bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 144: Good Neurological Survival After Cardiac Arrest with Initial Shockable Rhythm Increased Year by Year but with Unshockable Rhythm Did Not in Japan
Authors: Hanada Hiroyuki , Nonogi Hiroshi , Nagao Ken
Published: July 2021

Backgrounds:
Early good cardiopulmonary resuscitation (CPR) and early defibrillation are essential for good neurological survival (GNS) in out-of-hospital cardiac arrest (OHCA). Both automated external defibrillator (AED) equipped in public place and CPR educated people in Japan have been increased. We hypothesized that GNS in patients resuscitated from initial shockable rhythm have been increasing in Japan and that GNS from initial unshockable rhythm might not.

Methods and Results:
From January 2005 through December 2012, we conducted a prospective, population-based, observational study involving the consecutive patients across Japan who had OHCA (n= 925,288). We identified 73,751 witnessed cardiogenic cardiac arrest with the age >18 years old and transported to hospitals within 60 minutes from the witness. Among them, 18,436 cases had the initial shockable rhythm of ventricular fibrillation (VF) or pulsless ventricular tachycardia (VT) and 55,315 cases had the initial unshockable rhythm of pulseless electrical activity (PEA) or asystole (Asys). GNS was defined as cerebral performance category scale 1 or 2 one month after the arrest. Results were shown in the figure. Although the rate of increase in number of OHCA with unshockable arrest over the year was greater than that with shockable arrest, GNS ratio was increasing only in OHCA with shockable arrest.

Conclusion:
Good neurological survival resuscitated from initial arrest rhythm with VF/VT had been increasing year by year, but that with PEA/Asys was very low and not changed these 8 years in Japan. We need new strategy for those OHCA patients with initial unshockable rhythm.
Abstract 14637: Influence of Age on Perioperative Major Adverse Cardiovascular Events and Mortality Risks in Elective Non-cardiac Surgery
Authors: Hansen Peter W , Gislason Gunnar H , Joergensen Mads Emil , Køber Lars , Jensen Per F , Torp-Pedersen Christian , Andersson Charlotte
Published: July 2021

Background and Aims:
Advanced age increases risk of perioperative cardiovascular complications and might therefore pose reluctance to subject elderly patients to surgery. We examined the impact of high age on perioperative major adverse cardiovascular events (MACE) and mortality in a nationwide cohort of patients undergoing elective surgery.

Methods:
All Danish patients aged ≥20 years undergoing non-cardiac, elective surgery in 2005-2011 were identified from nationwide administrative registers. Risks of 30-day MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, or cardiovascular death) and all-cause mortality were analysed by multivariable logistic regression models (adjusted for major comorbidities, revised cardiac risk index, cardiovascular pharmacotherapy, body mass index, and surgery type).

Results:
A total of 386,818 procedures were included; mean age 56 years (min-max 20-104), 44% women. In total 1,297 (0.34%) had perioperative MACE and 1,449 (0.37%) died. Odds ratios increased with higher age for both MACE and mortality (Figure). Each 10-year higher age was associated with odds ratio 1.87 (1.78-1.98) for MACE, and 1.86 (1.77-1.95) for mortality. In total of 19,849 procedures were performed in patients 81-90 years of age, and 1,662 on patients ≥90 years. The crude MACE and mortality rates were 331 (1.7%) and 388 (2.0%) among 81-90 years old, and 50 (3.0%) and 67 (4.6%) for those aged ≥90 years.

Conclusion:
The risk of mortality and major adverse cardiovascular events within 30 days after surgery increased linearly with advanced age. However, despite advanced age the absolute event rates were relatively modest and below 5% even for people aged ≥90 years.
Abstract 14657: Andexanet-alfa and PER977 (Arapazine) Correct Blood Loss in a Rabbit Liver Laceration Model - Only Andexanet Reverses Markers of fXa-mediated Anticoagulation
Authors: Hollenbach Stanley , Lu Genmin , DeGuzman Francis , Tan Siusze , Pratikhya Pratikhya , Pandey Anjali , Conley Pamela , Curnutte John T
Published: July 2021

As use of oral fXa inhibitors has increased, so has the need for an antidote to treat the major side effect of these drugs - bleeding. Andexanet alfa (AnXa) (PRT064445), a recombinant fXa derivative, reverses fXa inhibitor-mediated anticoagulation in animals and humans by sequestering the fXa inhibitor in a 1:1 molar ratio, reducing both anti-fXa activity and plasma free fraction of fXa inhibitor, and restoring normal thrombin generation, PT, and aPTT. These parameters correlate closely with reduced blood loss in a rivaroxaban-treated rabbit liver laceration model. Aripazine (PER) (PER977; Perosphere, Inc.) is a small molecule that has been reported to reverse the anticoagulant effects of a broad range of anticoagulants (fXa and thrombin inhibitors; heparins) by direct binding. We synthesized PER and compared it to AnXa in this same liver laceration model at PER doses of 0.3, 3 and 30 mg/kg, and observed reductions in blood loss of 27%, 16% and 76%, respectively (
p
<0.02 for 30 mg/kg dose only). There was an unexpected dose-responsive, but non-significant, trend toward decreased blood loss in non-anticoagulated rabbits with PER alone, with the 30 mg/kg dose showing a 23% decrease. The reduction in blood loss between the two agents was similar at the highest dose studied (76% decrease for 75 mg AnXa/rabbit [ASH 2012] and 76% decrease for 30 mg/kg PER in this study). PER dose groups, however, did not show reduction in riva-induced increases in PT, aPTT or anti-fXa activity. Moreover, there was no change in total plasma concentration of riva after PER administration compared to the 6-fold increase seen with AnXa due to its high affinity for riva and redistribution of riva from the extravascular to the intravascular compartment. Unlike the ~1:1 molar ratio needed for AnXa to sequester riva, a 30:1 PER:Riva molar ratio was needed to reduce blood loss. While the mechanism of action (MOA) for AnXa has been well characterized in preclinical and clinical studies, the mechanism of prevention of blood loss with PER in this model is unclear. In summary, the MOA of PER differs from that of AnXa, where direct (1:1) binding of AnXa to the fXa inhibitor decreases the free fraction of the anticoagulant, reverses PD markers and restores normal hemostasis. Further investigation of PER is required.
Abstract 14681: Uber Analysis of Cardiopulmonary Exercise Test Variables and Mortality in Patients with Heart Failure: the Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) Project
Authors: Shafiq Ali , Brawner Clinton A , Aldred Heather E , Hassan Raakesh , Vasko Stepahanie , Ehrman Jonathan K , Selektor Yelena , Tita Christina , Velez Mauricio , Williams Celeste T , Lanfear David E , Keteyian Steven J
Published: July 2021

Introduction:
Numerous metrics derived from the cardiopulmonary exercise test (CPX) are associated with outcomes among patients with heart failure with reduced ejection fraction (HFrEF). However few studies have examined the independent prognostic value of all variables assessed simultaneously.

Purpose:
Retrospective analysis to describe the relationship between all CPX measures and the composite outcome of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT).

Methods:
Patients (n= 1,201; 33% female; age= 55 ± 13 y) with a CPX between 1997 and 2010 and confirmed HFrEF (ejection fraction [EF] < 40%) were identified. Death data through 2011 was obtained from the National Death Index. The association with the composite endpoint was evaluated separately for 30 CPX measures with adjustment for age, gender, EF, and beta-blocker therapy using Cox regression. Forward stepwise Cox regression was performed to identify which of the CPX variables contribute the most to outcome prediction.

Results:
During a median follow-up of 3.75 years there were 576 (48%) events. When tested separately, nearly all CPX variables (except heart rate reserve/metabolic reserve and peak respiratory exchange ratio) were associated (p<0.05) with the composite endpoint. The top 5 predictors are shown in the Table. Stepwise Cox regression revealed that only % predicted peak oxygen uptake (VO
2
, Wald= 76.1), ventilatory power (peak systolic blood pressure/V
E
-VCO
2
slope, Wald= 58.0), and EF (Wald= 27.0) independently predicted outcomes.

Conclusion:
When considering all variables measured during a CPX test, % predicted peak VO
2
was the variable with the strongest independent association to outcomes in this cohort of patients with HFrEF. The % predicted peak VO
2
may represent a key variable in determining when to consider a patient for an LVAD or CT.
Abstract 14689: Regional Aortic Wall Shear Stress Mapping Implicates Hemodynamics in Human Bicuspid Aortopathy
Authors: Guzzardi David G , van Ooij Pim , Barker Alex J , Martufi Giampaolo , Olsen Katherine E , Di Martino Elena S , Chen Yong-Xiang , Markl Michael , McCarthy Patrick M , Malaisrie S C , Puthumana Jyothy J , Belke Darrell D , O’Brien Edward R , Mewhort Holly E , Svystonyuk Daniyil A , Carr James , Bonow Robert O , Fedak Paul W
Published: July 2021

Introduction:
A suspected genetic cause for bicuspid aortic valve (BAV) aortopathy has led to aggressive resection strategies. Using 4D flow MRI, we documented increased regional wall shear stress (WSS) in BAV patients. Local hemodynamics may exacerbate extracellular matrix (ECM) degradation leading to disease progression. If validated, preoperative regional hemodynamic assessment could be used to guide more targeted patient-specific aortic resection. For the first time, we correlated regional WSS with aortic tissue remodeling in BAV patients.

Methods & Results:
BAV patients (N=11) undergoing ascending aortic resection received preoperative 4D flow MRI with regional WSS differences mapped. Paired aortic wall samples (from same-patient with elevated WSS paired to normal WSS regions) were collected during surgery and compared using histology (pentachrome), biomechanics (biaxial mechanical testing), and ECM regulation (protein expression). Patient mean age: 49±18 years; mean aortic diameter: 4.6±0.7cm (range: 3.6 - 6.3cm); 55% had R+L fusion pattern; 36% had severe aortic stenosis. All patients had heterogeneous WSS patterns with regions of elevated WSS adjacent to those of normal WSS. By histology, regions of increased WSS showed greater medial elastin fragmentation, fibrosis, and cystic medial necrosis compared to adjacent areas of normal WSS. Regions of increased WSS showed increased elastic modulus (fold change±SD: 1.53±0.68; P=0.06, N=5) and collagen stiffness (1.37±0.49; P=0.07, N=5) compared to normal WSS regions suggesting altered distensibility. Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (1.49±0.71, P=0.02), MMP-1 (1.62±0.84; P=0.01), MMP-2 (1.49±1.00; P=0.06), MMP-3 (1.23±0.36; P=0.02), MMP-7 (1.57±0.75; P=0.02), and TIMP-2 (1.26±0.33; P=0.01) in elevated WSS regions suggesting ECM dysregulation consistent with aortic remodeling.

Conclusions:
In BAV aorta, regional WSS corresponds with local histologic abnormalities, altered biomechanics, and ECM dysregulation. These novel data strongly implicate local hemodynamics as a mediator of BAV aortopathy. With further validation, 4D flow MRI could be used to guide personalized resection strategies.
Abstract 147: Cyclosporine a as a Neuro- and Cardioprotective Agent After Cardiopulmonary Resuscitation in a Rat Model
Authors: Knapp Jürgen , Roewer Joachim , Böttiger Bernd W , Popp Erik
Published: July 2021

Background:
The immunosuppressant drug cyclosporine A (CsA) is a direct inhibitor of the mitochondrial permeability transition pore which is the common end point of many pathways of ischaemic pre- and postconditioning. We studied the neuro- and cardioprotective effect of CsA after cardiac arrest (CA) in a rat model of cardiopulmonary resuscitation.

Methods and Results:
Following institutional approval by the Governmental Animal Care Committee rats were subjected to 6 min of CA and were randomly and investigator-blinded allocated either to placebo (n=15) or interventional group (n=15, 10 mg/kg body weight CsA intravenously) after restoration of spontaneous circulation (ROSC). Before CA (baseline) as well as 1 h and 3 h after ROSC, continuous measurement of stroke volume (SV), ejection fraction (EF), preload adjusted maximum power (PAMP) and end diastolic volume (EDV) was performed using a conductance catheter. One day, 3 days, and 7 days after ROSC neurological outcome was evaluated by a tape removal test. After seven days of reperfusion coronal brain sections were analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells.

Animals treated with CsA had a higher SV (96 [93; 107] vs. 78 [73; 94] μl, p=0.02), higher EF (58 [51; 63] vs. 42 [35; 51] %, p=0.002), and higher PAMP (4.8 [3.9; 6.1] vs. 2.3 [2.0; 2.6] mW/μl
2
, p<0.001). EDV remained stable in the CsA group 3 h after ROSC in comparison to baseline (160 [143; 181] vs. 157 [148; 192] μl, p=0.56), whereas it increased in the placebo group (169 [153; 221] vs. 156 [138; 166] μl, p=0.05). More neurons survived after administration of CsA (2.5 [1.6; 4.9] vs. 0.7 [0.4; 1.4] Nissl-positive cells/100 pixel; p=0.005). Animals in the CsA group needed less than half of the time in the tape removal test 7 days after ROSC than placebo treated animals without reaching statistical significance (26 [22; 51] vs. placebo 53 [38; 56] s; p=0.13). CsA treatment did not affect number of TUNEL-positive cells and survival rate.

Conclusion:
Pharmacological treatment with CsA after successful CPR attenuates myocardial dysfunction and reduces neuronal damage.
Abstract 14735: Carotid Artery Stenting and Carotid Endarterectomy are Comparable Among Medicare Beneficiaries Treated in Routine Clinical Practice
Authors: Jalbert Jessica J , Nguyen Louis L , Gerhard-Herman Marie D , Williams Lauren A , Chen Chih-Ying , Liu Jun , Kumamaru Hiraku , Rothman Andrew T , Jaff Michael R , Seeger John D , Benenati James F , Schneider Peter A , Aronow Herbert D , Johnston Joseph A , Brott Thomas G , Tsai Thomas T , White Christopher J , Setoguchi Soko
Published: July 2021

Introduction:
The relative performance of carotid artery stenting (CAS) and carotid endarterectomy (CEA) among Medicare beneficiaries in routine clinical practice has not been established.

Objective:
To compare the performance of CAS relative to CEA among Medicare beneficiaries.

Methods:
We linked Medicare data (2000-2009) to the Society for Vascular Surgery’s Vascular Registry (SVS-VR; 2005-2008) and to the NCDR® Carotid Artery Revascularization and Endarterectomy Registry (CARE; 2006-2008/9). Medicare patients aged ≥66 years undergoing CAS or CEA were followed from the procedure date for the outcomes of death, stroke/transient ischemic attack (TIA), peri-procedural myocardial infarction (MI) or a composite endpoint for these outcomes. We derived high-dimensional propensity scores using registry and Medicare

data to control for patient-level factors and adjusted for provider-level factors including past-year CAS/CEA physician and hospital volume, hospital ownership, teaching affiliation, and hospital size in a Cox regression model comparing CAS to CEA.

Results:
Among 5,254 SVS-VR (1,999 CAS and 3,255 CEA) and 4,055 CARE (2,824 CAS and 1,231 CEA) patients, CAS patients were more often at higher surgical risk (SVS-VR: 96.7% vs. 44.5%; CARE: 71.3% vs. 44.7%) and had a higher comorbidity burden. Crude outcome risks for death and stroke/TIA were lower for CEA. Adjusting for patient-level factors drove estimates downwards for CAS relative to CEA but only after further adjustment for provider-level factors did the performance of CAS and CEA become comparable on all outcomes (figure 1).

Conclusion:
Performance of CAS and CEA among Medicare beneficiaries was comparable after accounting for patient- and provider-level factors, which is consistent with landmark trials. Further studies are needed to understand the role of heterogeneity in provider-level characteristics.
Abstract 14774: Rescue of Diabetes-related Impairment of Ischemia-mediated Neovascularization With Fenofibrate Treatment
Authors: Rajamani Kushwin , Yuan Jun , Lecce Laura , Jenkins Alicia , Keech Anthony , Ng Martin
Published: July 2021

Background:
Fenofibrate, a PPARα agonist, reduced amputation events in the Fenofibrate Intervention and Event Lowering in Diabetes study among 9795 patients, the mechanisms of which are unknown. We hypothesised that fenofibrate may attenuate diabetes-related impairment in ischemia-mediated neovascularization.

Methods:
Hindlimb ischemia was induced in a murine model of streptozotocin induced diabetes mellitus (DM) in wildtype and PPARα receptor knockout mice (KO) with/without fenofibrate (30mg/kg/day in high fat diet). Ischemic recovery was assessed by laser doppler, foot movement and capillary density analysis. Key angiogenic events (tubulogenesis) and expression of thioredoxin-interacting protein (TXNIP) mRNA and protein following normal and high glucose (5 vs 25mM glucose) environments were determined in cultured endothelial cells (ECs), with/without selective PPARα receptor antagonist (10μM MK886) and agonist (10μM WY14643).

Results:
DM profoundly impaired blood flow recovery following hindlimb ischemia (0.51±0.04[n=5] vs 0.34±0.03[n=5];p<0.001). Fenofibrate (FF) restored DM-related impairment in blood flow recovery (0.53±0.04[n=5] vs 0.34±0.03[n=5];p<0.01), capillary density (1.48±0.03 vs1.20±0.04;p<0.01), foot movement scores to levels of non-diabetic controls. Similar findings for fenofibrate were observed in diabetic PPARα KO mice. In vitro, fenofibric acid (FA) rescued hyperglycemia-induced impairment in EC tubulogenesis (87.8 vs 58.3% of control;p<0.05) by a PPARα-independent mechanism. FA prevented hyperglycemia-induced overexpression of TXNIP (mRNA: 1.20±0.16 vs 1.84±0.28 folds of control;p<0.01) an exquisitely glucose-sensitive regulator of angiogenesis, in a PPARα-independent manner. Furthermore, overexpression of TXNIP abrogated the protective effects of FA.

Conclusions:
Fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis via a largely PPARα-independent mechanism. Improved neovascularization may therefore explain in part the reduced amputations seen with fenofibrate in type 2 diabetes. These findings provide a novel mechanistic understanding for fenofibrate action and may provide a platform for new drug targets.
Abstract 14789: A Rare Case of Primary Cardiac Leiomyosarcoma Involving the Left Ventricle
Authors: Khalid Hafiz D , Grunloh Danielle S , Bhatti Ahsan M , Rhee Benjamin J , Orakzai Sarwar
Published: July 2021

Case Report:
A 73 year old female was admitted to our hospital with complaints of acute shortness of breath on exertion and chest tightness accompanied with non-exertional left arm pain. Her prior history was significant for hypertension. Vital signs were significant for tachycardia. EKG revealed sinus tachycardia and low voltage QRS complexes. Cardiac Biomarkers were negative. CXR on admission showed massive cardiomegaly.

(A) Echocardiography, Off Axis, Apical long axis view showing a large mass attached to the LV apex surrounded by large pericardial effusion. Pericardiocentesis was performed and 1200ml of bloody fluid was removed.

(B) Cardiac MRI was performed which revealed a mass arising from the inferolateral wall of Left Ventricle measuring 6.5x4.9x6.2 cm

Left thoracotomy, wedge biopsy of left ventricular mass was performed. (C, D)Pathological analysis confirmed well differentiated Leiomyosarcoma (grade 1 of 3) FNCLCC grading system. Tumor was strongly positive for vimentin, smooth muscle myosin and desmin.
Abstract 14822: Impact of Proportional Assist Ventilation on Skeletal Muscle Reoxygenation and Central Hemodynamic During Constant Work Rate Exercise in Chronic Heart Failure
Authors: Borghi-Silva Audrey , Nery Luiz Eduardo , de Almeida Dirceu R , Neder Jose Alberto
Published: July 2021

Introduction:
Progressive chronic heart failure slows the recovery of microvascular oxygen delivery and utilization, which produce deleterious implications to exercise capacity. Respiratory muscle unloading can enhance the responses to exercise thereby allowing a closer matching between skeletal muscle oxygen delivery and utilization in patients with chronic heart failure (CHF).

Hypothesis:
We reasoned that noninvasive ventilation administered by proportional assisted ventilation (PAV) could accelerate skeletal muscle reoxygenation after high intensity exercise in CHF humans. To test this hypothesis, we conducted a study with 12 patients with stable CHF who were randomized to receive PAV or sham ventilation during high-intensity constant work exercise and compared the effects of these interventions on oxygen pulmonary (O2p), cardiac output and [[Unable to Display Character: ∆]][deoxi-Hb+Mb] off kinetics.

Methods:
Twelve patients with CHF (NYHA class II and III and left ventricle ejection fraction= 26±9%) underwent two high-intensity, constant-work rate (80% peak) cycle ergometer tests receiving PAV or sham ventilation. Off-exercise kinetics of the primary component of oxygen uptake, an index of fractional oxygen extraction by near infrared spectroscopy (~[[Unable to Display Character: ∆]][deoxy-Hb+Mb]) in the vastus lateralis) and cardiac output (QT) by impedance cardiography were assessed.

Results:
PAV significantly accelerated the recovery of O2p when compared with sham τ = 56±22 vs. 77±42s, respectively, p<0.05). Interestingly, PAV was associated with faster fractional O2 extraction (~[[Unable to Display Character: ∆]][deoxy-Hb+Mb] by near-infrared spectroscopy) (τ= 31±19 vs. 42±22s, respectively, p<0.05) . In addition, kinetics of QT were significantly faster with PAV than sham (τ = 39±22 vs. 78±46s, respectively, p<0.05).

Conclusions:
These data indicate that PAV has beneficial effects on recovery of muscle metabolism and central hemodynamics after high-intensity exercise in CHF patients.

Financial Support: FAPESP 2009-01842-0
Abstract 14842: Satellite Based Urban Land Cover and Proximity to Urban Center are Independent Predictors of Hypertension in a Southeast Asian Population
Authors: Thanikachalam Mohan , Lane Kevin J , Sunderarajan Jahnavi , Harivanzan Vijaykumar , Thanikachalam Sadagopan
Published: July 2021

Background:
Urbanization is linked to higher prevalence of cardiovascular disease (CVD). Hypertension (HTN) is a major risk factor for CVD. In this study we assess the impact of urbanization on prevalence of HTN in a population-based study in South India.

Methods:
In the cross-sectional analysis 8080 participants (mean age 42 years; 58% women) spread over 65 x 80 km area constituted the study sample. MODIS satellite derived land cover data at a 1 km x 1 km resolution was obtained and joined to each participant’s geolocated residential position in ArcGIS to assign urban and rural (crops, trees, shrubs and grass land cover) designations. Simultaneously, participants’ residential position in relation to urban center was assessed. The study included sytolic (SBP) and diastolic (DBP) blood pressure, anthropometric, socioeconomic, psycosocial, physcial activity assessemnts and blood work. HTN was defined as SBP ≥ 140 or DBP ≥ 90 or reported history of HTN.

Results:
Based on the land cover data the mean SBP and DBP (mmHg) in men (SBP: 131 ± 21; DBP: 81 ± 12) and women (SBP: 125 ± 20; DBP: 77 ± 11) living in urban environment were significantly higher when compared to men (SBP: 122 ± 18; DBP: 77 ± 11) and women (SBP: 117 ± 18; DBP: 74 ± 10) in rural environments [p < 0.001]. There was a significantly higher prevalence of HTN in urban men (42.1%) when compared to rural men (26.4%) [p < 0.001]. Similarly, the prevalence of HTN was higher in urban women (28.3%), when compared to rural women (19.1%) [p < 0.001]. After controlling for age, BMI, smoking, blood sugar, LDL and socioeconomic, physical activity, anxiety and stress levels, both men (OR = 1.94; 95% CI: 1.64, 2.9) and women (OR = 1.51; 95% CI: 1.28, 1.8) living in urban land cover were more likely to have HTN compared to those living in non-urban land cover. In the proximity analysis after multivariate adjustments, men (OR = 2.25; 95%CI: 1.78, 2.83) and women (OR = 1.87; 95%CI: 1.47, 2.38) residing within 0-20 km distance from urban center had significantly higher odds of HTN than the 60-80 km reference group.

Conclusions:
Living in an urban environment is associated with increased prevalence of HTN independent of other risk factors. Future research is needed to determine what components of the urban environment contribute to increased levels of HTN.
Abstract 14849: Gender Differences in Impact of CYP2C19 Polymorphism and Low Grade Inflammation on Coronary Spasm in Patients with Vasospastic Angina (VSA)
Authors: Akasaka Tomonori , Hokimoto Seiji , Tabata Noriaki , Sakamoto Kenji , Tsujita Kenichi , Kojima Sunao , Kaikita Koichi , Ogawa Hisao
Published: July 2021

Background:
Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. CYP2C19 localized in vascular smooth muscle and endothelium contributes to the regulation of vascular tone and homeostasis. However, it is unknown whether CYP2C19 genotype is associated with the vascular tonus in patients with VSA. The aim of this study was to examine the impact of CYP2C19 genotype on coronary artery spasm in patients with VSA.

Methods:
We examined the distribution of CYP2C19 genotype in patients with VSA (n=129) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Moreover, we measured the level of high-sensitive CRP (hs-CRP) as a degree of low glade inflammation in each group.

Results:
The ratios of CYP2C19 genotype (EM, IM, and PM) were 30, 42, and 28% in VSA group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in VSA than in control (28% vs 19%, P=0.026). In VSA group, the ratios of CYP2C19 genotype were 36, 44, and 20% in male, and 20, 39, and 41% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (41% vs 20%, P<0.001). Moreover, the level of hs-CRP was significantly higher in VSA group than in control group (0.17±0.367 vs 0.10.±0.240, P=0.02). When patients were stratified by gender, the level of hs-CRP was significantly higher in VSA group in female (0.11±0.198 vs 0.06±0.105, P=0.031) and male (0.20±0.438 vs 0.12±0.277, P=0.044). Multivariate analysis for coronary spasm indicated high age, hypertension, and high level of hs-CRP as predictive factors among all subjects. PM is a predictive factor for coronary spasm in female group only (OR3.1, 95%RI 1.525-6.317, P=0.002), but not in male (OR0.829, 95%RI 0.453-1.518, P=0.543).

Conclusion:
The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary artery spasm and the regulation of coronary tonus, especially in female.
Abstract 14873: Is There Difference in Clinical Outcomes Following Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS) between Hospitals With and Without Onsite Cardiac Surgery Backup?
Authors: Akasaka Tomonori , Hokimoto Seiji , Tabata Noriaki , Sakamoto Kenji , Tsujita Kenichi , Kojima Sunao , Kaikita Koichi , Ogawa Hisao
Published: July 2021

Background:
Based on 2011 ACCF/AHA/SCAI PCI guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, recent data suggests that there is no significant difference in clinical outcomes following primary or elective PCI between hospitals with and without onsite cardiac surgery. The proportion of PCI centers without onsite cardiac surgery comprises approximately more than half of all PCI centers in Japan. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI to ACS.

Methods:
From Aug 2008 to March 2011, subjects (n=2288) were enrolled from the Kumamoto Intervention Conference Study (KICS), which is a multicenter registry, and enrolling consecutive patients undergoing PCI in 15 centers in Japan. Patients were assigned to two groups treated in hospitals with (n=1954) or without (n=334) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored other events those were non-cardiovascular deaths, bleeding complications, revascularizations, and emergent CABG.

Results:
There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery (9.6%vs9.5%; P=0.737). There was also no significant difference when events in primary endpoint were considered separately. In other events, only revascularization was more frequently seen in hospitals with onsite cardiac surgery (22.1%vs12.9%; P<0.001). Kaplan-Meier analysis for primary endpoint showed that there was no significant difference between two groups (Log Rank P=0.943). By cox proportional hazards model analysis for primary endpoint, without onsite cardiac surgery was not a predictive factor for primary endpoint (HR 0.969, 95%CI 0.704-1.333; P=0.845). We performed propensity score matching analysis to correct for the disparate patient numbers between two groups, and there was also no significant difference for primary endpoint (6.9% vs 8.0%; P=0.544).

Conclusions:
There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.
Abstract 14884: Patients with Renal Impairment Derive Long-Term Benefit from Cardiac Resynchronization Therapy: Results from the MADIT-CRT Long-Term Follow-Up
Authors: Daimee Usama , Moss Arthur , Goldenberg Ilan , Solomon Scott , McNitt Scott , Polonsky Bronislava , Klein Helmut , Zareba Wojciech , Kutyifa Valentina
Published: July 2021

Background:
Whether patients with renal impairment experience benefit from cardiac resynchronization therapy plus an implantable cardioverter-defibrillator (CRT-ICD) during long-term follow-up is unknown.

Hypothesis:
We assessed the hypothesis that baseline renal function affects long-term risk of all-cause mortality and heart-failure events (HFEs) as well as benefit derived from CRT-ICD.

Methods:
We evaluated the impact of renal function in 1274 patients with mild heart failure and left-bundle branch block enrolled in MADIT-CRT. Patients with BUN>70 mg/dl or creatinine>3.0 mg/dl were excluded from the trial. Two subgroups were created based on the estimated glomerular filtration rate (GFR): GFR<60 and GFR≥60 ml/min/1.73 m2. Patients were studied over a follow-up period of 7 years for the end points of all-cause mortality and HFEs.

Results:
There were 413 patients with baseline GFR<60 ml/min/1.73 m2 (mean 48.1±8.3). Relative to those with GFR≥60 ml/min/1.73 m2 (mean 79.6±16.0), the low-GFR patients experienced greater risk of death (HR=2.14, 95% CI: 1.57-2.91, p<0.0001) and HFEs (HR= 1.31, 95% CI: 1.02-1.69, p=0.03). In both GFR groups, CRT-ICD relative to ICD alone was associated with significantly lower risk of death (GFR<60: HR=0.63, 95% CI: 0.42-0.94, p=0.024, absolute risk reduction [ARR]=12%; GFR≥60: HR=0.65, 95% CI: 0.42-0.99, p=0.049, ARR=8%) [Figure]. Similarly, there was significant reduction in the risk of HFEs (GFR<60: HR=0.36, 95% CI: 0.25-0.53, p<0.0001, ARR=27%; GFR≥60: HR= 0.42, 95% CI: 0.31-0.57, p<0.0001, ARR=17%).

Conclusion:
In conclusion, in mild heart failure patients, moderate renal dysfunction is associated with higher risk of all-cause mortality and HFEs relative to mildly impaired-to-normal renal function. While patients in both groups derive long-term benefit from CRT-ICD with similar relative reductions in all-cause mortality and HFEs, the greater absolute benefit occurs in patients with moderate renal disease.
Abstract 14897: Gender Differences and Flow Category Effects on Left Ventricular Remodelling in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction
Authors: Lin Weiqin , Kuntjoro Ivandito , Tay Edgar , Kong William , Yeo Tiong Cheng , Poh Kian Keong
Published: July 2021

Introduction:
Gender differences in the pattern of adaptive left ventricular (LV) hypertrophy to pressure overload from aortic stenosis (AS) has previously been identified. Differential effects in low versus normal-flow AS have not been investigated. We aim to examine effect of gender on LV remodeling in patients with low flow (LF) compared with normal flow (NF) AS.

Methods:
We studied 486 patients over a 12-year period with severe AS (valve area <1cm2) and preserved left ventricular ejection fraction (LVEF ≥50%). They were divided into LF (stroke volume index <35 ml/m2) and NF. Parameters were compared between genders.

Results:
There were 287 (59%) females, 93 (32%) were LF. In both genders, LV was smaller with lower mass index and higher relative wall thickness in the LF group. In the NF group, although aortic valve area index (AVAI) was larger in the females, mean gradient, peak velocity, degree of LV hypertrophy and LVEF were similar between the genders. LV volumes and LA dimensions were significantly smaller and larger in females respectively. Conversely in the LF group, all parameters indicate consistently more severe AS in males (Table). LVEF was lower and LV mass indexed to body surface area was higher in males (Table). The gender differences of end diastolic LV volume and LA dimension were similar between the categories. Valvuloarterial impedance was elevated and systemic compliance was reduced in the LF group in both genders compared to the NF group (Table).

Conclusions:
In patients with severe AS and preserved LVEF, LV appears smaller with lower mass and higher remodeling in LF compared to NF. Greater gender disparity in LV remodeling is documented in LF. Further studies on the prognostic significance are warranted.
Abstract 14908: The Success Rate of Automatic Pacing Threshold Determination Functions Differ among the Brands: What Was the Best Brand in a Far-East Single Center?
Authors: Hashiguchi Naotaka , Ueda Marehiko , Miyazawa Kazuo , Ishimura Masayuki , Kajiyama Takatsugu , Kanaeda Tomonori , Kobayashi Yoshio
Published: July 2021

Introduction:
Reliable automatic pacing threshold determination functions offer a reduced follow-up examination time and safe remote monitoring. Further, the success rate and accuracy of the automatic pacing threshold determination function have not been sufficiently clarified.

Methods:
We evaluated 456 patients (male/female: 269/187, age: 70.4±13.3 years, pacemakers/defibrillators: 341/115) with cardiac implantable devices that had an automatic pacing threshold measurement function (the atrium and ventricle/ ventricle only: 298/158). We measured their pacing thresholds with both the automatic and manual methods at periodic device examination visits. Patients who had a high threshold (>4.0V/0.4ms) or out-of-range lead impedance (>2000 or <200Ω) were excluded from the analysis.

Results:
An automatic pacing threshold was obtained successfully in 206/274 (75.2%) patients in the atrium and in 392/443 (88.5%) in the ventricle. The automatic pacing threshold differed from the manual threshold by more than 1.0mV at the same pulse width in 12 (4.0%) patients in the atrium and in 5 (1.1%) in the ventricle. The success rate of the automatic pacing threshold determination differed depending on which generator manufacturer was used. The success rate for each manufacturer (Medtronic, St. Jude Medical, Biotronik and Sorin) was 167/173 (96.5%), 9/64 (14.1%), 30/37 (81.1%), and 0/0 in the atrium, and 223/224 (99.6%), 79/102 (77.5%), 68/85 (80.0%), and 22/32 (68.8%) in the ventricle, respectively. Regarding the success rate, Medtronic devices were superior to the others in both the atrium and ventricle (P<0.001-P=0.039). St. Jude Medical devices were inferior to the others in the atrium (p<0.001). There were no other significant factors affecting the success rate. The correlation between the pacing threshold measured by the automatic method and that by the manual method was significant in the atrium (r=0.558, P<0.001) and ventricle (r=0.779, P<0.001).

Conclusions:
The success rate of the automatic pacing threshold determination depended on which generator manufacturer was used. The measurable threshold values using the automatic method were acceptably correlated with those measured by the manual method.
Abstract 14928: Adverse Outcomes Following Transcatheter Aortic Valve Replacement (TAVR) in Patients with Low Flow-Low Gradient (LFLG) Aortic Stenosis (AS)
Authors: Patel Jay N , Gadhvi Sonya , Salama Michael , Rios-Rojas Lilana , Islam Shahidul , Mattana Joseph , Goncalves John , Schwartz Richard , Marzo Kevin , Hafiz Abdul M
Published: July 2021

Introduction:
LFLG severe AS (stroke volume index <35 mL/m2 or cardiac index <3.0 L/min/m2 and transvalvular aortic gradient <40 mmHg) is associated with worse clinical outcomes following surgical aortic valve replacement. However, there is paucity of data regarding impact of low left ventricular flow and transvalvular gradient on outcomes following TAVR. We evaluated the impact of baseline LFLG on outcomes following TAVR in patients with severe AS at our institution.

Hypothesis:
Patients with LFLG severe AS undergoing TAVR will have a higher rate of adverse clinical outcomes.

Methods:
In a retrospective single center registry, we analyzed the clinical, 2D doppler-echocardiographic and outcome data in consecutive patients who underwent TAVR with the Edwards Sapien transcatheter aortic valve for symptomatic severe AS at our tertiary care hospital from March 2012 to April 2014. Patients with LFLG were compared to non-LFLG patients. Background medical data, clinical endpoints (defined by the Valve Academic Research Consortium-2), length of stay (LOS), readmissions and mortality, were compared between the two groups. Wilcoxon rank-sum and Fisher’s exact tests were used to evaluate the hypothesis.

Results:
LFLG was found in 66 (32%) out of 206 patients. Baseline characteristics were comparable between the LFLG and non-LFLG group, except significant difference in STS scores (12.1±8 vs. 9.9±8, p=0.011), prior aortic valve surgery (16.7% vs. 6.4%, p=0.041) and atrial fibrillation/flutter (57.6% vs. 29.3% (p<0.001). Overall, peri-procedural complications were similar between both groups, however, LFLG patients required: longer ICU monitoring (113.8±175 vs. 67.3±97 hours, p=0.01), longer hospital LOS (14.2±11.7 vs. 10.5±7.7 days, p=0.032). These patients had a non-significant trend toward 30 day mortality (7.6 vs. 4.3%, p=0.335) but a significantly higher 1-year all-cause mortality (19.7% vs. 9.3% p=0.044).

Conclusions:
LFLG patients had higher co-morbidities but comparable peri-procedural complications and short-term mortality. However this group was associated with longer hospitalizations and higher 1-year all-cause-mortality following TAVR. Further studies are needed to fully define outcomes in LFLG patients.
Abstract 14944: Elevated Peak Immune Monitoring Early After Transplantation is Associated with Angiographic Cardiac Allograft Vasculopathy
Authors: Cheng Richard , Azarbal Babak , Yung Aaron , Liou Frank , Patel Jignesh K , Kobashigawa Jon A
Published: July 2021

Introduction:
Early immune monitoring (IM) as measured by adenosine triphosphate release from activated lymphocytes is associated with coronary plaque progression by intravascular ultrasound.

Hypothesis:
Elevated IM is also associated with angiographic cardiac allograft vasculopathy (CAV).

Methods:
Patients transplanted between January 2007 and December 2011 with early post-transplant IM assays and annual angiographic follow-up were included. IM score was defined as the peak value of assays performed between two-months to mid-year after transplantation. A receivers operating characteristics (ROC) analysis was performed to determine an optimal IM assay cutoff. International Society of Heart Lung Transplantation CAV grading was used, 1 for mild, 2 for moderate, and 3 for severe. Patients were divided into two groups based on the cutoff score, and freedom from angiographic CAV was compared.

Results:
232 patients were included in the analysis. Mean age at transplantation was 56.7 ± 11.8 years and 25.9% were female. Peak IM assays occurred at 104.1 ± 43.7 days after transplantation, with an average of 3.2 ± 1.8 assays measured per patient. A ROC analysis determined an optimal IM assay cutoff of 458 ng ATP/ml. Group 1, n = 178, was defined as having peak IM assays <458 ng ATP/ml. Group 2, n = 54, was defined as having peak IM assays ≥458 ng ATP/ml. Mean peak IM assays for Group 1 and Group 2 were 243.1 ± 115.5 and 592.9 ± 155.5 ng ATP/ml, respectively. Mean clinical and angiographic follow-up were 4.0 ± 1.5 and 3.5 ± 1.6 years, respectively. As demonstrated in Figure 1, CAV1 occurred in 80 of 178 patients (44.9%) in Group 1, and 35 of 54 patients (64.8%) in Group 2, p-value 0.008 (Log Rank). CAV2/3 occurred in 6 of 178 patients (3.4%) in Group 1, and 8 of 54 patients (14.8%) in Group 2, p-value 0.002.

Conclusions:
Early elevated peak IM is associated with decreased freedom from angiographic CAV and suggests the potential use of IM in the tailoring of immunosuppression regimens for preventing CAV.
Abstract 14945: Electronic Cigarettes Are Effective for Smoking Cessation: Evidence From a Systematic Review and Meta-analysis
Authors: Rahman Muhammad A , Hann Nicholas R , Wilson Andrew M , Mnatzaganian George , Worrall-Carter Linda
Published: July 2021

Introduction:
Smoking is the leading cause of preventable death worldwide. Finding effective interventions for smoking cessation has proven difficult and existing interventions have limited consumer appeal. Electronic cigarettes (e-cigarettes) are becoming increasingly popular and a possible role for them in smoking cessation is being debated. Our objective was therefore to analyse existing research to investigate whether use of e-cigarettes is an effective smoking cessation method.

Hypothesis:
We assessed the hypothesis that use of e-cigarettes is an effective smoking cessation method.

Methods:
A systematic review of articles in English of any publication date was conducted by searching PubMed, Web of Knowledge and Scopus databases. Published studies investigating the effectiveness of e-cigarettes for smoking cessation among current smokers were included. Studies were systematically reviewed, and meta-analyses were conducted using the Mantel-Haenszel fixed-effect and random-effects models. Heterogeneity and quality of the selected studies were also evaluated.

Results:
Six studies were selected, including two randomised controlled trials, two cohort studies and two cross-sectional studies, and included 7,551 participants. Meta-analyses included 1,242 participants on whom complete smoking cessation data was available. Of these, 224 (18%) reported smoking cessation after using nicotine-enriched e-cigarettes for a minimum period of six months. Use of such e-cigarettes was positively associated with smoking cessation with a pooled Effect Size of 0.20 (95%CI 0.11-0.28). Nicotine filled e-cigarettes were more effective in achieving cessation compared to

those without nicotine (pooled Risk Ratio 2.29, 95%CI 1.05-4.97). Use of e-cigarettes was also effective in reducing smokers’ daily cigarette consumption. The studies included were heterogeneous, (I
2
=93%, p<0.001). A meta-regression model showed that 98% of this heterogeneity was caused by study design and gender variation.

Conclusions:
In conclusion, available literature suggests that the use of e-cigarettes may be an effective alternate smoking cessation method. Further research is required to investigate this among both genders.
Abstract 14952: Volumetric Echocardiographic Particle Image Velocimetry (V-Echo-PIV)
Authors: Falahatpisheh Ahmad , Kheradvar Arash
Published: July 2021

Introduction:
The two-dimensional (2D) echocardiographic particle image velocimetry technique that was introduced in 2010 received much attention in clinical cardiology. Cardiac flow visualization based on contrast echocardiography results in images with high temporal resolution that are obtainable at relatively low cost. This makes it an ideal diagnostic and follow-up tool for routine clinical use. However, cardiac flow in a cardiac cycle is multidirectional with a tendency to spin in three dimensions rather than two-dimensional curl. Here, for the first time, we introduce a volumetric echocardiographic particle image velocimetry technique that robustly acquires the flow in three spatial dimensions and in time: Volumetric Echocardiographic Particle Image Velocimetry (V-Echo-PIV).

Methods:
V-Echo-PIV technique utilizes matrix array 3D ultrasound probes to capture the flow seeded with an ultrasound contrast agent (Definity). For this feasibility study, we used a pulse duplicator with a silicone ventricular sac along with bioprosthetic heart valves at the inlet and outlet. GE Vivid E9 system with an Active Matrix 4D Volume Phased Array probe at 30 Hz was used to capture the flow data (Figure 1).

Results:
The 3D particle field was obtained with excellent spatial resolution without significant noise (Figure 1). 3D velocity field was successfully captured for multiple cardiac cycles. Flow features are shown in Figure 2 where the velocity vectors in two selected slices and some streamlines in 3D space are depicted.

Conclusions:
We report successful completion of the feasibility studies for volumetric echocardiographic PIV in an LV phantom. The small-scale features of flow in the LV phantom were revealed by this technique. Validation and human studies are currently in progress.
Abstract 14962: Weekend versus Weekday Admission and Morality from Acute Coronary Syndrome
Authors: Khoshchehreh Mahdi , Groves Elliott , Tehrani DavidM. , Malik Shaista
Published: July 2021

Introduction:
ACS is a common condition requiring urgent diagnosis and intervention. Previous smaller studies show poor outcomes for time-sensitive medical conditions during weekend admissions, however whether these associations persist is not known.

Hypothesis:
We assessed in-hospital mortality and utilization of invasive cardiac procedures following acute coronary syndrome (ACS) admissions on the weekend versus weekdays in the United States.

Methods:
We used the 2009 Nationwide Inpatient Sample to examine differences in all-cause in-hospital mortality between weekend versus weekday admitted patients with a principal diagnosis of ACS. Adjusted logistic regression and hierarchical logistic regression analyses were used to identify if weekend admission was associated with decreased utilization of procedural intervention and increased subsequent complications as well.

Results:
We identified 1054674 ACS admissions of which 22.1% were weekend admissions. Adjusted mortality for patients with NSTEMI was higher for weekend admissions [OR: 1.13; 95%CI: 1.10-1.16] and patients were significantly less likely to receive percutaneous coronary intervention, coronary artery bypass grafting, thrombolytic therapy, or coronary angiography on their first day of admission [OR: 0.68, 95%CI: 0.66-0.69]. Further, for weekend admitted ACS patients who underwent procedural interventions, in-hospital mortality and complications were higher compared to weekday admitted patients. Weekend admitted patients remained significantly less likely to receive a PCI, CABG, thrombolytic therapy, or coronary angiography (Adjusted OR: 0.73, 95% CI: 0.72-0.74).

Weekend admission was associated with longer hospital stay for NSTEMI patients. (Length of stay>3 days: OR: 1.20 (95%CI: 1.18-1.22).

Conclusions:
For ACS patients, weekend admission is associated with higher mortality and lower utilization of invasive cardiac procedures, and those who did undergo these interventions had higher rates of mortality and complications than their weekday counterparts. We speculate that access to diagnostic and interventional procedures maybe contingent on decreased staff and lower weekend coverage that may impact regular workflow.