bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14937: Depressive Symptoms Were Not Associated With Cardiac Event-free Survival in Heart Failure Patients With Adequate Intake of Vitamin D
Authors: Song Eun Kyeung , Kang Seok-Min , Moser Debra K , Lennie Terry A
Published: July 2021

Introduction.
Low levels of vitamin D and severe depressive symptoms have been associated with increased proinflammatory cytokines that predict cardiovascular disease. However, little is known about the relationships among depressive symptoms, vitamin D deficiency, and cardiac events in patients with heart failure (HF).

Hypothesis.
We hypothesized that the link of depressive symptoms to cardiac event-free survival would differ between patients with vitamin D adequacy and deficiency.

Methods.
A total of 232 patients with HF (age 66±8 years, 34% female) completed the Patient Health Questionnaire-9 to assess depressive symptoms and were split into 2 groups using the standard PHQ-9 cutoff point of 10. Nutrition Analysis program was used to determine average daily intake of vitamin D through a 3-day food diary. Patients with > 85% probability of deficiency were defined as having a diet deficient in vitamin D. Covariate data on age, gender, body mass index, NYHA class, ejection fraction, comorbidities, and prescribed medications were obtained from review of medical records. Patients were followed for 2 years to determine time to first event of hospitalization or death. Hierarchical Cox proportional regression was used to examine our hypothesis.

Results.
106 patients (46%) had depressive symptoms and 116 patients (50%) had vitamin D deficiency. During 2 years, 88 patients (38%) were hospitalized or died due to cardiac problems. Depressive symptoms were associated with vitamin D deficiency (

X
2

=4.45,
p
= .035). In patients with vitamin D deficiency, depressive symptoms (HR=2.56, 95% CI=1.28-5.21) predicted shorter event-free survival after controlling for all covariates, whereas there was no difference in cardiac event-free survival between patients with depressive symptoms and no depressive symptoms in patients with vitamin D adequacy (
p
= .185) .

Conclusions.
The data suggest that depressive symptoms were not associated with cardiac event-free survival in HF patients with adequate intake of vitamin D. Future study is required to determine whether vitamin D adequacy could play a protective role in the impact of depressive symptoms on cardiac event-free survival in patients with HF.
Abstract 14983: Consistent Healthy Lifestyle Practice and Health-Related Quality of Life Trajectories in Older Age: The Chicago Heart Association Detection Project in Industry (CHA) Health Surveys
Authors: Vu Thanh Huyen T , Daviglus Martha L , Allen Norrina B , Liu Kiang , Garside Daniel B , Lloyd-Jones Donald M
Published: July 2021

Background:
Healthy lifestyle (HL) practices such as not smoking, frequent exercise and having normal BMI are related to better health-related quality of life (HRQoL). However, data on associations of long-term patterns on the combined effects of these HL practices in older age and in HRQoL is limited.

Methods:
We included 4,074 participants mean age 70 in 1996 from the CHA study who participated in a health survey in 1996 and at least two more in 2001, 2003, and 2012. HRQoL was assessed by Health Status Questionnaire-12 (HSQ-12) on health perception, and physical and mental well-being. The higher the HSQ-12 score, the better the quality of life. The number of HL practices was defined as a sum of the following three HL factors: never smoked, exercised frequently, and had a normal BMI.

Results:
Using Group-Based modelling, we identified three HL practice trajectories [practiced high (15.8%), medium (45.0%), and low number (39.1%) over time], and three HSQ-12 score trajectories for the total sum of scores and for the physical and mental component score separately (see Table for group identifications). With adjustment for age, sex, race, education attainment, marital status, alcohol intake, and comorbidities in 1996, odds ratios (95% confidence intervals) for having the best (high score and slow decline) QoL over 16 years of follow-up were highest in persons who maintained a high and moderate number of HL practices compared to those with a low number of HL practices were 8.72 (6.23-12.22) and 2.54 (1.92-3.37), respectively; findings were similar for having moderate (medium score and fast decline) QoL over time, and after stratifying by sex.

Conclusions:
Highly maintained healthy lifestyle practices in older ages is associated with high score and slow decline in health-related quality of life over time. This finding underscores the importance of consistently maintaining ideal healthy lifestyle practices in older age for better maintenance of quality of life.
Abstract 14991: Dantrolene Cannot Inhibit Aberrant Ca
2+
Release and Arrhythmias Without Calmodulin in Pressure Overload Heart Failure
Authors: Fukui Go , Yamamoto Takeshi , Kato Takayoshi , Maeda Takako , Nishimura Shigehiko , Hino Akihiro , Suetomi Takeshi , Ono Makoto , Mochizuki Mamoru , Oda Tetsuro , Okuda Shinichi , Kobayashi Shigeki , Yano Masafumi
Published: July 2021

Background:
We have been reported that dantrolene (DAN) binds to N-terminal domain of the cardiac ryanodine receptor (RyR2) and corrects the aberrant Ca
2+
leak. We have been also reported that DAN enhances binding affinity of Calmodulin (CaM) to RyR2 in failing cardiomyocytes. In this study, we investigated whether CaM is essential for the anti-arrhythmogenic effect of DAN using pressure-overload heart failure induced by transverse aortic constriction (TAC).

Methods and results:
Pressure overload to 12 weeks old mice was induced by TAC using a 27-gauge needle. Cardiomyocytes isolated from mice 8 weeks after TAC operation were used in the present study. The survival rate of our TAC mice at 8 weeks after TAC operation was 32 %. LV end-diastolic dimension was significantly enlarged and LV ejection fraction was significantly decreased. Lethal arrhythmias were frequently observed after 2 mg epinephrine infusion in TAC mice, but not in Sham mice. All following experiments were done under 1 μM of KN93 to avoid the effect of CaMKII. The Ca
2+
spark frequency (SpF: s
-1
·100 μm
-1
; by fluo3) was much higher in TAC than in Sham cardiomyocytes {TAC (n=10): 7.6±4.7; Sham (n=5): 5.7±1.9; p<0.01}. Addition of DAN to saponin-permeabilized TAC cells normalize Ca
2+
spark frequency {(n=5): 5.6±1.4}. This effect of DAN disappeared after suramin, CaM remover from RyR2, treatment {(n=4): 7.2±3.2}. Spontaneous Ca
2+
transients (SCaT) were measured during sequential pacing of intact cardiomyocytes from 1 Hz to 5 Hz. SCaT was rarely observed in Sham cells even at 5 Hz pacing, whereas it was observed in 20 % of TAC cells. Pre-incubation with DAN to intact TAC cells normalize inceidence of SCaT (11 %). After suramin incorporation, effect of DAN was abolished (19 %).

Conclusions:
In conclusion, CaM is essential for the channel stabilization effect of DAN. DAN corrects the aberrant domain-domain interaction, and as the result, CaM binding affinity to the RyR2 improves. These are the possible mechanism underlying anti-arrhythmogenic effect of DAN.
Abstract 15051: True Public Access Defibrillator Coverage is Overestimated
Authors: Sun Christopher L , Demirtas Derya , Brooks Steven C , Morrison Laurie J , Chan Timothy C
Published: July 2021

Background:
Out-of-hospital cardiac arrests (OHCAs) occur at all times of the day and night. Immediate access to an AED increases survival. However, most public-location AEDs are placed in buildings without 24 hour access.

Objective:
To measure fixed-location public AED coverage of OHCAs by time of day and day of week in a Canadian urban setting.

Methods:
We identified all atraumatic public OHCAs occurring in Toronto, Canada from Jan. 2006 – Aug. 2014. We obtained a list of registered AEDs from Toronto Emergency Medical Services as of March 2015 and determined the hours that each AED was available based on operating hours of the building housing the AED. We counted the number of OHCAs that occurred within 100 m of an AED (“assumed 24/7 coverage”) and the number that occurred both within 100 m of an AED and when the AED was available (“actual coverage”). Statistical analysis was performed using a χ
2
test.

Results:
We identified 2440 atraumatic public OHCAs and 737 registered AED locations. A total of 451 OHCAs were covered under assumed 24/7 coverage. In terms of actual coverage, 354 OHCAs were covered, representing a coverage loss of 25.5%. The figure shows coverage decreased by 8.6% during the day (8am-3:59pm), 28.6% in the evening (4pm-11:59pm), and 48.4% at night (12am-7:59am); the differences were statistically significant (p<0.001). During the evenings, nights, and weekends the coverage loss was 31.6%, which is when the majority (66.1%) of the OHCAs occurred. The largest coverage losses were found in schools (39.7%), industrial facilities (39.3%), recreation facilities (37.1%), and offices (35.7%). Transportation facilities, long term care homes and homeless shelters had no coverage loss.

Conclusion:
One out of every four OHCAs in proximity of an AED occurs when that AED is inaccessible due to lack of 24/7 access. When deciding on candidate locations for placement of AEDs, temporal access should be considered to maximize the number of lives saved.
Abstract 15115: Including Intra- and Post-operative Factors in Delirium Predictive Rule After Coronary Artery Bypass Graft Could Increase Its Accuracy
Authors: Ding Shu , Feng Xinwei , Tao Xiangjun , Lu Sai , Su Pixiong , Shen Yuzhi , Zhao Haibo , Wu Ying
Published: July 2021

Objectives:
Postoperative Delirium (POD) frequently occurs after coronary artery bypass graft (CABG). Patients screened with an appropriate POD predictive rule (PR) may benefit from targeted preventive treatment. The accuracy of current available PRs, however, remained modest with the C statistic below 0.75, partially because none of which include intra- and post-operative (IPOP) as well as preoperative (preop) risk factors at the same time. Since POD is a postoperative (postop) phenomenon, IPOP factors might play important roles. This study aimed to develop and validate a PR based on perioperative (periop) factors to predict POD after CABG.

Methods:
This prospective study included two cohorts (derivation [n = 132] and validation [n = 53]) of patients who underwent first isolated CABG. POD was assessed using the Confusion Assessment Method for Intensive Care Unit twice daily until 5 days after operation. Logistic regression and a bootstrap resampling procedure were used for model development and internal validation. Rule performance was measured with the C statistic. Points were assigned to each variable and a simplified rule was derivated to identify subjects at low, moderate, and high risk of POD based on their total risk score. The proportion of subjects with POD in each risk group was calculated.

Results:
The PR included 5 periop factors: age (≥68y), female, intraoperative intra-aortic balloon pump use, postop atrial fibrillation and serum IL-6 ≥ 478 pg/ml at 18th hour. The relative risk of POD in moderate (2~5 points) and high risk group (6~8 points) were 6.7 and 10.9 folds higher compared with low risk group (0~1 point), respectively (Fig A). The model C statistic was 0.861 (Fig B) in the derivation cohort, 0.829 in internal validation, and 0.754 in validation cohort.

Conclusion:
We developed a POD PR for patients undergoing CABG, which includes IPOP risk factors as well as preop risk factors. The new developed rule demonstrated more powerful in predicting POD after CABG.
Abstract 15137: Detection of Diffuse Myocardial Fibrosis using Multi-slice T1 Mapping by Slice Interleaved T1 (STONE) Sequence in Patients With Hypertrophic Cardiomyopathy
Authors: Kato Shingo , Roujol Sébastien , Jang Jihye , Basha Tamer , Berg Sophie , Kissinger Kraig V , Goddu Beth , Appelbaum Evan , Maron Martin , Manning Warren J , Nezafat Reza
Published: July 2021

Introduction:
In hypertrophic cardiomyopathy (HCM), there are significant variations in left ventricular (LV) wall thickness and fibrosis, which necessitates a volumetric coverage. Slice-interleaved T1 (STONE) mapping sequence allows for the assessment of native T1 time with complete coverage of LV myocardium.

Hypothesis:
We hypothesized that STONE sequence is useful for the assessment of regional native T1 time abnormality in HCM patients.

Methods:
Twenty-four septal HCM patients (56±16 years) and 10 healthy adult control subjects (57±15 years) were studied. Native T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 sec free-breathing scan. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices (basal-, mid- and apical-slice) and evaluated the relationship between LV native T1 time and wall thickness. Late gadolinium enhanced (LGE) MRI was acquired to assess presence of myocardial enhancement.

Results:
In HCM patients, LV native T1 time was significantly elevated compared to healthy controls, regardless of presence or absence of LGE (mean native T1 time; LGE (+) segments (n=27), 1139±55 msec; LGE (-) segments (n=351), 1118±55 msec; healthy control (n=160),1065±35 msec; p<0.001 by one-way ANOVA, 6 segments were excluded from analysis due to artifacts). Among 351 segments without LGE, native LV T1 time was diffusely elevated over the 16 segments (Figure). Significant positive correlation was found between LV wall thickness and native LV T1 time (y=1013+8.7x, p<0.001).

Conclusions:
In HCM, substantial number of segments without LGE showed elevated native T1 time, and native T1 time was correlated with LV wall thickness. Multi-slice T1 mapping by using STONE sequence could be advantageous to overcome limited cardiac coverage of conventional single-slice T1 mapping technique and to accurately detect the diffuse myocardial fibrosis in HCM patients.
Abstract 15149: Short-term Exposure to Fine Particulate Matter Air Pollution Preferentially Increases the Risk of ST-Elevation Acute Coronary Events
Authors: Meredith Kent G , Pope C A , Muhlestein Joseph B , Anderson Jeffrey L , Cannon John B , Hales Nicholas M , Le Viet T , Horne Benjamin D
Published: July 2021

Introduction:
Air pollution is associated with greater cardiovascular event risk, but which types of events and the specific at-risk individuals remain unknown.

Hypothesis:
Short-term exposure to fine particulate matter (PM
2.5
) is associated with greater risk of acute coronary syndromes (ACS), including ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (USA).

Methods:
ACS events treated at Intermountain Healthcare hospitals in Utah’s urban Wasatch Front region between September 10, 1993 and May 15, 2014 were included if the patient resided in that area (N=16,314). A time-stratified case-crossover design was performed matching the PM
2.5
exposure at the time of event with periods when the event did not occur (referent), for STEMI, NSTEMI, and USA. Patients served as their own controls. Odds ratios (OR) were determined for exposure threshold versus linear, non-threshold models.

Results:
In STEMI, NSTEMI, and USA patients, age averaged 62, 64, and 63 years; males constituted 73%, 66%, and 68%; current or past smoking was prevalent in 33%, 25%, and 26%; and significant coronary artery disease (CAD) (defined as ≥1 coronary with ≥70% stenosis) was found among 95%, 75%, and 74%, respectively. Short-term PM
2.5
exposure was associated with ACS events (Table).

Conclusions:
Short-term exposure of PM
2.5
was strongly associated with greater risk of STEMI, especially in patients with angiographic CAD. No association with NSTEMI was found, and only a weak effect for USA. This study supports a PM
2.5
exposure threshold of 25 μg/m
3
, below which little exposure effect is seen, while the effect is linear above that level.
Abstract 15161: Adiponectin Exerts a Protective Role Against Vascular Remodeling During Hypertension
Authors: Ghantous Crystal M , Hanache Sarah , Kobaissy Firas , Zeidan Asad
Published: July 2021

Introduction:
Hypertension is associated with leptin production and ROS formation in vascular smooth muscle cells (VSMC) and contributes to vascular remodeling. Adiponectin (ADQ) has a cardioprotective role on the heart, but the protective role of ADQ on VSMC during hypertension has not been fully elucidated yet.

Hypothesis:
Mechanical stretch/hypertension is associated with a low ADQ/leptin ratio in VSMC, leading to VSMC remodeling.

Methods:
To mimic hypertension, the rat portal vein was cultured either mechanically stretched with 1.2 gram weights (due to the force-length relationship normalized to the human force of stretch during hypertension and the longitudinal orientation of its VSMC) or left unstretched. ADQ, leptin, eNOS, p-ERK1/2 and p-AKT expression in VSMC was evaluated by Western blot. The protective effect of adiponectin (5-10 μg/ml; 15 min-24 hr) was investigated on ROS formation by DHE staining and on hypertrophy by protein synthesis via [
3
H]leucine incorporation.

Results:
Mechanical stretch for 24 hr reduced the expression of ADQ in VSMC (0.49 ± 0.08 fold, n=6, p<0.05) and increased leptin (2.51 ± 0.39 fold, n=6, p<0.05) compared to controls. Stretch (24 hr) decreased ADQ mRNA expression by 0.31 ± 0.11 fold (n=7, p<0.05) and ADQ receptor R2 by 0.51 ± 0.21 fold (n=7, p<0.05) but had no effect on ADQ receptor R1 (n=8). This effect of stretch was associated with increased protein synthesis by 1.39 ± 0.06 fold (n=6, p<0.05), while exogenous ADQ significantly inhibited stretch-induced hypertrophy (n=6, p<0.05). Stretch (15 min) increased p-ERK1/2 and p-AKT by 2.10 ± 0.25 and 4.03 ± 0.61 fold respectively (n=5, p<0.05), but ADQ reduced p-ERK1/2 and p-AKT by 0.82 ± 0.26 and 0.55 ± 0.25 fold respectively (n=3, p<0.05) in stretched vessels. eNOS expression decreased by 0.70 ± 0.06 fold (n=5, p<0.05) after stretch for 24 hr, while ADQ increased eNOS in stretched veins by 2.02 ± 0.41 fold (n=3, p<0.05). Stretch for 1 hr increased ROS by 5.69 ± 0.13 fold (n=3, p<0.05), whereas ADQ significantly inhibited ROS in stretched vessels (1.71 ± 0.22 fold, n=3).

Conclusion:
Mechanical stretch reduces the ADQ/leptin ratio in VSMC. ADQ plays a protective role against vascular remodeling during hypertension by affecting eNOS, ERK, AKT, ROS and hypertrophy.
Abstract 15174: Failing Aortic Tissue Valves in Patients at High Surgical Risk: Comparison of Outcomes After Transcatheter Aortic Valve-in-valve Procedures and Redo Surgical Aortic Valve Replacement
Authors: Silaschi Miriam , Wendler Olaf , Castro Liesa , Seiffert Moritz , Lubos Edith , Blankenberg Stefan , Reichenspurner Hermann , Schäfer Ulrich , Treede Hendrik , MacCarthy Philip , Conradi Lenard
Published: July 2021

Objectives:
Transcatheter aortic valve-in-valve implantation (ViV) is an innovative treatment for failed tissue valves (TV) in patients at high surgical risk. However, direct comparative data with standard repeat surgical aortic valve replacement (RE-SAVR) is scarce. We aimed to compare outcomes after ViV to conventional RE-SAVR in two European centers with established interventional programs.

Methods:
Retrospectively we explored in-hospital databases for patients ≥60 years, treated for degenerated TV. Patients with endocarditis and combined procedures were excluded. Primary endpoints were adjudicated according to VARC-2 criteria.

Results:
Between 2002 and 2015, 130 patients were treated for isolated failure of aortic TV’s (ViV: n=71, RE-SAVR: n=59). In ViV, Edwards Sapien valve (ESV) was most frequently used (n=36) but implanted into larger TV’s (CoreValve TV size: 22.2±1.3mm vs. ESV TV size: 24.1±2.0mm, p<0.01). Both age and logistic EuroSCORE I were higher in ViV compared to RE-SAVR (78.6±7.5 vs. 72.9±6.5 ys, p<0.01; 25.1±18.9 vs. 16.8±9.4%, p<0.01). Thirty-day mortality was not significantly different with 4.2% (3/71) after ViV vs. 5.1% (3/59) post RE-SAVR (p=1.0). Device success was achieved in 54.9% (n=39) in ViV and all RE-SAVR patients (p<0.01). Perioperative stroke was not observed after ViV and in 2 patients after RE-SAVR (3.4%, p=0.2). Intensive-care stay was longer after RE-SAVR (3.4±2.9d vs. 1.9±1.8d, p<0.01). Following ViV, 22.5% (n=16) of patients had mild aortic regurgitation, vs. 11.3% (n=8; p=0.25) after RE-SAVR. Mean transvalvular pressure gradients at discharge were higher post ViV (19.3±7.3 vs.12.2±5.6mmHg, p<0.01). Rate of permanent pacemaker implantation was lower after ViV (9.9% vs. 27.1%, p<0.01). Survival at 90- and 180-days was 93.8% and 91.8% vs. 94.4% and 94.4% after ViV and RE-SAVR respectively (p=0.87).

Conclusion:
Despite a higher risk profile, early mortality was not different between the two treatment arms. Although ViV resulted in elevated postoperative transvalvular pressure gradients and therefore a lower rate of device success, mortality after 180-days was similar to RE-SAVR. At present, both techniques serve as complementary approaches and allow individualized patient care.
Abstract 15178: The Clinical Characteristics of Patients With Ischemia-oriented or Coronary Computed Tomography Angiography-oriented Percutaneous Coronary Intervention, a Report From the Multicenter Registry
Authors: Fujita Jun , Kohsaka Shun , Ueda Ikuko , Inohara Taku , Maekawa Yuichiro , Kawamura Akio , Kanazawa Hideaki , Hayashida Kentaro , Tabei Ryota , Tohyama Shugo , Seki Tomohisa , Suzuki Masahiro , Sano Motoaki , Fukuda Keiichi
Published: July 2021

Background:
Myocardial perfusion scintigraphy (MPS) plays a pivotal role in the evaluation of ischemia. Coronary computed tomography angiography (CTA) is emerging to evaluate anatomical features for stable ischemic heart disease (SIHD). This study aimed to identify the clinical characteristics of ischemia (MPS) or anatomy (CTA)-oriented percutaneous coronary intervention (PCI) patients for SIHD.

Methods and Results:
Data were analyzed from 4197 SIHD patients undergoing PCI in The Japan Cardiovascular Database (N = 11,258) between September 2008 and April 2013. MPS was used to evaluate 1070 (25.5%) patients. Significant ischemia (SI) was defined as more than 10% ischemic region. CTA was performed in 1433 patients, and patients with ischemia evaluation and unavailable results were excluded. A total of 694 patients (16.5%) were evaluated as CTA group. CTA-oriented PCI patients had milder illness in their background (Table). More than half of patients had multivessel disease (CTA vs non-SI vs SI; 51.6, 66.3, 71.9%). Incomplete revascularization ratio was significantly lower in CTA group (0.6, 2.2, 3.1%, p = 0.003). However, CTA-oriented PCI patients and SI patients had significantly more complications than non-SI patients (6.6, 3.8, 8.2%, p = 0.022), especially post-procedural infarction (2.4, 0.5, 3.0%, p = 0.032) (Figure).

Conclusions:
Even though CTA-oriented PCI patients had incomplete revascularization less frequently, they experienced more complications. These results indicate that functional assessment is important to predict in-hospital complications, and physicians need to give their attention to CTA-oriented PCI patients as well as SI patients.
Abstract 15187: Shear Stress-regulated Mir-27b Controls Pericyte Recruitment
in vitro
and
in vivo
and Contributes to Vessel Maturation
Authors: Demolli Shemsi , Doddaballapur Anuradha , Stark Konstantin , Boon Reinier A , Eckart Ankathrin , Korff Thomas , Hecker Markus , Manavski Yosif , Lucas Tina , Massberg Steffen , Devraj Kavi , Liebner Stefan , Kaluza David , Dimmeler Stefanie
Published: July 2021

Vessel maturation involves recruitment of mural cells. Laminar shear stress is a major trigger for vessel maturation. However, the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs are small non-coding RNAs, which post-transcriptionally control gene expression. Since shear stress regulates various miRs, we hypothesize that flow-induced miRs inhibit repulsive cues and facilitate mural cell coverage.

Laminar shear stress for 72h induces the up-regulation of miR-27b (2.8±0.24-fold vs static, p<0.05) in cultured endothelial cells (ECs) and in mouse femoral artery segments that were exposed to physiological shear stress ex vivo (1.5±0.14-fold vs no flow, p<0.05). Predicted targets for miR-27b include members of the semaphorin (SEMA) family (known to regulate repulsive signaling) and angiopoietin-2 (Ang2), which causes vessel destabilization. MiR-27b overexpression reduces SEMA6A (63.5±13.5%), SEMA6D (58±26%), and Ang2 (51.5±11%) expression.

To determine whether miR-27b controls pericyte recruitment, we tested the effect of endothelial miR-27b on adhesion of pericytes. Overexpression of miR-27b increased the adhesion of pericytes (p<0.05) and inhibition of miR-27b reduced pericyte adhesion in vitro (p<0.05). In an in vitro matrigel assay, overexpression of miR-27b increased pericyte coverage of endothelial cell tubes (155±45%, p<0.05), whereas inhibition of miR-27b reduced pericyte coverage (81±15%). In addition, overexpression of miR-27b in vitro increases barrier function (p<0.05) in endothelial cell-pericyte co-culture assays whereas inhibition of miR-27b decreases barrier function (p<0.05). Silencing of SEMA6A and SEMA6D rescued the reduced pericyte adhesion that is caused by miR-27 inhibition (p<0.05). Furthermore, inhibition of SEMA6D increases barrier function. In vivo inhibition of miR-27a/b significantly increased edema (p<0.05) in the uterus which was associated with a significantly reduced pericyte coverage of the vessels (p<0.05).

Taken together, our data demonstrate that shear stress regulate miR-27b, which targets Ang2 and semaphorins, thereby controlling pericyte adhesion and coverage in vitro and in vivo.
Abstract 15191: Left Atrial Volume as an Independent Predictor of Congestive Heart Failure in Patients With Atrial Fibrillation
Authors: Suwa Yoshinobu , Miyasaka Yoko , Tsujimoto Satoshi , Maeba Hirofumi , Shiojima Ichiro
Published: July 2021

Backgound:
Left atrial (LA) enlargement has been proposed as a barometer of diastolic dysfunction and a predictor of congestive heart failure (CHF) in patients with sinus rhythm. Whether LA volume predicts CHF in patients with atrial fibrillation (AF) is not well known.

Methods:
To determine the clinical importance of LA volume in the prediction of CHF in patients with AF, AF patients referred for clinically-indicated echocardiogram, without a history of significant mitral valve disease, congenital heart disease, pacemaker, or cardiac surgery, in 2007-2008 were prospectively included and followed forward them up to September 2014. LA volume was measured using the biplane area-length formula. CHF was ascertained using the Framingham criteria. Cox proportional hazards modeling was used to assess the risk factors of CHF development.

Results:
Of 456 AF patients who met all study criteria (mean 70 ± 10 year-old, 67% men, 62% hypertension, 26% diabetes, LV ejection fraction 68 ± 13%, LA volume 52 ± 24 mL/m
2
), 46 (10%) developed CHF events during a mean follow-up of 44 ± 31 months. CHF events were significantly increased with advancing age (HR 1.4, 95%CI 1.0-2.0, P<0.05), but not with sex. In a multivariate Cox proportional hazards model, greater indexed LA volume (per 10 mL/m
2
; HR 1.2, 95% CI 1.1-1.3, P<0.01) was independent of age (HR 1.04, 95% CI 1.01-1.07, P=0.03), sex (P=0.77), history of CHF (P=0.58), hypertension (P=0.38), diabetes (P=0.89), and LV ejection fraction (HR 0.95, 95% CI 0.93-0.96, P<0.001) for the prediction of CHF development. The Kaplan-Meier estimate of cumulative CHF-free survival by indexed LA volume was shown (Fig.).

Conclusions:
In our cohort with AF, LA volume predicted CHF developments, independent of LV systolic function and other cardiovascular comorbidities, which appears to be clinically useful information for risk stratification.
Abstract 15221: Pulmonary Artery Banding Induces NF-κB activated Inflammation and Deteriorates RV Function
Authors: Yoshida Keimei , Abe Kohtaro , Tanaka Mariko , Shinoda Masako , Kuwabara Yukimitsu , Saku Keita , Hirooka Yoshitaka , Oka Masahiko , Sunagawa Kenji
Published: July 2021

Background:
Right ventricular (RV) dysfunction contributes to poor prognosis in patients with pulmonary hypertension. Although pulmonary artery banding (PAB) induces RV inflammation, its mechanisms are poorly understood.

Hypothesis:
We assessed the hypothesis that RV pressure overload induced by PAB leads to RV dysfunction through NF-κB-mediated inflammation and fibrosis.

Methods and Results:
We banded the main PA using an 18-gauge needle in adult Sprague-Dawley rats (BW: 180-220g). We measured hemodynamics and analyzed immunohistochemistry of RV at Day 1, 3, 7 and 14 after PAB (n=4-6, each group). PAB time-dependently increased RV systolic pressure (sham: 31.1±5.7 vs. Day14: 73.2±11.8mmHg, p<0.01), RV end-diastolic pressure (RVEDP) (sham: 1.5±0.9 vs. Day14: 5.8±2.1mmHg, p<0.05) and RV hypertrophy (ratio of RV/LV+septum weight) (sham: 0.29±0.04 vs. Day14: 0.68±0.08, p<0.01) with high expression of activated p65 (NF-κB). PAB increased inflammatory cells, mainly CD68 positive macrophages (sham: 5.6±1.6 vs. Day1: 46.4±9.7 cell/mm2, p<0.01), and fibrosis areas (Masson trichrome staining) time-dependently (sham: 0.7±0.2 vs. Day14: 7.6±0.8%, p<0.01). Chronic administration of NF-κB inhibitor, pyrrolydine-dithiocarbamate (PDTC, 200mg/kg/day, orally, from Day 0 to 28), in PAB rats (n=4-7, each group) markedly decreased RVEDP (vehicle: 9.0±0.7 vs. PDTC: 3.4±1.3mmHg, p<0.01), attenuated the expression of activated p65 and infiltration of CD68 positive macrophages (vehicle: 24.1±10.4 vs. PDTC: 5.6±2.0 cell/mm2, p<0.01), and reduced fibrosis (vehicle: 8.7±1.1 vs. PDCT: 2.4±0.8%, p<0.01) (Figure).

Conclusions:
These findings indicate that PAB immediately activates NF-κB and increases macrophage infiltration. Second, chronic treatment with PDTC attenuates NF-κB activation and macrophage infiltration in RV, leading to reduced fibrosis as well as RVEDP. NF-κB inhibition may be a therapeutic target for the RV dysfunction.
Abstract 15241: Proteinase-activated Receptor 1 Antagonist Inhibited the Progression of Monocrotaline Induced Pulmonary Hypertension in Rats
Authors: Kuwabara Yukimitsu , Abe Kohtaro , Hirano Mayumi , Hirooka Yoshitaka , Sunagawa Kenji , Hirano Katsuya
Published: July 2021

Introduction:
Pulmonary hypertension (PH) is characterized by thrombus formation, vasoconstriction and vascular remodeling. The normal pulmonary artery, in contrast to the systemic artery, has a unique property to contract in response to thrombin via thrombin receptor Proteinase-activated receptor 1 (PAR1).

Hypothesis:
We hypothesized that PAR1 plays a key role in the pathogenesis and pathophysiology in PH and examined the therapeutic effects of PAR1 antagonist on PH.

Methods and Results:
Adult male SD rats developed PH after a single subcutaneous injection of 60 mg/kg monocrotaline (MCT) on day 0. The indexes of pulmonary vascular resistance (PVR: RV systolic pressure/cardiac output) and RV hypertrophy (RVH: RV/LV+septum) increased from 0.33±0.03 (normal, n=5) to 1.3±0.1 mmHg•min/mL (MCT, n=10, p<0.01) and from 0.28±0.01 (n=6) to 0.49±0.02 (n=15, p<0.01), respectively, on day 21. We administered PAR1 antagonist (atopaxar: 30mg/kg/day, p.o.) on day 0 (preventive protocol) or day 14 (treatment protocol) of MCT injection. In comparison with MCT rats, the preventive and treatment protocols significantly reduced PVR (0.68±0.09 and 0.89±0.11 mmHg•min/mL, n=8 and 10, p<0.01 and p<0.05) and RVH (0.37±0.02 and 0.40±0.03, n=10 and 12, p<0.01 and p<0.05). Atopaxar had no effect on systemic blood pressure. In the isolated perfused lung preparations, a bolus infusion of 300 nmol PAR1-activating peptide elevated pulmonary arterial pressure by 0.33±0.08 mmHg in the normal (n=6) and 11.8±2.4 mmHg in MCT (n=9; p<0.01 vs. normal), while attenuated in the preventive protocol (1.99±0.96 mmHg, n=6). Atopaxar significantly prolonged the survival periods of MCT rat (median survival time: 26 days, n=17) in both preventive (median survival time: more than 56 days, n=14, p<0.01) and treatment (median survival time: 30 days, n=17, p<0.05) protocols.

Conclusion:
The PAR1 activity increased in MCT rats. Inhibiting the increased activity of PAR1 was effective in preventing the progression of PH without decreasing systemic blood pressure. PAR1 is thus a potentially novel therapeutic target for the treatment of PH.
Abstract 15285: Prognostic Value of 6-year Change in High Sensitivity Cardiac Troponin-T for Risk of Heart Failure, Heart Failure Subtype, and Death
Authors: Mcevoy Bill , Ndumele Chiadi E , Chen Yuan , Solomon Scott D , Steffes Michael , Nambi Vijay , Ballantyne Christie , Blumenthal Roger , Coresh Josef , Selvin Elizabeth
Published: July 2021

Background:
Serial changes in high-sensitivity cardiac troponin-T (hs-cTNT) indicate progressive subclinical myocardial damage and have been associated with heart failure (HF) and death in asymptomatic older adults. Whether these associations exist in middle-age and whether serial hs-cTNT is more strongly associated with HF with reduced ejection fraction (HFREF) or HF with preserved ejection fraction (HFPEF) is poorly understood.

Methods:
We studied 8,838 participants of the Atherosclerosis Risk in Communities Study, initially free of coronary heart disease and HF, who had hs-cTNT measured at two time-points, 6 years apart. Using proportional hazards regression, we examined the association of absolute and relative change in hs-cTNT with incident HF hospitalization or death. Sensitivity analyses for HFPEF and HFREF were also conducted.

Results:
Mean age at baseline was 57 years, 57% were female and 21% were black. Over a maximum of 16 years follow-up there were 965 HF events and 1813 deaths. In adjusted models, incident detectable hs-cTNT (≥5ng/L) was associated with subsequent HF (Hazard Ratio [HR] 1.86, 95% Confidence Interval [CI] 1.53-2.25) and death (1.46 [1.28-1.68]). HRs were larger for incident hs-cTNT elevation (≥14ng/L) but similar for those with a relative increase >50% from baseline hs-cTNT (Table). In contrast, risk was lower for relative reductions >50% from baseline hs-cTNT. Temporal increases in hs-cTNT were associated with both HFREF and HFPEF in categorical analyses, however, when modeled continuously (per SD increase), absolute 6-year hs-cTNT change appeared to be more strongly associated with HFPEF hospitalization (HR 1.30 [1.06-1.60]) than with HFREF hospitalization (1.08 [0.88-1.33]).

Conclusions:
Absolute and relative change in hs-cTNT were independently associated with incident CHD, HF and death, even after adjustment for baseline hs-cTNT. Associations were generally consistent for both the HFREF and HFPEF phenotypes
Abstract 15302: Deficiency of Myeloid Membrane-bound Thrombomodulin Attenuates Vascular Inflammation in Abdominal Aortic Aneurysm
Authors: Wu Hua-Lin , Wang Kuan-Chieh , Shi Guey-Yueh
Published: July 2021

Introduction:
Thrombomodulin (TM), a glycoprotein predominantly expressed in endothelial cells, has been well known for its anti-coagulant and anti-inflammatory properties. Paradoxically, we recently found a promoting role of monocytic membrane-bound TM in experimental sepsis.

Hypothesis:
We assessed the hypothesis that membrane-bound TM may participate in vascular inflammation and the development of abdominal aortic aneurysm (AAA).

Methods and Results:
Characterization of the CaCl
2
-induced AAA in mice revealed that TM expression was mainly localized in vascular smooth muscle cells (VSMCs) and infiltrating macrophages. To investigate the function of membrane-bound TM in vivo, transgenic mice with myeloid- (LysMcre/TM
flox/flox
) and VSMC-specific (SM22-cre
tg
/TM
flox/flox
) TM ablation and their wild type counterparts were generated. In the CaCl
2
-induced AAA model, myeloid TM-deficient mice (n=12) but not VSMC TM-deficient mice (n=8), when compared with their wild-type respective controls (TM
flox/flox
, SM22-cre
tg
/TM
+/+
), showed attenuated accumulation of macrophages, reduced production of proinflammatory cytokines and suppressed levels of matrix metalloproteinase-9, thereby preventing progressive aortic dilatation.
In vitro
TM-deficient macrophages had reduced proinflammatory mediator production, macrophage-endothelial cell adhesion and intracellular oxidative stress (e.g., reactive oxygen species [ROS]) versus TM wild-type macrophages. In addition, deficiency of TM in hyperlipidemic mice (ApoE
-/-
/LysMcre/TM
flox/flox
, n=9) conferred protection against angiotensin II-infused AAA, compatible with dramatically diminished aortic ROS production and matrix metalloproteinase activities. Finally, human AAA samples (n=6) showed that TM signals were predominantly localized to infiltrating macrophages, implicating the potential involvement of monocytic membrane-bound TM in human diseases.

Conclusion:
Membrane-bound TM in macrophages plays a critical role in the development of AAA by enhancing macrophage-endothelial cell adhesion, proinflammatory mediator elaboration and intracellular ROS production.
Abstract 15309: Resource Reduction by Use of Pediatric Chest Pain Standardized Clinical Assessment and Management Plan
Authors: Saleeb Susan F , McLaughlin Sarah R , Graham Dionne A , Friedman Kevin G , Fulton David R
Published: July 2021

Using a Standardized Clinical Assessment and Management Plan (SCAMP) for pediatric patients presenting to clinic with chest pain, we evaluated the cost impact associated with implementation of the care algorithm. Previously, we analyzed charges for 406 patients (7-21 yrs) with chest pain seen in 2009, prior to introduction of the SCAMP, and predicted 21% reduction of overall charges had the SCAMP methodology been used. The SCAMP recommended an echocardiogram for history, exam, or ECG findings suggestive of a cardiac etiology for chest pain. Resource utilization for 1520 patients evaluated by the SCAMP from 12/11-4/14 was reviewed in this study. Compared to the 2009 cohort, patients evaluated in the SCAMP presented with similar rates of exertional chest pain (33%, SCAMP vs. 37%, 2009) and significant past medical history (1% vs. 1%). The SCAMP cohort had fewer abnormal physical exam findings (1% vs. 4%) and ECG abnormalities (3% vs. 6%), and more pertinent family history (4% vs. 1%). Echocardiograms were additionally recommended by the SCAMP for exertional syncope (1%), pain worse by supine position, or radiation to the back, jaw, or left arm (5%). Ancillary testing for concurrent symptoms was reduced compared to the 2009 cohort (Figure 1) and compared to predicted: Holter (4% vs. 6%), event monitors (3% vs. 8%), MRI (<1% vs. 1%). Stress testing was not recommended though 4% underwent evaluation. Adherence to SCAMP guidelines for recommended testing approached 80%; slightly fewer echocardiograms were actually performed than recommended. Total testing charges were reduced by an estimated 30% ($740,000) despite a small increase in echocardiogram utilization, and overall charges were reduced by 17% by use of the Chest Pain SCAMP. Given the low incidence of cardiac disease historically as well as detected by the SCAMP algorithm (<1%), further modifications to the algorithm should refine indications for echocardiography, particularly related to exertional symptoms.
Abstract 15323: How Often Should Chest Compressions be Paused to Assess the Cardiac Rhythm? A Systematic Review and Meta-analysis
Authors: Reynolds Joshua C , Raffay Violetta , Lang Eddy , Morley Peter T , Nation Kevin
Published: July 2021

Objectives:
Most guidelines recommend pausing chest compressions at 2-min intervals to analyze the cardiac rhythm. We assessed the literature on the optimal interval at which to pause chest compressions in adults for cardiac rhythm analysis in any setting.

Methods:
To conduct this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane databases through January 2, 2015, including human studies addressing any two different intervals of rhythm analysis. We excluded animal studies, manikin studies, case reports, editorials, and studies published only in abstract form. We assessed for bias per the Cochrane Handbook criteria for randomized controlled trials (RCT) and observational studies, then used GRADE methodology to evaluate the quality of evidence for functional outcome, survival, and return of spontaneous circulation. Two reviewers independently screened titles/abstracts, and resolved disagreement by consensus. We summarized study results using RR for RCTs and OR for observational studies. Meta-analyses were performed with Mantel-Haenszel random effects model.

Results:
Of 1,135 papers identified, 8 were included (3 RCT and 5 observational studies) encompassing 15,242 subjects. Quality of evidence was very low or low (downgraded for risk of bias and indirectness). RCT comparing specific time intervals (3-minutes vs. immediate analysis; 1-minute vs. 2-minutes; 3-minutes vs. 1-minute) demonstrated no benefit in either arm. Meta-analyses of 5 observational studies demonstrated moderate pooled benefit of a bundled ‘minimally interrupted chest compression’ protocol dictating 200-compression intervals over historical controls treated with 1- or 3-minute intervals per the 2000 guidelines (ROSC: OR 1.9, 95% CI 1.3, 2.7; survival to discharge: OR 2.9, 95% CI 2.1, 3.8; good functional outcome: OR 2.9, 95% CI 1.6, 5.4). No pooled estimate had significant heterogeneity.

Conclusion:
We found no quality evidence to support pausing chest compressions at any singular interval to assess the cardiac rhythm in adults in cardiac arrest in any setting. Very low quality evidence suggests improved outcomes in patients receiving a bundled 200-compression interval protocol compared to 1- or 3-minute intervals.
Abstract 15331: Ventricular Conduction and Repolarization Prolongation Noted During Right Ventricular Pacing as Predictors of Ventricular Arrhythmias and Cardiac Mortality in Subjects With Cardiomyopathy
Authors: Del Carpio Freddy , Gharacholou Shahyar M , Scott Christopher S , Nkomo Vuyisille , Lopez-Jimenez Francisco , Asirvatham Samuel J
Published: July 2021

Introduction:
Clinical predictive value of transient prolonged ventricular conduction and repolarization during right ventricular (RV) pacing have not been studied.

Hypothesis:
Ventricular conduction and repolarization prolongation during RV pacing predict risk of arrhythmic and mortality events.

Methods:
Electrophysiology studies in 501 patients with cardiomyopathy (CM) were reviewed. Duration changes of QRS and QT interval during pacing from the RV apex were measured. Subjects were followed up for a mean of 3.2 years for arrhythmic events and total mortality.

Results:
Participants had a mean age 65 yrs, 80% male, 74% funcional class II or III, and a mean EF of 33.1%. A paced QRS duration > 190 ms was associated with more severe CM and in multi-variable analysis it was associated with a 3.5 times higher risk of ventricular arrhythmias or appropriate defibrillator therapy (HR 3.5, 95% CI 2.3-5.4, p<0.01) and 2.6 times higher risk of total mortality or arrhythmic events (HR 2.6, 95% CI 2.3-3.4, p<0.01) compared to a paced QRS duration <190 ms, independent of baseline EF or baseline QRS duration, and after adjustment for electrophysiology study results, baseline functional class, type of cardiomyopathy and other relevant clinical factors. Similarly a QTc interval during RV pacing > 620 ms was associated with a 2.7 times higher risk of arrhythmic events compared to a QTc interval during RV pacing < 620 ms.

Conclusions:
Prolongation of ventricular conduction (QRS > 190 ms) and repolarization (QTc > 620 ms) observed during RV pacing in subjects with CM are associated with higher risk of arrhythmic events, defibrillator therapies and all-cause mortality.
Abstract 15339: Molecular Analysis of Epigenetic Modification Process in Distressed Cardiomyocytes May Explor Indication of Mitral Valve Surgery for Advanced Heart Failure Associated With Non-ischemic Dilated Cardiomyopath
Authors: Kashiyama Noriyuki , Miyagawa Shigeru , Toda Koichi , Nakamura Teruya , Yoshikawa Yasushi , Fukushima Satsuki , Saito Shunsuke , Yoshioka Daisuke , Ito Emiko , Harada Akima , Takeda Maki , Ueno Takayoshi , Kuratani Toru , Sawa Yoshiki
Published: July 2021

Introduction:
Mitral valve (MV) surgery for functional mitral regurgitation (MR) associated with advanced heart failure (HF) is a surgical challenge with surgical indication not clearly established. It was recently reported that the epigenetic modification, such as methylation or acetylation of histone H3, is closely related to functional reversibility of cardiomyocytes in advanced HF.

Hypothesis:
We herein hypothesized that epigenetic profiles in the left ventricle (LV) may be associated with clinical outcome of MV surgery for non-ischemic dilated cardiomyopathy (NIDCM)-causing advanced HF.

Methods:
Thirteen patients diagnosed as having NIDCM underwent chordal sparing MV replacement for severe MR associated with low ejection fraction (EF) (<35%) between 2012 and 2015. Intraoperatively biopsied LV tissue was immunohistologically labeled by histone H3 lysine 9 tri-methylation (H3K9me3) and acetylation (H3K9ac), and then the scores ranging from 0 to 12 were assigned as intensity and percentage of positive staining cardiac cell nuclei.

Results:
Four patients (31%) necessitated left ventricular assist device (LVAD) implantation for persistent low output syndrome post-MV replacement, and one patient died of cardiac failure on day 260. Preoperative factors assessed by routine echocardiogram or right heart catheter study, such as LVEF (26±3 vs 24±6%, p=0.49), LV end-systolic dimension index (159±49 vs 188±58 ml/m2, p=0.42), or mean pulmonary arterial pressure (27±11 vs 22±9mmHg, p=0.42), were not a predictive factor of LVAD implantation post-MV surgery. In contrast, preoperative LV stroke work index (LVSWI) was significantly lower in the patients who had LVAD implantation (13±2 vs 22±7 g·m/m2/beat, p=0.02). In addition, the scores of H3K9me3 and H3K9ac were significantly lower in the patients with LVAD implantation (3.0±0.7 vs 6.5±1.9, p<0.01 and 4.1±0.7 vs 8.9±1.9, p<0.01, respectively) and closely correlated with preoperative LVSWI.

Conclusions:
Reduced H3K9 methylation and acetylation in cardiomyocytes was closely related to preoperative poor LV performance and represented poor clinical outcome after MV replacement in advanced NIDCM, suggesting that these parameters may be useful factors in determining the surgical indication.