bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9393: Anxiety and Depressive Symptoms Have Inverse Relationships With Cardiac Depolarization by ECG: MESA Study
Authors: Peacock James , Whang William , Alcantara Carmela , Nazarian Saman , Shah Amit J , Shea Steven , Soliman Elsayed Z , Muntner Paul , Shimbo Daichi
Published: April 2024

BACKGROUND:
Depression and anxiety are predictors of poor cardiac prognosis. Lower T wave amplitude by resting electrocardiogram (ECG) has been correlated with adverse outcomes such as myocardial infarction, cardiac mortality, and sudden cardiac death. We therefore examined the relationship between depressive and anxiety symptoms and T wave amplitude in the Multi-Ethnic Study of Atherosclerosis (MESA).

METHODS:
Men and women 45 to 84 years old, free of clinically apparent cardiovascular disease, were recruited between July 2000 and August 2002 from six US communities. Resting 12-lead ECGs were collected, depressive symptoms were measured with the Center for Epidemiologic Studies-Depression scale (CES-D) and anxiety symptoms were measured with the Spielberger Trait Anxiety scale. Linear regression models with maximum T wave amplitude in microvolts as the dependent variable and depression and anxiety scores as independent variables were utilized for analysis. Participant were excluded for any of the following: QRS duration >120 msec, major ECG abnormalities according to the Minnesota Code, or use of antiarrhythmic, antidepressant, or antipsychotic medication.

Results:
Of 6814 MESA participants, 5388 met the inclusion criteria and were retained for analysis. Depressive symptom scores and anxiety scores were moderately correlated (r=0.55). With simultaneous inclusion in multivariable models that adjusted for cardiovascular disease confounders, depressive symptoms were associated with lower T wave amplitude, while symptoms of anxiety were associated with higher T wave amplitude.

CONCLUSION:
In this group of men and women without known cardiovascular disease, depressive symptoms were associated with lower T wave amplitude while anxiety symptoms were unexpectedly associated with higher T wave amplitude. Further investigation of the associations of these negative mood states with cardiac repolarization is warranted.
Abstract 9416: Undiagnosed Peripheral Arterial Disease (PAD) is Common in Patients Referred for Stress Tests Without a History of Atherosclerotic Heart Disease
Authors: Narula Amar , Choy Shan Alana , Benenstein Ricardo , Konigsberg Matthew , Duan Daisy , Phillips Larry , Saric Muhamed , Reynolds Harmony R
Published: April 2024

Background:
The ankle brachial index (ABI) is a highly sensitive and specific method to diagnose peripheral arterial disease (PAD). Abnormal ABI (≤0.9 or ≥1.4) predicts cardiovascular events and mortality, independent of traditional risk factors. Post-exercise ABIs can identify additional individuals with hemodynamically significant PAD.

METHODS:
ABI was measured at rest and immediately post-exercise in patients referred for stress testing without known carotid, coronary, or peripheral atherosclerotic disease. ABI was classified as normal (1-1.39), borderline (0.91-0.99), low (≤0.9), or consistent with poorly compressible arteries (≥1.4). Abnormal post-exercise ABI was defined according to guidelines as a ≥20% decrease in ABI or a decline in ankle systolic blood pressure of ≥30 mmHg. ABIs were measured using automated oscillometric cuffs, which correlate well with Doppler and have excellent specificity.

RESULTS:
223 patients were enrolled in this ongoing study at the time of analysis, 108 of whom had post-exercise measurements. At rest, 20/223 (9%) had poorly compressible arteries, 7/223 (3.1%) had borderline ABI, and 1/223 (0.5%) had low ABI. Of those with normal ABI for whom post-exercise ABI was obtained, 34/108 (31.5%) had abnormal post-exercise ABI. Among patients with PAD by ABI, rates of use of aspirin (12/35), statins (9/35), and ACE-inhibitor/angiotensin receptor blockers (10/35) were low. Only 2 of 35 patients diagnosed with PAD had abnormal stress tests. 12 of the 223 patients overall had positive stress tests for ischemia.

CONCLUSIONS:
ABI measurement in patients referred for stress testing led to a diagnosis of peripheral vascular disease (poorly compressible arteries or PAD) in 24.6% of patients, despite low rates of ischemia on clinically indicated stress tests. ABI screening in this patient population may improve our ability to target use of guideline-recommended therapies for the prevention of cardiovascular events.
Abstract 9434: Post-infarct Treatment With Microrna145 Protects the Heart Against Myocardial Ischemia-reperfusion Injury Through Acceleration of Myocyte Autophagy
Authors: Higashi Kenshi , Yamada Yoshihisa , Kumazaki Minami , Aoyama Takuma , Baba Shinya , Minatoguchi Shingo , Ninigaki Kazuhiko , Takemura Genzou , Akao Yukihiro , Minatoguchi Shinya
Published: April 2024

Background:
We previously reported that microRNA145 (miRNA145) attenuates the ischemia-reperfusion injury. However, the mechanism how miRNA145 reduces the myocardial infarct size is still unclear.

Objective:
We aimed to investigate whether post-infarct treatment with miRNA145 reduces myocardial infarct size and its precise mechanism in a rabbit model of myocardial infarction.

Methods:
Male Japanese white rabbits underwent 30 min of coronary occlusion followed by 14 days of reperfusion. Rabbits received intravenous injection of saline (control group, n=7) or 0.035 mg/kg of miRNA145 encapsulated with liposome (miRNA145 group, n=7) immediately after reperfusion. At 14 days after reperefusion, rabbits were sacrificed and the hearts were removed. The area at risk and infarct areas were measured by evans blue dye and TTC staining, respectively. The infarct size was calculated as a percentage of the risk area of the left ventricle. Heart tissues were sampled and the morphological changes were investigated by electron microscopy, and the expression of LC3B, an indicator of autophagy, was assessed by western blot analysis. In another series of experiments, rat myoblast H9C2 were treated with 20 nM of miRNA145 and investigated the morphological changes by electron microscopy and the expression of LC3B by western blot analysis.

Results:
Post-infarct treatment with miRNA145 significantly reduced the myocardial infarct size (16.0±3.1 %) as compared to the control (28.7±6.1 %) group. Post-infarct treatment with miRNA145 significantly improved LV remodeling and improved ±dp/dt as compared to the control group. Both in vitro myoblast and in vivo experiments, treatment with miRNA145 induced autophagic changes such as autophagosome and autolysosome, and activated LC3B.

Conclusions:
It is suggested that post-infarct treatment with miRNA145 attenuated ischemia-reperfusion injury through acceleration of myocyte autophagy. The miRNA145 may be a promising strategy for treatment of acute myocardial infarction.
Abstract 9552: A Novel Human Cardiac Troponin T upstream Open Reading Frame Peptide Assists in the Diagnosis and Prognosis of NSTEMI Patients
Authors: Pemberton Chris J , Lee Jacqui , Bailey Mark , Aldous Sally , Young Joanna , Than Martin , Troughton Richard W , Richards Mark
Published: April 2024

Introduction:
High sensitivity assays for cardiac troponin (cTn) have reduced time to NSTEMI diagnosis but 5-10% of NSTEMI patients still remain cTn negative within 2 hours of presentation. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) could improve sensitivity to detect NSTEMI within 2 hours of hospital presentation.

Methods:
We developed a specific immunoassay for TnTuORF and measured plasma levels alongside NT-proBNP (Roche Elecsys), standard TnI (Abbott Architect), hsTnT (Roche Elecsys) and hFABP (Hycult Biotech) in 501 patients presenting to Christchurch Hospital, New Zealand with chest pain necessitating rule-out of ACS. Samples were taken at t=0, 1, 2 and 12-24 hours (index TnI) post-presentation along with all demographic, clinical and laboratory information. Correlation analysis was conducted using Spearman’s rank test. Biomarker diagnostic and prognostic efficiencies (AUC, sensitivity, specificity) were conducted using ROC analysis. P<0.05 was considered significant.

Results:
Plasma TnTuORF tended to display a negative relationship with TnI and hsTnT (r=-0.054, P=0.252) and did not diagnose NSTEMI (AUC=0.446, P=0.117). Instead, when applied as the denominator in a ratio with TnI/hsTnT (Table 1), TnTuORF could improve the sensitivity of both assays, but with reductions in specificity. The ratio TnI x hsTnT/TnTuORF (termed TroponinPLUS) gave the best sensitivity and detected 98% of NSTEMI patients. TroponinPLUS could predict death at 45 days (AUC=0.814, P=0.016, sensitivity = 0.80, specificity = 0.72) and 1 year (AUC=0.741, P<0.001, sensitivity = 0.67, specificity = 0.70).

Conclusion:
This is the first demonstration of a circulating uORF peptide. The ratio of total cTn to TnTuORF (TroponinPLUS) improved early detection of NSTEMI and has good prognostic ability. We conclude TnTuORF measurement may assist in NSTEMI diagnosis and prognosis.

Table 1. ROC data - NSTEMI diagnosis
Abstract 9629: Cathepsin K-Mediated Noich1 Activation Contributes to Neovascularization in Response to Hypoxia
Authors: Hu Lina , Cheng Xian Wu , Shi Guo-Ping , Jang Haiying , Inoue Aiko , Yamamura Yumiko , Wu Hongxian , Takeshita Kyosuke , Okumura Kenji , Murohara Toyoaki , Kuzuya Masafumi
Published: April 2024

Background:
Cysteine proteases play important roles in human pathobiology. This report shows the participation of cathepsin K (CatK) in ischemia-induced neovascularisation.

Methods and Results:
Left femoral artery ligation-induced ischemia in mice showed increased CatK expression and activity. CatK-deficient young and aged mice showed impaired functional recovery following hind ischemia. These mice also showed reduced levels of cleaved Notch1 (c-Notch1), vascular endothelial growth factor (VEGF), Flt-1 and phospho-Akt proteins of the ischemic muscles.
In vitro
, CatK knockdown reduced the levels of c-Notch1, VEGF and Flt1, essential molecules for angiogenesis and vasculogenesis. Together, the effects of CatK knockdown led to defective endothelial cell invasion, proliferation and tube formation. Recombinant human CatK degrades gama-secretase substrate in time- and dose dependent manners, suggesting CatK is involved in Notch1 activation. This was reinforced by the finding that CatK inhibition impairs Notch1 activation in response to hypoxia with no change in known gama-secretase activity.CatK-deficiency decreased circulating EPC-like CD31+/c-Kit+cells in mice of both ages. Transplantation of bone-marrow-derived mononuclear cells from CatK+/+ mice restored neovascularisation in CatK -/- mice.

Conclusions:
CatK activity controls neovascularisation via partial modulation of Notch1 signaling activation in response to hypoxia. Thus, CatK has a critical role in vascular formation and represents a new therapeutic target for vascular disease.
Abstract 9690: Impact of Lesion Morphology on Angiographic and Clinical Outcomes in Patients With Chronic Total Occlusion After Successful Recanalization With Drug-eluting stents. A Multislice Computed Tomography Study
Authors: Ito Tsuyoshi , Tsuchikane Etsuo , Nasu Kenya , Kimura Masashi , Terashima Mitsuyasu , Kinoshita Yoshihisa , Habara Maoto , Suzuki Takahiko
Published: April 2024

Background:
Which subgroup of patients with chronic total occlusion (CTO) would be likely to derive a benefit from percutaneous coronary intervention (PCI) in the drug-eluting stent (DES) era has not yet been fully clarified. The aim of this study was to investigate the morphological characteristics of CTO associated with angiographic and clinical adverse outcomes after PCI with DES using multislice computed tomography (MSCT).

Methods:
In this study, 263 patients who underwent MSCT before CTO-PCI were followed clinically (the median follow-up was 4.0 years). Of these, 1 year follow-up angiography was performed in 203 patients. Lesion morphology was assessed with MSCT. Angiographic restenosis, reocclusion, and MACE (a composite of cardiac death, stent thrombosis and target lesion revascularization) were analyzed.

Results:
MACE was observed in 36 patients (13.6%). Occlusion length was longer (39.5±19.9 mm vs. 22.3±13.7 mm, p<0.01), minimal vessel area was smaller (11.2±5.7mm
2
vs. 14.5±5.6mm
2
, p<0.01) and severe calcification (involving >50% of the coronary wall on cross sectional image) was more common (36% vs. 12%, p<0.01) in the MACE group. In multivariate analysis, occlusion length (Odds ratio (OR); 1.06, p<0.01), minimal vessel area (OR; 0.48, p<0.01) and severe calcification (OR; 3.57, p<0.01) were independent predictors of the MACE. Receiver operating characteristic analysis provided the cut-off value of occluded length (25.4 mm; area under the curve (AUC) 0.79; sensitivity 0.86, specificity 0.62) and minimal vessel area (11.9 mm
2
; AUC 0.69; sensitivity 0.62, specificity 0.72) to predict the MACE. We defined occluded length >25.4mm, minimal vessel area <11.9mm
2
and severe calcification as CT-derived risk factors. Angiographic restenosis (60% vs. 12% vs. 7%, p<0.01), reocclusion (29% vs. 2% vs. 2%, p<0.01), and MACE (43% vs. 6% vs. 3%, p<0.01) rates were significantly higher in patients with more than 2 risk factors than in those with 1 and 0.

Conclusions:
MSCT characteristics associated with angiographic and clinical adverse outcomes after CTO-PCI were occluded length, vessel area, and the degree of calcification.
Abstract 9797: Nur77 Inhibits Pulmonary Artery Smooth Muscle Cell Proliferation Though Targeting the STAT3/Pim-1/NFAT Axis
Authors: Liu Yan , Zhang Jian , Yi Bing , Chen Ming , Qi Jia , Sun Jian Xin
Published: April 2024

The orphan nuclear receptor 4A (NR4A) family plays critical roles in the regulation of cell proliferation, differentiation, and survival in cardiovascular system. However, the molecular mechanism underlying the regulation of NR4A receptor expression and its functional significance in pulmonary artery smooth muscle cell (PASMC) proliferation remain unclear. Here we investigated whether NR4A family regulates PASMC proliferation, and if so, to determine the mechanism involved. By using quantitative real-time PCR (qRT-PCR), we showed that orphan nuclear receptor Nur77 was the most abundant member of NR4A family expressed in rat PASMCs, as compared to other two members, NOR-1 and Nurr1. In rat PASMCs, the expression of Nur77 was robustly induced in response to several pathologic stimuli implicated in pulmonary artery hypertension (PAH), such as hypoxia, 5-hydroxytryptamine (5-HT), platelet derived growth factor (PDGF), and endothelin-1. Importantly, the protein levels of Nur77 are significantly increased in the lungs of monocrotaline (MCT) induced PAH rats. Furthermore, we demonstrated that 5-HT, a potent mitogen for PASMC, markedly up-regulated the Nur77 expression, through mitogen activated protein kinases/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway in rat PASMCs. Overexpression of Nur77 markedly inhibited 5-HT induced cell proliferation, and the expression of Cyclin D1 and proliferating cell nuclear antigen (PCNA) in rat PASMCs. Moreover, knockdown of Nur77 augments the 5-HT induced PASMC proliferation. Mechanistically, we demonstrated that Nur77 specifically interacts with STAT3, thus inhibiting its phosphorylation and the expression of its target genes, such as Pim-1, NFATc2, and survivin in PASMCs, which are critical for the PASMC proliferation and the development of PAH. These results indicate that Nur77 is a novel negative regulator for PASMC proliferation through inhibiting the STAT3/Pim-1/NFAT axis. Modulation of Nur77 activity may potentially represent a novel therapeutic strategy for the treatment of PAH.
Abstract 9813: Verifying Cardiac Mechanics From 3D-Wall Motion Tracking Processed for Rotation Determination
Authors: Ravi Sreyas , Meman Goshina , Zhu Meihua , Streiff Cole , Park Austin , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
This study assessed 3D-Wall Motion Tracking (3D-WMT) for determining rotation of a pumped heart model.

Methods:
Latex balloons were sutured inside the LV of 10 pig hearts and attached to a pulsatile pump. The heart phantom and a Toshiba Matrix Array PST-25SX 2.5 MHz Transducer were fixed within a water filled tank. The hearts were firmly attached to a rotating plate at the base and lightly affixed at the apex, and pumped at a stroke volume of 50ml while the base of the heart was variably rotated at 0, 3,5,7,10,12 and 15 degrees. Three images were acquired at each rotation setting and a 3D WMT program was used to assess cardiac rotation.

Results:
The 3D-WMT derived rotation angles were found to be most precise at physiologically normal values (3-5°), but consistently underestimated at angles greater than 5°. For the 3D-WMT calculated rotation, the mean and standard deviation at 0°,3°,5°,7°,10°,12°,15° was 1.049° ± 0.688°, 2.80° ± 0.647°, 4.178° ± 0.835°, 5.723° ± 0.851°,7.809° ± 0.815°, 9.131° ± 1.481°,11.144° ± 1.307°, respectively. The P value is less than 0.0001 A Bland Altman plot showed 96% of data were within a 95% confidence interval and a slight underestimation.

Conclusions:
Despite observed underestimation at higher degrees of rotation, Toshiba 3D-WMT may provide clinically important determinations of LV rotation.
Abstract 9855: Presence of J-waves or Slurs in Chest Pain Patients Predicts Higher Mortality in those Diagnosed as Acute Myocardial Infarction
Authors: Abächerli Roger , Twerenbold Raphael , Reichlin Tobias , Schmid Hans-Jakob , Frölicher Vic , Osswald Stefan , Müller Christian
Published: April 2024

BACKGROUND:
Although early repolarization is known as a benign, J-waves or slurs on the R wave downslope have recently been associated with sudden cardiac death. We investigated the presence and prognostic significance of R wav downslope phenomena in patients presenting chest pain at the emergency department.

METHODS:
We performed a retrospective study of 747 chest pain patients. The presence of a J-wave or slurs in the 12-lead resting ECG recorded at the emergency department was defined as a QRS notching and or QRS slurring of more than 0.1mV relative to the PR-interval (QRSonset) as coded by a single observer using enhanced imaging (RA). Final diagnosis was adjudicated by two independent cardiologists having access to all acquired data including a 2 year follow-up period.

Results:
Of the participants (mean of age 61.9, 67.1% males), 16% had an acute myocardial infarction, 17% an unstable angina, 12% with cardiac symptoms other than CAD, 46% non-cardiac symptoms and 9% symptoms of unknown origin. There was a significant correlation between patients presenting J-waves/slurs and days in hospital (p=0.04), know hypertonia (p=0.003), known CAD (p=0.05), prior MI (p=0.04), and presence of T negativity (p=0.005) but no significant correlation with ST-segment elevation or depression. There was a significant lower survival rate (0.90 versus 0.94, p=0.03, HR=1.81) in presence of J-waves primarily due to the AMI subgroup (0.72 versus 0.94, p=0.002, HR=4.71).

CONCLUSIONS:
From this analysis we found an overall association between comorbidities and the presence of J-waves or slurs at the emergency department. A significant higher mortality rate in patients J-waves or slurs was only found in patients who evolved AMI.
Abstract 9982: Long-term Administration of Type-I Interferon Leads to Premature Atherosclerosis
Authors: Diao Yanpeng , Lee Pui , Sautina Larysa , Mohandas Rajesh , Segal Mark
Published: April 2024

Introduction:
Disease states such as SLE, CMV, and HIV are associated with elevated type I interferon (IFN-I) and increased cardiovascular risk. Previously we have demonstrated that IFN-I has detrimental effects on endothelial progenitor cells that could contribute to the atherosclerosis. However, the relationship between IFN-I and smooth muscle progenitor cells (SMPC), cells derived from the bone marrow that can differentiate into mature SMC, has not been determined. We hypothesized that IFN-I could induce premature atherosclerosis by increasing the number of SMPC in the bloodstream and increasing the number of immature SMC within the vasculature.

Methods:
In vitro, SMPC isolated from wild-type (WT) and IFN receptor knock-out (IFNR-KO) animals, were cultured in medium plus or minus IFN-1. In vivo, two mice models of long-term IFN-I exposure (electroporation of an IFN-I plasmid, or Q 3 day IFN-I i.p. injection for 3 months) were studied and the number of SMPC and degree of atherosclerosis were analyzed.

Results:
The number of SMPC from WT animals was significantly increased when cultured in medium plus IFN-I. However, IFN-I had no effect in the SMPC from IFNR-KO mice. Increased SMPC numbers were also observed in mice treated with or that expressed IFN-I. In addition, atherosclerotic-like lesions were found in the arterial wall in WT mice expressing IFN-I. Within the lesions we observed CD34+/smooth muscle α-actin+ expressing cells (Fig). These cells did not express smooth muscle myosin heavy chain, suggesting that they were immature SMC.

Conclusions:
For the first time we demonstrated that elevated IFN-I levels, found in a number of disease states, could lead to an atherosclerosis-like lesion. In concert with our previous work, this work suggests a complex interplay between the bone marrow, circulating cells, and the vessel wall leading to IFN-I mediated atherosclerosis. This has profound implications for cardiovascular disease in a number of disease states.
Abstract 10103: Improvement in Survival With Favorable Neurological Outcome in Elderly Japanese Patients With Out-of-Hospital Cardiac Arrest: A Nationwide Observational Cohort Study
Authors: Funada Akira , Goto Yoshikazu , Maeda Tetsuo , Teramoto Ryota , Yamagishi Masakazu
Published: April 2024

Introduction:
Although older age is associated with worse prognosis after cardiac arrest, little is known about the improvement in survival of very elderly patients with out-of hospital cardiac arrest (OHCA).

Hypothesis:
We aimed to evaluate the survival trends and predictors of favorable prognosis in this population.

Method:
We analyzed the records of 607,147 OHCA events obtained from a prospectively collected nationwide Utstein-style Japanese database from 2008 to 2012. The end-point was 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2).

Results:
In total, 334,730 OHCA patients aged ≥75 years were eligible for analyses. The overall 1-month CPC 1-2 rate was 0.88% (2,933/334,730). OHCA aged 75-84 years had better 1-month CPC 1-2 rate than those ≥85years (1.18% [2,067/174,781] vs 0.54% [866/159,949], p <0.0001). The 1-month CPC 1-2 rate improved in OHCA aged ≥75 years (0.73% [433/59,595] in 2008 to 0.96% [708/73,487] in 2012, p for trend <0.001), even in only OHCA aged ≥85 years (0.42% [115/27,163] in 2008 to 0.65% [241/36,860] in 2012, p for trend <0.0001). Multivariate logistic regression analysis indicated that bystander-witnessed arrest (adjusted odds ratio [aOR] 5.7, 95% confidential interval [CI] 5.2–6.3, p <0.0001) and initial shockable rhythm (aOR 10.6, 95% CI 9.8–11.5, p <0.0001) were significantly associated with 1-month CPC 1-2 rates of OHCA aged ≥75 years. OHCA with bystander witness and initial shockable rhythm had a higher 1-month CPC 1-2 rate than the others (11.14% [1,061/9,520] vs 0.58% [1,872/325,210], p <0.0001, aOR 19.1, 95% CI 17.6–20.7, p <0.0001). The 1-month CPC 1-2 rate of OHCA with initial unshockable rhythm also improved 0.42% (239/56,927) in 2008 to 0.60% (420/70,583) in 2012 (p for trend <0.001); however, in OHCA without bystander witness, the 1-month CPC 1-2 rate did not improve between 2008 (0.19% [71/36,736]) and 2012 (0.28% [125/45,224]) (p for trend = 0.080).

Conclusion:
Data drawn from a large subset of elderly patients in Japanese registry suggest that rate of 1-month CPC 1-2 from OHCA have significantly improved during the study period; however, the OHCA outcome differed by bystander-witness and first documented rhythm.
Abstract 10244: Heartmatters Challenge: Therapeutic Lifestyle Program Reduces Cardiovascular Risk Factors and Weight in First Responders Using Personalized Nutrition, Phone-based Coaching and Online Food Journaling
Authors: Gill Rosalynn D , Thai Ngoc H , Jones Briana E , Ghosh Debanjali , Mehan Michael R , Jack Kepra , McCarthy Megan M , Dansinger Michael L
Published: April 2024

Objective:
Premature CVD death is common among first responders. Effective risk reduction programs are urgently needed to address this public health concern. We tested the one year effectiveness of a lifestyle-based intervention program in police officers and firefighters in the Boston and Phoenix areas.

Methods:
173 participants with excess abdominal fat or CVD risk were assigned to a one year intervention or control group using cluster randomization by city. The intervention was comprised of a personalized nutrition plan based on an algorithm combining laboratory results with food preferences, phone coaching to encourage adherence to lifestyle recommendations including healthy eating and exercise and online food journaling.

Results:
130 participants remained in the study for one year (68 intervention; 62 control). In the intervention group the mean weight loss from baseline was 4.8% (4.9 kg, p<0.01) at 6 months and 3.1% (3.2 kg, p<0.01) from baseline at 1 year; waist circumference reduction was 3.6% (4.1 cm, p<0.01) at 6 months and 3.2% (3.6 cm, p<0.01) at 1 year. Large HDL particles increased 64.4% (9.0 mg/dL, p<0.01) at 6 months and 29.6% (3.8 mg/dL, p<0.01) at 1 year; HDL-C increased 9.3% (3.3mg/dL, p<0.01) at 6 months and 8.4% (3.5 mg/dL, p<0.01); and LDL-C decreased 2.6% (5 mg/dL, NS) at 6 months and increased 1.7% (+0.2 mg/dL, NS) at 1 year. There was no meaningful change in the control group. Adherence to the lifestyle program was a major contributor to individual success over the year. An adherence score was developed based on coaching frequency. Participants with adherence scores above the mean (N=21) reduced LDL-C levels 8.8 mg/dL whereas participants with adherence scores below the mean (N=47) exhibited an increase of 4.2 mg/dL (p<0.05). Other favorable trends included greater weight loss (5.4kg vs 2.1 kg, (NS)), greater increases in large HDL particles (5.9mg/dL vs 2.8 mg/dL (NS)) and greater waist circumference reduction ( 5.3 cm vs 2.6 cm (NS)).

Conclusions:
Clinically meaningful reductions in CVD risk are achievable in actual practice using carefully designed lifestyle programs in combination with phone-based coaching and online food journaling tools. These data support the use of such programs on a national level.
Abstract 10452: The SYMPLICITY HF Feasibility Study: Twelve Month Outcomes of Renal Denervation in Patients With Chronic Heart Failure and Renal Impairment
Authors: Krum Henry , Cohen Sidney A
Published: April 2024

Introduction:
Renal dysfunction often develops in patients with heart failure with low ejection fraction due to hemodynamic and neurohumoral dysfunction leading to increased risk for mortality.

Methods:
The multi-center, prospective, open label Renal Denervation in Patients With Chronic Heart Failure & Renal Impairment (SYMPLICITY HF) trial enrolled NYHA Class II-III patients with left ventricular ejection fraction (LVEF) <40% and estimated glomerular filtration rate (eGFR) 30 to 75 mL/min/1.73m
2
. Subjects with systolic blood pressure < 90 mm Hg were excluded. The primary objective was to evaluate both the safety and physiologic response of renal denervation therapy on cardiac and renal function with the Symplicity™ renal denervation system using the Symplicity Flex™ catheter (Medtronic, Inc).

Results:
A total of 39 patients were enrolled (Table). No vascular complications occurred during the procedure. Available at AHA 2015 will be outcomes to 12 months follow up, including safety, cardiac function by echocardiography, and renal function by eGFR. Additionally, 9 subjects participated in a sub study that evaluated cardiac and renal noradrenaline spillover, muscle sympathetic nerve activity, and electrophysiological parameters by Holter monitor.

Conclusions:
Twelve-month outcomes in SYMPLICITY HF will provide initial insights into the safety and cardiac and renal physiologic impact of renal denervation in patients with heart failure.
Abstract 10854: Ghrelin Promotes Functional Angiogenesis in a Mouse Model Of Critical Limb Ischemia Through Activation of Pro-angiogenic MicroRNAs
Authors: Katare Rajesh , Rawal Shruti , Munasinghe Pujika E , Dixit Parul , Tsuchimochi Hirotsugu , Inagaki Tadakatsu , Fujii Yutaka , Umetani Keiji , Kangawa Kenji , Shirai Mikiyasu , Schwenke Daryl
Published: April 2024

Background:
Current therapeutic strategies for the treatment of critical limb ischemia (CLI) have only limited success. Recent
in vitro
evidence in the literature, using cell lines, proposes that the peptide hormone ghrelin may have angiogenic properties.

Objective:
To investigate if ghrelin could promote post-ischemic angiogenesis in a mouse model of CLI and identify the mechanistic pathway(s) that underpin ghrelin’s pro-angiogenic properties.

Methods and Results:
CLI was induced in male CD1 mice by femoral artery ligation. Animals were then randomized to receive either vehicle or ghrelin (Ghr,150μg/kg/sc) for 14 consecutive days. Subsequently, Synchrotron Radiation microangiography was used to assess hindlimb perfusion. Ischemia alone stimulated the generation of new microvessels typically having an ID < 80 μm, however, the magnitude of ‘angiogenesis’ was significantly augmented in ghrelin-treated mice (13.9 ± 1.3 vessels in CLI+Ghr mice vs. 7.6 ± 0.9 vessels in CLI+Vehicle mice,
P
< 0.05). Moreover, the newly formed vessels of only the ghrelin-treated CLI mice were both structurally and functionally normal; evident by robust endothelium-dependent vasodilatory responses to acetylcholine. Histological analysis showed marked increase in the number of arterioles in Ghrelin treated group (81±8/mm
2
in vehicle treated group vs. 134±11/mm
2
in Ghrelin treated group, P<0.01, n=5), confirming the angiography data. Molecular analysis revealed that ghrelin’s angiogenic properties were linked to activation of pro-survival Akt/VEGF/Bcl-2 signaling cascade, thus reducing the apoptotic cell death and subsequent fibrosis. Furtherstill, ghrelin treatment activated pro-angiogenic (miR-126, -132 and -27a) and anti-fibrotic (miR-30a) microRNAs while inhibiting anti-angiogenic (miR-92a and -206) microRNAs. Further,
in vitro
knockdown of miR-126 and miR-132 in human umblical vein endothelial cells markedly attenuated the angiogenic potential of ghrelin, as evaluated by decreased proliferation and tube forming capacity (P<0.05).

Conclusion:
Ghrelin therapy significantly restored the blood flow to the ischemic hind limb by accelerating the formation of new functional arterioles through activation of pro-angiogenic microRNAs.
Abstract 10858: Significant Association Between Washout Ratio of Renal 123i-metaiodobenzylguanidine and Muscle Sympathetic Nerve Activity in Patients With Hypertension
Authors: Okabe Yoshitaka , Murai Hisayosi , usui souichiro , Furusho Hiroshi , Takamura Masayuki
Published: April 2024

Background:
Simplicity HTN-3 trial showed the negative result for renal denervation (RDN) in patient with resistant hypertension. One of limitations was that no appreciate evaluation of renal sympathetic nerve activity (RSNA) was applied before and after RDN. 123I-MIBG has been used to assess the cardiac sympathetic nerve activity. However, it remains unclear whether 123I-MIBG in kidney would reflect sympathetic nerve activity. In this study, we investigated the relationship renal 123I- MIBG and muscle sympathetic nerve activity (MSNA).

Methods:
31 hypertensive patients were included in this study. MSNA was recorded from the peroneal nerve to evaluate direct sympathetic nerve activity to peripheral vascular bed. Images of 123I-MIBG were taken using the low-medium-energy general purpose collimator. An 111MBq dose of 123I-MIBG was injected intravenously at rest for the MIBG study. 123I-MIBG planar and SPECT studies were performed at 20min (early) and 3hr (delayed) after injection. In the planar study, a region of interest (ROI) was set over the heart and a rectangular ROI on the upper third of the mediastium and kidney cortex. The early and delayed heart-to-mediastinum average count ratios (H/M) and kidney-to-mediastinum average count ratios (K/M) were calculated. Washout rate (WR) of heart and kidney were also calculated.

Results:
Average systolic and diastolic blood pressure was 118±18/67±15 mmHg. Average estimated glomerular filtration rate was 71.5±22.4 ml/min/1.73m2 that was not related to renal 123I-MIBG. As expected, MSNA had significant negative relationship with delayed H/M in cardiac 123I-MIBG image (r=-0.37, p<0.01) and positive relationship with WR of cardiac 123I-MIBG (r=0.45, p<0.01). With regard to kidney, WR of 123I-MIBG of each left and right renal MIBG showed a significant correlation with MSNA (right kidney: r=0.56, p<0.01, left kidney: r=0.60, p<0.01, respectively), but not with early and delayed K/M in renal 123I-MIBG.

Conclusions:
Our study showed that WR of renal 123I-MIBG was associated with MSNA, indicating that WR of renal 123I-MIBG might reflect RSNA. These results suggest that renal 123I-MIBG might be available to assess sympathetic nerve activity as well as MSNA.
Abstract 10888: Impact of Sodium Bicarbonate on Survival in Patients With Prolonged Out-of-Hospital Cardiac Arrest; SOS-KANTO study 2002 & 2012
Authors: Shinozaki Koichiro , Ogasawara Tomoko , Oda Shigeto , Sakurai Atsushi , Tahara Yoshio , Yohemoto Naohiro , Nagao Ken , Yaguchi Arino , Morimura Naoto ,   SOS-KANTO 2012 Sudy Group
Published: April 2024

Introduction:
The impact of sodium bicarbonate (SB) usage on survival outcomes in patients who have prolonged cardiac arrest (CA) remains unclear. A change in the overall use of SB has occurred over the last decade due to changes in ILCOR recommendations. This natural experiment in the SB use provides an opportunity to explore the association of SB and possible benefits in survival from CA.

Objective:
To evaluate the association between SB use and outcomes of CA patients; and to describe temporal patterns of SB use and factors related to SB usage

Methods:
In 2002-03 and 2012-13, we identified 9,592 and 16,452 patients, respectively, from two cohorts in Japan. All adult OHCA patients were included. Patients who gained return of spontaneous circulation in pre-hospital settings were excluded as prolonged CA was selected. The primary and secondary outcomes were successful hospital admission and 1 month survival. Factors associated with SB usage were assessed by multivariable logistic regression analysis.

Results:
Overall SB usage decreased from 17.3% (n=6,652) in 2002, to 9.7% (n=10,970) in 2012. Patients who received SB had significantly higher rates of admission compared with non-SB patients during both time periods (33.8% vs. 15.4% in 2002, and 39.3% vs. 17.2% in 2012, respectively, p<.001) and significantly higher 1m-survival (4.8% vs. 2.1%, and 4.1% vs. 1.9%, p<.001). Logistic regression demonstrated that SB use was significantly associated with admission (adjusted odds ratio, 2.74 [95%CI 2.29-3.27], p<0.001 in 2002, and 2.68 [2.27-3.18], p<0.001 in 2012) and 1m-survival (2.07 [1.42-3.01], p<0.001, and 1.55 [1.05-2.29], p=0.03) adjusting for possible confounders. Intubation and defibrillation within the ER were most associated with SB usage in both cohorts, while blood pH, potassium levels, and cause of poisoning were not associated with SB use in either cohort.

Conclusions:
SB usage was associated with increased survival rates in patients with OHCA transported to the ED in CA. Factors related to current CPR guidelines, that suggest more prolonged ED efforts such as intubation and defibrillation are associated with SB use. Surprisingly blood pH showed no association with SB use. Additional studies on the optimal role for SB during CA seem warranted.
Abstract 10940: Distensibility of the Pulmonary Circulation During Exercise in Heart Failure
Authors: Dhakal Bishnu P , Malhotra Rajeev , Pappagianopoulos Paul P , Eisman Aaron S , Lewis Gregory D
Published: April 2024

Background:
Pulmonary vascular distensibility (PVD) permits the pulmonary arteries to increase in size to accommodate increased blood flow and is measured as the percent increase in pulmonary vessel diameter per mmHg increase in pressure. We hypothesized that impaired PVD is related to reduced functional capacity in patients with heart failure (HF) or pulmonary arterial hypertension (PAH).

Methods and Results:
Patients with HF and preserved ejection fraction (HFpEF, n=48), HF and reduced ejection fraction (HFrEF, n=55), PAH (n=18), and age matched controls (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PVD was lowest in the PAH group (mean±SD 0.36±0.25% per mmHg) and intermediate in the HFpEF and HFrEF groups (0.92±0.39 and 0.84±0.33% per mmHg, respectively) compared to controls (1.39±0.32, P<0.0001 for all three, Fig. 1A). PVD was strongly associated with measurements of right ventricular-pulmonary vascular function during exercise including change in RVEF (ρ=0.39, P<0.0001, Fig. 1B) and change in pulmonary vascular resistance (ρ=-0.51, P<0.0001) with exercise. PVD was an independent predictor of peak VO2 in a multivariate model that included age, gender, hemoglobin, resting cardiac index, resting LVEF, and resting mean pulmonary artery pressure. 14 out of 26 HFrEF patients who were treated with sildenafil (25-75 mg orally TID) for 12 weeks demonstrated a 24.6% increase in PVD (p=0.015) compared to no change in PVD in those treated with placebo (n=12).

Conclusions:
Pulmonary vascular distensibility is reduced in patients with HF and PAH and is closely related to functional capacity and RV systolic function during exercise. Furthermore, distensibility was modifiable with selective pulmonary vasodilator therapy, suggesting that distensibility of the pulmonary vessels may be an important therapeutic target in the treatment of HF and pulmonary hypertension.
Abstract 10944: The Optimal Definition of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions
Authors: Parsh Jessica , Seth Milan , Briguori Carlo , Grossman Paul , Solomon Richard , Gurm Hitinder
Published: April 2024

Background:
Multiple definitions exist for contrast induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions (PCI). It is unknown which definition is best associated with adverse events and whether this association is stable across patients with various degrees of baseline renal function.

Hypothesis:
We hypothesized that commonly used CI-AKI definitions would not be stable in risk prediction for mortality across the spectrum of renal function. Further, we sought to identify the optimal CI-AKI definition which would be both highly predictive of mortality and stable in its association regardless of baseline renal function.

Methods:
We applied logistic regression models to multiple current CI-AKI definitions to examine the impact of baseline renal function on a candidate CI-AKI definition’s correlation with the adverse outcome of mortality. We then utilized Likelihood ratios to examine candidate definitions and identify those where association with mortality remained constant regardless of baseline serum creatinine (SCr). These definitions were then assessed for specificity, sensitivity and positive and negative predictive values to identify an optimal definition.

Results:
Our study cohort comprised of 119,554 patients who underwent PCI in the state of Michigan between 2010-2014. Most commonly used definitions were not associated with mortality in a constant fashion across baseline renal function. Of the 266 candidate definitions examined, 16 definition’s association with mortality was not significantly altered by baseline SCr. CI-AKI defined as an absolute increase of SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for mortality.

Conclusions:
We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50%. Further work is needed to validate this definition in independent studies, in other clinical settings, and to establish its utility for clinical trials and quality improvement efforts.
Abstract 10997: Catheter Ablation of Non-paroxysmal Atrial Fibrillation Using Sinus Rhythm Defragmentation Plus Low Voltage Zone Homogenization After Pulmonary Vein Isolation: 30 Months’ Outcome From Nonrandomized Comparison With Stepwise Approach
Authors: Yang Gang , Yang Bing , Wei Youquan , Zhang Fengxiang , Ju Weizhu , Chen Hongwu , Li Mingfang , Gu Kai , Lin Yazhou , Wang Benqi , Cao Kejiang , Kojodjojo Pipin , Chen Minglong
Published: April 2024

Introduction:
The high prevalence of postprocedural atrial tachycardia (AT) reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat non-paraxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low voltage zones (LVZ) and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium (LA) after circumferential pulmonary vein isolation (CPVI) and cavotricuspid isthmus (CTI) ablation in NPAF patients is superior to the widely practiced step-wise approach for NPAF ablation.

Methods and Results:
86 consecutive patients with NPAF (persistent or longstanding) were enrolled in study group. Following CPVI, CTI ablation and cardioversion to SR, high density mapping of LA was performed. Areas with LVZ and SR-AE were targeted for further homogenization and elimination respectively. 78 consecutive sex- and age- matched NPAF patients who were treated with the stepwise approach served as the historical control group. AF recurrence was assessed with Holters and regular clinic visits. In the study group, 92% (79/86) were successfully cardioverted after CPVI and CTI ablation. The remaining 8% (7/86) underwent further ablation in a stepwise approach to restore SR. Among the patients converted to SR, 70% (55/79) had LVZ and SR-AE and received additional ablation whereas in 30% (24/79) without SR-AE or LVZ, no further ablation was performed. Over the similar follow-up period (30 ± 8 vs. 33 ± 10 months), 66% (57/86) were free from recurrence and 3.5% (3/86) developed postprocedural AT after a single procedure in study group, compared to 37% (29/78) overall success rate and 30% (24/78) AT incidence in control group. (P=0.011 and P=0.0003, respectively).

Conclusions:
A strategy of selective electrophysiological substrate modification in sinus rhythm after CPVI and CTI ablation is clinically more effective than the stepwise approach for NPAF ablation.
Abstract 11016: Bag3 Regulates Contractility and Ca Homeostasis in Adult Mouse Ventricular Myocytes
Authors: Feldman Arthur M , Wang JuFang , Song Jianliang , Zhang Xue-Qian , Tilley Douglas D , Gao Erhe , Koch Walter J , Gordon Jennifer , Khalili Kamel , Cheung Joseph Y
Published: April 2024

Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations are associated with familial dilated cardiomyopathy and reduced BAG3 expression was observed in murine transverse aortic constriction and porcine myocardial infarction models. BAG3 is expressed in the sarcolemma and t-tubules in adult myocytes. To simulate reduced BAG3 expression in disease states, we downregulated BAG3 in adult myocytes by shRNA (shBAG3). Despite ~50% reduction in BAG3 by shRNA, expression of α-subunit of L-type Ca channel, SR Ca-ATPase, Na/Ca exchanger, α1- and α2-subunits of Na-K-ATPase, and ryanodine receptor was unchanged. At baseline, BAG3 downregulation had no effect on myocyte contraction and [Ca]i dynamics. After isoproterenol, BAG3 downregulation resulted in reduced myocyte contraction amplitudes, shortening and re-lengthening velocities, lower systolic [Ca]i and [Ca]i transient amplitudes, and prolongation in both APD50 and APD90. L-type Ca current (ICa) and sarcoplasmic reticulum (SR) Ca content but not Na/Ca exchange current or SR Ca uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes. On the other hand, BAG3 overexpression resulted in enhanced myocyte contractility after isoproterenol. In addition, BAG3 overexpression rescued the depressed contraction amplitudes in myocytes overexpressing the HIV protein Tat, and improved myocardial contractility in Tg26 (HIV-1 transgenic) mice. We conclude: (1) BAG3 modulates myocyte contraction, Ca dynamics and action potential duration by regulating ion channels and provides a novel paradigm for contractile dysfunction and increased arrhythmia risks in familial dilated cardiomyopathy; (2) BAG3 is a therapeutic target for cardiomyopathy including HIV-associated cardiomyopathy.
Abstract 11497: Focal Hibernating Myocardium -A Novel Method to Assess Ventricular Arrhythmogencity Using Molecular Imaging
Authors: Abdulghani Mohammed , Miller Brian , Smith Mark , Chen Wengen , Ume Kiddy L , Bob-Manuel Tamunoinemi , Imanli Hasan , Saliaris Anastasios , See Vincent , Shorofsky Stephen , Dilsizian Vasken , Dickfeld Timm
Published: April 2024

Introduction:
Hibernating myocardium is associated with increased ventricular tachyarrhythmias and sudden cardiac death. Current algorithms aim to detect only large areas of left ventricular hibernation, likely to respond to revascularization and improve LV EF. However, no current tools allow the determination of small and focal hibernating areas within the ischemic substrate, which could act as VT trigger and substrate modulators, and initiate or maintain ventricular arrhythmias.

Methods:
Custom-made Matlab-based software was developed to perform quantitative segmental analysis. Patients with ischemic cardiomyopathy undergoing VT ablation underwent pre-procedural FDG and Rubidium-PET/Technicum SPECT to determine the metabolic and perfusion characteristics of the LV myocardium. After co-registering the voxel-based tracer intensity information was transferred into a 36 x 21 +1 matrix (757 segments analysis). After normalization comparative analysis identified functional categories of LV myocardium (normal:>75% uptake perfusion[p]/metabolism[M]; hibernation: P and MP+20% or P>50% but P+20%; matched scar P and M<50%).

Results:
Software was evaluated on metabolism/perfusion scans of 8 patients undergoing VT ablation. While all patients had reported scar, only 2/8 patients (25%) had clinically identified area of hibernation using the currently clinically employed nuclear medicine algorithm. All DICOM files were successfully uploaded into the software module, transformed and analyzed using the pre-specified functional categories of LV myocardium. Post-analysis polar plots of all patients demonstrated matched scar as seen during the clinical read. However, focal areas of hibernation were detected in all patients using the 757 algorithm analytical tool (100% vs. 25% for 757 segmental vs. standard clinical analysis, P<0.001) often adjacent to pre-specified scar category.

ConclusioN:
The novel quantitative 757 segmental analysis is able to detect and localize focal areas of hibernation in all patients with ischemic VT substrate. This allows the use of molecular imaging techniques to identify potentially proarrhythmic VT trigger and modulators and design novel diagnostic and therapeutic strategies.