bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19492: Successful Reversed Polarity Defibrillation With the Wearable Cardioverter Defibrillator
Authors: Bianco Nicole , Szymkiewicz Steven J
Published: March 2022

Introduction:
Published literature suggests that switching the direction of the external defibrillation pathway does not impact the efficacy of the shock. Consequently, the European Resuscitation Council Guidelines for Resuscitation 2010 states that it does not matter, for defibrillation success, which electrode is placed in either position. The primary objective of this study was to evaluate if these results are consistent for the asymmetrical electrodes of a wearable defibrillator, which uses two large posterior and one apical self-gelling defibrillator electrodes.

Methods:
Six swine were fibrillated and defibrillated at each energy level (75J, 100J, 125J, or 150J) during apex-posterior defibrillation comparing an initially positive apex electrode (standard) with an initially negative apex electrode (reversed) using a customized wearable cardioverter defibrillator (WCD, LifeVest®, ZOLL). The first three swine received the standard shocks first, while the last three swine received the reversed shocks first. If the first shock did not convert the rhythm, rescue shocks were delivered by either the WCD at 150J or an external defibrillator at 200J until conversion took place. Shock success and ECGs were recorded for all shocks. Fisher’s exact test was used to determine P-values.

Results:
Six swine were studied (average wt = 28.3 ± 3.0 kg, range: 24.0-31.8 kg). All energy levels (75J, 100J, 125J, and 150J) were tested at least once using both normal and reversed electrodes on all pigs. The first-shock results (excluding the rescue shocks) are shown in the figure below. No animal died from irreversible VF, asystole, or pulseless electrical activity during the study. No differences in defibrillation success were found to be significant at any energy level.

Conclusions:
In this animal model of VF, the polarity of the apex-posterior shocks did not influence transthoracic defibrillation success by the asymmetric electrodes of the WCD.
Abstract 19494: 3D Volumetric Assessment of Coronary Plaque Change in Asymptomatic Subjects in Response to Therapy Using CT Angiography
Authors: Sandfort Veit , Ahlman Mark , Mallek Marissa , Broersen Alexander , Sams Andrew , Bluemke David A
Published: March 2022

Introduction:
Studies using intravascular ultrasound have demonstrated that plaque can regress after statin treatment. However, due to the invasive nature of this method data on asymptomatic individuals is scarce. CT angiography (CTA) data on change in plaque volume has shown variable success and has been evaluated mainly in high risk individuals. The aim of this study was to determine the change in coronary plaque in asymptomatic subjects undergoing statin treatment.

Methods:
Study subjects were recruited from an ongoing study (‘Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression’). CTA (320-slice) was performed at baseline and after 2 years using a consistent protocol (kVp 120 or 100 kVp, iodine dose base on body weight). Plaque lesions (n = 100) were measured at baseline and follow up using customized tools to align coronary datasets based on anatomic landmarks. Plaque components were assessed by stratification of change in plaque volume by age.

Results:
The mean subject age was 64 years (81 % male). The mean Framingham risk was 11%. The median statin dose was 40 mg simvastatin or equivalent. Plaque characterization showed that younger subjects had a significantly higher proportion of non-calcified plaque subcomponents compared with older subjects (86% vs 62% respectively, p ≤ 0.01). The median change in total and non-calcified plaque volume was +2.9% and -5.9% respectively (not statistically significant from 0). Overall 36% of the lesions showed progression of non-calcified plaque while 64% showed regression. Of note, older subjects (over 65y) showed progression of total plaque volume while younger subjects showed no significant change. Younger subjects experienced more reduction in non-calcified plaque volume compared with older subjects (median -12.1% vs -2% respectively, p=0.02).

Conclusions:
Approximately 2/3 of the lesions showed plaque regression with 40 mg equivalent simvastatin dose over two years. Younger subjects (≤ 65 years) had larger percentages of soft plaque than older subjects, and showed significantly more regression of non-calcified plaque in relationship to statin therapy. Change in plaque using 3D volumetric registration of CTA data appears feasible and may help determine response to therapy.
Abstract 19512: Aortic Annulus Sphericity Index is Predictive of Significant Aortic Regurgitation After Transcatheter Aortic Valve Replacement
Authors: Williams Zack J , Medranda Giorgio A , Brahmbhatt Kunal , Hafiz Adbul M , Calixte Rose , Gaztanaga Juan , Ray Beevash , Marzo Kevin , Schwartz Richard , Green Stephen
Published: March 2022

Introduction:
Aortic regurgitation (AR) is a known occurrence post Transcatheter Aortic Valve Replacement (TAVR), and has significant impact on morbidity and mortality.

Hypothesis:
We hypothesize that the degree of circularity of the aortic annulus on pre-TAVR computed tomography (CT) predicts development of post-TAVR moderate or severe AR.

Methods:
In this observational, retrospective study, we reviewed data on 350 TAVR patients at our institution from 2012-2015. Using CT, aortic annulus measurements were collected to evaluate the size of the aortic annulus and calculate the Sphericity Index (SI). SI was calculated by dividing the long diameter of the aortic annulus by the short diameter of the aortic annulus. Post-TAVR Transthoracic Echocardiograms (TTEs) were used to determine degree of AR prior to discharge. Significant AR was defined as moderate or severe AR. A Receiver Operating Characteristic (ROC) curve was used to validate SI. We use Youdin Index (d2) to determine the optimal cutoff point of SI. All Analyses were done using SAS 9.4 ®.

Results:
The 350 patients had a mean age of 83.3 ± 7.2 years, BMI was 27.3 ± 5.5 kg/m2, 46.6% were male, and 92.3% were non-Hispanic White. The mean SI was 1.26 ± 0.09. Using Youdin Index the optimal SI cutoff was 1.33 and corresponds to the 75th percentile of deviation from a circle. There were 5.5% of patients with an SI of 1.33 or less who developed significant AR post-TAVR. In contrast, 22.4% of patients with an SI above 1.33 developed significant AR post-TAVR (p < 0.001). Sensitivity was 53% and specificity was 81%.

Conclusion:
Currently, there are no non-invasive pre-TAVR methods to predict development of significant AR post-TAVR. We have determined that the SI, used to measure the degree of circularity of the aortic annulus, is a non invasive measurement that can be used to predict the development of significant AR. SI measurements greater than 1.33 predict AR and provide more insight for pre-TAVR evaluation.
Abstract 19521: Slow and Prolonged Inflations of Percutaneous Transluminal Angioplasty is as Effective as Stenting in Peripheral Vascular Interventions
Authors: Meraj Perwaiz M , Doshi Rajkumar , Vijayaraghavan Pavitra , Helfgott Daniel , Shah Niraj
Published: March 2022

Background:
The benefit of stent implantation over percutaneous transluminal angioplasty (PTA) in patients undergoing peripheral vascular interventions (PVI) has not been well described. Original data supporting stents over PTA was in an era without routine atherectomy, and more recent data including chronic total occlusions (CTO) and longer lengths demonstrated no difference.

Method:
551 patients undergoing PVI were identified from January 2011 to January 2015. Success was defined by a composite improvement of ankle brachial index (ABI) to over 0.9, an ultrasound velocity of less than 250 m/s, or Rutherford classification improvement. All PTA was performed over a slow inflation over 5 minutes. A Pearson chi-square and multivariate analyses were used to determine results.

Results:
274 (49.72%) patients received PTA alone and 277 (50.28%) received stents. Although more patients with diabetes and longer lesion length were in the PTA group, stenting did not improve the individual or composite success endpoints. Even when correcting for these differences in a multivariate analysis.

Conclusion:
PTA is as effective as stenting even in patients with diabetes and long lesion lengths (over 100mm). More data is necessary as drug eluting balloon angioplasty has been shown to improve patency over PTA, however the more slow and prolonged inflations in PTA may be responsible for these findings.
Abstract 19527: Relation Between Quantitative Coronary Cta and Myocardial Ischemia by Adenosine Stress Ct Myocardial Perfusion
Authors: van Rosendael Alexander R , Kroft Lucia J , de Graaf Michiel A , Broersen Alexander , Bax Jeroen J , Scholte Arthur J
Published: March 2022

Background:
Increasing stenosis severity is related to reduced myocardial blood flow during hyperemia. Stenosis percentage is a moderate predictor for myocardial ischemia. It is known that coronary plaque morphology and composition may improve discrimination. Integration of quantitative coronary CTA (QCT) and adenosine stress CT myocardial perfusion (CTP) provides this information. The aim of this study was to assess the relation between coronary stenosis severity and plaque characteristics by QCT and ischemia diagnosed by CTP.

Methods:
We evaluated 84 patients who underwent both coronary CTA and adenosine stress CTP. Stenosis percentage and additional plaque characteristics (lesion length, mean plaque burden, plaque volume, remodeling index) were determined. Subsequently, the coronary lesions were related to presence of lesion specific ischemia measured with CTP.

Results:
Atherosclerosis was present in 146 coronary arteries. 21% (33/146) of the lesions caused downstream ischemia. Stenosis percentage (p<0.001), mean plaque burden (p<0.001), plaque volume (p=0.021), lesion length (p=0.033), maximal plaque thickness (p=0.021), dense calcium volume (p=0.005) were higher in hemodynamically significant lesions. Only 1 (3%) of 37 coronary lesions ≤ 40% stenosis was related to ischemia. Between 41%-60%, 61%-80%, >81%, respectively, 17% (11/61), 34% (11/31) and 59% (10/17) were hemodynamically significant.

Conclusion:
Increasing stenosis percentage measured by QCT is related to higher prevalence of hemodynamically significant lesions measured with adenosine stress CTP. However, stenosis severity cannot accurately detect ischemic lesions. Coronary plaque volume, mean plaque burden, lesion length, maximal lesion thickness, and dense calcium volume were other characteristics that were related to ischemia, potentially leading to improved discrimination of intermediate to severe stenotic coronary lesions for downstream ischemia.
Abstract 19547: FOXO3 Genotype Strongly Impacts Coronary Heart Disease Mortality in Three Populations
Authors: Willcox Bradley J , Morris Brian J , Tranah Gregory J , Chen Randi , Masaki Kamal H , He Qimei , Willcox D. Craig , Allsopp Richard , Moisyadi Stefan , Poon Leonard W , Rodriguez Beatriz , Newman Anne B , Harris Tamara B , Cummings Steven R , Liu Yongmei , Parimi Neeta , Evans Daniel S , Donlon Timothy A
Published: March 2022

The
G
allele of the
FOXO3
SNP
rs2802292
has a strong, consistently replicated protective association with longevity. We investigated the effect of
FOXO3
genotype on coronary heart disease (CHD) mortality - a major cause of mortality worldwide. We genotyped DNA collected in 1991-93, at Exam 4 of the Honolulu Heart Program (HHP), from 3,584 American males of Japanese ancestry aged 71-93 years. Study participants were followed for up to 9 years for CHD mortality and for up to 11 years in a replication cohort - the Health Aging and Body Composition (Health ABC) study. Health ABC is a prospective observational study of 3,075 well functioning, community-dwelling, male and female, white and black Americans, aged 70-79 years at baseline. Cox proportional hazards models demonstrated that Americans of Japanese, white and black ethnicity who were
G
allele carriers had a combined risk reduction of 31% for CHD mortality (HR = 0.69; 95% CI, 0.58-0.82;
P
=0.00002). Reduction in risk of death from CHD was 38% in Japanese, 24% in whites and 29% in blacks. This finding remained virtually unchanged when included in a multivariable model of common CHD risk factors. We subsequently assessed the contribution of
FOXO3
genotype, relative to other common risk factors, to CHD mortality in these populations by estimating population attributable risk (PAR). In the Americans of Japanese ancestry, PAR for the
TT
(non-protective) genotype was high, at 24%, equivalent to hypertension (24%), and greater than diabetes (21%), hypercholesterolemia (12%) and ever smoking (6%). PAR for
FOXO3
genotype was lower at 9% and 3% in white and black Americans, respectively, principally due to lower prevalence of the
TT
(risk) genotype. We subsequently measured C-reactive protein (CRP) in a population subsample, and found lower blood CRP levels in
G
allele carriers (
P
<0.05), suggesting a potential link to inflammation. In conclusion, the
G
allele of the
FOXO3
SNP
rs2802292
has a major protective effect on CHD mortality, possibly related to lower blood levels of inflammation. The findings support further research on potential mechanisms and point to FoxO3 as a potential target therapeutic target.
Abstract 19548: Comparison of a Novel Four Dimensional CT Myocardial Strain Analyzing Technique With MRI, TTE, and Endomyocardial Biopsy
Authors: Takaoka Hiroyuki , Funabashi Nobusada , Ozawa Koya , Nakayama Takashi , Kobayashi Yoshio
Published: March 2022

Introduction:
Myocardial strain is a new indicator of myocardial characteristics and function, mainly evaluated by transthoracic echocardiography (TTE) or magnetic resonance imaging (MRI) techniques that rely on dynamic two dimensional images.

Hypothesis:
We hypothesized that utilizing the full capability of four dimensional (4D) volumetric 320 slice CT image data with retrospective ECG gating we could provide additional information on myocardial morphology, characteristics and function on Novel 4D CT myocardial stain analysis (developed with PhyZioDynamics, Zio).

Method:
We retrospectively analyzed ten subjects with various rare and un- typical myocardial diseases diagnosed by 320 slice CT using retrospective ECG gating and dose modulation. Some diagnoses were confirmed using MRI, TTE or endomyocardial biopsy (EMB). 4D CT myocardial strain analysis confirmed their diagnosis (see fig). Areas with maximum strain are colored red and decreasing strain, yellow, green, blue, and finally no color (=no strain).

Results:
Case 1 had a large, idiopathic fat deposit in the left ventricle (LV) that could be observed using enhanced CT with a low CT attenuation area. On 4D CT strain analysis, the fat deposit showed no strain. Case 2 had cardiac amyloidosis confirmed by EMB and Case 3 had type 2 hypertrophic cardiomyopathy (HCM). MRI showed late gadolinium enhancements (LGE) in both cases. At corresponding sites, no strain was observed by 4D CT. Other cases analyzed were dilated cardiomyopathy with focal LGE on MRI, subendocardial myocardial infarction with enlarged LV myocardium, etc.

Conclusion:
This is the first report worldwide of a 4D CT myocardial strain analyzing technique that utilizes full volumetric data. Our new technique uses ordinary cardiac CT data acquired with retrospective ECG gating, to provide detailed additional information on myocardial characteristics and function in addition to LV ejection fraction volume data and information on coronary arteries.
Abstract 19549: Automated External Defibrillation: Not That Easy! Untrained Laypeople Place AED Pads Poorly
Authors: Bødtker Henrik , Stærk Mathilde , Lauridsen Kasper G , Jæger André , Løfgren Bo
Published: March 2022

Introduction:
Public access defibrillation is recommended to increase survival. Automated external defibrillators (AED) have therefore been widely deployed and are available in public places. AEDs are claimed to be easy to use without requirements for training. The aim of this study was to investigate the ability of untrained laypersons to correctly place AED pads.

Methods:
Untrained laypeople were invited to participate. Participants were asked to operate a training AED (Lifepak® CR-T AED Trainer, PhysioControl) and place pads according to instructions fra the AED. Pads were placed on an anatomically realistic male resuscitation torso with arms (AMBU® Man, AMBU). Positioning of pads was digitally photographed and compared to the recommended pad position i.e. left apical pad in the left mid-axillary line, approximately level with the V6 ECG electrode and right sternal pad to the right of the sternum, below the clavicle. Digital data analysis was performed using ImageJ (version 1.46r) and distance from the center of the AED pads to the recommended pad position was calculated.

Results:
In total 40 volunteers (female: 60%, mean age 48.6 years) participated. The distance from the recommended left apical pad position was (median; 25% and 75% percentile) 8.6 (6.5; 10.4) cm while distance from the recommended right sternal pad position was (median; 25% and 75% percentile) 2.4 (1.6; 3.7) cm. In total, 95% of participants placed the left apical pad more than 5 cm from the recommended position. The right sternal pad was less often (12.5%, p<0.0001) placed more than 5 cm away from recommended position. The left apical electrode was often placed too medial (Figure 1). Only, 12.5% of participants moved the left arm of the manikin to help place the left apical pad correctly.

Conclusions:
Untrained laypeople place AED pads poorly. The left apical pad is often misplaced medially. AED voice prompts and pad design should be further developed to guide untrained users to correct pad placement.
Abstract 19562: PKG-I[[Unable to Display Character: ɑ]] Oxidative Activation Regulates Small Artery Myogenic Tone Through Calcium Sparks and the BK Channel
Authors: Khavandi Kaivan , Baylie Rachael , Ahmed Majid , Sugden Sarah , Eaton Philip , Nelson Mark T , Greenstein Adam
Published: March 2022

Small resistance arteries function in a state of partial constriction generated by vascular smooth muscle cells (VSMC) in response to intraluminal pressure (‘myogenic constriction’). Collectively, the degree of myogenic constriction determines peripheral resistance and so influences systemic blood pressure. cGMP-dependent protein kinase (PKG) is widely implicated in vascular physiology, but until now has been assumed to play no role in modulation of this important vascular function on the basis that inhibitors of cGMP have no influence on pressure-induced tone. Recent identification of a novel redox mechanism by which PKG can be activated independently of the ‘classical’ NO-sGC-cGMP pathway made it important to revisit PKG’s role in these processes. To examine the relative contribution of these pathways, a transgenic mouse model was utilized, in which a single point mutation precludes activation via oxidative dimerization of PKG, whist preserving classical activation by cGMP. Diameter studies of small arteries from this ‘knock-in’ model were investigated in a pressure-myograph system, and demonstrated reduced constitutively functioning BKCa channel activity in these animals, and in consequence markedly enhanced myogenic constriction. Through imaging of calcium sparks with a spinning disc confocal microscope, the loss of BKCa channel function was shown to be due to diminished VSMC calcium sparks. Patch clamp electrophysiological studies showed that the amplitude and frequency of spontaneous transient outward currents were also reduced, consistent with these findings. Pharmacological studies using both pressure and wire myography with the application of the oxidant hydrogen peroxide provided a signal that myogenic tone initiates oxidant-induced activation of PKG. Western blot analysis of vessels fixed during relevant functional responses confirmed that generation of pressure-induced tone triggers oxidant activation of PKG. Finally, optical monitoring confirmed elevated ROS production with the induction of tone. Our results provide a conceptual framework by which vascular tone is modulated through release of ROS and oxidant-activation of PKG through calcium signalling. This may have important implications for blood pressure.
Abstract 19577: Race and Sudden Cardiac Death: Findings From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Deo Rajat , Khodneva Yulia , Safford Monika M , Judd Suzanne , Soliman Elsayed Z , Shlipak Michael G , Albert Christine M
Published: March 2022

Introduction:
Blacks, as compared to whites, have a higher burden of cardiovascular disease (CVD) risk factors and CVD. Recent studies have reported a higher burden of sudden cardiac death (SCD) in blacks; however, it remains unclear whether this elevation in SCD risk is independent of racial differences in risk factor profiles and prevalent CVD.

Methods:
We examined the association between black race and SCD in participants with and without a history of CVD at baseline in the REGARDS study, a prospective, longitudinal cohort of 29,695 participants ≥45 years (55% women, 41% black) from across the United States. SCD was defined as sudden pulselessness from a presumed cardiac origin that occurred out of hospital or in the emergency room.

Results:
Over a median [IQR] of 6.0 [4.5-7.3] years of follow-up, 388 SCD events occurred. Compared to whites, blacks had less education, lower income and a higher burden of CVD risk factors. In the entire population, the age-adjusted SCD incidence rates per 1000 person-years were 2.6 (95% CI, 2.3-3.0) for blacks versus 1.7 (95% CI, 1.4-1.9) for whites, (HR=1.47; 95% CI 1.20-1.79). This elevated risk was attenuated after controlling for CVD risk factors and became non-significant after controlling for prevalent CVD (Table 1). Among the subgroup of 22,507 participants without CVD at baseline, SCD risk remained elevated in blacks (HR=1.90; 1.35-2.68) even after controlling for CVD risk factors and medication use (Table 1). In contrast, there was no elevation in SCD risk among the participants with prevalent CVD at baseline. The association between black race and SCD was stronger in those without compared to those with a history of CVD (p=0.001).

Conclusions:
The higher risk of SCD risk associated with black race, compared to whites, is partially explained by the higher prevalence of CVD and its risk factors in blacks. However, there remains a higher SCD risk associated with black race among those without CVD not explained by standard CVD risk factors.
Abstract 19579: An Experimental Evaluation of the Compliance Mismatch Effects for Four Stent-graft Devices and a Multi-layer Flow Modulator (MFM) Device for the Treatment of Abdominal Aortic Aneurysms
Authors: Sultan Sherif , Stefanov Florian , Morris Liam , Hynes Niamh
Published: March 2022

Purpose:
To experimentally investigate the arterial wall/device compliance mismatch of four stent-graft devices and a multi-layer flow modulator within the supra- and infra-renal locations for the treatment of Abdominal Aortic Aneurysms (AAA).

Methods:
Five devices were tested under physiologically flow conditions within a flow simulator system comprising of a patient-specific thin-walled flexible AAA model with replicated intraluminal thrombus (ILT) supported by the spinal column. Arterial pressure/diameter measurements were monitored and recorded at the supra- and infra-renal regions and various hemodynamic indicators were obtained to assess the effects of compliance mismatch.

Results:
At the suprarenal region, all devices except the Excluder™, significantly decreased the compliance by 10 - 21% (p<0.002) and increased the stiffness values by 5 - 21% (p<0.001). At the infrarenal region, three devices (Endurant™ and Excluder™) significantly decreased the compliance by 13 - 26% (p<0.001), while the other three devices (MFM™, Zenith™ and Fortron™) did not significantly change the aortic compliance (p>0.057). There was a variation of 10.9 - 16.0 m/s in pulse wave velocities with an increase of 8 - 238% (p<0.001) in the reflection coefficient for all devices. The Excluder™ and Endurant
TM
devices doubled the infrarenal unstented median elastic modulus value (p<0.001).

Conclusions:
Commercially available endovascular devices lower the arterial wall compliance and increase the wall stiffness at the stent/arterial wall interface by varying amounts. The Excluder™ was found to be the most compliant in the surprarenal region, while the MFM™ device was the most compliant in the infrarenal region.
Abstract 19616: Regadenoson Administration During Pharmacological Stress Test Causes Prolonged Qtc Interval
Authors: Rafiq Arsalan , Chughtai Tausif , Ashraf Umair , Raiszadeh Farbod , Megalla Sherry , Afshar Maryam , Bella Jonathan N , Kamalakkannan Gayathri
Published: March 2022

Background:
Post-marketing reports have shown prolongation of QT interval with Regadenoson (Reg). We sought to investigate incidence of corrected QT (QTc) prolongation with Reg and its effect on ventricular arrhythmias in our clinical population.

Methods:
We conducted a retrospective analysis of 844 consecutive patients who underwent Reg myocardial perfusion imaging. EKG was analyzed for QTc and presence of ventricular ectopy. QTc was measured at baseline, 2 minutes after Reg injection and 3 minutes in recovery. Prolonged QTc interval was defined as >470 milliseconds (ms) in women and >450ms in men. Demographic data, medical history and medications were also obtained from medical records.

Results:
Mean age was 61 ± 11 years, 53% were females. We noticed statistically significant increase in mean QTc at 2 min (460.2 ± 49) compared to baseline (441.4 ± 41.7) (p <0.0001). QTc interval was also increased at recovery (454.5 ± 42.7) compared to baseline (p <0.001). QTc was prolonged in 231 (27.37%), 327 (38.74%) and 248 (29.38%) at baseline, 2min and recovery respectively. There were no clinically significant ventricular arrhythmias that required intervention in any of our patients. The number of new premature ventricular contractions (PVCs) after Reg injection was not significantly higher when we compared patients who had higher QTc interval at 2min compared to baseline (p=0.3). The number of new PVCs after Reg injection was significantly higher amongst patients whose baseline QTc interval was higher compared to those whose recovery-QTc interval higher (7% vs. 4%, with p=0.03).

Conclusion:
Qtc interval was prolonged after Reg administration during pharmacological stress testing. Higher baseline QTc and not the post Reg QTc predicted increased PVCs. Caution may be needed in patients undergoing Reg with baseline prolonged QTc.
Abstract 19620: Impact of D-dimer for Prediction of Occult Cancer in Patients With Unprovoked Venous Thromboembolism
Authors: Han Donghee , Cho In-Jeong , Shim Chi Young , Chang Hyuk-Jae , Hong Geu-Ru , Ha Jong-Won , Chung Namsik
Published: March 2022

Introduction:
Unprovoked venous thromboembolism (VTE) is related higher incidence of occult cancer. However, routine screening for cancer in this population is still controversial. D-dimer is a biomarker reflecting the activation of hemostasis and fibrinolysis. D-dimer is clinically used to exclude VTE, also related in patients with malignancy.

Hypothesis:
We aimed to explore the predictive value of d-dimer level for detecting occult cancer in patients with unprovoked VTE.

Methods:
We retrospectively analyzed 840 patients who diagnosed deep vein thrombosis or pulmonary thromboembolism. Among them, 175 (20.8%) patients who diagnosed with unprovoked VTE selected to participate in this study. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated for incidence of occult cancer as well as d-dimer level reference to patient without occult cancer.

Results:
During follow-up for 5.0±1.9 years, 30 of 840 patients diagnosed cancer in this population. The primary origin of tumor was 6 (20%) of stomach, 6 (20%) of lung, 4 (13%) of colon and others. Number of patients with metastatic cancer was 17 (57%). Log d-dimer was significantly higher in occult cancer group than unprovoked VTE without cancer (3.5 ± 0.5 vs. 3.2 ± 0.5, p=0.009). When the patients with unprovoked VTE were divided by d-dimer according to Youden index, high d-dimer (≥2432) was associated with higher prevalence of occult cancer (26.9% vs. 9.2%, p=0.002). In logistic regression analysis, d-dimer is independently associated with occult cancer (OR: 3.93, 95% CI: 1.46-10.54, p=0.007) after adjusted gender, age, type of VTE (i.e., deep vein thrombosis or pulmonary thromboembolism) and tumor markers. In addition, d-dimer is more significantly associated with patients who diagnosed cancer with distant metastasis (OR: 4.31, 95% CI: 1.16-15.99, p=0.029)

Conclusions:
High level of d-dimer concentrations are indicator of an increased risk of occult cancer in patients with unprovoked VTE.
Abstract 19633: Comparison of Angiotensin II Receptor Blocker versus Beta-blocker Therapy in Genetically Classified Children With Marfan Syndrome
Authors: Gonzalez Erica E , D’Alessandro Lisa C , Viswanathan Nitya K , Morris Shaine A , Milewicz Dianna M
Published: March 2022

Background:
Children with Marfan syndrome (MFS) treated with angiotensin II receptor blocker (ARB) or beta-blocker (BB) therapy show a reduction in the rate of aortic root (AR) growth, yet substantial variability in effect remains. Adult data suggests that patients with haploinsufficient (HI) mutations may be more responsive to ARBs compared with dominant negative (DN) mutations. This study sought to assess the effect of genotype on the rate of AR growth in children treated with either ARB or BB.

Methods:
A retrospective review of all individuals with MFS assessed at our institution since 1980 was undertaken; those with ≥2 echocardiograms a minimum of 1 year apart and a documented disease-causing fibrillin-1 (FBN1) mutation were included. One patient with infantile MFS was excluded given extremely AR growth. Genotypes were classified by predicted protein effect as either HI or DN. Multivariable longitudinal linear regression analysis was used to compare average rate of AR growth by genotype and medical therapy using serial echocardiographic data.

Results:
Overall 41 children were included, including 18 with HI and 23 with DN mutations. Males comprised 58%. There was no difference in median age at first echo (HI 5.4 years, IQR 3.9-9.3 vs. DN 5.2 years, IQR 3.4-10.6 years, p=0.97), follow-up time (HI 5.8 years, IQR 4.6-8.2 vs. DN 4.9 years, IQR 3.3-8.7, p=0.35), AR dimension (HI 26 mm, IQR 23-29 vs DN 26 mm, IQR 22-37, p=0.81), or AR z-score (HI 3.0, IQR 2.3-4.0 vs DN 3.4, IQR 2.4-4.2, p=0.58). AR growth rate was greater in children with DN mutations (z-score annual change HI -0.04 vs DN +0.07, p<0.0001). When evaluating AR growth only in patients on ARB or BB monotherapy, patients on ARB with DN mutations grew significantly faster than those on BB therapy with DN mutations (p=0.02).

Conclusions:
In our cohort, patients with MFS and DN mutations had slower growth on BB therapy compared to those on ARB therapy. Genetic testing may play an important role in targeted medical therapy in MFS.
Abstract 19642: Consistent Benefit of Ticagrelor Both Early and Late in Patients With Prior MI in PEGASUS-TIMI 54
Authors: Bonaca Marc P , Storey Robert F , Theroux Pierre , Steg P. Gabriel , Bhatt Deepak L , Im KyungAh , Magnani Giulia , Oude Ophuis Ton , Ruda Mikhail , Parkhomenko Alexander , Isaza Daniel , Kamensky Gabriel , Goudev Assen , Hu Dayi , Montalescot Gilles , Jensen Eva C , Held Peter , Braunwald Eugene , Sabatine Marc S
Published: March 2022

Objectives:
Ticagrelor reduced the risk of CV death, MI or stroke in stable patients with prior MI in PEGASUS-TIMI 54. We investigated the consistency of ticagrelor’s efficacy and safety over time and quantified the magnitude of benefit in patients who tolerated ticagrelor for the first year, analogous to the clinical situation of extending therapy in patients after 1 year.

Methods:
PEGASUS-TIMI 54 randomized pts with a prior MI (median 1.7 yrs prior to randomization) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily or placebo. The rate CVD/MI/stroke and TIMI major bleeding were analyzed for the pooled ticagrelor doses compared to placebo for the first year of observation and then as a landmark analysis beginning after the first year in all patients alive at that time point.

Results:
21,162 patients were randomized and followed for a median of 33 months, with 29% of patients ≥5 yrs from their most recent MI by the end of the trial. The rate of CVD/MI/stroke in the placebo arm remained roughly constant over the trial at ∼3%/y. Ticagrelor significantly reduced CVD/MI/stroke both over the first year (HR 0.84, 95% CI 0.71-0.98, P=0.029, Figure Left) and after year one (HR 0.85, 95% CI 0.74-0.97, P=0.017, Figure Right), with the event curves continuing to diverge through the end of follow-up. TIMI Major bleeding was increased with ticagrelor within the first year (HR 3.46, 95% CI 2.07-5.77) but numerically less so after the first year (HR 2.06, 95% CI 1.43-2.96). When examining patients who successfully completed one year of treatment, continued ticagrelor significantly reduced CVD/MI/Stroke by over 20% over the following two years (HR 0.79, 95% CI 0.68-0.91).

Conclusion:
Patients with a history of MI remain at persistent risk for CVD/MI/Stroke over time. Ticagrelor reduces this risk during the first year as well as in the subsequent years of treatment, supporting prolonged therapy.
Abstract 19657: Histone Variant H2a.z And Cdk9 Differentially Regulate Transcriptional Rates During Cardiac Hypertrophy
Authors: Shin Hyewon , Yang Zhi , Sayed Danish , He Minzhen , Abdellatif Maha
Published: March 2022

Genome-wide modifications in basic transcriptional activity underlie cardiac development and disease. We have previously reported that transcriptional regulation by RNA polymerase II (pol II) distinguishes different functional gene categories. In particular, transcription of constitutive, housekeeping, genes is regulated by a pause/release mechanism vs. de novo recruitment of pol II to cardiac-specific and inducible genes during cardiac hypertrophy in mice. Our objective is to identify the epigenetics and nuclear proteins that distinguish these transcriptional patterns. Using chromatin immunoprecipitation-deep sequencing (ChIP-Seq) we identified relatively high levels of H2A.z at the transcriptional start site of all housekeeping and inducible genes that exhibited only minimal or no changes in the heart before or after induction of pressure overload. In contrast, however, all cardiac-specific genes were consistently devoid of H2A.z. We also identified the specific interaction between H2A.z and acidic nuclear protein 32e (ANP32e), which inhibits the dephosphorylation and deactivation of cyclin-dependent kinase 9 (Cdk9) by protein phosphatase 2A (PP2A) and enhances its recruitment to chromatin. Accordingly, cardiac-specific and inducible genes diverge with regards to their regulation by Cdk9, where pressure overload induces a strict decrease vs. increase of Cdk9, respectively, at the promoter and gene body regions of these gene categories. Paradoxically, the reduction in Cdk9 in the former genes is accompanied by an increase in pol II levels, with a net result of little or no change in transcriptional rates. On the other hand, inducible genes are characterized by high levels of de novo recruitment of both pol II and Cdk9, with a sharp increase in transcriptional rates, which was specifically and completely inhibited by knockdown of Cdk9, or its inhibitors 5, 6- dichloro-1-β-D-ribofuranosyl-1H-benzimidazole or inhibitor II. Thus, the differential recruitment of H2A.z and Cdk9 determines the elongational rate of pol II that discriminates between the transcriptional rates of pressure overload-induced v. constitutively-expressed cardiac-specific genes.
Abstract 19679: Is Major Bleeding Risk for Oral Anticoagulants Similar Among Newly Initiated Non Valvular Atrial Fibrillation Patients?
Authors: Lip Gregory Y , Pan Xianying , Kamble Shital , Kawabata Hugh , Mardekian Jack , Masseria Cristina , Bruno Amanda , Hemant Phatak
Published: March 2022

Aim:
The purpose of this study was to compare the risk of first major inpatient/outpatient bleeding event among non valvular atrial fibrillation (NVAF) patients newly initiated with warfarin versus non-vitamin K antagonist oral anticoagulants (NOACs) including apixaban, dabigatran, or rivaroxaban.

Methods:
Retrospective cohort study was conducted using MarketScan® database from 01/2012 to 12/2013. NVAF patients 18+ years with ≥1 year baseline period were included if they were newly prescribed an oral anticoagulant from 01/01/ 2013 to 12/31/2013. Major bleeding on anticoagulant was defined as inpatients and/or outpatient bleeding on the index drug during the supply duration or within 30 days after the last supply day of the last prescription. A Cox proportional hazards model was used to estimate the hazard ratios (HR) of major bleeding adjusted for age, sex, baseline comorbidities, and comedications.

Results:
Among 29,338 NVAF patients newly initiated on an oral anticoagulant, 2,402 (8.19%) were on apixaban, 4,173 (14.22%) on dabigatran, 10,050 (34.26%) on rivaroxaban and 12,713 (43.33%) on warfarin. Patients initiating warfarin (72.5±11.9 yrs) and apixaban (69.3±12.3 yrs) were older as compared to rivaroxaban (67.3±12.2 yrs) and dabigatran (66.8±12.1 yrs). Patients initiating warfarin were higher risk as compared to those initiating NOACs in terms of CHA
2
DS
2-
VASc score (3.22±1.65) and higher Charlson comorbidity index (CCI) score of 2.37±2.33 (p <0.0001 across all treatments). After adjusting for baseline characteristics, as compared to patients newly initiated on warfarin, patients newly initiated on apixaban or dabigatran had significantly lower risk of major bleeding (Table).

Conclusion:
Among newly anticoagulated NVAF patients in the real world setting, initiation with apixaban or dabigatran was associated with significantly lower risk of major bleeding compared to initiation on warfarin.
Abstract 19694: Reduction in Non-hemorrhagic Stroke With Ezetimibe/Simvastatin Compared With Simvastatin Alone in the IMPROVE-IT Trial
Authors: Wiviott Stephen D , Giugliano Robert P , Blazing Michael A , Cannon Christopher P , Zhou Jing , Murphy Sabina A , Tershakovec Andrew M , Musliner Thomas A , Eugene Braunwald
Published: March 2022

Background:
Statins have been demonstrated to reduce ischemic stroke. Intensive therapy with ezetimibe/simvastatin (E/S) in IMPROVE-IT significantly reduced the occurrence of cardiovascular events in patients post ACS compared to placebo/simvastatin (S). We evaluated the effect of E/S vs S on stroke outcomes.

Methods:
We determined the KM-rate of stroke, by type,during the median 6 year follow-up in 18,144 patients treated with E/S vs S in the IMPROVE-IT trial. Stroke was adjudicated and divided into non-hemorrhagic (NH), hemorrhagic (H), or unknown (U) by a blinded clinical event committee. Stroke reductions were adjusted to absolute change in LDL-C for comparison to prior studies.

Results:
There were 641 (3.5%) subjects with stroke during follow up, including 533 non-hemorrhagic, 102 hemorrhagic, and 14 unknown strokes. Overall, stroke tended to be reduced with E/S (4.2 vs 4.8%; HR 0.86, CI 0.73-1.00, p=0.052), with a significant reduction of NH stroke (3.4 vs 4.1%; HR 0.79, CI 0.67-0.94, p=0.008, Figure), but a numerical increase in H stroke (0.8 vs 0.6%; HR 1.38, CI 0.93-2.04, p=0.11, Figure). Results were similar when NH/U strokes were combined. When adjusted for LDL reduction, the NH stroke reduction appears to be similar to greater than the extent previously reported with statin therapy alone (figure).

Reductions in NH strokes were consistent across major demographic and lipid subgroups. Of note, in 1071 patients with prior stroke or TIA, a known high-risk group, the absolute benefit of E/S was particularly marked for NH strokes; 9.9vs 14.7% (HR 0.61 (0.41-0.91, NNT 21), though benefit remained in those without prior stroke 3.1 vs 3.5% (HR 0.84, CI 0.70-1.01, NNT 250, Pint=0.16). No difference in hemorrhagic stroke was noted in either group.

Conclusions:
Lipid lowering therapy with E/S was superior to S in the incidence of non-hemorrhagic stroke through a median of 6 years; there was a large absolute benefit in patients with prior stroke or TIA.
Abstract 19710: Comparison of Clinical Outcomes With the Utilization of Monitored vs. General Anesthesia in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Kiramijyan Sarkis , Ben-Dor Itsik , Koifman Edward , Magalhaes Marco A , Didier Romain , Escarcega Ricardo O , Baker Nevin C , Negi Smita I , Kang Won Yu , Lipinski Michael J , Minha Sa'ar , Gai Jiaxiang , Torguson Rebecca , Okubagzi Petros , Satler Lowell F , Pichard Augusto D , Waksman Ron
Published: March 2022

Introduction:
There is no clear consensus in regard to the optimal anesthesia utilization in TAVR. The objective of this study was to contribute to the observational literature in evaluating the impact of monitored anesthesia care (MAC) vs. General Anesthesia (GA) in TAVR.

Hypothesis:
No difference in short- or long-term mortality in patients undergoing TAVR with MAC vs. GA.

Methods:
All consecutive patients who underwent transfemoral TAVR from May 2007 through March 2015 at the MedStar Washington Hospital Center had prospectively collected data and were retrospectively analyzed for this study. Furthermore, the cohort was dichotomized into two groups: TAVR under MAC vs. GA as planned method of anesthesia. The primary endpoints included 30-days and 1-year mortality outcomes. The secondary endpoints included: all in-hospital VARC-2 safety outcomes, mean post-procedural hospital and ICU stays, and reasons and rates for intra-procedural conversion of MAC to GA.

Results:
A total of N=533 consecutive patients (51% male, mean-age 83 years) who underwent TAVR under MAC (n=467) vs. GA (n=66) were evaluated. Significant baseline, procedural and in-hospital outcomes are depicted in the figure. 12% of the MAC patients required conversion to general anesthesia (figure). The MAC group had shorter post-procedural hospital (6 vs. 7.9, p=0.023) and similar ICU (2.4 vs. 2.8, p=0.355) length of stays in days vs. the GA group, respectively. The 30-days and 1-year mortality outcomes were similar between the two groups (figure).

Conclusions:
TAVR under controlled monitored anesthesia is feasible and safe, and can be performed in the majority of cases, therefore avoiding the need for general anesthesia and resulting in shorter post-procedural hospital stays. Most common cause for conversion of MAC to GA is cardiac instability and hypotension. TAVR procedures should be planned with MAC as the default strategy for anesthesia.
Abstract 19713: The Electrocardiographic Effects of Intranasal Formulations of a New Calcium Channel Blocker, MSP-2017, are Consistent With a Potential Treatment of Paroxysmal Supraventricular Tachycardia: Results of a Phase I Dose Escalation Study
Authors: Plat Francis , Broughton Archer , Douville Philippe , Sager Philip T , Soh Bob , Wight Douglas
Published: March 2022

Introduction:
MSP-2017 is a new L-type calcium channel antagonist developed to be self-administered intranasally to convert episodes of PSVT into sinus rhythm.

Hypothesis:
This phase 1 study was designed to determine safety, tolerability of two formulations (A and B) of MSP-2017 and to test whether the effects on ECG intervals (PR, QTc) and HR were significantly different from placebo.

Methods:
A double-blind, dose-escalation, placebo-controlled study was conducted in healthy males, consisting of 7 cohorts each including 6 subjects on active drug and 2 on placebo. Cohorts 1 to 5 subjects received 2 single doses of 3.5, 7, 14, 30, 60 mg of MSP-2017 formulations A and B, 3 days apart, and cohorts 6 and 7 subjects received a single dose of 105 and 140 mg of MSP-2017 formulation B only due to lack of PK differences compared to formulation A. Twenty-four hour Holter recordings were performed at screening and on dosing Days 1 and 3. ECGs were analyzed prior to dosing and at 0.5, 1.5, 3, 5, 7, 10, 15 min post-dose and less frequently until 1440 min post-dose.

Results:
The intranasal administration of MSP-2017 was safe and well tolerated. The largest mean placebo-corrected PR increase was observed early, with a peak effect of 20 msec (90% CI: 14.9 to 25.1) at 12 minutes with 60 mg, 19.5 msec (90% CI: 8.4 to 30.5) at 10 min with 105 mg, and 24 msec (90% CI: 15.3 to 32.7) at 12 min with 140 mg of MSP-2017. At lower doses the peak effect was lower and time to onset longer. MSP-2017 did not have a notable effect on QRS intervals but had a dose-related effect on HR. HR increase with both formulations of MSP-2017 was different from placebo at all dose levels. Seven minutes post-dose mean HR increase reached 7, 21.4, 32.2 and 37.4 bpm at 30, 60, 105 and 140 mg doses, respectively. MSP-2017 caused a shortening of the QT duration corrected for individual heart rate (QTcI) at high doses but without dose-dependence.

Conclusions:
MSP-2017 caused significant PR prolongation at early time points after dosing, with 20 msec at higher doses (60, 105 and 140 mg) and smaller effects beyond 50 min post-dose. The HR increase and the QTcI shortening suggest a sympathetic stimulation may have contributed to these ECG changes. These results are consistent with a potential positive clinical effect to be tested in patients with PSVT.
Abstract 19716: Zebrafish Larvae as a Model System For High-throughput Screens of Early-stage Atherosclerosis
Authors: Bandaru Manoj K , Ranefall Petter , Emmanouilidou Anastasia , Tao Lingjie , Larsson Anders , Ledin Johan , Wählby Carolina , Ingelsson Erik , den Hoed Marcel
Published: March 2022

Introduction:
A high-cholesterol diet has been reported to induce vascular deposition of lipids and oxidized LDL cholesterol in macrophages and other cell types in 15 day-old zebrafish larvae. However, results were based on small samples, and little is known about the heterogeneity of effect within and between conditions, the image quantification procedure used, and the influence of dietary energy. We intend to perform large-scale genetic and compound screens for coronary heart disease, and aimed to confirm or refute if zebrafish larvae are a suitable model system.

Methods:
In total, 940 transgenic zebrafish larvae were fed on one of six diets between 5 and 10 days post-fertilization (dpf), to examine main effects of, and interactions between dietary energy and cholesterol. At 10 dpf, we assessed body length and acquired optical sections of the dorsal aorta and caudal vein using an automated positioning system, fluorescence microscope and CCD camera. Atherogenic traits were quantified using a custom-written image analysis pipeline in Ilastik, CellProfiler and ImageJ, and larvae were used to assess whole body levels of total cholesterol, triglycerides and glucose using enzymatic assays. Associations were adjusted for body length, ether - used to prepare the high-cholesterol diet - and batch.

Results:
A high-energy diet resulted in elevated triglyceride levels (p=7.8E-3) - especially in the presence of high dietary cholesterol (p-interaction=0.01) - and in more vascular infiltration by lipids (p=1.0E-12), and co-localising lipids and macrophages (p=0.04), independently of dietary cholesterol. A high-cholesterol diet resulted in higher glucose levels (p=2.1E-3), and in more vascular infiltration by lipids (p=0.01), and co-localising lipids and neutrophils (p=0.04), and lipids, neutrophils and macrophages (p=0.01), independently of dietary energy. Qualitative analyses showed that vascular lipid deposits typically contain oxidised LDL cholesterol, and are located at bifurcation sites of the endothelium.

Conclusions:
Zebrafish larvae represent a promising model system for high-throughput, image-based screens of early-stage atherosclerosis, and dietary energy and cholesterol induce distinct atherogenic traits as early as 10 dpf.