bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17853: Activation of AMP-activated Protein Kinase (AMPKα) by AICAR Attenuates Klotho Deficiency-induced Endothelial Dysfunction, Arterial Stiffening and Hypertension
Authors: Lin Yi , Sun Zhongjie
Published: July 2021

Background:
Arterial stiffening and hypertension are progressive aging-related disorders. Klotho (KL) is a recently-discovered anti-aging gene but its role in the pathogenesis of endothelial dysfunction, arterial stiffening and hypertension is not fully understood.

Methods and Results:
Heterozygous
Klotho
deficiency (
KL
+/-
) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Plasma KL in KL heterozygeous mice (+/-) is about a half of that of the WT mice. Pulse wave velocity (PWV), an index of arterial stiffening, was increased in
KL
+/-
mice but not in WT mice fed on HFD for 4 weeks. Systolic blood pressure and blood glucose levels were increased earlier with greater magnitudes in
KL
+/-
mice than in WT mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of
KL
+/-
mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in
KL
+/-
mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in
KL
+/-
mice fed on HFD.

Conclusions:
Klohto deficiency promotes HFD-induced endothelial dysfunction, arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of endothelial AMPKα activity.
Abstract 17865: The Presence of Left Ventricular Scar in Atrial Fibrillation is associated with Major Adverse Cardiovascular Events
Authors: Suksaranjit Promporn , Akoum Nazem , Wilson Brent D , Biskupiak Joseph , Chang Lowell , Velagapudi Krishna , Navaravong Leenhapong , Damal Kavitha , Rassa Allen , Bieging Erik , Marrouche Nassir , McGann Christopher J
Published: July 2021

Introduction:
Left ventricular (LV) scar identified by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD) and cardiomyopathies. We studied the prognostic significance of LV-LGE in patients with atrial fibrillation (AF).

Methods:
We studied 778 consecutive patients referred for radiofrequency ablation of AF who underwent CMR exams between June 2006 and January 2013. Patients with history of CAD, prior myocardial infarction (MI), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) were excluded (24 patients). The presence of LV-LGE was assessed by two independent observers who were blinded to the clinical data and outcomes. The endpoint of interest was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, MI and ischemic stroke. MACE was determined by systematic retrospective review of electronic medical records and ICD-9 codes. Univariate and multivariate analysis were performed to identify predictors of MACE.

Results:
Of the 754 patients who met the inclusion criteria, 60% were male with an average age of 64 years and 87% had LV ejection fraction ≥ 55%. LV-LGE was found in 46 (6%) patients. There were 32 MACE over the mean follow up period of 53 months. The MACE rate was 13% in AF patient with LV-LGE compared to 3.7% in patient without LV-LGE (p = 0.002). In univariable analysis, age (HR 1.05, CI 1.01-10.9, p = 0.005), prior stroke (HR 1.64, CI 1.08-2.49, p = 0.021), CHADS2 (HR 1.75, CI 1.34-2.27, p < 0.001), CHA2DS2-VASc (HR 1.32, CI 1.15-1.52, p < 0.001), left atrial fibrosis (HR 1.66, CI 1.41-1.96, p < 0.001) and LV-LGE (HR 3.68, CI 1.52-8.95, p = 0.004) were significantly associated with MACE. In multivariate analysis, age and LV-LGE were independent predictors of MACE.

Conclusions:
In this large cohort of AF patients, LV -LGE is shown to be an independent predictor of MACE.
Abstract 17870: Hemodynamic Performance of Transcatheter Prosthetic Valve is Superior to that of Surgical Prosthetic Valve for Aortic Valve Stenosis with Small Aortic Root
Authors: Maeda Koichi , Kuratani Toru , Torikai Kei , Mizote Isamu , Ichibori Yasuhiro , Onishi Toshinari , Nakatani Satoshi , Sakata Yasushi , Ueno Takayoshi , Toda Koichi , Sawa Yoshiki
Published: July 2021

Introduction:
Surgical aortic valve replacement (SAVR) in a small aortic root is still challenging with regard to the surgical technique and prosthesis size selection, which often causes patient-prosthesis mismatch (PPM). On the other hand, because a prosthetic valve of transcatheter aortic valve replacement (TAVR) is tightly implanted inside a native valve, larger effective orifice area (EOA) may be gained. The aim of this study is to prove that hemodynamic performance after TAVR is superior to that after SAVR.

Methods:
160 patients, who underwent SAVR (n=36; age 75.1±5.6 years) and TAVR (n=124; age 82.4±6.8 years) for aortic valve stenosis, were enrolled. Preoperative ECG-gated multi-slice CT (MSCT) and echocardiography immediately before a discharge were performed in all patients. PPM was defined as the effective orifice area index ≤0.85cm2/m2 and we compared and examined hemodynamic performance after TAVR and SAVR.

Results:
Although the mean body size was significantly smaller (p<.05) in TAVR than that in SAVR (1.44±0.15 vs 1.51±0.20 m2), there were no significant differences in the diameters of annulus (23.2±1.6 vs 23.3±2.8 mm), valsalva sinus (29.8±2.6 vs 29.9±4.4 mm), and ST junction (25.2±2.8 vs 24.8±3.5 mm) on preoperative MSCT findings. Postoperative echocardiography revealed significantly less Vmax (2.2±0.4 vs 2.5±0.5 m/s, p<.0001), less mean pressure gradient (10.1±3.6 vs 14.5±5.0 mmHg, p<.0001), and larger EOA (1.62±0.29 vs 1.45±0.36 cm2, p<.005) in TAVR compared to SAVR, respectively. Consequently, PPM was more frequently in SAVR compared to TAVR (33.3 vs 8.9%; p<.0007). In multivariate analysis in SAVR identified small ST junction with only predictive factor of PPM (odds ratio [OR], 2.08; 95% CI, 1.23-4.36; p<.005; area under the receiver-operating characteristic curve [AUC], 0.84). On the other hand, regarding TAVR, large BSA was only predictive factor of PPM (p<.05).

Conclusions:
The hemodynamic performance of transcatheter prosthetic valve is superior to that of surgical prosthetic valve in a patient with small aortic root, in particular, small ST junction. TAVR should be considered in patients with anticipated PPM if the surgical risk is similar to TAVR.
Abstract 17960: Influence of a Weight Management Intervention for Overweight and Obese Cardiac Rehabilitation Patients on Macronutrient Dietary Intake and Use of Weight Loss Strategies
Authors: Barnason Susan A , Pullen Carol , Zimmerman Lani , Schulz Paula
Published: July 2021

Introduction:
The majority of cardiac patients who enter cardiac rehabilitation (CR) are overweight. However, few patients lose enough weight to reduce their risk for heart disease.

Purpose:
To examine the influence of a weight management (WM) intervention for overweight and obese CR patients on the outcomes of dietary macronutrient (protein, carbohydrate, and fat) intake and use of WM strategies.

Methods:
Overweight or obese CR patients were randomized to a 12-week WM intervention (n=22) or usual care (UC) (n=21) group. Baseline, 4- and 6-month data were obtained after cardiac revascularization [coronary artery bypass surgery (CABS) or percutaneous coronary intervention (PCI)]. The 3-day diet diary, analyzed with the Minnesota Nutrition Data System V5.0, measured dietary macronutrient intake. The Diet and Exercise Self-Management survey measured subjects’ use of WM strategies.

Results:
Using RM ANCOVA, there were no significant group * time interactions controlling for % of calories from dietary fat, carbohydrate or protein intake at baseline. There were significant main effects by group, with the WM group having a significantly [F(1, 38)=4.2, p=.04] lower % intake of calories from dietary fat (29.9% compared to 34.1% for the UC group); and a significantly [F(1,38)=8.5, p=.006] higher % intake of calories from protein intake (23.7% compared to 19.9% for the usual care group). At 4-months after CABS or PCI, the WM group reported significantly higher use of WM diet behavior strategies for self-monitoring diet intake [F(1,38)=11.3, p=.002], planning [F(1,38)=9.7, p=.003], preparing and buying [F(1,38)=12.2, p=.001], and portion control [F(1,38)=7.8, p=.008].

Conclusions:
The WM intervention influenced percentages of macronutrient dietary intake consistent with heart healthy diet recommendations. The WM intervention had an impact on improving reported use of weight loss strategies. Findings support the importance of a WM intervention for overweight and obese cardiac patients to improve weight outcomes not achieved in CR participation alone. Further research in a larger, controlled study is needed to examine how WM strategies can be integrated as an augmented intervention into standard CR.
Abstract 17964: Right Ventricular Reverse Remodeling during Long-Term Continuous-Flow Left Ventricular Assist Device Support in Patients with Dilated Cardiomyopathy
Authors: Saito Tetsuya , Toda Koichi , Miyagawa Shigeru , Nakamura Teruya , Yoshikawa Yasushi , Fukushima Satsuki , Yoshioka Daisuke , Kawamura Masashi , Harada Akima , Sawa Yoshiki
Published: July 2021

Introduction:
Although right ventricle (RV) failure as well as left ventricle (LV) failure can be of major concern in the treatment for severe heart failure, in clinical situation, only LV assist devices (LVAD) have been implanted despite the presence of RV failure. However, the circulatory and histological changes in the failed RV after long term continuous-flow (CF)-LVAD support have not been fully elucidated. In this study, we hypothesized that CF-LVAD long term support may ameliorate RV failure and have a positive impact on the distressed pathology of RV.

Methods:
This study included 16 dilated cardiomyopathy (DCM) patients who required long-term LVAD support, for 852 ± 84(129-1607) days, before heart transplantation (HTx). Echocardiograms were performed to analyze LV and RV functions. Transmural LV tissues and RV tissues sampled before LVAD implantation and after LVAD explantation were histopathologically analyzed for LV and RV remodeling.

Results:
Echocardiography showed significantly reduced LV end-diastolic and end-systolic dimensions during CF-LVAD support (73 ± 11 mm to 63 ± 13.6 mm, 67 ± 12 mm to 57 ± 17 mm, P<0.05, respectively). Regarding RV function, right ventricular end-diastolic dimension (RVDd) tended to decrease (48 ± 11 mm to 43 ± 10 mm, P=0.10) and the trans tricuspid pressure gradient (TRPG) was significantly decreased during long-term LVAD support (31 ± 14.8 mmHg to 12 ± 3.2 mmHg, P=0.01). Histopathologically, the sizes of cardiomyocytes in both the LV and the RV were significantly decreased during CF-LVAD support (left: 33.1±5.1 μm to 29.1±4.0 μm, P=0.05, right: 25.5 ± 2.4 μm to 21.6 ± 3.2 μm, P=0.01) and interstitial fibrosis tended to decrease in the RV (29.5 ± 3.1 % to 19.7 ± 7.2 %, P=0.10) despite there being no change in the LV (24.9 ± 10.8 % to 27.1 ± 12.1 %, P=0.14).

Conclusion:
Long-term CF-LVAD support ameliorates RV failure, possibly by reducing afterload on the RV followed by unloading of LV pressure overload, and thereby exerts a positive impact on RV reverse remodeling.
Abstract 17991: Angulation Range of Coronary Artery During the Cardiac Cycles is a Key Factor Inducing Stent Fracture; Demonstration by an in vitro Accelerated Durability Test
Authors: Iwasaki Kiyotaka , Arai Jun , Ohba Takafumi , Tokutake Hirotsugu , Xiaodong Zhu , Umezu Mitsuo
Published: July 2021

Introduction:
Stent fracture (SF) is recognized as one of the unsolved issues inducing restenosis or thrombosis. Hinge motion has been identified as a predictor of SF. The aim of this study is to elucidate SF probability of current drug eluting stents (DESs) against angulation ranges during the cardiac cycles, utilizing an in vitro accelerated durability tester.

Methods:
A cyclic-bend accelerated durability tester we have developed was used. Stents were deployed in elastic bend-artery replicas those mechanical stiffness was adjusted to that of referenced human coronary artery (stiffness parameter β=30±2). Three-link L605 CoCr stent (Xience Prime, Abbott Vascular), 2-link MP35N CoCr stent (Resolute Integrity, Medtronic), and 2-link PtCr stent (Promus Element, Boston Scientific) were chosen as test subjects. Influences of magnitude of angulation ranges on incidences of SF were investigated under the following bend conditions from 130 to 100 degrees (angular difference during the cycle (AD): 30 degrees), from 130 to 90 degrees (AD: 40 degrees), and from 130 to 80 degrees (AD: 50 degrees), respectively. Under each bend condition, three samples for each stent were tested for 1.0х10
8
cycles at 20Hz, those duration is equivalent to 2.5 years in vivo.

Results:
Under the AD of 30 degrees, multiple and single strut fracture were observed for each one of three L605 CoCr and MP35N CoCr stents, whereas no fracture was observed for PtCr stents. Under the severer ADs of 40 degrees and 50 degrees, all the three L605 CoCr and MP35N CoCr stents were multiply fractured, whereas PtCr stents had one single-strut-fracture and two multiple-strut-fractures among each three stents under the above conditions. These data indicated that PtCr stent platform has higher resistance to SF among wide ranges of cyclic-bend angulations. The total numbers of stent strut fractures of L605 CoCr, MP35N CoCr, and PtCr stents were 3, 1, 0 in the AD of 30 degrees, 20, 8, 1 in the AD of 40 degrees, and 18, 13, 4 in the AD of 50 degrees. Links were frequent sites of SF for CoCr stents, whereas crowns were those for PtCr stents.

Conclusions:
This study elucidated differences in fracture resistance against cyclic angulation ranges during the cardiac cycles and the critical angulation ramges for current three DESs.
Abstract 18012: Modeling of a Rare SCN10A Variant (A1886V) Linked with Early-Onset Atrial Fibrillation Shortens Atrial Action Potential Duration
Authors: Abraham Robert L , Savio-Galimberti Eleonora , Yang Tao , Roden Dan M , Darbar Dawood
Published: July 2021

Introduction:
SCN10A encodes the tetrodotoxin-resistant sodium channel isoform Nav1.8, which is variably expressed in neuronal tissue and heart and has been associated with atrial fibrillation (AF). We resequenced the SCN10A gene in 274 early-onset AF probands and identified a rare non-synonymous variant (A1886V) that co-segregated with AF in a kindred. In-vitro electrophysiological studies revealed that this variant displayed a “gain-of-function” phenotype with increased peak (INa-peak) and late (INa-L) sodium currents.

Hypothesis:
Here, we hypothesized that the increased peak and late INa associated with A1886V variant might modulate atrial action potential duration (APD) and thus increase susceptibility to AF.

Methods:
We used 2 Clancy-Rudy INa Markov models modified to fit wild-type (WT) and A1886V variant. Modeled currents were incorporated into the Courtemanche-Ramirez-Nattel model of human atrial AP. The overall SCN10A/Nav1.8 contribution to the total INa was simulated in the 5-50% range of WT-SCN5A/Nav1.5 current, and for each overall SCN10A magnitude, the contribution of A1886V compared to WT was simulated in the 0-to-100% range. Cycle-length used was 1000 ms (frequency 1 Hz).

Results:
While the precise magnitude of SCN10A atrial expression (WT and A1886V) has not yet been determined, simulation of a range of contributions of each component to atrial AP demonstrated incremental morphology changes with removal of the “spike and dome” and triangularization of AP associated with progressive shortening of APD90 (301 ms at 0% SCN10A contribution; 281 ms at 10% SCN10A [100% WT, 0% A1886V]; 261 ms at 10% SCN10A [0% WT, 100% A1886V]) (Table).

Conclusion:
Computational modeling of A1886V-SCN10A rare variant linked with familial AF surprisingly shortened atrial APD by removal of phase 1 “spike and dome” and augmentation of atrial AP “triangularization”, providing a potential mechanism for increased AF susceptibility.
Abstract 18075: Prevalence and Predictors of the Absence of Obstructive Epicardial Coronary Artery Disease in Patients Referred for Index Coronary Angiography
Authors: Löffler Adrián I , Ouellette Michelle L , Workman Virginia K , Beller George A , Bourque Jamieson M
Published: July 2021

Background:
As many as 62.4% of patients undergoing elective coronary angiography have no obstructive epicardial coronary artery disease (CAD). These patients have substantial morbidity and are inadequately characterized. Our aim was to identify the prevalence and predictors of the absence of epicardial obstructive CAD and to assess the clinical characteristics of this population.

Methods:
We conducted a retrospective analysis of consecutive patients undergoing index coronary angiography. Patients with known CAD, a history of myocardial infarction, or an emergent indication were excluded, as were those evaluated for transplantation or valvular/cardiac surgery. Obstructive CAD was defined as a stenosis ≥70% (≥50% left main). We performed multivariable logistic regression of clinical variables, peak troponin levels, and stress findings to identify predictors of the absence of obstructive epicardial CAD.

Results:
The study population included 935 patients with median age of 62 years and 10-year ASCVD risk score of 17.7%; 55.6% of the patients were male, 35.1% had diabetes, 77.3% had hypertension, and 67.8% had hyperlipidemia. No obstructive CAD was found in 442 patients (47.3%). Ten variables were independent predictors of the absence of obstructive CAD in a multivariable analysis (Table 1). In the 258 patients who underwent stress imaging, a negative stress ECG (OR 3.1 (1.6-6.0), p<0.001) and absence of ischemia on stress imaging (OR 3.6 (1.9-6.8), p<0.001) were additional independent predictors.

Conclusion:
Despite a cohort with substantial cardiac risk factors and an intermediate median ASCVD risk score, the prevalence of index angiograms without obstructive epicardial CAD was high. Traditional markers of disease were predictors, including positive troponin and stress imaging; however the model was only 78% predictive. Additional research is needed to better characterize patients referred for catheterization without obstructive CAD.
Abstract 18085: Heart Healthy Living: A community Based, Culturally Sensitive Cardiovascular Disease Education Program for Chinese Women at Roxbury Tenants of Harvard
Authors: Liu Laura , Sauris Aileen , Rodriguez Fatima , Foody Joanne
Published: July 2021

Background:
Acculturation is strongly associated with increased cardiovascular disease (CVD) risk and risk factors among Chinese immigrants into Western societies. There is a paucity in community-based health interventions targeted towards Chinese immigrants, and a growing need to develop such programs among this rapidly expanding population. We adapted the Heart Healthy Living (HHL) seminar series, a tailored health, nutrition, and physical activity education program, to address the challenges that Chinese immigrants face.

Methods:
HHL is a six week culturally suitable CV health program targeted towards Chinese women residing at Roxbury Tenants of Harvard (RTH). Each session was held in Chinese and consisted of an interactive lecture component on CVD prevention, followed by an exercise activity. Each participant completed a validated Heart Disease Knowledge Questionnaire (HDKQ) both pre- and post-seminar series, in addition to blood pressure, weight, height, and waist circumference measurements at each time.

Results:
A total of 30 women registered with median age of 65.5 years old. At baseline, 33% of the women suffered from hypertension and 30% of women had BMI considered at minimum “overweight” at an average of 26.33 kg/m2 with a mean waist circumference of 32.6 inches (+/- 4.3 inches). Overall, there were no significant changes in weight, blood pressure, or waist circumference. However, we found a 117% increase in proficiency of CVD knowledge in the HDKQ, from 34.6% correct to 75.3% correct upon completion of the seminar series (Figure 1).

Conclusions:
There was a profound increase in CVD literacy with HHL completion. Not unexpectedly, there were no changes in metrics taken during the seminar series. Longer and larger studies are necessary to determine reproducibility and changes in measurements taken. Furthermore, one year follow up and long-term interventions are necessary to assess the translation of knowledge into health-related outcomes.
Abstract 18114: Prevalence of Left Atrial Appendage Thrombus in Oncologic Patients with Atrial Fibrillation
Authors: Memon Nada , Briceno David F , Bhalja Mehul R , Banchs Jose
Published: July 2021

Introduction:
There is considerable evidence that the left atrial appendage (LAA) is a common site for thrombus formation and its characteristics pose varying risks for having embolic events. Furthermore, atrial fibrillation has been found to occur with an increased frequency in patients with malignancies. The lack of evidence of standardized treatment strategies in the cancer population forces physicians to take an individualized approach to atrial fibrillation and stroke prevention. Herein, we describe the LAA characteristics in a cancer population with atrial fibrillation.

Hypothesis:
Cancer patients have an increased risk of LAA thrombus formation in atrial fibrillation.

Methods:
This is a retrospective study to determine the prevalence of LAA thrombus in a cohort of oncologic patients with atrial fibrillation. Two hundred and forty-five patients underwent transesophageal echocardiogram (TEE) at MD Anderson Cancer Center during the period 2000-2013 for atrial fibrillation evaluation.

Results:
LAA thrombus was identified in 6.5% of patients (16 of 245). During follow up, three of these patients had experienced a stroke (19%). The mean age was 67 with 5 females (31%) and 11 males (69%). Fifteen patients were white. The majority of patients had solid tumors (75%, 12 of 16). The mean CHADS2 score was 1.3 +/- 0.9 and the mean left ventricular ejection fraction on transthoracic echo was 57 +/- 9%. Spontaneous echo contrast was noted on TEE in 56% of patients (9 of 16). Five patients were on antiplatelet therapy and 9 were on oral anticoagulants. Oncologic, TEE, and clinical data are detailed below (Table 1).

Conclusions:
The prevalence of LAA thrombus and stroke in cancer patients with atrial fibrillation is significant. These findings may be a reflection of the enhanced inflammatory state of cancer. This data suggest that LAA thrombus evaluation is critical in determining the anticoagulation strategy in atrial fibrillation patients with cancer.
Abstract 18130: Quantitative Heart Measures Are More Predictive of 1-Year Mortality Than Weight-Based Donor-Recipient Matching in Heart Transplantation
Authors: Taimeh Ziad , Murad Khalil , Colvin Monica , Duval Sue , Martin Cindy , John Ranjit , Eckman Peter
Published: July 2021

Introduction and hypothesis:
Donor-recipient matching in heart transplantation (HT) is heavily dependent on weight. The limited pool of donor hearts mandates efforts to expand that pool without compromising outcomes. We evaluated the impact of matching based on quantitative heart measures (QHMs) on 1-year survival after HT.

Methods:
Data from the United Network for Organ Sharing (UNOS) registry was used to calculate QHMs of both donors and recipients of HT. QHM uses validated mathematical models derived from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort based on height, weight, age, and sex to estimate total ventricular mass (TVM), total ventricular end-diastolic volume (TVV), and total cardiac volume (TCV). The matching level of each donor-recipient pair was assessed for each QHM; matched ±25%, undersized and oversized. Association between matching level (by weight, and by each QHM) and 1-year mortality rates were then analyzed.

Results:
We identified a total of 37,265 donor-recipient pairs between 1987 and 2013. Matching by weight did not have any 1-year mortality (p=0.43) benefit. Under-sizing or over-sizing by TCV had significantly higher 1-year mortality (p<0.001). Over-sizing by either TVM or TVV had significantly higher 1-year mortality (p<0.001, p=0.024, respectively) (Table and Figure).

Conclusions:
In HT, donor-recipient matching by QHMs derived from height, weight, age, and sex may offer advantages for making decisions about organ suitability over a weight-based algorithm.
Abstract 18134: Cardiomyocyte Overexpression of the alpha1A-Adrenergic Receptor in the Rat Protects Post-Infarct Heart Failure through Angiogenesis and the MEK-ERK Pathway
Authors: Zhao Xin , Pachon Ronald , Yan Lin , Lee Grace , Sui Xiangzhen , Beniamen Daniella , Balaji Poornima , Ho David , Vatner Dorothy E , Graham Robert M , Vatner Stephen F
Published: July 2021

α1A-Adrenergic receptors (α1A-AR) are important for regulating cardiac contractility, but whether they regulate coronary vessels is not known. To examine this we investigated the effects of chronic, complete coronary artery occlusion (CAO) in rats with cardiac myocyte-restricted transgenic (TG) α1A-AR overexpression, since protection of the heart with complete CAO requires increased blood flow. 4 weeks after permanent left anterior descending CAO TG rats displayed improved contractility vs. non-transgenic littermates (NTL) (n=8/group, p<0.05): 23% higher in LV dP/dt (7188±167mmHg/s), 13% higher in LV ejection fraction (57±0.9) and 23% lower in end-systolic wall stress (LVSWS) (79±6dynes/cm2) compared to NTLs. The scar size at 4 wks after CAO was significantly smaller in TG rats (18±2%) compared to NTL rats (28±3%), p<0.05, but more importantly there were increased blood vessels within the scar in the TG rat hearts suggesting angiogenesis. This was confirmed using colored microspheres to measure coronary blood flow, which was higher in area at risk in TGs (1.4±0.2ml/min/g) as compared to NTLs (0.5±0.08ml/min/g), p<0.05. This increased blood flow was further supported by a 41% increase in arterial density within the ischemic zone compared to NTLs at 2 weeks after CAO. In addition, capillary density was also found to be significantly increased, by 18% in the remote zone, compared to 2109 caps/mm2 in NTL. Utilizing an In vitro model, treatment with 25μM A61603 for 48 hours in cultured NTL neonatal myocytes resulted in an increase in VEGF-A secretion into the culture media and 26% increase in vascular tubule formation in HUVECs by a paracrine mechanism coinciding with an increased VEGF-A concentration compared to vehicle treated myocytes. Since VEGF is linked to the MEK-ERK signaling pathway, we blocked this mechanism by chronically administering the MEK blocker, U0126, sc. In these rats LV function was no longer different after 4 wks permanent CAO in TG and WTL treated with the blocker. Therefore, overexpression of cardiac myocyte specific α1A-AR in rats protected against cardiac dysfunction and remodeling associated with chronic myocardial infarction through the MEK-ERK pathway and via angiogenesis with a VEGF-A related paracrine mechanism.
Abstract 18164: Obesity Paradox in the Extremely Obese: Evaluaion of In-Hospital and Long Term Clinical Outcomes After Percutaneous Coronary Interventions
Authors: Singh Maninder , Mishra Abhishek , Sporn Daniel
Published: July 2021

Introduction:
Data regarding "obesity paradox" in patients with extreme obesity undergoing percutaneous coronary interventions (PCI) is limited and conflicting. We assessed clinical outcomes in patients with extreme obesity (Ex-Ob) compared to lean patients.

Methods:
From a single center prospective observational registry data, we assessed 1366 patients who underwent PCI from 01'-12'. We compared in-hospital and long term clinical outcomes between lean (body mass index (BMI ≤ 25kg/m2 , N=923) and Ex-Ob (BMI ≥40 kg/m2, N=443) patients.

Results:
The mean follow up duration was 3.6±2 yrs. Baseline characteristics are shown in table 1. Ex-Ob patients were younger, included fewer males and had higher frequency of cardiovascular co-morbidities (diabetes, hypertension, hyperlipidemia). There was no significant difference between the two groups with regards to in-hospital outcomes (death, major adverse cardiovascular events (MACE) or bleeding events). After multivariate adjustment for baseline differences, Ex-Ob patients had better long term overall (adj OR-0.63, 95%CI=0.41-0.95, p=0.029) and MACE free survival (adj OR-0.62, 95%CI=0.44 - 0.87, p=0.006) as compared to lean patients (Table 2 & Fig 1).

Conclusion:
Although there was no difference in short term outcomes, obesity paradox was observed in patients with extreme obesity with regards to long term clinical outcomes after PCI.
Abstract 18178: Cardiac Index Declines During Long-term LVAD Support
Authors: Kalathiya Rohan J , Chaisson Jordan M , Stevens Gerin R , Sciortino Christopher M , Shah Ashish S , Whitman Glenn J , Russell Stuart D , Tedford Ryan J
Published: July 2021

Background:
It is increasingly common for patients to be supported by left ventricular assist devices (LVADs) for an extended period of time. At our institution, we have anecdotally noticed a decline in functional status during the course of prolonged LVAD therapy. Our objective was to analyze hemodynamic and echocardiographic data of patients with at least 2 years of ongoing LVAD support.

Methods:
We retrospectively reviewed all patients who underwent HeartMate II implantation between 2005 and 2012. Of the 131 patients reviewed, we identified 20 patients who were supported by LVADs for at least 2 years and had right heart catheterization (RHC) in both the initial postoperative period and at 2-3 year follow-up. No patients were on inotropic therapy at the time of RHC.

Results:
The mean times of initial and follow-up post-LVAD RHCs were 59 ± 41 days and 889 ± 160 days, respectively. Cardiac index (CI) declined by an average of 0.4 L/min/m2 over the study period (p=0.04). Other than a reduction in transpulmonary gradient, no other hemodynamic differences were observed. There was a statistically significant worsening of aortic insufficiency (AI) at follow-up. However, when dichotomized by the median change in CI (-0.4 L/min/m2), there is no difference in AI between groups (p =0.60). In fact, 2 of the 3 patients with moderate AI had an increase in CI. There were no differences in pump speed, mean pressure, aortic valve opening, or lactate dehydrogenase between initial and follow up periods (Table 1).

Conclusion:
In the first study to report long term hemodynamic follow up in patients supported by HeartMate II LVADs, cardiac index significantly declined over time. The decline was not the result of worsening right ventricular function or valvular regurgitation nor a difference in pump speed or blood pressure. This is a potentially worrisome finding, especially for destination therapy patients. Further studies are needed to understand what factors may contribute to this decline.
Abstract 18180: Excellent Negative Predictive Value of Pulmonary Vein CT Angiogram in Detecting Left Atrial Appendage Stasis and Thrombus in a Large Clinical Cohort
Authors: Wang Lin , Koss Elana , Rapelje Kathleen , Kampfer Stephanie , Meng Hong , Reichek Nathaniel , Levine Joseph , Madhavi Kadiyala , Cao Jie J
Published: July 2021

Background:
While TEE is well established for detection of left atrial appendage (LAA) stasis and thrombus the role of pulmonary vein CT angiography (CTA) is controversial. We investigated the negative predictive value (NPV) of pulmonary vein CTA in detecting LAA stasis and thrombus in a large clinical cohort.

Methods:
Consecutive patients with a history of atrial fibrillation (AF) who had undergone pulmonary vein CTA and TEE within 24 hours were reviewed. TEE findings included LAA stasis (grade 1 to 4) and thrombus. Negative TEE findings were defined as no or grade 1 stasis and the absence of thrombus. CTA was performed using a bolus tracking protocol without ECG gating. In addition to qualitative evaluation of LAA filling defects, signal intensity of the LAA tip and ascending aortic blood signals were assessed. Using TEE as a reference standard, CTA was assessed for its NPV in detecting LAA stasis and thrombus.

Result:
In 833 patients, the median age was 61±11 years and 75% were male. During TEE 40% of patients were in AF or atrial flutter. There were 809 (97.1%) negative TEEs, 10 (1.2%) with grade 2 stasis, 9 (1.1%) with grade 3, and 5 (0.6%) with grade 4. Two patients with thrombi also had grade 4 stasis. Among 670 CTA negative patients, 669 (99.9%) were negative by TEE with only one false negative with grade 2 stasis by TEE. The NPV of CTA was excellent (99.9%) while the positive predictive value (PPV) was limited (14.1%) due to frequent false positive findings which did not differ significantly between patients in AF and patients in normal sinus rhythm. Quantitative analysis of signal intensity in the LAA tip did not improve PPV significantly, while the NPV remained high. Receiver operating characteristic analysis showed that the PPV and NPV using an LAA tip blood signal intensity cutpoint of ≤100 HU or a ratio of LAA tip/aorta blood signal intensity of ≤0.59 were 26%, 92%, and 12%, 100%, respectively.

Conclusion:
While PPV is limited, pulmonary vein CTA has excellent NPV and is a promising alternative to TEE for exclusion of clinically significant LAA stasis and thrombus. Confirmation of these findings in prospective multicenter clinical trials may lead to substantial reductions in the need for TEE in management of AF.
Abstract 18267: Effect of the Stress by Supercooling on Cell Proliferation and Immunogenicity of Transplanted Human Induced Pluripotent Stem (iPS) Derived Cardiomyoctes
Authors: Moriguchi Hisashi
Published: July 2021

BACKGROUND:
Cell preservation is essential for cell transplantation. I examined the effects of the stress by supercooling on the transplantation of human induced pluripotent stem (iPS) derived cardiomyoctes.

METHODS:
Human iPS derived cardiomyoctes were cultured for 20 days (control group), cryopreserved by supercooling macine for 1 week, and rapidly thawed and cultured for 20 days. Proliferation was compared among control and cryopreserved human iPS derived cardiomyoctes by constructing growth curves. Growth factors, cytokines, biochemical features, and cell cycle phase were measured immediately before and after cryopreservation by supercooling, and immunogenicity was evaluated from growth curves generated from human iPS derived cardiomyoctes after 7 days in mixed-lymphocyte culture. Control or cryopreserved human iPS derived cardiomyoctes were transplanted into pig connective tissues and evaluated histologically 2 weeks later.

RESULTS:
Cryopreserved human iPS derived cardiomyoctes proliferated more effectively than control cells (P<0.001). Levels of basic fibroblast growth factor and transforming growth factor-β1 were significantly higher (P<0.001), and those of interleukin (IL)-6 and IL-8 were significantly lower after cryopreservation (P<0.001). Fewer peripheral blood lymphocytes were produced in cryopreserved cells than in noncryopreserved cells (P=0.01), and the cell cycle phase of cryopreserved human iPS derived cardiomyoctes shifted primarily to G2 + M from G1 + G0. Noncryopreserved and cryopreserved human iPS derived cardiomyoctes both survived in connective tissue.

CONCLUSION:
The stress by supercooling can increase the proliferation of human iPS derived cardiomyoctes and also reduce the immunogenicity of the human heart cells.
Abstract 183: Outcomes for Major Trauma Patients in Counties Without Trauma Centers Are Worse: Nationwide Population-Based Research in Taiwan
Authors: Harnod Dorji , Chang Chu Hui , Chang Ray E
Published: July 2021

Background:
Some articles proved indirect-transfer the major trauma patients to the trauma centers had non-significant different outcomes with the patients direct-transfer to the centers. But the outcomes for the major trauma patients in the counties without trauma centers still can be worse. So we did a population based research by using the NHIRD data for the results.

Methods:
From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2006 to 2008, all of the trauma patients were identified from the database by the ICD-9-CM system. ICDMAP-90 was used for calculating the Injury Severity Score (ISS) as the variable controlling the disease severity. The patients of major trauma were defined as ISS more than fifteen. We used the diagnosis one year before the trauma admission for calculating Charlson Comorbidity Index (CCI). The first hospitals and the second transferred hospitals that the major trauma patients admitted, and the areas of the first hospitals were recognized in our data bank. The condition of transfer, age, genders, intubation, ICU admission, ISS, CCI, and the triage classifications were adjusted in a logistic regression model for further analysis.

Results:
There were 2497 major trauma patients (ISS more then 15). The total mortality rate was 12.49%. The variables like age, intubation, ICU admission, ISS and CCI were significant for mortality, but the condition of transfer was not significant in our model. After controlling all the factors, the major trauma patients that first admitted in the areas with no trauma centers have a significant higher risk of mortality (OR=1.73, P=0.005).

Conclusions:
Our results hint that, although indirect-transfer for the major trauma patients have insignificant difference in mortality with the direct transfer patients, the counties with no trauma centers have significant higher mortality rates in major trauma patients. Further researches are needed for investigating the possible reasons.
Abstract 18332: EphrinB2/EphB4 Signaling controls the Dose-Dependent Switch between Normal and Aberrant Angiogenesis by VEGF
Authors: Groppa Elena , Sacchi Veronica , Brkic Sime , Trani Marianna , Heberer Michael , Gianni-Barrera Roberto , Banfi Andrea
Published: July 2021

Vascular Endothelial Growth Factor-A (VEGF) is the master regulator of vascular growth and it can induce either normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo, and not on the total amount. However, stimulation of pericyte recruitment by co-expression of Platelet Derived Growth Factor-BB (PDGF-BB) could prevent aberrant structures despite heterogeneous and high VEGF levels and switch to homogeneously normal angiogenesis.

Here we dissected the role of specific pericyte-mediated signaling pathways in the switch between normal and aberrant angiogenesis by VEGF.

Monoclonal populations of transduced myoblasts were used to homogeneously express specific VEGF doses, inducing either normal or aberrant angiogenesis, and were further transduced to secrete soluble blockers of the TGFβ-1/TGFβ-R, Tie2/Angiopoietin or EphB4/EphrinB2 pathways (LAP, sTie2Fc and sEphB4, respectively). Two weeks after implantation into mouse limb muscles, neither TGFβ nor Angiopoietin blockade altered the normal angiogenesis by low VEGF, whereas EphrinB2/EphB4 inhibition caused a switch to aberrant angioma-like structures, similar to the effects of blocking pericyte recruitment. Conversely, gain-of-function of EphB4 signaling by systemic treatment with recombinant EphrinB2-Fc completely prevented aberrant angiogenesis by high VEGF levels and yielded normal networks of mature capillaries.

We recently found that VEGF over-expression in muscle induces angiogenesis without sprouting, but by circumferential enlargement and longitudinal splitting (intussusception). EphB4 inhibition increased both endothelial proliferation and the diameter of initial enlargements induced by low VEGF (4 days), leading to a failure of splitting and progressive angioma growth. However, it did not interfere with pericyte recruitment, contrary to high VEGF alone. Conversely, EphB4 stimulation decreased both endothelial proliferation and the diameter of enlargements induced by high VEGF to values similar to low VEGF alone, and accelerated splitting into pericyte-covered capillary networks.

In conclusion, EphrinB2/EphB4 signaling can prevent VEGF-induced aberrant angiogenesis by regulating intussusception.
Abstract 18339: Weight Loss with Low Carbohydrate Diets Improves Flow Induced Vasodilation in Resistance Arteries
Authors: Bian Jing-Tan , Szczurek Mary , Ranieri Christine , Grizelj Ivana , Cavka Ana , Robinson Austin , Marsh Gordon , Li Kevin , Sanyaolu Rasheed A , Shinde Shruti , Phillips Shane A
Published: July 2021

Introduction:
Obesity is associated with microvascular dysfunction and reduced nitric oxide (NO). We tested the hypothesis that NO-dependent, flow induced vasodilation in microvessels is improved by low carbohydrate diets designed for weight loss.

Methods:
Obese female adults (BMI = 32.0 ± 0.6 kg/m
2
, pre & post, n=22) were randomly assigned to a low carbohydrate (LC) diet for weight loss (LCWL, n=11, 500 calorie/day deficit). All meals were prepared for 6 weeks (10% carbohydrate, 30% protein, 60% fat). Resistance arteries (RAs, internal diameter of 16021 μm, n=22) were dissected from gluteal subcutaneous fat biopsies at weeks 0 (pre) and 6 (post). Vessels were cannulated and exposed to pressure gradients (Δ10-Δ100 cmH
2
O), with or without L-NAME (10
-4
M, inhibitor of eNOS), PEG-catalase (PEG-CAT, 500 Units/ml, scavenger of H
2
O
2
), indomethacin (INDO, 10
-5
M, inhibitor of cyclooxygenase), or pioglitazone (PIOG, 10
-5
M, PPARγ agonist) and to papaverine (10
-4
M), pre and post LC. NO or H
2
O
2
in RAs

was measured by fluorescence microscopy.

Results:
LC diets reduced BMI (post 32.7±0.8% vs. pre 31.4±1.0%, p<0.01), and increased flow-induced vasodilation (FID, post 81 ± 3% vs. pre 63 ± 4%, at Δ100 cmH
2
O (p<0.01) that was reduced by L-NAME and PEG-CAT (p<0.05). Consistently, vascular NO (fluorescence ratio: 1.5 ± 0.3, post vs. pre, p<0.05) and H
2
O
2
(2.6 ± 1.2, p<0.05) were increased with flow, and inhibited by L-NAME and PEG-CAT, respectively. INDO reduced FID in post, less (p<0.05) than in pre LC. There was no effect of pioglitazone on FID both in pre and in post (p>0.05). Endothelium independent responses to papaverine were similar in pre and post LC.

Conclusion:
We found that after 6 weeks of WL on low carbohydrate diet, 1) BMI was reduced, and microvascular vasodilator reactivity was improved; 2) microvascular NO and H
2
O
2
generation were increased; and 3) there was no effect of pioglitazone on FID in resistance arteries. These data indicate that weight reduction on low carbohydrate diet is critical for improved and endothelium-dependent microvascular function.
NIH
(
R01HL095701
).
Abstract 18473: Rates and Risk Factors for Faster Aortic Root Growth in Pediatric Patients with Marfan Syndrome
Authors: Viswanathan Nitya , Pedroza Claudia , Morris Shaine A
Published: July 2021

Background:
Marfan Syndrome (MS) is associated with progressive aortic dilation and aortic dissection. Aortic dissection is typically preceded by aortic dilation. The goal of this study is to identify factors associated with faster rates of aortic root dilation in children with MS.

Methods:
Patients undergoing serial transthoracic echocardiograms (TTE) with MS were retrospectively identified from an institutional database. Those with >2 TTEs over 1 year apart and <21 years of age at first TTE were included. TTEs performed after aortic surgery were excluded. Using multivariable longitudinal linear regression analysis, sex, medication, presence of ectopia lentis, need for scoliosis surgery and infantile type of MS were evaluated for associations with rate of change in aortic root dimension and aortic root z-score over time.

Results:
Of 240 patients with MS, 146 were included. Median age at first TTE was 8.1 yrs (range 0-20.9 years), median length of follow up 6.5 years (range 1.0-20.1 years), and median number of studies was 8 (range 2-25). Sixty-one percent were male. Of the 146 patients, 123 (84%) were documented to be on medical therapy: 14 angiotensin receptor blocker (ARB), 66 B-Blocker (BB), 10 prior history of both, 5 BB+ARB, 27 were in the Pediatric Heart Network medication trial, 1 ACE inhibitor. Sixteen patients underwent root replacement surgery at a median age of 14.6 years (range 1.8-24). No patients had aortic dissection. Three patients had infantile MS. All of these patients underwent root replacement at 1.8, 2 and 4 years of age. Two underwent subsequent aortic root replacement at 6 and 8 years old. Mean rate of aortic root growth in the cohort was 0.12cm/year, and mean change in z-score was 0.02/year (p=0.23 compared to expected rate of no change). The only variable associated with faster root growth was infantile MS (1.3cm/year, p<0.001; z-score change of 6.9/year, p<0.001). There was no significant difference in the rate of aortic root growth between patients who received therapy with BB vs. ARB vs. BB+ARB.

Conclusions:
Children with MS did not have a significant change in aortic root z-score over time, and the only factor associated with more rapid aortic root growth was infantile type MS.
Abstract 18516: Regional Dysfunction of Left Atrial Appendage and its Association with Stroke in Atrial Fibrillation
Authors: Alissa Abdullah A , Inoue Yuko , Cammin Jochen , Tang Qiulin , Fishman Elliot , Taguchi Katsuyuki , Ashikaga Hiroshi
Published: July 2021

Background:
Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF.

Methods:
Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model.

Results:
A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score.

Conclusions:
LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.