (IQR 7.2, 19.2) months after SMVR. None were on calcium channel blockers, nitrates, or direct arterial vasodilators. Following SMVR, significant reverse remodeling was seen with reductions in indexed left atrial volume and left ventricular parameters except end systolic volume (Table). ECV decreased from a mean 28.3% to 26.0% (p=0.01) (Table). No significant correlation was seen between changes in left sided CMR parameters and ECV (p=NS).

Conclusion:
In this pilot study of patients with significant chronic mitral regurgitation undergoing valve repair, a reduction in extracellular volume fraction was seen after 6 months or more, suggesting a decrease in myocardial fibrosis alongside reverse structural remodeling. Larger studies are needed to substantiate these findings and evaluate the clinical significance of ECV changes beyond cardiac reverse remodeling in patients undergoing mitral valve repair.