bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19452: Long-term Outcomes in Adults With Congenital Heart Disease Evaluated for Heart Transplantation
Authors: Hickey Gavin , Elliott Andrea , Hindes Morgan , Maul Tim , Ramani Ravi , Mathier Michael , Cook Stephen
Published: July 2021

Background:
The prevalence of adult congenital heart disease (ACHD) patients with heart failure is increasing. No guidelines exist for evaluation and listing for heart transplant (HT) in ACHD. We sought to review the outcomes of HT committee decisions [accepted and transplanted (T), accepted awaiting transplant (A), deferred (D), ineligible (I)].

Methods:
This was a retrospective analysis performed on ACHD (≥ 18 yrs) referred for HT between 2000-2014. Data on demographics, CHD severity, NYHA class, imaging, exercise testing, catheterization and HT committee decision were recorded. Primary outcome was all-cause mortality. Analysis was completed to identify variables that were statistically different amongst groups.

Results:
Sixty-two ACHD were included in analysis, A (n= 17) I (n=14) T (n=22) D (n=9), NYHA class III-IV (98%), CHD of great complexity (74%). Median time to HT, after listing, was 3 mo. (mean 5.5). Survival was significantly lower in the group awaiting transplant compared to all other groups (p<0.001): A (18.6%) I (65.3%) T (78.3%) D (100%) (
Fig
). Among those who had not been transplanted, several variables were significantly different (p<0.05) including: systolic BP, alb, BNP, Hct, right atrial pressure and peak oxygen consumption. For those awaiting transplant with pulmonary hypertension (PH) mortality was 100% but 40% for those without PH (p<0.1).

Conclusion:
Waitlist mortality in the ACHD population is high. Given poor outcomes while on the waitlist, earlier listing may improve survival. Specific variables were statically different among patients not transplanted and there was a high mortality in those with PH. These may have contributed to the difference in survival among groups and may impact HT committees in the evaluation and listing for HT.
Abstract 19477: Transthoracic Bioimpedance Monitoring Predicts Readmission After Hospitalization for Heart Failure: Preliminary Results From the SENTINEL-HF Study
Authors: Darling Chad E , Dovancescu Silviu , Riistama Jarno , Saczynski Jane , Kini Nisha , Sert Kuniyoshi Fatima , Rock Joseph , Meyer Theo E , Goldberg Robert J , McManus David D
Published: July 2021

Introduction:
Patients and health systems are focused on reducing readmissions for patients with acute decompensated heart failure (ADHF). Readmission after hospitalization is often secondary to HF decompensation, but it remains challenging to identify patients at-risk. Bioimpedance is a validated marker of thoracic fluid accumulation. We examined whether changes in bioimpedance, measured using a Fluid Accumulation Vest (FAV), predicted subsequent HF decompensation in patients discharged after ADHF.

Methods:
Participants included 83 patients hospitalized for ADHF. Subjects were trained on the use of a FAV-smartphone dyad to obtain and transmit a 5-minute bioimpedance measurement once daily for 45-days after discharge.(see Figure) The outcome of interest, HF-related readmission was assessed using participant report and medical records. Sensitivity, specificity, negative and positive predictive values were calculated to describe the efficacy of the bioimpedance alert algorithm as a predictor of HF readmission.

Results:
Subject characteristics: mean age 68 ± 11 years, 36% female, 92% white, mean ejection fraction of 44 ± 19%. 49 participants completed the 45-day follow-up and had sufficient, daily FAV data for analysis. Our main outcome of HF-related rehospitalization occurred in 8% of patients during follow-up. The decompensation detection algorithm demonstrated a sensitivity of 75%, specificity of 47%, positive/negative predictive values of 11% and 96%, respectively.

Conclusions:
The preliminary results of this ongoing study suggest that HF readmissions may be predicted with modest sensitivity by our current decompensation detection algorithm. Further refinement of our transthoracic bioimpedance system may offer possibilities for reducing HF readmissions by enabling identification and treatment of outpatients at risk for readmission.
Abstract 19486: Does the Association Between Adherence to Statin Medications and Mortality Depend on the Measurement Approach? A Retrospective Cohort Study
Authors: Alsabbagh MHD Wasem , Eurich Dean , Lix Lisa , Wislon Thomas , Blackburn David F
Published: July 2021

Background:
Optimal adherence to statin medications is associated with reduced mortality rates. However, it is not clear if the estimated benefits of statin adherence are influenced by the method used to measure adherence.

Objective:
To contrast the association between all-cause mortality and statin adherence when two different measurement approaches are used: (i.e., fixed summary measurement versus repeated measurement).

Methods:
A
retrospective cohort study was conducted using
administrative data from Saskatchewan, Canada between 1994 and 2008. Eligible individuals received a statin prescription following discharge from a hospitalization for acute coronary syndrome (ACS). Adherence was measured using proportion of days covered (PDC) expressed either as: 1) a fixed summary measure, or 2) as a repeatedly measured covariate. Cox proportional hazards models were used to test the association between each adherence measure and mortality after covariate adjustment.

Results:
Among 9,051 eligible individuals, optimal adherence (≥80%) modeled with a fixed summary measure was not associated with mortality (adjusted HR 0.97, 95% CI 0.86 to 1.09). In contrast, optimal adherence defined by the repeated measures approach was associated with a 25% reduction in the risk of death (adjusted HR 0.75, 95% CI 0.67 to 0.85).

Conclusions:
Unlike summary measure, the repeated measures approach appears to provide a significant reduction of all-cause mortality of adherence to statins. This effect may be a result of the repeated measures approach being more sensitive, or more prone to survival bias. Therefore, we recommend comparing different measurement approaches whenever possible.
Abstract 19498: Scavenger Receptor BI (SR-BI) Deficiency Uncouples Obesity From Glucose Intolerance in Mice
Authors: Hoekstra Menno , Ouweneel Amber B , Van Eck Miranda
Published: July 2021

Introduction:
Scavenger receptor BI (SR-BI) is a multi-purpose player in cholesterol metabolism. Interestingly, several studies in humans have suggested that a significant relationship exists between the presence of common variants in the SR-BI gene and a higher body mass index. We therefore evaluated the contribution of SR-BI to high fat diet-induced obesity in mice.

Methods and Results:
Male SR-BI knockout (SR-BI KO; N=10) and wild-type (WT; N=9) mice were fed a diet containing 45% energy as fat for 12 weeks. SR-BI KO mice exhibited a worsened metabolic plasma profile as compared to WT controls with higher fasting levels of free cholesterol (+111%; P<0.001), cholesterol esters (+84%; P<0.001), triglycerides (+40%; P<0.01), and glucose (+20%; P<0.01). Daily food intake was similar in the two types of mice; 4.5±0.3 g for SR-BI KO vs 4.1±0.3 g for WT. Importantly, the relative increase in body weight over time was significantly greater in SR-BI KO mice (+51%) as compared to WT controls (+33%; two-way ANOVA P<0.001 for genotype). The exacerbated increase in body weight could be attributed to a higher white adipose tissue mass (correlation coefficient R=0.87; P<0.001). High fat diet-fed WT mice were glucose intolerant, but remained resistant to atherosclerosis. In contrast, atherosclerotic lesions could be readily detected in the aortic root of SR-BI KO mice (6.9±1.5 x 10
3
μm
2
; P<0.001), while their glucose tolerance was remarkably higher compared to that of controls (oral glucose tolerance test AUC 484±68 mM.min for SR-BI KO vs 875±130 mM.min for WT; P<0.05). SR-BI deficiency thus uncouples obesity from glucose intolerance in mice.

Conclusions:
Our studies for the first time show that a proper SR-BI function inhibits the development of obesity in mice. Furthermore, these data imply that SR-BI may serve as therapeutic target to overcome the glucose intolerance normally associated with the presence of (morbid) obesity.
Abstract 19506: Relevance of Fibroblast Growth Factor 21 in Cardio-metabolic Diseases
Authors: Damrauer Scott M , Zhao Wei , Rashid Ashif , Frossard Phillipe , Danesh John , Rader Daniel J , Saleneeh Danish
Published: July 2021

Background:
Fibroblast growth factor 21 (FGF-21) is an adipokine produced predominantly in the liver and is a metabolic regulator of glucose and lipid metabolism. Circulating FGF-21 levels have been shown to be independently associated with a host of cardio-metabolic traits, including: BMI and adiposity, metabolic syndrome, diabetes, cholesterol and triglycerides, and cardiovascular disease outcomes. Despite these epidemiological observations, causal relationships between FGF-21 and cardio-metabolic outcomes remain uncertain.

Objectives:
To identify the cross-sectional correlates of FGF-21 levels and to explore the causal relationship between FGF-21 and cardio-metabolic traits using a Mendelian randomization based approach.

Methods & Results:
FGF-21 levels were measured by ELISA in 9,572 participants from the Pakistan Risk of Myocardial Infarction Study (PROMIS), a multi-ethnic case-control study aimed at identifying genetic and non-genetic determinants of cardio-metabolic diseases. Log serum FGF-21 levels were weekly but significantly correlated with measures of obesity (BMI r=0.1, p < 0.0001) and serum lipids (total cholesterol r=0.08, p < 0.0001; LDL-C r=0.06, p < 0.0001; log triglycerides r=0.15, p < 0.0001); there was, however, no significant association with biochemical indicators of glycemic control. A Genome Wide Association Study (GWAS) was conducted to identify genetic determinants of FGF-21 levels; genetic variants were further assessed for specific associations with FGF21 levels in order to to identify instruments suitable for Mendelian Randomization studies. Variants that specifically increased FGF21 levels were not found to be associated with either Type-2 diabetes (80,000 cases and 230,000 controls) or coronary heart disease (63,746 cases and 130,681 controls).

Conclusions:
Although FGF-21 is weekly correlated with a number of cardiovascular risk factors; however its relationship to cardio-metabolic outcomes is less likely to be causal.
Abstract 19591: Long-term Renal Function Following Worsening Renal Function Precipitated by Aggressive Diuresis: Insights From the DOSE Trial Limited Dataset
Authors: Simon Jennifer , Hall Isaac E , Onyebeke Chukwuma O , Schaub Jennifer , Brisco Meredith A , Modesto Karen , Assefa Mahlet , Testani Jeffrey M
Published: July 2021

Background:
Worsening renal function (WRF) is a common complication of the treatment of acute decompensated heart failure and can be precipitated by aggressive diuresis. The DOSE trial randomized patients to a high vs. low intensity loop diuretic strategy. Notably, the rate of WRF during the 72-hour intervention period was increased with the high dose strategy but post-discharge non-renal outcomes were similar. However, the long term renal outcomes in patients with WRF precipitated by aggressive diuresis have not been described.

Objective:
To determine the long term renal outcomes of patients with WRF in the high and low dose arms of the DOSE trial.

Methods:
Participants of the DOSE trial with data on renal function at baseline and 60 days were studied. To maximize the number of events, WRF was defined as any worsening in estimated glomerular filtration rate (eGFR) from randomization to 72 hours.

Results:
In total, 224 patients (72.7%) in the DOSE trial population had data on renal function available at baseline and 60 days. Of this subset, 102 patients (45.5%) experienced WRF at 72 hours and these patients had an average 16.7 ± 12.0% worsening in eGFR. In patients with WRF that were randomized to the high dose strategy (n=58) eGFR improved from 44.9 ± 22.4 ml/min/1.73m
2
at 72 hours to 53.1 ± 30.0 ml/min/1.73m
2
(p<0.001) at 60 days. Notably, eGFR was not significantly different at 60 days compared to baseline in these patients (p=0.18). However, in patients with WRF randomized to the low dose strategy (n=44), eGFR did not significantly improve from 72 hours to 60 days (46.4 ± 18.1 ml/min/1.73m
2
to 48.8 ± 22.4 ml/min/1.73m
2
, p=0.34) and eGFR at 60 days was significantly worse than baseline (p=0.02).

Conclusion:
In the DOSE trial, WRF precipitated by an aggressive loop diuretic strategy was transient and not associated with worse eGFR at 60 days whereas WRF in the absence of aggressive diuresis was associated with long term decline in renal function. The mechanism underlying WRF may be important in driving long term renal outcomes.
Abstract 19598: Estimation of Population Sodium Intake in Different Countries: Comparison of 24-h Dietary Recall With 24-h Urine Collection
Authors: Wen Xiaoxiao , Stamler Jeremiah , Van Horn Linda , Daviglus Martha L , Dyer Alan R , Elliott Paul , Chan Queenie , Ueshima Hirotsugu , Miura Katsuyuki , Okuda Nagako , Wu Yangfeng , Zhao Liancheng
Published: July 2021

Introduction:
Twenty-four-hour (24-h) urine excretion is the “gold standard” for estimation of sodium intake. Sodium intake assessed by 24-h dietary recall has been reported to correlate with urinary sodium excretion, and is considered reliable for assessing population sodium intake. However, the validity of 24-h dietary recall across countries has rarely been studied. The present study aims to compare the 24-h dietary recall with 24-h urine collection for the estimation of population sodium intake in different countries.

Methods:
Data from the International study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) were used in the analyses, including 4680 men and women ages 40-59 years from 17 population samples in China, Japan, UK and USA. Four 24-h dietary recalls and two timed 24-h urine samples were collected for each participant; the averages of the dietary and urinary sodium measurements were used. The correlation and difference between the two methods were then explored and compared across countries.

Results:
After adjustment for population sample and gender, a significant correlation was found in all four countries between dietary and urinary sodium measurements (r=0.33, 0.45, 0.36 and 0.46 for China, Japan, UK and USA respectively, P<0.01 for all). The mean difference of sodium measurements between dietary recalls and urine collection was small for Japan (3.9 mmol), UK (2.9 mmol), and USA (-3.5 mmol), whereas it was large for China (-54.0 mmol). Further, population average sodium intake was over- or under-reported by about 2% for Japan, UK and USA participants with use of urinary sodium excretion as the reference, while the sodium intake was under-reported by 24% for Chinese.

Conclusions:
The correlation of sodium intake estimated by the two methods is similar (0.33-0.46) for the four countries, and the 24-h dietary recall data demonstrate great accuracy in assessing sodium intake at the population level for Japan, UK and USA. For Chinese populations, however, the 24-h urine collection is preferable to the 24-h dietary recall since dietary recalls yielded considerable underestimation of sodium intake.
Abstract 19637: Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990- 2011
Authors: Bikdeli Behnood , Punnanithinont Natdanai , Akram Yasir , Lee Ike , Desai Nihar R , Ross Joseph S , Krumholz Harlan M
Published: July 2021

Background:
Surrogate endpoint trials can test strategies more efficiently, but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. We sought to determine recent trends in the publication of cardiovascular trials with surrogate outcomes.

Methods:
We identified cardiovascular trials with primary surrogate endpoints published in NEJM, Lancet, and JAMA from January 1990 to December 2011. Trends in publication of surrogate endpoint trials, and the success of the trials in meeting their primary endpoint were evaluated. We also tracked the above three journals for publication of clinical outcome trials on the interventions tested in surrogate trials.

Results:
We screened 3016 articles and identified 848 primary hypothesis cardiovascular trials, which included 220 surrogate endpoint trials. There was an increase over time in the number of surrogate endpoint trials (P=0.01). From the total of 220 surrogate trials, 157 (71.4 %) were positive for their primary endpoint. Sixty (27.5%) surrogate trials were followed by at least one clinical outcome trial. Among these 60 surrogate trials, in 24 cases the outcomes trial results validated the positive surrogates; whereas in 21 subsequent outcome trials were negative following positive results on a surrogate. However, we identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit (Figure).

Conclusions:
Cardiovascular surrogate outcomes trials are common, frequently show superiority of the tested intervention and are infrequently followed by a prominent outcomes trial. However, when there was a high profile clinical outcomes study, half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it.
Abstract 19671: Contemporary Patterns of Utilization and Safety Outcomes of Catheter Ablation of Atrial Flutter in the United States
Authors: Pau Dhaval , Patel Nileshkumar J , Badheka Apurva O , Deshmukh Abhishek , Viles-Gonzalez Juan
Published: July 2021

Introduction:
Atrial flutter ablation has been increasingly offered as first line therapy and has been safely performed over the past few decades. However, limited data exists regarding current utilization and trends in adverse outcomes arising from this procedure. The aim of our study was to examine the frequency of adverse events attributable to atrial flutter (AFL) ablation and the influence of hospital volume on safety outcomes.

Hypothesis:
We hypothesize an association between hospital volume and adverse outcomes.

Methods:
With the use of the Nationwide Inpatient Sample, we identified 89,638 AFL patients treated with catheter ablation from 2000-2011. We investigated common complications including cardiac perforation and tamponade, pneumothorax, stroke, transient ischemic attack, vascular access complications, and in-hospital death. We defined these complications by using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes.

Results:
The overall frequency of complications was 3.17%, with combined cardiac complications (1.44%) being the most frequent. Cardiac complications were followed by vascular complications (0.78%), respiratory complications (0.88%), and neurological complications (0.05%). The in-hospital mortality was 0.17%. Low hospital volume (<50 procedures) was significantly associated with increased adverse outcomes. In addition, there was a small, insignificant rise in overall complication rates over time.

Conclusions:
The overall complication rate was 3.17% in patients undergoing AFL ablation. There was a significant association between low hospital volume and increased adverse outcomes. This suggests a need for future research into identifying the safety measures in AFL ablations and instituting appropriate interventions to improve overall AFL ablation outcomes.
Abstract 19672: Comparison of Major-bleeding Risk and Health Care Costs Among Treatment-naïve Non-valvular Atrial Fibrillation Patients Initiating Apixaban, Dabigatran, Rivaroxaban or Warfarin
Authors: Amin Alpesh , Keshishian Allison , Xie Lin , Baser Onur , Price Kwanza , Vo Lien , Singh Prianka , Bruno Amanda , Mardekian Jack , Tan Wilson , Singhal Shalabh , Patel Chad , Odell Kevin , Trocio Jeffrey
Published: July 2021

Objective:
The study aim was to compare major bleeding risk and health care costs after initiating oral anticoagulants (OACs) for treatment-naïve non-valvular atrial fibrillation (NVAF) patients.

Methods:
Patients in the Medicare advantage population prescribed apixaban, rivaroxaban, dabigatran or warfarin were selected from the Optum Research Database 01JAN2013-31DEC2014. The first OAC prescription date was designated as the index date. Patients were required to have a NVAF diagnosis, continuous health plan enrollment for 6 months and no OAC claims before the index date. Patients were classified into four cohorts based on their index OAC prescription. Major bleeding events, identified by the Cunningham algorithm plus additional bleeding sites, were compared using a Cox proportional hazards model. Health care costs were calculated per patient per month and compared using generalized linear models.

Results:
The study included 36,260 patients: 3,762 apixaban, 2,677 dabigatran, 8,740 rivaroxaban, and 21,081 warfarin patients. CHA2DS2-VASc score was higher in apixaban patients (4.2) compared to dabigatran and rivaroxaban (both 4.0; p<0.001), but lower than in warfarin patients (4.3; p<0.001). After adjusting for baseline characteristics, apixaban patients were significantly less likely to have a major-bleeding event within one year of treatment initiation compared to rivaroxaban (HR=0.69; 95% CI=0.59-0.81) and warfarin (HR=0.71; 95% CI=0.61-0.82) patients and trended towards numerically lower major bleeding compared to dabigatran patients (HR=0.87; 95% CI=0.72-1.06). Major bleeding-related medical costs were lower in apixaban patients ($53) compared to rivaroxaban ($111) and warfarin ($138) patients (p<0.001) and similar to dabigatran patients ($44, p=0.370). Furthermore, apixaban patients incurred lower all-cause medical costs ($1,646) compared to dabigatran ($1,974, p=0.02), rivaroxaban ($1,909, p=0.002) and warfarin ($2,162, p<0.001) patients.

Conclusion:
In a large national Medicare advantage population, treatment-naïve NVAF patients treated with apixaban were significantly less likely to have a major-bleeding event compared to those prescribed rivaroxaban or warfarin and had significantly lower medical costs.
Abstract 19684: Nitric Oxide Protects From Cardiac Ischemia/reperfusion Damage by Blocking Activation of Extracellular Matrix Metalloproteinase Inducer EMMPRIN Through Binding to Caveolin3
Authors: Cuadrado Irene , Martin Ana M , Saura Marta , Zamorano Jose L , Zaragoza Carlos
Published: July 2021

Introduction:
Nitric Oxide (NO) induces cardiac protection by still unknown mechanisms. We previously found that Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a target of NO during ischemia/reperfusion (IR). Hypothesis: EMMPRIN is glycosylated at different locations, and high glycosylated forms of EMMPRIN are required for matrix metalloproteinase downstream activation in several cell types. In hearts subject to IR NO may inhibit EMMPRIN glycosylation.

Methods:
A surgical model of coronary artery occlusion.

Results:
We found that iNOS null mice show high glycosylated (active) forms of EMMPRIN, whereas NO producing mice also show low glycosylated EMMPRIN. Likewise, NO producing mice exhibit a significant level of cardiac protection, as shown by increased left ventricle ejection fraction detected by high frequency ultrasound, and decreased area of infarction as shown by ex vivo TTC staining. To test whether low glycosylated forms of EMMPRIN may play a role in iNOS WT cardiac protection, we found that EMMPRIN binds to caveolin-3 in healthy hearts, however, I/R prompted the disruption of low glycosylated EMMPRIN from caveolin-3 in iNOS null mice in a time dependent manner whereas a significant low glycosylated portion of EMMPRIN remained bound to caveolin-3 in iNOS WT mice. To study this effect in more detail, we found that caveolin-3 binding to low glycosylated forms of EMMPRIN, prevents downstream EMMPRIN-mediated extracellular matrix degradation through matrix metalloproteinase activation. I/R damage resulted more severe in caveolin-3 null mice, where no low glycosylated EMMPRIN was detected after reperfusion. Conclusions: We show for the first time that caveolin-3 induces nitric oxide mediated cardiac protection by preventing glycosylation of EMMPRIN in mouse hearts.
Abstract 19719: Super Flexible Heart Replica With Vacuum Casting Technique Reproduces Real Structure and Texture of the Heart Fascinating Simulation Surgery in Complicted Congenital Heart Disease
Authors: Shiraishi Isao , Kurosaki Ken-ichi , Kanzaki Suzu , Hatanaka Katsunori , Ichikawa Hajime
Published: July 2021

Introduction:
Precise understanding of 3D anatomy is crucial for successful surgical operation in complicated congenital heart disease (CHD). We have developed a new technology that reproduces accurate and extremely flexible polyurethane biomodels of complicated CHD suitable for simulation surgery and medical education.

Hypothesis:
A novel 3D printing technique employing with stereolithography followed by vacuum casting is suitable for simulation surgery in complicated CHD.

Methods:
Thirty five replicas of CHD were produced with this technique; diagnosis included tetralogy of Fallot, pulmonary atresia with ventricular septal defect, double outlet right ventricle, persistent truncus arteriosus, hypoplastic left heart syndrome, interrupted aortic arch, congenitally corrected transposition of the great arteries, and so on. Three-dimensional volumetric datasets of MSCT angiography of CHD were converted into standard triangulated language files to make plastic stereolithographic biomodels representing outer and inner surface of the heart. Then, another outer mold was made with urethane using the outer surface biomodels as a cast. Then, rubbery polyurethane was injected between the outer and inner molds under the vacuum condition. After solidification, the molds were carefully removed and the final biomodels were obtained.

Results:
Wide variety of accurate and flexible biomodels of complicated CHDs from neonates to adults were reproduced. This technology allowed surgeons to precisely understand the internal chambers of the heart and allowed them to perform simulation surgery by way of cutting and suturing like a real heart tissue.

Conclusions:
These super flexible and accurate polyurethane biomodels were instructive for surgeons to understand the complex structures and hemodynamics of the disease and also helpful for planning the individual surgical operation of complicated CHD.
Abstract 19720: Jay D. Coffman Early Career Investigator Award: Comparative Efficacy of Initial Endovascular Revascularization vs. Supervised Exercise Training in Patients With Intermittent Claudication: A Meta-analysis of Randomized Controlled Trials
Authors: Pandey Ambarish , Banerjee Subhash , Ngo Christian , Mody Purav , Marso Steven , Brilakis Emmanouil S , Armstrong Ehrin J , Giri Jay , Bonaca Marc P , Pradhan Aruna , Kumbhani Dharam
Published: July 2021

Introduction:
Current guidelines recommend supervised exercise training (SET) as the initial treatment modality for patients with intermittent claudication (IC), in addition to optimal medical therapy. The role of endovascular revascularization (ER) as a primary treatment option has been controversial. We performed a meta-analysis to compare the efficacy of initial ER vs. initial SET in patients with IC using data from randomized controlled trials.

Methods:
The primary outcome was treadmill-measured maximum walking distance (MWD) at the end of follow-up. Secondary outcomes included resting ankle brachial index (ABI) and treadmill-measured ischemic claudication distance (ICD) on follow-up. Risk of adverse limb events (revascularization, amputations) was also compared between the two groups. Random effects models were used for all analyses.

Results:
We included 1,145 patients from nine trials with a mean follow up duration of 13.7 months (42% aortoiliac lesions; 35% stent use; mean baseline ABI 0.64 vs. 0.67 for ER vs. SET). Follow-up MWD was not significantly different between patients undergoing ER vs. SET [Weighted mean difference (WMD) (95% CI): 19.1 m (-79.6 to 117.8 m); publication bias p=0.86]. Metaregression did not identify significant differences based on stent use or presence of aortoiliac disease. ICD was also similar between the two groups [WMD (95% CI): 36.1 m (-99.4 to 171.5 m)]. In contrast, patients undergoing ER had higher resting ABI on follow-up [WMD (95% CI): 0.14 (0.11 to 0.17), p<0.0001]. Adverse limb event rates were similar [5.4% vs. 8.2%, p=0.21].

Conclusion:
Compared with initial SET, initial ER significantly improves resting ABI values. Although longer walking distance and lower rates of adverse limb events also appeared favorable for ER, these differences were not statistically significant in these intermediate term studies. Longer-term studies and those incorporating contemporary revascularization techniques are necessary.
Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents
Authors: Ito Yoshitaka , Naito Kazuhiro , Waseda Katsuhisa , Takashima Hiroaki , Kurita Akiyoshi , Ando Hirohiko , Maeda Kazuyuki , Sakurai Shinichiro , Suzuki Akihiro , Saka Yuki , Mizuno Tomofumi , Kato Isao , Suzuki Yasushi , Amano Tetsuya
Published: July 2021

Background:
While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT.

Methods:
A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score<4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion.

Results:
Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score.

Conclusion:
High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.
Abstract 19834: MicroRNA-148a Inhibits Expression of Plasminogen Activator Inhibitor-1: Mechanistic Implications for Obesity-associated Thrombosis
Authors: Blokhin Ilya O , Devor Eric J , Ramachandran Shyam , Doddapattar Prakash , Jin Hong , Chauhan Anil K , McCray Paul B , Leslie Kimberly K , Lentz Steven R
Published: July 2021

Obesity is an epidemic in developed countries and is associated with an increased incidence of arterial and venous thrombosis. The mechanisms of obesity-induced thrombosis, however, are not well defined. In the current study, we tested the hypothesis that diet-induced obesity causes alterations in microRNA expression that may predispose to thrombosis. To induce obesity, C57Bl/6J mice were fed a 60% high fat diet. Compared with lean mice, obese mice had elevated fasting levels of glucose and insulin resistance, and exhibited acceleration of carotid artery thrombosis after photochemical injury (P<0.01) and increased susceptibility to venous thrombosis induced by inferior vena cava ligation (P<0.05). Plasma levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis secreted by adipocytes and endothelial cells, were elevated 3-fold in obese mice, suggesting a potential mechanism of thrombosis in diet-induced obesity. TaqMan low-density microRNA arrays detected downregulation of 41 microRNAs in plasma exosomes from obese mice (P<0.05). Bioinformatic analysis of the downregulated microRNAs in relation to the PAI-1 3’-UTR identified microRNA-148a as a potential inhibitor of PAI-1 expression in obesity. We found that levels of PAI-1 mRNA were increased 4.5-fold (P<0.05) and levels of microRNA-148a decreased 4-fold (P<0.05) in white adipose tissue from obese mice compared with lean mice. Transfection of primary adipocytes or a murine endothelial cell line (MS-1) with a microRNA-148a mimetic resulted in 50-70% downregulation of PAI-1 expression (P<0.05), demonstrating a causal inverse relationship between microRNA-148a and PAI-1 mRNA. Our findings suggest that downregulation of microRNA-148a in diet-induced obesity may promote thrombosis through loss of repression of PAI-1 expression at the mRNA level.
Abstract 19844: Stromal Interaction Molecule 1 is Essential for the Maintenance of Cardiac Metabolism
Authors: Collins Helen E , Pat Betty M , Litovsky Silvio H , Young Martin E , Chatham John C
Published: July 2021

The ER/SR Ca
2+
sensor, Stromal Interaction molecule 1 (STIM1), a key regulator of store-operated calcium entry is expressed in cardiomyocytes and has been implicated in regulating hypertrophic signaling. We have recently shown that mice with a cardiomyocyte-restricted deletion of STIM1 develop dilated cardiomyopathy. Given the importance of Ca
2+
in regulating cardiac metabolism we examined whether a lack of STIM1 alters cardiac metabolism. We found that hearts isolated from 20 week
cr
STIM1-KO mice exhibit significant changes in cardiac metabolism, observed by a significant reduction in both glucose oxidation (0.75 ± 0.06 v 0.46 ± 0.04 μmol/min/g dry wt,
p
< 0.01) and net lactate release (15.38 ± 1.29 v 10.23 ± 0.87 μmol/min/g dry wt,
p
<0.02) in an isolated perfused working heart model in comparison to control mice. These changes occurred independent of any changes in contractile function or oleate oxidation (0.22 ± 0.03 v 0.26 ± 0.02 μmol/min/g dry wt,
ns
). Consistent with a reduction in glucose oxidation we also found significant increase in the expression of Pyruvate dehydrogenase kinase and a reduction in the expression of GLUT4 protein levels.

Hearts from 20 week
cr
STIM1-KO contained an increased number of lipid droplets (3.35 ± 0.35 v 2.08 ± 0.20, no of lipid droplets per 4400x grid square,
p
<0.002) and increased triglyceride levels (51.95 ± 5.84 v 32.55 ± 2.41 v 36.05 ± 1.73 mg/dL,
p
< 0.05) in comparison to age-matched controls and
cr
STIM1-KO
+/-
hearts respectively. In addition to these metabolic changes there were was also significant disruption in mitochondrial morphology and structure in
cr
STIM1-KO; interesting these same abnormalities were also present in
cr
STIM1-KO
+/-
hearts. We found that 12 week
cr
STIM1-KO
+/-
and
cr
STIM1-KO hearts contained smaller mitochondria compared to controls and that
cr
STIM1-KO were significantly smaller than
cr
STIM1-KO
+/-
(1140.6 ± 28.3nm v 973.9 ± 15.8nm v 887.3 ± 17.1nm,
p
< 0.01)

These data demonstrate for the first time a novel yet critical role for STIM1 in regulating cardiac metabolism and in maintaining mitochondrial morphology and organization. This work was supported by NIH grant R21-HL-110366 (JCC) and an American Heart Association Greater Southeast Postdoctoral fellowship 15POST25260004 (HEC).
Abstract 19878: Burden of Systolic and Diastolic Left Ventricular Dysfunction Among Hispanics in the United States - Insights From the Echocardiographic Study of Latinos (ECHO-SOL)
Authors: Mehta Hardik , Armstrong Anderson , Swett Katrina , Shah Sanjiv , Allison Matthew A , Hurwitz Barry , Bangdiwala Shrikant , Dadhania Rupal , Kitzman Dalane , Arguelles William , Lima Joao , Youngblood Marston , Schneiderman Neil , Daviglus Martha L , Spevack Daniel , Talavera Gregory , Raisinghani Ajit , Kaplan Robert C , Rodriguez Carlos J
Published: July 2021

Introduction:
Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanic/Latino adults. Hypothesis: Among Hispanic/Latino adults, prevalence of clinical HF and subclinical cardiac dysfunction is high.

Methods:
Adult participants of Hispanic/Latino origin were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL). Left ventricular systolic dysfunction (LVSD) was defined as an ejection fraction (EF) less than 50%; left ventricular diastolic dysfunction (LVDD) was defined using the Redfield and American Society of Echocardiography criteria. Baseline diagnosis of clinical HF was defined according to self-report; and those with cardiac dysfunction without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction.

Results:
Of the 1818 participants (mean age 56.4 years; 42.6% male) enrolled in ECHO-SOL, 52.7% had some form of cardiac dysfunction. The prevalence of LVSD was 3.6%, while LVDD was detected in 53.5%. Participants with LVSD were more likely to be males and current smokers and have lower socioeconomic status (all p<0.05). Female sex, hypertension, diabetes, higher body-mass index and renal dysfunction were more common among those with LVDD (all p<0.05). LVSD prevalence did not vary by Hispanic/Latino background group; however, in age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost two-fold more likely to have LVDD compared to those of Mexican backgrounds. Prevalence of clinical HF with LVSD was 7.3%; prevalence of clinical HF with LVDD was 3.6%. Among those with cardiac dysfunction, 96.2% of the cardiac dysfunction was subclinical or unrecognized. Among those with cardiac dysfunction, prevalent coronary heart disease was the only factor independently inversely associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.14; 95% confidence interval: 0.05-0.38).Conclusion: Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, and there is a high prevalence of diastolic dysfunction. This suggests that Hispanics/Latinos are a high-risk population for the development of clinical HF.
Abstract 19900: Impact of Baseline Fitness in Young Adulthood and Age Related Fitness Changes on Cardiac Structure and Function in Middle Age: The CARDIA Study
Authors: Pandey Ambarish , Allen Norrina , Ayers Colby , Reis Jared , Moreira Henrique , Sidney Steve , Jacobs David R , Chow Lisa , Rana Jamal , De Lemos James , Carnethon Mercedes , Berry Jarett D
Published: July 2021

Introduction:
Low cardiorespiratory fitness (CRF) in mid-life is a significant risk factor for heart failure (HF) at a later age. However, the contribution of CRF in early adulthood to HF risk is not well understood. Because of the established association of subclinical abnormalities in left ventricular (LV) structure and function with HF risk, we studied the association between early life CRF levels and measures of LV structure and function in middle-age.

Methods:
We included the Coronary Artery Risk Development in Young Adults (CARDIA) study participants who had a maximal exercise treadmill test (modified Balke protocol) at year 0 and an echocardiogram at year 25. Percent change in CRF [ΔCRF (%)] was calculated in the subgroup of participants who had a repeat CRF test at year 20. Associations of baseline CRF and ΔCRF (%) with measures of LV structure [end-diastolic volume (LVEDV), relative wall thickness (RWT)] and function [global longitudinal strain (GLS), Septal & Lateral E/e`] were assessed using multivariable linear regression.

Results:
We included 3,433 participants (baseline age: 25 years, 55% women) in the study. After adjustment for baseline characterstics, cumulative cardiovascular risk factor burden, and baseline and follow up body mass index (BMI), lower baseline CRF was associated with higher septal E/e`(β = -0.05, p = 0.01), higher lateral E/e` (β = -0.06, p = 0.008), and lower LVEDV (β = 0.07, p = 0.004). In contrast, CRF was not associated with GLS (p = 0.22) and RWT (p=0.27). Among participants with repeat CRF test (n =2,544), ΔCRF (%) was associated with LVEDV but not with measures of LV function. The association of baseline CRF with E/e` did not attenuate after additional adjustment for ΔCRF (%) (Table).

Conclusions:
Lower CRF in young adulthood is associated with subclinical abnormalities in diastolic function in middle age. These findings suggest that low CRF may identify young adults at increased risk of HF with preserved ejection fraction in later life.
Abstract 19925: Novel Pre-implant Characteristics Associated With 12 Month Risk of Gastrointestinal Bleeding Among Patients Supported With Continuous Flow Left Ventricular Assist Device Therapy
Authors: Shi Yang , Rappelt Matthew , Yousefzai Rayan , Sulemanjee Nasir , Zwicke Dianne , Hastings Thomas , Cheema Omar , Downey Francis , Crouch John , Thohan Vinay
Published: July 2021

Introduction:
Continuous-flow Left Ventricular Assisted Device (CF-LVAD) therapy is increasingly utilized for patients with end stage heart failure. Among the most common and unpredictable complications after CF-LVAD is gastrointestinal bleeding (GIB).

Hypothesis:
We hypothesize that pre-implant characteristics are associated with GIB post-implant of a CF-LVAD. The aim of this analysis is to identify novel pre-implant factors that influence risk of post-implant GIB.

Methods:
All CF-LVAD implants between January 2006 and December 2014 among patients who survived more than 15 days were included and followed for 12 months. Primary event was GIB and patients were censored at time of re-implant, heart transplant, or death. Student’s t-test was used to compare continuous variables and chi-square test for categorical variables. Cox Proportional Hazards model was used to identify univariate and multivariable models predicting GIB.

Results:
Among the total 257 patients included, 65 (25.3%) were identified as having a GIB. Baseline differences and their independent univariate hazard ratio (HR) are noted in Table 1. Using stepwise selection and developing a multivariable model, prior GI abnormalities (HR=2.12, p<0.01), prior percutaneous coronary intervention (PCI: HR=2.65, P<0.01) and chronic obstructive pulmonary disease (COPD: HR=1.73, P<0.01) remained statistically significant predictors of GIB (Table 2).

Conclusions:
We describe novel risk factors (history of GI abnormalities, prior PCI, COPD) as predictors for developing GIB post CF-LVAD implantation. We advocate a closer examination of these risk factors when evaluating patients for CF-LVAD therapy.
Abstract 19944: Targeted Therapy of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: Safety and Efficacy in Comparison to IPAH in Compera
Authors: Rosenkranz Stephan , Hoeper Marius M , Huscher Doerte , Pittrow David , Opitz Christian F
Published: July 2021

Background:
While targeted therapies are available for idiopathic pulmonary arterial hypertension (IPAH), evidence based treatment recommendations for pulmonary hypertension (PH) associated with heart failure and preserved ejection fraction (HFpEF) are lacking.

Methods and Results:
Out of 5,935 patients in the prospective COMPERA registry, we analyzed patients with “typical” IPAH (n=421, ≤2 of the following risk factors: BMI >30 kg/m2, hypertension, CAD, diabetes and atrial fibrillation at the time of diagnosis), “atypical” IPAH (n=139, >2 risk factors) or PH-HFpEF (n=226) who received targeted PH therapies. Patients with PH-HFpEF, when compared to “typical” and “atypical” IPAH were older (73±8 vs. 62±17 and 71±9 years), had a higher BMI (30 vs. 26 and 32 kg/m2), and more comorbidities (98% vs. 73% and 100%, all p<0.001), respectively. However, mean PAP (46±9 vs. 47±13 and 44±11 mmHg), cardiac index (2.2±0.7 vs. 2,3±0,8 and 2,2±0,8 l/min), and mixed venous oxygen saturation (62±7 vs. 62±10 and 63±9%, all ns) were almost identical. As compared to “typical” and “atypical” IPAH, PH-HFpEF patients had a higher PAWP (20±4 vs. 9±3 and 10±4 mmHg), resulting in a lower calculated PVR (559±270 vs. 861±477 and 784±844 dyn.s.cm-5). Survival at 1, 2 and 3 years post diagnosis was not different between groups. PDE-5 inhibitors were the most common form of initial PH treatment in PH-HFpEF (94%), and combination therapy was less common compared to “typical” or “atypical” IPAH at 1 year (7% vs. 44% and 26%). All 3 groups responded to targeted PH therapies at 12 months, while treatment effects were less pronounced in PH-HFpEF: Compared to baseline, the median increase of the 6MWD at 1 year was 29, 50, and 60 m, respectively. Treatment discontinuations occurred more frequently in patients with PH-HFpEF than in IPAH, either because of side effects or lack of improvement.

Conclusions:
Despite almost identical alterations of pulmonary artery pressure and cardiac output, patients with PH-HFpEF differed with respect to age, comorbidities and certain hemodynamic features when compared to “typical” or “atypical” IPAH. All groups responded to targeted PH therapy, however tolerability and efficacy of PH drugs were reduced in patients with PH-HFpEF while survival was not different.
Abstract 19965: Metabolomic Signature of Fermented Milk Consumption Linked With Lower Prevalence of First-diagnosed, Stable Coronary Artery Disease
Authors: Teren Andrej , Beutner Frank , Vogel Anika , Ceglarek Uta , Scholz Markus , Schuler Gerhard , Thiery Joachim
Published: July 2021

Introduction:
Currently available epidemiologic studies examining the potential cardiovascular effects of milk and fermented milk products (FMP) are conflicting. Hypothesis: We aimed to assess the metabolomic signature of milk-containing nutrients, intake of which associates with the extent of stable coronary artery disease (CAD).

Methods:
We recruited 1301 patients (median age 62 years [interquartile range: 53-69]; men 809 [62.2%]) admitted for suspected stable CAD. Prior to coronary angiography, all patients answered a validated semi-quantitative Food-Frequency-Questionnaire. In addition, venous blood was collected from each patient for whole blood metabolomic analysis of 26 amino acids and 26 acylcarnitines, applying the targeted mass-spectrometry-based method. Obstructive CAD (obCAD) was represented by ≥ 1 coronary stenosis > 50%. Non-obstructive CAD (nobCAD) was defined by angiographic presence of coronary atherosclerosis without any coronary stenosis > 50%.

Results:
Patients with obCAD (n =515) showed lower median FMP intake (134.5 g/die [IQR: 83.1-214.5]) than patients with nobCAD (n=264; 150.7 g/die [IQR: 78.8-257.0]; p<0.001), and patients with no CAD (n=522; 168.2 g/die [IQR: 101.2-265.9; p<0.001]), respectively. We found no between-group difference in average milk intake (obCAD: 27.9 g/die [IQR: 3.2-93.1]; nobCAD: 27.5 g/die [IQR: 4.1-95.0]; no CAD: 40.4 g/die [IQR: 4.5-94.7]; NS). When considering each subgroup of FMP separately, higher yoghurt intake was in inverse, independent association with prevalence of obCAD (OR 95%CI: 0.867 [0.774-0.970]; p=0.002), and nobCAD + obCAD (OR 95%CI: 0.876 [0.785-0.978]; p=0.018), respectively. Upon adjustment for relevant confounder, increased FMP consumption correlated with lower blood concentrations of acylcarnitines (r= -0.062; p=0.032); in particular C2 (r= -0.105; p<0.001), C4 (r= -0.082; p=0.004), C4OH (r= -0.070; p=0.013), C5 (r= -0.072; p=0.015), C8 (r= -0.069; p=0.017), and C141 (r= -0.097; p=0.001).

Conclusion:
Increased consumption of fermented milk was linked with lower prevalence of stable coronary artery disease and associated with decreased blood concentrations of short- and medium-chain saturated, and long-chain monounsaturated fatty acids.