bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13812: Pulmonary Function Predicts Cardiac Function, Structure & Clinical Outcome in Chronic Heart Failure: Results From the Myovasc Study
Authors: Heidorn Marc W , Müller Felix , Steck Stefanie , Schuch Alexander , Tröbs Sven O , Buch Gregor , Sebastian Göbel , Schulz Andreas , Panova-Noeva Marina , Wagner Bianca , Lackner Karl J , Gori Tommaso , Muenzel Thomas , Wild Philipp , Prochaska Jürgen
Published: May 2021

Introduction:
A growing body of evidence suggests a relevance of pulmonary function in the pathophysiology of heart failure (HF). Comprehensive data on the role of forced expiratory volume in 1 second (FEV1) in the development & progression of HF is limited.

Hypothesis:
Given this background, we hypothesized, that (FEV1) is associated with deteriorated left ventricular (LV) functional as well as structural status, & predicts specific clinical outcome in HF.

Methods:
Data from the MyoVasc Study (n=3,289) were analysed. Comprehensive clinical phenotyping including body plethysmography for the evaluation of FEV1 & standardized echocardiography were performed during a five-hour investigation in a dedicated study center. Worsening of HF (comprising transition from asymptomatic to symptomatic HF, HF hospitalization, & cardiac death) was assessed during a structured follow-up with subsequent validation & adjudication of endpoints.

Results:
Information on FEV1 was available in 2,998 individuals (age 35-84 years; 34.1% female, mean FEV1 92.4[% predicted]). In multivariable regression analysis adjusted for age, sex, height, cardiovascular risk factors (CVRF) & clinical profile, FEV1
per-1SD
was an independent predictor of reduced LV ejection fraction (β:-1.6[95%CI -2.0;-1.3]), elevated E/E’-ratio (β:0.82[0.64;0.99]), & increased LV mass/Height
2.7
(β:1.6[1.1;2.1]) (for all, P<0.001). During a median follow-up of 2.3 (interquartile range 1.1; 4.0) years, FEV1
per-1SD
predicted worsening of HF (hazard ratio(HR) 1.46[1.30;1.65], P<0.001) independent of age, sex, height, CVRF & comorbidities. This finding was consistent among the single components of the primary study endpoint: FEV1
per-1SD
predicted an increased risk for transition to symptomatic HF (HR 1.57[1.19;2.06]), HF hospitalization (HR 1.35[1.16;1.57]) & for cardiac death (HR 1.84[1.49;2.26]) (for all, P<0.001). FEV1
per-1SD
remained an independent predictor of worsening of HF after additional adjustment for NT-proBNP (HR 1.25[1.08;1.45], P=0.002).

Conclusion:
Impaired FEV1 is directly linked to the pathophysiology of HF & represents a strong & independent predictor of HF outcome highlighting its potential value to advance risk prediction in HF.
Abstract 13814: Semaglutide Reduces Mace Consistently Across Baseline Triglyceride Levels in Patients With Type 2 Diabetes: A Post Hoc Analysis of the Sustain 6 and Pioneer 6 Trials
Authors: Verma Subodh , Leiter Lawrence A , Michelsen Marie M , Orsted David , Rasmussen Soren , Bhatt Deepak L
Published: May 2021

Introduction:
Elevated triglyceride (TG) levels may predict CV events, although this has not been evaluated in large contemporary trials. The effects of glucagon-like peptide-1 receptor agonists on major adverse CV events (MACE) across TG levels are not fully characterized. SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) were randomized, CV outcomes trials investigating once-weekly and oral semaglutide vs placebo, respectively, in patients with type 2 diabetes at high CV risk. We performed a
post hoc
analysis to assess the effect of semaglutide vs placebo on the primary endpoints, MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), and its components in these two trials pooled, across baseline TG levels.

Methods:
The risk of first MACE with semaglutide vs placebo was evaluated across three baseline TG groups (≤151, >151-≤205, and >205 mg/dL). The effect of semaglutide vs placebo on MACE was estimated with Cox regression by TG level categorically, and continuously when adjusting for baseline TG and high-density lipoprotein-cholesterol (HDL-C) levels. The impact of statin treatment was also assessed.

Results:
In total, 6,417 patients had baseline TG measurements: 3,191 (49.7%) ≤151, 1,459 (22.7%) >151-≤205, and 1,767 (27.5%) >205 mg/dL; mean (±SD) TGs were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively. Overall, semaglutide reduced TGs vs placebo by 5% in SUSTAIN 6 and 6% in PIONEER 6 (p<0.01). The incidence of MACE with placebo increased across increasing TG levels
(Figure)
. Semaglutide generally reduced the risk of MACE and its components vs placebo across TG groups. Results were consistent when evaluating TGs as a continuous variable (adjusting for baseline TG and HDL-C levels), and regardless of statin treatment.

Conclusions:
In this post hoc analysis of SUSTAIN 6 and PIONEER 6, over half of patients had elevated TG levels (>151 mg/dL). Semaglutide consistently reduced the risk of MACE vs placebo across baseline TG levels.
Abstract 13822: Comparison of Produced Potential Delay in Superior Vena Cava During Right Pulmonary Vein Isolation Between High-power Short-duration and Conventional Settings
Authors: Hijioka Naoko , Kaneshiro Takashi , Amami Kazuaki , Yamada Shinya , Ishida Takafumi , Takeishi Yasuchika
Published: May 2021

Background:
Recently, a high-power short-duration (HP-SD) setting has been introduced in atrial fibrillation (AF) ablation. Ablation using this setting reduces collateral tissue damage by shortening the conductive heating phase compared to conventional setting. However, the lesion characteristics have not been rigorously evaluated during ablation procedure. We hypothesized that superior vena cava (SVC) potential could be affected by excessive transmural lesions in anterior-superior right pulmonary vein isolation (PVI), adjacent to posterior aspect of SVC. Therefore, we compared the produced potential delay in SVC between HP-SD and conventional settings.

Methods and Results:
The consecutive 42 patients (61±10 years, 32 men) who underwent PVI for drug refractory AF were analyzed. Before introduction of HP-SD setting to AF ablation in November 2018, 14 patients underwent right PVI with conventional setting with output of 20-30 W (Conventional group). In the remaining 28 patients after then, right PVI was performed using HP-SD setting with output of 45-50 W (HP-SD group). We compared total radiofrequency energy and mean contact force along the anterior superior right PVI line between the 2 groups. Moreover, the produced SVC potential delay was calculated after anterior superior right PVI and compared between the 2 groups. Total radiofrequency energy delivered (6138 J vs. 6139 J, P = 0.999) and the mean contact force (17.2 g vs. 20.2 g, P = 0.100) in the anterior superior right PV did not differ between the HP-SD and Conventional groups. However, the produced SVC potential conduction delay after anterior superior right PVI was significantly longer in Conventional group compared to HP-SD group (6.2 ms vs. 0.5 ms, P < 0.001).

Conclusions:
Our data suggest that HP-SD setting caused less collateral tissue damage than conventional setting during PVI. The significant produced SVC potential delay might be a surrogate marker of collateral tissue damage by conductive heating phase in PVI.
Abstract 13826: Lipoprotein (a) Levels Among Children Diagnosed With a Primary Hypercholesterolemia
Authors: Uzun Duygu , Anne Premchand , Maciejko James
Published: May 2021

Introduction:
The American Academy of Pediatrics (AAP) recommends universal lipid screening in all children beginning at nine years of age. Although not a component of the lipid profile, an elevated lipoprotein (a) (Lp(a)) (≥30 mg/dL) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in adults. Plasma Lp(a) levels are a product of the Lp (a) gene, which is fully expressed by 5 years of age, and remains relatively unchanged into adulthood. Limited number of studies have examined Lp(a) levels in children diagnosed with a primary hypercholesterolemia.

Hypothesis:
To determine the frequency of Lp(a) excess, defined as ≥30 mg/dL, among children diagnosed with a primary hypercholesterolemia (i.e., Familial Hypercholesterolemia (FH), Familial Combined Hyperlipidemia (FCH), Polygenic Hypercholesterolemia (PH).

Methods:
We reviewed the Ascension St. John Children’s Center Lipid Clinic database between 8/1/2012 and 12/31/2019. Only children diagnosed with a primary hypercholesterolemia and having a baseline Lp(a) assessment were included. FH was diagnosed using the Dutch Lipid Score. PH was diagnosed as an elevated LDL-C level not associated with a monogenic mutation or a secondary cause. FCH was diagnosed as an elevated LDL-C in combination with any triglyceride elevation in the absence of secondary causes.

Results:
One-hundred and twenty patients were evaluated (mean age: 12.1 ± 2.0 years). Seventy-eight percent (93) of the children were white and 52% (62) were male. The frequency of an Lp(a) excess was 44% (53) in this group. The frequencies of Lp(a) excess by diagnosis, and the median Lp(a) and mean LDL-C levels are displayed in Table 1.

Conclusions:
Lp(a) excess is relatively frequent among children diagnosed with a primary hypercholesterolemia. Since an Lp(a) excess is an ASCVD risk factor, it should be considered clinically relevant when determining the baseline LDL-C level at which a lipid-lowering agent is initiated in children.
Abstract 13846: Growth Differentiation Factor 15 and Risk of Clinical Bleeding Events in the Atherosclerosis in Communities (ARIC) Study
Authors: Mathews Lena , Ding Ning , Ishigami Junichi , Al Rifai Mahmoud , Hoogeveen Ron C , Coresh Josef , Christie Ballantyne M , Selvin Elizabeth , Matsushita Kunihiro
Published: May 2021

Introduction:
Growth differentiation factor 15 (GDF15), a cytokine growth factor, is a predictor of bleeding in people with cardiovascular disease (CVD). Potential mechanisms include direct inhibition of platelet activity or as a marker of tissue vulnerability.

Hypothesis:
We hypothesized that GDF15 will also be associated with bleeding in individuals without a history of CVD.

Methods:
We studied the association of GDF15 with clinical bleeding events among 9,850 ARIC participants without prior bleeding and CVD at baseline (mean age 60 years, 57% female, 21% black). Serum levels of GDF15 were measured in relative fluorescence units using DNA-based aptamer technology (SOMA scan assay). Bleeding events were ascertained using discharge codes. We examined incidence rates for bleeding using Poisson models, hazard ratios (HRs) of incident bleeding using Cox models, and the improvement in risk prediction of bleeding using the Harrell’s-
c
statistic with the addition of GDF15 to established predictors in a commonly used bleeding risk score.

Results:
There were 1,291 hospitalizations with bleeding during a median follow up of 22.1 years through 2018, with the majority (87.8%) being gastrointestinal bleeding. The incidence rate of bleeding per 1,000 person-years was 3.4 in the highest quartile of GDF15 and 1.8 in the lowest quartile. The highest quartile of GDF15 was associated with an adjusted HR of 1.52 (95% CI 1.27-1.81) for total bleeding and 1.55 (1.28-1.88) for gastrointestinal bleeding compared to the lowest quartile. The addition of GDF15 to a validated bleeding risk score improved the
c-
statistic by 0.030 (0.010-0.50) from 0.640 to 0.669.

Conclusions:
Higher levels of GDF15 were robustly associated with bleeding hospitalizations and improved risk prediction beyond conventional bleeding risk factors. Our results suggest the etiological contributions of GDF15 to bleeding and its potential usefulness for risk classification of bleeding in individuals without CVD.
Abstract 13863: Outcomes of Hybrid Convergent Procedure in Patients With Persistent and Longstanding, Persistent Atrial Fibrillation
Authors: Crossen Karl , Foley Lisa D , Stone James , Ferguson Edward , Talton David , Garrett Edward , Askew Judah , Kyker Keith
Published: May 2021

Introduction:
The primary indications for AF ablation are to reduce symptoms, time in AF and burden of medical management. Catheter ablation has suboptimal outcomes in persistent/longstanding persistent AF, however the hybrid Convergent procedure (combined endocardial and epicardial ablation) has shown promising results. The study objective was to evaluate outcomes of Convergent hybrid procedure for AF.

Methods:
The Convergent procedure involves a cardiac surgeon ablating the pulmonary veins (PV) and left atrial posterior wall epicardially via subxyphoid or transdiaphragmatic access. The EP then endocardially isolates the pulmonary veins and other AF triggers evident during mapping. A retrospective analysis of outcomes at a mean follow up of one year after Convergent ablation was performed. The composite burden score, which is a summation of a) AF burden, b) frequency of symptoms, and c) AAD status was calculated at baseline and at various follow-up intervals (see Table 1).

Results:
Fifty-seven consecutive highly symptomatic AF patients received Convergent ablation between October 2014-March 2019 at a single center. Baseline parameters were mean age 65.9 ± 9.2 years, 39% female, 52% LVEF, 4.3±4.3 years in continuous AF. Primary safety events were similar to those reported with endocardial catheter ablation. Of 57 patients, 29 (51%) had continuous rhythm monitors and the rest received ECG every 3-6 months until last follow-up. At a mean follow up of 350±122 days, 77% patients either had no AF or were free from AF at least 95% of the time. The composite burden score significantly reduced during 1 year since Convergent ablation (p<0.001, Figure 1).

Conclusion:
Convergent hybrid procedure is safe and reduces the burden of AF as shown by sustained improvement in AF symptoms, reduction in AAD usage and reduction in time in AF. A heart team approach where the cardiac surgeon and EP collaborate is effective in the treatment of persistent/long-standing persistent AF.
Abstract 13864: In-hospital Management and Outcomes of Acute Myocardial Infarction Before and During the Coronavirus Disease 2019 Epidemic
Authors: Huang Bing , Yan Hui , Cao Guiqiu , Chen Jing , Jiang Hong
Published: May 2021

Introduction:
The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. This study sought to share our experiences with in-hospital management and outcomes of acute myocardial infarction (AMI) before and during the COVID-19 epidemic.

Methods and Results:
We retrospectively analyzed consecutive AMI patients, including those with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), from February 1, 2020, to April 15, 2020 (case group), and from January 1, 2019, to December 31, 2019 (control group) and conducted a 1:1 ratio-matched case-control study. Fifty-three AMI (31 STEMI, 22 NSTEMI) patients during the COVID-19 epidemic were matched to 53 AMI patients before the epidemic. Baseline characteristics were comparable between the groups. STEMI patients in the case group had a longer delay time, less primary or remedial PCI and more emergency thrombolysis than those in the control group. Less coronary angiography and stenting were performed in AMI patients in the case group than in the control group. Although there were no statistically significant differences in clinical outcomes between the two groups, STEMI patients in the case group had more than a three-fold increase in mortality rates. AMI combined with COVID-19 infection was associated with higher rates of mortality than AMI alone.

Conclusions:
The COVID-19 epidemic has resulted in significant reperfusion delays in STEMI patients and has a marked impact on the treatment options selection in AMI patients. This epidemic also results in more than a three-fold increase in mortality rates in STEMI patients, although the differences were not statistically significant.
Abstract 13869: Inflammatory Changes in the Lungs of Rats Exposed to E-cigarettes Without Marijuana, Vitamin E Oil, or Nicotine
Authors: Shi Jianru , Kleinman Michael T , Arechavala Rebecca J , Herman Dave , Hasen Irene , Ting Amanda , Wangde Dai , Carreno Juan , Chavez Jesus , Zhao Lifu , Kloner Robert A
Published: May 2021

Background:
Recently, the clinical entity of EVALI (E-cigarette or vaping product use associated lung injury) was described and has similarities to COVID -19 pneumonia. We determined in a quantitative manner the inflammatory changes in the lungs associated with EVALI in a rodent model that does not include use of marijuana, vitamin E oil, or nicotine, which had been implicated as a cause.

Methods:
Adult Sprague Dawley rats were exposed to either pure air (n=5) or electronic cigarette (eC) vapor (propylene glycol/vegetable glycerin, tobacco flavoring) using a device with a nickel-chromium alloy (NC) heating element at 70 Watts (n=6) for 2 hours. The e-liquid did not contain nicotine, marijuana, or Vitamin E oil. Rats were euthanized within a few days of exposure and H&E-stained lung sections were assessed. Inflammatory cells were counted from 10 random areas per section at 20х magnification.

Results:
Alveolar structure appeared normal in the air group (Figure, panel C); the eC group using the NC heating element showed alveolar inflammation (D). The numbers of inflammatory cells per high power field in the lung parenchyma were significantly greater in the rats exposed to eC using NC heating element (67.5 ± 44.5) compared to the air group (6.7 ± 0.3; P < 0.001, Kruskal-Wallis test). The predominant cell type was mononuclear and secondary were neutrophils. Other features included accumulation of fibrin and inflammatory cells in the lumen of the trachea (A); thickened alveolar walls; and red blood cell congestion (D). Inflammation of the nasal passages was also observed (B). Exposure of rats to e cigarettes using a stainless steel heating element did not result in EVALI, and the amount of inflammatory cells was closer to air exposed rats (7.2± 0.4).

Conclusion:
Vaping using a nichrome heating element at high power leads to respiratory tract pathology and a significant increase in the number of inflammatory cells in the alveoli. EVALI occurred without marijuana, vitamin E oil or nicotine.
Abstract 13871: Plasmacytoid Dendritic Cell-derived Interferons Mediate Myocardial Ischemia-reperfusion Injury by Activating Type I Interferon Receptor
Authors: Zhang Aimee , Marsh Katherine , Kron Irving , Yang Zequan
Published: May 2021

Introduction:
We have previously demonstrated type I interferon (IFN-I) is elevated during and mediates myocardial ischemia-reperfusion injury (IRI).

Hypothesis:
Plasmacytoid dendritic cells (pDCs) secrete IFN-I to exacerbate myocardial IRI by activating IFN-I receptor (IFNAR).

Methods:
C57BL/6 (WT) and IFNAR1 knockout (KO) mice underwent 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion. At the end of reperfusion, plasma was obtained and hearts were harvested for TTC-Phthalo-blue staining to calculate infarct size (IS), denoted as a percentage of the ischemic risk region (RR). In pDC-depleted mice, WT mice were treated with PDCA-1 antibody (250 μg via intraperitoneal injection) on days 1, 3, 5, 7 prior to undergoing IRI on day 11. Control mice were treated with isotype IgG. For IFNAR blockade, IFNAR1 antibody (MAR1-5A3 2.0 μg/g) was administered as an IV bolus to WT mice 5 minutes before reperfusion.

Results:
Flow cytometry demonstrated that PDCA-1 antibody treatment had no effect on the number of splenic conventional dendritic cells (1.87±0.33% vs. 1.55±0.12% in IgG control, p=NS), but significantly reduced splenic pDCs by 60% (0.47±0.01% vs. 1.41±0.29% in IgG control, p<0.05. Figure). pDC-depleted mice had significantly smaller IS compared to control after IRI (31.4±2.8 vs. 51.1±6.0, p<0.05. Figure). At the end of reperfusion, plasma levels of IFNα and IFNβ were significantly elevated in IgG control but not in pDC-depleted mice. RRs were comparable in WT mice with/without IFNAR1 blockade and congenic IFNAR1 KO mice following IRI. WT control and IgG control mice had similar IS (53±4 vs. 49±4, p=NS). IS was significantly reduced by greater than 30% in IFNAR1 mAb-treated mice and IFNAR1 KO mice (p<0.05 vs. controls).

Conclusions:
pDCs are activated during myocardial IRI and secrete IFN-I, which subsequently activates IFNARs and exacerbates IS. This pathway presents potential new therapeutic targets to attenuate myocardial IRI.
Abstract 13872: Cue Restricted Smoking Increases Quit Rates With Varenicline
Authors: Scholz Jaqueline , Abe Tania O , Gaya Patricia , Moraes Iana R , Bellini Bianca , Tomaz Paulo R , Santos Juliana R , Santos Paulo C , Tonstad Serena
Published: May 2021

Introduction:
Varenicline effectively helps smokers quit by reducing withdrawal symptoms and blocking the reward of smoking. However, most quitters return to smoking within 1 year. “Cue-restricted smoking” is a behavioral technique designed to increase quit rates by asking smokers attempting to quit to restrict smoking to the standing position, while alone, in an isolated area facing a wall, with the cigarette as the only stimulus.

Hypothesis:
We compared the effectiveness of cue-restricted smoking cessation advice versus standard target quit date advice from day 8 of initiating varenicline in smokers making a quit attempt at the Smoking Cessation Service at the Prevention Department of the Heart Institute, Sao Paulo, Brazil.

Methods:
Using retrospective clinic records we compared quit rates in 281 smokers (50% males) instructed in the cue-restricted smoking cessation method during 2016-18 to quit rates in 324 smokers (46% males) advised to completely stop smoking on the target quit date which we previously used during 2011-14. All were prescribed varenicline for 12 weeks alone, with the addition of bupropion if needed after 4 weeks. Follow-up consisted of behavioral support at 4-6 visits during active drug treatment and telephone counselling at 24 and 52 weeks. The smoking cessation rate was confirmed with expired carbon monoxide at the 12-week clinic visit and only by telephone at 52 weeks.

Results:
The mean age of smokers was 49 ±12 years both groups and the number of cigarettes smoked daily was similar (18/day in the cue-restricted versus 19/day in the target quit day group). The smoking cessation rate at 12 weeks was 75% in the cue-restricted versus 45% in the target quit day group (relative risk 1.8; 95% confidence interval 1.4-2.2; p<0.001). At 52 weeks the quit rate was 65% vs 34% respectively (relative risk 1.9; 95% confidence interval 1.5-2.4; p<0.001).

Conclusion:
Cue restricted smoking substantially increased the chance of quitting compared with standard advice during treatment with varenicline . These results should be further studied in a randomized controlled trial.
Abstract 13875: Pulmonary Artery Pressure Guided Heart Failure Management Reduces Hospitalizations Across All Stages of Chronic Kidney Disease
Authors: Raval Nirav Y , Velika Ali , Adamson Philip , Williams Christopher , Brett Marie-elena , Costanzo Maria Rosa
Published: May 2021

Introduction:
Pulmonary artery pressure (PAP)-guided treatment reduces heart failure hospitalizations (HFH) in randomized and “real world” studies. Underlying CKD in HF patients portends poorer outcomes. This analysis was performed to determine if benefit of PAP-guided HF therapy persists with increasing CKD severity.

Methods:
This retrospective cohort study was conducted in NYHA Class III HF recipients of the PAP sensor enrolled in the CardioMEMS Post Approval Study. Patients were subdivided into quartiles of glomerular filtration rates estimated by MDRD equation (eGFR). Rates of HFH 1 year before versus 1 year after PAP sensor implantation were compared across quartiles of eGFR using the Andersen-Gill Cox proportional hazards model, while accounting for competing risk of death, advanced HF therapies, and progression to end-stage kidney disease. Multivariate analysis was performed to identify independent predictors of CKD (baseline eGFR < 90 mL/min/1,73m
2
) progression.

Results:
Among 1200 PAP sensor recipients, 1119 had concomitant CKD with CKD stages 3 and 4 occurring in 754 patients (67.4%). In CKD patients, 40.6%, 42.1%, and 17.3%, respectively, demonstrated worse, unchanged, or improved CKD stage. Compared to 12 pre-implant months, HFH rates dropped in 12 months after implant across all eGFR quartiles (Table). PA systolic, diastolic, and mean pressures decreased from baseline to 24 months in all GFR quartiles. The baseline mean PAP as a continuous variable independently predicted CKD progression (OR: 1.027, p= 0.0006).

Conclusion:
Reduction of HFH by PAP-guided therapy occurred across CKD stages in a large HF population receiving the CardioMEMS sensor after Food and Drug Administration approval. Thus, PAP monitoring enables safe HF therapy optimization even in patients with advanced CKD. Since higher baseline mean PAP independently forecasts CKD worsening, HF patients with this unfavorable hemodynamic value require intensified monitoring.
Abstract 13885: Phenotyping Risk Profiles for Heart Failure With Preserved and Reduced Ejection Fraction Among Breast Cancer Survivors
Authors: Vasbinder Alexi , Cheng Richard , Ray Roberta , Langford Dale , Barac Ana , Anderson Garnet , Simon Michael , Caan Bette , Branch Mary , Shadyab Aladdin , Saquib Abu Taiyab Nazmus , Reding Kerryn
Published: May 2021

Introduction:
Breast cancer (BC) survivors (BCS) are at increased risk for incident heart failure (HF). In this population, the risk for HF with preserved ejection fraction (HFpEF) has been understudied compared to HF with reduced EF (HFrEF). The purpose of this study was to estimate 1) the incidence of HFpEF and HFrEF, and 2) the phenotypic profiles conferring risk for incident HFpEF and HFrEF in BCS.

Methods:
This Women’s Health Initiative analysis was conducted in women with invasive BC stages I-IV in the Medical Records Cohort (MRC). Those with pre-existing HF were excluded. Exposures of interest were lifestyle factors [e.g. body mass index (BMI)], comorbidities [e.g. hypertension, diabetes, and myocardial infarction (MI)], and BC treatment. Lifestyle factors and comorbidities most proximal and prior to BC diagnosis were assessed. In the MRC, BC and HF as well as left ventricular EF (LVEF) were ascertained through chart review and physician-adjudication. LVEF ≥50% was classified as HFpEF; and <50% for HFrEF per AHA/ACC guidelines. Cox proportional hazards models estimated risks of HFpEF and HFrEF. Follow up time began at BC diagnosis and HF events were recorded through March 1, 2019. All models adjusted for age at BC diagnosis.

Results:
In 2,250 BCS, 153 developed HF after BC during a median follow-up of 7.3 years. Of those, 49 had HFrEF and 75 had HFpEF. The cumulative incidences of HFrEF and HFpEF over follow-up were 7.3% and 4.6%, respectively. Diabetes and MI were associated with both HFpEF and HFrEF (Table). Smoking, BMI ≥30, and hypertension were associated with HFpEF. Anthracycline use was associated with HFrEF but not HFpEF (p=0.03).

Conclusions:
In BCS, lifestyle factors were associated with incident HFpEF, whereas anthracycline use was associated with a higher risk for HFrEF. Understanding risk factors associated with incident HFpEF and HFrEF in BCS is important to guide the implementation of risk profile-specific preventative measures and interventions.
Abstract 13892: Self-care is Poor in Lay Caregivers of Patients With Heart Failure, Especially If Caring More Than Eight Hours Daily
Authors: Matus Austin , Thomas Gladys , Garo Jenna , Luciani Michela , Ausili Davide , Riegel Barbara
Published: May 2021

Introduction:
Most patients with HF are living at home with care provided to them by loved ones. Informal caregiving is demanding and stressful, may exceed the caregiver’s ability to adapt, and many eventually become care recipients themselves. Engaging in self-care may improve caregivers’ health.

Purpose:
To describe the self-care behaviors of HF caregivers and compare self-care behaviors based on hours of daily caregiving.

Methods:
Using a cross-sectional design, we analyzed enrollment data from lay caregivers in the iCare4Me clinical trial testing the efficacy of a virtual support intervention promoting caregiver self-care. All caregivers were providing informal care to someone with HF for ≥ 8 hours/week. Self-care behaviors were measured with two instruments: Health Self-Care Neglect scale (9 dichotomous items summed for a final score) and the Self-Care Inventory (3 scales: Self-Care Maintenance, Monitoring, and Management with standardized scores 0-100; higher scores, better self-care). A Health Self-Care Neglect score ≥ 2 is considered poor self-care. A Self-Care inventory score < 70 is considered inadequate. Hours of caregiving were self-reported.

Results:
The sample (n=40) was mostly older adults (56 ± 13.2 years, female 97.5%) and many were Black (37.5%). Caregivers reported caregiving (10.8± 8.4 hours/day, range 1-24 hours/day). Differences in self-care were observed between those caregiving > 8 hours (n=18, 18.4 ± 6.6) vs. ≤ 8 hours/day (n=22, 4.6± 2.6). Mean Health Self-Care Neglect was higher in caregivers reporting ≥ 8 hours/day compared to < 8 hours (6.7 ± 2.0 vs. 4.9 ± 2.1, p=0.004). The most commonly neglected areas of self-care were “Put off recreational activities you enjoy” and “Taken medications improperly”. All Self-Care Inventory scale scores were inadequate (Maintenance 69.1 ± 17.1, Monitoring 63.7 ± 21.8, Management 58.2 ± 18.9). Those providing care for ≥ 8 hours/day reported significantly poorer Self-Care Maintenance (64.1 ± 11.7 vs. 73.9 ± 19.4, p=0.03).

Conclusion:
Self-care is poor in all the caregivers, but especially among those responsible for caregiving relatively more hours/day. Interventions to improve caregivers’ self-care are needed.
Abstract 13897: Native T1-mapping by Cardiac MRI as a Biomarker of Remodeling in Boys With Duchenne Muscular Dystrophy
Authors: Dual Seraina A , Maforo Nyasha G , McElhinney Doff B , Prosper Ashley , Wu Holden , Maskatia Shiraz A , Renella Pierangelo , Halnon Nancy J , Ennis Daniel
Published: May 2021

Cardiac magnetic resonance (CMR) is an important tool to assess cardiac disease progression in boys with Duchenne muscular dystrophy (DMD), with native (pre-contrast) myocardial T1-mapping considered a possible biomarker of fibrosis. Due to its thin wall and highly trabeculated structure, the right ventricle (RV) remains understudied in DMD despite pre-clinical evidence of RV involvement. After determining the most robust method of obtaining RV-T1, we assessed the hypothesis that RV-T1 distinguishes healthy controls from boys with DMD. Boys with DMD (N=27) and age-matched healthy control boys (N=17) were prospectively enrolled for a 3T CMR exam (Skyra, Siemens). The CMR exam included standard functional imaging, LGE imaging, and native T1 maps acquired at diastasis. Native RV-T1 was evaluated in four regions of interest (ROIs): 1 pixel (px) along the RV centerline, 3px dilated RV centerline, a segment within the RV lateral wall, and the RV inferior wall (Figure 1). Robustness was assessed in controls only and was defined as an acceptable number of pixels, coefficient of variation (COV) per ROI, percentage of readable images, and lowest inter-observer variability across three observers. Subsequently, a t-test assessed the difference between boys with DMD and controls using the most robust RV ROI. Comparing the four ROIs, we found an average size of the ROI of 65, 196, 23, 25 px; a COV of 13.4%, 16.6%, 6.0%, 9.9%; and 75%, 75%, 93%, 81% of readable images. Intra-class correlation (0.75) was highest and both mean bias (20ms) and limits of agreement (100ms) were lowest for the RV 1px ROI. Using the 1px ROI, the RV-T1 was higher and more variable in boys with DMD compared to controls (1526 [1457,1650] ms vs. 1432 [1390,1486] ms; p<0.0001). Native RV-T1 is elevated in boys with DMD, if measured along a 1px centerline ROI. The methods described herein may enable using native RV-T1 as a biomarker of fibrosis in DMD and other pathologies. Correlation with functional indices is pending.
Abstract 13902: Gender Differences in Lipoprotein Parameters in Cardiovascular Disease Risk; The Framingham Offspring Study
Authors: Ikezaki Hiroaki , Lim Elise , Liu Ching-Ti , Cupples L Adrienne , Asztalos Bela F , Murata Masayuki , Furusyo Norihiro , Schaefer Ernst J
Published: May 2021

Introduction:
Elevated serum lipoprotein cholesterol levels have been considered as atherosclerosis cardiovascular disease (ASCVD) risk factors. However, gender differences among these lipoproteins have not become clear.

Hypothesis:
Our hypothesis was that gender differences exist with regard to serum lipoprotein cholesterol levels and the risk of ASCVD risk in the prospective Framingham Offspring Study.

Methods:
A total of 1300 men and 1676 women, none of whom had ASCVD at baseline, were followed for a median time of 16 years for new onset fatal or non fatal myocardial infarction or stroke, coronary angioplasty or bypass, or carotid or peripheral vascular surgery (302 of 1300 or 23.2% of men and 226 of 1676 or 13.5% of women developed). At baseline, standard risk factors including fasting total and high density lipoprotein (HDL) cholesterol, and triglycerides were assessed, as were direct, small dense, and large low density lipoprotein (LDL) cholesterol and LDL triglyceride (LDL-TG), remnant lipoprotein cholesterol and lipoprotein(a) were measured. Univariate and multivariate analyses were carried out to assess relationships to disease risk.

Results:
All parameters were associated with ASCVD risk on univariate analysis. On multivariate analysis after controlling for all standard risk factors (age, hypertension, use of anti-hypertensive medication, diabetes, smoking, total cholesterol, HDL cholesterol, and use of cholesterol lowering medication), only lipoprotein(a) was significant in men with a 1.26 hazard ratio (P = 0.009), while small dense LDL cholesterol and LDL-TG, but not lipoprotein(a), were significant risk factors in women (hazard ratios 1.65 and 1.35, P = 0.007 and 0.015, respectively). Using the pooled cohort equation, only lipoprotein(a) added significant risk information in men and only small dense LDL cholesterol and LDL-TG added significant risk information in women.

Conclusions:
Our data indicate that men are at significantly higher disease risk then women, and that elevated lipoprotein(a) is a significant independent ASCVD risk factor in men, while small dense LDL cholesterol and LDL-TG are significant independent ASCVD risk factors in women after controlling for all other standard cardiovascular disease risk factors.
Abstract 13909: A Novel Photon-powered Biologic Gel for Enhanced Wound Healing in a Peripheral Arterial Disease Model
Authors: Zhu Yuanjia , Jung Jinsuh , Anilkumar Shreya , Thakore Akshara D , Farry Justin M , Wang Hanjay , Woo Y Joseph Y
Published: May 2021

Introduction:
Synechococcus elongatus
is a cyanobacterium that grows photoautotrophically. We hypothesized that a biologic gel containing
S. elongatus
could provide O
2
via photosynthesis to ischemic tissue due to peripheral arterial disease to accelerate wound healing.

Methods:
Sodium hyaluronate powder was mixed with cyanobacterial growth media BG11 at 2wt% to create the gel.
S. elongatus
was added at 100 million cells/mL to create the biologic gel. Wistar rats (control, n=12; gel, n=10; biologic gel in light, n=13; biologic gel in dark, n=10), after femoral artery ligation, received an ipsilateral wound of 1cm in diameter on the tarsal surface using electrocautery. Wound dressings were changed daily. Lesions were harvested on day 7 for histology evaluation, and blood samples were collected.

Results:
Rat tarsal tissue O
2
level had the largest fold change after applying biologic gel in light (7.0±1.5) compared to the control (1.7±0.3,
p
=.004), gel (2.6±0.4,
p
=.0007), and biologic gel in dark groups (1.8±0.3,
p
<.0001). Tarsal lesions after 7 days of treatment are shown in
Fig.1A
. Compared to controls, average wound areas were the smallest in rats receiving biologic gel in light on days 3, 5, and 7 (
Fig.1B
). Rats that received biologic gel in light took 12±1.1 days to heal, faster than the control, gel, and biologic gel in dark groups (
Fig.1C
). C-reactive protein level was zero for all rats, and none had positive blood culture. There was no difference in complete blood count on day 7 among the groups. Rats that received biologic gel in light compared to other groups demonstrated less tissue destruction and enhanced remodeling on day 7 (
Fig.1D-K
).

Conclusions:
The sodium hyaluronate-
S. elongatus
biologic gel was effective in accelerating wound healing in a peripheral arterial disease model by delivering oxygen to ischemic tissues. This photon-powered biologic gel shows potential for application as a novel wound dressing capable of promoting tissue formation and remodeling.
Abstract 13910: Importance of Non-invasive Estimates of Left Ventricular Filling Pressures in Critically Ill Patients
Authors: Ahmed Abdelrahman M , Wiley Brandon , Jentzer Jacob C , Anavekar Nandan S , Jaffe Allan S
Published: May 2021

Introduction:
The presence of cardiac dysfunction predicts adverse outcomes in the intensive care unit (ICU). We explored the relationship of cardiac injury and left ventricular (LV) systolic and diastolic dysfunction (LVDD) to outcomes in critically ill patients.

Methods:
This is a retrospective analysis of adult medical ICU admissions from May, 2018 through October 2019. Patients with elevated high-sensitivity troponin T (hs-cTnT) and an echocardiogram performed within 72 hours of admission were included. Patients were classified as having normal LV diastolic function, isolated LVDD, concomitant LV diastolic and systolic dysfunction (LVDDSD) or indeterminate LV diastolic function based on American Society of Echocardiography 2016 guidelines. LV systolic dysfunction was defined as an ejection fraction (EF) < 50%.

Results:
Overall, 222 patients were included. LVDD was seen in 123 patients (55.4%). Thirty patients (13.5%) were classified with indeterminate diastolic function and 56 normal diastolic function (25.2%). Of those with LVDD , 59.3% had LVDDSD while isolated LVDD was seen in 40.7%.Patients with LVDDSD had a higher median hs-cTnT at baseline compared to patients with isolated LVDD [102ng/L IQR (50-257) vs. 77 ng/L (33.5-166); p=0.047]. Medial e’ velocity and tricuspid valve systolic regurgitant velocity were often associated with LV systolic dysfunction (p=0.0172 and 0.0013, respectively). LVDDSD was associated with a longer length of stay than patients with isolated LVDD [2.9 (1.6-4.0) vs.1.8 (1.1-3.3); p-value 0.03].Twenty-nine patients died during their ICU stay (13%). Patients with LVDDSD had 9.6-fold higher odds of dying in the ICU than patients with isolated LVDD (p=0.0048). Reduced medial e’ velocity (OR 0.63, CI 0.4-1.0, p=0.0285) and increased E/e’ (OR 1.08, CI 1.01-1.15, p=0.0192) were associated with ICU mortality. The association between LVEF<50% and ICU mortality was less pronounced (OR 0.95, CI 0.01-0.98; p=0.0023).

Conclusions:
Concomitant LV systolic and diastolic dysfunction and measures of increased cardiac filling pressures are strong predictors of mortality.
Abstract 13916: Quality of Life Measured in First-line Therapy for Paroxysmal Atrial Fibrillation: A Comparison Between Cryoballoon Catheter Ablation versus Antiarrhythmic Drug Therapy
Authors: Pavlovic NIkola , Kuniss Malte , Velagic Vedran , Hermida Jean-Sylvain , Healey Stewart , Arena Giuseppe , Badenco Nicolas , Meyer Christian , Chen Jian , Iacopino Saverio , Anselme Frederic , Chierchia Gian-Battista
Published: May 2021

Introduction:
The Cryo-FIRST study (NCT01803438) demonstrated that pulmonary vein isolation (PVI) with cryoballoon catheter ablation (CA) is superior to antiarrhythmic drug (AAD) therapy as a first line treatment for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation (PAF). Earlier CA may also be beneficial for improving quality of life (QoL).

Hypothesis:
We hypothesized that PVI with cyroballoon CA is superior to AAD therapy for improving QoL in treatment naïve patients with PAF.

Methods:
Patients with symptomatic PAF free of heart disease who had not been administered AAD therapy for >48 hours were enrolled at 18 sites in 9 countries. Patients were randomized (1:1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD therapy (Class IC or III). Subjects were followed at 1, 3, 6, 9, and 12 months. QoL was evaluated using the Atrial Fibrillation Effect on Quality of Life (AFEQT) and SF-36 v2 questionnaires. Health domains and component scores from the SF-36 were transformed to norm-based T scores. Mean adjusted differences between arms were compared at each follow-up.

Results:
Of the 218 patients randomized (age 52±13 years, 68% male) 86% completed the 12-month follow-up. Crossovers occurred in 9% of subjects (N=20, CA-to-AAD: N=1, AAD-to-CA: N=19). There were no group differences in baseline AFEQT or SF-36 scores. The mean AFEQT summary score was more favorable in the CA vs. AAD group at 12 months (88.9 vs. 78.1 points, respectively). The adjusted difference was 9.9 points (95%CI: 5.5-14.2;
P
< .0001, Figure). A significant adjusted mean difference favoring CA was observed for the SF-36 physical component score at months 3 (1.8 points, p=0.031) and 9 (2.0 points, p=0.018). No other differences were observed in the physical or mental component scores between groups.

Conclusions:
Cryoballoon CA was superior to AAD therapy for improving AF-specific QoL in treatment naïve patients with symptomatic PAF.
Abstract 13921: Targeting Receptor-Interacting Protein 140 to Modulate Energy Metabolism in the Failing Heart
Authors: Yamamoto Tsunehisa , Pruzinsky Elizabeth , Batmanov Kirill , Kelly Daniel P
Published: May 2021

The nuclear receptors, peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and their co-regulator PPARγ coactivator-1α (PGC-1α), control postnatal cardiac mitochondrial biogenesis and energy metabolism. During the development of heart failure (HF), the activity of PGC-1/PPAR/ERR is reduced resulting in diminished capacity for fatty acid oxidation (FAO) and ATP production potentially contributing to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PGC-1/PPAR/ERR in skeletal muscle and adipose tissue. We hypothesized that RIP140 represses cardiac energy metabolism in the normal and failing heart. Accordingly, we targeted
Nrip1
(encoding RIP140) using a muscle creatinine kinase (MCK)-driven Cre recombinase to generate striated muscle-specific RIP140 knockout (msRIP140 KO) mice. msRIP140 KO mice appeared normal at baseline with no difference in survival or cardiac systolic function compared to littermate controls. RNA-sequence analysis demonstrated that the expression of genes involved in a wide array of mitochondrial energy metabolic pathways including FAO, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and branched-chain amino acid (BCAA) degradation pathways were upregulated in msRIP140 KO ventricles, and in msRIP140 KO skeletal muscle. msRIP140 KO mice exhibited significantly less cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload. Next, cardiac-specific (cs) RIP140 KO mice were generated and subjected to transverse aortic constriction/apical myocardial infarction surgery (TAC/MI), an established HF model. csRIP140 KO mice exhibited less cardiac remodeling and systolic dysfunction compared to littermate controls, along with less downregulation of metabolic genes and induction of cardiac stress (
Nppa
and
Nppb
) and fibrosis response markers (
Tgfb2
and
Col3a1
). We conclude that RIP140 serves as a global co-repressor of cardiac energy metabolic genes in the adult heart and that modulation of RIP140 activity could prove to be a novel therapeutic approach for HF.
Abstract 13929: Methadone Lengthens Both Early and Late Ventricular Repolarization in Patients Undergoing Maintenance Therapy in an Urban Narcotic Treatment Center
Authors: Tisdale James E , Tomaselli Muensterman Elena , Titus-Lay Erika , Jaynes Heather , Walroth Todd , Williams Gabriela , Moe Paul , Wilbrandt Michelle , Ott Carol
Published: May 2021

Introduction:
Methadone, a racemic mixture of
S
- and
R
-enantiomers, prolongs the QT interval and causes torsades de pointes. Methadone has been shown to lengthen late ventricular repolarization, represented by the T
peak-Tend
interval, which is modulated primarily by I
Kr
and I
Ks
. However, it is unknown whether methadone prolongs early ventricular repolarization, represented by the heart rate-corrected J-T
peak
(J-T
peak
c) interval, which is regulated primarily by L-type calcium and late sodium currents. In addition, the relationship between stereospecific serum methadone and metabolite concentrations and effects on J-T
peak
c and T
peak
-T
end
intervals are unknown.

Hypothesis:
1) Methadone lengthens both J-T
peak
c and T
peak
-T
end
, and 2) Methadone effects on J-T
peak
c and T
peak
-T
end
correlate with serum
S
- and
R
-methadone and
S
- and
R
-metabolite [ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)] concentrations.

Methods:
Patients (n=81) on steady state maintenance methadone therapy at an urban narcotic treatment center who had undergone a pre-methadone 12-lead ECG within the previous 6 months were identified and asked to return for a followup ECG during steady-state methadone therapy. In a subset (n=41), blood was obtained to determine serum
S
- and
R
-methadone and
S
- and
R
-EDDP concentrations.

Results:
Compared to baseline, methadone lengthened mean ± SD J-T
peak
c (225 ± 26 vs 232 ± 28 ms, p=0.02) as well as T
peak
- T
end
(80 ±14 vs 90 ± 16 ms, p<0.00001). Serum concentrations of
S
-methadone correlated with J-T
peak
c [R
2
= 0.41 (95% CI 0.11-0.65), p=0.007]. Serum
R
-methadone concentrations also correlated with J-T
peak
c [R
2
= 0.47 (0.17-0.68), p=0.002]. In addition, serum concentrations of
S
- and
R
-EDDP correlated with J-T
peak
c [R
2
= 0.39 (0.09-0.63), p=0.01] and [R
2
= 0.38 (0.07-0.62), p=0.02], respectively. There were no significant correlations between serum
S
- and
R
-methadone or S- and R-EDDP concentrations with T
peak
- T
end
intervals.

Conclusions:
Methadone lengthens both early and late ventricular repolarization, suggesting that methadone’s ion channel effects may extend beyond inhibition of I
Kr
. Serum
S
- and
R
-methadone and
S
-and
R
-EDDP concentrations are associated with effects on J-T
peak
c intervals.