bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14318: Long Noncoding RNA Differentiation Antagonizing Non-protein Coding RNA 201 Ameliorates Endothelial Dysfunction via Sponging MicroRNA-216a
Authors: li rongxia , Yang Shujun , Chen Yu , Zhang Weili
Published: May 2021

Background:
Endothelial dysfunction contributes to the initiation of atherosclerosis, which has been associated with the long noncoding RNAs (lncRNAs). However, the role of lncRNAs in endothelial function remains largely unknown. This study aimed to investigate whether the differentiation antagonizing non-protein coding RNA 201 (DANCR201) regulated the endothelial function.

Methods and Results:
The whole transcriptome sequencing was conducted to identify differentially expressed lncRNAs in the peripheral blood from patients with coronary artery diseases who had coronary calcified plaques (n=10), vulnerable plaques (n=5), and control subjects without coronary plaques (n=10). The characteristics of plaques were determined by the coronary computed tomography angiography. The results showed that DANCR201 was significantly downregulated in patients with vulnerable plaques compared to those with calcified plaques and control subjects. The RNA fluorescence in situ hybridization showed that DANCR201 was localized in both cytoplasm and nuclei. Next, we assessed the role of DANCR201 in endothelial function. In the replicative aging model of human umbilical vein endothelial cells (HUVECs), DANCR201 was found to decrease in senescent passage 20 cells compared with young passage 3 cells. Furthermore, DANCR201 overexpression in HUVECs significantly repressed monocytes adhesion to endothelium, inhibited the expression of pro-inflammatory cytokines interleukin 1β, intercellular cell adhesion molecule 1, tumor necrosis factor α, and promoted the abilities of endothelial proliferation and migration, indicating that DANCR201 was a protective factor for endothelial function. Bioinformatics analysis of miRNA-lncRNA interactions indicated that DANCR201 contained a candidate binding sequence of miR-216a which had been reported to promote the endothelial dysfunction through NF-κB pathway. The luciferase assay further showed that DANCR201 specifically combined with miR-216a.

Conclusions:
Our data indicated that DANCR201 can improve endothelial function via sponging miR-216a, ultimately maintaining vascular normalization. DANCR201 maybe a potential therapeutic target for atherosclerotic plaque progression and instability.
Abstract 14327: Tricuspid Valve Annular Area Correlations and Determinants in Healthy Controls and Patients With Severe Mitral Regurgitation
Authors: Kapadia Sohum , Krishnaswamy Amar , Griffin Brian P , Wierup Per , SCHOENHAGEN Paul , Harb Serge
Published: May 2021

Introduction:
Concomitant tricuspid valve (TV) repair during mitral valve (MV) surgery based on annular dilation rather than the degree of regurgitation (TR) has been shown to be beneficial and is supported by the guidelines.

Hypothesis:
Assess the correlations between tricuspid and mitral annular areas (TVA and MVA, respectively) indexed to body surface area (BSA) measured by cardiac computed tomography (CT), and identify the determinants of the TVA in normal and diseased states.

Methods:
We included 50 consecutive controls (no valvular heart disease undergoing coronary CTA), 50 primary mitral regurgitation (PMR) patients referred for robotic repair, and 25 functional MR (FMR) patients referred for percutaneous therapy, without significant associated TR (≤2+ TR). We used dedicated CT software (Aquarius, TeraRecon) to perform the annular measurements. A mid-diastolic phase acquisition (~70%) was used

Results:
Patients with FMR were older (median age [25th, 75th] = 70 years [63,77.5] vs. 55 [48,59] in PMR and 48 [38,55] in controls), had more clinical comorbidities, and lower ejection fraction (32% [23,40] vs. >60% in both other groups). TVA was significantly correlated to MVA in controls (r≥0.5; p<0.001), as well as in patients with PMR and FMR. (Figure 1). Table 1 shows the univariate correlations and multivariate determinants of the TVA. In the multivariate analysis, the MVA, RA area, and LVEDV were the independent predictors of TVA. Interestingly, the MVA was the most important predictor (β= 0.420, p<0.001).

Conclusion:
In individuals without valvular heart disease and in patients with severe MR (PMR and FMR) with ≤ 2+ TR, the TVA was largely determined by the MVA.
Abstract 14345:
Cardiopulmonary Best Abstract Award:
Improves Right Ventricular - Pulmonary Arterial Coupling and Right Ventricular Function in the Pulsar Study: A Phase 2, Double-blind, Placebo-controlled, Randomized Study to Compare the Efficacy and Safety of Sotatercept versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)
Authors: McLaughlin Vallerie , Gomberg-maitland Mardi , Manimaran Solaiappan , Lu Jonathan , Gibbs Simon , Barron Carrie
Published: May 2021

Background:
The right ventricle (RV) and pulmonary arteries become uncoupled as RV function deteriorates in PAH, a consequence of pulmonary vascular remodeling which is ultimately fatal. Restoration of RV-PA coupling and RV function is a crucial aim of PAH treatment. Preclinically, sotatercept, a first-in-class fusion protein, has been shown to reverse right heart remodeling and improve right heart structure and function and acts by suppressing TGF-β signaling and rebalancing BMPR2 signaling. The PULSAR study (NCT03496207, EudraCT 2017-004738-27) released positive topline results earlier this year.

Methods:
The PULSAR study enrolled 106 patients with WHO Group 1 PAH and WHO functional classes (FC) II-III; age ≥18; pulmonary vascular resistance of ≥5 Wood units by right heart catheterization; stable PAH standard of care (SOC) therapy (all combinations allowed). Sotatercept was administered by SC injection every 21 days for a 24-week double-blind, placebo-controlled treatment period in 3 arms: placebo + SOC, 0.3 mg/kg sotatercept + SOC, 0.7 mg/kg sotatercept + SOC. 2D Doppler echocardiography was performed at baseline and 24 weeks and read in a central laboratory. RV-PA coupling was assessed by TAPSE/PASP.

Results:
Significant improvement was seen in LS mean (SE) change from baseline to week 24 in RV-PA coupling, RVFAC, RVEDA, RVESA, PASP, and RAP in both sotatercept dose level groups vs placebo. No changes were seen in TAPSE or, notably, in CO. For RV-PA coupling, all patients started below the 0.31 mm/mmHg prognostic threshold; both treatment arms improved above that threshold by 24 weeks while the placebo arm remained below.

Conclusions:
In the PULSAR study, treatment with sotatercept compared to placebo was associated with statistically significant improvements in RV-PA coupling and RV function. Sotatercept has the potential to be a new treatment option for PAH patients with consistent and encouraging effects on RV-PA coupling and RV function.
Abstract 14365: Identification of MicroRNAs and Their Target Genes in Microvascular Disease in Diabetes
Authors: Gao Lei , Tsuji Hosokawa Atsumi , Cabrera Jody Tori O , Zhou Tong , Makino Ayako
Published: May 2021

Cardiovascular disease is the leading cause of death in patients with diabetes. Among coronary vascular defects, obstructive coronary artery disease (CAD) is the primary cause of cardiac mortality. However, there is growing evidence that patients with coronary microvascular disease (CMD, also known as non-obstructive coronary disease) also experience chest pain and occasional heart attack. Furthermore, recent studies show that diabetes is the risk factor of CMD. However, the molecular mechanisms by which diabetes develops CMD is not fully understood. MicroRNAs (miRNAs) are a non-coding small RNA that regulates gene expression at the post-transcriptional level, and the change of miRNA profile is implicated in many diseases. In this study, we identified the core miRNAs which are involved in the development of coronary endothelial dysfunction in diabetes. We used an inducible type 2 diabetic (T2D) mouse model generated by high-fat diet and a single injection of low-dose streptozotocin. Our T2D mice did not show detectable atherosclerotic plaque, but developed CMD evidenced by reduced coronary flow velocity reserve. We conducted a miRNA array using mouse coronary endothelial cells (MCECs) isolated from diabetic and control mice, and selected seven miRNAs based on the result. Next, real-time PCR assays were carried out with seven miRNAs and found that miR210 and miR342-5p were downregulated, and miR378 was upregulated in MCECs of diabetic mice compared to the control. To identify the target genes of miR342-5p and miR378, we inhibited miR342-5p or overexpressed miR378 in MCECs. After testing 93 genes that are involved in endothelial functions, we found that inhibition of miR342-5p decreased the levels of
Atp2a3
,
Opa1
,
Sod3
, and
Vegfb
, whereas miR378 overexpression significantly decreased
Aggf1, HK1, Mapk3, Pak1, Panx1, Stim1, Stim2, Vcam1,
and
Vegfb
and increased
Casp2
and
Gja1
. Western blotting data revealed that the expression levels of Affg1, Opa1, and Pak1 were significantly decreased in the MCECs from diabetic mice compared to the control. In summary, these data suggest that miR342-5p and miR378 could be a potential therapeutic target for CMD in diabetic patients, and
Affg1 Opa1 and Pak1
are the downstream mRNAs of miR342-5p or miR378.
Abstract 14370: Rapidly Improving Adherence to Guideline-Directed Medical Therapies in Metropolitan Heart Failure Systems of Care
Authors: Tomei Jacqueline , Kiser Robin Y , Mallas-Serdynski Lynn , Scharnott Michelle , Bolles Michele M , Chahoud Georges , Saltzberg Mitchell , Yancy Clyde
Published: May 2021

Background:
The 2017 AHA/ACC/HFSA Focused Update of the 2013 ACC/AHA Guidelines for the Management of Heart Failure provided additional support for the clinical use of ACEI, ARBs or ARNIs in conjunction with Evidence-Based Beta Blockers and Aldosterone Antagonists in HFrEF, otherwise known as Guideline-Directed Medical Therapy (GDMT). Although these updates clarified the benefits of GDMT to patient outcomes, low rates of adherence at the provider level for both hospitalized and ambulatory patients continue to be seen.

Methods:
With the objective of rapidly improving GDMT utilization, as well as improving patient outcomes, the American Heart Association initiated a multidisciplinary collaborative in three metropolitan markets - Chicago, Milwaukee, and St. Louis. Utilizing Get With The Guidelines®-Heart Failure (GWTG-HF), 40 hospitals tracked patients discharged with a primary diagnosis of heart failure and entered data from their inpatient and 30-days post-acute record. An initiative benchmark group was created to track progress and revisions were made to the post-acute care form. Hospitals were provided targeted consultation using hospital-specific data compared to regional and initiative benchmarks. The initiative provided exclusive professional education, including webinars, collaboration meetings, and best-practice recommendations.

Results:
Between January 1, 2019 and December 31, 2019, 10,532 patients with a primary diagnosis of heart failure, were entered into GWTG-HF from the 40 initiative hospitals, in which 3807 had an EF of <40%. A comparison from Q1 to Q4, 2019 of the mean adherence for GDMT was performed at discharge and yielded the following results: ACEI/ARB or ARNi from 89.3% to 91.6%, Evidenced-Based Beta Blockers from 90.3% to 94.2% and Aldosterone Antagonist from 53.6% to 64.7%; At 30-Days the mean adherence for Q1 and Q4 were calculated as follows: ACEI/ARB or ARNi from 60.4% to 72.9% and Aldosterone Antagonist from 28.2% to 55.3%. Evidence-Based Beta Blocker was only captured for Q3 and Q4, 2019 and the mean adherence improved from 70.3% to 73.8%.

Conclusions:
The multi-city quality initiative early results show a positive correlation in improving adherence to GDMT in both the hospital and ambulatory setting.
Abstract 14372: Identification of the Genes That Are Involved in Severe Pulmonary Hypertension in Type 2 Diabetic Mice
Authors: Zheng Qiuyu , Tsuji-Hosokawa Atsumi , Cabrera Jody T , Wang Jian , Makino Ayako
Published: May 2021

Pulmonary hypertension (PH) is a progressive disease characterized by increased pulmonary vascular resistance. Increasing evidence shows that diabetes increases the risks of PH, and diabetic priming leads to severe PH. However, the molecular mechanism by which preconditioning of diabetes results in severe PH is still unknown. It has been shown that endothelium serves as a key regulator of vascular tone, and endothelial cell dysfunction is implicated in the development of PH and diabetes-related vascular complications. Therefore, we identified the genes that contribute to the development of severe PH in diabetic mice with a focus on endothelial function. We first determined the effect of chronic hypoxia (10% O
2
, 4 weeks) on hemodynamics in type 2 diabetic (T2D) mice. We used inducible T2D mice (generated by high-fat diet and a low-dose streptozotocin injection) and spontaneous T2D mice (TALLYHO/Jng). Diabetic mice exhibited a slight increase in right ventricular systolic pressure (RVSP), and chronic hypoxia led to a further rise in RVSP in both inducible and spontaneous T2D mice. We isolated pulmonary endothelial cells (MPEC) from normoxia-exposed control mice (CN), hypoxia-exposed control mice (CH), normoxia-exposed diabetic mice (DN), and hypoxia-exposed diabetic mice (DH) to examine the levels of 92 genes using real-time PCR. Nighty two genes were selected based on their functions, which are significantly related to endothelial function. We found that 27 genes were significantly changed among 4 groups. We then examined the protein levels of genes that were related to apoptosis and glycolysis. Western Blot data indicated that the protein level of GAPDH was significantly increased in CH and DH compared to CN and DN. In addition, hypoxic exposure in diabetic mice (DH) significantly increased HK2 protein level compare to hypoxia-exposed control mice (CH). These data suggest that precondition of diabetes increases susceptibility to developing PH due partly to altering gene expression of
HK2
and
Gapdh
in MPECs. Since HK2 and GAPDH are a crucial regulator of glycolysis, alteration of glycolysis is expected in hypoxia-exposed diabetic mice. Our study revealed the key molecules which could be used for treating severe PH in diabetes.
Abstract 14375: Does Race Provide Protection From New Onset Atrial Fibrillation After Typical Flutter Ablation in Male Veteran Patients?
Authors: Lin Aung N , Peng Gary , Obeng-Gyimah Edmond , Pothineni Naga K , Winn Soe P , Yang Ya-wen , Hall Samantha N , Ali Aasima , Deo Rajat , RILEY Michael P , Epstein Andrew E , Arkles Jeffery , Dixit Sanjay
Published: May 2021

Introduction:
Patients undergoing typical atrial flutter (AFL) ablation remain at risk of developing atrial fibrillation (AF). However, it is unknown whether common risk factors associated with AF occurrence, particularly race, bear out in this population.

Hypothesis:
We sought to compare the occurrence of new AF in male veteran African-American (AA) and Caucasian (Cau) patients with AFL following successful cavo-tricuspid isthmus ablation.

Methods:
A retrospective review of patients undergoing AFL ablation between 2002 and 2019 was performed. Patients with prior history of AF were excluded. Records were reviewed and demographics, comorbidities and post-ablation outcomes including new AF and stroke were recorded. The overall incidence of AF and cases per 1000 person-years (CPTPY) were determined.

Results:
The study cohort comprised 217 patients (age: 66±9.3 years, AA: 97 [45%], Cau:108 [50%]; see Table) with a mean follow-up of 55±42 months after AFL ablation. New AF was detected in 30 (31%) AA and 45 (42%) Cau patients (p=0.21 by Log Rank test). Overall incidence of AF was 78 CPTPY (67 and 91 CPTPY cases in AA and Cau patients, respectively). Time to occurrence of AF was earlier in Cau than AA patients (p=<0.001). New stroke events occurred in 9 (4.4%) patients (4 AA, 5 Cau; p=0.86).

Conclusions:
Male AA and Cau patients have similar significant risks for developing AF and experiencing stroke after AFL ablation.
Abstract 14377: Therapeutic Potential of Clinical Grade Human Induced Pluripotent Stem Cell-derived Cardiac Tissues for a Rat Myocardial Infarction Model: A Pre-clinical Study for a Cell Transplantation Therapy
Authors: Osada Hiroaki , Masumoto Hidetoshi , Kawatou Masahide , Ikeda Tadashi , Tabata Yasuhiko , Minatoya Kenji , Yamashita Jun K
Published: May 2021

Introduction:
Transplantation of three-dimensional bioengineered cardiac tissues composed of pluripotent stem cell-derived cardiovascular cell lineages is reported to hold potential for functional recovery on pre-clinical studies. We aimed to evaluate therapeutic and myocardial regenerative potential of clinical grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) on a rat myocardial infarction (MI) model.

Methods:
Clinical grade hiPSC lines established from a healthy volunteer were simultaneously differentiated into cardiovascular cell lineages. We seeded the cells on temperature responsive culture dishes to form cell sheets. HiCTs were generated by stacking 5 cell sheets with insertion of gelatin hydrogel microspheres (GHMs) to promote oxygen and nutrition supply and transplanted onto an athymic rat MI model (n=6). Echocardiography and histological analysis at 12 weeks after surgery were conducted and compared to those in animals with sham surgery (n=9) and with cell sheet stacks without GHMs [GHM(-), n=6]. Some of HiCT-transplanted rats were subjected to tissue clearing and two-photon excitation microscopy (TPEM) to assess graft vascularization.

Results:
Flow cytometry revealed cellular components after differentiation as follows: 52.0±1.4% of cardiomyocytes (cardiac isoform of troponin-T
+
:cTnT), 9.9±0.7% of vascular endothelial cells (VE-cadherin
+
) and 14.1±1.8% of vascular mural cells (PDGFRβ
+
). Echocardiography revealed significantly lower left ventricular end diastolic volume (LVEDV) and higher left ventricular ejection fraction (LVEF) in HiCT group [sham vs GHM(-) vs HiCT: LVEDV; 1.5±0.1 vs 1.3±0.05 vs 0.9±0.03 mL, p<0.0001 / LVEF; 59.7±2.2 vs 67.4±0.6 vs 82.7±0.9 %, p<0.0001]. HiCT group showed significantly larger engraftment [GHM(-) vs HiCT; 12 week; 0.1 ± 0.1 vs 1.8 ± 0.6 mm
2
; p<0.05]. Engrafted graft tissues were composed of cTnT / α-Actinin-positive cardiomyocytes which exhibited obvious striated structure. TPEM revealed host to graft vascular connection at 2 weeks after HiCT transplantation.

Conclusions:
HiCTs derived from clinical grade hiPSC potentially serve as a stem cell-derived cellular product in cardiac regenerative therapy for foreseeable clinical applications.
Abstract 14386: The 2020 ESC-ACVC Quality Indicators for the Management of Acute Myocardial Infarction Applied to the FAST-MI Registries: Validity Criteria Compared to the 2017 Definitions
Authors: Schiele Francois , Bueno Hector , Rossello Xavier , Leonardi Sergio , Masoudi Frederick , Tubaro Marco , Gale Chris P , Puymirat Etienne , Ferrieres Jean , Ecarnot Fiona , DANCHIN Nicolas , Simon tabassome , Meneveau Nicolas
Published: May 2021

Introduction:
In 2020, the European Society of Cardiology-Acute Cardio Vascular Care (ESC-ACVC) updated the 2017 Quality Indicators (QI) for the management of acute myocardial infarction (AMI). We compared 2017 vs 2020 indicators in terms of feasibility, potential for improvement, association with outcomes, and suitability for center benchmarking.

Methods:
Data were extracted from three French nationwide cohorts (FAST-MI 2005, 2010 and 2015), using data from AMI survivors at discharge. Applicability and potential for improvement were estimated for each QI by the denominator and numerator. The association between the composite QIs and 1 year mortality were assessed using multivariate logistic regressions. Center benchmarking was based on the mean of the opportunity-based composite QIs (CQI) and the All or None Composite QI.

Results:
The 2017 and 2020 QIs were measured in 12,660 /13,130 patients discharged alive, respectively. The rates of attainment ranged from 15% to 96% (Figure, left). The mean value of the Composite QI was 0.71 in 2017 versus 0.64 in 2020 (p<0.01). Quartiles of CQI were significantly associated with risk-adjusted 1 year mortality for 2017 and 2020 CQI (Figure, right). Addition of the quartiles of the 2020 CQI improved the discrimination indices. Attainment of the 2020 All-or-None Composite QI was observed in 12% of cases, and was associated with a 63% lower odds of death. The opportunity-based Composite QI and the All-or-None QI were suitable for center benchmarking.

Conclusion:
Compared to the 2017 QIs, the 2020 updated QIs for AMI can be measured in existing registries, and show greater potential for improvement, a comparable association with mortality and similar suitability for center benchmarking.
Abstract 14387: Dose-Related Reductions in Blood Pressure With a RNA Interference (RNAi) Therapeutic Targeting Angiotensinogen in Hypertensive Patients: Interim Results From a First-In-Human Phase 1 Study of ALN-AGT01
Authors: Huang Stephen A , Taubel Jorg , Fiore Giuseppe , Dewland Peter , Bakris George L , Desai Akshay S , Cheng Yansong , Agarwal Sagar , Harrop Jamie , Nguyen Huy V , Lu Jiandong , Foster Don , Vaishnaw Akshay , Kim Jae B
Published: May 2021

Background:
Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides and plays a key role in hypertension pathogenesis. We evaluated the effect of ALN-AGT01, a subcutaneous investigational RNAi therapeutic targeting hepatic AGT synthesis, on blood pressure in hypertensive patients.

Methods:
As part of a phase 1 program designed to assess the safety and tolerability of ALN-AGT01, we conducted a multicenter study randomizing patients aged 18-65 years with mild to moderate hypertension (mean seated systolic blood pressure [SBP] of >130 and ≤165 mmHg after washout of antihypertensive medication) 2:1 to ascending single doses of ALN-AGT01 or placebo. Change from baseline in BP at 8 weeks was measured by ambulatory BP monitoring (ABPM). We report interim results as of May 14, 2020.

Results:
Sixty patients (mean age 52 years, 45% female, mean baseline 24h SBP 139 +/- 7 mm Hg) were enrolled in ascending dose cohorts of 10 mg, 25 mg, 50 mg, 100 mg, or 200 mg. Dose-related reductions in serum AGT levels were observed (figure), with reductions >90% in the 100 and 200 mg dose cohorts. AGT remained durably reduced through 12 weeks after single dose administration. Concomitant reductions in BP from baseline were observed with AGT knockdown, with an over 10 mm Hg reduction of mean 24-hour SBP observed at Week 8 after single doses of 100 mg or 200 mg. No symptomatic hypotension, treatment-related serious adverse events, or clinically significant elevations in blood creatinine or potassium were seen.

Conclusions:
Single dose administration of ALN-AGT01 to hypertensive patients resulted in dose-related reductions in serum AGT and BP over 8 weeks without hypotension or other related serious adverse events. Durable AGT knockdown to 12 weeks supports further evaluation of once quarterly or potentially less frequent dose administration.
Abstract 14403: Troponin as a Powerful Predictor of Mortality in Critically Ill Covid-19 Patientsmulticenter Analysis in 159 Patients
Authors: Qutrio Baloch Zulfiqar , Ali Abbas , Alabcha Abdullah , boumegouas manel , Do Steven , Ip Randy , Wilcox Matt , Ip John
Published: May 2021

Introduction:
Certain cardiac biomarkers have been shown to predict survival in patients infected with COVID-19. However. The use of Troponins, CPK and LDH in predicting the outcome in patients who are critically ill and require advanced respiratory support is less clear.

Methods:
We performed a multicenter analysis of 159 consecutive patients with confirmed COVID-19 who were admitted to Intensive Care Unit (ICU) between March 01, 2020 and April 30, 2020. Patients were then followed until May 23, 2020. Demographic data (age, sex, race, BMI) were recorded. Cardiac biomarkers (CPK, Troponins, BNP, LDH) were analyzed. Patient status was classified either alive or deceased at the end of follow up period.

Results:
Mean patient age was 66+/-15 and 53% were male. Mean BMI was 31+/- 9. Mean hospital ICU stay was 11+/-8 days. Mortality rate of this ICU cohort at the end of follow-up was 63%. Fifty-five (34%) patients were discharged from the hospital. A multivariate logistic regression analysis identified 2 factors (Age >62 HR 2.4, 95% CI 1.21-4.676, p<0.01 and elevated Troponin >0.5 HR 3.45, 95% CI 1.01-11.8, p 0.048) has significant and independent contributions to the likelihood of survival (Fig 1 and Fig 2). Fig 1 KM curve of different strata of Troponin levels Fig 2 KM curve of 2 strata of Age

Conclusion:
Elevated Troponins level are common in critically ill COVID-19 patients. The highly predictive value of Troponins in survival may indicate possible cardiac involvement of COVID-19 infection as a determinant of mortality. Early and serial determination of Troponin values can provide risk stratification for these patients and timely aggressive intervention may decrease mortality.
Abstract 14430: Effect Modification of Statin Therapy on the Relationship of Low-density Lipoprotein Cholesterol With Incident CKD in Us Veterans
Authors: Hsiung Jui-Ting , Marroquin Maria , Kalantar-Zadeh Kamyar
Published: May 2021

Background:
Studies suggests that in the general population, hyperlipidemia may confer higher risk of developing chronic kidney disease (CKD). But, there is conflicting data as to whether statins can protect renal function or slow renal degradation. We sought to examine the impact of statins on the association of low-density lipoprotein cholesterol (LDL) and risk of incident CKD.

Methods:
Our cohort included 1,439,756 US veterans without chronic kidney disease (CKD), but with LDL measured between 2004-2006, who were followed until 2014. Incident CKD was defined as over 3 estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.73m
2
at least 90 days apart. Patients with a statin prescription at the time of LDL measurement were identified. Cox models were used to estimate the associations between LDL with incident CKD. Model adjustments include demographics, comorbidities, smoking status, prescription of fibrate or niacin, body mass index, albumin, high-density lipoprotein cholesterol, and triglycerides.

Results:
The cohort included 5% females, 16% African Americans, 26% diabetics, and 30% statin-users, with a mean age of 60±13 years. The median [IQR] of LDL and eGFR were 109 [88,133] mg/dL and 83 [72,94] mL/min/1.73m
2
, respectively. A J-shaped association between LDL and incident CKD were observed in both those on statin and not on a statin after adjustment. Low LDL (<70 mg/dL) was associated with a higher risk of incident CKD compared to the reference (LDL 70-<100 mg/dL) regardless of statin use. High LDL ≥160 mg/dL was associated with the highest of risks of incident CKD (HR: 1.08, 95% CI: 1.04, 1.13, and HR: 1.10, 95% CI: 1.07, 1.12, for statin use and no statin use, respectively).

Conclusion:
Both high and low LDL were associated with higher incident CKD risk independent of statin use in this US veteran cohort. Further studies are needed to understand how to manage cardiovascular disease risk by lowering LDL while simultaneously reducing risk of CKD.
Abstract 14434: Identification and Predictors for Cardiovascular Disease Risk Equivalents Among Adults With Diabetes Mellitus
Authors: Zhao Yanglu , Malik Shaista , Budoff Matthew J , Correa Adolfo , Ashley Kellan E , Selvin Elizabeth , Watson Karol E , Wong Nathan D
Published: May 2021

Background:
It is not well quantified if diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent depends on DM severity and other CVD risk factors.

Methods:
We pooled 4 US community-based cohorts (ARIC, JHS, MESA, FHS Offspring) and classified subjects by baseline DM/CVD status. DM+/CVD- was further classified by DM duration, HbA1c control or DM medication. Hazard ratios (HR) were estimated for CVD during a median follow-up of 14 years. Subgroup analysis comparing the HR of DM+/CVD- vs. DM-/CVD+ was done by CVD risk factors. We integrated all factors that impacted DM-conferred CVD risk and defined one with DM+/CVD- as CVD risk equivalent when his/her CVD risk was as high or higher than that if he/she had DM-/CVD+. CVD risk profile and event risk were compared between the CVD risk equivalent subgroups in DM+/CVD-.

Results:
The pooled cohort included 27,732 adults (mean age of 58 years, 45% males). CVD event rates per 1000 P-Y were 16.3, 33.3, 40.9 and 69.0 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. DM participants with HbA1c≥7%, DM duration over 10 years, or DM medication use had similar CVD risk as those with DM-/CVD+ while those without these factors had lower CVD risk; DM+/CVD- had similar CVD risk as those DM-/CVD+ among women, age <55 years, White race, or high triglyceride groups (Figure). Among those with DM+/CVD-, 17.5% were found to be CVD risk equivalents. Compared to those non-CVD risk equivalent DM, they had lower 10-year PCE scores (14.8% vs. 22.7%, p<0.0001) however higher actual CVD event rates (44.9 vs. 31.0 per 1000 P-Y).

Conclusion:
Among CVD-free adults with DM, fewer than 20% are actually CVD risk equivalents. Poor HbA1c control, long DM duration, and current diabetes medication use were identified as predictors of CVD risk equivalent status and DM was more detrimental for CVD risk if one is female, younger age, White, or with high triglycerides. These risk enhancing factors should be considered in the treatment decision.
Abstract 14436: Nightly Lower Body Negative Pressure Redistributes Blood Volume and Prevents Maladaptive Vascular Remodeling Induced by Microgravity
Authors: Dias Katrin A , Hearon Christopher M , Babu Gautam , Marshall John E , Macnamara James P , Leidner James , Gillespie Michael , Peters Kirsten , LEVINE Benjamin D
Published: May 2021

Introduction:
During space flight and ground based simulations of microgravity, transmural distending pressure increases in resistance vessels above the level of the heart, causing maladaptive vascular remodeling over time. Lower body negative pressure (LBNP) mimics gravity by redistributing blood volume and reinstating hydrostatic gradients, and may preserve vascular structures above the heart while in microgravity.

Methods:
Ten healthy subjects (5 female, 29 ± 9 years) completed three days of supine (0°) bed rest with and without eight hours of nightly LBNP (-20mmHg) in a randomized, crossover design. Area and volume of the choroid, a highly vascularized layer of the eye sensitive to changes in hydrostatic gradients, were assessed using optical coherence tomography on the first and last day of bed rest. Central venous pressure (CVP) was measured during spontaneous breathing with a peripherally inserted central catheter.

Results:
CVP increased significantly from the seated to supine position (+9.1 ± 2.4mmHg, P < 0.001), leading to choroid engorgement over three days of supine bed rest (choroid area: +0.09 mm
2
95% CI 0.04 to 0.13, P = 0.0014; choroid volume: +0.37 mm
3
95% CI 0.19 to 0.55, P = 0.0011). Nightly LBNP caused a sustained reduction in supine CVP (5.7 ± 2.2mmHg to 1.2 ± 1.4mmHg, P < 0.001), indicating effective redistribution of blood volume and significantly attenuated the increase in choroid area (3.5% control vs. 0.9% LBNP, P = 0.0164) and volume (3.8% control vs. 1.8% LBNP, P = 0.0040) compared to control (Figure).

Conclusions:
Nightly LBNP caused caudal redistribution of blood volume that partially reinstated hydrostatic gradients and mitigated the increase in choroid area and volume by 74% and 53%, respectively. These findings illustrate that normalizing transmural distending pressures during simulated microgravity preserves vascularized structures above the level of the heart and may prevent adverse remodeling during long duration spaceflight.
Abstract 14449: Not So Harmless: Marijuana Use and In-hospital Outcomes After Percutaneous Coronary Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Yoo Sang Gune K , Seth Milan , Earl Thomas , Ruwende Cyril , Karve Milind , Shah Ibrahim , Hill Thomas , Gurm Hitinder S , Sukul Devraj
Published: May 2021

Introduction:
Marijuana use is increasing as more states are legalizing it for both recreational and medicinal uses. Although studies have suggested an association between marijuana use and cardiovascular risk, there are limited data on outcomes after percutaneous coronary intervention (PCI) among marijuana users.

Hypothesis:
We hypothesize that marijuana users are at an increased risk of adverse outcomes after PCI compared with non-users.

Methods:
Between 1/1/2013 and 10/1/2016, self-reported marijuana use was collected by the Blue Cross Blue Shield Michigan Cardiovascular Consortium (BMC2), a state-wide registry of all patients who underwent PCI at 48 non-federal hospitals in Michigan. In-hospital outcomes included post-procedural stroke, transfusion, bleeding, acute kidney injury (AKI), and death. We used 1:1 propensity matching and multivariable logistic regression techniques to adjust for differences in baseline characteristics between marijuana users and non-users.

Results:
Among 113,477 patients, 3,970 (3.5%) self-identified as marijuana users. Compared with non-users, marijuana users were more likely to be younger (53.9 vs. 65.8), male (79.2% vs 66.8%), cigarette smokers (73.0% vs. 26.8%), present with ST-elevation myocardial infarction (27.3% vs. 15.9%), and have fewer cardiovascular comorbidities. After matching (n=3,803 per group), compared with non-users, marijuana users had significantly increased risks of bleeding (5.2% vs. 3.4%; aOR 1.54 [1.20-1.97], p<0.001) and stroke (0.3% vs 0.1%; aOR 11.01 [1.32-91.67]; p=0.026), and a decreased risk of AKI (2.2% vs 2.9%; aOR 0.61 [0.42-0.87]; p = 0.007). There were no differences in the risks of transfusion or death.

Conclusions:
Marijuana use was associated with significantly increased risks of stroke and bleeding after PCI. As marijuana use continues to grow, clinicians and patients should be aware of the increased risks of post-PCI complications in these patients.
Abstract 14450: Association of Trajectory of High Sensitivity C-reactive Protein and Incident Heart Failure in African Americans: The Jackson Heart Study
Authors: Hamid Arsalan , Yimer Wondwosen , Oshunbade Adebamike A , Khan Shahzeb , Kipchumba Rodney K , Kamimura Daisuke , Pandey Ambarish , Mentz Robert J , CLARK Donald , Fox Ervin R , Berry Jarett D , Stacey Richard , Shah Amil , Correa Adolfo , Butler Javed , Hall Michael E
Published: May 2021

Introduction:
Elevation in the inflammatory marker high sensitivity C-reactive protein (hsCRP) is associated with worse outcomes in patients with heart failure (HF). We aimed to determine if baseline or trajectory of hsCRP levels over time predict incident HF hospitalization.

Methods:
Jackson Heart Study (JHS) participants’ (n=4203 African Americans) hsCRP levels were measured over 3 visits (visit 1: 2000 to 2004; visit 2: 2005 to 2008; visit 3: 2009 to 2013). We assessed the association of a single hsCRP level measurement at baseline (visit 1) with incident HF hospitalization using Cox proportional hazard models. Furthermore, we assessed the association of trajectory of hsCRP over repeated measurements (visit 1-3) with incident HF using a joint model, which incorporates estimated hsCRP from a linear mixed effects model into a Cox hazards model to predict incident HF hospitalization while incorporating trajectory of hsCRP over visits. All hazard ratios (HR) are presented as an increase in hsCRP by 1 standard deviation on a Log
2
scale.

Results:
At baseline, mean age of participants was 55±13 years, 63.4% were women, and mean hsCRP level was 0.5±0.7 mg/dl. Over a median follow-up of 12 years, 353 (8.4%) participants were hospitalized with incident HF. After adjustment for covariates, baseline hsCRP was not associated with increased risk of incident HF hospitalization (Table, p>0.05). However, increases in hsCRP levels on follow-up were associated with a significantly increased risk of incident HF hospitalization (Table, p<0.05).

Conclusions:
While an elevated hsCRP level at one time point may not be associated with incident HF, the increasing trajectory of change in hsCRP over time is predictive of increased risk for incident HF hospitalization in African Americans. These data support the role of increased inflammatory status in the development of heart failure.
Abstract 14459: The Cardioprotective Effect on Energy Metabolism of Empagliflozin in Heart of Type 2 Diabetes Model Mouse
in vivo
Authors: Yamamoto Masamichi , Kitai Yuichirou , Yamamoto Shigenori , Pieper Michael P , Kotobuki Yutaro , Yasui Atsutaka , Yanagita Motoko
Published: May 2021

Chronic pathological conditions, such as type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodelling energy metabolic pathways and impairing cardiac contractility. The major source of myocardial energetics has been reported to shifts from OXPHOS in normal conditions to glycolysis in heart failure. Therefore, we decided to focus on the effect of empagliflozin on energy metabolic status in the heart.Recently, we generated two types of transgenic mice to monitor energy metabolism, intracellular ATP levels (iATP Tg) and mitochondrial ATP levels (mATP Tg) using FRET biosensor “ATeam” in the whole body, organ, and cellular levels as well as in beating heart. We intercrossed these mice with db/db, a mouse model of type 2 diabetes, and examined the energy metabolism of the heart in the empagliflozin -treated or non-treated groups.db/db;iATP Tg mice were fed EMPA-containing diets (30 mg/kg b.w., day) from 7 weeks of age for 10 weeks, and the ATP levels in the heart were measured by imaging with a fluorescence microscope. The results showed that, unlike the lowered ATP levels in the placebo group, the intracellular ATP level in the heart was significantly increased in the empagliflozin-treated group. Also, the ATP level was recovered in this empagliflozin-treated group to the same level as the wild type.Next, 8 weeks-old db/db;mATP Tg mice received a single dose of empagliflozin (30 mg/kg b.w.) via oral gavage after 4 hr of fasting. After another 3 hr of fasting, monitor the mitochondrial ATP level of the heart in vivo under the fluorescent microscope. The results showed that, unlike the placebo group, the ATP level in the mitochondria of the heart was significantly increased in the empagliflozin-treated group.These results suggest that empagliflozin may restore normal remodelling of energy metabolism in type 2 diabetic hearts.
Abstract 14466: Characterisation of Recent Trends in Cardiovascular Risk Factors in Younger Patients With Ischaemic Stroke
Authors: Bhat Aditya , Gan Gary , Makarious David , Tan Elizabeth , Chen Henry , Wolfe Nigel , Lee Lina , Burdusel Camelia , Nunes Maria Carmo , Chow Clara K , Tan Timothy
Published: May 2021

Introduction:
Strokes in the young are associated with a disproportionately large economic and social impact in addition to their clinical effects. Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes mellitus and smoking) are key drivers of cardiovascular disease including strokes, however recent temporal trends in the young stroke population have not been characterised.

Hypothesis:
The proportion of patients with non-SMuRFs are on the rise in a cohort of younger patients with ischaemic stroke/transient ischaemic attack.

Methods:
Consecutive patients aged <65 years with clinical and/or radiological diagnosis of ischaemic stroke or transient ischaemic attack in a tertiary referral centre (2013-2017) were retrospectively appraised. The demographic and clinical comorbidities of these patients were assessed including their SMuRF profile. The prevalence over time and clinical associations of patients with no SMuRFs were studied and compared to patients with SMuRFs.

Results:
Of 487 patients (53.49±9.13yrs, 60% men) analysed, 23% did not have SMuRFs. The proportion of “non-SMuRF” patients increased over time (see Figure; p<0.01) and this trend was not influenced by age (p=0.48) or gender (p=0.68). The presence of SMuRFs was not associated with in-hospital outcomes, however patients without SMuRFs were significantly less likely to be discharged on blood pressure (p<0.01) and lipid-lowering therapies (p=0.03).

Conclusions:
The proportion of young stroke patients without SMuRFs is substantial and has increased over time. Our findings highlight the need for further research to better understand the mechanisms underlying stroke development in this population and whether less risk factor treatment of this population could impact longer term outcomes.
Abstract 14471: Prognostic Impact of Sarcopenia in Men versus Women With Acute Decompensated Heart Failure and Preserved Left Ventricular Ejection Fraction
Authors: Kimura Takanari , Hikoso Shungo , Daisaku Nakatani , Tamaki Shunsuke , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Yasumura Yoshio , Yamada Takahisa , Sakata Yasushi
Published: May 2021

Background:
Sarcopenia is associated with poor prognosis in chronic heart failure. Fat-free mass index (FFMI) is an indicator of resting energy expenditure and has been used for the clinical diagnosis of sarcopenia. However, the prognostic impact of sarcopenia diagnosed by FFMI remains to be elucidated in patients admitted with acute decompensated heart failure (ADHF) and preserved LVEF (HFpEF), relating to gender.

Methods:
Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka. We studied 621 patients who survived to discharge (men, n=281 and women, n=340). Fat-free mass (FFM) was estimated by the formula [FFM (kg) = 7.38 + 0.02908 х urinary creatinine (mg/day)] and normalized by the square of the patient’s height in meters to calculate FFMI at discharge. Sarcopenia was defined as FFMI <17 kg/m2 in men and <15 kg/m2 in women. The endpoint was all-cause death.

Results:
During a follow-up period of 1.5±0.8 yrs, 102 patients died (men, n=46 and women, n=56). At multivariate Cox analysis, FFMI was significantly associated with the mortality independently of age, estimated glomerular filtration rate, NT-proBNP and LVEF in both men (p=0.0155) and women (p=0.0223). Patients with sarcopenia had a significantly higher risk of all-cause death than those without sarcopenia in both genders (Figure).

Conclusions:
In this multicenter study, sarcopenia diagnosed by FFMI was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF in both genders.
Abstract 14486: Validation of the Intermountain Risk Score and Get With the Guidelines-Heart Failure Score in Predicting 30 Day and 1 Year Mortality
Authors: Engelsgjerd Erik K , Horne Benjamin D , Benziger Catherine P
Published: May 2021

Background:
The Intermountain Risk Score (IMRS) predicts mortality in heart failure (HF) patients utilizing common, inexpensive tests in conjunction with patient age and sex. IMRS has not been validated for Essentia Health (EH)’s patient population nor compared to various pre-existing scores in this population.

Methods:
Individuals were selected from the American Heart Association’s Get With The Guidelines®- HF (GWTG-HF) registry as patients to evaluate in a retrospective study. This patient population consists of consecutive inpatients age ≥18 admitted with a HF diagnosis at EH from 7/2017 through 6/2019. IMRS was derived using common HF laboratory measures (complete blood count and basic metabolic profile), age, and sex. EH is a large rural health care system in MN, WI, and ND.

Results:
A total of 703 individuals (mean age: 74.20, 44.38% female) were studied. The 30-day IMRS predicted 30 day mortality for both sexes (Females N=312: OR=1.19 (95% confidence interval: 1.08, 1.32) per +1, p<0.001; Males N=391: OR=1.23 (1.12, 1.36) per +1, p<0.001). The 1-year IMRS predicted 1-year mortality (Females: OR=1.14 (1.06, 1.23) per +1, p<0.001; Males: OR=1.28 (1.18, 1.38) per +1, p<0.001). Using sex-specific cut offs for IMRS, females had better 30-day risk stratification in moderate to high risk groups compared to low risk reference group (Mod-risk: OR=5.90 (1.35, 25.85), p=0.018; high-risk: OR=9.63 (2.12, 43.72), p=0.003) vs. men (Mod-risk: OR=1.52 (0.61, 3.79), p=0.37; high risk: OR=4.53 (1.92, 10.65), p<0.001). The GWTG-HF risk score was significant for 30-day (OR=1.29 (1.16, 1.44) per +1, p<0.001) and 1-year mortality (OR=1.23 (1.13, 1.35) per +1, p<0.001) but was only calculated in 292 patients (41.5%).

Conclusions:
The Intermountain Risk Score is a useful predictor of 30-day and 1-year mortality for heart failure patients in a large rural healthcare system. The GWTG-HF risk score also predicts 30-day and 1-year mortality but is often not calculated due to not all variables being collected at each hospital visit (i.e. ejection fraction). The IMRS risk score uses simple variables that most patients have on admission and future study to evaluate cost-effectiveness as a prospective tool for initial risk estimation is warranted.
Abstract 14497: Mri Effects on Pacemaker/ICD Within the Magnetic Field; An Intra-observer Variability Study
Authors: Biederman Robert W , Gevenosky Loretta , Rayarao Geetha , WILLIAMS RONALD , Lombardi Richard , Shah Moneal , Farah Victor , Dahiya Garima , Wetzel Adam , Doyle Mark
Published: May 2021

Introduction:
The evolution of pacemaker/ICD safety in the magnetic field has triggered considerable interest in more clinical routine use. However, many limitations to widespread adoption of this seemingly implausible idea just a few years ago remain: unresolved impact of the high magnetic field, RF amplitude and oscillatory forces on electronics with possible high field damage to capacitor, solenoid and microcircuitry. However, given recent vender refinements over the last 10 years, we hypothesized that the impact on such circuitry may be far less than expected.

Method:
Consecutive interrogation of 940 pts who underwent clinically indicated MRI were evaluated over 5 years. This cohort was comprised of neuro/neurosurgical (72%), orthopedic (11%) and cardiac (17%) cases. Routine interrogation was performed within 10 min of entry into the bore of a dedicated Cardiac MRI (GE, 1.5T, WI). As well, reinterrogation was performed within 10 min of departure MRI (average 21±12min). At the time of interrogation pre and post MRI, a separate, repeat interrogation was performed within 5 min of each other such that 2 sets of PM/ICD parameters were obtained pre and post MRI.

Result:
No complications to either pt or device occurred during the MRI comprising 564 PMs and 376 ICDs. A cardiologist was present guiding the interrogation, configuration, and reconfiguration of the PM/ICD as well was present for entire MRI. There were no significant differences in common clinical parameters. More importantly, there was no difference in any parameter when compared in any order pre to post MRI scan. See Table.

Conclusion:
Intrinsic variability and inherent changes triggered by MRI environments are clinically insignificant and statistically negligible thereby removing yet another of the last remaining fears and apprehensions for primary PM/ICD failure and destruction as we move towards a more uniform acceptance of this technology for clinically meaningful use, dissemination and acceptance.