bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17121: Reduction in Total Cardiovascular Events With Long-term Use of Ticagrelor in Patients With Prior Myocardial Infarction in the PEGASUS-TIMI 54 Trial
Authors: Murphy Sabina A , Bonaca Marc P , Goto Shinya , Bhatt Deepak L , Steg Philippe Gabriel , Storey Robert F , Deenadayalu Naveen , Kuder Julia F , Magnani Giulia , Theroux Pierre , Nicolau José C , López-Sendón Jose , Dalby Anthony J , Goudev Assen , Ardissino Diego , Corbalan Ramon , Jensen Eva C , Held Peter , Braunwald Eugene , Sabatine Marc S
Published: July 2021

Background:
Long-term dual antiplatelet therapy with aspirin plus ticagrelor, a direct-acting reversibly-binding P2Y12 receptor antagonist, was recently shown in the PEGASUS-TIMI 54 trial (NCT01225562) to be superior to aspirin alone in preventing major adverse cardiovascular events in patients with a prior MI. Whereas prior analyses focused on time to first event, we hypothesized that total events including those beyond the first event would also be reduced with ticagrelor.

Methods:
We evaluated all primary endpoint (PEP) events (CV death, MI, stroke) during a median 33 month follow-up in patients randomized to ticagrelor (60 mg or 90 mg) vs placebo in the PEGASUS-TIMI 54 trial. Negative binomial regression & other sensitivity models were used.

Results:
Among 21,162 patients, there were 1,830 PEP events (85% first events, n=1,558 and 15% subsequent events, n=272). Of the total PEP events, 1,041 were MIs (56.9%), 338 were strokes (18.5%), and 451 were CV deaths (24.6%). In patients with a PEP event, 86.3% had 1 event, 11.0% had 2 events, and 2.8% had 3 or more events (maximum 6). Total PEP events were reduced 17% with ticagrelor 60 mg vs placebo (incidence-rate ratio [IRR] 0.83, 95% CI 0.72-0.95, p=0.006) and 17% with ticagrelor 90 mg vs placebo (IRR 0.83, 95% CI 0.73-0.95, p=0.007). A Wei-Lin-Weissfeld time-to-event model showed similar reductions. In terms of irreversible harm events, for every 1000 patients treated for 3 years, ticagrelor would prevent 18 primary endpoint events, including (depending on the dose) 5 CV deaths, 8-11 MIs, and 3-4 strokes, and cause only 0 or 1 excess fatal bleeds or ICH (Figure).

Conclusions:
Patients with prior MI remain at high risk for recurrent vascular events. The addition of ticagrelor to aspirin significantly reduces the burden of total vascular events.
Abstract 17129: Differences in Work Activities and Compensation of Male and Female Cardiologists in Community Practice in 2013
Authors: Jagsi Reshma , Biga Cathie , Poppas Athena , Rodgers George P , Walsh Mary N , White Patrick J , McKendry Colleen , Sasson Joseph , Schulte Philip J , Douglas Pamela
Published: July 2021

Background:
Despite laudable efforts to increase gender diversity in cardiology, much remains unknown about the experiences - including working activities and pay - of those women who have joined this still predominantly male specialty.

Hypothesis:
We hypothesized that a gender difference in compensation would exist on unadjusted analyses and that this could be explained by differences in the many personal, job, and practice characteristics measured in our dataset.

Methods:
Using the 2013 annual practice survey of MedAxiom, a subscription-based service provider for cardiology practices, we described personal, job, and practice characteristics of cardiologists from 161 practices and their salary by gender. Multivariable linear regression analysis and the Peters-Belson technique of labor economics were applied to evaluate gender differences.

Results:
Of 2679 subjects, 229 (8.5%) were female and 2450 male. Women were more likely to have specialized in general/non-invasive cardiology (53.1% vs 28.2%), and a lower proportion (11.4% vs 39.3%) reported an interventional subspecialty compared to men. Numerous job characteristics differed by gender, including the proportion working full-time (79.9% of women vs 90.9% of men, p<0.001), number of half-days worked (median 422 for women vs 433 for men, p=0.001), and wRVUs generated (median 7430 for women vs 9301 for men, p<0.001). Median salary was $394,586 (IQR: $256,064; $518,277) among women and $502,251 ($381,417; $621,306) among men. Peters-Belson analysis revealed that the women in this sample would have been expected to have a mean salary of $432,631, based on their productivity and other characteristics, had they been male, but the actual observed mean salary among women was $400,882 (unexplained difference=$31,749, 95% CI $16,303 - $48,028). Multivariable linear regression analysis yielded significant results similar in direction and magnitude.

Conclusions:
This study provides novel information about the diverse jobs held by men and women practicing cardiology in the US today. The observed gender difference in compensation, which remained substantial and significant even after adjusting for differences in multiple measures of productivity and job activity, merits attention.
Abstract 17142: Increased Adherence to Patient Follow-up Visits within 7 dDys in Heart Failure Patients are Associated With Reduced Readmission Rates in MI and WI
Authors: Thethi Indermohan , Thomas Kathie , Mallas-Serdynski Lynn
Published: July 2021

Background & Objectives:
Heart failure (HF) is the leading cause of hospitalization among adults aged 65 or older. Despite advancements in medical therapy, HF readmission rates remain high. The average cost of each HF readmission is about $13,000. High rates of readmissions can lead to penalties of up to 3% of Medicare reimbursement, the reduction of costs, & the improvement of quality of care and patient outcomes, which makes reduction vital to hospitals. Having a follow up visit within 7 days of hospital discharge may help reduce HF readmissions. The objective of the abstract is to quantify the change in 7 day follow up visits and 30 day readmissions as part of the Get With The Guidelines (GWTG) HF quality improvement (QI) initiative.

Methods:
GWTG HF is an in-hospital quality initiative designed to improve care by promoting adherence to the latest scientific guidelines. A retrospective review was conducted of HF discharges from 19 hospitals using GWTG HF in Wisconsin and Michigan from 2011-2014. Readmission rates were determined from Centers for Medicare and Medicaid Services data.

Results:
19 hospitals demonstrated improvement in the percentage of HF patients undergoing a follow-up visit within 7 days of hospital discharge when using GWTG HF as a QI program. As the percentage of HF patients receiving a follow-up visit within 7 days of hospital discharge increases, the number of readmissions decreases by 3% or 413 discharges over 4 years, which resulted in $5,369,000 cost savings.

Conclusions:
An in-hospital QI program, such as GWTG HF, improves the percentage of HF patients receiving a follow-up visit with 7 days of hospital discharge. Adherence to patient follow up visits for HF patients within 7 days of discharge leads to reduction in readmission rates. This translates into significant healthcare cost saving directly related to readmission in this patient category. Larger studies using a higher number of hospitals participating in quality programs is recommended.
Abstract 17143: Shorter Length of Stay is Associated With Significantly Lower 30-day All-cause Readmission and 30-day All-cause Mortality in Older Medicare Beneficiaries Hospitalized for Heart Failure
Authors: Arundel Cherinne , Ahmed Ali , Khosla Rahul , Faselis Charles , Morgan Charity , Zhang Sijian , Blackman Marc , Fletcher Ross D , Wu Wen-Chih , Fonarow Gregg C , Deedwania Prakash , Butler Javed , Deftereos Spyridon , Aronow Wilbert S , Anker Stefan D , Allman Richard M
Published: July 2021

Background:
A shorter hospital length of stay, encouraged by Prospective Payment System Act, may result in suboptimal care and early discharge. Heart failure (HF) is the leading cause for 30-day all-cause readmission. However, it is unknown whether hospitalized HF patients with a shorter length of stay may have higher 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act.

Methods:
The 8049 Medicare beneficiaries hospitalized for HF and discharged alive from 106 U.S. hospitals (1998-2001) had a median length of stay of 5 days (interquartile, 4-8 days), of which 4272 (53%) had length of stay ≤ 5 days. Using propensity scores for length of stay 1-5 days, we assembled a matched cohort of 2788 pairs of patients with length of stay 1-5 and ≥6 days, balanced on 32 baseline characteristics.

Results:
30-day all-cause readmission occurred in 19% and 23% of matched patients with length of stay 1-5 and ≥6 days, respectively (HR, 0.79; 95% CI, 0.70-0.89; Figure, left panel). When the length of stay of the 8049 pre-match patients was used as a continuous variable and adjusted for the same 32 variables, each day longer hospital stay was associated with a 2% higher risk of 30-day all-cause readmission (HR, 1.02; 95% CI, 1.01-1.03; p<0.001). Among matched patients, HR for 30-day HF readmission associated with length of stay 1-5 days was 0.84 (95% CI, 0.69-1.01; p=0.063). 30-day all-cause mortality occurred in 4.6% and 6.2% of matched patients with length of stay 1-5 and ≥6 days, respectively (HR, 0.73; 95% CI, 0.58-0.91; Figure, right panel). These associations persisted throughout 12 months post-discharge.

Conclusions:
Among hospitalized patients with HF, length of stay 1-5 days (vs. longer) was associated with significantly lower 30-day all-cause readmissions and all-cause mortality that persisted throughout first year post-discharge.
Abstract 17146: Molecular Imaging of Chemokine Receptor Type 4 Following Myocardial Infarction
Authors: Thackeray James T , Wang Yong , Derlin Thorsten , Wittneben Alexander , Bankstahl Jens P , Ross Tobias L , Wester Hans-Jürgen , Wollert Kai C , Bengel Frank M
Published: July 2021

Chemokine receptor type 4 (CXCR4) is involved in the process of post-infarct inflammation and has emerged as a therapeutic target to support myocardial recovery. We aimed to non-invasively track regional tissue CXCR4 expression after myocardial infarction (MI) using the novel specific radioligand 68Ga-pentixafor (PTX) and positron emission tomography (PET). C57Bl/6 mice underwent coronary artery ligation (n=24) or no surgery (n=7). Serial PET images were acquired using PTX (10MBq) at 3d and 7d post-MI. The infarct territory was localized by a subsequent 18F-deoxyglucose scan. Fusion PET images revealed increased PTX uptake in the infarct region at 3d compared to remote myocardium (% injected dose per gram (%ID/g); 0.9±0.1 vs 0.4±0.1, p<0.01). This increase partially receded by 7d (0.7±0.1, p<0.05 to 3d). Activity in the remote myocardium was lower than in the infarct territory, as confirmed by autoradiography and sequential histopathology. FACS analysis showed infiltration of CD45-positive leukocytes in the left ventricle proportional to PTX uptake (x106, ctl 0.2±0.1; d3 1.6±0.6; d7 0.5±0.2; p=0.04). Modulation of the imaging signal was possible by co-injection of the CXCR4 inhibitor AMD3100 (50μg), which lowered the infarct signal by 21% at 3d post-MI (p<0.05). Similarly, oral administration of enalapril, which is known to lower leukocyte trafficking to the infarct, evoked a significant reduction of infarct/remote PTX uptake by 18% at d3. A parallel modest reduction of CD45-positive cells (-22% at d3, -50% at d7, p=0.02) was observed on FACS analysis. In summary, 68Ga-PTX provides a non-invasive measurement of CXCR4 expression in the damaged region post-MI, and may provide a novel method to evaluate targeted therapy to modulate inflammation and infarct repair.
Abstract 17177: Crosstalk and Synergism Between Local Brain-derived and Exogenous 17β-Estradiol in Regulating Rapid, Pro-survival Signaling in the Hippocampus Following Global Cerebral Ischemia
Authors: Wang Ruimin , Vadlamudi Ratna , BRANN Darrell W
Published: July 2021

Cardiac arrest-induced global cerebral ischemia (GCI) can lead to death of hippocampal CA1 neurons and cognitive impairment. Previous work has shown that the steroid hormone, 17β-estradiol (E2) is strongly neuroprotective against GCI, an effect that involves, in part, rapid signaling via the membrane estrogen receptor, GPR30. To gain greater insight into E2 actions, the current study examined: 1) whether GPR30 expression in the hippocampus changes after CGI, and 2) the role and potential crosstalk/synergism between local (brain-derived) and exogenous E2 in regulation of GPR30 and rapid prosurvival signaling after GCI. GCI was induced in adult ovariectomized female rats by a 4-vessel occlusion model (12-min occlusion). Vehicle or low diestrous levels of E2 were administered chronically by minipump beginning at the time of ovariectomy. The results showed that GPR30 expression in the hippocampal CA1 was unchanged at 3h, but significantly decreased at 1d and 3d after GCI. In contrast, aromatase expression showed an initial decrease at 3h, a rebound at 1day, and a robust elevation at 3 days after CGI. Administration of exogenous E2 increased both GPR30 and aromatase expression at 3h, 1d and 3d after GCI. Interestingly, central administration of the aromatase inhibitor, letrozole or aromatase antisense (AS) oligonucleotides abolished exogenous E2 enhancement of GPR30 and aromatase at 3d after GCI. Furthermore, letrozole and aromatase-AS treatment attenuated exogenous E2-induced phosphorylation/activation of prosurvival ERK1/2 and CREB following GCI, as well as exogenous E2-induced enhanced expression of BDNF, PSD95 and synaptophsin. As a whole, the results suggest that local-derived E2 may help mediate beneficial protective effects of exogenous E2 after GCI to enhance GPR30 expression, increase activation of ERK1/2-CREB-BDNF pro-survival signaling, and improve synaptic function.
Abstract 17182: Patterns of Discontinuation for Non-vitamin K Oral Anticoagulants in Atrial Fibrillation: Results From the ORBIT-AF II Registry
Authors: Steinberg Benjamin A , Simon DaJuanicia N , Thomas Laine , Ansell Jack , Gersh Bernard J , Fonarow Gregg C , Hylek Elaine , Kowey Peter R , Mahaffey Kenneth W , Peterson Eric D , Piccini Jonathan P
Published: July 2021

Background:
Oral anticoagulation (OAC) is effective at preventing stroke in patients with atrial fibrillation (AF), yet warfarin is often poorly tolerated. Non-vitamin K oral anticoagulants (NOACs) are as or more effective as warfarin, yet their tolerance and persistence in clinical practice is not known.

Methods:
We assessed patterns of persistent OAC use among 2,345 AF patients starting on therapy in the ORBIT-AF II registry (71% starting on a NOAC, and 29% on warfarin).

Results:
By 6 months, 364 (22%) patients started on a NOAC had discontinued or changed initial therapy versus 143 (21%) started on warfarin initially (p=0.5). Among warfarin users, patients who switched or discontinued therapy were of similar age (median ages 72 and 74 vs. 74 for stable users, p=0.7) and CHA2DS2-VASc scores (mean 98 and 3.66 vs. 3.84, p=0.4). Among NOAC users, those who discontinued treatment were younger (median age 68 vs. 73 for those who switched and 72 for stable users; p=0.0004), and lower CHA2DS2-VASc scores (3.02 vs. 3.58 and 3.47, respectively; p=0.0008). The median time to change or discontinuation was more rapid in those started on a NOAC vs warfarin (97 days vs. 122 days, p=0.003). Among those on warfarin at baseline, 7.6% (n=52) were switched to a NOAC within 6 months, whereas transitions from NOAC to warfarin was 2.5% (n=42).Transitions among NOACs occurred in 9.8%, 3.2%, and 5.5% of patients on baseline dabigatran, rivaroxaban, and apixaban, respectively. Physician preference was the most common reason for both OAC and warfarin changes (Table). Drug cost was the primary reason for change of therapy in 15% of NOAC users (vs. 0 for warfarin).

Conclusions:
At 6-month follow-up, one in five newly started on OAC had discontinued or changed. These rates of change were similar among warfarin and NOAC treated patients. Cost concerns drove discontinuation in a modest number of patients, however, cost concerns were more prevalent in NOAC-treated patients.
Abstract 17193: Inhibiting Late Sodium Current Attenuates Isoproterenol-Induced Transient Inward Current and Delayed Afterdepolarizations in Ventricular Myocytes
Authors: Song Yejia , El-Bizri Nesrine , Rajamani Sridharan , Belardinelli Luiz
Published: July 2021

Introduction:
The β-adrenergic agonist isoproterenol (ISO) is known to induce the arrhythmogenic transient inward current (I
Ti
) and delayed afterdepolarization (DAD) via a stimulation of L-type Ca
2+
current. Recent studies found that ISO-induced DADs in cardiac tissues are inhibited by GS967, a selective blocker of the late Na
+
current (I
NaL
). Thus, we hypothesize that I
NaL
contributes to the actions of ISO, and selective inhibition of this current will reduce ISO-induced I
Ti
and DADs.

Methods:
Transmembrane currents and action potentials of rabbit and guinea pig (GP) ventricular myocytes were recorded using the whole-cell patch-clamp technique. ISO (0.1 μM), GS967 (1 μM) and the Na
+
channel blocker tetrodotoxin (TTX, 3 μM) were used in the experiments.

Results:
In rabbit myocytes, application of ISO caused an increase in the amplitude of I
NaL
from -0.10±0.03 to -0.32±0.04 pA/pF (n = 17, p < 0.05). The ISO-stimulated I
NaL
was inhibited by GS967 and TTX. In one series of experiments, ISO increased the I
NaL
from -0.14±0.04 to -0.35±0.06 pA/pF, and GS967 applied in the presence of ISO reduced the current to -0.14±0.03 pA/pF (n = 9, p < 0.05). In another series of experiments, the amplitude of I
NaL
was increased by ISO from -0.17±0.08 to -0.41±0.09 pA/pF, and was decreased to -0.09±0.08 pA/pF when TTX was applied with ISO (n = 5, p < 0.05). Application of ISO also induced I
Ti
and DADs. GS967 applied in the presence of ISO inhibited the amplitude of I
Ti
by 52±6%, from -1.79±0.30 to -0.87±0.16 pA/pF (n = 8, p < 0.05). Consistent with the inhibition of I
Ti
, GS967 suppressed the amplitude of ISO-induced DADs by 56±12%, from 6.54±1.59 to 3.22±1.27 mV (n = 5, p < 0.05). Similarly, in GP myocytes ISO-induced I
Ti
and DADs were decreased by GS967 from -1.14±0.21 to -0.73±0.16 pA/pF (n = 7, p < 0.05) and from 7.16±0.59 to 4.67±0.24 mV (n = 5, p < 0.05), respectively.

Conclusions:
An increased I
NaL
is likely to contribute to the proarrhythmic effects of ISO in cardiac myocytes. GS967 significantly attenuated ISO-induced I
NaL
, I
Ti
and DADs, suggesting that inhibiting this current could be an effective strategy to antagonize the arrhythmogenic actions of β-adrenergic stimulation.
Abstract 17211: Edoxaban versus Warfarin in Patients With Atrial Fibrillation in the US FDA Approval Population: An Analysis From the ENGAGE AF-TIMI 48 Trial
Authors: Eisen Alon , Giugliano Robert P , Ruff Christian T , Nordio Francesco , Gogia Harinder S , Awasty Vivek R , Henderson David A , Mercuri Michele , Rutman Howard , Antman Elliott M , Braunwald Eugene
Published: July 2021

Background:
Edoxaban (edo), a QD oral direct factor Xa inhibitor, is non-inferior to warfarin for preventing stroke or systemic embolism (SE) in mod-high risk pts with AF. Due to reduced protection from ischemic stroke in pts with CrCl >95 ml/min, the US FDA approved the higher dose edo regimen in pts with AF and a CrCl 15-95 ml/min (60mg QD if CrCl 50-95 ml/min; 30mg QD if CrCl 15-50 ml/min) without dose reduction for weight
<
60 kg or use of P-glycoprotein (P-gp) inhibitors. We report here for the first time the clinical characteristics, efficacy and safety of the FDA-approved population.

Methods:
From the ENGAGE AF-TIMI 48 trial population, we excluded pts who received the lower-dose edo regimen (30/15 mg), had CrCl >95 ml/min, or were dose-reduced for weight≤ 60 kg or potent P-gp use. The 1° efficacy endpoint was stroke/SE and principal safety endpoint was major bleeding. Efficacy data are from the ITT cohort in the overall study period, unless otherwise specified.

Results:
There were 9387 pts with CrCl 15-95 ml/min randomized to either warfarin or edo 60/30 mg per the FDA label followed for 2.8 yrs (median). These pts were older (74 vs 64 yrs), more likely women (40 vs 33%), and had higher CHADS
2
and HAS-BLED scores compared to pts not included in the FDA label, but were balanced by randomization group. The annualized rate of stroke/SE on-treatment was 1.11% with edo vs. 1.72% with warfarin (HR vs. warfarin 0.64 [0.51-0.81], p<0.001). Rates in the ITT cohort were 1.63% and 2.02% with edo and warfarin, respectively (HR 0.81 [0.67-0.97], p=0.023). Ischemic stroke rates were similar (1.31 vs 1.39%, HR 0.94, p=0.97). Edo significantly reduced hemorrhagic stroke, CV death, major and intracranial bleeding events (Fig).

Conclusion:
Among high risk pts in the ENGAGE AF-TIMI 48 trial who represent the FDA approval population and dosing regimen of edo, treatment with edo 60/30 mg is superior to warfarin in the prevention of stroke/SE and reduces major bleeding, intracranial hemorrhage, and CV death.
Abstract 17220: Treatment Persistence and Discontinuation With Rivaroxaban, Dabigatran and Warfarin for Stroke Prevention in Patients With Non-valvular Atrial Fibrillation
Authors: Coleman Craig , Tangirala Muralikrishna , Evers Thomas
Published: July 2021

Introduction:
Continuous use of oral anticoagulant (OAC) therapy is essential for reducing the risk of stroke in patients with non-valvular atrial fibrillation. To date, no single study has compared persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users.

Hypothesis:
To compare persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users with non-valvular atrial fibrillation.

Methods:
A retrospective cohort analysis of the United States MarketScan claims databases was performed. This included adult patients newly initiated on rivaroxaban, dabigatran or warfarin between 1 November 2011 and 31 December 2013 with a baseline CHA2DS2-VASc score ≥2, ≥2 atrial fibrillation diagnosis codes (427.31) and ≥6 months of continuous medical and pharmacy benefits prior to OAC initiation (index date). Propensity score matching was performed in a two-step process to match patients on rivaroxaban with dabigatran 1:1 and with warfarin 1:1. Patients were followed until the earliest of in-hospital death, end of continuous enrolment or end of study period. Persistence was defined as absence of refill gap of >60 days. Discontinuation was defined as no additional refill for >90 days and through end of follow-up. Cox proportional hazards models were estimated to examine hazard ratios (HRs) of OAC non-persistence and discontinuation.

Results:
A total of 32,634 patients were included (N=10,878/OAC group). At 3 months’ follow-up, treatment persistence was 79.2%, 69.6% and 70.9% for rivaroxaban, dabigatran and warfarin users, respectively, dropping to 70.2%, 57.8% and 58.8% after 6 months, 60.1%, 44.7% and 42.0% after 1 year and 50.4%, 30.6% and 26.5% after 2 years. On regression, rivaroxaban use was associated with a decreased hazard of non-persistence compared with dabigatran (HR=0.64; 95% confidence interval [CI] 0.62-0.67) and warfarin (HR=0.62; 95% CI 0.59-0.64), and a decreased rate of discontinuation versus dabigatran (HR=0.61; 95% CI 0.58-0.64) and warfarin (HR=0.65; 95% CI 0.62-0.68).

Conclusions:
This matched patient analysis indicated significantly higher persistence and lower discontinuation rates with rivaroxaban compared with dabigatran and warfarin.
Abstract 17223: Compositional Lipoprotein Changes With Omega-3 Carboxylic Acids in Patients With Hypertriglyceridemia Paired With Low HDL-C: A Substudy From the ESPRIT Trial
Authors: Davidson Michael H , Oscarsson Jan , Kvarnström Mats , Loss Larrye , Lundström Torbjörn
Published: July 2021

Introduction:
STRENGTH (NCT02104817) is a 13,000-patient cardiovascular (CV) outcomes trial testing the hypothesis that high-CV-risk patients on statins with hypertriglyceridemia paired with low levels of high-density lipoprotein cholesterol (HDL-C) will have a reduction in incidence of major adverse CV events with omega-3 carboxylic acids (OM3-CA) 4 g/day compared with corn oil control. At present, the triglyceride (TG)-lowering mechanisms by which OM3-CA therapy may reduce CV risk are uncertain.

Methods:
In the ESPRIT trial (NCT01408303), patients (n=277) on statins who had fasting TG ≥200 mg/dL and <500 mg/dL and HDL-C <40 mg/dL for men and <45 mg/dL for women (also STRENGTH inclusion criteria) received either OM3-CA 4 g/day or olive oil (OO) 4 g/day for 6 weeks. The primary efficacy end point was percentage change in non-HDL-C from baseline to 6 weeks. We evaluated the lipoprotein compositional changes associated with non-HDL-C reduction.

Results:
Least-squares mean difference in HDL2:HDL3 ratio increased by 12% (p=0.004), while apolipoprotein (Apo)B100, ApoB48 and PCSK9 were not significantly affected. The sum of the change in the highly atherogenic subfractions, very-low-density lipoprotein cholesterol (VLDL-C) + small LDL-C + remnant lipoprotein-C, was strongly correlated with TG reduction (0.732; p<0.001) and percentage change in plasma eicosapentaenoic acid + docosahexaenoic acid + docosapentaenoic acid (–0.281; p<0.001).

Conclusions:
Compared with OO, OM3-CA 4 g/day significantly lowers non-HDL-C in patients with hypertriglyceridemia and low HDL-C by lowering VLDL-C, small LDL-C and remnant lipoprotein-C. Large LDL-C is raised without modifying ApoB100, ApoB48 or PCSK9 levels. STRENGTH will determine whether these lipoprotein compositional changes in this high-risk population will result in a CV benefit.
Abstract 17229: Synergistic Inhibition of Retinoblastoma1 and Meis2 Promotes Robust Proliferation of Adult Cardiomyocytes
Authors: Pandey Raghav , Fritz Jamie , Ahmed Rafeeq P
Published: July 2021

Background:
Cardiac remodeling and heart failure post myocardial Infarction (MI) is mainly due to inadequate regenerative capacity of mammalian heart, which is attributed to limited proliferative potential of adult cardiomyocytes (ACMs). In our recent study, we identified miR-1825 as a master regulator, which induces ACM proliferation through recruiting other proliferation inducing miRs, including miR-199a. In this study, we hypothesize that miR-1825 promotes proliferation through miR-199a mediated inhibition of cell cycle inhibitors Retinoblastoma1 (Rb1) and Meis2.

Methods and Results:
ACMs were isolated from 8-12 week old male rats and were transfected with cel-miR-67 (control), miR-1825, miR-199a, siRNA against Rb1 and Meis2 both individually and in combination (siRb1, siMeis2, siRb1+siMeis2). To label proliferating ACMs, EdU (5 μM) was added each day for 5 days and cells were harvested/fixed for staining, protein, and RNA analysis. Immuno-staining was performed for EdU, pH3 (mitotic marker), and Troponin-I. Similar to our previous reports, miR-1825 induced 23±0.4% and miR-199a induced 14.8±0.5% proliferation, as shown by EdU+ ACMs. In addition, we identified siRNA mediated silencing of Rb1 and Meis2 promoted 8.7±2.8% and 3.8±1.4% increase in proliferation, whereas simultaneous inhibition of both Rb1 and Meis2 induced robust (23±5.0%) proliferation of ACMs. Mitosis, as identified by p-H3+ACMs, following individual and combined silencing of Rb1 and Meis2 was observed to be 2.6%, 2.2%, and 7.6%, respectively. Western blotting confirmed silencing of Meis1/2 and Rb1 (0.14±0.02 fold) in miR-1825 transfected ACMs. Computational prediction and luciferase assay revealed a direct binding site for miR-199a on the 3’UTRs of both Rb1 and Meis2. Following miR-199a transfection, we found a 0.29±0.06 fold and 0.09±0.07 fold reduction of chemiluminescent activity with Rb1-3’UTR and Meis2-3’UTR, respectively. In addition, binding sites for miR-199a on both Rb1-3’UTR and Meis2-3’UTR are conserved across species as indicated by in-silico analysis.

Conclusion:
miR-1825 and miR-199a mediated simultaneous silencing of cell cycle inhibitors Rb1 and Meis2 promotes robust proliferation of ACMs. This can be used to regenerate ischemic myocardium.
Abstract 17230: Early Continuous EEG Biomarkers Predicts Neurologic Outcome in Post-cardiac Arrest Rats
Authors: Oh Joosuk , Jinka Tulasi , Ren Xiaodan , Stacey William C , Neumar Robert W
Published: July 2021

Introduction:
Hypothermic targeted temperature management (TTM) has greatly improved post-cardiac arrest patient outcomes, but also makes prognostication more difficult. In this study, we tested the hypothesis that early continuous EEG biomarkers are associated with neurologic outcome in post-cardiac arrest rats treated with normothermic and hypothermic TTM.

Methods:
Male rats were instrumented for continuous telemetric EEG (cEEG) recording and then subjected to 8-minute asphyxia cardiac arrest. Eight rats that achieved ROSC underwent either normothermic or hypothermic TTM (37 ± 0.5 °C or 33 ± 0.5 °C) for 24 hours and cEEG monitoring up to 72 hours. Quantitative EEG analysis determined the power density of delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) and sigma (13-18 Hz) frequency bands in all 10 second windows. The mean spectral power and Spearman correlation with time for the first 12 hours after return of spontaneous circulation (ROSC) were calculated and correlated with best neurologic function score (NFS) and survival with good NFS (NFS ≥ 450 out of 500).

Results:
Over all rats tested, the mean delta band power in the first 12 hours after ROSC was inversely correlated with best neurologic function score and associated with poor outcome (Table and Figure). There was no statistical difference in other frequency bands. Similar findings were present when stratifying into normothermic and hypothermic treatment groups.

Conclusions:
This study suggests that, the early power density of delta frequency bands from cEEG is a potential predictor of neurologic outcome in a mixed population of rats treated with normothermic and hypothermic TTM.
Abstract 17237: Overweight Associated With Advanced Biventricular Remodeling and Increased Morbidity in Adults With Repaired Tetralogy of Fallot
Authors: Kochav Jonathan D , Ghoshhajra Brian , DeFaria Yeh Doreen , Singer Sean , Staziaki Pedro V , Bhatt Ami B
Published: July 2021

Background:
Individuals with repaired tetralogy of Fallot (rTOF) often develop progressive pulmonary regurgitation (PR) and right ventricular (RV) dilation after initial repair, placing them at risk of arrhythmia, right heart failure, and sudden cardiac death. MRI research has led to body surface area (BSA)-indexed RV end-diastolic volume cutoffs (RVEDV>160ml/m2) for timing of pulmonary valve replacement (PVR), a strategy potentially limited by rising rates of obesity in this population.

Hypothesis:
Indexing RV volumes to actual BSA may underestimate disease progression in overweight patients.

Methods:
This retrospective analysis identified adults with rTOF and significant PR who underwent MRI for evaluation of RVEDV prior to consideration of PVR. Charts were reviewed for major adverse clinic events including death, heart failure, and sustained arrhythmia. Chamber volumes were indexed to BSA, as well as ideal BSA (defined by weight set to achieve BMI of 25).

Results:
58 adults with rTOF who met inclusion criteria were identified; 43% were overweight (BMI>25). Compared with normal weight individuals, overweight patients were older at MRI (44±12 vs 30±10 years, p<0.001) and definitive repair (9±8 vs 3±3 years, p=0.002), and more likely to have staged repair (56% vs 24%, p=0.01). Overweight patients had more advanced RV (RVEF 40±11% vs 55±33%, p=0.03) and LV (LVEF 53±12% vs. 59±13%, p=0.02) systolic dysfunction, as well as larger LVEDV (84±26 vs 65±15ml/m2, p=0.001) and RVEDV (152±50 vs 139± 61ml/m2, p=0.37) when indexed to ideal BSA. Overweight patients had higher incidence of arrhythmia (58% vs 20%, p=0.04), and decompensated HF (15% vs 0%, p=0.06) prior to MRI. Indexing RVEDV to ideal BSA in the overweight population led to reclassification of 4 patients meeting criteria for PVR (15 vs 11, p<0.001) meeting established criteria for PVR (RVEDV>160ml/m2), 3/4 of whom had clinical arrhythmia prior to MRI.

Conclusions:
Overweight patients with rTOF not only demonstrate advanced biventricular remodeling, but also experience negative clinical outcomes. Indexing RV volume to actual BSA may underestimate chamber size, whereas indexing to ideal BSA may identify high risk patients at risk for cardiac outcomes who could benefit from PVR.
Abstract 17250: Ranolazine Use Following Initial Anti-anginal Therapy Is Associated With Lower Health Resource Utilization Among U.S. Veterans With Chronic Stable Angina
Authors: Bress Adam , Dodson John , Sauer Brian , DuVall Scott , Crook Jacob , Reese Thomas , Hartsfield Cindy , Koch Bruce , Nelson Richard , LaFleur Joanne
Published: July 2021

Introduction:
While clinical trials show improvement in angina symptoms with ranolazine, it is unclear whether this improvement translates into reduced health resource utilization (HRU). We, therefore, sought to analyze whether HRU declined at one year after ranolazine initiation within a large integrated health system.

Methods:
This was a historical cohort study using nationwide Department of Veterans Affairs (VA) data. We compared participants with a diagnosis of coronary artery disease and chronic stable angina who were prescribed ranolazine, as monotherapy or add-on, following an initial trial of ≥ 1 anti-anginal agent versus alternative secondary agents between 01/01/2006 and 12/31/2013. We addressed confounding through inverse probability (IP) of treatment weighting. We used IP-weighted regression models to evaluate adjusted risk ratios and incident rate ratios for coronary revascularizations, hospitalizations, emergency room (ER) visits, and costs within one year.

Results:
Of 37,060 patients identified, IP weighted treatment groups comprised 4,766 patients prescribed ranolazine and 32,261 prescribed an alternative agent as their second or third anti-anginal. There were no significant differences in baseline characteristics between treatment groups after IP weighting. In the IP-weighted outcome analysis, coronary artery bypass graft surgeries were significantly lower with ranolazine. All-cause, atrial fibrillation (AF) and heart failure (HF) specific hospitalizations, and total costs were significantly lower in the ranolazine group.

Conclusions:
Among patients with CSA prescribed a second or third anti-anginal pharmacotherapy, ranolazine was associated with fewer all-cause hospitalizations, hospitalizations for AF and HF, ER visits and total costs. These findings suggest that the reduction in angina symptoms seen in other studies of ranolazine may translate into lower HRU compared to conventional pharmacotherapies.
Abstract 17251: Enhanced Late Sodium Current Predisposes Cardiomyocytes From Aged Guinea Pigs to the Arrhythmogenic Effects of Hydrogen Peroxide
Authors: Song Yejia , Rajamani Sridharan , Belardinelli Luiz
Published: July 2021

Introduction
Aging is associated with both a decreased tolerance to oxidative stress and an increased incidence of cardiac arrhythmias. This study examined the hypotheses that 1) ventricular myocytes from aged guinea pigs (GPs) are more susceptible than those from young GPs to hydrogen peroxide (H
2
O
2
)-induced arrhythmic activity, and 2) the vulnerability of aged myocytes to actions of H
2
O
2
may be attributed to an enhanced late Na
+
current (I
NaL
).

Methods
The action potential duration (APD) and I
NaL
of ventricular myocytes isolated from one-month old (young myocytes) and one-year old (aged myocytes) GPs were determined using the whole-cell patch-clamp technique.

Results
H
2
O
2
(200 μM) caused a greater prolongation of the APD and induced more early afterdepolarizations (EADs) in aged, than in young, myocytes. The effect of H
2
O
2
was time-dependent. During a 7-min exposure to H
2
O
2
alone, the APD of young and aged myocyte was prolonged by 9±3% and 35±5%, respectively. When H
2
O
2
was applied in the presence of the I
NaL
blocker GS967 (0.1 μM), the APD of aged myocytes was prolonged by only 16±8%. H
2
O
2
alone induced EADs in 6% and 71% of young and aged myocytes, respectively, and failed to induce EADs when applied in the presence of GS967 (Figure). The magnitude of I
NaL
was significantly larger in aged (-0.496±0.044 pA/pF) than in young (-0.239±0.016 pA/pF) myocytes. KN-93 (10 μM) and AIP (2 μM), blockers of Ca
2+
/calmodulin-dependent protein kinase II (CaMKII), but not KN-92 (inactive analog of KN-93, 10 μM), significantly reduced the I
NaL
of aged myocytes to -0.213±0.023 pA/pF and -0.166±0.010 pA/pF, and the I
NaL
of young myocytes to -0.167±0.019 pA/pF and -0.165±0.021 pA/pF, respectively.

Conclusions
1) Cardiomyocytes from aged GPs are more susceptible to the arrhythmogenic effects of H
2
O
2
; 2)

CaMKII-mediated increase in I
NaL
may underlie the vulnerability of aged myocytes; 3) Inhibition of I
NaL
may be beneficial for maintaining electrical stability under oxidative stress.
Abstract 17258: Effects of Aerobic Exercise Intensity on Ambulatory Blood Pressure Monitoring and Vascular Responses in Resistant Hypertension: A Cross-over Trial
Authors: Porto Santos Lucas , Moraes Ruy S , Vieira Paulo J , Waclavowsky Gustavo , Umpierre Daniel
Published: July 2021

Introduction:
Patients with resistant hypertension are usually exposed to poor blood pressure (BP) control, resulting in clinical vulnerability, possibility of device-based procedures (denervation), and cumulative costs with drug therapy. Regular aerobic exercise promotes marked benefits in hypertension, including the subset of resistant patients. However, little is known about acute effects of exercise on patients with resistant hypertension.

Hypothesis:
We hypothesized that a single aerobic session would reduce BP and improve vascular variables. Thus, we compared ambulatory BP and vascular parameters in response to two intensities of aerobic sessions and a non-exercise control session in patients with resistant hypertension.

Methods:
After a maximal exercise test, 18 patients (54±6 years, 30.2±4.9 kg/m2) participated in three interventions in random order, crossover design, and on separate days: control session (45’ of rest), light intensity (LI) and moderate intensity (MI) sessions (45’ of aerobic exercise at 50% and 75% of HRmax, respectively). Ambulatory BP monitoring (Space Labs, 90702) comprised a 19h period after each session. Vascular variables were measured at the non-dominant forearm by venous occlusion plethysmography (Hokanson Inc) before and up to 1h after all sessions.

Results:
Compared with control session, both exercise sessions reduced ambulatory systolic BP in a 5h period (LI: -7.7±2.4mm Hg and MI: -9.4±2.8mm Hg, p<0.01), whereas only LI session reduced diastolic BP (-5.7±2.2mm Hg, p<0.01). In addition, LI induced lower values in systolic and diastolic BP during 10h-daytime (-3.8±1.3mm Hg and -4.0±1.3mm Hg, respectively, p<0.02), nighttime (-6.0±2.4 mm Hg and -6.1±1.6mm Hg, respectively, p<0.05) and in diastolic BP during 19h (-4.8±1.2mm Hg, p<0.01). Forearm blood flow decreased only at minute 50 after LI (p<0.05), with no other changes. In control and LI sessions, forearm vascular resistance increased at the end of 1h recovery period and in MI session, it decreased immediately after the intervention (p<0.05).

Conclusions:
A single aerobic exercise session in light or moderate intensities induces beneficial changes in ambulatory BP in resistant hypertension, with advantages in effect length for lighter intensities.
Abstract 17308: Leukoaraiosis is Associated With Atrial Fibrillation and Greater Disability at 90-days in Patients Hospitalized With a Cardioembolic Stroke
Authors: Karmarkar Ameeta , Helenius Johanna , Henninger Nils , McManus David D
Published: July 2021

Introduction:
Atrial fibrillation (AF) has been associated with a poor post-stroke prognosis. AF has been linked to increased leukoaraiosis (LA) burden, which is associated with greater functional impairment after stroke.

Hypothesis:
We hypothesized that AF is associated with the severity of LA burden and thus impacts 90-day outcomes in patients hospitalized with acute cardioembolic ischemic stroke.

Methods:
We retrospectively analyzed 317 consecutive patients with acute cardioembolic ischemic stroke enrolled in the University of Massachusetts Medical Center’s Stroke Registry between 2010 and 2014. Stroke mechanism was determined according to the Causative Classification System. LA burden was graded on MRI using the Fazekas scale. Infarct volume was quantified on diffusion weighted images. Neurological deficit severity was assessed at admission according to the National Institutes of Health Stroke Scale (NIHSS). We evaluated the degree of disability using the modified Rankin score (mRS) at 90 days. Participants were categorized as having excellent (mRS 0-1), or poor (mRS 2-6) status.

Results:
A total of 132 patients were classified as having a definite (n=81) or probable (n=51) cardioembolic stroke. Of these, 54 (41%) had AF (previously known or newly documented). Compared to patients without AF, patients with AF were older (p=0.001), more likely to be receiving antihypertensives(p=0.008) and anticoagulants (p<0.05 each), were associated with a poor outcome at 90 days.

Conclusions:
We observed that AF was related to severity of LA and that LA burden was an independent predictor of significant disability 90-days post-discharge. Further study is needed to investigate the links between AF, LA, and outcomes after cardioembolic stroke.
Abstract 17309: Validation of a Novel Prediction Tool for Circulatory Etiology Death After Cardiac Arrest
Authors: Bascom Karen , Dziodzio John , Vasaiwala Samip , Mooney Michael , Patel Nainesh , McPherson John , McMullan Paul , Unger Barbara , Nielsen Niklas , Friberg Hans , Kern Karl , Seder David ,   International Cardiac Arrest Registry (INTCAR)-Cardiology Rsch Group
Published: July 2021

Introduction:
Post-resuscitation cardiac arrest (CA) triage to urgent angiography, percutaneous intervention, and mechanical circulatory support is hampered by inconclusive risk stratification, especially among patients without ST elevation myocardial infarction (STEMI). We analyzed registry data to develop a prediction tool to determine the risk of circulatory-etiology (CV) death in patients without STEMI, and validated it in a separate cohort.

Methods:
Using the International Cardiac Arrest Registry (INTCAR)-Cardiology data set and stepwise linear regression with an inclusion rule of P≤0.1, we determined demographic and clinical factors independently associated with CV death, and created a weighted prediction model for patients presenting after CA without STEMI. The model was then validated in a separate, larger cohort from INTCAR. This project was approved by the Maine Medical Center IRB.

Results:
Of 468 patients in the derivation cohort, 90 met criteria for the endpoint. In the multivariable model, age greater than 65 (OR=2.4, p=0.0001), preexisting coronary disease (OR=1.9, P=0.0065), diabetes (OR=1.8, P=0.01), in-hospital arrest (OR=1.5, P=0.1), time from collapse to return of circulation (TTROSC) greater than 25 minutes (OR=1.7, p=0.02), shock at presentation (OR=3.9, P<0.0001), and EF<30% on first echo (OR=1.6, P=0.05) were independently associated with CV death. Using weighted predictors (age>65 =1, prior CAD =1, diabetes =1, in-hospital arrest =1, TTROSC>25 =1, admission LVEF<30% =1, shock =2,), an additive score of 0-2 predicted CV death in 8.5% and ≥3 in 34% in the derivation cohort. In the validation cohort, which comprised 1197 patients, of whom 263 met criteria for CV death, a score of 0-2 was associated with 13.1% and ≥3 with 35.1% CV death, respectively.

Conclusions:
A simple bedside prediction tool can predict high (34-35.1%) vs. low (8.5-13.1%) risk of circulatory-etiology death in cardiac arrest survivors without STEMI. This model could be used to risk-stratify cardiac arrest survivors, and aid in the triage of patients to appropriate and cost-effective post-resuscitation treatments.
Abstract 17321: Aspirin Use is Associated With Improved Survival in Severely Thrombocytopenic Cancer Patients With Acute Myocardial Infarction
Authors: Feher Attila , Parameswaran Rekha , Stein Eytan M , Gupta Dipti
Published: July 2021

Objective:
Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin therapy is not known in thrombocytopenic cancer patients who experience an acute myocardial infarction (AMI).

Methods:
Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as platelet count <50 cells k/μL within 7 days of AMI. Demographics, aspirin use, survival and bleeding outcomes were collected. T-tests and Fisher exact tests were used to compare continuous and categorical variables. Survival rates were calculated using the Kaplan-Meier product limit method; groups were compared with log-rank statistic.

Results:
118 patients with hematologic malignancies had AMI. 58/118 (49%) had sTP. 25/58 (43%) of those with sTP received aspirin. Patients were mostly male (70%, n=83), mean age 69±11 years, mean follow up 3.6 years. Non-Hodgkin’s lymphoma was the most common hematologic diagnosis (36%, n=42). Survival was significantly worse in patients with sTP vs. no sTP (23% vs. 50% at 1 year, log rank p=0.008). When compared to no sTP with AMI, patients with sTP and AMI were less likely to receive aspirin (83% vs 43%, p=0.0001), thienopyridine (27% vs 3%, p=0.0005) and to undergo coronary angiography (30% vs. 5%, p=0.0005) and revascularization (17% vs. 3%, p=0.03). Cancer patients with sTP and AMI who received aspirin had improved survival when compared to those not treated with aspirin, (92% vs. 70% at 7 days, 72% vs. 33% at 30 days and 32% vs. 13% at 1 year, log rank p=0.008). No fatal bleeding events occurred. Thrombolysis in Myocardial Infarction (TIMI) major bleeding occurred in one patient without sTP.

Conclusions:
In hematologic malignancy patients with AMI and sTP the use of aspirin was associated with improved survival without increase in major bleeding.