bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12532: Left Ventricular Diastolic Dysfunction and Exercise Intolerance in Type 2 Diabetes Patients With Endothelial Dysfunction
Authors: Sugimoto Tadafuni , Dohi Kaoru , Onishi Katsuya , Horiguchi Masahide , Takamura Takeshi , Seko Tetsuya , Kasai Atsunobu , Ito Masaaki
Published: July 2021

Introduction:
Endothelial dysfunction plays a central role in the pathogenesis of diabetic vascular disease.

Hypothesis:
Although resultant left ventricular diastolic dysfunction is hypothesized to reduce exercise capacity, limited data exist on the relation between endothelial function, left ventricular diastolic function and exercise capacity in patients with type 2 diabetes.

Methods:
We recruited 231 subjects with type 2 diabetes, a preserved ejection fraction, a negative stress test and a sodium-restricted diet. All subjects underwent a brachial artery flow-mediated dilation (FMD) measurement, a transthoracic echocardiography and a standard submaximal Bruce protocol treadmill exercise test during the hospitalization period for diabetes education program.

Results:
Impaired FMD (%FMD 8) were found in 193 subjects (84%) and 174 subjects (75%), respectively, of which 11 (5%) had diastolic dysfunction (E/E’ >15). Mean E/E’ by quartile (Q) were: Q1 6.9, Q2 8.9, Q3 10.4, and Q4 14.0. E/E’ was inversely correlated with %FMD (2.9 ± 4.3%, r = -0.19, p = 0.003) and exercise duration (460 ± 150 sec, r = -0.30, p <0.001). Compared with subjects in Q4, those in Q1, Q2 and Q3 had longer exercise duration (Q1 500 ± 150 sec, Q2 510 ± 140 sec, Q3 460 ± 140 sec and Q4 390 ± 140 sec, p <0.001). After adjustment for potential confounders including age, gender, smoking, body mass index, medication for hypertension, diabetes duration of more than 5 years, HbA1c and systolic blood pressure, %FMD and exercise duration were significantly associated with E/E’ (β = -0.17 and -0.18, p = 0.006 and 0.014) in all subjects.

Conclusions:
Diabetes patients with impaired endothelial function have impaired left ventricular diastolic function potentially leading to exercise intolerance.
Abstract 12536: Lower Thromboembolic and Bleeding Events With Uninterrupted Warfarin Compared to Interrupted Warfarin and Heparin Bridging in Atrial Fibrillation Ablation. Evidence From a Meta-Analysis
Authors: Nairooz Ramez , Sardar Partha , Chatterjee Saurav , Aronow Wilbert S , Gould Kenneth L
Published: July 2021

Introduction:
Optimal anticoagulation strategy in patients undergoing atrial fibrillation ablation (AFA) is controversial. Trials comparing uninterrupted warfarin (UW) with interrupted warfarin and heparin bridging (IW) peri-procedural in AFA are inconsistent in showing decreased thromboembolic and bleeding events with UW. We sought to perform a meta-analysis comparing both strategies in AFA.

Methods:
We searched online databases till May 2014 for case-control studies that compared patients undergoing AFA with UW versus IW. Studies without a control arm, and those that included patients not on anticoagulation peri-procedural were excluded. We used odds ratio and random effects model. When event rates were less than 1% we used Peto Odds ratio. We explored the hypothesis that UW decreased thromboembolic events with equal bleeding rates compared to IW therapy in patients undergoing AFA.

Results:
Our search yielded 13 observational and 1 randomized trial. A total of 17628 patients were included, of those 7964 on UW vs 9664 on IW. Patients on UW had lower combined Stroke and TIA compared with IW (Odds ratio (OR) 0.29, 95% confidence interval (CI) [0.12, 0.72]; p=0.007). Consistently Stroke were lower with UW (Peto OR 0.21, 95% CI [0.13, 0.33]; p<0.0001) and TIA (Peto OR 0.25, 95% CI [0.13, 0.51]; p=0.0001). Major bleeding events were also lower with UW (OR 0.73, 95% CI [0.57, 0.94]; p=0.02) as well as minor bleeding (OR 0.36, 95% CI [0.23, 0.56]; p<0.0001) compared to IW. Cardiac tamponade were equal with both strategies (POR 0.84, 95% CI [0.61, 1.16]; p=0.3).

Conclusion:
In AFA, UW decreases the incidence of stroke and TIA with lower major and minor bleeding events compared to IW. These results recommend use of UW rather than IW strategy in AFA.
Abstract 12544: Dimethyloxalylglycine Treatment of Brain-Dead Donor Rats Improves Both Donor and Graft Left-Ventricular Function After Heart Transplantation
Authors: Hegedüs Peter , Li Shiliang , Korkmaz Sevil , Radovits Tamás , Alsaid Samer , Karck Matthias , Merkely Béla , Szabó Gábor
Published: July 2021

Introduction:
Cardiac transplantation is the most effective treatment of end-stage heart failure. Brain dead (BD) donors are currently the only reliable source for cardiac grafts. However, hemodynamic instability and cardiac dysfunction have been demonstrated in BD donors and this could therefore also affect posttransplant graft function.

Hypothesis:
Based upon the protective effect of Prolyl-Hydroxylase (PHD)-Hypoxia Inducible Factor (HIF)-1 pathway against ischemia/reperfusion injury (IRI), we tested the hypothesis that treatment of BD donor rats with the PHD inhibitor dimethyloxalylglycine (DMOG) results in a better graft heart condition in recipients after heterotopic transplantation.

Methods:
Lewis rats were injected with one shot DMOG (30 mg/kg i.v.) (n=7) or equal volume of physiological saline (n=7) and maintained BD for 5h by a subdurally placed and inflated balloon catheter. Controls were sham-operated (n=11). Then, hearts were explanted, stored in cold preservation solution, heterotopically transplanted and after 1.5h reperfusion left-ventricular (LV) graft function was evaluated
in vivo
. Myocardial histological and molecular biological analyses were performed.

Results:
BD was associated with decreased LV function. DMOG treatment of BD animals resulted in better load-independent contractility and end-diastolic stiffness parameters (ESPVR E'
max
(mmHg/μl): BD+DMOG: 3.7±0.6 vs BD: 3.1±0.5; EDPVR (mmHg/μl): BD+DMOG: 0.13±0.03 vs BD: 0.31±0.06 p<0.05). Following transplantation, DMOG treatment of BD donors significantly improved altered LV systolic and diastolic function (at 80μL volume dP/dt
max
(mmHg/s): BD+DMOG: 2284±213 vs BD: 1854±124 p<0.05; dP/dt
min
(mmHg/s): BD+DMOG: 1586±183 vs BD: 1154±74, p<0.05; Tau-W (ms): BD+DMOG: 33±4 vs BD: 43±9 p<0.05). Significantly lower myocardial inflammatory cell infiltration, necrosis, and DNA-strand breakage were evident in DMOG treated BD group compared to BD group.

Conclusions:
Pre-treatment of BD heart donors with DMOG resulted in a significantly better LV graft function after transplantation. These results support the view that preconditioning of BD donors through the activation of HIF-1 pathway has a protective role against myocardial IRI after transplantation.
Abstract 12549: Circulating Irisin is a Novel Biomarker Providing Prognostic Information in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Hanatani Shinsuke , Izumiya Yasuhiro , Kimura Yuichi , Onoue Yoshiro , Araki Satoshi , Ogawa Hisao
Published: July 2021

Introduction:
Reduced skeletal muscle function link to poor prognosis in patients with chronic heart failure (HF). Irisin is a newly identified muscle-derived protein found in human serum. The gene expression of irisin precursor fibronectin domain containing protein 5 in skeletal muscle is associated with exercise tolerance in HF patients.

Hypothesis:
Irisin could be a useful biomarker for disease severity and future adverse cardiovascular events in patients with HF with reduced ejection fraction (HFrEF).

Methods and results:
We measured serum irisin levels in 84 patients with HFrEF. HFrEF was defined as left ventricular ejection fraction≦50% and meet the Framingham criteria of HF. Serum irisin concentrations were measured by ELISA. The endpoint of this study was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. Serum irisin levels were negatively correlated with serum high sensitive troponin T levels (r=-0.24, p=0.048). Right heart catheterization revealed that serum irisin levels had significant negative correlation with pulmonary capillary wedge pressure (r=-0.23, p=0.044). In receiver operating characteristic (ROC) analysis, cut-off values of irisin and BNP for prediction of one-year events were 55.548 ng/mL and 324.8 pg/mL, respectively. Kaplan Meier curve demonstrated that the event-free rate was decreased in the low irisin (≦cut-off value) group (log-rank test p=0.024). The combination of low irisin and high BNP (≧cut-off value) identified patients with a significantly higher probability of adverse events (p=0.008). Multivariate Cox hazard analysis identified low levels of irisin (≦cut-off value) (hazard ratio [HR]: 3.08; 95% confidence interval [CI]: 1.31-7.21, p=0.01) and ischemic etiology (HR: 3.32; 95% CI: 1.50-7.35, p=0.003) as independent predictors of mortality and cardiovascular events. ROC analysis revealed that irisin achieved an area under the curve (AUC) of 0.67 for one-year events (p=0.031), and that the AUC increased when irisin was added to BNP level (alone: 0.64, BNP+irisin: 0.74).

Conclusions:
Irisin could be a useful biomarker for evaluating disease severity and providing incremental prognostic information in patients with HFrEF.
Abstract 12600: Microrna From Atrial Tissue Harvested During Transseptal Puncture as a Predictor for Non-pv Trigger in Patients Undergoing Af Ablation: Preliminary Results From a Pilot Study
Authors: Di Biase Luigi , Baker Aaron , Yan Xue , Lee Jason , Santoro Francesco , Trivedi Chintan , Mohanty Sanghamitra , Mohanty Prasant , Bai Rong , Sanchez Javier , Horton Rodney , Gallinghouse G. Joseph , Burkhardt J. David , Natale Andrea
Published: July 2021

Introduction:
Catheter ablation of atrial fibrillation (AF) is the most valid therapeutic option to achieve rhythm control. Pulmonary veins (PV) are the most known trigger of AF, although recently we have become more aware of the importance of non-PV triggers. Expression of microRNA (miRNA) has been shown to be regulated in many cardiovascular disease. We sought to study expression patterns of miRNA in patients (pts) with AF undergoing ablation to facilitate their application as both diagnostic and prognostic markers.

Methods:
As part of the standard procedure for AF ablation a double transseptal sample of myocardial tissue is obtained via a transseptal needle. The small piece of atrial septal tissue can be retrieved from the needle as a result of piercing the atrial septum. MiRNA was hybridized to microarrays to determine relative levels of miRNAs in the samples. For a subset of the miRNAs we validated expression through quantitative real time PCR. All pts underwent PV-antrum and non-PV trigger ablation guided by isoproterenol challenge test.

Results:
Atrial tissue of 11 pts undergoing AF ablation has been utilized for MiRNA assessment. Mean age was 61.27 ± 10.5 years and 8 (72.7%) pts were male. Six (54.5 %) pts had paroxysmal AF. During the ablation non-PV triggers were detected in 8 (72.7 %) pts. Recurrence of AF occurred in 3(27.3 %) pts. Expression of miR-21, miR-26a and miR-29a was higher in pts with non-PV triggers, while miR-30c had lower expression in pts who had recurrence of atrial tachyarrhythmias. Spearman’s nonparametric correlation coefficient was calculated and miR-21, miR-26a, miR-29a were positively correlated with non-PV triggers (r = 0.58, p=0.06 for all three miRNAs), while miR-30c level had inverse correlation (r = (-) 0.78 %, p=0.005) with recurrence (Figure).

Conclusions:
Expression of miR-21, miR-26a, miR-29a correlates with the presence of non-PV triggers. This information could be clinically relevant in planning patient specific procedures.
Abstract 12693: Influence of Resting Heart Rate and Changes in Resting Heart Rate on Cardiovascular Outcomes From the Atherosclerosis Risk in Communities Study
Authors: Vazir Ali , Claggett Brian , Shah Amil , Skali Hicham , Cheng Susan , Ballantyne Christie M , Aguilar David , Vardeny Orly , Solomon Scott D
Published: July 2021

Background:
Resting heart rate (HR) and change in resting heart rate (ΔHR) over time are associated with increased risk of adverse outcome in patients with established heart failure (HF). We assessed whether the most recent HR and ΔHR are associated with cardiovascular (CV) outcomes in participants enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study.

Methods:
We studied 15,680 participants with HR recorded at baseline (age 54±6 years, women 55%, African American 27%) and over 3 follow-up visits with a median time interval between visits of 3.0 (IQR 2.9-4.0) years. ΔHR from the preceding visit was calculated. Participants were followed up for a median of 22.7 (19.8-23.7) years. We related baseline and most recent resting HR and ΔHR to all cause mortality and CV outcomes adjusting for established baseline and time-updated risk factors and medications.

Results:
Baseline and most recent HR and ΔHR were associated with all-cause mortality and CV outcomes (table), however most recent HR and ΔHR were more strongly associated with outcomes compared to baseline HR. Every 10bpm increase in HR from the preceding visit was associated with a 29%, 30% 22% and 15% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively. Every 10 bpm higher most recent HR was associated with a 34%, 41% 23% and 14% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively.

Conclusion:
In a community-based cohort, the most recent resting HR and ΔHR are strongly associated with outcomes; higher resting HR and increases in HR over time are associated with the greatest magnitude of risk.
Abstract 12747: Protein Profiling for Survival Outcome Prediction in Out-of-Hospital Cardiac Arrest Patients
Authors: Huang Chien-Hua , Tsai Min-Shan , Chang Wei-Tien , Hsu Hsin-Yun , Chen Wen-Jone
Published: July 2021

Introduction:
Outcome prediction is still a challenge for out-of-hospital cardiac arrest (OHCA) patients in early post-cardiac arrest period. Changes of protein expression after cardiac arrest and resuscitation could be biomarkers for outcomes prediction. Single biomarker can not reach adequate power to predict outcome due to the complexity of pathophysiological cascades in post-cardiac arrest period. Protein profiling can measure multiple biomarkers at a time point and can provide better information for outcome prediction.

Hypothesis:
Identify the association of survival to discharge outcome and biomarkers changes by protein profiling in cardiac arrest patients

Methods:
Total 99 adult non-traumatic OHCA patients with sustained ROSC were enrolled for the study. There were 45 patients survival to hospital discharge. Blood were sampled at 24 hours after cardiac arrest. Protein profiling for 21 different biomarkers, which included brain, heart, inflammatory reactions, oxidative stress and coagulation markers, was measured by suspension microarray assay. Clustering analyses were carried out using Multi-Experiment Viewer (MeV v4.8.1).

Results:
Heat maps were generated to visualize the Log2 values relative to median values of overall patient sample pool. Based on the performed statistical analysis to narrow down the biomarker panel, we investigated samples respectively by employing only the significant parameters for the Hierarchical Clustering (HCL) analysis. Nine candidate biomarkers (IL-6, IL-8, IL-10, MCP-1, MDA-LDL, Cystatin C, PAI-1, NT-Pro-BNP and S100B) identified respectively from samples pools were applied. The discrimination based on the selected parameters was 76.3% to be accurately clustered in HCL analysis. When adding these biomarkers into clinical variables (age, sex, Apache II, hypothermia, shockable rhythm, CPR duration), receiver-operating characteristic curve analysis showed high prediction power for survival to discharge (area under curve = 0.9378, p<0.01)

Conclusion:
Protein profiling with suspension microarray can demonstrate the pattern of biomarkers in various pathophysiological changes after cardiac arrest. It has the potential to help predicting the outcome in OHCA patients.
Abstract 12760: Left Ventricular (LV) Remodeling in Aortic Regurgitation Differs From Athlete’s Heart With Similar LV Volumes and is Closely Related to Different Fiber Stress Distribution
Authors: Broch Kaspar , deMarchi Stefano , Massey Richard , Aakhus Svend , Gullestad Lars , Urheim Stig
Published: July 2021

Introduction:
Elite endurance athletes often develop left ventricular dilatation comparable to that observed in aortic regurgitation (AR).

Hypothesis:
We hypothesized that the LV remodeling observed in athlete’s heart differs from that seen in AR, and that the difference may be attributed to different fiber stress distribution.

Methods:
Thirty asymptomatic patients with moderate to severe AR, 15 age matched elite endurance athletes (Athl) and 17 age matched healthy controls (C) where analyzed with 3D speckle tracking echocardiography. We calculated the ratio between peak systolic circumferential (CS) - and peak systolic longitudinal strain (LS) and end-systolic (ES) circumferential (ESSc) and meridional (ESSm) fiber stress.

Results:
LV ejection fraction in C, Athl and AR patients was (61 ± 2, 61 ± 3 and 62 ± 3%, respectively, p=NS). LV end-diastolic volume was 78 ± 11, 112 ± 13 and 117 ± 20 ml/m
2
in C, Athl and AR, respectively, (C vs AR and Athl, p<0.01, AR vs Athl, p=NS). A non-uniform contraction pattern with a rightward shift of the LS strain curve was observed in AR (Figure 1). The CS/LS ratio was 0.91 ± 0.11, 0.91 ± 0.16 and 1.12 ± 0.24 in C, Athl and AR, respectively, (AR vs C and Athl, p<0.01, C vs Athl, p=NS). Consistently, the ESSc/ESSm ratio was similar in C and Athl (1.75 ± 0.08 and 1.74 ± 0.07, respectively, p=NS) and lower in AR patients (1.67 ± 0.07, AR vs C and Athl, p<0.01), indicating a relative increase in meridional fiber stress in the AR group (Figure 2).

Conclusions:
We have demonstrated that LV remodeling in AR patients differs from athlete’s heart with similar LV volumes, and may be attributed to a shift in the circumferential-meridional fiber stress ratio in AR patients.
Abstract 12803: Galectin-3 is a Prognostic Biomarker for Patients After Transcatheter Aortic Valve Implantation
Authors: Baldenhofer Gerd , Spethmann Sebastian , Laule Michael , Eilers Bjoern , Sanad Wasiem , Dreger Henryk , Baumann Gert , Stangl Karl , Stangl Verena , Knebel Fabian
Published: July 2021

Introduction:
Until now, a reliable biomarker to predict the short- or long-term outcome for patients undergoing TAVI is still missing. Galectin-3, a novel marker indicative for myocardial fibrosis, has prognostic value in heart failure. Our goal was to investigate whether galectin-3 is suited for risk assessment in TAVI patients.

Methods:
We included 101 patients undergoing TAVI in this prospective, single-center, observational study. Baseline galectin-3 levels were correlated to the VARC 30-day safety and one-year efficacy endpoint as well as to total mortality and cardiovascular events at one year.

Results:
The VARC 30-day safety endpoint was reached by 24 patients. At one year, 43 patients met the VARC efficacy endpoint, 16 patients died, and 23 cardiovascular events were recorded. At baseline, mean galectin-3 level for the entire group was 18.1 (± 11.1) ng/ml. Of the 101 patients, 36 had a galectin-3 value above the cut-off value of 17.8 ng/ml. These patients had significantly higher systolic pulmonary artery and capillary wedge pressures. The hazard ratio in patients with galectin-3 > 17.8 ng/ml was 3.36 (95 % confidence interval, CI: 1.47 - 7.69; p = 0.004) for the VARC 30-day safety endpoint, 5.12 (95 % CI: 2.10 - 12.47; p < 0.001) for one-year cardiovascular events, and 4.48 (95 % CI: 1.56 - 12.91; p = 0.005) for all-cause mortality. This prediction remained stable even after adjusting for possible confounders including age, sex, glomerular filtration rate, and NT-proBNP. Furthermore, the prediction was even more valuable when combining galectin-3 with NT-proBNP for cardiovascular events (HR = 6.39; CI: 2.87-23.89; p < 0.001) and all-cause mortality (HR = 8.28; CI: 2.01-23.59; p < 0.001).

Conclusions:
Elevated galectin-3 levels are independently associated with adverse outcome after TAVI. Combining galectin-3 with NT-proBNP provides additive predictive value of risk stratification.
Abstract 12840: In vivo Visualization of ATP Dynamics Under Hypoxia Reveals That G0/G1 Switch Gene 2 Provides Ischemic Tolerance Through the Increase of ATP Production
Authors: Kioka Hidetaka , Kato Hisakazu , Asano Yoshihiro , Sakata Yasushi , Kitakaze Masafumi , Takashima Seiji
Published: July 2021

Introduction:
We have recently established the method for the selective measurement of intra-mitochondrial ATP levels ([ATP]mito) and have identified the hypoxia-inducible protein G0/G1 switch gene 2 (G0s2) as a positive regulator of mitochondrial oxidative phosphorylation by cultured cardiomyocyte-based experiments. However, the energy metabolism in cultured cells may be much different from that in the living tissue. In this study, we examined the in vivo role of G0s2 under hypoxia by using a novel real-time in vivo ATP imaging technique in zebrafish heart.

Methods and Results:
We first established the in vivo ATP imaging technique by introducing a FRET-based ATP biosensor named Mit-ATeam into zebrafish heart (Mit-ATeam zebrafish). This system also allows us the simultaneous evaluation of cardiac function. Using Mit-ATeam zebrafish, we successfully observed a decline in [ATP]mito and cardiac function under hypoxic stress and the recovery of these parameters by sequential re-oxygenation. Cardiac specific G0s2 transgenic zebrafish had significantly stronger tolerance against hypoxic stress than wild type zebrafish, while mutant G0s2 transgenic zebrafish did not. In addition, we generated a chimeric zebrafish model in which G0s2 was regionally overexpressed to examine whether focal overexpression of G0s2 could preserve regional cardiac function under hypoxia. Only G0s2-overexpressing cardiomyocyte populations showed enhanced contractility with increased [ATP]mito in hypoxia compared to the control region (i.e. non-G0s2-overexpressing cardiomyocyte populations). Furthermore, we detected enhanced protein expression of G0s2 protein in the risk area in canine ischemic preconditioned heart, suggesting the possible involvement of G0s2 in ischemic preconditioning mediated cardioprotection.

Conclusions:
These results suggest that G0s2 functions as a guardian of ischemic myocardium and could become a therapeutic target for ischemic heart diseases. Additionally, this study is the first to connect cardiac energy metabolism and function in living animal in real-time.
Abstract 12877: Malnutrition Assessed by Geriatric Nutritional Index Provides the Additional Long-Term Prognostic Information to Renal Dysfunction in Patients Admitted for Acute Decompensated Heart Failure
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Kawai Tsutomu , Takahashi Satoshi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Seo Masahiro , Fukunami Masatake
Published: July 2021

Backgrounds:
Renal dysfunction has emerged as one of the most potent prognostic indicators in patients with heart failure. Hospitalization for acute decompensated heart failure (ADHF) isassociated with a high mortality after discharge. Malnutrition is also associated with poor outcome in ADHF pts. However, there is no information available on the long-term prognostic significance of malnutrition, relating to renal dysfunction in ADHF patients.

Methods and Results:
We studied 305 consecutive ADHF patients discharged with survival. Nutritional status was evaluated by Geriatric Nutritional Risk Index (GNRI) calculated as follows: 14.89 x serum albumin (g/dl) + 41.7 x body mass index/22. During a follow-up period of 4.2±3.2 yrs, 69 patients had cardiovascular death (CVD). At multivariate Cox analysis, GNRI at discharge (p=0.003) and estimated glomerular filtration rate (GFR) (p=0.03) were significantlyassociated with CVD, independently of systolic blood pressure, serum sodium level and prior heart failure hospitalization. Receiver-operator curve analysis revealed that GNRI of 88 was a fair discriminator for CVD (AUC 0.698 (95%CI 0.628-0.768), p<0.0001). In patients with renal dysfunction defined as low GFR (<the median value:54.5ml/min/1.73m
2
), CVD was significantly more frequently observed in pts with than without low GNRI <88 (52% vs 26%, p<0.0001, the adjusted hazard ratio (HR):2.7 (95%CI 1.5-4.8)). Furthermore, in group without renal dysfunction, pts with low GNRI had the significantlyincreased risk, compared to those with high GNRI>88 (28% vs 6%, p<0.0001, the adjusted HR:4.7 (95%CI 1.6-13.4)).

Conclusion:
Malnutrition Assessed by Geriatric Nutritional Index provides the long-term prognostic information in patients admitted for acute decompensated heart failure, irrespective of renal dysfunction.
Abstract 12932: Day of the Week and Acute Heart Failure Admissions: Relation With Acute Myocardial Infarction, Length of Stay and Readmission Rate
Authors: Shah Mahek , Patnaik Soumya , Davila Carlos , Lu Marvin , Junpaparp Parichart , Buppajarnthum Saranya , De Venecia Toni Anne , Chandorkar Aditya
Published: July 2021

Background:
The day of the week has been inconsistently linked to the length of hospital stay (LOS) and even mortality in patients with heart failure (HF). With Medicare expenditure for HF hospitalizations exceeding 17 billion USD a year, there has been an increased focus on measures that could decrease HF readmissions. While reduced physician staffing, poor quality of care and lesser supervision may be seen on weekends, its role in predicting a worse outcome is unclear.

Methods:
All patients with HF as the admitting diagnosis between 1/1/2003 and 12/31/2013 were included. The admissions were stratified based on the day of admission and an association with outcomes as LOS, new acute myocardial infarction (AMI) or readmission for HF was analyzed.

Results:
From the 22,287 admissions included, 4,874 (22%) were on the weekend. The average age (69+/-15 years in both groups, p=0.98) and risk factors as hypertension, diabetes, hyperlipidemia, chronic kidney disease and coronary artery disease were similar between weekend and weekday admissions. More male admissions were seen on weekdays (48% vs. 46%, p=0.034) and the patients admitted on weekends experienced 25% more AMIs (p=0.005). The mean daily admission rate was significantly higher on weekdays (6.1+/-0.8/day vs. 4.2+/-0.6/day, p<0.001) with Monday and Sunday having the highest and lowest rates (6.58/day vs. 4.23/day respectively). There were lesser patient discharges on weekends than weekdays (13% vs. 87%). The LOS was similar for weekday and weekend admissions (5.7+/-6.1 vs. 5.5+/-5.8 days, p=0.125) but Friday was associated with the longest stay in the week (6+/-6.1 days vs. 5.6+/-6 days, p=0.001). The maximum and minimum 30 day readmission rate was seen in patients who were discharged on Friday and Saturday respectively with 18% more readmissions in those discharged on Friday compared to Saturday.

Conclusions:
Weekends may see lesser HF admissions than weekdays but the risk of an AMI is higher in these patients. Friday admissions were associated with the maximum LOS and Friday discharges with the highest readmission rate. A better understanding of the hurdles faced during weekends with directed research and subsequent remediation of the issues can potentially improve HF care and related clinical outcomes.
Abstract 12941: Disease Progression in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Ventricular Tachycardia: A Longitudinal Study With Unipolar Voltage Mapping
Authors: Santangeli Pasquale , Liuba Ioan , Tschabrunn Cory , Riley Michael , Garcia Fermin , Bala Rupa , Hutchinson Mathew , Supple Gregory , Lin David , Frankel David , Schaller Robert , Callans David , Zado Erica , Marchlinski Francis
Published: July 2021

Introduction:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is believed to result in progressive fibrofatty replacement of the RV myocardium with development of multiple ventricular tachycardia (VT) circuits. Endocardial unipolar voltage mapping has been shown to reliably identify epicardial and endocardial (epi-endo) scar in ARVC.

Hypothesis:
We studied the prevalence and mechanisms of disease progression in patients with ARVC and VT through longitudinal unipolar voltage mapping studies.

Methods:
Eighteen consecutive patients (age 38±14 years) who fulfilled the revised Task Force criteria for ARVC underwent two detailed sinus rhythm endocardial unipolar voltage maps (mean 348±118 points) performed a median of 36 months apart (interquartile range 21 to 36 months, minimum 9 months) as part of VT ablation procedures. Epi-endo scar was defined using established unipolar voltage cutoff (5.5 mV). The extent of RV scar and total RV volume was measured by a dedicated software. A >5% increase in RV scar area or volume over follow-up was considered significant.

Results:
At baseline, all patients had evidence of epi-endo RV scar (mean 141±82 cm
2
; 56±27% of the RV surface area). After a mean follow-up of 49±36 months, no significant progression of unipolar voltage scar was observed (mean 159±83 cm
2
, P=0.14; 63±27% of the RV surface area, P=0.07). Specifically, only 3 (17%) patients presented with progression of the RV scar >5%. The RV volumes increased during follow-up (from 206±74 mL to 258±77 mL, P=0.0003), with the majority of patients (15/18, 83%) having a significant increase in the RV volume (mean increase = 38.9%). Only 3 (17%) patients had no change in both RV scar size and volume over time.

Conclusions:
In patients with ARVC and VT, progressive RV dilatation is almost uniformly observed, while rapid epi-endo scar progression is rare. These findings suggest that aggressive epi-endocardial substrate ablation should provide long-term VT control, and further research is needed to identify the mechanism(s) for and to prevent ongoing RV dilatation in these patients.
Abstract 12944: Patients With Acute Coronary Syndrome, Compared to Those With Stable Angina Pectoris, Have Increased Bright Spots at the Culprit Site by Optical Coherence Tomography
Authors: Minami Yoshiyasu , Phipps Jennifer E , Hoyt Taylor , Feldman Marc D , Jang Ik-Kyung
Published: July 2021

Background:
Recent studies reported that bright spots detected by optical coherence tomography (OCT) represent more complex plaques including macrophages and cholesterol crystals. We hypothesized that the density and area of bright spots would be greater at the culprit lesion in patients with acute coronary syndrome (ACS) compared to those with stable angina pectoris (SAP).

Aim:
To compare the density and extent of bright spots in the culprit lesion between patients with ACS and with SAP.

Methods:
We identified 14 ACS and 17 SAP patients who underwent pre-PCI OCT imaging of the culprit lesion. Cases with poor image quality or left main disease were excluded. Bright spots within superficial 125μm of the vessel wall were identified in a 5mm length segment at the culprit site. The density was calculated as the number of bright pixels identified by the algorithm divided by the number of pixels in each frame (total 25 frames in one case). The area of bright spots was also calculated.

Results:
There were no significant differences in the baseline characteristics including mean age (65.9 ± 10.2 vs 65.2 ± 9.32 yrs, P=0.83) and the prevalence of coronary risk factors between ACS and SAP. Mean and maximum density of bright spots was significantly greater in ACS than in SAP (Table). The area of bright spots was also significantly larger in ACS. Among ACS patients, a subgroup with plaque rupture (n=11) had much greater mean density and area compared with SAP (1.20 [0.41-1.73] vs 0.44 [0.21-0.58], P=0.01, 5.32 [1.88-8.07] vs 2.06 [0.97-2.64], P=0.01).

Conclusions:
Using the novel algorithm, we demonstrate that the density and area of bright spots are significantly greater in ACS than in SAP. This result suggests that the measurement of bright spots can be useful to determine plaque vulnerability.
Abstract 12973: High-Intensity Focused Ultrasound (HIFU) Promotes Angiogenesis in a Rat Model of Peripheral Arterial Disease
Authors: Nazer Babak , Ghahghaie Farzin , Kokhlova Tatiana , Perez Camilo , Crum Lawrence , Matula Thomas , Hata Akiko
Published: July 2021

Shock wave therapy (SWT) delivers single pulses of pressure to tissue, and promotes angiogenesis in animal models and humans with PAD and CAD. HIFU applies pulses of multiple pressure waves, which may be more efficient. We hypothesized that setting HIFU intensity to replicate peak negative pressures (-6 MPa) typically used for SWT would lead to greater angiogenesis. Eight week-old female Sprague-Dawley rats underwent left femoral artery excision to induce hindlimb ischemia, and the right hindlimb was used as an internal control. Rats were randomized to three groups (n=10 each): SWT (0.10 mJ/mm2), HIFU (1.054 MHz, 1 ms pulse duration), and sham therapy. Both treatments were applied at a pulse repetition frequency of 5 Hz, 200 pulses per spot, for six spots along the hindlimb. Rats were treated three times weekly for two weeks, and hindlimb perfusion was assessed with a Moor LDI Laser Doppler scanner. Compared with pre-treatment baseline (Fig 1A), HIFU improved the ratio of left:right perfusion by 23.6 ± 4.5% (mean ± SEM; Fig 1B), SWT by 17.0 ± 5.9%, and sham by 4.7 ± 3.4% (Fig 1C). Immunohistochemistry of gastrocnemius muscle was performed using anti-CD31 (PECAM) antibody, and microvascular density was quantified using ImageJ software. Both HIFU and SWT increased microvascular density in the left hindlimb (223 ± 4 and 217 ± 5 vessels/hpf, respectively) compared with sham (196 ± 7, p = 0.0001 for HIFU, p = 0.01 for SWT), but there was no significant difference between HIFU and SWT. RT-PCR was performed to examine the level of VEGF mRNA. HIFU increased left:right VEGF mRNA compared with sham (2.98 ± 0.69 vs 1.17 ± 0.23, p = 0.03), whereas SWT did not exhibit a significant change compared with sham (0.75 ± 0.20, p = 0.19). In conclusion, HIFU may be a potential non-invasive therapy for promotion of angiogenesis and reperfusion for PAD patients. Further research is needed to define a dose-response relationship of HIFU-mediated angiogenesis, and to elucidate its pro-angiogenic mechanisms.
Abstract 13082: On-Pump Cardiac Surgery in Humans Induces Myocardial Nitric Oxide Synthase Dysfunction via S-Glutathionylation of eNOS
Authors: Jayaram Raja , Goodfellow Nicky , Zhang Mei Hua , Reilly Svetlana , Crabtree Mark , DeSilva Ravi , Sayeed Rana , Casadei Barbara
Published: July 2021

Background and Aims:
The mechanism responsible for LV dysfunction after cardiac surgery is only partially understood. In isolated rat hearts subjected to a prolonged ischemia-reperfusion protocol, LV dysfunction was associated with uncoupling of endothelial nitric oxide synthase (eNOS) activity secondary to oxidation of the NOS co-factor, tetrahydrobiopterin (BH4). Here we investigated the effect of cardiopulmonary bypass (CPB) and reperfusion on myocardial NOS activity and ROS production in 116 patients who underwent elective cardiac surgery.

Results:
Paired samples of the right atrial appendages (RAA) were obtained prior to venous cannulation of the right atrium (PRE) and after myocardial reperfusion (POST). Atrial superoxide (O2-) release increased significantly after reperfusion (in RLU/sec/mg: from 37.83 ± 3.71 to 65.02 ± 6.01 in the POST samples; p < 0.001, n = 46 samples from 23 patients) due to uncoupling of NOS activity (D-NAME - L-NAME = ΔO2- in RLU/sec/mg: from - 31.47 ± 9.15 PRE to 40.75 ± 11.84 POST; p < 0.001 in n = 36) and increased mitochondrial and NOX2 oxidase activity (by 309% and 149%, respectively, P<0.001). POST atrial content of BH4 was reduced by 32% (P=0.001), as was the activity of the rate-limiting enzyme in BH4 synthesis, GTP-cyclohydrolase 1 (GTPCH1, by 50%, P<0.001). NOS activity (HPLC detection of 14C L-Arginine to L-Citrulline conversion) decreased significantly after reperfusion (by 60%; p < 0.001) whereas the protein content of NOS isoforms remained unchanged. Surprisingly, the PRE-POST difference in NOS activity was not affected by BH4 supplementation (10 μM) or NOX2 inhibition with the gp-91-ds tat peptide. Instead, we identified increased eNOS s-glutathionylation as the main mechanism responsible for NOS uncoupling after reperfusion. Reversing NOS s-glutathionylation with dithiothreitol (DTT: 100 μM; n=18) completely restored NOS activity after reperfusion (p =0.34).

Conclusions:
Our findings indicate that NOS s-glutathionylation, rather than BH4 depletion, accounts for NOS dysfunction in patients after cardiac surgery and CPB. Although myocardial NOX2 activity is increased after reperfusion, NOX2 do not appear to be the source of oxidative stress responsible for NOS dysfunction under these conditions.
Abstract 13111: Determinant of Sucessful Implantation of a Novel Autologous Valve Substitute (Biovalve) with Transcatheter Technique
Authors: Takewa Yoshiaki , Nakayama Yasuhide , Kishimoto Satoru , Date Kazuma , Sumikura Hirohito , Kanda Keiichi , Tajikawa Tsutomu , Tanaka Takaharu , Taenaka Yoshiyuki , Tatsumi Eisuke
Published: July 2021

Introduction:
There are some attempts to use tissue-engineered materials for heart valvular substitutes, but it is not clear what is determinant of successful implantation of the substitutes. It is generally thought that appropriate cell migration into an implanted graft tissue is essential in order to sufficiently exert the functions as a native valve.

Hypothesis:
We are developing a novel autologous aortic valve (Biovalve), using simple, safe and economical in-body tissue engineering which is based on a tissue encapsulation phenomenon in the living body. In this study, we investigated key factors in hitogenesis when the Biovalve was implanted in a large animal model with transcatheter technique.

Methods:
Biovalves were prepared by 2-month embedding of the molds, assembled using plastic rods in the subcutaneous spaces of goats. After extracting the molds and removing the plastic rods only, Biovalve were constituted from completely autologous connective tissues. We combined the Biovalve with a metaric stent for transcatheter implantation. Twenty Biovalve Stents were implanted in the aorta (n=16) and the pulmonary artery (PA) (n=4) in situ with transcatheter apical approach technique.

Results:
The Biovalve Stents were successfully implanted in both aortic and PA postion. They were extracted every month (maximum 6 months) after implantation to observe their cell migration process. The leaflets of the Biovalve kept their shape and elasticity even after 6 months and neither calcification nor thrombi were observed. Histological examination showed the cell migration inside the Biovalve body and laminar endothelialization on the surface of the valve leaflets even in 1 month after implantation. Their histogenesis have gradually advanced in 6 months without any hyperplasia, but were interrupted when the Biovalve tissues were not attached enough on the native vascular wall surface.

Conclusions:
The Biovalve satisfied the higher requirements of systemic and pulmonary circulation in goats for 6 months with the histogenic potential that was mainly induced by cell migration from the native vascular tissues contacting with the Biovalve.
Abstract 13131: The Priority of Coronary Arteriography and Therapeutic Hypothermia After Return of Spontaneous Circulation in Patients With Out-of-hospital Cardiac Arrest. the Result of Sos-kanto 2012 Study
Authors: Hagiwara Shuichi , Oshima Kiyohiro , Murata Masato , Aoki Makoto , Hayashida Kei , Sakurai Atsushi , Nagao Ken , Yaguchi Arino , Morimura Naoto
Published: July 2021

Aim:
To evaluate the priority of coronary angiography (CAG) and therapeutic hypothermia therapy (TH) after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA).

Patients and Methods:
SOS-KANTO 2012 study is a prospective, multicenter (69 emergency hospitals) and observational study and includes 16,452 patients with OHCA. Among the cases with ROSC in that study, we intended for patients treated with both CAG and TH within 24 hours after arrival. Those patients were divided into two groups; patients in whom TH was firstly performed (TH group), and the others in whom CAG was firstly done (CAG group). We statistically compared the prognosis between the two groups. SPSS Statistics 22 (IBM, Tokyo, Japan) was used for the statistical analysis. Statistical significance was assumed to be present at a p value of less than 0.05.

Result:
233 patients were applied in this study. There were 86 patients in the TH group (M/F: 74/12, mean age; 60.0±15.2 y/o) and 147 in the CAG group (M/F: 126/21, mean age: 63.4±11.1 y/o) respectively, and no significant differences were found in the mean age and M/F ratio between the two groups. The overall performance categories (OPC) one month after ROSC in the both groups were as follows; in the TH group, OPC1: 21 (24.4%), OPC2: 3 (3.5%), OPC3: 7 (8.1%), OPC4: 8 (9.3%), OPC5: 43 (50.0%), unknown: 4 (4.7%), and in the CAG group, OPC1: 38 (25.9%), OPC2: 13 (8.8%), OPC3: 15 (10.2%), OPC4: 18 (12.2%), OPC5: 57 (38.8%), unknown: 6 (4.1%). There were no significant differences in the prognosis one month after ROSC between the two groups.

Conclusion:
The results which of TH and CAG you give priority to over do not affect the prognosis in patients with OHCA.
Abstract 13133: Silencing of Angiopoietin-like Protein 3 (
ANGPTL3
) in IHH- Hepatocytes Results in Increased Insulin Sensitivity and Reduced Triglyceride-rich VLDL Secretion
Authors: Tikka Anna M , Laurila Pirkka-Pekka , Soronen Jarkko , Metso Jari , Ehnholm Christian , Jauhiainen Matti
Published: July 2021

AIMS:
Homozygosity of loss-of-function mutations in ANGPTL3 -gene results in familial combined hypolipidemia (FHBL2,OMIM #605019) characterized by reduction of all major plasma lipoprotein classes VLDL, LDL, HDL and low circulating free fatty acids, glucose and insulin levels. Thus complete lack of ANGPTL3 in humans not only affects lipid metabolism but also whole-body insulin and glucose balance. Our aim was to investigate the function of ANGPTL3, a hepatic secretory protein, in promoting hypolipidemia and hepatic insulin sensitivity.

METHODS:
We used wild type and ANGPTL3-silenced human immortalized hepatocytes (IHH) to investigate the effect of ANGPTL3-silencing on hepatic VLDL secretion and glucose uptake.

RESULTS:
We demonstrate that insulin downregulates hepatic secretion of ANGPTL3 and triglyceride-enriched VLDL1-type particles in a dose dependent manner. Similar effect on VLDL secretion was demonstrated with a treatment of PPAR[[Unable to Display Character: ƴ]] agonist rosiglitazone. We further show that ANGPTL3-silenced cells display a more pronounced shift from the secretion of TG-enriched VLDL1-type particles to a secretion of lipid poor VLDL2-type particles during insulin stimulation. Silencing of ANGPTL3 improved hepatic glucose uptake by 20-50 % depending on the glucose and insulin concentration, resulted in a trend towards increased AKT/PKB phosphorylation upon insulin stimulation and downregulated fasting induced transcription factor PGC1α and its downstream targets.

CONCLUSION:
Our results indicate a similar function of both insulin and rosiglitazone regarding regulation of ANGPTL3 and VLDL secretion in hepatocytes, and suggest that insulin and PPAR[[Unable to Display Character: ƴ]] might mediate some of their functions via ANGPTL3. Our results give more insight into the liver specific role of ANGPTL3 and links silencing of ANGPTL3 with Insulin sensitivity. Since humans with elevated levels of ANGPTL3 display hyperlipidemia and insulin resistance it might be beneficial to target ANGPTL3 silencing in the liver, the major site of ANGPTL3 expression, to balance lipid and glucose homeostasis and lower risk for cardiovascular diseases.
Abstract 13220: Cardiovascular Impact of Testosterone Therapy in Men with Low Testosterone Levels
Authors: Anderson Jeffrey L , May Heidi T , Lappé Donald L , Bair Tami L , Le Viet T , Muhlestein Joseph B
Published: July 2021

Introduction:
Epidemiologic studies have identified low testosterone (T) levels as an independent risk factor for cardiovascular (CV) and total mortality. However, the impact of T therapy on CV outcomes is controversial. A small trial in older men at high risk was stopped early due to increased CV events (NEJM 2010; 363:109). A recent observational study in veterans suggested modest risk (JAMA 2013; 3310:1829). We sought to assess the impact of T supplementation and achieved T levels across Intermountain Healthcare (IHC) facilities using a virtual controlled study design.

Methods:
IHC electronic medical records were searched between 1996 and 2011 to identify subjects who had a low initial total T level, a subsequent T level, and ≤3y follow-up. Levels were correlated with T supplement use. Primary outcomes were a composite of death, nonfatal myocardial infarction, and stroke (MACE) and death alone (D). Hazard ratios (HRs) comparing groups of persistent low (<212 ng/dL, n=1142), normal (212-742 ng/dL, n=2634), and high (>742 ng/dL, n=1919) achieved T were calculated by Cox regression, adjusting for 17 baseline variables.

Results:
A total of 5,695 men (age 62.3 ± 9.3 y, diabetes: 28%, CAD: 22%) were studied. Event rates at 1 and 3-y by T level, and adjusted HRs, are shown in the Table. Overall 3-y rates of MACE and D were 8.6% and 6.4%, respectively. Subjects supplemented to normal/high T had reduced 3-y MACE (HR 0.55, 95% CI 0.46-0.67) and D (HR 0.43, CI 0.35-0.54) compared to persistent low T subjects, with no signal for effect attenuation for MACE or D with higher T. Results were similar for 1-y MACE (HR 0.51, p<0.0001) and D (HR 0.38, p<0.0001).

Conclusions:
In a large general healthcare population, T therapy in men with low T was associated with reduced MACE and D over 3-y compared to no or ineffective supplementation. Resolving the difference in CV risk impact of T therapy between this, and previous studies, warrants a large randomized clinical trial in a similar, younger population.
Abstract 13242: Insulin Treated Patients With Diabetes Derive Reduction in Mortality From Cardiac Resynchronization Therapy - Results From the Madit-Crt in Trial Experience
Authors: Szepietowska Barbara , Kutyifa Valentina , Ruwald Martin H , Solomon Scott D , Ruwald Anne-Christine H , McNitt Scott , Polonsky Slava , Moss Arthur , Zareba Wojciech
Published: July 2021

Methods:
We aimed to analyze the risk for death and HF and the effect of CRT on HF/death in diabetic patients with or without insulin treatment compared to none diabetic population. The study comprised 1278 patients with left bundle branch block in the MADIT-CRT trial with an average follow-up of 3.3y. We used time dependent survival analysis and Cox proportional hazards regression method.

Results:
In ICD arm patients with diabetes receiving insulin treatment had 2.4-fold higher risk of all-cause mortality (p=0.008), and 2.2-fold higher risk of HF (p<0.001) when compared to non diabetic patients, and 2.8-fold higher risk of death (p=0.01), and 1.6-fold higher risk of HF (p=0.06) when compared to patients with diabetes not treated with insulin. Treatment with CRT-D was associated with a significant 75% risk reduction in all-cause mortality (hazard ratio [HR ] 0.25; 95% confidence interval [CI]: 0.08-0.77; p=0.016) in patients with diabetes receiving insulin. Noteworthy, during the 3-year follow-up, reduction in all-cause mortality was not observed in patients not treated with insulin or in patients with no diabetes (interaction p-value=0.038). Significant risk reduction in HF and in HF/death after CRT treatment was observed across all three investigated groups. There were not significant differences in left ventricular reverse remodeling after CRT-D among diabetic patients with or without insulin treatment compared to the nondiabetic population.

Conclusions:
Patients with insulin treated diabetes derive significant reduction in mortality and heart failure after implantation of cardiac resynchronization therapy. Patients with diabetes and no insulin and patient without diabetes benefit from CRT by reduction of HF events.