bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18078: Strain rather than Diastolic Parameters correlates with Heart Failure Risk Factors
Authors: Yang Hong , Negishi Kazuaki , Nolan Mark , Wang Ying , Wright Leah , Marwick Thomas
Published: July 2021

Background:
Stage B heart failure (SBHF) is currently defined by structural heart disease (previous MI, LV remodelling, hypertrophy and low EF). The roles of functional measures (global longitudinal strain [GLS] and diastolic dysfunction [DD]) as markers of SBHF are undefined.

Method:
Pts >65 yo with ≥1 HF risks (hypertension, type 2 diabetes, obesity, previous chemotherapy, F/H of HF or previous cardiac history) were recruited from the local community. All subjects underwent questionnaires, 6-minute walk (6MW) and echocardiography. Abnormal echo was defined by GLS (-18%), LV mass index (LVMI) (95 for female, 115 for male, g/m2), 6MW (455 meters), E/e’ (12, medial), DecT (<140 or >240 ms) and LAVI (≥32 ml/m2).

Results:
Of 236 pts (age 71±5, 47% men), 22% had one, 42% had two and 36% had >2 listed HF risk factors. There were significant associations of #HF risks with reduced GLS (p=0.008 for trend), increased LVMI (p=0.002) and shorter 6MW (p=0.004). There were no significant associations with diastology measurements, including increased mitral annular E/e’ (p=0.67), deceleration time (p=0.61) and mitral E/A (p=0.46) (Table). The relative risk of abnormal GLS in those with more than one risk is 1.38 (95%CI 1.05-1.81; p=0.019), increased LVMI 1.31 (1.00-1.74; p=0.055), shorter 6MW 1.22 (0.99-1.49; p=0.059).

Conclusion:
In asymptomatic pts with HF risks, GLS (but not DD) showed an association with number of risks, similar to LVMI and 6MW distance.
Abstract 18096: Screening of Abdominal Aortic Aneurysm during Transthoracic Echocardiography
Authors: Kato Takao , Kimura Masahiro , Funasako Moritoshi , Nakane Eisaku , Izumi Toshiaki , Haruna Tetsuya , Inoko Moriaki
Published: July 2021

Introduction:
We previously reported that the prevalence of abdominal aortic aneurysm (AAA) in patients who underwent scheduled transthoracic echocardiography (TTE) was higher than that of AAA in patients who underwent abdominal ultrasonography (AUS). However, the patient backgrounds differed significantly between the two groups.

Hypothesis:
We hypothesized TTE detected AAA as similarly as AUS, one of standard methods for the screening of AAA.

Methods:
A total of 7,619 patients who were scheduled for TTE from 2009 to 2010 in our hospital were prospectively included. The abdominal aorta was evaluated at the end of the routine protocol. All patients who received scheduled abdominal ultrasonography (AUS) during the same period, a total of 15,433 patients, were included. The patients with known AAA and those without consent were excluded. In order to compare the TTE group to AUS group, we developed a propensity score for profiles of patients who received TTE or AUS for potential confounding bias. Specifically, a multivariate logistic regression model was fit with TTE or AUS as a dependent variable, which included age, sex, numbers of comorbidities, and the presence of each comorbidity. Consequently, 4,388 patients in each group were matched for analyses.

Results:
In propensity-matched patients, AAA was detected in 59 patients of TTE group and 48 patients of AUS group and the prevalence of the detection of AAA was not different between TTE and AUS (p=0.331). Positive associations were observed between AAA detected and male sex (adjusted odds ratio [OR], 3.25; 95% CI, 2.05-5.15; P<.001), older age (adjusted OR, 1.029; 95% CI, 1.01-1.046; P<.001), having ischemic heart disease (adjusted OR, 1.78; 95% CI, 1.04-3.03; P=0.033), and having hypertension (adjusted OR, 2.16; 95% CI, 1.38-3.38; P=001).

Conclusions:
TTE detected AAA as similarly as AUS. This result suggested that additional examination of the abdominal aorta during scheduled TTE was efficient for the screening of AAA.
Abstract 18110: Impact of Stroke Severity on Clinical Outcomes in Patients who had Infective Endocarditis With Cerebral Complications
Authors: Murai Ryosuke , Funakoshi Shunsuke , Kaji Shuichiro , Sasaki Yasuhiro , Kim Kitae , Kitai Takeshi , Kobori Atsushi , Ehara Natsuhiko , Kinoshita Makoto , Tani Tomoko , Koyama Tadaaki , Furukawa Yutaka
Published: July 2021

Background:
The treatment strategy in active infective endocarditis (IE) with cerebral complications still remains unclear. We sought to analyze the association of the neurological deficit level with the clinical outcomes in IE patients with stroke.

Methods and Results:
Clinical data were retrospectively reviewed in 141 consecutive patients with active left-sided IE with cerebral complications. To evaluate the severity of stroke, the National Institute of Health Stroke Scale (NIHSS) was assessed in all patients on admission. There were 116 (82%) patients with cerebral infarction including 9 hemorrhagic infarctions and 57 (40%) patients with cerebral hemorrhage. We divided the patients according to NIHSS; severe stroke group (NIHSS>16: n=19) and non-severe stroke group (NIHSS≤16: n=122). Early surgery in the active phase (within 2 weeks after the initial diagnosis) was performed in 64 patients (6 severe stroke group and 58 non-severe stroke group), and the conventional treatment strategy was applied in 77 patients (13 severe stroke group and 64 non-severe stroke group). In the conventional treatment group, 37 patients (36 severe stroke group and 1 non-severe stroke group) underwent late surgical intervention. A mean follow-up period was 4.5 years. In-hospital death was significantly lower in non-severe stroke group (12% versus 53%, p<0.001). In addition, the freedom rate from IE-related death was significantly higher in patients with non-severe stroke than those with severe stroke (84±4 % versus 37±13 % at 5-year, p<0.001). Multivariate Cox proportional hazard analysis showed that NIHSS (HR=1.074; 95% CI 1.042-1.107: p<0.001), logistic EuroSCORE (HR=1.026; 95% CI 1.010-1.042: p=0.002), conventional treatment (HR=3.478; 95% CI 1.477-8.193: p=0.004), and aortic valve involvement (HR=3.091; 95% CI 1.460-6.546: p=0.003) were significantly associated with IE-related mortality (p<0.001).

Conclusions:
Severity of stroke was strongly associated with clinical outcomes in IE patients with cerebral complications. Therapeutic strategy for IE patients with stroke might have to be customized according to severity of neurological deficit.
Abstract 18141: Is There Systolic Myocardial Mechanical Dysfunction in Patients With Different Degrees of Diastolic Dysfunction and Normal Ejection Fraction?
Authors: Barros-Gomes Sergio , Pellikka Patricia A , Dispenzieri Angela , Villarraga Hector R
Published: July 2021

Introduction:
Diastolic dysfunction has been characterized in relation to the relaxation and compliance properties of the left ventricle; limited information exists regarding its relationship to systolic function as assessed by deformation imaging.

Objectives:
To determine if there is left ventricular systolic dysfunction detected by global longitudinal strain (GLS) measured by two dimensional speckle tracking echocardiography in patients with immunoglobulin light chain (AL) amyloidosis with different degrees of diastolic dysfunction and normal ejection fraction (EF).

Methods:
Consecutive biopsy-proven AL patients with preserved EF (≥ 55%) who had a comprehensive echocardiogram performed and strain analysis were included. Cohort was divided into 5 groups according to the different grades of diastolic dysfunction: Group 0: normal filling pressures; Group 1: abnormal relaxation; Group 2: pseudo-normal pattern; Group 3: reversible restrictive; Group 4: fixed restrictive. Images were acquired and performed on a Vivid 9 from the 3 apical views, and analyzed on vendor-specific software (Echo-PAC, GE). GLS was averaged from the 16 segments, and their means compared by ANOVA and each pair with Student’s t test.

Results:
A total of 858 patients were included, mean age was 63.7 years ± 10.1, and 61.5% were male. From those, 205 (24%) were in group 0; 299 (35%) in group 1; 255 (30%) in group 2; 65 (7%) in group 3; and 34 in group 4 (4%). GLS means measurements were -18.95 ± 2.4, -16.86 ± 3.4, -15.60 ± 3.9, -12.31 ± 3.0, and -10.48 ± 3.3, respectively (P<0.0001). All individual GLS values were significantly different statistically when compared between each group (P<0.01 for all pairs; figure).

Conclusions:
Longitudinal systolic mechanical function is progressively impaired in AL amyloid patients as diastolic dysfunction progresses, despite normal EF. This systolic dysfunction provides insights into the intrinsic relationship between the components of the cardiac cycle.
Abstract 182: Prehospital Intravenous Epinephrine May Boost Survival of Patients with Traumatic Cardiopulmonary Arrest
Authors: Chen Shi-Yi , Chen Yen-Pin , Chiang Wen-Chu , Ko Patrick Chow-In , Wang Hui-Chih , Yang Chih-Wei , Huang Edward Pei-Chuan , Chong Kah-Meng , Liu Sot Shih-Hung , Chen Wei-Ting , Chen Jiun-Wei , Lee Yi-Chia , Hsieh Ming-Ju , Ma Matthew Huei-Ming
Published: July 2021

Background:
Prehospital resuscitation for patients with major trauma emphasized load-and-go principle. However, for those with traumatic cardiopulmonary arrest (TCPA), the role of prehospital intravenous epinephrine (PIE) remained unclear. This study aimed to evaluate the effectiveness of PIE in patients with TCPA.

Method:
We analyzed data from an Utstein registry for out-of-hospital cardiac arrest in Taipei to test the association between PIE and outcomes of TCPAs. Enrollees were adult patients (≧18 year-old) with TCPA. Patients with signs of obvious death like decapitation or rigor mortis, or with existing do-not-resuscitation order were excluded. Primary outcome was survival to admission, and secondary outcome was survival to discharge. A subgroup analysis was performed by stratified total prehospital time.

Result:
From Jun 1, 2010 to May 31, 2013 there were total 514 cases enrolled. PIE was administrated in 43 (8.4%) cases. Patients who received PIE were more likely with witnessed collapse, initial shockable rhythm, placement of advanced airway, longer total prehospital time and less blunt injury. Patient number with survival to admission and survival to discharge was 101 (19.6%) and 20 (3.9%), respectively. In parsimonious models, the adjusted odds ratios (AOR) of PIE was 2.57 (95% confidence interval (CI) 1.24-5.31) on primary outcome (Figure 1), and 3.53 (95%CI 0.84-15.47) on secondary outcome. Subgroup analysis showed increased ORs of PIE in cases with longer prehospital time (Figure 2).

Conclusion:
Among patients with TCPA, PIE was associated with increased survival to admission in an Asian metropolitan area, especially for those with longer prehospital time.
Abstract 18218: In Vitro Characterization of Andexanet Alfa (PRT064445), a Specific fXa Inhibitor Antidote versus Aripazine (PER977), a Non-specific Reversal Agent
Authors: Lu Genmin , Kotha Jayaprakash , Cardenas Juan M , Herr Michael J , Pandey Anjali , Curnutte John , Conley Pamela B , Jennings Lisa K
Published: July 2021

New oral fXa inhibitors have been increasingly adopted for VTE or AF treatment in the outpatient setting instead of warfarin. Andexanet alfa (AnXa) is a modified, recombinant human fXa molecule developed as a specific antidote to reverse anticoagulant activity of fXa inhibitors during episodes of serious bleeding or before urgent surgery. PER977, a small molecule under development by Perosphere, Inc., is reported to reverse the effect of a broad range of anticoagulants (fXa and thrombin inhibitors, LMWH). In order to compare AnXa and PER977 mechanisms of action, we studied the in vitro activity of both agents in the presence or absence of fXa inhibitors rivaroxaban, apixaban, edoxaban or enoxaparin. In a buffer system containing purified human fXa with physiologic Ca
2+
(5 mM), AnXa dose-dependently reversed oral fXa inhibitor activity. Reversal activity was not observed for any fXa inhibitor with PER977 over a wide concentration range (≤2 mM). In human plasma, AnXa reversed both direct and ATIII-dependent fXa inhibitors, whereas no reversal effect by PER977 was detected. In the absence of a fXa inhibitor, PER977 potentiated fX activation by fIXa in a buffer system (purified human fX, fIXa and 5mM Ca
2+
). Similar cofactor activity was observed with polylysine, indicating that PER977 may have properties similar to poly-cationic molecules. Procoagulant activity was observed in human plasma with PER977 at low concentrations (≤100 μM) as measured by clotting (aPTT) or thrombin generation, but inhibition in these assays was seen at higher concentrations ( ~1 mM). PER977 also potentiated human platelet activation as determined by P-selectin expression induced by 10 μM ADP. Platelet aggregation, whole blood hemolysis, or complement activation testing showed no effect with either AnXa or PER977. These data indicate that PER977 does not reverse the anticoagulant activity of a direct or indirect fXa inhibitor in vitro. Its observed in vivo effect on blood loss in animals may not be mediated by direct interaction of PER977 with the inhibitor, but may be in part attributed to an off-target effect, suggested by its potential procoagulant activity. In contrast, AnXa acts as a specific antidote to fXa inhibitors by sequestering them with a defined stoichiometry (1:1 molar ratio).
Abstract 18229: Heart Transplantation for Genetic Cardiomyopathies is Associated With Favorable Long-Term Survival and Graft Outcomes
Authors: Taimeh Ziad , Vakil Kairav , Martin Cindy , Jain Renuka , Colvin Monica
Published: July 2021

Introduction and hypothesis:
Genetic cardiomyopathies (GNCM) are a spectrum of myocardial disorders that can lead to heart failure, and frequently portend the need for heart transplantation. Post-transplant outcomes in this subgroup of patients have not been examined in a large, multicenter transplant cohort.

Methods:
Patients who underwent first-time heart transplantation in the United States between 1987 and 2012 were retrospectively identified from the United Network for Organ Sharing database. Patients with hypertrophic cardiomyopathy (HOCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular non-compaction (LVNC) constituted the GNCM group. Primary outcome was survival. Secondary outcomes included rejection, cardiac allograft vasculopathy (CAV), and graft failure.

Results:
Of the 49,417 transplant recipients identified, 997 recipients (mean age 36±20 years; 55% males; 79% Caucasian) had GNCM (HOCM n=836; ARVC n=83; LVNC n=78). Patients transplanted for GNCM had significantly higher 1, 5 and 10 year survival rates compared to those without GNCM (86%, 76%, 66% vs. 82%, 69%, 50%, respectively, log-rank p<0.001) (Figure 1A). After adjusting for age, sex, and race in multivariate Cox regression analysis; GNCM was associated with favorable post-transplant survival, with a hazard ratio of 0.70 (95% confidence interval 0.58-0.86; p=0.001). While the incidence of rejection was similar in GNCM compared to non-GNCM (43% vs. 40%, p=0.11), the incidences of CAV and graft failure were significantly lower compared to non-GNCM (24% vs 32%, p<0.001, and 9% vs 15%, p<0.001, respectively). The survival rates for HOCM, ARVC, and LVNC, were all similar to each other but significantly higher compared to non-GNCM (log-rank p<0.001) (Figure 1B).

Conclusions:
Patients with GNCM seem to have better post-transplant survival and graft outcomes than patients transplanted for other cardiomyopathies.
Abstract 18247: Inhibition of PKCβ2 Attenuates Myocardial Ischemia Reperfusion Injury in Diabetic Rat Through Cavolin-3-dependant Akt Activation
Authors: Liu Yanan , Jin Jiqin , Li Haobo , Huang Huansen , Irwin Michael G , Xia Zhengyuan
Published: July 2021

Background:
Activation of PKCβ has been shown to play a critical role in myocardial ischemia/reperfusion (MI/R) injury in hearts from non-diabetic rodents. Our recent studies showed that PKCβ2 is overexpressed in the myocardium of diabetic rats that were associated with more severe post-ischemic MI/R injury relative to non-diabetic rats. We hypothesized that myocardial PKCβ overexpression is a major contributor responsible for the exacerbation of MI/R injury in diabetes and that PKCβ inhibition can attenuate MI/R injury in diabetes.

Methods and results:
Five-week streptozotocin-induced diabetic rats were treated with the selective PKCβ inhibitor ruboxistaurin (RBX, 1 mg/kg/day delivered via oral gavage) for 4 weeks, starting from 1 week after diabetes induction, before inducing MI/R achieved by 30 min of left descending coronary artery ligation followed by 2 hours of reperfusion. Cardiac function was measured using pressure-volume conductance system. In
in vitro
study, cardiac H9C2 cells were exposed to high glucose (30 mM/L) and subjected to 4 hours hypoxia followed by 4 hours reoxygenation (H/R) in the with or without selective PKCβ2 inhibitor CGP53353 (1 mol/L), siRNAs of PKCβ2 or Caveolin (Cav)-3. Cell apoptosis and mitochondrial transmembrane potential were respectively assessed by TUNEL and JC-1 staining. At the end of reperfusion, RBX significantly decreased myocardial infarct size (% of area at risk, 35±5% vs. 49±3% in control,
P
<0.05) and attenuated cardiac dysfunction, and increased cardiac protein expression of Cav-3 and phosphorylated/activated Akt (p-Akt) in diabetic rats (All
P
<0.05 vs. control). H/R significantly increased H9C2 cell injury under high glucose condition evidenced as increased TUNEL-positive and JC-1 monomeric cells (All
P
<0.05 vs. control), which was associated with increased PKCβ2 phosphorylation and decreased Cav-3 protein expression. Either CGP53353 or PKCβ2 siRNA significantly attenuated all these changes and enhanced p-Akt. Cav-3 gene knockdown significantly reduced p-Akt and increased post-hypoxic cell injury despite of concomitant reduction in PKCβ2 phosphorylation.

Conclusions:
PKCβ2 inhibition with RBX protects diabetic hearts from MI/R injury through Cav-3-dependent activation of Akt.
Abstract 18257: Cardiovascular Response to Energy Drink Consumption in Healthy Adults
Authors: Svatikova Anna , Covassin Naima , Somers Krishen , Soucek Filip , Kara Tomas , Ruzek Lukas , Bukartyk Jan
Published: July 2021

Introduction:
An increasing number of healthy adults consume energy drinks to enhance their physical and mental performance. Energy drinks contain caffeine and multiple other “natural” stimulants and their combined effects on cardiac hemodynamics in healthy individuals are unclear.

Hypothesis:
We hypothesized that drinking a commercially available energy drink,
Rockstar
, compared to a placebo drink, increases resting blood pressure and heart rate in healthy adults, and these increases would be further accentuated by stress conditions.

Methods:
We enrolled 25 healthy, normotensive subjects (14 males), aged 29±1 years, with body mass index 24.5±1 kg/m
2
, in a randomized, double-blind, placebo-controlled, crossover study. Each subject consumed a placebo drink and a commercially available
Rockstar
energy drink (473 ml), in random order on two separate study days. Blood pressure and heart rate responses were recorded and compared before and 30 minutes after drink consumption, both at rest and then in response to physical, mental and cold stressors.

Results:
The
Rockstar
energy drink induced a 6±1% increase in resting systolic blood pressure, compared to 3±1% with the placebo drink (P=0.0078). Diastolic blood pressure increased by 7±1% vs 0±1% with the placebo drink (P=0.0007; Figure 1). Heart rate increased similarly in both groups, by 5±2% in the energy drink group vs. 7±2% in the placebo group. Blood pressure and heart rate increases during the stress stimuli (sustained handgrip, mental stress and cold stress) did not differ between energy drink and placebo.

Conclusions:
Drinking a commercially available
Rockstar
energy drink significantly increases resting blood pressure in young healthy adults. Blood pressure increases are not further accentuated by exercise, mental or cold pressor stress stimuli. These hemodynamic changes induced by energy drink consumption could predispose to cardiovascular events.
Abstract 18291: Computed Tomography Angiography Can Replace Cardiac Catheterization in the Surgical Planning of Select Neonates with Major Aortopulmonary Collaterals
Authors: Bauser-Heaton Holly , Peng Lynn , Perry Stanton B , Feinstein Jeffrey A , Hanley Frank L , Chan Frandics P
Published: July 2021

Introduction:
Neonates with Tetralogy of Fallot (TOF) and major aortopulmonary collaterals (MAPCAs) routinely undergo cardiac catheterization in the neonatal period. We have recently incorporated CT angiography into the neonatal evaluation with the hope of eliminating catheterization in those not needing neonatal intervention. We reviewed our experience with CT angiography and its accuracy in determining the need for neonatal intervention.

Methods:
Retrospective review of all patients from April 2005-October 2013 with MAPCAs who had both CTA and cardiac catheterization during the first 120 days of life and within 14 days of one another. The radiologist and interventionalist responsible for reading the studies were blinded to the results of the procedures and each other’s readings. The need for neonatal intervention as predicted by CTA was compared to the ultimate, cath-based decision.

Results:
19 patients (mean age 3.73 days, range 1-9 days of age) were included in the study. In all patients CT was able to predict the need for surgical intervention correctly. CTA was found to be 87% sensitive, 93% specific and 91% sensitive with respect to number of MAPCAs, origin and distribution.

Conclusion:
CT angiography can accurately predict the need for neonatal intervention. In those not requiring neonatal intervention, neonatal cardiac catheterization is not required. CTA may also aid in guiding the subsequent, pre-operative catheterization but cannot replace it. This algorithm eliminates neonatal catheterization in the majority of TOF/MAPCAs patients, and with it the associated risks, and radiation, as well as substantially reducing the cost of the initial hospitalization.
Abstract 18342: Inducible Cardiomyocyte-Specific Deletion of Stromal Interaction Molecules Results in Cardiomyopathy in Mice
Authors: Murugesan Saravanakumar , Sullivan Ryan D , Mancarella Salvatore
Published: July 2021

Background:
Stromal interaction molecules (STIM1 and STIM2) are sarco/endoplasmic calcium sensors ubiquitously expressed in mammalian cells. Upon Ca2+ store discharge STIM proteins oligomerize in proximity of the plasma membrane to activate the Ca2+ selective channels (Orai) and trigger Ca2+ entry. While this mechanism is widely accepted to be the main source of calcium in non-excitable cells, in cardiomyocytes the calcium-induced calcium-release is the major controller of myocardial function, and the presence of STIM in these cells appears somewhat puzzling. Here we investigated the role of STIM in cardiomyocytes and its role in regulating cardiac contractility and intracellular Ca2+ dynamics.

Methods:
We have generated an inducible cardiac-specific STIM1 knockout (STIM KO) mouse model to elucidate the role of STIM in the myocardium. Echocardiography was used to evaluate structure and function of the left ventricle. Heart rate was monitored continuously in conscious mice by telemetry. Cell dimensions, shortening, and relaxation were determined by videomicroscopy and calcium transients by fura 2.

Results:
Echocardiographic analyses revealed development of dilated cardiomyopathy with a significant reduction of left ventricular fractional shortening (39.91±4.05% vs. 22.41±7.92%, p<0.01). Histological and morphological analyses confirmed a dilated cardiomyopathy characterized by enlarged ventricular chambers. Electrocardiography showed higher heart rate in the STIM1 KO mice with no differences in P-wave duration and QRS interval while Q-T interval was reduced in the STIM1 KO mice as compared to the WT mice. Sarcomere length and cell shortening measurements in freshly isolated cardiomyocytes from STIM1 KO mice confirmed the reduced contractility associated with a reduction of time to 50% relaxation (283±13ms vs. 258±8ms, p<0.05) . Intracellular calcium transient analysis in STIM1 KO cardiomyocytes showed a higher peak amplitude and a time to 50% decay of calcium significantly accelerated.

Conclusions:
Our data demonstrate that STIM proteins play an important role in the maintaining normal cardiac function in the adult heart and reveal that STIM plays an important role during cardiac repolarization.
Abstract 18371: Higher Treatment Persistence of Non-Vitamin K Antagonist Oral Anticoagulants than Vitamin K Antagonists at 1 Year in Non-Valvular Atrial Fibrillation in Real-World Practice
Authors: Martinez Carlos , Wallenhorst Christopher , Katholing Anja , Freedman Ben
Published: July 2021

Introduction:
Oral anticoagulants (OAC) are under-utilised in atrial fibrillation (AF). Even patients prescribed an OAC may stop taking the drug soon after treatment initiation, particularly with Vitamin K Antagonists (VKA). The Non-VKA OAC (NOAC) drugs offer greater ease of use, and persistence is likely to be higher.

Aim:
To determine persistence on treatment in the first year after inception of NOACs and VKA in incident AF in real-world clinical practice.

Methods:
We studied 24,467 OAC-naïve patients with incident non-valvular AF diagnosed between Jan 2011-Feb 2014, mean age 73.9 ± 12.5, 45.6% female, in a very large UK primary care database (Clinical Practice Research Datalink, CRPD), with full linkage to medication use. Follow up was for a mean of 1.2 ± 0.9 years. The proportion of OAC initiation in the 90 days after first-time AF and of those remaining on OAC one year after initiation were estimated using competing risk survival analyses censoring for use of alternative OAC.

Results:
NOAC drugs prescribed included Rivaroxaban, Dabigatran and Apixaban. Overall, 12,579 (51.4%) were commenced on an OAC: 11,888 on VKA and 691 on NOAC, within 90 days after incident AF. Amongst all OAC users, the proportion taking NOAC increased from 0.3% in 2011 to 12.3% in 2014. Persistence, defined as the proportion still taking the OAC after one year, declined over the 12 months to 54.3% for VKA and 80.7% for NOAC (Table). Persistence was significantly greater for NOAC than VKA at all time points.

Conclusions:
There is a progressive fall in VKA use amongst OAC naïve patients with AF in real-world practice to only 54% at 1 year. This contributes to under-utilisation of anticoagulation in AF and would result in an increased rate of stroke. Persistence was significantly improved with NOACs compared to VKA, and this factor alone could lead to reduced stroke burden with increasing uptake of the NOACs.
Abstract 18390: Ang II activates the RhoA Exchange Factor Arhgef1 in Humans
Authors: Carbone Maria-Luigia , Brégeon Jérémy , Devos Nabila , Blanchard Anne , Azizi Michel , Pacaud Pierre , Jeunemaitre Xavier , Loirand Gervaise
Published: July 2021

Introduction:
Although a causative role for RhoA-Rho kinase signaling has been recognized in the development of human hypertension, the molecular mechanism(s) as well as the RhoA exchange factors (GEFs) responsible for the over activation of RhoA remain unknown. Arhgef1 has been recently identified as a RhoA GEF involved in Ang II-mediated regulation of vascular tone and hypertension in mice.

Hypothesis:
Here we assessed the hypothesis that Arhgef1 is activated and involved in the activation of RhoA-Rho kinase signaling by Ang II in humans.

Methods:
We used in vitro stimulation of human coronary artery smooth muscle cells and human peripheral blood cells (PBMC) by Ang II (0.1 μmol/L), and PBMC isolated from normotensive subjects before and after activation of the renin-angiotensin system by a low-salt diet for 7 days (checked by the increase in plasma aldosterone and active renine). Activation of Arhgef1 was monitored by measuring its tyrosine phosphorylation by western blot and phosphorylation of the Rho kinase target MYPT was used to measure the activity of RhoA/Rho kinase signaling.

Results:
In vitro, Ang II induced activation of Arhgef1 in human vascular smooth muscle cells and PBMC. Silencing of Arhgef1 expression by siRNA in human vascular smooth muscle cells inhibited Ang II-induced activation of RhoA-Rho kinase signaling (0.67±0.12 vs 3.21±0.91relative to unstimulated condition, n=4, P<0.05). In normotensive subjects, activation of the renin-angiotensin system by a low-salt diet stimulated Arhgef1 activity in PBMC (1.26±0.12-fold over basal level, n=39, P<0.05). This activation was associated with an increase activity of RhoA-Rho kinase signaling (1.33±0.14-fold over basal level, n=39, P<0.05).

Conclusions:
Our results show that Ang II stimulates Arhgef1 activity and strongly suggest that Arhgef1 mediates Ang II-induced RhoA activation in humans. Moreover, we show for the first time that measurement of RhoA GEF activity in PBMC might be a useful method to evaluate RhoA GEF activity in humans.
Abstract 18479: Cohort Under-Ascertainment of Prevalent Atrial Fibrillation Using the Baseline 12-Lead ECG: Implications for Atrial Fibrillation “Prediction”
Authors: Dukes Jonathan W , Whooley Mary A , Marcus Gregory M
Published: July 2021

Introduction:
Many major cohort studies base their ascertainment of prevalent AF on the enrollment electrocardiogram (ECG). The sensitivity of this approach remains unknown. It is critical to exclude all incident AF analyses because AF itself can have important anatomic and physiologic effects.

Hypothesis:
The sensitivity of AF ascertainment by baseline ECG alone is poor.

Methods:
The Heart and Soul Study (H&S) enrolled 1024 ambulatory men and women with established coronary artery disease between September 2000 and December 2002 from four sites within the San Francisco Bay Area. We identified all H&S participants receiving care at the Veterans Administration (VA) (n=425), a single payer system with comprehensive electronic medical records. A baseline study ECG was performed on all subjects. A thorough review of electronic medical records was performed by an electronic key word query. All available ECGs were directly reviewed and overread by a board certified electrophysiologist. Paper charts for all non-VA hospital admissions after study enrollment were also directly reviewed.

Results:
The 425 participants were followed for a median 10.5 years (interquartile rage [IQR] 5.7 [[Unable to Display Character: –]] 11.8). Prevalent AF was identified in 23 participants (5.4%) by baseline study ECG, and 77 participants (18%) by thorough chart review (p<0.001). Compared to chart review, ascertainment of prevalent AF by baseline ECG had a sensitivity of 30% and a specificity of 100% (ROC area 0.649). If only participants with prevalent AF on baseline ECG were excluded (hence misclassifying 54, or 13% of all participants, as having no history of AF), 139 (35%) of participants would have been classified as developing incident AF. In contrast, after excluding all participants with prevalent AF determined by chart review, 84 (24%) are categorized as developing incident AF.

Conclusion:
Despite common practices in major cohort studies, the sensitivity of the baseline ECG for prevalent AF is poor. This may lead to common misclassification of prevalent AF participants as developing incident AF, resulting in the false identification of “predictors” of AF that are in fact due to extant AF.
Abstract 18519: Withdrawal of Antiplatelet Therapy Results in Worse Short-term Prognosis in Patients Undergoing Elective Major Noncardiac Surgery
Authors: álvarez-García Jesús , Vives-Borrás Miquel , Llao Joan I , Ferrero-Gregori Andreu , Bausili Marc , Díaz Rubén , Gil María A , Moral Victoria , Paniagua Pilar , Rodriguez Mireia , Urrutia Mónica C , Sionis Alessandro , Pelaez Xavier
Published: July 2021

Background:
The decision whether to discontinue antiplatelet therapy in patients undergoing major noncardiac surgery can be clinically challenging. There is insufficient clinical evidence to establish comprehensive guidelines and most of recommendations are based on expert consensus.

Objective:
To evaluate the effectof withdrawal of antiplatelet therapy on 30-day postoperative outcome in subjects undergoing elective major noncardiac surgery.

Methods:
A retrospective cohort study was performed in 1630 patients, 40 years and older, who underwent major noncardiac surgery. Age, gender, risk factors, previous chronic heart or lung disease, renal function, anemia and concomitant treatment were used in a binary logistic regression to determine the impact of withdrawal of antiplatelet therapy on prognosis. The primary outcome measure was a composite of 30-day postoperative mortality or cardiovascular events (cardiac arrest, myocardial infarction, stroke or pulmonary embolism). Results: Five percent of patients presented the composite primary outcome measure of 30-day postoperative mortality or cardiovascular events. Antiplatelet therapy was withdrawn in 11.4% of patients (table). Discontinuation of antiplatelet therapy was associated with a significant increase in the primary outcome measure (OR 2.27; CI95%: 1.16-4.46).

Conclusions:
In a contemporary cohort of patients undergoing noncardiac surgery, withdrawal of antiplatelet therapy was associated with a worse short-term prognosis. There is an urgent need for further research in this field.
Abstract 18541: Gastric Bypass Surgery is Associated with a Marked Reduction in Circulating High Sensitivity Cardiac Troponin I Concentrations: Comparison with Intensive Lifestyle Intervention
Authors: Lyngbakken Magnus N , Omland Torbjørn , Nordstrand Njord , Norseth Jon , Hjelmesæth Jøran , Hofsø Dag
Published: July 2021

Introduction:
Morbid obesity is associated with increased cardiac mass and cardiovascular risk. Circulating high sensitivity cardiac troponin I (hs-TnI) concentrations reflect cardiac mass and hemodynamic stress and are strongly predictive of subsequent risk of heart failure and premature death. The impact of weight loss induced by gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on circulating hs-TnI is unknown.

Hypothesis:
Weight loss induced by GBS and ILI is associated with reduced circulating hs-TnI concentrations.

Methods:
The Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention study was a controlled clinical trial conducted from December 2005 to June 2009 at the Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway. A group of 139 morbidly obese subjects were treated either with GBS or ILI. Biochemical and clinical indices of cardiovascular and metabolic health were assessed at baseline and after 12 months of follow-up. Blood samples for hs-TnI analyses were available from 136 participants (94 female), out of whom 74 received GBS.

Results:
At baseline median hs-TnI levels were 2.35 (1.38-4.40) ng/L in the ILI group and 2.40 (1.28-3.95) ng/L in the GBS group (ns). After 12 months of follow-up, hs-TnI had decreased significantly more in the GBS group than in the ILI group (1.10 ng/L vs. 0.20 ng/L; p=0.002) (see Figure). Variables associated with the change in hs-TnI concentrations by univariate analyses included intervention group (p=0.002), changes in body mass index (p=0.002), body weight (p=0.003), waist circumference (p=0.04), serum total cholesterol (p=0.009), serum triglycerides (p=0.002) and HbA1c (p=0.017).

Conclusions:
In patients with morbid obesity, GBS was associated with a significantly greater reduction in hs-TnI than ILI, suggesting that bariatric surgery and/or large weight loss unloads the stressed heart and may lead to reduced cardiac mass and hemodynamic stress.
Abstract 18551: Predictors of Heart Failure and Death in a High Risk Diabetic Population: The DAVID-Berg Study
Authors: Gori Mauro , Canova Paolo , Calabrese Alice , Cioffi Giovanni , Iacovoni Attilio , Grosu Aurelia , Fontana Alessandra , Ferrari Paola , De Maria Renata , Taddei Filippo , Filippi Alessandro , Rutili Maria Rosaria , Donzelli Luigi , Parolini Marina , Gavazzi Antonello , Senni Michele
Published: July 2021

Introduction:
Diabetic subjects are at high risk of heart failure (HF) and death. Few data are available on the predictive value of NTproBNP, ECG, and echocardiogram in this population

Hypothesis:
A screening strategy with NTproBNP, ECG, and echo may improve prediction of HF/death events in a diabetic population in HF-stages A & B, beyond clinical data

Methods:
In 2008, among 4047 subjects aged >55 and <80 yrs treated by three general medicine group practices, the DAVID-Berg study enrolled all subjects with diabetes &/or hypertension &/or cardiovascular disease, without history/symptoms/signs of HF (n=623). Subjects underwent clinical visit, 12-lead ECG, echocardiogram, NTproBNP point of care testing.

Recently data on HF/death events have been prospectively collected for all diabetic subjects included in the study (n=198)

Results:
Median age of the study population was 69 yrs, 62% were men, mostly hypertensive (86%) with known cardiovascular disease (44%). During a median follow-up of 5.2 [4.9,5.5] yrs there were 45 HF/death. At Cox regression analyses univariate predictors of events were known cardiovascular disease, insulin therapy, chronic kidney dysfunction (CKD), NTproBNP≥300 pg/mL, abnormal ECG (atrial fibrillation &/or LV hypertrophy &/or bundle branch block &/or Q wave), left atrial volume index (LAVI)≥40 mL/m
2
, LV ejection fraction (LVEF)≤55%, and LV mass index. At multivariate analyses (stepwise forward selection applied to univariate predictors), clinical variables (CKD and known cardiovascular disease), ECG (HR 2.66 [95% CI 1.08-6.55]), LAVI≥40 mL/m
2
(HR 2.50 [95% CI 1.28-4.89]), and LVEF≤55% (HR 2.70 [95% CI 1.45-5.04]) remained significantly associated with the outcome. Adding sequentially NTproBNP, ECG, and echo (LAVI, LVEF) to clinical data improved event prediction (Figure)

Conclusions:
High risk diabetic subjects may be correctly risk stratified integrating sequentially clinical data with NTproBNP, ECG, and echocardiogram
Abstract 18574: Empagliflozin Reduces Systolic Blood Pressure in Dipper and Non-Dipper Patients with Type 2 Diabetes and Hypertension
Authors: Chilton Robert , Tikkanen Ilkka , Crowe Susanne , Johansen Odd Erik , Broedl Uli C , Woerle Hans J , Hach Thomas
Published: July 2021

In a Phase III randomized trial (EMPA-REG BP™), patients with type 2 diabetes (T2DM) and hypertension (defined as mean seated office systolic blood pressure [SBP] 130-159 mmHg and diastolic BP [DBP] 80-99 mmHg at screening) received empagliflozin (EMPA) 10 mg (n=276), EMPA 25 mg (n=276) or placebo (PBO; n=271) once daily in the morning for 12 weeks (mean [SD] age 60.2 [9.0] yrs, HbA1c 7.90 [0.74] %, 24-h SBP 131.4 [12.3] mmHg, 24-h DBP 75.0 [7.8] mmHg). We assessed changes from baseline in SBP (mean 24-h, awake-time, sleep-time) via ambulatory BP monitoring at week 12 in patients categorized as dippers (sleep-time mean SBP ≤90% of awake-time mean; n=417) or non-dippers (sleep-time mean SBP >90% of awake-time mean; n=350).

Baseline mean (SD) 24-h SBP (mmHg) was 129.9 (11.6) in dippers and 133.1 (12.4) in non-dippers. Adjusted mean (SE) changes from baseline in mean 24-h SBP (mmHg) in dippers were -0.2 (0.7) with PBO vs -3.8 (0.6) and -3.9 (0.7) with EMPA 10 and 25 mg, respectively (both p<0.001), and in non dippers were 1.0 (0.7) with PBO vs -1.6 (0.7) with EMPA 10 mg (p=0.013) and -3.8 (0.7) with EMPA 25 mg (p<0.001). Hourly mean SBP patterns over 24 h for dippers and non-dippers were maintained with EMPA 25 mg (Figure) and 10 mg. Adjusted mean (SE) changes from baseline in awake-time SBP (mmHg) in dippers were -0.5 (0.7) with PBO vs -4.6 (0.7) with EMPA 10 and 25 mg (both p<0.001), and in non dippers were 1.3 (0.8) with PBO vs -2.2 (0.8) with EMPA 10 mg (p=0.002) and -4.2 (0.7) with EMPA 25 mg (p<0.001). Adjusted mean (SE) changes from baseline in sleep-time SBP (mmHg) in dippers were 0.4 (0.8) with PBO vs -2.6 (0.8) with EMPA 10 mg (p=0.007) and -2.2 (0.8) with EMPA 25 mg (p=0.022), and in non-dippers were 0.1 (0.9) with PBO vs -0.5 (0.9) with EMPA 10 mg (p=0.603) and -3.2 (0.8) with EMPA 25 mg (p=0.006). There were no apparent differences in heart rate with EMPA vs PBO in dippers or non-dippers.

In patients with T2DM and hypertension, EMPA 10 mg and 25 mg significantly reduced SBP vs PBO in dippers and non-dippers.
Abstract 18576: Hypoxia Induces Phenotypic Switching of Human Pericytes Into Smooth Muscle Cells That is Associated With Changes in Pericyte-specific Non-coding RNA Expression
Authors: Zehendner Christoph M , Demolli Shemsi , Michalik Katharina , Jaé Nicolas , Wagner Jasmin , John David , Uchida Shizuka , Zeiher Andreas M , Dimmeler Stefanie
Published: July 2021

Background:
Pericytes are pivotal for endothelial barrier integrity, angiogenesis, organ function and wound healing. While endothelial hypoxic reponses are well explored, knowledge on the effects of hypoxia on human pericytes (hPC) is sparse. Non-coding RNAs (ncRNAs) control gene expression by various mechanisms, but their functions in hPC remain unknown. We hypothesized that hypoxia influences the hPC-specific transcriptome and hPC phenotype.

Methods:
hPC were validated by analyzing established pericyte expression markers via qRT-PCR and immunofluorescence (IF). Subsequently, hPC and HUVEC were subjected towards hypoxia (24h 1%O
2
), and next generation RNA deep sequencing (RNAseq) was performed. hPC viability following hypoxia was analyzed by CalceinRed assay.

Results:
hPC expressed specific pericyte markers (Desmin, NG2, alphaSMA, PDGFRb) on mRNA and protein level. Cell viability of hPC was not affected by hypoxia. RNAseq revealed that 109 coding genes are significantly regulated in both HUVEC and hPC, whereas 520 coding genes were significantly regulated specifically in hPC (P<0.05, n=3). Interestingly, we identified a number of smooth muscle cell (SMC)-related genes that were increased in hypoxic hPC. The increase of the prototypic SMC marker alphaSMA was confirmed by qRT-PCR (2.23±1.18 fold induction) and IF. We observed a significant regulation of 6 ncRNAs, which were commonly regulated in HUVEC and in hPC, including the known hypoxia-induced miR-210 cluster (HUVEC: 7.86±0.09; hPC: 7.1±0.72 fold induction). Further 36 hPC-specific ncRNAs were identified, among them 25 long intergenic ncRNAs (lincRNAs) and 10 antisense RNAs (P<0.05,n=3). Notably, lincRNA H19, that is known to be important for muscle cell differentiation, was strongly upregulated in hypoxic hPC (4.24±1.1 fold induction, P<0.001,n=3).

Conclusion:
Hypoxia triggers hPC differentiation towards a SMC phenotype that is associated with a significant change in hPC-specific ncRNA expression without affecting hPC viability. The functions of the newly identified ncRNAs are currently investigated. Our findings may be relevant to understand the role of pericytes in persistent vascular constriction and vessel destabilization in stroke or myocardial infarction.
Abstract 18614: Long-term Psychosocial Outcomes of Congenital Heart Disease: Neurocognitive Performance, Quality of Life, Psychosocial Adjustment and Psychiatric Morbidity of Adolescents and Young Adults Surviving Their Disease
Authors: Areias Maria Emilia G , Melo Stefanie , Lopes João Pedro , Rodrigues Filipa , Nascimento Ana Catarina , Cerqueira Daniela , Gomes Liliana , Estrela Anabela , Miranda Joana , Vilacova Filipa , Moura Cláudia , Soares Joana , Peixoto Bruno , Quintas Jorge , Areias José Carlos
Published: July 2021

Objectives:
to study neurocognitive performance (NP) of CHD patients and to determine whether is related to parameters of fetal development registered at birth, head circumference (HC), weight (W) and length (L) and neonatal parameters (APGAR 1, 5); to study their quality of life (QOL), psychiatric morbidity (PM), psychosocial adjustment (PSA) and traits of personality (TP).

Methods:
266 CHD patients, 148 male, aged from 12 to 30 years (mean= 18.00 ± 3.22), 103 cyanotic, and 119 healthy controls (56 males, mean=18.41±3.20) participated. Clinical data were collected. Neuropsychological assessment included Wechsler’s Digit Test (direct and reverse) and Symbol Search, Rey’s Complex Figure, BADS’s Key Searching Test, Color-Word Stroop Test, Trail Making Test (A, B) and Logical Memory Task. Participants were interviewed on social support, family educational style, self-image, physical limitations, completed a psychiatric interview (SADS-L) and self-report questionnaires on QOL (WHOQOL-BREF), PSA (YSR and ASR) and TP (NEOPI-R). HC, W and L and APGAR were collected.

Results:
CHD patients had a significantly worse NP than healthy controls in all tests, and the cyanotic worse than the acyanotic patients (but not significantly). Several correlations were apparent between fetal parameters (HC, W and L) and neuropsychological abilities in CHD. However, low weight at birth, cyanosis and male gender are the main predictors of bad NP later on in CHD patients (R=0.414; R2=0.171; F=5.787; p=0.001; β=1.654; t=2.858; p=0.005; β=1.881; t=2.377; p=0.020; b=1.624; t=2.062; p=0.042). We found a 15.3% lifetime prevalence of psychopathology (18.5% in females). Comparing to normal population, our patients have better QOL in environmental (t=6.907; p=0.000), social relationships (t=5.102; p=0.000) and general dimensions (t=2.558; p=0.011). Complex CHD reported worse QOL in physical dimension (U=3576.500; p=0.001) than those with moderate/mild forms of disease; Female patients showed worse PSA, with more withdrawal, anxiety/depression and internalization.

Conclusion:
CHD patients have worse NP than controls; low weight at birth, male gender and the presence of cyanosis predict bad NP in CHD patients; patients seem to be more prone to PM, worse PSA and SP.
Abstract 18728: Discovery Lipidomic and Metabolomic Profiling Predicts Longitudinal Changes in Metabolic Risk Factors
Authors: Willinger Christine M , Yin Xiaoyan , Juhasz Peter , Courchesne Paul , Muntendam Pieter , Gordon Neal , Adourian Aram , Larson Martin G , Levy Daniel
Published: July 2021

BACKGROUND:
Metabolic syndrome is associated with increased risk for cardiovascular disease and type 2 diabetes, but the molecular mechanisms underpinning its constituent risk factors are unclear. We sought to identify predictive markers of metabolic risk by testing for associations of lipids and metabolites with longitudinal changes in metabolic traits.

METHODS:
Discovery liquid chromatography-tandem mass spectrometry profiling of 154 lipids and gas chromatography-mass spectrometry profiling of 119 metabolites was conducted on plasma samples from 554 Framingham Heart Study participants with baseline and follow-up clinic examinations (5-7 years later) at which body mass index (BMI), triglycerides (TG), HDL cholesterol (HDL-C), and glucose were measured. Analytes were tested for association with longitudinal changes (Δ) in metabolic traits using general linear models, and multimarker panels were selected using forward selection.

RESULTS:
Our single marker analyses revealed distinct signatures of longitudinal changes in metabolic risk factors. Markers associated with ΔBMI were 1-palmitoyl lysophosphatidic acid (LPA 16:0; p=2.8x10
-4
), its precursor lysophosphatidylcholine (LPC 16:0; p=6.7x10
-5
), and four other LPC species. Subclasses of sphingomyelins (SMs) were associated with changes in TG, HDL-C, and glucose. Sphingadiene (d18:2) variants were associated with ΔHDL-C [SM(d18:2/24:1), p=2.8x10
-6
; SM (d18:2/20:0), p=1.2x10
-4
]. Canonical SMs were associated with ΔTG [SM (d18:1/16:0), p=1.8x10
-5
; SM (d18:1/17:0), p=2.1x10
-5
]. Two dihydrosphingosine (d18:0) variants were associated with Δglucose [SM 36:0, p=5.0x10
-5
; SM (d18:0/24:0), p=3.2x10
-4
]. Metabolite markers for ΔTG included quinic acid (p=9.1x10
-5
) and sitosterol (p=1.0x10
-4
). Top markers were selected in multimarker panels that explained a significant proportion of longitudinal change in each metabolic trait (2.5-15.3%) beyond baseline covariates.

CONCLUSIONS:
Using lipidomic and metabolomic profiling in parallel, we identified lipid-centric signatures of longitudinal changes in metabolic traits and demonstrated their predictive power. Our results suggest that specific derangements in lipid metabolic pathways may underlie metabolic risk.