bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13186: Prevalence, Predictors, and Outcomes of Both True- and Pseudo-resistant Hypertension in the Action to Control Cardiovascular Risk in Diabetes Trial (ACCORD)
Authors: Chiu Nicholas , Lauffenburger Julie , Franklin Jessica , Choudhry Niteesh
Published: May 2021

Introduction:
Resistant hypertension (RH) has been poorly studied due to the difficulty distinguishing RH from medication non-adherence—exclusion of which is necessary to accurately diagnose RH. Therefore, little is known about prevalence, predictors, and outcomes of true RH, particularly for patients with diabetes.

Objective:
To characterize prevalence, predictors, and outcomes of true RH under a definition accounting for adherence in a study with strict adherence monitoring.

Methods:
We analyzed data from 1838 patients in the standard BP arm of ACCORD. Patients were classified into 3 mutually-exclusive groups: “true RH”, “pseudo-RH” (i.e., patients with BP treatment levels that would classify them as having RH, but who were non-adherent), and “Other” (i.e., those without “true RH” or “pseudo-RH” classifications). Predictors of true- and pseudo-RH were identified with logistic and boosted regression models. Relationship between true RH and primary composite outcome of nonfatal MI, nonfatal stroke, or cardiovascular death was evaluated with cox models.

Results:
Among 1838 participants with complete information, 489 (26.6%) met the definition of true RH, and 94 (16.1%) of RH patients had “pseudo-RH” on ≥1 visit over the first 12 months. Multivariable predictors of RH included: baseline SBP ≥160 mmHg (OR=8.79; 95CI:5.70-13.68), baseline SBP between 140-159 (OR=2.91; 95CI:2.13-4.00) compared to SBP <140, additional baseline BP medication (OR=3.40; 95CI:2.83-4.11), macroalbuminuria (OR=2.35; 95CI:1.50-3.67), CKD (OR=1.53; 95CI:0.99-2.33), history of stroke (OR=1.73; 95CI:1.04-2.82), and black race (OR=1.39; 95CI:1.02-1.88); Overall, multivariable model had a cross-validated C-statistic of 0.80, indicating strong discriminative ability. “True RH” patients had a 65% increased hazard in primary outcome compared with other groups (HR=1.65; 95 CI:1.13-2.42).

Conclusions:
The majority of patients classified as RH had “true RH,” with only 16% being “pseudo-RH” due to non-adherence. True RH is more common among those who are black, have macroalbuminuria, CKD, history of stroke, higher baseline SBP, and are taking more baseline anti-hypertensives. “True RH” patients are at increased risk for cardiovascular and mortality events.
Abstract 13193: Association of Abnormal P-wave Indices With Brain MRI Infarcts: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Reyes Jorge L , Norby Faye L , Wang Wendy , Parikh Romil , Oldenburg Niki C , Lutsey Pamela L , Jack Clifford R , Johansen Michelle C , Gottesman Rebecca F , Soliman Elsayed Z , Alonso Alvaro , Chen Lin Y
Published: May 2021

Introduction:
We recently reported that abnormal P-wave indices (PWI)—ECG markers of atrial cardiomyopathy (AC)—are associated with an increased risk of dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. The mechanisms, however, remain unclear, but may include silent ischemia.

Hypothesis:
Abnormal PWI are associated with higher prevalence of cortical infarcts on MRI, suggesting cardioembolism as a potential mechanism.

Methods:
ARIC-NCS participants (mean age, 72.2±5.3 years; 60% women; 29% black) who underwent 3T brain MRI scans in 2011-2013 were included. Abnormal PWI included P-wave terminal force in lead V1 [(PTFV1) defined as ≥4000 μV*ms] and P-wave duration [(PWD) defined as >120 ms], which were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, cerebral microbleeds (CMB), and markers of small vessel disease [white matter hyperintensities (WMH) and lacunar infarcts]. We used weighted multivariable logistic and linear regression analyses.

Results:
Of the 1,850 participants, 464 had abnormal PTFV1 and 415 had prolonged PWD. After multivariable adjustment including AF, abnormal PTFV1 and PWD were significantly associated with 26-44% increased odds of cortical and lacunar infarcts
(Table)
. Although PWD was associated with CMB in Model 1, the association was no longer significant after multivariable adjustment. Finally, abnormal PWIs were not associated with WMH after adjusting for stroke and AF (P >0.5).

Conclusions:
Abnormal PWI are associated with higher prevalence of cortical infarcts, suggesting cardioembolism with silent ischemia as a possible mechanism underlying the association of AC with dementia. More research is needed to evaluate other mechanisms such as cerebral small vessel disease.
Abstract 13301: Clinical Implications of Hepatic Hemodynamic Evaluation by Abdominal Ultrasonographic Imaging in Patients With Heart Failure
Authors: Hotsuki Yu , YOSHIHISA Akiomi , Ichijo Yasuhiro , Watanabe Koichiro , Sato Yu , Kimishima Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Oikawa Masayoshi , Kobayashi Atsushi , Takeishi Yasuchika
Published: May 2021

Background:
It has been reported that liver stiffness assessed by transient elastography is correlated with right atrial pressure (RAP), which is an important hemodynamic parameter in patients with heart failure (HF). We aimed to clarify clinical implications of hepatic hemodynamic evaluation (liver congestion and hypoperfusion) by abdominal ultrasonography in patients admitted for the treatment of decompensated HF.

Methods and Results:
We performed abdominal ultrasonography, right-heart catheterization (RHC), and echocardiography in HF patients (n=342) at stable condition after treatment, then followed up for cardiac events such as cardiac death and re-hospitalization due to worsening HF. Regarding liver congestion, liver stiffness assessed by shear wave elastography of the liver (SWE) was significantly correlated with RAP determined by RHC (R=0.343, P<0.01) and right atrial end systolic area determined by echocardiography (R=0.293, P<0.01). With regard to liver hypoperfusion, peak systolic velocity (PSV) of the celiac artery was correlated with cardiac index determined by RHC (R=0.291, P<0.001) and tricuspid annular plane systolic excursion determined by echocardiography (R=0.251, P=0.004). Importantly, cardiac event rate was highest in HF patients with high SWE and low PSV (
Figure
, subset 4). In the Cox proportional hazard analysis, the combination of high SWE and low PSV was a strong predictor of cardiac events (HR 4.811, 95% CI 1.562-14.818).

Conclusions:
Abdominal ultrasonography based evaluations of intrahepatic congestion and hypoperfusion predict adverse prognosis in HF patients.
Abstract 13304: Liver Dispersion Predicts Adverse Outcomes in Patients With Heart Failure
Authors: Hotsuki Yu , Yoshihisa Akiomi , Watanabe Koichiro , Sato Yu , Kimishima Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Oikawa Masayoshi , Kobayashi Atsushi , Takeishi Yasuchika
Published: May 2021

Background:
It has been recently reported that liver stiffness assessed by transient elastography reflects right atrial pressure (RAP), and is associated with worse outcome in patients with heart failure (HF). However, the relationship between liver dispersion (LD, a novel indicator of liver viscosity) determined by abdominal ultrasonography and RAP, and prognostic impacts of LD on HF patients have not been fully examined. We aimed to clarify associations of LD with parameters of liver functional test (LFT) and right-heart catheterization (RHC), and cardiac event such as cardiac death and worsening HF in patients with HF.

Methods and Results:
We performed abdominal ultrasonography, LFT, RHC, and followed up cardiac events including cardiac death and unplanned hospitalization due to HF in patients with HF (n=157). We examined associations of LD with parameters of LFT and RHC. There were significant correlations between LD and circulating levels of gamma-glutamyl transferase (R=0.197, P=0.018), cholinesterase (R=-0.301, P=0.001), and 7S domain of collagen type IV (P4NP 7S, a marker of fibrosis, R=0.334, P<0.001), but not with RAP (R=0.067, P=0.514) or cardiac index (R=-0.038, P=0.667). During the follow up period (median 305 days), 6 cardiac deaths and 18 unplanned hospitalization due to HF occurred. In the Kaplan-Meier analysis (
Figure
), cardiac event rate was significantly higher in the high LD group (LD ≥10.0 (m/s)/kHz, n=79) than in the low LD group (LD < 10.0 (m/s)/kHz, n=78; log-rank, P=0.007). In the multivariable Cox proportional hazard analysis, high LD was found to be an independent predictor of cardiac event (hazard ratio 3.274, 95% confidence interval 1.203-8.912, P=0.020).

Conclusions:
LD assessed by abdominal ultrasonography reflects liver fibrosis rather than liver congestion, and is associated with adverse prognosis in HF patients.
Abstract 13331: Impact of Longer Hemodialysis Vintage With Higher Serum Phosphorus Level on Clinical Outcomes in Patients With Chronic Limb-threatening Ischemia
Authors: Higashino Naoko , Iida Osamu , MITSUTOSHI ASAI , Masuda Masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Kanda Takashi , TSUJIMURA Takuya , Matsuda Yasuhiro , Hata Yosuke , Uematsu Hiroyuki , Toyoshima Taku , Nohara Hiroaki , Kusuda Masaya , Sakio Takashige , Nakawatase Satoshi , Mano Toshiaki
Published: May 2021

Background:
Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI).

Methods:
The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model.

Result:
One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing.

Conclusion:
Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.
Abstract 13334: Cardio-ankle Vascular Index Reflects Impaired Exercise Capacity and Predicts Adverse Prognosis in Patients With Heart Failure
Authors: Watanabe Koichiro , YOSHIHISA Akiomi , Sato Yu , Hotsuki Yu , Ichijo Yasuhiro , KIMISHIMA Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Takeishi Yasuchika
Published: May 2021

Aims:
We aimed to clarify the associations of cardio-ankle vascular index (CAVI) with exercise capacity and prognosis in patients with heart failure (HF).

Methods and Results:
We recruited clinical data of total of 273 patients hospitalized for treatment of decompensated HF, and underwent both CAVI and cardiopulmonary exercise testing at stable condition in prior to hospital discharge. For the prediction of impaired peak oxygen uptake (VO
2
) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. According to the multiple logistic regression analysis, high CAVI was independently associated with impaired peak VO
2
(odds ratio 2.055, 95% confidence interval 1.015-3.960, P = 0.045). We divided these patients based on CAVI: the low CAVI group (CAVI < 8.9, n = 178, 65.2%) and the high CAVI group (CAVI ≥ 8.9, n = 95, 34.8%). We compared the patients’ characteristics and cardiac events such as cardiac death and re-hospitalization due to worsening HF between the two groups. The high CAVI group was older (69.0 vs. 58.0 years old, P < 0.001) and showed lower body mass index (22.9 vs. 23.8 kg/m
2
, P = 0.018). With respect to laboratory data, levels of estimated glomerular filtration rate were lower in the high CAVI group than in the low CAVI group (56.1 vs. 64.2 mL/min/1.73 m
2
, P = 0.001). During the post-discharge follow-up period of median 1,544 days, 76 cardiac events occurred. The Kaplan-Meier analysis showed that cardiac event rates was higher in the high CAVI group than in the low CAVI group (
Figure
, Log-rank P = 0.021). In the multivariable Cox proportional hazard analysis, high CAVI was found to be an independent predictor of cardiac events (hazard ratio 1.765, 95% confidence interval 1.123-2.773, P = 0.014).

Conclusions:
High CAVI independently associated with impaired exercise capacity accompanied by a high cardiac event rate in HF patients.
Abstract 13352: Decreased Absolute Lymphocyte Count and Increased Neutrophil Lymphocyte Ratio With Immune Checkpoint Inhibitors-associated Myocarditis
Authors: Drobni Zsofia D , Zafar Amna , Zubiri Leyre , Zlotoff Daniel , Alvi Raza , Lee Charlotte , Hartmann Sarah , Gilman Hannah K , Villani Alexandra-Chloe , Nohria Anju , Groarke John D , Sullivan Ryan J , Reynolds Kerry L , Zhang Lili , Neilan Tomas G
Published: May 2021

Introduction:
Myocarditis due to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event (irAE).

Hypothesis:
Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil lymphocyte ratio (NLR) and the development of other irAEs; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis.

Methods:
This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI irAEs. We leveraged clinical testing where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events (MACE) was also tested.

Results:
In those who developed myocarditis, there was a decrease in ALC from baseline (1.6 K/μL, IQR 1.1-1.9) to admission (1.1 K/μL, IQR 0.7-1.3, p<0.001, Panel A). Similarly, among those who developed myocarditis, there was an increase in NLR from baseline (3.5, IQR 2.3-5.4) to admission (6.6, IQR 4.5-14.1, p<0.001, Panel B). There was no change in patients treated with an ICI who did not develop myocarditis. Among those who developed myocarditis, a greater decrease in ALC or increase in NLR was associated with a higher heart rate and a lower blood pressure at admission. In follow-up, there were 20 events; larger decreases in ALC or increases in NLR were associated with MACE (Panel C and D).

Conclusions:
A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR were associated with subsequent MACE.
Abstract 13360: The Association Between Food Insecurity and Cardiovascular Mortality in the United States From 2011 to 2017 - A Longitudinal Analysis
Authors: Wang Stephen Y , Venkataramani Atheendar S , Roberto Christina A , Eberly Lauren A , Groeneveld Peter W , Khatana Sameed Ahmed M
Published: May 2021

Introduction:
Prior analyses suggest a link between food insecurity and cardiovascular (CV) health but are limited by cross-sectional designs. We investigated whether longitudinal changes in food insecurity are independently associated with CV mortality.

Methods:
Using National Center for Health Statistics data, we determined annual U.S. county-level age-adjusted CV mortality rates for non-elderly (20-64 years old) and elderly (65 years and older) adults. County-level food insecurity rates were obtained from the
Map the Meal Gap
project. We examined CV mortality trends by quartiles of average annual percent change (APC) in food insecurity. Using a Poisson fixed effects estimator, we assessed the association between longitudinal changes in food insecurity and CV mortality rates after accounting for time-varying demographic (proportion of residents who were male, black, Hispanic), economic (median household income, unemployment, poverty, education attainment, and housing vacancy rates), and healthcare access (insurance coverage, density of healthcare providers and hospital beds) variables.

Results:
Between 2011 and 2017, mean food insecurity rates decreased from 14.7% to 13.3%. In counties in the highest quartile of APC for absolute value change in food insecurity, non-elderly CV mortality increased from 82.2(SD=33.9) to 87.4(SD=37.3) per 100,000 individuals (p<0.001), while in counties in the lowest quartile of APC, mortality was stable [60.8(SD=22.2) to 60.0(SD=23.0) per 100,000 individuals, p=0.64]. Elderly CV mortality significantly declined in all quartiles [1643.3(SD=315.7) to 1542.7(SD=299.4) per 100,000 (p<0.001) in the highest quartile and 1408.3(SD=225.9) to 1338.6(SD=213.8) per 100,000 (p<0.001) in the lowest quartile). A 1 percentage point increase in food insecurity was independently associated with a 0.83% (95% CI 0.42 - 1.25, P<0.001) increase in CV mortality for non-elderly adults. This was not significant for elderly adults (-0.06%, 95% CI -0.39 - 0.28, P=0.74).

Conclusion:
From 2011 to 2017, an increase in food insecurity was independently associated with an increase in CV mortality rates for non-elderly adults in the U.S. Interventions targeting food insecurity may play a role in improving community CV health.
Abstract 13370: The Relationship Between Longitudinal Changes in Left Ventricular Ejection Fraction and Survival From 57,823 Patients in a Large Regional Health System
Authors: Jing Linyuan , Fielden Samuel , Wehner Gregory J , Leader Joseph , Haggerty Christopher M , Fornwalt Brandon
Published: May 2021

Introduction:
An intriguing U-shape relationship between left ventricular ejection fraction (LVEF) and survival has recently been reported, with LVEFs of 60-65% associated with the lowest mortality risk. In heart failure, LVEF recovery has been linked to improved outcomes; however, the relationship between changes in LVEF (ΔLVEF) and survival in a general clinical population has not been studied. We hypothesized that ΔLVEF would have a non-linear relationship with all-cause mortality.

Methods:
A total of 194,599 echocardiograms from 57,823 patients with physician-reported LVEF were identified from Geisinger health records, along with dates of death or last living encounter, age, sex, smoking status, height, weight, and active diagnoses. ΔLVEF for a given echocardiogram was calculated for 136,776 studies as the difference between the most recent previous and current LVEF. Cox Proportional Hazards Regression was used to relate interaction between ΔLVEF and current LVEF to all-cause mortality while adjusting for confounders.

Results:
Death occurred in 15,419 patients who underwent 39,562 (29%) echocardiograms. Median follow up duration was 3.6 years (IQR, 1.3-7.2), and median time between tests was 1.0 year (IQR, 0.2-2.3). The interaction between LVEF and ΔLVEF (
P
< 0.001) demonstrated that a stable LVEF of 60-65% was associated with the best survival (Figure). A decreased LVEF was universally associated with increased mortality, while LVEFs that had increased showed non-linear interactions. In general, an LVEF of 35-55% that had increased from the previous test was associated with a similar or slightly lower mortality than the same LVEF that was unchanged or had decreased, while an LVEF >55% that had increased was associated with an increase in mortality risk compared to those with a stable LVEF.

Conclusions:
Changes in LVEF have a non-linear relationship with all-cause mortality. In general, a constant, stable LVEF associates with the lowest risk of mortality.
Abstract 13383: The Vascular Endothelial Barrier: A Novel Therapeutic Target for Preventing Atrial Fibrillation
Authors: Mezache Louisa , Struckman Heather , Phillips Anna , Baine Stephen , Greer-short Amara , Gyorke Sandor , Radwanski Przemyslaw , Hund Thomas J , Veeraraghavan Rengasayee
Published: May 2021

Atrial fibrillation (AF), the most common arrhythmia, is associated with inflammation and vascular dysfunction. AF patients have elevated levels of vascular endothelial growth factor (VEGF; 90-580 pg/ml), which promotes vascular leak and edema. We have previously identified edema-induced disruption of sodium channel (Na
V
1.5) -rich intercalated disk (ID) nanodomains as a novel arrhythmia mechanism. We hypothesized that (i) elevated VEGF levels promote AF by disrupting ID nanodomains, and slowing atrial conduction, and (ii) protection of the vascular barrier can prevent these arrhythmias. Clinically-relevant VEGF levels (500 pg/ml, 60 minutes) increased FITC-dextran extravasation (99.3% vs. 24.3% in vehicle controls) in WT mouse hearts, consistent with increased vascular leak. Electron microscopy revealed ID nanodomain swelling, near both gap junctions (perinexi; 64±9nm vs 17±1nm) and mechanical junctions (63±4nm vs 27±2nm) in VEGF-treated hearts relative to controls. Super-resolution STORM microscopy revealed Na
V
1.5 enrichment at perinexi (9±2 fold) and N-cadherin-rich sites (7±1 fold) relative to non-junctional ID sites in control hearts. VEGF reduced Na
V
1.5 enrichment at both sites (6±1 and 4±1 fold, respectively), consistent with Na
V
1.5 translocation from ID nanodomains. Atrial conduction, assessed by optical mapping, was slowed by VEGF (10±0.4 cm/s vs 21.3±1.3 cm/s at baseline). VEGF increased atrial arrhythmia burden both
ex vivo
(80% vs 0% in vehicle controls) and
in vivo
(70% vs 20% in vehicle controls). Next, we tested two strategies shown to prevent vascular barrier breakdown. Blocking connexin43 hemichannels (αCT11 peptide) decreased both incidence (40%) and duration (1.45±3.42s) of VEGF-induced arrhythmias. Likewise, blocking pannexin1 channels (Panx1-IL2 peptide) shortened VEGF-induced arrhythmias (2.48±0.83s). Mefloquine and spironolactone, which are small molecules that respectively inhibit Cx43 hemichannels and pannexin channels, were also found to effectively prevent VEGF-induced atrial arrhythmias. These results highlight VEGF-induced vascular leak as a novel mechanism for AF, and suggest vascular barrier protection as an anti-arrhythmic strategy.
Abstract 13407: Trends in Discharge Prescription of Digoxin After Norwood Operation: An Analysis of Data From the Pediatric Health Information Systems Database (PHIS)
Authors: Obyrne Michael L , Song Lihai , HUANG JING , Goldberg David J , Gardner Monique A , Ravishankar Chitra , Rome Jonathan J , Glatz Andrew C
Published: May 2021

Background:
Quality improvement efforts have focused on reducing interstage mortality for infants with hypoplastic left heart syndrome (HLHS). In 2016 two publications reported that digoxin use was associated with reduced interstage mortality. The degree to which these findings have affected real world practice has not been evaluated.

Methods:
A multicenter retrospective cohort study of rates of digoxin prescription at discharge was performed of neonates with HLHS surviving to discharge without transplant from 1/2006-12/2018 at PHIS hospitals. A difference in difference analysis was performed using mixed effects models to adjust for measurable covariates (known arrhythmia, prematurity, renal insufficiency, etc.) with the hypothesis that the likelihood of digoxin prescription increased after 1/2016. Inter-hospital practice variation was measured, calculating the median odds ratio (MOR). Likelihood of furosemide and aspirin prescriptions were studied as falsification tests.

Results:
Over the study period 6091 subjects from 35 hospitals were included. Likelihood of receiving digoxin, furosemide, and aspirin are depicted (Figure). After adjusting for measurable covariates, discharge after 1/2016 was associated with increased odds of receiving digoxin (OR: 3.9, p<0.001). No association was seen between date of discharge and furosemide (p=0.26) or aspirin (p=0.12). Prior to 1/2016, the likelihood of receiving digoxin was decreasing (OR: 0.9 per year, p<0.001), while after 1/2016 the likelihood has increased (OR: 2.4 per year, p<0.001). Significant inter-hospital variation in the likelihood of receiving digoxin was seen (MOR=3.5, p<0.001 with no significant difference before and after 2016).

Conclusion:
The use of digoxin increased after publication of data about potential benefit in the interstage period. However, despite concerted quality improvement efforts, there is persistent large magnitude inter-hospital variation in practice.
Abstract 13418: Inter-relation of Parity and Coronary Artery Calcium With Cardiovascular Disease Events: The Multi-ethnic Study of Atherosclerosis
Authors: Vu Kimberly , Nguyen Khoa , Evans Jonathan , FAN WENJUN , Mongraw-chaffin Morgana , Budoff Matthew J , Wong Nathan D , Michos Erin D
Published: May 2021

Introduction:
Coronary artery calcium (CAC) is a measure of subclinical atherosclerosis and predicts cardiovascular disease (CVD) events. Greater parity, or number of live births, has been shown to relate to CVD. We examined whether the relation of parity to CVD events may depend on the presence and extent of subclinical atherosclerosis measured by CAC.

Methods:
We studied 3151 women free of CVD at baseline in the Multi-Ethnic Study of Atherosclerosis, a prospective study of CVD. Participants were stratified by parity categories of 0-1 (reference), 2-3, and ≥4 and by baseline CAC categories of 0, 1-99, and 100+. We compared the incidence of CVD (myocardial infarction, stroke, resuscitated cardiac arrest, and coronary heart disease deaths) per 1000 years based on parity across levels of CAC over 13 years. Cox regression determined the joint association of parity and CAC on the incidence of CVD.

Results:
Women with greater parity had a higher prevalence of any CAC and CAC≥100 (p<0.01); among those with CAC, parity related to greater mean CAC scores (175, 184, and 284, respectively) (p<0.01). Women with greater parity also had greater incident CVD (7.1%, 8.7%, and 11.3% for 0-1, 2-3, and ≥4 live births, respectively, p-trend =0.01) and extent of CAC directly related to the incidence of CVD within parity groups. However, the association of parity with CAC was attenuated after adjustment for age, race, income, smoking and other risk factors. Parity also directly related to the incidence of CVD within CAC categories (
Figure
); however, from Cox regression analyses, these relations were attenuated when adjusted for age, ethnicity and other risk factors.

Conclusion:
In unadjusted analyses, we show parity to be associated with the prevalence of any or significant CAC, extent of CAC among those with CAC>0, as well as the incidence of CVD events, overall and according to the presence and extent of CAC. However, the association of parity with CVD risk was attenuated after adjustment for other factors.
Abstract 13427: Extracellular Vesicles Improve Heart Function Without Inducing the Generation of New Cardiomyocytes
Authors: Lima Correa Bruna , El harane Nadia , Perotto Maria , Desgres Manon , Guillas Chloe , Alayrac Paul , PIDIAL LAETITIA , BELLAMY VALERIE , tence noemie , Baron Emilie , Autret Gwennhael , Kamaleswaran Keirththana , Vilar Jose , Alberdi Antonio , Renault Nisa , Gnecchi Massimiliano , Menasche Philippe , Silvestre Jean-Sebastien
Published: May 2021

Introduction:
Extracellular Vesicles (EV) recapitulate the benefits of cell therapy for heart repair. Their mechanism of action remains unsettled.

Hypothesis:
EV may contribute to heart repair by
de novo
cardiogenesis.

Methods:
To answer this question, we used 2 bi-transgenic mouse models: the fate-mapping MerCreMer/ZEG and the Mosaic Analysis With Double Markers (MADM). Myocardial infarction was induced by permanent coronary artery ligation. Those with a LVEF ≤ 45% were treated 3 weeks later with EV (from human iPS-derived cardiovascular progenitor cells; 10x10
9
particles) or PBS, injected under echo guidance in the peri-infarcted area (MerCreMer/ZEG: n=15/group and MADM: n=6/group). To track endogenous cardiomyocyte (CM) proliferation, we used EdU labeling in MerCreMer/ZEG delivered by osmotic pumps implanted for 7-10 days post-injection and biphoton microscopy in MADM models. Cardiac function was assessed 4-6 weeks after injection by echocardiography and MRI, blinded to treatment group. Hearts were then subjected to histological and transcriptomic analyses (qPCR and genome-wide microarray).

Results:
In PBS controls, EF remained stable over time in MerCreMer/ZEG mice and decreased from 34.5% ± 6.0% to 30.7% ± 7.5% in MADM mice by the end of the study. Conversely, EV injections increased EF from 32.1% ± 9.5% to 36.1% ± 7.45 % in MerCreMer/ZEG and from 36.2 %± 8.7% to 40.5% ± 8.9% in MADM mice. A significant difference in the change from baseline was found between EV and controls: 20.7% ± 10.5 % (p=0.048) and 28.0% ± 11.0 %, (p=0.045) for MerCreMer/ZEG and MADM groups, respectively. This improvement was confirmed by MRI in MerCreMer/ZEG mice (p=0.05). Improvement in EF was unrelated to the appearance of new CM, as shown by the absence of difference in TnT+/EdU+/GFP+ cell numbers and the lack of activation of the YAP/TAZ pathway between control and EV groups. However, EV reduced infarct size by 11.9% ± 5.75% (p=0.04), which was accompanied by decreased expression of 4 pro-fibrotic genes (Col1a2, Col3a1, Lox, Col1a2 by qPCR) in heart tissue and a 2.13X overexpression of the anti-fibrotic miRNA 133a-1 compared to controls (n=3/group; p=0.001).

Conclusions:
EV likely improve cardiac function by modulation of fibrosis rather than by
de novo
cardiogenesis.
Abstract 13441: D-dimmer is a Predictor of Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy
Authors: Oikawa Masayoshi , Yaegashi Daiki , Yokokawa Tetsuro , Misaka Tomofumi , Sato Takamasa , KOBAYASHI ATSUSHI , YOSHIHISA Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: May 2021

Background:
D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD).

Methods and Results:
Consequtive 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) were enrolled and followed up for 12 months. Cancer types were as follows: breast cancer (n=112), lymphoma (n=37), ovarian or uterine cancer (n=18), leukemia (n=13), multiple myeloma (n=6), bone cancer (n=4), and others (n=12). All patients underwent echocardiography and blood test at baseline, 3-month, 6-month, and 12-month. The patients were divided into 2 groups based on the value of D-dimer (>1.5 μg/ml or ≦1.5 μg/ml) at baseline before chemotherapy: High D-dimer group (n=52) and Low D-dimer group (n=150). At baseline, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index, and B-type natriuretic peptide levels were similar between two groups. Time-dependent decrease in LVEF was observed after chemotherapy in high D-dimer group (baseline, 66±5%; 3-month, 63±7%; 6-month, 62±7%; 12-month 62±6%; P=0.005, figure), but not in low D-dimer group. Time-dependent increase in troponin I was similarly observed after chemotherapy in both groups. The occurrence of CTRCD was higher in high D-dimer group than in low D-dimer group (11.5% vs. 4.0%, P=0.048). When we set the cut-off value of baseline D-dimer at 1.65 μg/ml from ROC analysis, sensitivity, specificity, and area under the curve to predict CTRCD were 50%, 77%, and 0.679, respectively. Multivariable logistic analysis revealed that baseline D-dimer was an independent factor to predict the decrease in LVEF more than 10% after cardiotoxic chemotherapy (odds ratio 1.210, 95% confidence interval [1.020-1.440], P=0.025).

Conclusion:
Baseline D-dimer is a pivotal parameter to predict CTRCD.
Abstract 13451: Upregulation of CaMKII and Contrast Changes of Cardiac β
1
- and β
3
-Adrenergic Signaling Pathways in a Humanized Angiotensinogen Model of Hypertension
Authors: Cheng Heng Jie , Cao Jing , Sun Xiaoqiang , Liu Yixi , Chen Zhe , Kitzman Dalane , Herrington David , Zhao David , Cheng Che
Published: May 2021

Background:
The transgenic rats expressing the human AGT gene [TGR (hAGT) L1623] (hAogen) is an established humanized model of hypertension. Recently we further found that this model is associated with declines in cardiac contractile function and β-adrenergic receptor (AR) reserve. However, the molecular basis is unclear. It has been suggested that pivotal restructuring of β-AR system is a critical determinant of the dysfunctional β-AR regulation in several cardiovascular diseases, including hypertension. But the alterations of subtypes of β-ARs have not been systemically evaluated in this model. Furthermore, there is significant crosstalk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in the abnormal contractile phenotype of cardiac hypertrophy. However, the changes in cardiac CaMKII in this model are unknown. We tested the hypothesis that in hAogen, CaMKII and β
3
-AR are upregulated in the myocardium, but β
1
-AR is down-regulated, which are important causes of cardiac dysfunction and β-AR desensitization.

Methods:
We compared LV myocyte CaMKIIδ expression and activity and β
1
- and β
3
-AR expression and determined myocyte functional performance and [Ca
2+
]
i
transient ([Ca
2+
]
iT)
response to β -AR stimulation in myocytes obtained from 6 Sprague Dawley (SD) control and 6 haogen male adult rats.

Results:
Compared with SD, in hAogen LV myocytes, β
3
-AR protein level significantly increased (26%, 0.29 vs 0.23), but β
1
-AR protein level (26%, 0.4 vs 0.54) significantly decreased. The CaMKIIδ protein levels (16%, 0.50 vs 0.43) and CaMKIIδ phosphorylation (at Thr287) (35%, 0.27 vs 0.20) were significantly increased. These changes were followed by significantly reduced cell contraction (dL/dt
max
, 102.1vs 138.8μm/s), relaxation (dR/dt
max
, 94.0 vs 104.7 μm/s) and [Ca
2+
]
iT
(0.15 vs 0.21). ISO-stimulated increases in dL/dt
max
(42% vs 60%), dR/dt
max
(36% vs 51%) and [Ca
2+
]
iT
(20% vs 31%) were also significantly reduced.

Conclusions:
The upregulation of LV myocyte CaMKIIδ and contrast changes in β
3
-AR and β
1
-AR may be the important cause of the abnormal contractile phenotype and β-AR desensitization in this humanized angiotensinogen model of hypertension of TGR (hAGT) L1623.
Abstract 13452: Sex Differences in Presentation, Management, and Outcomes Among Patients Hospitalized With Acute Pulmonary Embolism
Authors: Pribish Abby M , Beyer Sebastian , Krawisz Anna K , Weinberg Ido , Carroll Brett J , Secemsky Eric A
Published: May 2021

Introduction:
The presence of gender disparities in cardiovascular disease has been well-described, but there is a paucity of data regarding the impact of gender on the presentation, management and outcomes of acute pulmonary embolism (PE).

Hypothesis:
We hypothesized that there are no gender-based differences in PE management or outcomes.

Methods:
We identified all patients admitted to our institution with acute PE from 8/1/2012-7/1/2018. We stratified presenting characteristics, management and outcomes between women and men. Outcomes included major bleeding, survival, 90-day readmission, and 90-day recurrent venous thromboembolism (VTE). Inverse probability of treatment weighting was used to evaluate the independent association between sex and in-hospital and short-term outcomes.

Results:
The study included 2031 patients with PE, 53.2% of whom were women. Women had a higher mean age (63.8 years vs 62.3 years, P=0.04). PE severity was similar between women and men (massive: 4.9% vs 3.6%; submassive: 43.9% vs 41.8%; P=0.19), but women were more likely to present with dyspnea (59.8% vs 52.0%, P<0.001) and had higher median NT-pro-BNP levels (605 pg/mL [IQR 143-2582] vs 319 pg/mL [IQR 82-1576], P<0.001). Although the comorbidity burden was similar, women were less likely to have a history of PE (19.3% vs 24.2%, P=0.01), smoking (43.1% vs 53.3%, P<0.001), or myocardial infarction (6.6% vs 9.7%, P=0.01). In unadjusted analyses, women were less likely to survive to discharge (92.4% vs 94.7%, P=0.04), but after adjustment, there was no gender-based survival difference. There were also no gender differences in PE-related diagnostic studies, use of advanced therapies, or other short-term outcomes, before and after adjustment (p>0.05 for all) (Fig 1).

Conclusions:
In this large PE cohort from a tertiary care institution, women had different comorbidity profiles and PE presentations than men. Despite this, there were no gender disparities in PE management or outcomes.
Abstract 13455: Predicting Emergency Department Disposition at Triage for Suspected Patients With Acute Coronary Syndrome Using Machine Learning Algorithms
Authors: Frisch Stephanie O , Bouzid Zeineb , Zègre-Hemsey Jessica , CALLAWAY Clifton W , Devon Holli A , Sejdic Ervin
Published: May 2021

Introduction:
Overcrowded emergency departments (ED) and undifferentiated patients make the provision of care and resources challenging. We examined whether machine learning algorithms could identify ED patients’ disposition (hospitalization and critical care admission) using readily available objective triage data among patients with symptoms suggestive of acute coronary syndrome (ACS).

Methods:
This was a retrospective observational cohort study of adult patients who were triaged at the ED for a suspected coronary event. A total of 162 input variables (k) were extracted from the electronic health record: demographics (k=3), mode of transportation (k=1), past medical/surgical history (k=57), first ED vital signs (k=7), home medications (k=31), symptomology (k=40), and the computer generated automatic interpretation of 12-lead electrocardiogram (k=23). The primary outcomes were hospitalization and critical care admission (i.e., admission to intensive or step-down care unit). We used 10-fold stratified cross validation to evaluate the performance of five machine learning algorithms to predict the study outcomes: logistic regression, naïve Bayes, random forest, gradient boosting and artificial neural network classifiers. We determined the best model by comparing the area under the receiver operating characteristic curve (AUC) of all models.

Results:
Included were 1201 patients (age 64±14, 39% female; 10% Black) with a total of 956 hospitalizations, and 169 critical care admissions. The best performing machine learning classifier for the outcome of hospitalization was gradient boosting machine with an AUC of 0.85 (95% CI, 0.82–0.89), 89% sensitivity, and F-score of 0.83; random forest classifier performed the best for the outcome of critical care admission with an AUC of 0.73 (95% CI, 0.70–0.77), 76% sensitivity, and F-score of 0.56.

Conclusion:
Predictive machine learning algorithms demonstrate excellent to good discriminative power to predict hospitalization and critical care admission, respectively. Administrators and clinicians could benefit from machine learning approaches to predict hospitalization and critical care admission, to optimize and allocate scarce ED and hospital resources and provide optimal care.
Abstract 13463: Left Atrioventricular Coupling Index as a Prognostic Marker: The Multi-ethnic Study of Atherosclerosis
Authors: Pezel Theo , Ambale Venkatesh Bharath , De Vasconcellos Henrique D , Kato Yoko , Shabani Mahsima , Xie Eric , Heckbert Susan R , Post Wendy S , Shea Steven , Allen Norrina B , Watson Karol E , Wu Colin , Bluemke David , Ac Lima Joao A
Published: May 2021

Introduction:
The left atrium (LA) and left ventricle (LV) parameters have both prognostic value for cardiovascular (CV) events. We hypothesize the left atrioventricular coupling to be a strong predictor of CV events.

Hypothesis:
This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) and to assess its predictive value for CV events in a population without a history of CV diseases at baseline.

Methods:
A total of 4,124 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent a cardiac MRI study. The LACI was defined by the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume by MRI. Cox proportional hazard models were built to predict the endpoints of atrial fibrillation (AF), heart failure (HF), CV death and hard CV disease (CVD) defined by myocardial infarction, resuscitated cardiac arrest, fatal and non-fatal stroke or CV death. In univariable and multivariable Cox analyses, the association between LACI and time-to-event was analysed, adjusting for 14 covariables including traditional CV risk factors and biomarkers.

Results:
A total of 1151 CV events were observed during a median (IQR) follow-up period of 15.9 (12.9-16.6) years. LACI was associated with AF (HR 2.14, 95%CI [1.97-2.32]), HF (HR 1.70, 95%CI [1.56-1.86]), hard CVD (HR 1.34, 95%CI [1.22-1.48]), and CV death (HR 1.53, 95%CI [1.38-1.70]; for all p<0.0001). In multivariate analysis, LACI had a significant independent association for AF (HR 1.86, 95%CI [1.69-2.04]), HF (HR 1.47, 95%CI [1.33-1.60]), hard CVD (HR 1.25, 95%CI [1.12-1.40]), and CV death (HR 1.29, 95%CI [1.15-1.50; for all p<0.001). LACI showed better discrimination than the multivariate model for AF (C-statistic: 0.84 vs 0.79), HF (0.82 vs 0.80), hard CVD (0.77 vs 0.76), and CV death (0.84 vs 0.83).

Conclusions:
The LACI is a predictor of incident HF, AF, hard CV disease, and CV death in MESA.
Abstract 13465: Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Known Myocardial Infarction
Authors: Pezel Theo , Garot Philippe , Kinnel Marine , Hovasse Thomas , Toupin Solenn , Unterseeh Thierry , Morice Marie Claude , Champagne Stéphane , Louvard Yves , Sanguineti Francesca , Garot Jerome
Published: May 2021

Introduction:
Several studies have demonstrated the consistently high prognostic value of stress perfusion cardiovascular magnetic resonance (CMR). This prognostic value in patients with known myocardial infarction (MI) is poorly described.

Hypothesis:
To assess the prognostic value of vasodilator stress perfusion CMR in patients with known MI.

Methods:
We prospectively included consecutive patients with known MI referred for vasodilator stress CMR with dipyridamole. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent non-fatal myocardial infarction (MI).

Results:
Of 1602 patients with known MI (68 ± 17 years, 78% men), 1556 (97%) completed the CMR protocol, and among those 1401 (90%) completed the follow-up (median follow-up 5.7 (3.9-7.6) years). Reasons for failure to complete CMR included ECG-gating problems (n=13), intolerance to stress agent (n=12), renal failure (n=12), declining participation (n=4) and claustrophobia (n=5). Stress CMR was well tolerated without occurrence of death or severe adverse event. Patients without inducible ischemia experienced a substantially lower annual event rate of MACE (3.1%) than those with 1 or 2 segments of ischemia (4.5%), than those with 3 to 5 segments of ischemia (21.5%), than those with 6 or more segments of ischemia (45.7%, for all p<0.01). Using Kaplan-Meier analysis, the presence of myocardial ischemia identified the occurrence of MACE (hazard ratio HR 3.52; 95% confidence interval CI: 2.67 - 4.65;
p
<0.001). In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, the presence of inducible ischemia was an independent predictor of a higher incidence of MACE (HR 2.84; 95% CI: 2.14 to 3.78;
p
<0.001).

Conclusions:
Stress CMR is technically feasible and has a good discriminative prognostic value to predict the occurrence of MACE in patients with known MI.
Abstract 13477: Feasibility and Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Atrial Fibrillation
Authors: Pezel Theo , Sanguineti Francesca , Kinnel Marine , Landon Valentin , Hovasse Thomas , Toupin Solenn , Garot Philippe , Unterseeh Thierry , Champagne Stephane , Louvard Yves , Morice Marie Claude , Garot Jerome
Published: May 2021

Introduction:
Because most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with atrial fibrillation (AF) is unknown.

Hypothesis:
To assess the feasibility and the prognostic value of vasodilator stress perfusion CMR in patients with AF.

Methods:
Between 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease (CAD) and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiogram before and after CMR. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.

Results:
Of 639 patients (72±9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed the follow-up (median 5.1 years); 80 had a MACE. Stress CMR was well tolerated. Using Kaplan-Meier analysis, the presence of ischemia or LGE was associated with the occurrence of MACE (HR 7.56; 95% CI: 4.86-11.80 and HR 2.41; 95% CI: 1.55-3.74 respectively; for both
p
<0.001). In a multivariable Cox regression including clinical and CMR indexes, the presence of ischemia or LGE was an independent predictor of MACE (HR 5.98; 95% CI: 3.68-9.73 and HR 2.61; 95% CI: 1.89-3.60 respectively; for both
p
<0.001).

Conclusions:
In patients with AF, stress perfusion CMR is feasible, safe and has a good discriminative prognostic value to predict the occurrence of MACE.