bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12314: The Long-Term Effect of Coronary Atherosclerosis and Apnea Hypopnea Index During Rapid Eye Movement on Posttraumatic Stress Disorder
Authors: Ahmadi Naser , Hajsadeghi Fereshteh
Published: July 2021

Introduction:
Posttraumatic-stress-disorder(PTSD) is associated with subclinical-atherosclerosis as well as rapid-eye-movement(REM) apnea-hypopnea-index(AHI). This study investigated the relation of coronary-atherosclerosis measured by coronary-artery-calcium(CAC), REM-AHI with cardiovascular(CV)-mortality in PTSD.

Hypothesis:
There is a direct relation between CAC and REM-AHI with increased CV-mortality in PTSD.

Methods:
This study is consist of 634 veterans without-known-CAD(age:58±11years,86%men) underwent CAC-scanning and overnight poly-somnography for clinical-indications. Psychological-health-status(PTSD vs. non-PTSD)was measured and they were followed for median of 36-months. Multivariable-Cox-regression-analyses were employed to assess the relation of REM-AHI and CAC, with CV-mortality in PTSD.

Results:
At follow-up (figure 1), the death-rate was higher in the PTSD(17%) than non-PTSD(10.4%)(p=0.001). Regression-analyses revealed a significant-linkage between PTSD and CAC as well as PTSD and REM-AHI with CV-mortality. The relative-risk of CV-mortality was 5.72(95%CI:2.46-13.34,p=0.0001) in PTSD and CAC>0 as compared to non-PTSD with CAC=0. Similarly, the relative risk of CV-mortality was 3.22 (95%CI:1.17-8.85, p=0.02) in PTSD and REM AHI≥30 as compared to non-PTSD with REM AHI0 which was more prominent in PTSD(p=0.001). A significant linkage of CAC and REM-AHI with increased CV-mortality in PTSD was noted in which the relative-risk of CV-mortality in PTSD was 6.44 (95%CI:3.64-11.37,p=0.001) in combined CAC>0 and REM AHI≥30 as compared to non-PTSD.

Conclusions:
1)PTSD is associated with the coronary-atherosclerosis and increased CV-mortality, 2)PTSD is associated with REM obstructive-sleep-apnea and predicts CV-mortality and 3) There is an independent significant linkage of PTSD with REM obstructive-sleep-apnea as well as coronary-atherosclerosis, and increased risk of CV-mortality.
Abstract 12334: How Much Exposure to Resuscitation Do Emergency Medical Service Personnel Get?
Authors: Dyson Kylie , Bray Janet , Smith Karen , Bernard Stephen , Straney Lahn , Judith Finn
Published: July 2021

Objectives:
The exposure of emergency medical service personnel (paramedics) to out-of-hospital cardiac arrest (OHCA) and resuscitation procedures could be an important factor in skill maintenance and quality of care. This study aims to describe paramedic exposure to OHCA resuscitation in the state of Victoria, Australia (population 5.8 million).

Methods:
We extracted and linked data from the Victorian Ambulance Cardiac Arrest Registry (VACAR) and Ambulance Victoria’s employment dataset for the period 2003-2012. Paramedics were considered to have ‘exposure’ to OHCA if they attended a case where resuscitation was attempted. Individual rates were calculated for annual exposure (number of OHCA exposures for each paramedic/years employed in study period) and days between exposures (total paramedic days/total number of exposures).

Results:
Over the 10-year period, there were 49,107 OHCAs and 5,673 paramedics employed. Resuscitation was attempted in 44% of patients. An average of 3.2 (SD±1.1) paramedics attended each case. The median average exposure of paramedics was 2.2 (IQR=1.2-3.5) OHCAs/year. The proportion with no exposures in a year increased from 39% in 2003 to 43% in 2012 (
p
=0.036). OHCA exposure was significantly less in those employed part-time or casual (
p
<0.001), in a rural area (
p
<0.001) or with a lower qualification (
p
<0.001) (Table). Annual exposure to pediatric and traumatic OHCAs was particularly low (Table). Paramedics were exposed to an average of 0.006 OHCAs/day, meaning it would take an average of 163 days be exposed to OHCA and up to 12.5 years for rare cases, such as pediatric OHCAs.

Conclusion:
Our study identified paramedic exposure to resuscitation is low and has decreased over time. This highlights the importance of supplementing paramedic exposure with other methods, such as simulation, to maintain resuscitation skills. This may be particularly important to paramedics with low exposure and for rare case types, such as pediatric OHCA.
Abstract 12411: Prognostic Value of Cardiovascular Magnetic Resonance-Derived Indices of Right Ventriculo-Arterial Coupling and Internal Mechanical Work in Pulmonary Hypertension
Authors: Abouelnour Amr , Doyle Mark , Thompson Diane , Yamrozik June , Williams Ronald , Shah Moneal , Soma Siva K , Murali Srinivas , Benza Raymond , Biederman Robert W
Published: July 2021

Objectives:
External cardiac work performed is represented by the area within the ejection loop (P-V) and correlates poorly with the heart’s total energy demands until the internal work component is added. Further, the ratio of the arterial elastance (E
a
) to the ventricular end-systolic elastance (E
max
) is a measure of ventriculo-arterial coupling. We investigated the impact of both indices of right ventricular (RV) performance on outcome in patients with pulmonary hypertension (PH).

Methods:
Cardiac magnetic resonance (CMR) studies of a retrospective consecutive cohort of 115 PH pts (61±14 yrs) were examined for RV volumetrics, functional indices and the presence of RV late gadolinium enhancement (LGE) from 2008-2014. Right heart cath (RHC) parameters were included in the analysis (performed within 1±1.5 mo of CMR) as was 3D RV mass and RVEF. The E
a
/E
max
ratio was derived in part as RV end-systolic volume (ESV)/RV stroke volume. Internal mechanical work was estimated as RVESV*(RV-ES pressure- RV-ED pressure). Patients were followed up to 5 yrs.

Results:
During follow-up, 42/115 (37%) pts had a MACE. On a multivariable logistic regression analysis, the strongest predictor of MACE was the internal RV mechanical work followed in order by E
a
/E
max
versus

mean pulmonary artery pressure, RV mass, RV EF, and RV LGE. The strongest predictors of time to MACE were the RV internal mechanical work (χ
2
=10.8) and E
a
/E
max
ratio (χ
2
=9.2). Kaplan-Meier analysis of time to MACE for quartiles of RV internal mechanical work and E
a
/E
max
are shown in Figure 1A & B.

Conclusions:
Higher RV internal mechanical work and E
a
/E
max
are both markers for worsening prognosis in PH patients; E
a
/E
max
having the added advantage of being an entirely non-invasive CMR derivation and statistically equivalent. Both metrics were superior to standard clinical metrics including RV LGE, RVEF, PA pressure and RV mass and for the first time address integrated cardio-pulmonary physiology as early markers for MACE.
Abstract 12421: Single Beat Simultaneous Left Atrioventricular Strain-Volume Analysis Using Speckle Tracking Echocardiography
Authors: Omar Alaa M , Abdel-Rahman Mohamed A , Sabe-Eleish Zaid H , Rifaie Osama , Pedrizzetti Gianni , Sengupta Partho P
Published: July 2021

Introduction:
Assessment of cardiac mechanics in relation to left atrial (LA) and ventricular (LV) structural (shape and volume) changes represent a foundation for assessing cardiac remodeling in heart failure (HF) patients. We tested the feasibility of assessing simultaneous LA and LV volumes and deformation within an index cardiac cycle as a marker of total left heart structural and functional remodeling in HF.

Methods:
Echocardiography was performed in total 101 patients, which included 77 patients with HF (50 had normal EF (HFNEF) and 27 had reduced EF (HFREF)) and 24 young subjects with no structural heart disease (controls) (table 1). Two-dimensional speckle tracking was performed in apical 2- and 4- chamber views for simultaneous measurement of LV and LA volumes and deformation. Peak longitudinal average atrio-ventricular strain (AVS) and early diastolic strain rate (AVSR-E), in addition to the total left heart volume (TLV) during LV systole and diastole (TLVsystole, TLVdiastole), were measured. Occurrence of major adverse cardiac events (MACE) was defined during follow up.

Results:
In comparison with younger controls, patient with HF showed higher TLV and nearly 50% reduction in AVS and AVSR-E (table 1). These differences persisted even after adjusting for age. During a median follow up of 7 months, MACE occurred in 15 patients (5 hospitalization for heart failure, 1 cerebrovascular stroke, and 9 cardiac deaths). AVS and AVSR-E were predictors for MACE after adjusting for age (HR=0.9, 95% CI: 0.81 to 0.99, p=0.038; HR= 0.14, 95% CI: 0.02 to 0.89, p=0.037; respectively). AVS and AVSR-E had similar diagnostic values in predicting MACE (AUC= 0.77 and 0.79; p=0.001 and <0.001 respectively), with higher event free survival seen for AV-S>14.5%, and AVSR-E>0.92 s-1 (Figure 1).

Conclusion:
Single beat combined assessments of LA-LV strain and strain rates may be useful integrated markers of total left heart function.
Abstract 12435: Coronary Artery Calcium Score of Zero Predicts Lower All-Cause Mortality Over a Long-Term Follow-Up
Authors: Knapper Joseph T , Lebeis Taylor , Southmayd Geoff , Sandesara Pratik , Blaha Michael J , Berman Daniel , Quyyumi Arshed , Budoff Michael J , Min James K , Valenti Valentina , Callister Tracy Q , Giambrone Ashley E , Shaw Leslee J
Published: July 2021

Background:
Coronary artery calcium (CAC) scoring has been shown in numerous studies to correlate well with adverse cardiovascular outcomes. In particular, a CAC score of zero has been linked with excellent survival. However, the majority of studies report only short-term follow-up results, and there is little data available on the long-term significance of a zero CAC score.

Methods:
A total of 9,074 (53±10 years, 60% male) consecutive asymptomatic individuals, free of known coronary heart disease (CHD), underwent CAC Agatston scoring for cardiovascular risk assessment. CHD risk factors were prospectively obtained by patient interview. Unadjusted and risk-factor adjusted Cox proportional hazard modeling was used to estimate time to all-cause mortality (median follow-up=14.7 years) by CAC subsets and was compared to general population mortality estimates.

Results:
Of all patients enrolled, 4,537 (50.0%) had a CAC score of zero. Annual all-cause mortality, based on adjusted Cox hazard modeling, was significantly lower in both men and women with a CAC score of zero than would be predicted for the general population (see
Figure
). The median reduction in projected annual mortality was 68.4% for men and 51.2% for women, with the degree of mortality reduction increasing with age. Compared to a CAC score of zero, even a low-risk CAC score of 1-10 was associated with an increased risk of all-cause mortality (HR = 4.19, 1.97, 2.44
*
, 1.82
*
, and 1.70
*
at 1, 3, 5, 10, and 15 years of follow-up, respectively), though importantly this effect did not reach statistical significance until 5 years of follow-up.

Conclusion:
A CAC score of zero is associated with a markedly decreased risk of all-cause mortality compared to the general population, and its significance increases with both age and length of follow-up.
Abstract 12444: Outcomes After Starting Beta-Blockade Within a Clinically Sensible Period Before Major Elective Noncardiac Surgery
Authors: Wijeysundera Duminda N , Ko Dennis T , Wijeysundera Harindra C , Yun Lingsong , Beattie W. Scott
Published: July 2021

INTRODUCTION:
Guidelines recommend that perioperative beta-blockade be started days to weeks before surgery. Nonetheless, all randomized trials except for the controversial DECREASE trials started treatment ≤1 day before surgery, while most observational studies did not distinguish between long-term beta-blockade versus beta-blockers started for perioperative reasons. We thus conducted a population-based cohort study of the effectiveness of beta-blockade started within a clinically sensible period (8-60 days) before surgery.

METHODS:
Following research ethics approval, we conducted a cohort study of patients (≥66 years) who underwent major elective noncardiac surgery from 2003 and 2012 in Ontario, Canada. Propensity-score methods were used to form a matched cohort that reduced important differences between patients who started beta-blockers 8-60 days before surgery versus controls (no beta-blockers within 1 year before surgery). We measured the association of beta-blockade with 30-day (death, MI, stroke) and 1-year (death) outcomes post-surgery. Subgroup analyses were performed based on Revised Cardiac Risk Index class and history of prior CAD.

RESULTS:
The cohort included 4268 beta-blocked patients and 154,357 controls. Metoprolol (median daily dose 50 mg) was prescribed to 36% of beta-blocked patients, atenolol (median 25 mg) to 26%, and bisoprolol (median 5 mg) to 37%. In the matched cohort (n=8492), beta-blockade was not associated with death (RR 0.96; CI 0.70-1.32), MI (RR 0.92; CI 0.72-1.17), and stroke (RR 1.31; CI 0.68-2.52) at 30-days, or death at 1-year (Figure). Associations with outcomes did not differ significantly across subgroups.

CONCLUSIONS:
Outcomes were not altered in patients who start perioperative beta-blockade within a clinically sensible period before surgery. A large randomized trial is needed to determine if the continued use of perioperative beta-blockade in clinical practice is justified.
Abstract 12455: Evaluation of N-Terminal Pro-B-type Natriuretic Peptide as a Therapeutic Response Biomarker in Group I Pulmonary Arterial Hypertension
Authors: Wolfson Aaron M , Maitland Micheal L , Thomeas Vasiliki , Glassner Cherylanne , Gomberg-Maitland Mardi
Published: July 2021

Purpose:
Goal directed management of left heart failure with an NT-proBNP target-based approach has some evidence of providing a survival benefit. To evaluate the potential utility of serial NT-proBNP measurements for goal-directed therapy in right heart failure we retrospectively assessed NT-proBNP as a predictor for survival in Group I pulmonary arterial hypertension (PAH) patients.

Methods:
We identified 103 Group I PAH patients from a pulmonary hypertension registry who had baseline elevated NT-proBNP prior to either the initiation or escalation of therapy and at least two serial NT-proBNP measurements. In a two-step process, we (1) estimated baseline NT-proBNP and slope (rate of change of NT-proBNP) with a linear mixed-effects model using all patient data and then (2) compared the power of serial versus single measurements in predicting survival with measured and model-derived values of baseline NT-proBNP with a Receiver Operative Characteristic (ROC) curve analysis . Survival was determined using the Kaplan-Meier methodology.

Results:
ROC curve analysis revealed significantly higher AUC for model-derived NT-proBNP values compared to the measured values (AUC: for baseline 0.74 vs 0.66, p= 0.009; for slope 0.78 vs 0.66, p= 0.02). Optimal cutpoints for prediction of survival on baseline NT-proBNP were 2012 (measured) vs. 1810 (model-derived) pg/mL. The optimal cutpoint for model-derived change in NT-proBNP was -0.004 log10pg/mL/month. Sensitivity, specificity, and negative predictive values for the three predictor variables were: 64%, 67%, 80% (measured baseline NT-proBNP), 61%, 80%, 81% (model-derived baseline NT-proBNP) and 73%, 57%, 85% (model-derived slope).

Conclusions:
In PAH patients, serial NT-proBNP measurements better predict survival than single measurements. This retrospective finding reveals that changes in NT-proBNP are associated with overall survival in PAH patients, and set initial target values for a pilot prospective study of NT-proBNP goal-directed therapy.
Abstract 12459: Is Ejection Fraction <50% the Optimal Threshold for Referral for Valve Replacement in Patients With Severe Aortic Stenosis? Impact of Ejection Fraction on Post-Operative Outcome
Authors: Dahl Jordi S , Eleid Mackram F , Michelena Hector , Scott Christopher , Suri Rakesh , Schaff Hartzell V , Pellikka Patricia A
Published: July 2021

Introduction:
In asymptomatic patients with severe aortic stenosis (SAS), left ventricular (LV) ejection fraction (EF) <50% is generally considered to be the threshold for referral for aortic valve replacement (AVR).

Hypothesis:
We investigated the importance of LVEF on long-term outcome after AVR in symptomatic and asymptomatic SAS patients and studied whether LVEF < 50% is the optimal threshold for referral for AVR.

Methods and Results:
We retrospectively identified 2017 patients with SAS (aortic valve area (AVA)<1cm2, mean aortic valve gradient ≥40 mm Hg, or indexed AVA <0.6 cm2/m2) who underwent surgical AVR from January 1995 to June 2009 at our institution. Patients were divided into 4 groups depending on preoperative LVEF (<50% in 300 (15%) patients, 50-59% in 331 (17%), 60-69% in 908 (45%), and ≥70% in 478 (24%)). The primary end-point was all-cause mortality. During follow-up of 5.3±4.4 years, 1056 (52%) died. Five-year mortality rate increased with decreasing LVEF (41% (n=106), LVEF<50%); 35% (n=98), LVEF 50-59%; 26% (n=192), LVEF 60-69%; 22% (n=90), LVEF≥70%, p<0.0001). Compared to patients with LVEF≥60%, patients with LVEF 50-59% had increased mortality (HR 1.58, p<0.001), with a similar risk increase in both symptomatic (HR=1.56, p<0.001) and asymptomatic patients (HR 1.58, p=0.006, Figure). In a Cox regression analysis corrected for standard risk factors, LV mass index, AVA, and stroke volume index, LVEF was predictive of all-cause mortality (HR=0.89 per 10%, p<0.001). When this multivariable analysis was repeated in the subset of 1333 patients with no history of coronary artery disease, LVEF was still associated with all-cause mortality (HR=0.90 per 10%, p=0.009).

Conclusion:
In patients with SAS undergoing AVR, patients with LVEF 50-59% have also increased mortality compared to patients with LVEF>60%, suggesting that a different LVEF threshold should be used when referring for AVR.
Abstract 12506: Therapeutic Strategy for Efficient Reduction of Serum Uric Acid With Allopurinol versus Benzbromarone in Hyperuricemic Patients With Cardiovascular Disease ~ A Randomized Crossover Study (TERAO study) ~
Authors: Kojima Sunao , Kojima Shinobu , Soejima Hirofumi , Ogawa Hisao
Published: July 2021

Introduction:
Hyperuricemia is considered to be a marker of future cardiovascular events. Uricosuric agents and urate synthesis inhibitors has been widely used in hyperuricemic patients.

Hypothesis:
We assessed the hypothesis that the different mechanism of these drugs has an impact on urine albumin-creatinine ratio (ACR) associated with cardiovascular risks.

Methods:
A total of 14 hyperuricemic patients (serum uric acid levels >7 mg/dL) with cardiovascular disease were randomly assigned and treated with either benzbromarone, 25mg once daily, or allopurinol, 200 mg twice daily for 2 weeks, followed by a 2-week washout period, then a 2-week crossover phase.

Results:
Serum uric acid levels were comparable and similarly reduced with benzbromarone (8.4±1.1→4.8±1.3 mg/dL, P<0.0001) and allopurinol (8.4±1.0→5.1±0.9 mg/dL, P<0.0001). However, allopurinol significantly reduced urine ACR compared with benzbromarone (Figure 1). A logistic regression analysis revealed that influential clinical factors on reduced urine ACR were not observed except for allopurinol administration. The change of urine ACR was positively correlated with the change of urinary urate-creatinine ratio (UCR), indicating a substitution for xanthine oxidase activity (Figure 2).

Conclusions:
In this short-term, crossover study in hyperuricemic patients with cardiovascular disease, a treatment with xanthine oxidase inhibitor resulted in a reduction of urine ACR. These results represent a novel potential therapeutic approach with antioxidant strategy, which may lead to a reduction of future cardiovascular events. These preliminary findings require confirmation in larger clinical trials.
Abstract 12541: Features and Causes of Death of Patients With Atrial Fibrillation Seen in French Hospitals in 2012
Authors: Fauchier Laurent , Samson Adeline , Chaize Gwendoline , Gaudin Anne-Françoise , Vainchtock Alexandre , Bailly Cécile , Cotté François-Emery
Published: July 2021

Introduction/Hypothesis:
Atrial fibrillation (AF) has been associated with worse clinical outcomes in many cardiovascular (CV) disease states. There is a lack of data on real world specific causes of deaths in AF patients. The objective of this study was to provide features and causes of deaths of patients with AF seen in French hospitals.

Methods:
This French cohort study was based on the national hospitalization database (PMSI) covering hospital care for the entire population. All discharged dead patients in 2012 with a previous diagnosis of AF were identified. Cause of death was defined as the principal diagnosis of the last hospitalization stay. Thromboembolic risk scores (HAS-BLED, HEMORR2HAGES and ATRIA) and bleeding risk scores (CHADS2 and CHA2DS2-VASc) calculations were based on a 5-year look-back period of medical history.

Results:
In 2012, 533,044 AF patients were identified through the PMSI; among them 50,165 (9.4%) died in French hospitals. Deceased patients were older than patients discharged alive (82.3±9.3 vs. 78.0±11.4; p<0.001). They more often suffered from hypertension (73% vs. 70%), diabetes (27% vs. 24%), renal failure (39% vs. 23%), cancer (30% vs. 19%) and, liver failure (9% vs. 5%) (p<0.001 in all cases). Mean stroke and bleeding risk scores were significantly higher for dead patients: CHADS2 was 2.7±1.3 vs. 2.3±1.3 (p<0.001), CHA2DS2-VASc was 4.6±1.6 vs. 4.0±1.8 (p<0.001), HAS-BLED was 2.6±1.1 vs. 2.2±1.1 (p<0.001), HEMORR2HAGES was 3.0±1.4 vs. 2.3±1.5 (p<0.001) and ATRIA was 4.4±2.4 vs. 3.3±2.4 (p<0.001). Cardiovascular (CV)-related deaths represented 34% of all deaths, including heart failures (15.0%), strokes (8.5%), hemorrhages (1.4%) and, TIA/Systemic embolism (1.3%) (cf. Table1).

Conclusions:
In this systematic analysis of a real-life contemporary AF population, about 10% of deaths were related to stroke/TIA/SE. Despite CV events were a major cause of deaths; a greater part of deaths was related to non-CV causes.
Abstract 12583: C-Type Natriuretic Peptide Improves Left Ventricular Systolic and Diastolic Functional Performance at Rest and During Exercise After Heart Failure
Authors: Cheng Che Ping , Hasegawa Hiroshi , Morimoto Atsushi , Cheng Heng-Jie , Little William C
Published: July 2021

Background:
In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise (Ex). C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family produced by the vascular endothelium and heart is elevated in HF. However, its functional effects are unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and lusitropic actions may prevent this abnormal Ex response after HF.

Methods:
We assessed the effects of CNP on LV functional performance at rest and during submaximum Ex (3.5-5.5 mph for 6-8 min) in 10 instrumented dogs with pacing-induced HF. Since CNP mediated its biological actions via cGMP, we also measured plasma cGMP levels in response to CNP infusion at rest before and after HF.

Results:
CNP (2 μg/kg plus 0.4 μg/kg/min, iv, 20 min) caused a similar increase in cGMP levels before (7.2±3.8 to 24.7±4.9 pmol/ml) and after HF (20.2±4.4 to 71.6±5.0 pmol/ml). After HF, at rest, CNP reduced LV end-systolic pressure (P
ES
, CNP: 93 vs Baseline: 104 mmHg), arterial elastance (E
A
, 8.3 vs 11.7 mmHg/ml) and end-diastolic pressure (P
ED
, 37.2 vs 42.4 mmHg) (p<0.05). The peak mitral flow (dV/dt
max
, 201±51 vs 160±34ml/sec) was also increased due to decreased minimum LVP (LVP
min
, 17.1 vs 23.8 mmHg) and the time constant of LV relaxation (t, 40±4 vs 48±6 msec) (p<0.05). In addition, the slope of LV end-systolic pressure-volume relations (E
ES
) was increased (5.6±0.7 vs 4.2±0.9 mmHg/ml). The LV-arterial coupling, quantified as E
ES
/E
A
, was improved (0.69±0.22 vs 0.48±0.16) (p<0.05). The beneficial effects persisted during Ex. At matched levels of Ex, treatment with CNP, Ex-induced significantly less increases in P
ES
(ΔP= 3.4±0.5 vs 7.4±0.8 mmHg), mean LAP (ΔP= -3.1±2.2 vs 3.6±2.9 mmHg), and LVP
min
(ΔP= -3.6±1.4 vs 1.4±1.2 mmHg) (p<0.05). With CNP, t was much shortened (Δ= -0.8±4.0 vs 2.8±3.2 ms), and the peak mitral flow

was further augmented (ΔdV/dt
max
,

75±20 vs 43±12 ml/sec) (p<0.05).

Conclusion:
After HF, the generation of cGMP in response to CNP is not blunted. CNP produces arterial vasodilatation and augments LV contraction, relaxation, diastolic filling and LV arterial coupling, thus improving LV performance, both at rest and during Ex after HF.
Abstract 12650: Unexpected Response to Atrial Fibrillation Reduction in Patients With Cardiac Resynchronization Therapy
Authors: Assadi Hamid , Shenasa Hossein , Heidary Shahriar , Shenasa Mohammad
Published: July 2021

Background:
Cardiac resynchronization therapy (CRT) is known to improve left ventricular (LV) systolic function and symptoms of systolic heart failure. The effect of CRT on atrial fibrillation (AF) burden is less clarified.

Methods:
18 patients mean age of 77 ± 11 (72% male) underwent CRT implantations. There were no changes to concomitant anti-arrhythmic medication and permanent AF patients were excluded. Echocardiograms were obtained six month before and after device implantation. LV ejection fraction (LVEF), LV end diastolic dimension (LVEDd), left atrial (LA) dimension, and magnitude of mitral regurgitation (MR) were measured by echocardiogram before and after CRT. The burden of AF was evaluated by 24-hour Holter monitoring before and by device arrhythmic log after implantation. There were no concomitant medication changes. The results were later divided into presence (Group I) and absence (Group II) of paroxysmal or persistent AF. No patient was in permanent AF at the time of CRT implantation.

Results:
LVEF improved after CRT in both groups. Patients with AF showed the most beneficial effects of LVEF with average improvement of 41% (P-value=0.004) in comparison to 13% improvement in patients without AF (P-value=0.044). The LVEDd was improved by 11.9% in patients with AF (P-value=0.01) while it was improved by only 5.6% in patients without AF (P-value=0.08). LA Dimension was decreased by 4.4% in patients with AF (P-value=0.038). MR was reduced on average from moderate to mild for both groups. The number of AF episodes and duration of the AF were also decreased in all of our AF patients.

The pre and post effect of CRT in patients with and without AF is shown in the table below:

Conclusions:
The AF burden in patients who received CRT was significantly reduced. There were excellent correlations between improvement of LVEF, LVEDd, LA dimension, and AF burden. This may be due to LV and LA remodeling. Further studies need to elaborate the mechanisms of this finding.
Abstract 12659: Hepatoma-Derived Growth Factor Related Protein-3 as a Novel Endothelial Ligand
Authors: LeBlanc Michelle , Wang Weiwen , Guo Feiye , Shen Chen , Chen Rui , Wang Feng , Li Wei
Published: July 2021

Background:
Endothelial ligands extrinsically regulate a broad spectrum of vascular functions with therapeutic potentials, but are traditionally identified on a case-by-case basis with technical challenges. We recently developed open reading frame phage display (OPD) for unbiased identification of phagocytosis ligands. In this study, we identified hepatoma-derived growth factor related protein-3 (HRP-3) as a putative endothelial ligand by OPD. We hypothesized that HRP-3 is a novel endothelial growth factor, capable of promoting endothelial cell (EC) growth and migration.

Methods and Results:
We performed 3 rounds of
in vivo
phage binding selection in mice with an OPD library, screened enriched phage clones by next generation DNA sequencing, and identified HRP-3 as one of the putative endothelial ligands. To confirm the finding, clonal phages displaying HRP-3, VEGF and GFP were generated and analyzed for their binding to human umbilical vein endothelial cells (HUVECs). The results show that HRP-3-Phage and VEGF-Phage had significantly higher binding to HUVECs than GFP-Phage. Functional analysis showed that purified recombinant HRP-3 significantly increased the proliferation of HUVECs at 24 and 48 h, whereas VEGF induced significant growth only at 48 h. Consistent with these findings, HRP-3 significantly stimulated cell proliferation by MTT assay.
In vitro
wound-healing assay indicated that both HRP-3 (500 ng/ml) and VEGF (50 ng/ml) significantly promoted the migration of HUVECs into the denuded area. To dissect the downstream signaling pathway, we demonstrated that HRP-3 significantly induced ERK1/2 phosphorylation in HUVECs after 10 min treatment. Similar effects of HRP-3 and VEGF on EC growth, migration, and ERK activation were also verified using human aorta endothelial cells.

Conclusions:
Our findings demonstrate that HRP-3 is a novel ligand, capable of promoting proliferation and migration of ECs. The pro-growth effect of HRP-3 is at least partially mediated through ERK pathway activation. These results in turn support the broad applicability of OPD for the systematic discovery of endothelial ligands.
Abstract 12676: C-Terminal Residues of Phospholamban are Critical Determinants of the Quaternary Structure and Function of the Calcium ATPase Regulatory Complex
Authors: Abrol Neha , Smolin Nikolai , Ceholski Delaine K , Young Howard S , Robia Seth L
Published: July 2021

Rationale:
A naturally occurring missense Leu-39stop (L39X) mutation in phospholamban (PLB) results in truncation of the C-terminal transmembrane domain, leading to cardiomyopathy and premature death in humans.

Objective:
The goal of this study was to determine the structural and regulatory role of the C-terminal residues of PLB in the membranes of living cells.

Methods and Results:
We fused fluorescent protein tags to PLB and cardiac Ca
2+
ATPase (SERCA) to investigate the role of PLB C-terminal residues for membrane localization, PLB oligomerization and SERCA regulation. Alanine substitution of C-terminal residues significantly altered fluorescence resonance energy transfer (FRET) from PLB to PLB and SERCA to PLB. Notably, substitution mutation V49A had profound effects on pentamer structure and regulatory complex conformation, increasing and decreasing probe separation distance, respectively. Progressive deletion of only a few C-terminal residues resulted in significant loss of PLB membrane anchoring and mislocalization to the cytoplasm and nucleus. Selective permeabilization of the plasma membrane by saponin resulted in diffusion of fluorescently labeled PLB out of the cells, consistent with solubilization of truncated proteins. Molecular dynamics simulations recapitulated decreased bilayer anchoring for truncated PLB. C-terminal truncations resulted in progressive loss of PLB-PLB FRET, due to a decrease in the apparent affinity of PLB oligomerization. We quantified a similar decrease in the SERCA-PLB binding affinity, and loss of inhibitory potency as quantified by Ca
2+
-dependent ATPase activity. However, despite decreased SERCA-PLB binding, intermolecular FRET was paradoxically increased as a result of a 14.5 Å decrease in the distance between donor and acceptor fluorophores.

Conclusions:
We conclude that PLB C-terminal residues are critical for membrane anchoring and quaternary structure determination of PLB pentamer and PLB-SERCA regulatory complex. The loss of membrane registration restraint by C-terminal residues (especially V49) causes displacement of PLB to an alternative position on SERCA. The data are compatible with a model in which PLB binds to the canonical inhibitory binding site and an additional novel site.
Abstract 12680: Efficacy and Safety of Edoxaban Compared With Warfarin in Patients With Atrial Fibrillation and Heart Failure: Insights From Engage-AF TIMI 48
Authors: Magnani Giulia , Giugliano Robert P , Ruff Christian T , Murphy Sabina A , Nordio Francesco , Rutman Howard , Curt Valentin , ShI Minggao , Mercuri Michele , Braunwald Eugene , Antman Elliott M
Published: July 2021

BACKGROUND:
Atrial fibrillation (AF) and heart failure (HF) have emerged as the two epidemics of cardiovascular (CV) disease. The prevalence of AF increases with the severity of HF and contributes to HF disability. Among patients treated with vitamin K antagonists (VKAs), symptomatic HF is an independent risk factor for lower time in therapeutic range (TTR), which reduces the efficacy and safety of VKAs.

METHODS:
In the ENGAGE AF-TIMI 48 trial, both once-daily regimens of the direct oral factor Xa inhibitor edoxaban [high (HDE) and low dose (LDE)], were non inferior to warfarin (W) for prevention of stroke and systemic embolic events (SEE) in patients with AF and were associated with lower rates of bleeding. We evaluated the safety and the efficacy of edoxaban compared with W in patients with HF presenting with different severity of functional limitation (NYHA class).

RESULTS:
Among 21,105 patients enrolled 8,981(43%) had no history of HF, 9,489 (45%) had history of HF and a NYHA class I-II, whereas 2,635 (13%) had symptomatic HF with NYHA class III-IV. Patients with more severe HF symptoms had higher rates of stroke SEE, CV death and CV hospitalization (p<0.0005 for all) and among those treated with W we observed a lower mean TTR (62.6% vs. 70.0%, p<0.001). Compared with W, the efficacy of both edoxaban doses in reducing stroke or SEE was similar between patients with and without HF (HDE vs. W, p int=0.96; LDE vs. W, p int=0.63, Fig.) and there were no differences between NYHA classes. CV hospitalization was significantly reduced with HDE relative to W, without heterogeneity by different NYHA classes (p int=0.5, Fig.). Both edoxaban regimens reduced consistently major bleeding and intracranial hemorrhage, regardless of HF severity (Fig.).

CONCLUSION:
The relative efficacy and safety of both edoxaban regimens, compared to well-managed W in AF patients with HF, was consistent irrespective of the severity of functional class.
Abstract 12688: Long Term Use of Calcium Channel Blockers and Risk of Breast Cancer Development
Authors: Lam Uyen T , Knight Stacey , Bair Tami L , Le Viet T , Muhlestein Joseph B , Anderson Jeffrey L
Published: July 2021

Introduction:
Calcium channel blockers (CCBs) are a mainstay in treating hypertension (HTN). Recently, Li et-al published a population based case-control study (JAMA 2013; 289:2354) reporting CCB use to be associated with incident breast cancer (odds ratio 2.6). We prospectively analyzed 2 Intermountain Healthcare (IHC) databases (db) to confirm or refute this provocative report.

Methods:
Two separate analyses were conducted using general patients (GP) seen at IHC and patients undergoing coronary angiography (CV) at IHC facilities. Subjects were females aged 50-70 with no history of breast cancer. Those prescribed CCB were matched 1:1 to subjects not on CCB based on age, race, tobacco, alcohol, body mass index, HTN and follow up time. Multivariable Cox proportional hazards regression was used for the primary analysis of time to incident breast cancer by CCB use adjusting for history of other cancers and family history of breast cancer.

Results:
A total of 2612 GP subjects (cases/controls) and 1106 CV subjects (cases/controls) were studied. In the GP db, there was a statistically significant increased risk of breast cancer for subjects using CCB (HR=1.58; 95% CI: 1.10-2.26). Risk was also associated with a positive family history (HR=2.79; 1.96-3.97) and a personal history of cancer (HR=1.87; 1.07-3.26). Breast cancer predominantly developed in <5 y of follow up (64% of cases). However, a reverse relationship was found in the CV db, where the HR was 0.51 (95% CI: 0.27-0.97). This observation was found despite consistent associations with several secondary outcomes, including for incident diabetes, coronary and renal disease.

Conclusion:
A modest association between CCB use and incident breast cancer was observed in the GP db, but results were not reproducible in the CV db. Given lack of a credible mechanism and failure of previous randomized CCB studies to detect a signal, we interpret these modest and conflicting associations to likely represent uncorrected confounding, e.g. prescriber bias or drug interactions. Similarly, we believe the results of Li et-al may represent confounding. Given the important role of CCBs in clinical medicine, further studies are warranted, including randomized trials to assess CCB safety with respect to breast cancer risk.
Abstract 12691: The Combination of Depression and Diabetes is Associated With Short-Term Risk of Death and Myocardial Infarction Among Patients Undergoing Angiography for Acute Coronary Syndrome
Authors: May Heidi T , Knight Stacey , Anderson Jeffrey L , Horne Benjamin D , Le Viet T , Bair Tami L , Muhlestein Joseph B
Published: July 2021

Background:
Depression and diabetes have been shown to be associated with adverse cardiovascular (CV) events. However, whether there is an increased risk when both conditions are present is unknown.

Methods:
Patients of the Intermountain Heart Collaborative Study were studied if they underwent angiography for acute coronary syndrome (ACS) and had no prior history of CV disease (no CAD [coronary artery disease], MI [myocardial infarction], stroke, or heart failure). Patients were stratified based on their diabetes and depression status: none, diabetes only, depression only, and diabetes and depression. Multivariable Cox hazard regression was utilized to evaluate the association of diabetes/depression groups to death and MI at 30 days, 6 months, and 1 year.

Results:
A total of 4,321 (62.7% male; 61.3±12.9 years) patients were studied. The distribution of patients within each diabetes/depression category was: no depression or diabetes: 74.9% (3,236), diabetes only: 18.5% (800), depression only: 4.4% (192), diabetes and depression: 2.2% (93). A total of 46.2% presented with an MI and 61.4% were diagnosed with CAD. Those with both a diabetes and depression diagnosis were at greater risk of short-term death and, in particular, MI (Table).

Conclusion:
Among those without a history of CV disease undergoing angiography for ACS, the presence of both diabetes and depression indicated a higher risk of short-term death and, in particular, incident MI, than either one alone or neither diagnosis. Such patients may need greater care and evaluation following angiography for ACS in an effort to reduce short-term morbidity and mortality.
Abstract 12704: The Prognosis of Andersen-Tawil Syndrome is Not So Benign as Ever Thought
Authors: Kimura Hiromi , Itoh Hideki , Ohno Seiko , Fukuyama Megumi , Kato Kouichi , Ichikawa Mari , Fujii Yusuke , Makiyama Takeru , Horie Minoru
Published: July 2021

Rationale:
Andersen-Tawil syndrome (ATS) represents ventricular arrhythmia with abnormal U wave, periodic paralysis, and dysmorphysm, resulting from reduction of I
K1
current due to
KCNJ2
gene mutation. There are few reports about prognosis of ATS. In 2013, a French group reported that the prognosis of ATS was relatively benign under treatment. However, some our
KCNJ2
-positive patients show aborted cardiac arrest in their adult phase. Here, we examined long-term outcome in Japanese
KCNJ2
-positive ATS cohort.

Methods and Results:
In 32 probands with at least one of ATS features, we screened
KCNJ2, KCNQ1, KCNH2
, and
SCN5A
genes. Excluding 2 compound mutations and 1 double mutation cases, we found 14
KCNJ2
mutations in 23 probands (71%). We sent the inquiry sheet to all the attending physicians of probands and collected probands’ symptoms, ECGs, and history of cardiac events. For the average follow-up period of 79 months, four of 23 probands (17%) experienced syncope. Twenty-two of 23 (96%) patients showed ventricular arrhythmias, 10 patients (43%) showed periodic pararysis. We compared 23 probands dividing into two groups; one with syncope (n=4), another without syncope (n=19). There are no significant difference in gender, patient number of ventricular arrhythmia, periodic pararysis, and position of
KCNJ2
mutations. ECG findings such as HR (61bpm vs. 80 bpm), QTc (439 msec vs. 404 msec), QUc (668 msec vs. 650 msec), and Tpeak-Upeak interval (233 msec vs. 198 msec) showed no significant difference. The age of diagnosis was significantly higher in syncope group (32 ± 9 year old vs. 16 ± 10 year old, P=0.014). Aborted cardiac arrest (n=2, 50% vs. n=0, P=0.0046), beta blocker use (n=4, 100% vs. n=7, 37%, P=0.011) and ICD implantation (n=2, 50% vs. n=0, P=0.0046) were significantly higher in syncope group.

Conclusion:
We need to watch attentively
KCNJ2
positive probands even after childhood.
Abstract 12714: Early Repolarization With J-Point Elevation Predicts Mortality in the Hispanic Female Population
Authors: Shulman Eric , Aagaard Philip , Kargoli Faraj , Lener Steve , Fisher John , Gross John , Kim Sun , Palma Eugen , DiBiase Luigi , Ferrick Kevin , Krumerman Andrew
Published: July 2021

Introduction:
Early repolarization (ER) is associated with an increased risk of sudden cardiac death (SCD). However, the impact of ER may not be uniform across race and gender. An analysis from the Biracial Atherosclerosis Risk in Communities Study showed that ER was associated with SCD risk in Caucasians and highest in female Caucasians, while a study from Northern California found no association between cardiovascular mortality and ER in African Americans. Although Hispanics are the second largest segment of the population, little is known about the prevalence or prognostic implications of ER in this group. We investigated possible associations between automated ECG ER readings, defined as J-point elevation with ST segment elevation and overall mortality.

Methods:
ECG and EMR databases from a regional medical center from a largely Hispanic population were interrogated. Inclusion criteria included Hispanic ethnicity, age over 18 from 2000-2011. Outcomes were assessed using a Cox Proportional Hazards model with data from the Social Security Death Index.

Results:
There were n=34,354 Hispanics of which n=544 (1.6%) had ER. When controlling for age, gender, height/weight, systolic/diastolic BP, PR, QRS, QTc, heart rate, ejection fraction, CAD, CHF, myocardial infarction, DM, and malignancy there was no significant difference in mortality between overall subjects with and without ER (HR: 1.15, 95% CI: 0.89-1.50, p=0.294). However, significant interactions were present between gender and ER. In a multivariate regression model, ER was significantly predictive of overall mortality in females (HR: 1.91, 95% CI: 1.24-2.90, p=0.003), but not in males (HR: 0.88, 95% CI: 0.63-1.23, p=0.456) (Figure 1).

Conclusions:
ER is not associated with an increased risk of death in the overall Hispanic population; however, there is a higher risk of overall mortality in female population. ER may be more complex than initially suspected, which emphasizes a need for additional research.
Abstract 12797: Temporal Changes in Mortality Risk Post-Discharge After Hospitalization for Heart Failure
Authors: Cook Thomas D , Kalogeropoulos Andreas P , Fonarow Gregg C , Zea Ryan , Swedberg Karl , Zannad Faiez , Khan Hassan , Maggioni Aldo P , Konstam Marvin A , Gheorghiade Mihai , Butler Javed
Published: July 2021

Importance: In observational studies, the risk for adverse events among patients admitted for heart failure (HF) is highest immediately post-discharge and declines over time. This ‘vulnerable phase’ concept has led to research and quality of care initiatives focusing primarily on early post-discharge period. However, whether this risk trajectory represents lowering of individual patient risk or changes in the population risk profile is not known.

Methods:
Survival and longitudinal models were used to assess temporal changes in mortality risk post-discharge in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Post hoc analysis of EVEREST included 4017 patients >18 years old discharged alive after hospitalization for HF with an ejection fraction of <40% at 359 sites from 2003-2006 and randomized to receive oral tolvaptan or placebo.

Results:
After a median of 9.8 months, 971 patients died (24.2%). Mortality at 1 year was 24.2%. Cumulative mortality rate declined from 15.9/100 patient-years immediately post-discharge to 13.4 at 30 days and 12.8 at 90 days; it rose steadily thereafter. The risk variation between quintiles of baseline risk was considerably larger than the temporal variation within risk strata. In a longitudinal model assessing updated mortality risk after each follow up visit, mortality risk increased during the 90 days preceding readmission and then followed a trajectory similar to the index admission. The net increase in mortality attributable to readmission was ~37%.

Conclusions and Relevance:
Among hospitalized HF patients, although there is a transiently elevated risk in 90 days before and after discharge, the patient’s clinical risk profile rather than temporal change remains the main determinant of mortality risk.
Abstract 12801: Angled Lesions Have Higher Incidence of Vascular Injury and Incomplete Stent Apposition, as Compared to Non-Angled Lesions, Following Stenting: An Optical Coherence Tomography Study
Authors: Minami Yoshiyasu , Uemura Shiro , Lee Stephen , Kim Soo Joong , Park Chang-Bum , Dauerman Harold L , Jang Ik-Kyung
Published: July 2021

Backgrounds:
Angled lesions are reported to be associated with worse procedural and clinical outcomes. Recent
ex vivo
studies have demonstrated that an angled arterial wall is exposed to imbalanced mechanical stress, which can cause vessel injuries and incomplete stent apposition (ISA) following stent implantation.

Hypothesis:
We tested the hypothesis that the angled coronary lesions, compared to non-angled lesions, would have higher incidence of vascular complications and ISA following stent implantation using optical coherence tomography (OCT) in patients.

Methods:
A total of 245 lesions treated with a single DES [95 zotarolimus-eluting stent (ZES) and 150 everolimus-eluting stent (EES)] were analyzed using OCT. An angled lesion was defined as a lesion on a curve ≥45° (n=59) on an angiogram and non-angled lesion on a curve <45° (n=186). The frequency was expressed as the percentage of stents with at least one type of injury or strut malapposition. Vessel injury included edge dissection, in-stent dissection, thrombus, and tissue protrusion. ISA was defined when the distance between the center of strut and the vessel wall was >100μm in ZES and >90um in EES.

Results:
The incidence of edge dissection and tissue protrusion was not significantly different between the groups. However, the incidence of in-stent dissection (84.7% vs 63.4%, P<0.01), thrombus (55.9% vs 35.5%, P<0.01) and ISA (76.3% vs 44.6%, P<0.001) was significantly higher in the angled group. The multivariate analysis demonstrated that the lesion on angle ≥60° was the independent predictor for in-stent dissection [Odds ratio (OR) 4.37, P=0.03] and ISA [OR 7.37, P<0.01], and that the angle ≥45° was the independent predictor for thrombus [OR 2.94, P=0.01]. There was no difference in the OCT findings between the ZES and EES groups.

Conclusion:
Angled coronary lesions had higher incidence of in-stent dissection, thrombus and ISA compared with non-angled lesions following DES implantation as assessed by OCT.