bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14043: Association of Non-Alcoholic Steatohepatitis Assessed by Fib-4 Index and Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Hussain Aliza , NAMBI VIJAY , Selvin Elizabeth , Sun Wensheng , Matsushita Kunihiro , Yu Bing , Boerwinkle Eric , Kanwal Fasiha , Lutsey Pamela L , HEISS Gerardo M , Hoogeveen Ron C , Ballantyne Christie M
Published: May 2021

Introduction:
Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study

Methods:
We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score <1.45, intermediate for 1.45-3.25 and high for >3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors.

Results:
Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (<1.45), those with elevated FIB-4 >3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50).

Conclusions:
In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.
Abstract 14045: The Incidence and Associated Risk Factors of New-onset Atrial Fibrillation in the Medical Intensive Care Unit
Authors: Brunetti Ryan J , Zitelny Edan , Newman Noah , Dowell Jonathan , Singleton Matthew J , Bhave Prashant
Published: May 2021

Introduction:
New-onset AF (NOAF) in the medical ICU is associated with worse patient outcomes. The research on NOAF in this setting compared to that in the post-cardiothoracic and non-cardiac surgery patients is not as robust. For example, a 2019 literature review found that the reported incidence of NOAF in the medical ICU ranges between 1.7% and 43.9%. This retrospective single-center observational study examines the incidence and associated risk factors of this relatively understudied population.

Methods:
The total study population is comprised of 2682 consecutive patients with medical ICU stays in 2018. Post-operative patients as well as patients with preexisting AF were excluded. ICD-10 codes were used in conjunction with i2b2 to identify patients. Manual chart review confirmed those with NOAF during a 2018 ICU stay. These patients were compared with a control group comprised of 106 randomly-selected patients from the study population. Demographics and diagnoses were collected, along with length of stay (LOS), mortality at discharge and mortality after one year.

Results:
90 patients of the 2682 patient cohort (3.4%) developed NOAF during their ICU stay. Patients with NOAF were more likely to be older (67.7 vs. 56.5 years), have hypertension (75.6% vs. 62.3%) and have peripheral vascular disease (41.1% vs. 26.4%) compared to the control group. More importantly, NOAF was associated with an increased LOS of 16.5 days relative to 9.6 days in the control group. No significant difference was found in mortality between the two groups. The results of this preliminary analysis are summarized in
Table 1
.

Conclusions:
We found the incidence of NOAF in patients admitted to the medical ICU was 3.4%, and NOAF was associated with a significant increase in LOS. Upon completion of data extraction and multivariate analysis for the entire study population, we hope that this study will contribute to our understanding of the significance of NOAF in critically ill patients.
Abstract 14201: The Application of Hipsc-derived Cardiomyocytes Paced by Re-entrant Waves for Drug Assessment
Authors: Li Junjun , Minami Itsunari , Miyagawa Shigeru , Qu Xiang , HUA YING , Sawa Yoshiki , Liu Li
Published: May 2021

Introduction:
How to precisely evaluate response in newly developed medications in vitro may be a great concern in drug screening. We modified normal low-attachment culture dish and created closed-loop tissue ring from single hiPSC-CMs. We hypothesized that the re-entrant wave (ReW) could originate and pace the cardiac tissue ring, and the CMs under pacing could be matured and used for drug assessment.

Methods:
PDMS wells and pillars were mounted in low-attachment petri dishes (Figure 1A). 4 х 10
5
hiPSC-CMs were plated into the wells to form tissue ring where the ReW could spontaneously originate. After cultivation for 14 days, the hiPSC-CMs were evaluated by immunostaining and gene expression. Micro electrode array (MEA) were used to evaluating the CM response to different drugs.

Results:
The electrical signal recorded by MEA indicated that the ReWs could make the CMs beat at a much higher rate than the Control group (Figure 1B, 123.26 ± 10.36 bpm vs. 14.08 ± 4.53 bpm, p<0.0001). After 14 day culture, the ReW group demonstrated significantly higher expression of Troponin T (TnT2), myosin heavy chain 7 (β-MHC), and α-actinin. Interestingly, the α-actinin staining indicated alignment of CMs within the ReW group (Figure 1C). The CMs under ReW pacing showed robust response to several cardiac compounds including E4031, (hERG K+ channel blocker, Figure 1D and E), isoproterenol (β adrenoceptor agonist) and propranolol (beta-blocker). Both the field potential as well as the Ca
2+
transients showed correlated dose-dependent change and the recovering after washout of the drugs.

Conclusions:
The ReWs could spontaneously originate in the cultured cardiac tissue ring with enhancement of the maturation in the hiPSC-CMs and robust response to various drugs, indicating the system as a robust drug assessment system with multiple read-out methods.
Abstract 14216: Predictors of 30-day and 1-year Mortality After Transvenous Lead Extraction for Device Infection
Authors: Khine Kay , Gupta Ashwani , Saltzman Heath E , Kutalek Steven
Published: May 2021

Introduction:
The incidence of device infection is constantly increasing; requiring transvenous lead extraction (TLE). Data regarding predictors of short and long-term mortality after TLE for infection are limited.

Methods:
We collected data regarding 30-day and 1-year mortality of patients undergoing TLE at a university hospital between April 2004 and June 2015. Patients with less than 30-day follow up were excluded.

Results:
Out of total 1223 TLE procedures, 700 were performed for infectious indications. 30-day follow-up was available for 620 patients (88.6%) and 1-year follow up was available for 541 patients (77.3%). Overall 30-day mortality was 9% (4.3% for pocket infection, 12.3% for systemic infection) and 1-year mortality was 27.5% (16% for pocket infection, 35.8% for systemic infection). Patient age, end-stage renal disease, history of valve replacement, atrial fibrillation,
Staphylococcus aureus
infection, systemic infection, any procedural complication, elevated WBC count, low hemoglobin, need for CCU admission, need for pressor support, acute kidney injury, cardiogenic shock and need for blood transfusion were predictors of both 30-day and 1-year mortality in univariate analysis. Any retained fragment was predictor of 30-day mortality. Peripheral vascular disease and low platelet count were predictors of 1-year mortality. Patient age, history of valve replacement, need for pressor support and low hemoglobin were independent predictors of 30-day as well as 1-year mortality in multivariate analysis. End-stage renal disease, atrial fibrillation, elevated WBC count and need for CCU admission were independent predictors of 30-day mortality. Systemic infection, low platelet count and need for blood transfusion were predictors of 1-year mortality. Strongest predictor of 30-day mortality was history of valve replacement (Odds ratio 4.23) and strongest predictor of 1-year mortality was need for pressor support (Odds ratio 3.12).

Conclusions:
In conclusion, 30-day and 1-year mortality after device infection remains high despite successful TLE. Patient age, history of valve replacement, need for pressor support and low hemoglobin are independent predictors of both short and long-term mortality in multivariate analysis.
Abstract 14248: Efficacy and Safety of Bempedoic Acid in Patients Who Cannot Tolerate Statins: Pooled Analysis of 4 Phase 3 Clinical Trials
Authors: Laufs Ulrich , Banach Maciej , Bays Harold E , Catapano Alberico L , Duell P Barton , Goldberg Anne C , Gotto Antonio M , Leiter Lawrence A , Ray Kausik K , Bloedon LeAnne T , Ye Zhan , Mancini G
Published: May 2021

Introduction:
Some patients cannot tolerate statins mainly because of statin-associated muscle symptoms (SAMS). Bempedoic acid (BA) is a prodrug activated in the liver and not in skeletal muscle. BA has been shown to significantly lower LDL-C by a mean of ~18% in patients receiving background maximally tolerated statins and a mean of ~25% in patients with statin intolerance.

Objective:
Determine efficacy and safety of BA in statin-intolerant patients receiving no background statin therapy across 4 phase 3 clinical trials.

Methods:
Data were pooled from 4 randomized (2:1), placebo-controlled studies evaluating oral BA 180 mg once daily vs placebo for 12 to 52 weeks. Primary efficacy endpoint was LDL-C % change from baseline to week 12. Safety assessments included treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI), and laboratory values. For patients who reported SAMs, additional information around etiology and location were collected.

Results:
Of 3621 patients, 586 (394 BA; 192 placebo) reported intolerance to multiple statins because of SAMS or other AEs and received no statins during the studies. Mean baseline LDL-C was 148.7 mg/dL. After 12 weeks, BA significantly lowered LDL-C vs placebo (placebo-corrected, -26.5%;
P
< 0.001). Myalgia was the top reason for drug discontinuation, but was less common in the BA arm (17.7%) vs placebo (43.5%). CK > 5 х ULN was uncommon in both groups. Among AESIs
(Table)
, muscle disorders were reported by 12.7% (BA) vs 14.1% (placebo). Myalgia was less common with BA (4.6%) vs placebo (7.3%). Muscle spasms (4.1% vs 3.6%) and pain in extremity (3.3% vs 2.1%) were comparable between treatment groups. Muscular weakness was rare (0.5% BA, 1% placebo).

Conclusion:
Among the population of patients unable to use statins, BA significantly lowered LDL-C vs placebo without increasing muscle-related TEAEs. BA may be an appropriate lipid-lowering therapy for patients with hyperlipidemia who are statin intolerant.
Abstract 14307: Reduction in the Risk of Major Adverse Cardiovascular Events With Apabetalone, a Bet Protein Inhibitor, in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes According to Insulin Treatment: Analysis of the Betonmace Trial
Authors: Schwartz Gregory G , Nicholls Stephen J , Ginsberg Henry , JOHANSSON Jan , Kalantar-Zadeh Kamyar , Kulikowski Ewelina , Toth Peter P , Wong Norman , Sweeney Michael , Ray Kausik K ,   On behalf of the BETonMACE investigators
Published: May 2021

Introduction:
Use of insulin has been associated with worse CV outcomes in patients (pts) with type 2 diabetes T2D. Apabetalone (APB) is a novel selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. In the Phase 3 BETonMACE trial treatment with APB, compared with placebo, resulted in non-significantly fewer major adverse CV events (MACE: CV death, non-fatal MI or stroke) in 2425 pts with T2D and recent acute coronary syndrome (ACS).

Objective:
In this analysis of BETonMACE we examined the relationship of insulin use to MACE risk and its modification by APB.

Methods:
Baseline characteristics were compared in insulin-treated (INS) or not insulin-treated (no-INS) pts. The incidence of MACE and treatment hazard ratio (HR) were compared between these two subgroups.

Results:
829 (34.2%) pts received insulin at baseline, with or without other diabetes drugs. INS vs no-INS pts were more likely to be female (29 vs 24%), had longer duration of T2D (12.6 vs 6.4 yrs), higher HbA1c (8.4 vs 6.9%) and baseline glucose (156 vs 126 mg/dL), lower use of metformin (73 vs 87%) and sulfonylureas (21 vs 33 %), and higher use of SGLT2 inhibitors (16 vs 6%) and GLP1 receptor agonists (10 vs 2%). MACE in the placebo group was higher in INS than no-INS (17.4% vs 9.7%; HR 1.94; 95% CI 1.39-2.73; p=0.0001). Overall, APB was associated with fewer MACE (HR 0.82, 95% CI 0.65-1.04, p=0.11). The relative reduction in MACE with ABP was similar in INS (HR 0.78, 95% CI. 0.55-1.10, p=0.16) and no-INS (HR 0.87, 95% CI 0.63-1.21, p = 0.42, p
interaction
=0.64). The absolute reduction in MACE with APB was numerically greater among INS than non-INS (3.69 vs 1.30%).

Conclusions:
Pts with T2D and recent ACS treated with insulin are at high risk for MACE. High risk of MACE with insulin use is likely through association with other clinical characteristics prognostic for MACE. Insulin treatment may be a marker to identify pts with potential for large absolute reduction in MACE with APB.
Abstract 14313: Machine Learning for Prediction of Low Density Lipoprotein Cholesterol in Fasting and Non-fasting Patients With and Without HIV Infection
Authors: Rana Mariam N , Kim Chang , Longenecker Chris T , Al-Kindi Sadeer
Published: May 2021

Background:
Low-density lipoprotein cholesterol (LDL-C) is commonly estimated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) using predefined equations which assume fixed or varying relationships between these parameters and may under- or overestimate LDL-C. Machine learning (ML) algorithms allow prediction of complex non-linear relationships. We, therefore, sought to investigate the utility of ML to predict LDL-C in comparison with two widely-used methods (Friedewald and Hopkins).

Methods:
We identified 7397 direct LDL-C (4716 HIV, 2060 uninfected controls) measurements in the Women's Interagency HIV Study (WIHS), a prospective study of women with and without HIV undergoing serial assessments. We trained and optimized 5 ML methods (linear regression, random forest, gradient boosting machine, support vector machine, and neural networks) to predict LDL-C using TC, HDL-C, and TG in 80% of the measurements and tested model performance in a holdout test set (20% of the measurements).

Results:
Overall, the support vector machine model had the best performance characteristics, outperforming Friedewald’s and Hopkins methods with higher R
2
, lower root mean square error and lower mean absolute error. The support vector machine model performance remained superior in participant subgroups with and without HIV and those with non-fasting measurements. Model performance parameters for the test dataset are shown in the Figure.

Conclusions:
A support vector machine learning model predicts directly measured LDL-C more accurately than Friedewald and Hopkins methods, especially in non-fasting patients with HIV. Further studies are needed to provide external validation.
Abstract 14317: Kidney Function Deterioration is Dependent on Blood Pressure Levels: 11.2-year Follow-up in Diabetic Patients
Authors: SOEJIMA Hirofumi , Morimoto Takeshi , Okada Sadanori , Matsumoto Chisa , Nakayama Masafumi , Jinnouchi Hideaki , Masuda Izuru , Waki Masako , Saito Yoshihiko , Ogawa Hisao
Published: May 2021

Introduction:
Blood pressure (BP) is a significant predictor for chronic kidney disease (CKD).

Hypothesis:
We sought to evaluate whether the progression of CKD in diabetic patients, without a history of atherosclerotic events, is dependent on BP control.

Methods:
The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. We defined late-stage kidney disease (LSKD) as estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m
2
or hemodialysis. Among 2,536 JPAD patients, 27 patients were excluded for eGFR <30ml/min/1.73m
2
on registration. BP of the JPAD patients was recorded on average 8 times. Based on the mean value of systolic BP (SBP), we divided the patients into three groups: a High BP Group (n=607, SBP≥140 mm Hg); a Moderate BP Group (n=989, 140>SBP≥130 mm Hg); or a Low BP Group (n=913, SBP<130 mm Hg). We compared the incidence of LSKD among the three groups.

Results:
The mean eGFR (ml/min/1.73m
2
) was 75.1 in the High BP Group, 72.6 in the Moderate BP Group, and 75.7 in the Low BP Group on registration. During a 11.2-year follow-up, the incidence of LSKD was significantly higher in the High BP and Moderate BP Groups than in the Low BP Group (P<0.0018, Figure). Cox proportional hazards model analysis revealed that the High BP (HR, 1.57, P=0.049) and Moderate BP (HR, 1.52, P=0.037) were independent factors after adjustment for proteinuria≥±, age≥65 years, men, body mass index≥24 kg/m
2
, duration of diabetes ≥7.0 years, statin usage, aspirin usage, eGFR≥60 ml/min/1.73m
2
, and hemoglobin A1c ≥7.2 % (Figure).

Conclusions:
Our study demonstrated that SBP was independently associated with the progression to LSKD in diabetic patients, without a history of atherosclerotic events. SBP less than 130 mm Hg is recommended for diabetic patients to prevent progression to LSKD.
Abstract 14321: Administration of Laminin511 Combined With Prostacyclin Agonist Enhances Endogenous Stem Cell Recruitment in Acute Myocardial Infarction Model Rat
Authors: Sougawa Nagako , Miyagawa Shigeru , Harada Akima , Oda-Mochizuki Noriko , Sato-Nishiuchi Ryoko , Sekiguchi Kiyotoshi , Sawa Yoshiki
Published: May 2021

Backgroud:
Although treatment by endogenous stem cell recruitment is one of the promising therapeutic options for the damaged tissues, the therapeutic efficacy is not enough to repair the severely damaged heart. How to enhance migration of stem cells to injured site and confine them there may be key point to improve the therapeutic effects. In this study, we hypothesized that combined strategy of prostacyclin agonist (ONO1301), which is enhancer in stem cell recruitment, and laminin (LM) 511 as stem cell bed may enhance regeneration processes in failed heart.

Methods and Results:
To examine the therapeutic effect of ONO1301 and LM511, we administrated ONO1301 and LM511 immersed collagen sheet (Combination group), only LM511 immersed collagen sheet (LM group), only ONO1301 immersed collagen sheet (ONO group), and PBS immersed collagen sheet (control) to rat acute infarction model. Four weeks later, qPCR analysis and histological analysis revealed that the expression of cytokines related to cell migration or angiogenesis were significantly higher in the combination group as compared to the other groups. The number of mesenchymal stem cell (PDGFRα and CD90 double positive cells) tended to be higher in the combination group compared to the other groups (combination: 388 ± 7 cells/mm
2
, LM: 292 ± 34 cells/mm
2
, ONO: 216 ± 30 cells/mm
2
, control: 160 ± 34 cells/mm
2
). In addition, the number of matured arterioles which have both endothelial cells and smooth muscle cells was markedly higher in the combination group compared to the control group (combination: 616 ± 44 cells/mm
2
, control: 226 ± 60cells/mm
2
; p < 0.05). In addition, infarct size was remarkably reduced in the combination group than the other groups (combination: 11.5 ± 0.1%, LM: 14.8 ± 0.8%, ONO: 23.6 ± 2.9%, control: 29.2 ± 2.0%). Ultrasonographically, ejection fraction significantly improved in the combination group compared to the other groups (combination: 55.0 ± 0.9%, LM: 51.6 ± 1.4%, ONO: 46.9 ± 1.4%, control: 43.5 ± 2.9%).

Conclusion:
The combined administration of LM511 and ONO1301 promotes arteriogenesis by enhanced endogenous repair with declined infarct size and improved cardiac function in rat acute myocardial infarction model, proposing new therapeutic strategy for ischemic cardiomyopathy.
Abstract 14337: Antihypertensive Class and Cardiovascular Outcomes in Patients With HIV and Hypertension
Authors: Rethy Leah B , Feinstein Matthew J , Achenbach Chad J , Townsend Raymond R , Bress Adam P , Shah Sanjiv J , Cohen Jordana
Published: May 2021

Background:
People with HIV(PWH) have a high risk of hypertension and hypertension-related cardiovascular diseases (CVD).

Objectives:
Given unique pathways contributing to hypertension among PWH, we sought to determine whether antihypertensive class was associated with CVD events in PWH.

Methods:
Among veterans with HIV and new onset hypertension (2000-2019), we used propensity score-matching with Cox regression to evaluate the risk of CVD events (ischemic heart disease, heart failure, stroke) or death by initial antihypertensive class. In supplementary analyses we used marginal structural modeling to account for time-updated antihypertensive class and confounding.

Results:
Among 8041 PWH with hypertension, 24% were initiated on angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEi/ARB) monotherapy, 23% on thiazide/thiazide-like diuretic monotherapy, 13% on β-blocker monotherapy, and 11% on calcium channel blocker (CCB) monotherapy. Median (IQR) follow-up was 6.5 (3.2-10.5) years and 25% experienced a CVD event. In propensity score-matched analyses, β-blockers, but not CCBs or thiazide/thiazide-like diuretics, were associated with an increased risk of 1) CVD or death 2)incident CVD or death and 3)incident CVD compared with ACEs/ARBs (Incident CVD: HR [95% CI] β-blockers 1.90 [1.24, 2.89]; CCBs 1.02 [0.77, 1.34]; diuretics 1.06 [0.86,1.31];
Figure)
. Similar risks were associated with β-blockers in time-updated analyses. In veterans without CKD, initial ACEi/ARB use carried a lower risk of incident heart failure compared with all other classes.

Conclusions:
We observed high rates of CVD events in PWH with hypertension, and a high prevalence of β-blocker use for initial hypertension management, even among those without indications. Our findings highlight the potential harm associated with β-blockers and the possible benefit associated with ACEI/ARBs for hypertension management in PWH.
Abstract 14344: Prognostic Factors of Atrial Fibrillation Patients With Coronary Artery Disease: The Fushimi Af Registry
Authors: Masunaga Nobutoyo , Ogawa Hisashi , Aono Yuya , Ikeda Syuhei , DOI KOSUKE , Hamatani Yasuhiro , Fujino Akiko , An Yoshimori , ISHII MITSURU , Iguchi Moritake , Esato Masahiro , Tsuji Hikari , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: May 2021

Background:
Atrial fibrillation (AF) patients are likely to have concomitant coronary artery disease (CAD). A new strategy of antithrombotic therapy in AF patients with stable CAD was demonstrated in recent randomized clinical trials. Now that antithrombotic therapy for AF patients with CAD has reached a major turning point, it is important to know the prognostic factors in those patients.

Purpose:
In this study, we investigated clinical characteristics, cardiovascular events and prognostic factors in AF patients with CAD.

Methods:
The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow up data including prescription status were available in 4,441 patients from March 2011 to November 2019. Of 4,441 patients, 645 patients had a history of CAD at enrollment.

Results:
The mean age was 76.4±8.6 and 65.9% were male. Averages of CHA
2
DS
2
-VASc score and HAS-BLED score were 4.41 and 2.35, respectively. Oral anticoagulant (OAC) was prescribed in 52.9% of those patients and antiplatelet drug (APD) was prescribed in 70.4%. The combination of OAC and APD was prescribed in 36.0%. During follow-up period (median 1,495 days), cardiac death occurred in 51 patients, composite of cardiac death, myocardial infarction (MI) and stroke in 136, and major bleeding in 77 (1.8, 5.1 and 2.9 per 100 person-years, respectively). In multivariate analysis, factors associated with composite of cardiac death, MI and stroke in AF patients with CAD were low body weight (<=50kg) (hazard ratio [95% confidence interval]; 1.62 [1.07-2.47]), previous stroke (1.69 [1.13-2.52]), heart failure (1.47 [1.02-2.11]), hypertension (0.60 [0.41-0.87]) and diabetes mellitus (1.62 [1.13-2.32]). Furthermore, factors associated with major bleeding in AF patients with CAD were anemia (male: hemoglobin<12 g/dl, female: hemoglobin<11 g/dl) (1.82 [1.09-3.04]) and thrombocytopenia (<150,000 /μL) (3.02 [1.29-7.03]).

Conclusion:
In Japanese AF patients with CAD, low body weight, previous stroke, heart failure, hypertension and diabetes mellitus were associated with cardiovascular events, and anemia and thrombocytopenia were associated with major bleeding.
Abstract 14373: Efficacy and Safety of Antihypertensive Drug Classes: The Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Byrne Christina , Varshney Anubodh , Almarzooq Zaid , Kragholm Kristian H , Krogager Maria L , Vaduganathan Muthiah , Biering-srensen Tor , Olsen Michael H , Bhatt Deepak L , Pareek Manan
Published: May 2021

Purpose:
To assess the efficacy and safety of antihypertensive drug classes, including angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), beta blockers (BB), calcium channel blockers (CCB), and thiazide diuretics (TD), in subjects at high cardiovascular (CV) risk.

Methods:
SPRINT was a randomized, controlled, open-label trial in which individuals without diabetes aged ≥50 years, at high CV risk, and with a systolic blood pressure (SBP) 130-180 mmHg were randomized to intensive (SBP target <120mmHg) or standard BP control (SBP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, i.e., hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, and falls. Associations between baseline antihypertensive drug classes, efficacy, and safety outcomes, stratified by level of SBP control, were examined using Cox proportional-hazards regression.

Results:
Of 9361 participants, baseline use of antihypertensive agents was as follows: ACEi/ARB in 1317 (14%), BB in 911 (10%), CCB in 796 (9%), and TD in 979 (10%). A total of 1366 (15%) subjects did not have a record of being on an antihypertensive drug at baseline. In the intensive BP control group, use of a BB-based regimen at baseline was associated with a significantly higher risk of the primary outcome when compared with no medications (
Figure
). Similar patterns were observed for secondary efficacy endpoints. The risk of serious adverse events tended to be lower in patients receiving a treatment regimen containing either an ACEi/ARB or a TD compared with those receiving a regimen containing a BB or a CCB (
Figure
).

Conclusions:
In SPRINT, the risk of adverse events was lowest in patients who were not on an antihypertensive drug at baseline. ACEi/ARB-based and TD-based regimens appeared to have the best balance between efficacy and safety.
Abstract 14385: The Exist of Enlarged Left Ventricular Diastolic Volume is Not a Predictor of Irreversible Left Ventricular Systolic Function in Patients With Atrial Arrhythmia
Authors: Matsuda Hisao , Noda Airi , Nakayama Yui , Nakanishi Toru , Kasahara Mizuho , Warisawa Takayuki , Mizukoshi Kei , Takano Makoto , Mizuno Koichi , Kasagawa Akira , Yamada Marika , Nakajima Ikutarou , Miyazaki Hidekazu , Furukawa Toshiyuki , Harada Tomoo , Akashi Yoshihiro J
Published: May 2021

Introduction:
Atrial arrhythmia (AA) and left ventricular systolic dysfunction (LVSD) frequently co-exist, which loom as burgeoning public health problems. It is difficult to determine whether a tachycardia is the indicator or consequence of LVSD in patients with tachycardia and LVSD. Tachycardia mediated cardiomyopathy (TCM) raises a “chicken or egg” question. Regardless of the etiology, the patients with severe LVSD are considered as the candidate for the implantation of cardioverter defibrillator as primary prevention. It is well known that the LVSD improves after the successful treatment of AA in TCM population. However, enlarged left ventricular end-diastolic dimension (LVDd) is considered as a parameter of irreversible LVSD.

Hypothesis:
Enlarged LVDd could not be a predictor for irreversible LVSD in patients with AA.

Methods:
We assessed patients with persistent AA and heart failure (Ejection Fraction (EF) <45%) who were received aggressive rhythm control therapy and maintained sinus rhythm with catheter ablation, electrical cardioversion and anti arhythmic drugs. Echocardiographic parameters and brain natriuretic peptide (BNP) were evaluated before and after the treatment.

Results:
Twenty-five patients with persistent AA and LVSD (23 men; mean age 63.8±9.3 years) were enrolled in this study. After restored and maintained SR, EF and left ventricular end-systolic volume (ESV) and BNP were improved in all patients respectively (EF 30.7±10.7 to 54.0±7.3%, ESV; 82.1±32.4 to 50.6±24.1ml, BNP; 379.2±237.9 to 48.0±29.7pg/ml P<0.001). In the other hand, there were no significant improvement of LVDd and left ventricular end-diastolic volume (EDV) (LVDd; 54.7±7.6 to 54.3±5.5mm P=0.68, EDV; 120.1±37.9 to 108.2±38.0ml P=0.16). Enlarged LVDd >60mm were observed in 5 patients (25%) before the treatment. EF was normalized in patients with severe LVSD (EF<35%, n=13; 52%).

Conclusions:
The unnecessary device implantation could be avoided in patients with AA and severe LVSD with aggressive rhythm control therapy. Even in the patients with severe LVSD and enlarged LVDd, LVSD is reversible when AA exists.
Abstract 14390: The Cardiac Myosin Inhibitor, Ck-3772271, Attenuates Cardiac Fibrosis and Diastolic Dysfunction in the Dahl/salt Sensitive Rat Model of Heart Failure With Preserved Ejection Fraction
Authors: Xu Xihui , Hwee Darren T , Hartman James J , Wang Jingying , Wu Yangsong , McHugh Claire , Chin Eva R , Malik Fady I , Morgan Bradley P
Published: May 2021

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is characterized by underlying contractile dysfunction and progressive myocardial fibrosis and stiffness. CK-3772271 (CK-271) is a novel small molecule cardiac myosin inhibitor that reduces cardiac myosin ATPase activity and reduces cardiac contractility in unloaded isolated cardiomyocytes
in vitro
and in healthy rats and dogs
in vivo
. The effect of chronic CK-271 treatment on cardiac function and morphology was evaluated in the Dahl/Salt Sensitive (DSS) rat hypertension model of HFpEF.

Methods:
DSS male rats were fed either a control low salt (LS, 0.3% NaCl) or high salt (HS, 4% NaCl) diet to induce a hypertension-driven HFpEF disease phenotype. 6 weeks after HS diet treatment, DSS rats were randomized into two sub-groups: continued HS diet or a HS diet formulated with CK-271 (100 ppm) for an additional 6 weeks. Body mass, systolic blood pressure, and cardiac function were measured longitudinally. After 12 weeks of HS treatment, hearts were collected to assess cardiac fibrosis.

Results:
HS diet treatment increased systolic blood pressure (LS:132.2 ± 4.7 mm Hg vs. HS: 163.5 ± 4.0 mm Hg, mean ± SEM, p< 0.001) and caused cardiac hypercontractility as evidenced by an increase in the end-systolic pressure-volume relationship (LS: 0.8 ± 0.17 vs. HS: 2.1 ± 0.46 mm Hg/ml). HS diet also increased isovolumic relaxation time (IVRT) (LS: 16.8 ± 0.6 vs. HS: 22.8 ± 0.6 ms, p<0.0001), left atrial area (LS: 30.3 ± 0.8 vs. HS: 42.5 ± 2.2 mm
2
, p<0.0001) and cardiac fibrosis (LS: 3.4 ± 0.4 vs. HS: 5.0 ± 0.6 %). 6 weeks of CK-271 treatment reduced fractional shortening (HS: 53.8 ± 1.4 vs. HS+CK-271: 42.7 ± 1.0 %, p<0.0001) and reduced HS diet-induced diastolic dysfunction, including IVRT (HS: 22.8 ± 0.6 vs. HS+CK-271: 19.5 ± 0.5 ms, p<0.0001) and left atrial area (HS: 42.5 ± 2.2 vs. HS+CK-271: 35.4 ± 0.8 mm
2
, p<0.0001). Furthermore CK-271 reduced the development of cardiac fibrosis (HS: 5.0 ± 0.6 vs. HS+CK-271: 3.5 ± 0.3 %, p<0.05) induced by HS diet.

Conclusion:
The small molecule cardiac myosin inhibitor, CK-3772271, attenuated the development of cardiac hypercontractility, diastolic dysfunction and fibrosis in the DSS rat model of HFpEF. Cardiac myosin inhibition may be a novel approach to mitigate the development of HFpEF.
Abstract 14401: Elevated Levels of Angiotensin II Type 1 Receptor Autoantibodies Are Associated With Abnormal Echocardiogram Parameters in Women With Preeclampsia
Authors: Minhas Anum S , Zakaria Sammy , Mukherjee Monica , Boyer Theresa , Fedarko Neal , Vaught Arthur J
Published: May 2021

Introduction:
Preeclampsia (PEC) increases the long-term risk for heart failure with preserved ejection fraction (HFpEF). While the underlying pathogenesis is unknown, angiotensin II type 1 receptor autoantibodies (AT1-AA) have been implicated. AT1-AA bind agonistically to the AT1 receptor and may result in clinical manifestations of preeclampsia. We aimed to determine whether women with PEC have elevated AT1-AA levels compared to normotensive women (controls) during pregnancy and at 4 years postpartum, and whether AT1-AA levels correlate with abnormal echocardiographic parameters.

Methods:
We performed a prospective longitudinal cohort study comparing women with PEC (n=21) to controls (n=20). AT1-AA and echocardiographic measurements were obtained during pregnancy and 4 years postpartum. Linear regression analyses were performed to evaluate the association between AT1-AA levels and important echocardiographic parameters.

Results:
Mean AT1-AA level during pregnancy differed significantly between women with PEC versus healthy pregnant controls (10.21±3.20 vs 6.33±3.40 μg/ml, p<0.001). Women with PEC were more likely to be black and deliver at an earlier gestational age. Higher AT1-AA was associated with increased systolic/diastolic blood pressure, echocardiographic markers of biventricular systolic function (tricuspid annular systolic plane excursion and left ventricular (LV) ejection fraction), concentric LV hypertrophy and worsened diastolic function. AT1-AA remained persistently elevated at 4 years in women with PEC at baseline compared to controls (12.76±5.13 vs 4.47±1.49 μg/ml, p<0.001) (Figure 1).

Conclusions:
Women with PEC have elevated AT1-AA compared to controls, both during pregnancy and 4 years postpartum. Higher AT1-AA is associated with abnormal diastolic parameters, LV remodeling, and hyperdynamic biventricular function. These findings suggest that AT1-AA plays an important role in the risk of HFpEF in PEC.
Abstract 14404: The Fontan Udenafil Exercise Longitudinal Trial Subgroup Analysis
Authors: Goldberg David J , Gongwer Russell , Trachtenberg Felicia , Lubert Adam M , Rhodes Jonathan , Penny Daniel J , Petit Christopher J , Schumacher Kurt R , Ginde Salil , Williams Richard V , Yoon Ja Kyoung , Kim Gi Beom , Nowlen Todd T , DiMaria Michael V , Frischhertz Benjamin P , Wagner Jonathan B , McHugh Kimberly E , McCrindle Brian W , Cartoski Mark , Detterich Jon A , Yetman Angela T , John Anitha S , Richmond Marc E , Yung Delphine , Payne Ronald M , Mackie Andrew S , Davis Christopher K , Shahanavaz Shabana , Hill Kevin D , Almaguer Marisa , McBride Michael G , Goldstein Bryan H , Pearson Gail D , Paridon Stephen M
Published: May 2021

Background:
The Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT 02741115) demonstrated improvements in exercise capacity and ventricular performance following six months of treatment with udenafil (87.5 mg twice daily). In this analysis we evaluated whether subgroups within the population experienced a differential effect on exercise performance in response to treatment.

Methods:
The effect of udenafil on exercise was evaluated within subgroups defined by gender, race, ventricular morphology, and baseline peak oxygen consumption (VO
2
). Linear regression modeling evaluated for differential response to udenafil (interaction of subgroup with treatment arm). Individual subgroups were excluded if the number of participants was <5% of total. As the FUEL Trial was not powered for subgroup analysis, all analyses were viewed as exploratory.

Results:
Subgroup analyses demonstrated qualitative improvements in peak VO
2
, work rate at the ventilatory anaerobic threshold (VAT), VO
2
at VAT, and ventilatory efficiency (VE/VCO
2
) for those randomized to udenafil compared to placebo in all subgroups (Table). There was not a differential response to udenafil based on gender, race, ventricular morphology, or baseline peak VO
2
, although participants in the lowest tertile of baseline peak VO
2
and those with single left ventricles trended toward larger improvements.

Conclusion:
The relatively uniform improvement among subgroups in response to treatment with udenafil is consistent with the findings from the primary analysis of the FUEL trial. While the absence of a statistically significant differential effect between subgroups suggests that the effect of udenafil may not be gender, race, or morphology specific, and may not vary based on baseline exercise performance, the possibility of a larger improvements in those with poor baseline peak VO
2
and those with single left ventricle warrants further investigation.
Abstract 14445: The Prevalence of Coronary Risk Factors Among Patients Undergoing Their First Percutaneous Coronary Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Gurm Zoya , Seth Milan , Daher Edouard , Pielsticker Elizabeth , Qureshi M. Imran , Zainea Mark , Tucciarone Michael , Hanzel George , Sukul Devraj
Published: May 2021

Background:
Coronary artery disease (CAD) is the leading cause of death globally and risk factors for CAD are well established. Although there has been a decline in the incidence of CAD in recent years, understanding the risk factor profile of patients presenting with cardiac disease in contemporary practice may help define current unmet challenges in preventing CAD.

Objectives:
To evaluate the prevalence of CAD risk factors among patients undergoing percutaneous coronary intervention (PCI) and assess how they have changed over time.

Methods:
We assessed the prevalence of risk factors among patients without a history of prior myocardial infarction, PCI, or coronary artery bypass graft surgery who underwent PCI at 47 non-federal hospitals in the state of Michigan between 1/1/2010 and 3/31/2018 using the BMC2 PCI registry.

Results:
Our study cohort included 69,970 men and 39,106 women. Traditional risk factors were highly prevalent in this population: 34.4% of men and 31.0% of women were current or recent smokers, hypertension was present in 71.8% of men and 80.6% of women, hyperlipidemia was present in 65.0% of men and 68.9% of women, diabetes was present in 27.8% of men and 35.5% of women, and 44.8% of men and 48.0% of women were obese. Over the study period, the prevalence of diabetes (29% to 32%) and obesity (45% to 48%) increased while a decline in smoking prevalence was noted (34% to 31%). Most patients had 2 or more risk factors with 51.2% having three or more risk factors. Compared with nonsmokers, smokers presented over a decade earlier (age 56.8 versus 66.9 years, p < 0.0001) and obese patients presented 4.0 years earlier (age 61.4 versus 65.4 years, p < 0.0001) (Figure).

Conclusions:
Modifiable risk factors are widely prevalent among patients undergoing their first PCI. Population-level interventions aimed at controlling obesity and preventing smoking could significantly delay the onset of CAD and the need for PCI.
Abstract 14453: Ventilatory Inefficiency Associated With Stage a Heart Failure
Authors: Potter Elizabeth L , Woessner Mary N , Neil Christopher , Marwick Thomas H , Howden Erin
Published: May 2021

Introduction:
Peak oxygen utilisation (VO
2
) and ventilatory efficiency (VE/VCO
2
slope) provide strong prognostic information in symptomatic heart failure (HF). Transition from subclinical to symptomatic HF is poorly understood. Cardiopulmonary exercise testing (CPET) in subclinical HF may advance risk profiling.

Hypothesis:
HF risk factors are associated with metabolic and ventilatory abnormalities that may serve as risk markers.

Methods:
Sedentary subjects (n=81; 67 (66-72) years; 65% female; BMI 29.9[26.6-33.9] kg/m
2
) with ≥1 HF risk factors (Stage A HF, SAHF) without pulmonary disease and healthy sedentary subjects (controls, n=21; 70 (67-73) years; 52% female; BMI 25.1 [24-25.9] kg/m
2
) underwent treadmill CPET to determine peak VO
2
, ventilatory threshold (VT, V-slope method) and VE/VCO
2
slope (linear regression). Global longitudinal strain≤16%, diastolic dysfunction or left ventricular hypertrophy defined subclinical left ventricular dysfunction (LVD).

Results:
LVD was present in 41 (51%) with SAHF. CPET parameters did not differ by presence of LVD. There were no differences in peak RER or VT (% peak VO2) between controls and SAHF. VO
2
peak was higher in controls vs. SAHF (22.1±4.6 vs. 19.9±4.6ml/kg/min, p=0.047). VE/VCO
2
slope was markedly steeper in SAHF vs. controls (40.2±6.2 vs. 29.3±6.1, p<0.001) (Figure). VE/VCO
2
slope was >34 (prognostic in symptomatic HF) in 83% vs. 19% for SAHF vs. controls (p<0.001). BMI was the only independent predictor (β 0.45 (0.19-0.72, p=0.001) (r
2
0.16) of VE/VCO
2
slope (SBP and heart rate reserve were not). BMI was not associated with increment in respiratory rate or tidal volume (β0.18(-0.07-0.42) and β3.9 (-10.8-18.7)).

Conclusions:
Cardiorespiratory exercise parameters do not differ in SAHF by presence of LVD. Ventilatory inefficiency is pronounced in SAHF compared with healthy controls suggesting it may be a risk marker, but prognostic significance is unknown.
Abstract 14456: Left Atrial Pressure Overload in Relation to N-terminal Pro-brain Natriuretic Peptide Level on Prognosis in Patients With Heart Failure With Preserved Ejection Fraction With and Without Atrial Fibrillation
Authors: Hoshida Shiro , Shinoda Yukinori , tachibana koichi , Minamisaka Tomoko , Yamada Takahisa , Yasumura Yoshio , Tamaki Shunsuke , Hayashi Takaharu , Yano Masamichi , Hikoso Shungo , Sakata Yasushi
Published: May 2021

Objective:
We aimed to clarify the differences in the significance of the ratio of diastolic elastance (Ed) to arterial elastance (Ea), [Ed/Ea=(E/e’)/(0.9 х systolic blood pressure)], a relative index of left atrial (LA) pressure overload, in relation to N-terminal pro-brain natriuretic peptide (NT-proBNP) level on prognosis between patients with heart failure with preserved ejection fraction (HFpEF) with and without atrial fibrillation (AF).

Methods:
We studied 297 HFpEF patients hospitalized for acute decompensated heart failure (sinus rhythm/AF: 192/105). Blood testing and transthoracic echocardiography were performed before discharge. All-cause mortality was evaluated at >1 year after discharge.

Results:
During a median follow-up of 626 days, 47 patients (sinus rhythm/AF: 30/17) had all-cause mortality. In the subgroup with sinus rhythm, but not AF, Ed/Ea was significantly higher in patients with than without all-cause mortality. In a multivariate Cox hazard analysis, Ed/Ea was significantly associated with all-cause mortality independent of NT-proBNP in patients with sinus rhythm, but not with AF. Among patients with higher NT-proBNP levels, the effect of higher Ed/Ea on prognosis was prominent only in those with sinus rhythm (p=0.037).

Conclusions:
Ed/Ea provides additional prognostic information to serum NT-proBNP level for predicting all-cause mortality only in HFpEF patients with sinus rhythm. The prognostic risk factors differed between elderly HFpEF patients with and without AF.
Abstract 14467: Left Atrial Functional Index is a Predictor of Persistent/permanent Non-valvular Atrial Fibrillation
Authors: Bhat Aditya , Chen Henry H , Khanna Shaun , Gan Gary C , Fernandez Fernando , MacIntyre C. Raina , Tan Timothy C
Published: May 2021

Introduction:
Chronicity of atrial fibrillation (AF) has been associated with poor cardiovascular outcomes. Left atrial function index (LAFI) is a rhythm-independent measure of LA reservoir function adjusted for LA size and stroke volume and is an established marker of risk for cardiac disease states. We sought to evaluate the role of LA function by LAFI in predicting persistent/permanent AF.

Hypothesis:
LAFI is a predictor of chronicity of AF.

Methods:
Patients attending our institution between Jan 2013 and Dec 2017 were assessed. Patients with history of non-valvular AF who received transthoracic echocardiogram (TTE) evaluation were included. In these patients, we evaluated demographic profiles, AF history, clinical comorbidities and echocardiographic data. We excluded patients with valvular AF, poor quality TTE images and incomplete clinical data.

Results:
Of the 665 patients (67.78±13.62years, 52% male) included, 27.8% had persistent/permanent AF. Persistent/permanent AF was associated with older age (p<0.01), heart failure (p<0.01), diabetes mellitus (p=0.02), ischaemic heart disease (p=0.02), obstructive sleep apnoea (p=0.04), renal impairment (p<0.01), lower left ventricular ejection fraction (p<0.01), higher E/e’ (p<0.01), larger LA volume index (p<0.01) and lower LAFI (p<0.01). Multi-variable analysis revealed both heart failure (OR 3.024, 95%CI 1.737 to 5.265, p<0.01) and LAFI (OR 4.881, 95%CI 2.503 to 9.519, p<0.01) as independent predictors of persistent/permanent AF. Receiver operating characteristic curve showed LAFI (see Figure; AUC 0.75, 95%CI 0.703 to 0.793, p<0.01) of less than 16.5 to have a 70% sensitivity and 70% specificity in detecting persistent/permanent AF.

Conclusions:
LAFI, an echocardiographic measure of atrial mechanical function, may be a useful tool in risk stratification for patients with non-valvular AF.