bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17564: Long-term Risk of Stroke in Patients With Type 1 and Type 2 Diabetes Following Coronary Artery Bypass Grafting
Authors: Holzmann Martin , Nyström Thomas , Sartipy Ulrik
Published: July 2021

Background:
We performed a nationwide population-based cohort study to investigate the long-term risk of stroke after coronary artery bypass grafting (CABG) in patients with type 1 and type 2 diabetes.

Hypothesis:
Type 1 and type 2 diabetes is associated with an increased longterm risk of stroke after CABG.

Methods and Results:
All patients who underwent primary CABG in Sweden from 2000 through 2011 were included from the SWEDEHEART register. We excluded patients with prior stroke, and patients who had a stroke or died within 30 days of surgery. The National Diabetes Register was used to identify patients with type 1 and type 2 diabetes. Incident stroke (ischemic and hemorrhagic), and all-cause mortality was obtained by record linkage with the National Patient Register and the Cause of Death register. A total of 53 820 patients (type 1 diabetes (n=714), type 2 diabetes (n=10 054), no diabetes (n=43 052)) were included. During a mean follow-up of 7.4 years (398 337 person-years), in total, 8.0% (n=4 296) of the patients had a stroke: 7.3% (n=52) in patients with type 1 diabetes, 9.1% (n=915) in patients with type 2 diabetes, and 7.7% (n=3 329) in patients with no diabetes. The multivariable adjusted hazard ratio (95% confidence interval) for all stroke was 1.59 (1.20-2.11) in type 1 diabetes, and 1.32 (1.23-1.43) in type 2 diabetes compared to patients without diabetes. Figure 1 shows the age-adjusted cumulative incidence of stroke in relation to type 1 diabetes, type 2 diabetes and no diabetes.

Conclusions:
The long-term risk for stroke after CABG was higher in both patients with type 1 diabetes, and type 2 diabetes, compared to patients without diabetes.
Abstract 17573: Epinephrine Dosing Interval and Survival Outcomes During Pediatric In-hospital Cardiac Arrest
Authors: Hoyme Derek B , Patel Sonali S , Samson Ricardo A , Raymond Tia T , Nadkarni Vinay M , Atkins Dianne L
Published: July 2021

Background:
American Heart Association (AHA) guidelines recommend administration of epinephrine (epi) every 3 to 5 minutes during CPR to improve systemic blood pressure and coronary perfusion pressure. In adults with in-hospital cardiac arrest (IHCA), longer dosing intervals are associated with improved survival to hospital discharge. The purpose of this study is to investigate whether longer epi dosing intervals are associated with improved survival to hospital discharge after pediatric IHCA.

Methods:
A retrospective review of the AHA Get With The Guidelines-Resuscitation registry identified 1,260 pediatric IHCAs that met our inclusion criteria: index IHCA event; no vasoactive infusion in place or alternate vasoactive medication boluses; > 1 dose of epi administered; not located in delivery room, nursery, NICU or obstetrical units. For each arrest, an epi dosing interval was defined by dividing the duration of resuscitation after the first dose of epi by the total doses given. This was necessary as the database does not provide time of individual epi doses. For analysis, epi dosing intervals were categorized as 1 to <5 minutes/dose, 5 to <8 minutes/dose, and 8 to 10 minutes/dose. Multivariable logistic regression models were constructed controlling for age, gender, illness category, location of arrest, and arrest duration to evaluate the relationship of epi dosing intervals on survival to discharge. Odds ratios were calculated using the 1 to <5 minutes/dose interval as the reference.

Results:
Table 1 displays the descriptive characteristics of the patients and subsequent events. Adjusted odds ratio for survival to hospital discharge for dosing interval of 5 to <8 minutes was 1.454 (95% CI 1.014-2.084) and for 8 to 10 minutes was 1.945 (95% CI 1.094-3.459).

Conclusions:
Longer dosing intervals than those currently recommended by the AHA guidelines for epinephrine administration during pediatric IHCA are associated with improved survival to hospital discharge.
Abstract 17582: Monitoring Novel Anticoagulants Dabigatron, Rivaroxaban and Apixaban Using Modified Thrombelastography
Authors: Artang Ramin , Galloway Gregg , Dalsgaard Nielsen Jorn
Published: July 2021

Background:
Novel anticoagulants NOACS dabigatran DABI rivaroxaban RIVA and apixaban APIX do not require routine monitoring. There are situations where monitoring would be useful including bleedings, trauma, and thromboembolic events while on anticoagulation.

The aim of this in vivo study was to assess the anticoagulant effect of NOACS with novel modified TEG assay containing ecarin and factor Xa concentrate.

Methods:
9 healthy male volunteers were given single dose of oral DABI 150mg or RIVA 20mg or APIX 5mg and were phlebotomized at 0, 1 and 3 hours after intake of NOAC. Reaction time R was measured using TEG®5000. Concentrations (conc.) of DABI, RIVA and APIX were measured using chromogenic assay Biophen® DTI and DiXaI. Based on available literature on pharmacokinetics of NOACS, clinical range for each agent was estimated. The R values was correlated to the drug conc. and sensitivity SN, specificity SP, positive and negative predictive values (PPV&NPV) for the minimum therapeutic range of each agent was calculated.

Results:
Using Ecarin assay, R was highly correlated with DABI conc. r = 0.96, p < 0.0001. R value of >5.7 had 88% SN 100% SP, 100% PPV and 95% NPV for DABI conc. of >50ng/ml.

Using Factor Xa assay, R was highly correlated with RIVA conc. r = 0.89, p < 0.0001. R value of >4.8 had 94% SN, 100% SP, 100% PPV, and 92% NPV for RIVA conc. of >100ng/ml.

Using Factor Xa assay R was highly correlated with APIX conc. r = 0.86, p < 0.0001. R value of >4.3 had 93% SN, 100% SP, 100 PPV and 93% NPV for APIX conc. of >50ng/ml.

Conclusion:
We have for the first time demonstrated that TEG® point-of-care device can monitor the NOACS effect on the hemostasis with highly significant correlation with the drug levels of each agent. This novel technology is easy to use on whole blood without need for specialized expertise. Larger clinical studies are warranted for correlation of TEG findings and clinical outcome.
Abstract 17623: A Case of Biopsy-proven Immunoglobulin G4-Related Disease Associated With Multiple Giant Coronary Artery Aneurysms, Peripheral Arterial Aneurysms, End Stage Renal Disease, and Heart Failure
Authors: Benson Mark D , Byrne-Dugan Cathryn , Adler Dale , Feinberg Mark , Bhatt Deepak
Published: July 2021

A 54-year-old man with remote large cell non-Hodgkin’s lymphoma in remission following R-CHOP and severe atopic dermatitis was transferred from another hospital with a non-ST elevation myocardial infarction. Over the preceding year, the patient had suffered recurrent admissions for acutely decompensated heart failure with a newly depressed left ventricular ejection fraction (LVEF) of 20% by echocardiography and rapidly progressive end-stage renal disease of unclear etiology requiring the initiation of hemodialysis. Prior workup had demonstrated an infrarenal abdominal aortic aneurysm and bilateral common iliac artery aneurysms with subsequent computed tomography (CT) additionally demonstrating a superior mesenteric artery aneurysm. The patient was taken for immediate coronary arteriography, which demonstrated giant aneurysms in the left main and right coronary arteries, as well as multivessel severe stenoses. CT coronary angiogram demonstrated significant circumferential wall thickening throughout the coronary vasculature. Given concern for IgG4-related disease (IgG4-RD), a renal biopsy was pursued that confirmed the diagnosis. 18F-fluorodeoxyglucose positron emission tomography-CT identified only mild aortic inflammation. The patient was treated with high-dose steroids and rituximab. The serological inflammatory markers improved, and he underwent coronary artery bypass grafting. Pericardial, aortic adventitial, left internal mammary artery, and saphenous vein biopsies showed cardiovascular involvement of IgG4-RD. The patient has been maintained on rituximab with normalization of his LVEF and no recurrence of chest pain over the past eighteen months. IgG4-RD is a fibroinflammatory systemic disease newly described in 2003 and only recently found to involve the cardiovascular system with several reports of peripheral aneurysmal disease. To our knowledge, the current case represents the first report of a patient successfully treated for biopsy-proven IgG4-RD associated with coronary artery disease and left ventricular systolic dysfunction. IgG4-RD may represent a novel mechanism underlying some forms of peripheral and coronary arterial disease and may offer new insights into vascular biology.
Abstract 17627: Is the Post-menopausal Rise in PCSK9 Levels Due to Loss of the Estrogen Responsive Anti-atherogenic Protein, Heat Shock Protein 27? Insights Into a Potential New PCSK9 Lowering Therapy
Authors: Bakala N'Goma Jean-Claude , Shi Chunhua , Pulakazhi Venu Vivek Krishna , Chen Yong-Xiang , O'Brien Edward R
Published: July 2021

Introduction:
Previously we reported that elevated serum levels of Heat Shock Protein 27 represent a predictive biomarker of reduced cardiovascular clinical events. Moreover, attenuation of experimental atherogenesis, characterized by reduced cholesterol levels in both the artery wall and serum, can be achieved by augmenting serum HSP27 levels (e.g., with recombinant HSP27). PCSK9 plays a central role in regulating the abundance of hepatic LDL-receptors, and hence serum and plaque cholesterol levels. Interestingly, PCSK9 levels rise with menopause (Dallas Heart Study) and we previously published that HSP27 levels are markedly attenuated post-ovariectomy. Hence, we hypothesize that HSP27 augments hepatic cholesterol uptake via reductions in PCSK9 levels.

Methods / Results:
1. In vitro studies: HepG2 (liver) cells were maintained in culture for 24 hours with or without rHSP27. The hepatic levels of apoB100 did not change with rHSP27 treatment. ApoB100 containing lipoproteins were reduced in the cell culture media with rHSP27 treatment (Western Blot: p=0.008; ELISA: p=0.0025). rHSP27 treatment reduced hepatic PCSK9 protein levels (Western Blot: p=0.019), increased LDL receptor protein levels (Western Blot: p=0.001) and increased (fluorescent) LDL uptake (p=0.022). Levels of hepatic SREBP2 and HMG-CoA reductase proteins were unaltered with rHSP27 treatment.

2. In vivo studies: Female ApoE-/- mice fed high fat diet and injected weekly with rHSP27 or PBS for 8 weeks. Serum total cholesterol and plasma PCSK9 levels were ~20-40% lower in the rHSP27 treated vs. control mice. Mice treated with rHSP27 showed reductions in aortic lesion area of ~40% for en face and ~35% for cross-sectional sinus tissue sections.

Conclusions:
These findings suggest that HSP27, an endogenous estrogen responsive protein, can lower extracellular cholesterol levels by reducing PCSK9 expression. Hence there is promise for the development of HSP27 “replacement” therapy for the prevention and modification of atherosclerosis via reductions in PCSK9 expression. Current clinical studies examining the relationship between HSP27 and PCSK9 levels in women undergoing prophylactic ovariectomy for BRAC1/2 (i.e., the “Angelina Effect”) are ongoing.
Abstract 17655: Cost-effectiveness of Ivabradine as a Treatment for Systolic Chronic Heart Failure in the United States
Authors: Kansal Anuraag R , Cowie Martin , Kielhorn Adrian , Krotneva Stanimira , Taffazzoli Ali , Zheng Ying , Yurgin Nicole
Published: July 2021

Introduction:
To compare the long-term clinical, cost and quality of life outcome of ivabradine+ standard of care (SoC) versus SoC and assess the cost-effectiveness of ivabradine as a treatment to systolic chronic HF, a cost effectiveness model was developed from the perspective of US payers.

Hypothesis:
Ivabradine+SoC is a cost-effective treatment for systolic chronic HF compared to SoC in the US.

Methods:
A state-transition model was developed modeling the risk of death and HF-, non-HF CV-, and non-CV- related hospitalization and mortality over 10 years in a cohort of patients receiving ivabradine+SoC. As patients experienced more HF and non-HF CV hospitalizations in the model, they were subject to higher future risk of HF and non-HF CV hospitalization and lower quality of life. Hospitalization rates and costs by hospitalization type were taken from US claims data for patients in commercial and Medicare Advantage insurance plans. Mortality, utility inputs, and ivabradine treatment effect were derived from analyses of the pivotal randomized placebo-controlled SHIFT study. Both health and cost outcomes were discounted at 3% per year. One-way and multi-way sensitivity analyses were conducted.

Results:
In the commercially insured population based on a cost of $4,500 per year for ivabradine, the total costs over 10 years were $355,080 for a patient treated on ivabradine+SoC and $361,516 for a patient on SoC alone. The total lifetime drug cost of ivabradine ($27,201) was more than offset with cost-savings from reduction in hospitalization. Patients on ivabradine+SoC also had better health outcomes with an incremental improvement of 0.21 life-years and 0.24 quality-adjusted life years (QALYs) compared to SoC. Similar incremental health benefit was seen in the Medicare Advantage (0.20 QALYs) population, but the lower cost per hospitalization led to a modest increase in cost ($7,284). The incremental cost-effectiveness ratio was $36,944/QALY in the Medicare Advantage population.

Conclusions:
The results of this model indicate that ivabradine+SoC may be a less costly and more effective option compared to SoC in the commercial population and a cost-effective treatment option among Medicare Advantage patients.
Abstract 17684: A Novel System for the Rapid and Automated Detection of Atrial Fibrillation
Authors: Kruger Grant , Latchamsetty Rakesh , Langhals Nicholas B , Yokokawa Miki , Chugh Aman , Morady Fred , Oral Hakan , Berenfeld Omer
Published: July 2021

Introduction:
Home telemetry monitoring with accurate automated rhythm classification can have important clinical benefits in the timely diagnosis and appropriate management of patients with atrial fibrillation (AF). We clinically validated a novel personal e-Health device and algorithm developed to distinguish AF from sinus rhythm (SR).

Methods:
A handheld electrocardiogram (ECG) recording system (Maestro) and signal processing platform were developed. The Maestro provides an LCD interface that continuously shows an ECG, heart rate, and heart rhythm status. Twenty second ECG signals analogous to Lead I were acquired from 66 patients presenting to the arrhythmia clinic at the University of Michigan Hospital either in SR or AF. Electrograms were segmented into non-overlapping 6-second samples and one random segment per patient was selected for analysis by the Maestro system. Simultaneous 5 or 12 lead ECGs were obtained from these patients and 3 expert physicians blinded to the Maestro analysis identified the rhythm as SR or AF. The Maestro system applied several signal conditioning algorithms to each ECG sample. The dimensionless temporal R-R interval variability (VRR) index and spectral frequency dispersion metric (FDM) were computed.

Results:
The 2-dimensional scatter-gram of the samples demonstrated 2 distinct clusters of VRR and FDM for patients with SR and AF. The VRR index clusters for SR and AF patients were 0.018 ± 0.013 and 0.187 ± 0.073 (mean±std), respectively (p < 0.001). The FDM clusters for SR and AF patients occurred at 10.5 ± 5.916 and 15.892 ± 3.337, respectively (p < 0.001). We developed a Gaussian Mixed Model (GMM) classifier to distinguish between the AF and SR clusters. Only after the GMM classifier was obtained were the Maestro classifications compared to the physicians’ readings. The algorithm correctly categorized AF (N = 46) and SR (N = 20) for all Maestro segments analyzed with 100% specificity and sensitivity.

Conclusion:
The Maestro handheld telemetry unit utilizes a novel classification algorithm and was demonstrated to acquire and automatically analyze 6-second electrograms for rapid and accurate classification of patients in SR or AF in this initial clinical validation trial.
Abstract 17720: Unique Features of Metabolic Syndrome in High BMI College Football Players
Authors: Powers Edward M , Silver Heidi J , Seabolt Lynn A , Warren Abbie L , Kang Hakmook , Fitch Robert W , Niswender Kevin D
Published: July 2021

Background:
Metabolic syndrome in football players is a common, yet poorly understood phenomenon. With 88,000 college football players and one million high school football players, there is a large, at-risk population.

Hypothesis:
We hypothesized that metabolic syndrome in football players is driven by oxidative stress and positive energy balance.

Methods:
A single site, cross-sectional study was performed at Vanderbilt University Medical Center of high BMI college football players (n=33). Prevalence of metabolic syndrome was determined. Data related to diet composition, oxidative stress, inflammation, body composition, glucose disposition, lipoprotein metabolism, and endothelial function were assessed to identify drivers of the metabolic syndrome in this cohort.

Results:
Prevalence of clinical metabolic syndrome was 33% (11/33) despite high cardiorespiratory fitness in all players (Table 1). Elevated waist circumference, HDL, and elevated blood pressure were present together in 73% of cases. Cases had increased oxidative stress (F2-isoprostanes) and inflammation (CRP). Insulin resistance was not worse by HOMA. Visceral fat predicted HDL and CRP. Respiratory quotient was identical between groups but metabolomics revealed decreased TCA cycle intermediates in cases. There were no differences in caloric intake but cases had gained more weight (4.2 vs 2.0 kg, p=.06).

Conclusion:
High BMI collegiate football players have metabolic syndrome at unexpectedly high rates with a unique set of risk factors and unusual pathophysiology. They have low HDL despite normal triglyceride levels and no defects in glucose metabolism. These data suggest deleterious effects of positive energy balance and oxidative stress irrespective of exercise quantity. These results provide strong rationale to conduct larger, longitudinal studies.
Abstract 17783: Improved Aortic Valve Area Calculation Using a Novel Biplane Echo Continuity Equation
Authors: Leucker Thorsten M , Shapiro Edward P
Published: July 2021

The aim of this study was to improve the accuracy of transthoracic echo- cardiographic (TTE) assessment of the aortic valve area (AVA) in patients with aortic stenosis (AS).

The traditional continuity equation (CE) for determining AVA requires a measurement of left ventricular outflow tract (LVOT) area, which is calculated from a linear LVOT dimension using the parasternal long axis view, assuming circular geometry. However, routine use of multidetector computed tomography (MDCT) in patients undergoing evaluation for transcatheter aortic valve replacement (TAVR) has shown that the LVOT is elliptical rather than round. Assumption of circular geometry may introduce inaccuracies into AVA assessment.

A total of 61 patients (76 ± 11 years of age, 61% men) with isolated calcific AS (mean gradient 42 ± 9 mm Hg; ejection fraction 56 ± 11%) underwent Doppler TTE as part of pre TAVR or aortic valvuloplasty evaluation. AVA was calculated by TTE using two near- perpendicular planes (parasternal long axis and apical five chamber view) to evaluate the LVOT. A modified CE was used to calculate AVA (cm2) = (π((D1 x D2)/4)x LVOT VTI)/(AV VTI) in order to account for the elliptical rather than round shape of the LVOT. AVA measurements from the traditional and modified CE were compared to invasive AVA assessment.

Biplane (Figure, Panel B+D) vs. traditional single plane (Panel A+C) TTE measurement of the LVOT yielded a significantly improved positive correlation between TTE and invasive AVA assessment (r2=0.861 vs. 0.296) and a markedly reduced mean error (0.07 cm2 vs. 0.18 cm2), p<0.001.

Utilizing the proposed modified continuity equation greatly improves the accuracy of TTE guided AVA measurements. This simple calculation can be performed using standard TTE without additional costly equipment (ie, biplane transducers), without additional echo views (ie, more sonographer time), and without the need to subject patients to further invasive or non- invasive testing (ie, TEE or MDCT).
Abstract 17802: pH Sensitive Polyethylene Glycol-urokinase Nanogels Ameliorates the Severity of Ischemic Stroke in Rats by Effective Thrombolysis and Protection of Blood-brain Barrier
Authors: Cui Wei , Liu Ran , Jin Haiqiang , Huang Yining
Published: July 2021

Background:
pH sensitive polyethylene glycol-urokinase nanogels(PEG-UK) was reported previously as a new form of UK, which could release UK at certain pH value and has the same thrombolytic effect as naked UK on human clots in vitro. In this study, we evaluated its effect in rat model of ischemic stroke and further investigated possible mechanisms.

Methods:
Persistent middle cerebral artery occlusion were induced in adult Sprague-Dawley rats. pH distribution in the brain was mapped at 1 hour after ischemia through Needle type pH micro sensor and pH Optica Micro system. Thrombolytic effect of PEG-UK, such as dynamic levels of D-dimer, neurological deficts and infarction volume, were examined respectively. In spite of the overall performances, possible mechanisms were also explored, for example, the permeability of blood-brain barrier(BBB) reflected by Evans Blue(EB) leakage, BBB’s integrity via matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase protein-1 (TIMP-1) and Claudin5, and extent of apoptosis and neurotoxicity standed by Caspase9 and N-methyl-D-aspartic acid receptor 1(NMDAR1).

Results:
In ischemic hemisphere, pH value near cortex was obviously lower than that in deeper white matter. Averagely, occlusion for 1 hour induced the decline of pH value for about 0.49, and the lowest value reached to 6.32. Treatment with PEG-UK brought obvious alleviation of neurological deficts in acute phase(
P
=0.001). A significant reduction of relative infarction volume was also proved in PEG-UK rats(
P
<0.001). As to the permeability of BBB, the leakage of EB in PEG-UK group was the least among three groups(
P
=0.001). What’s more, the sustain of the expression of TIMP-1(
P
=0.032) and Claudin5(
P
<0.001) and the inhibition of upregulation of MMP9(
P
<0.001) were all concluded in PEG-UK group. Besides, both the expression of NMDAR1(
P
<0.001) and Caspase9(
P
=0.013) in PEG-UK treated rats were much less.

Conclusions:
Our findings indicated that treatment with PEG-UK ameliorated the severity of ischemic stroke, accompanied by neuroprotection through keeping the integrity of BBB and inhibiting apoptosis and neurotoxicity. PEG-UK may further inhibit hemorrhagic transformation by its BBB protection effect.
Abstract 17824: Gemcabene and Atorvastatin Alone and Combined Markedly Reduce LDL-C in LDL Receptor-deficient Mice, a Model of Homozygous Familial Hypercholesterolemia
Authors: Bisgaier Charles L , Auerbach Bruce J
Published: July 2021

Background:
Gemcabene (Gem) is a late-stage Phase 2 clinical candidate being evaluated for the reduction of low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemia (HoFH) patients. Combination therapy includes statins as standard of care to treat this genetic disorder. LDL-deficient (LDLr) mice have been widely used with lipid-lowering agents to demonstrate LDL-C lowering with good translation to clinical efficacy. We have previously shown that atorvastatin (Atorva) reduces LDL-C and apoB in the LDLr deficient mice and in casein-fed (endogenous hypercholesterolemic) rabbits.

Experiment and Results: In the current study, we assessed Gem and Atorva effects alone and in combination on reduction of LDL-C in chow-fed LDLr deficient mice, an animal model of HoFH. Baseline LDL-C and total cholesterol were 246±20 mg/dL and 329±23 mg/dL in these mice Female LDLr deficient mice (n=10) were treated with Atorva alone (60mg/kg/day), Gem alone (60/mg/kg/day) or the agents combined (Atorva + Gem)(each at 60 mg/kg/day) for 14 days. Following treatments with Atorva, Gem, and Atorva+Gem, fasting LDL-C reduced by 22%, 55% and 72%, respectively, and total cholesterol by 21%, 47%, and 58%, respectively; showing additional reduction of 50% LDL-C by Gem on top of Atorva alone. Since LDLr are absent in these mice, similar to HoFH patients, the LDL-C lowering by Gem could be due to reduced VLDL production rates. Indeed, our studies in rat hepatocytes and in apoB100-only mice (apobec-1 knockout) showed reduced radioactivity in cholesterol and triglyceride fractions in the hepatocytes and in the plasma and liver of mice administered 14C acetate, suggesting cholesterol and fatty acid synthesis inhibition as a mechanism of LDL-C lowering. Gem also enhances the clearance of VLDL in normal rats. We propose both mechanisms may contribute to LDL-C reduction in LDLr deficient mice. A more detailed kinetic study of Gem in LDLr deficient models is underway to verify these proposed mechanisms.

Conclusions:
Gemcabene alone and combined with atorvastatin significantly (55-72%) reduced LDL-C in this predictive in-vivo HoFH disease model. These findings suggest that treatment with Gem on top of standard of care therapy by statins may benefit HoFH patients.
Abstract 17830: Statin Use is Associated With a Reduced Risk of Intracerebral Hemorrhage Recurrence: A Population-based Cohort Study
Authors: Chou Mei-Chuan , Cheng Kai-Hung , Chu Chih-Sheng , Chang Yu-Han , Ke Liang-Yin , Lai Wen-Ter , Liu Ching-Kuan , Yang Yi-Hsin , Chen Chu-Huang
Published: July 2021

Background:
The safety of statin use in patients with intracerebral hemorrhage (ICH) is an unsettled issue of critical importance during stroke management. To assess the benefits and risks of statin use in ICH patients, we analyzed the big data from the Taiwan National Health Insurance Research Database (NHIRD) collected from a population known to have a higher ICH incidence than the Westerners.

Methods and Results:
A random sample of 1,000,000 subjects representative of the 23-million population registered in the NHIRD from 1997 to 2010 was used for this retrospective cohort study. The cumulative risks of ICH, ischemic stroke, and transient ischemic attack (TIA) were analyzed among three ICH cohorts: non-statin (NS; no statin use before or after ICH), statin (S; continued or initiated statin use after ICH), and statin-withdrawal (SW; statin use discontinued after ICH). A total of 2408 ICH patients (age 63.4±14.2 years, 62.5% male) were identified between 2000 and 2005 and followed for an average of 7.0 years. A Cox proportional hazard regression model was applied to estimate the hazard ratios (HRs) with adjustment for potential confounders. Compared to NS, S had a 71% (HR 0.29, CI 0.19-0.43; P<0.001) reduction in ICH recurrence (Figure). The risk of ICH recurrence decreased as a function of the increment of cumulative defined daily doses (P trend <0.0001). In contrast, SW had a 1.5-fold increase in ICH recurrence (HR 1.55, CI 1.09-2.22; P=0.016) and a 2-fold increase in ischemic stroke or TIA development (HR 2.01,CI 1.30-3.11; P=0.002).

Conclusions:
Based on this large database, continuation or initiation of stain use in ICH patients is associated with a reduced risk of ICH recurrence in a dose-dependent manner; discontinuation of statin use confers significant risks for both ICH recurrence and ischemic stroke/TIA development. Mechanistic studies are warranted to further validate the significance of this observation.
Abstract 17839: Transcatheter Annuloplasty Ring Multicentre Trial Report
Authors: Kuck Karl-Heinz , Vahanian Alec , Nickenig Georg , Alfieri Ottavio , Colombo Antonio , Baldus Stephan , Maisano Francesco
Published: July 2021

Aim:
Cardioband system enables percutaneous implantation of an adjustable “surgical-like” mitral annuloplasty ring using a transseptal approach. The aim of this study was to evaluate the feasibility, safety and up to 12 month outcome of Cardioband in patients with functional mitral regurgitation (FMR) in a multicentre study.

Methods and Results:
Between February 2013 and March 2015, 40 high-risk patients with significant FMR were enrolled at 6 sites in Europe. After a Heart Team evaluation all patients were screened by echocardiography and cardiac CT to assess feasibility. Echocardiographic data were analysed by an independent core-lab.

Mean age was 72±7 years, thirty patients were males (75%). Mean EuroScore II 9.0%±7.02% and median STS score 7.2 % (1.0%-34.0%). At baseline 93% of patients were in NYHA class III-IV with mean EF of 33.3±10% (15%-57%). Device implantation was feasible in all patients (100%). Acute procedural success (device successfully implanted with acute reduction of MR <2+) was achieved in 92% of the patients (37/40. After cinching of the device, an average of 20% reduction of the septo-lateral diameter was observed (from 37±5 mm to 29±5 mm; p<0.01). Thirty-day mortality was 5.0% (adjudicated unrelated to the device). At 6 months follow up (n=20) 80% of patients were in NYHA class I-II with significant improvement in quality of life (MLWHFQ from 38 to 18; p<0.05) and 85% of patients had MR≤2+. At 12 months follow up (n=14), 93% of patients had MR<2+).

Conclusions:
Transseptal direct annuloplasty with an adjustable “surgical-like” ring is feasible, with a comparable safety profile similar to other transcatheter mitral procedures. Effective reduction in MR severity is observed in most patients related to a significant septo-lateral dimension reduction. MR reduction is stable and consistent up to 12 months, with clinical benefit.
Abstract 17899: Prognostic Value of Persistent Hyponatremia in Patients With Chronic Heart Failure: A Prospective Comparative Study With Cardiac I-123 Metaiodobenzylguanidine Imaging
Authors: Seo Masahiro , Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Syunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Sato Yoshihiro , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Backgrounds:
Hyponatremia is associated with not only mortality, but also excessive neurohumoral drive including sympathetic overactivation in patients (pts) with chronic heart failure (CHF). However, the prognostic significance of persistent hyponatremia (per-hypoNa) remains to be unclear in CHF pts. Cardiac metaiodobenzylguanidine (MIBG) imaging, which is useful for the estimation of cardiac sympathetic nerve activity, provides prognostic information in CHF pts. We sought to investigate whether per-hypoNa would provide the additional prognostic information to MIBG imaging in CHF pts.

Methods:
We studied 103 CHF outpatients with LVEF <40% in our prospective cohort study. The cardiac MIBG heart-to-mediastinum ratio (H/M) washout rate (WR) were calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. We also measured serum sodium concentration at entry and every 6month for the initial 3 years. Per-hypoNa was defined that hyponatremia (<137mEq/L) was observed for more than 6 months.

Results:
During a follow up period of 8.0±4.0 years, 41 pts died. At multivariate Cox analysis, per-hypoNa (p=0.01) and abnormal WR (p=0.007) were significantly independently associated with the mortality, although H/M showed the significant association with the mortality at the univariate analysis. Pts with per-hypoNa had a significantly higher risk of mortality than pts without per-hypoNa (67% vs 35%, p=0.03). Pts with both per-hypoNa and abnormal WR had a significantly greater risk of mortality than pts with either per-hypoNa or abnormal WR (80% vs 48% p=0.01, adjusted HR 2.8[1.2-6.5]). Furthermore, pts with either per-hypoNa or abnormal WR also had a significantly greater risk of mortality than pts with neither per-hypoNa nor abnormal WR (48% vs 22% p=0.009, adjusted HR 2.6 [1.2-5.4]).

Conclusion:
The combination of persistent hyponatremia and cardiac MIBG imaging could provide the improved prediction of mortality in CHF pts.
Abstract 17955: Reduction in 30-day Rehospitalization After Discharge From a Heart Failure Admission in Patients Receiving LCZ696 versus Enalapril: PARADIGM-HF
Authors: Solomon Scott D , Packer Milton , Zile Michael , Rouleau Jean , Swedberg Karl , Desai Akshay , Shi Victor , Lefkowitz Martin , McMurray John J
Published: July 2021

Introduction:
The angiotensin receptor neprilysin inhibitor LCZ696 reduced cardiovascular death, heart failure hospitalization and all-cause mortality in patients with heart failure and reduced ejection fraction compared with enalapril.

Hypothesis:
We hypothesized that LCZ696 would reduce 30-day readmission after a heart failure hospitalization.

Methods:
PARADIGM-HF randomized 8399 patients with HF and reduced ejection fraction to either LCZ696 200mg bid or Enalapril 10mg bid. We assessed the risk of 30-day readmission for any cause following investigator reported and adjudicated hospitalization for heart failure. Admission and discharge dates were available for 2800 hospitalizations (95%) in 1638 patients.

Results:
Of 2800 HF hospitalizations, 1545 occurred in 871 patients in the enalapril group and 1255 occurred in 767 patients in the LCZ arm. Overall, 10.5% of these HF hospitalizations were followed by a repeat hospitalization for any cause within 30 days of discharge, and this occurred significantly less frequently in the LCZ arm (8.7%) relative to the enalapril arm (12.0%), in both unadjusted models and a random-effects logistic regression model accounting for the repeated HF hospitalizations experienced by some patients. We observed similar results in a sensitivity analysis restricted only to the first HF hospitalization for each patient. Further adjustment for baseline characteristics did not alter these findings. Similar effect sizes were observed for adjudicated heart failure hospitalizations.

Conclusion:
In patients admitted with heart failure in PARADIGM-HF, LCZ reduced 30-day readmissions for any-cause.
Abstract 17975: Anemia in Heart Failure With Preserved Ejection Fraction: Insights From the TOPCAT trial
Authors: O'Meara Eileen , Kenwood Christopher T , Anand Inder S , Desai Akshay S , De Denus Simon , Sweitzer Nancy K , Fleg Jerome L , Huynh Thao , McKinlay Sonja M , Pitt Bertram , Pfeffer Marc A , Rouleau Jean L
Published: July 2021

Introduction:
Anemia predicts higher rates of mortality and HF hospitalizations in patients with heart failure (HF). We sought to determine the factors associated with anemia in TOPCAT, a large randomized trial that tested the effects of spironolactone in patients with HF and preserved EF (HFpEF).

Methods:
Amongst the 3445 patients enrolled in TOPCAT, 3422 had available baseline hemoblobin. All significant factors assessed in baseline characteristic comparisons were put in a saturated multivariable logistic regression model along with randomized treatment assignment. The stepwise elimination method was used to obtain a parsimonious model identifying factors associated with anemia.

Results:
The overall prevalence of anemia (hemoglobin, Hgb < 12g/dL in women and < 13g/dL in men) was 28.5% (974 patients), with higher prevalence in patients enrolled in the Americas (41%) than in Russia/Georgia (15.4%). Previous hospitalization for HF, randomization in the Americas, older age, insulin-treated diabetes, orthopnea, peripheral edema, lower eGFR, lower diastolic BP, lower HR, and longer QRS duration were independent correlates of anemia; whereas female gender, white race, higher BMI, known dyslipidemia, left ventricular hypertrophy, and eating meals at home were independently associated with the absence of anemia (Table).

Conclusions:
Anemia in HFpEF is associated with multiple markers of increased cardiovascular risk, and of more advanced HF. We identified new factors associated with the absence of anemia, such as eating most meals at home. Complex interactions may underlie the observed relationships, including medications, and causality cannot be inferred from our observations.
Abstract 18012: Variability in the Utilization of Mechanical Circulatory Support in Cardiogenic Shock Complicating STEMI: Impact of Hospital PCI Volumes
Authors: Agarwal Shikhar , Sud Karan , Martin Joseph M , Menon Venu
Published: July 2021

Despite controversy about efficacy, mechanical circulatory support (MCS) is often utilized in patients with cardiogenic shock after ST elevation myocardial infarction (STEMI). We aimed to characterize the variability in MCS utilization in cardiogenic shock patients across hospitals in the US, according to annual volume of primary percutaneous interventions (PPCI).

Methods:
We used the 2003-2011 Nationwide Inpatient Sample for the study. All admissions with principal diagnosis of STEMI, with an additional diagnosis of cardiogenic shock, were identified using ICD 9 diagnosis codes. MCS devices were identified using ICD-9 procedure codes. All hospitals were divided into quartiles based on annual PPCI volume.

Results:
Of 372984 admissions with STEMI, we identified 32482 (8.5%) cases with cardiogenic shock during admission. Of these, MCS was utilized in 17415 (53.6%) patients. All hospitals treating cardiogenic shock patients were divided into quartiles such that quartiles 1-4 corresponded to hospitals performing
<
36, 37-68, 69-118 and ≥119 PPCIs annually. The number of cardiogenic shock patients treated in quartile 1, quartile 2, quartile 3 and quartile 4 hospitals were 1875, 4712, 8061 and 15853 patients respectively.

There was progressive increase in MCS utilization across hospital quartiles with increasing PPCI volume (Figure). MCS utilization in quartiles 1-4 hospitals was 44.9%, 55.2%, 57.6% and 58.5% respectively (p-trend<0.001). After adjustment for baseline, clinical and hospital characteristics (geographic location, teaching status, bed size), we still observed progressive increase in MCS utilization across the hospital quartiles (Figure).

Conclusion:
There was significant variability in MCS utilization among STEMI patients with cardiogenic shock, based on annual PPCI volume of the treating hospital. Increase in annual PPCI volume was correlated with an increase in MCS utilization in STEMI patients complicated by cardiogenic shock.
Abstract 18043: Factors That Influence the Decision for Ischemic Work-up in Hypertensive Emergency
Authors: Maludum Obiora , Mezue Kenechukwu , Biso Sylvia , Rodriguez-Ziccardi Mary , Alnabelsi Talal , Shah Mahek , Nwakile Chinualumogu , Figueredo Vincent
Published: July 2021

Background:
Hypertensive emergencies (HE) account for 3% of emergency room hospitalizations and it is estimated that 1-2% of America’s 50 million hypertensive patients will have at least one occurrence of HE in their lifetime. Recent studies have shown that cardiac troponin-I is elevated in a third of patients with HE, however the pathophysiology and significance of this elevation is still being explored. We tried to look at different factors that influence the decision to do ischemic work up in patients with HE.

Method:
Patients admitted to Albert Einstein Medical Center from 01/01/2005 to 08/30/2014 with a diagnosis of HE were included in this retrospective study. Patients were divided into two groups: those who had either cardiac catheterization or stress test, and those who had no ischemic work up. Demographic and clinical variables were collected. A cumulative risk score for coronary artery disease was calculated by assigning 1 point for each risk factor.

Results:
There were total of 187 patients with HE of which only 37 had ischemic work up. 20 out of the 37 patients who had ischemic work up had chest pain. Of the 20 patients only 3 were found to have significant coronary artery disease. Comparisons between the demographics and clinical predictors in both groups are shown in the table. Multivariate analysis shows chest pain to independently predict which patients were more likely to receive an ischemic work up (OR=4.7; 95% CI 1.6 to 7.6; p=0.001).

Conclusion:
In the setting of HE, our study shows that chest pain was the only single factor that independently predicts which HE patients are more likely to receive an ischemic work up. Elevated troponins or EKG changes alone were not found to independently predict the decision to perform an ischemic work up. This may reflect the pattern of clinical practice at our center. Large multi-center studies might be needed to explore this further and also assess the clinical outcomes of this decision making process.
Abstract 18053: Prognostic Value of Anatomic versus Functional Diagnostic Testing in Symptomatic Patients With Suspected CAD: The PROMISE Trial (PROspective Multicenter Imaging Study for Evaluation of Chest Pain)
Authors: Hoffmann Udo , Ferencik Maros , Udelson James E , Picard Michael H , Heitner John , Patel Manesh R , Huang Megan , Pencina Michael , Mark Daniel B , Fordyce Christopher B , Tardif Jean-Claude , Budoff Matthew , Nahhas George , Chow Benjamin , Kosinski Andrzej S , Lee Kerry L , Douglas Pamela S
Published: July 2021

Introduction:
Symptoms suggestive of coronary artery disease (CAD) are common, but no randomized comparison of the prognostic value of coronary computed tomographic angiography (CTA) vs. functional testing has been performed.

Methods:
Patients (10,003) with suspected CAD were randomized to functional testing (exercise ECG, nuclear stress, or stress echo) or CTA. Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. Cox proportional hazards models assessed the relationship of test results to a composite of time to death, myocardial infarction, or unstable angina, and the discriminatory ability of the two tests was compared using the C-index. Adjusted HRs for events in patients with abnormal vs. normal test results were determined for CTA and functional testing.

Results:
Overall, 4516 patients received CTA and 4572 functional testing as the randomized diagnostic test. The proportions of normal, mild, moderate, and severe abnormalities on CTA were 33.3%, 42.7%, 10.0%, and 14.0%, respectively, and for functional testing 78.9%, 8.5%, 4.2%, and 8.4% (P=0.001). Event rates over 26.0 months’ (IQR 18.0, 34.4) follow-up were similar: CTA 137/4516 (3.0%) vs. functional 132/4572 (2.9%). Compared to patients with normal CTAs, those with abnormal CTAs had increasing HRs for events with increasingly severe abnormalities, while only patients with moderate and severely abnormal functional testing had an increased HR for events (Figure). The probability of having an event given a normal test result was lower for CTA compared to functional testing (0.9% vs. 2.2%; HR 0.47 [95% CI 0.26, 0.83]; P=0.009), but not significantly different for other test strata. The overall prognostic performance (C-index) of CTA vs. functional testing was 0.72 (0.68, 0.76) vs. 0.64 (0.60, 0.69); P=0.022 (see KM curves in Figure).

Conclusions:
In symptomatic patients with suspected CAD, CTA has better prognostic value than functional testing.
Abstract 18054: Improved Myocardial Function After Whole Body Periodic Acceleration (pGz) in Established
mdx
Cardiomyopathy
Authors: Uryash Arkady , Lopez Jos R , McGowan Francis X , Berg Robert , Nadkarni Vinay , Adams Jose
Published: July 2021

Duchenne Muscular Dystrophy (DMD) cardiomyopathy (DMD-C) is progressive leading to heart failure and death. pGz is the sinusoidal motion of the body in a head-foot direction, which activates endothelial nitric oxide synthase (eNOS) to produce small amounts of eNO in heart via pulsatile shear stress. eNO is cardioprotective and important in varied signaling pathway. We recently showed improved muscle function using pGz in a mouse model of mdx

Hypothesis:
pGz may confer myocardial functional improvement in an established DMD-C.

Methods:
Male
MDX
mice were randomized (n=12) at 7-mo of age (an age where DMD-C is already established) to receive daily pGz (ƒ=480 cpm with a displacement Gz ± 3.0 mt/sec
2
) (MDX-pGz) (1hr/day for 8 weeks or time control (MDX), a separate age matched group of
wt
(n=6) to serve as non-diseased controls. At 9 mo of age, invasive analysis of the pressure-volume relationship of left ventricle (LV) was carried out with a Millar catheter and a dobutamine stress test performed. In a separate group of
mdx
mice, pGz was performed and immunoblotting analysis done to determine expression of utrophin (UTR), sarcoglycan β (SARCβ), Dytroglycanβ(DYSβ), eNOS and p-eNOS levels in heart.

Results:
Compared to
wt
,
mdx
mice had reduced LV pressure integral(LVPi) and lower dp/dt
max
. Treatment with pGz improved LVPi and dp/dt
max
. Survival to a Dobutamine stress test was: 100%
wt
, 80%
mdx
and 90% in
mdx
-pGz. pGz treatment preserved LVPi relationship and dp/dt
max
during dobutamine. pGz treatment to
mdx
mice increased UTR,(56% ), SARCβ (160% ),DYSβ (227%), eNOS(75%) and p-eNOS (37% ) from
mdx
expression levels (Figure, M±SD)

Conclusion:
pGz improves myocardial functional phenotype, and preserves myocardial function after dobutamine stress in
mdx
mice. pGz salutatory effect is associated with an increase in eNOS, p-eNOS UTR, SARCβ, DYSβ expression. This non-invasive and non-pharmacological intervention may constitute a new therapeutic approach to treat DMD cardiomyopathy.
Abstract 18092: Source of Galectin-3 in Human Heart Failure, Chronic Kidney Disease and Cardio-renal Failure
Authors: Hussain Imad , Alexander Mariam P , Maleszewski Joseph J , Pereira Naveen L , Redfield Margaret M
Published: July 2021

Background:
Galectin-3 (Gal-3) may promote cardiac and renal fibrosis in heart failure (HF). Plasma Gal-3 levels predict outcome in HF but are tightly correlated with renal function. The source of Gal-3 in human HF, chronic kidney disease (CKD) or cardio-renal failure (HF+CKD) is unclear.

Objective:
To assess Gal-3 presence and location in human heart or kidney tissue from patients with HF, CKD or HF+CKD.

Methods:
Plasma Gal-3 levels and LV tissue explanted at time of cardiac transplant in systolic HF (n=15) and autopsy renal sections from patients with normal kidneys (n=4), CKD (n=17) or CKD+HF (n=14) were examined (H&E, Masson’s trichrome and CD-68 and Gal-3 immunohistochemistry). In the systolic HF patients, we quantified the number of Gal-3+/CD-68+ cells per HPF in LV tissue and assessed the correlation with plasma Gal-3 levels. In autopsy renal tissue, we derived a Composite Gal-3 Score (CG3S) incorporating the % of Gal-3+ tubules per HPF, % of Gal-3+ cells/tubule per HPF, and intensity of Gal-3 staining and assessed the correlation of the CG3S with ante-mortem estimated glomerular filtration rate(eGFR). Renal macrophage Gal-3 staining was also assessed.

Results:
In systolic HF LV tissue, Gal-3 was present in macrophages rather than myocytes but Gal-3+/CD-68+ cells per HPF was not correlated with plasma Gal-3 levels (p> 0.9) which correlated inversely with eGFR (r = -0.89 for log Gal-3 vs eGFR, p<0.0001). In the kidney, Gal-3 was not present in macrophages but was localized to renal tubular cells (Figure). The CG3S increased exponentially as eGFR decreased (r = - 0.88 for log CG3S versus eGFR; p<0.0001) and this relationship was not different (p=0.44) in patients with or without HF (Figure). The log CG3S correlated with the degree of fibrosis (tubulointerstitial scarring) in the kidney (r=0.88; p<0.0001).

Conclusion:
Collectively, these data suggest that plasma Gal-3 is predominantly of renal tubular epithelial origin in human HF, CKD, and CKD+HF.