bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18889: Higher Serum Interieukin-6 is a Strong Postoperative Predictor of Delirium After Isolated Coronary Artery Bypass Graft Surgery
Authors: Sun Li , Ding Shu , Feng Xinwei , Wu Fangqin , Su Pixiong , Shen Yuzhi , Zhao Haibo , Wu Ying
Published: July 2021

Introduction:
Postoperative delirium (POD) is a common neuropsychiatric complication after coronary artery bypass graft (CABG) surgery and contributes to the morbidity and mortality. Although the pathogenesis of POD is largely unknown, surgery induced systemic inflammation might play a role. We examined the predictive values of serum interieukin-6 (sIL-6) level in predicting the occurrence of POD.

Methods:
Ninety nine patients undergoing the first time elective isolated CABG were consecutively recruited. All enrolled patients were assessed for POD twice a day for 5 days using the Confusion Assessment Method for Intensive Care Unit, and divided into either POD or non-POD groups. IL-6 levels were measured by ELISA (R&D Human IL-6 Quantikine) before operation (T0) and 6 (T6), 12 (T12) and 18 (T18) hours after operation. One-way repeated ANOVA was used to test the differences in trends and patterns of sIL-6 changes over time between the two groups. Logistic regression and ROC were performed to determine the predictive values of IL-6.

Results:
POD developed in 42.4% (42 of 99) patients. Among them, 90.4% POD occurred within the first 2 days after CABG. Patients with POD were older and more likely to be female. The sIL-6 levels were significantly higher in POD group than those in non-POD group with the highest levels at T6 and T12 (Figure 1). One-way ANOVA for repeated measures revealed interaction effects between time and group (with p values of <0.001 and 0.019). Logistic regression showed that sIL-6 level ≥491.37 pg/mL at T18 was a strong predictor of POD (OR=4.706, 95%CI 1.998-11.082, p<0.001) even after adjusting for age and female gender (OR=10.220, 95%CI 2.465-42.365, p=0.001), with a sensitivity and specificity of 66.7% and 68.4%, respectively.

Conclusions:
Higher sIL-6 level is an independent predictor of POD, and the sIL-6 level above 491.37pg/mL at 18 hours after CABG has a higher specificity in predicting the occurrence of POD.
Abstract 18892: Clinical and Hemodynamic Factors Influence the Risk of Pulmonary Hypertension in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights from the PARTNER I Trial and Registry
Authors: Lindman Brian R , Zajarias Alan , Maniar Hersh , Suri Rakesh M , Miller D. Craig , Webb John , Svensson Lars G , Xu Ke , Lin Fay , Wong Shing-Chiu , Babaliaros Vasilis , Thourani Vinod H , Douglas Pamela S , Lim Scott , Leon Martin B , Mack Michael J
Published: July 2021

Introduction:
Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS).

Hypothesis:
We hypothesized that clinical or hemodynamic factors might influence the relationship between significant PH and increased mortality.

Methods:
Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the PARTNER I randomized trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included. PH was defined as: none (mPAP<25 mmHg), mild (25 to <35), and mod/sev (≥35).

Results:
One year all-cause mortality was worse with increasing severity of PH: none (n=785, 18.6%), mild (n=838, 22.7%), and mod/sev (n=557, 25.0%) (p=0.01). The association between mod/sev PH (vs. no PH) and 1y mortality varied by sex and renal function (interaction p=0.03 and p=0.06, respectively). In females, mod/sev PH was associated with increased mortality (24.6% vs. 14.1%, HR 1.89, 95% CI 1.32-2.73); in males it was not (24.9% vs. 22.2%, HR 1.12, 95% CI 0.82-1.52). Additionally, mod/sev PH was associated with mortality in those with glomerular filtration rate (GFR) <40 (HR 1.76, 95% CI 1.28-2.42), but not in those with GFR ≥40. In a multivariable Cox PH model of patients with mod/sev PH, oxygen dependent lung disease, cerebrovascular disease, lower GFR, and lower baseline transvalvular mean gradient were each independently associated with increased 1y mortality (p<0.05 for all), whereas pulmonary artery compliance was the only hemodynamic variable associated with mortality (p=0.043) (Table).

Conclusions:
The relationship between mod/sev PH and increased mortality after TAVR is altered by sex and renal function. While lower pulmonary artery compliance is associated with increased mortality in patients with significant PH, clinical factors appear to be more influential in stratifying risk than hemodynamic indices.
Abstract 18901: Calgranulins S100A8, S100A9 and S100A12 are Novel Genes Modified by n-3 PUFA Supplementation and Evoked Endotoxemia in Humans
Authors: Ferguson Jane F , Xue Chenyi , Li Mingyao , Shah Rachana , Reilly Muredach P
Published: July 2021

Introduction:
We have previously identified genes involved in the adipose transcriptomic response to evoked endotoxemia in humans. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may modulate chronic low-grade systemic and adipose inflammation, conferring protection in cardiometabolic disease. However, given subtle effects of n-3 PUFA in vivo, intervention studies often lack power to detect effects on resting biomarkers. We applied unbiased transcriptomics (RNASeq) to human adipose tissue in healthy individuals following supplementation with n-3 PUFA in combination with evoked endotoxemia (LPS) as a unique genomic discovery model in n-3 PUFA modulation of inflammation.

Methods:
Using RNASeq we analyzed transcriptomes of adipose tissue biopsies from healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=7; 3600mg/day EPA/DHA) for 6-8 weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (LPS 0.6 ng/kg I.V.). We further explored candidate gene expression in response to n-3 PUFA and LPS using human monocytes and adipocytes in vitro.

Results:
The transcriptomic response to LPS was altered by n-3 PUFA supplementation. We found increased up-regulation of calgranulin genes in n-3 PUFA (S100A8 16-fold, p=0.002; S100A9 8-fold, p=0.002; S100A12 32-fold, p=0.01) compared with placebo (S100A8 2-fold, p=0.003; S100A9 1.4-fold, p=0.4; S100A12 5-fold, p=0.04). These inflammasome-activating genes may be involved in atherogenesis and inflammatory diseases, and may play a role in the recruitment of inflammatory cells to adipose tissue. We found differing calgranulin gene expression in vitro in adipocytes and monocytes after n-3 PUFA (up in monocytes, down in adipocytes post DHA p<0.001) and LPS treatment (n-3 PUFA dependent decrease in monocytes, increase in adipocytes) consistent with n-3 PUFA-dependent cell-type-specific responses to inflammatory activation.

Conclusions:
Unbiased transcriptomics and evoked inflammation permits enhanced genomic discovery in the context of nutritional intervention. A novel mechanism of n-3 PUFA protective effects in vivo may be through modulation of expression of calgranulin genes in response to innate immune activation.
Abstract 18902: Adaptive Servo-ventilation is More Effective in Dilated Cardiomyopathy Patients than Ischemic Cardiomyopathy Patients and Heart Failure with Preserved Ejection Fraction Patients
Authors: Ikeda Tatsunori , Fujimoto Manabu , Yamamoto Masakazu , Okeie Kazuyasu , Murai Hisayoshi , Usui Soichirou , Takamura Masayuki , Kaneko Shuichi
Published: July 2021

Introduction:
Central sleep apnea (CSA) is a common complication in heart failure patients (HF) and closely associated with poor prognosis. Adaptive servo-ventilation (ASV) is a new treatment for HF with CSA. Some study indicated ASV might improve cardiac function and its prognosis. However, there was little discussion by each background disease.

Methods and Results:
We examined 64 HF with CSA patients (involving 15 dilated cardiomyopathy (DCM) patients, 27 ischemic cardiomyopathy (ICM) patients, and 22 heart failure with preserved ejection fraction (HFpEF) patients) treated with ASV who had not been admitted to the hospital due to worsening HF in the 6 months before initiating ASV therapy. During 1 and 6 months observation, apnia-hypopnea index and brain natriuretic peptide were decreased significantly than baseline in all groups. There was similar in left ventricular ejection fraction in ICM and HFpEF groups during observation, however, in DCM group, there was significantly improved (29.3 +/- 14.3 to 36.5 +/- 12.4, and to 40.5 +/- 14.9%, P<0.01 compared with baseline). And left ventricular end systolic diameter was significantly shortened (53.7 +/- 11.1 to 30.4 +/- 11.5, and to 47.6 +/- 12.0 mm, P<0.01 compared with baseline), in spite of left ventricular end diastolic diameter was not changed.

Conclusions:
These results indicate that ASV is more effective in DCM patient with modifying hemodynamics and cardiac function than ICM and HFpEF patients.
Abstract 18908: Transcutaneous Aortic Valve Replacement - 30 Day and 1 Year Outcomes Using Conscious Sedation in Patients Stratified by STS Risk Score
Authors: Rajamanickam Anitha , Basnet Sandeep , Mucci Kaylan , Rao Ravinder , Yee Jimmy , Baber Usman , Dangas George , Kini Annapoorna , Adams David , Sharma Samin
Published: July 2021

Introduction:
Transcutaneous Aortic Valve Replacement [TAVR] is usually performed under general anesthesia [GA]. We sought to examine the feasibility and safety of monitored conscious sedation [CS] as opposed to GA .

METHODS:
196 patients [116 self expanding and 80 balloons expandable] underwent TAVR from December 2010 to August 2012 at our institution. 1 month follow up was completed on all patients and 1 year follow up was available on 105 patients. 39 patients [20%] underwent CS. Only one patient crossed over from CS to GA. We divided the patients into 3 groups [STS <8, STS of 8 to <12, STS ≥ 12 with the primary endpoints of all-cause mortality at 1 month and 1 year [See Table 1]

RESULTS:
Though the study did not meet statistical significance due to low number of patients, there was a trend towards improved mortality with CS. Also, there was no statically significant difference with regards to procedural complications including periprocedural MI, major bleeding, emergency CABG or major vascular complications. All 5 patients with periprocedural stroke had GA. The CS patients had a shorter length of stay [5 +2.87 days] as compared to GA patients [8 days+7.86 days]

CONCLUSION:
Use of CS suggested an improved mortality trend in higher risk patients [STS≥ 12]. This is of great importance as complications of GA, most importantly respiratory complications, are higher in the elderly TAVR patients and these can be avoided with CS . Also CS enables us to monitor neurological status during the procedure which is of vital importance given the high rates of stroke with TAVR
Abstract 18933: Regulation of Impaired Angiogenesis in Diabetes by Microrna26a
Authors: Icli Basak , Nabzdyk Christoph , Hernandez Jorge Lujan , Cahi Megan , Orgill Dennis , Feinberg Mark
Published: July 2021

Wound healing is a physiological reparative response to injury that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. In recent years, microRNAs (miRNAs) has been implicated in a wide-range of disease states. We have investigated the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to diabetic stimuli (e.g. high glucose, PKC activation) in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~2-fold) four days post wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to 80%), increased granulation tissue thickness (by 2.5 fold) and accelerated wound closure (by 50% after nine days) compared to scrambled anti-miR controls using a db/db mouse model of diabetes. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene, SMAD1, both at the mRNA and protein levels in ECs. In addition, increased SMAD1 levels correlated with increased ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27 nine days post-wounding of diabetic mice. Interestingly, inhibition of miR-26a increased migration and growth of both human microvascular ECs (HMVECs), human umbilical endothelial cells (HUVECs), and fibroblasts under normal glucose conditions. However, in the presence of high glucose, anti-miR-26a functional effects were abolished in fibroblasts, but not in HUVECs or HMVECs, suggesting cell-specific miR-26a regulated effects under diabetic conditions. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.
Abstract 18967: Analysis of Vitamin D Levels in Patients With and Without Statin-induced Myalgia - A Systematic Review and Meta-analysis of 7 Studies with 2416 Patients
Authors: Michalska-Kasiczak Marta , Sahebkar Amirhossein , Mikhailidis Dimitri P , Rysz Jacek , Muntner Paul , Toth Peter P , Jones Steven R , Rizzo Manfredi , Hovingh G. Kees , Farnier Michel , Lip Gregory Y , Banach Maciej ,   Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Published: July 2021

Introduction:
Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related muscle complaints, and symptomatic myalgia in statin-treated patients.

Hypothesis:
The aim of this meta-analysis was to investigate whether subjects with statin-induced myalgia have lower serum vit D levels compared with those who are asymptomatic.

Methods:
We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to March 2014) to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes.

Results:
The electronic search yielded 437 articles, of those 20 were scrutinized in the full text, of which 13 studies were considered unsuitable. The final analysis included 7 studies with 2416 statin-treated patients divided to subgroups of patients with (n = 666 [27.6%]) or without (n = 1750) myalgia. The combination of data from individual observational studies revealed a significantly lower vit D plasma concentration in the statin-induced myalgia compared with the asymptomatic subgroup with weighted mean difference -9.41 ng/mL(95% confidence interval (Cl): -10.17 to -8.64; p < 0.00001)
(figure)
.

Conclusions:
This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Well-designed, randomized controlled trials are necessary to establish whether vitamin D supplementation reduces risk for statin myalgia in patients with vitamin D deficiency.
Abstract 19049: CASK Regulates Sodium Channels Distribution and Function in Costameric Microdomain
Authors: Eichel Catherine A , Xianming Lin , Louault Florent , Dilanian Gilles , Delmar Mario , Hatem Stéphane N , Balse Elise
Published: July 2021

Introduction:
Proteins of the MAGUK family have emerged as key components in ion channels organization and regulation within specialized submembrane domains of cardiomyocytes. In this context, we investigated for the first time the expression, localization and function in the heart of the MAGUK protein CASK.

Methods and Results:
Surprisingly, no signal was detectable for CASK at intercalated discs, making CASK the first MAGUK to be excluded from these structures. On the contrary, CASK was located at the lateral membrane where it belonged specifically to the costameric dystrophin/glycoproteins complex (DGC). Since a lateral sub-population of Nav1.5 channels have been reported to interact with syntrophin, a member of DGC, we hypothesized that CASK could modulate Nav1.5 channels. Using high resolution 3-D deconvolution microscopy, we observed a co-localization of CASK and Nav1.5 in cardiomyocytes and co-IP experiments confirmed that the two proteins are in the same complex. Whole-cell patch-clamp recordings revealed a negative regulation by CASK of the sodium current INa carried by Nav1.5 channels in cardiomyocytes. Using super resolution scanning coupled to conventional cell-attached patch-clamp, we investigated the involvement of CASK on Nav1.5 function and localization in highly confined microdomains of the lateral membrane. INa was recorded in crests and T-tubules on freshly isolated cardiomyocytes obtained from adult rats injected with Adeno Associated Virus (eGFP-AAV-ShCASK or eGFP-AAV-ShScr). CASK silencing caused a drastic reduction of INa at the crest whereas it increased the current at the T-tubules suggesting that CASK retains Nav1.5 channels at the crest and prevents their clustering in T-tubules. In vivo CASK silencing in rat using an eGFP-AAV-ShCASK-injected was associated with a conduction slowing as indicated by the prolongation of the QRS duration, cardiac dilation and left ventricle systolic dysfunction.

Conclusion:
Taken together these results indicate that CASK is a major determinant of the organization of a subpopulation of Nav1.5 at the costamere of cardiomyocytes and that CASK-silencing induces electrical and morphological remodeling.
Abstract 19063: Mechanistic Comparison of “Nearly-Missed” versus “On-Target” Rotor Ablation
Authors: Avula Uma Mahesh R , Yamazaki Masatoshi , Honjo Haruo , Berenfeld Omer , Jalife José , Kodama Itsuo , Kamiya Kaichiro , Kalifa Jérôme
Published: July 2021

Introduction:
Recently, electrogram-based ablation strategies aiming at reentrant atrial fibrillation (AF) sources have demonstrated substantial efficacy. Still, the mechanisms by which these strategies modulate AF dynamics are unknown.

Objective:
Here, we employed advanced optical mapping approaches to examine AF dynamics before and after two distinct electrogram-based ablation strategies: highest dominant frequency sites/rotor ablation (DFmax/rotor, “on-target”); and complex fractionated atrial electrograms ablation (CFAE, “nearly-missed”).

Methods:
We implemented a high-resolution optical mapping set-up that enabled simultaneous epicardial and endoscopy guided endocardial recordings in Langendorff-perfused sheep hearts. After inducing AF in the presence of continuous perfusion of acetylcholine (ACh), we recorded optical movies from the left atrial free wall (LAFW) as well as the posterior left atrium (PLA). Then, DFmax regions (n=4) or CFAE regions harboring the highest wavebreak density (HWD, n=5) were targeted with a 4F ablation catheter (5-15W, 30-60 sec/point).

Results:
On-target DFmax/rotor point ablation resulted in a significant decrease in bi-atrial DFmax values (18.02±3.16 to 12.9±2.6, p<0.05, n=4) and AF termination after that a high frequency rotor was targeted (n=1). In contrast, LAFW point ablation in nearly-missed HWD regions- located at the boundaries of DFmax domains, in the vicinity of AF sources - did not significantly modulate AF frequency of excitation, (LAA DFmax: 15.16±4.98 to 14.26±3.38 Hz, n=5; p=0.205). Rather, DFmax domains relocated to PV-PLA regions (3/5 hearts) and to the roof (2/5 hearts). In another group of hearts (n=12), we examined 3-dimensional rotors- a.k.a scroll waves - dynamics during a progressive increase in ACh concentration from 0 to 0.2 μM. Under these conditions, scroll waves formed at the PLA reproducibly drifted to the LAFW along the free wall pectinate muscles, or other structures characterized by large myocardial thickness gradients.

Conclusions:
On-target DFmax/rotor ablation leads to large decreases in AF frequency and AF termination. In contrast, nearly-missed CFAE/HWD ablation leads to scroll wave relocation and/or drift along large myocardial thickness gradients.
Abstract 19086: Myofilament Proteins of the Naked Mole-rat Heart Reflect Low Basal Species Cardiac Function
Authors: Grimes Kelly M , Barefield David , Kumar Mohit , de Tombe Pieter P , Sadayappan Sakthivel , Buffenstein Rochelle
Published: July 2021

The naked mole-rat (NMR) is a mouse-sized rodent with a maximum longevity of >31 years. The species exhibits low basal heart rate (256 bpm) and cardiac output (7 ml/min) for its body size, as well as low fractional shortening (28%) for a rodent. However unlike other well-studied mammals, the NMR maintains cardiac reserve and diastolic function for at least 75% of its maximum lifespan - at ages equivalent to 90 year old humans. We questioned if this low basal cardiac function was due to NMR myofilament composition and function. NMR ventricles are comprised primarily of the β-myosin heavy chain isoform, which is associated with slowed myocardial contraction and increased efficiency. This is in stark contrast to mouse ventricles, which express predominately the α-isoform, and switch to the β-isoform upon experimental induction of heart failure. Compared to mice, NMR myofilament proteins such as cardiac troponin I and cardiac myosin binding protein-C display lower levels of phosphorylation. Such levels are indicative of decreased activation of myofilament proteins and may relate to the species’ low basal cardiac function. Both the NMR’s predominance of β-myosin heavy chain and the low basal level of myofilament phosphorylation present a phenotype much closer to that seen in human ventricles than in those of mice. Intriguingly, maximal force developed by skinned NMR cardiomyocytes is not significantly different to that of mouse cardiomyocytes (NMR: 70.9 ± 9.3mN/mm2 vs. mouse: 87.7 ± 0.6 mN/mm2). This is likely a reflection of the NMR’s ability to enhance cardiac function to the level of a mouse when stimulated, as is evident when both species are treated in vivo with dobutamine (3 μg/g i.p.). Such low basal cardiac function may put less overall strain on the heart over time and could be critical to the NMR’s ability to maintain cardiac function with age.
Abstract 19099: The Fractional Excretion of Urea is Substantially Altered by Diuretics in Heart Failure Patients: Implications for its Use in the Evaluation of Worsening Renal Function
Authors: Cheng Susan J , Laur Olga , Kula Alexander J , Onyebeke Chukwuma O , Coca Steven G , Perazella Mark A , Testani Jeffrey M
Published: July 2021

Background:
In the setting of acute decompensated heart failure (ADHF), significant renal dysfunction (RD) is a common both at presentation and during treatment. The fractional excretion of urea (FeUrea) is often recommended to differentiate “pre-renal” from intrinsic RD in patients receiving diuretics. However, the intra-renal physiology regulating urea reabsorption theoretically should be affected by high dose loop diuretics which are commonly utilized in ADHF.

Methods:
Heart failure patients presenting to the Yale Transition Care Clinic who received treatment with loop diuretics were enrolled (n=64). Urine was collected at baseline and 60-90 minutes following administration of loop diuretics. Possible AKI was defined as a presenting serum creatinine ≥0.3 mg/dl above the lowest outpatient level in the prior 12 months.

Results:
Overall, 75.9% of the cohort had an estimated glomerular filtration rate < 60 ml/min/1.73m^2 and 66.7% met criteria for possible AKI. As would be expected in a sodium avid HF population, the mean pre-diuretic FeUrea was 31.9 ± 10.2%. This was below the “pre-renal” FeUrea cutoff (<35%) in 62.5% of patients. Following administration of 160 mg (50 to 280) of IV furosemide equivalents, FeUrea increased by an average of 7.3 ±8.5% (p<0.0001). After diuretics, the percentage of patients with a “pre-renal” FeUrea decreased to 37.7% which translated into 42.5% of initially “pre-renal” patients no longer being classified as “pre-renal.” The change in FeUrea was unrelated to the diuretic induced urine output (r=0.19 p=0.14) or the dose of diuretic (r=0.17, p=0.20). There was significant individual variability in the change in FeUrea induced by loop diuretics (Figure) such that a loop diuretic “correction factor” would not be appropriate.

Conclusion:
Contrary to traditional wisdom, FeUrea does not appear to be a reliable tool to workup changes in renal function in ADHF patients receiving treatment with high dose loop diuretics.
Abstract 19108: Anticoagulation Treatment in High-Risk Medicare Advantage Patients with Non-Valvular Atrial Fibrillation
Authors: Bruno Amanda S , Trocio Jeffrey N , Wiederkehr Daniel , Abdulsattar Younos , Gdovin Joette , Brown Courtney , Dye Joseph T , Louder Anthony M , Mardekian Jack , Pasquale Margaret
Published: July 2021

OBJECTIVE:
Examine anticoagulation (AC) treatment in Medicare Advantage Prescription Drug (MAPD) plan members diagnosed with non-valvular atrial fibrillation (NVAF) and at high risk for stroke.

METHODS:
A retrospective analysis of claims data from a large US health plan was conducted. Patients with NVAF were identified between 1/1/2011 and 11/30/2013. Index date was based on NVAF diagnosis and patients were required to have ≥18 months of continuous enrollment: 6 months pre-index and 12 months post-index. Pre-index stroke risk was calculated using the CHADS
2
. Patients classified as high risk (CHADS
2
score ≥2) were included in the analysis. Post-index AC treatment options were warfarin and novel oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban. The proportion of high-risk patients with time in therapeutic range (TTR)≥60% was calculated among those receiving warfarin with ≥2 INR values within a 3-month period. Adherence among high-risk patients receiving a NOAC or warfarin without available INR values was calculated using the proportion of days covered (PDC)≥80%. Risk for major bleeding was also calculated using the HASBLED score. Descriptive statistics were used to summarize AC treatment.

FINDINGS:
Of 93,864 patients with NVAF, 70,646 were identified as high risk for stroke. Among them, 36,601 (51.8%) were treated with an AC while 34,045 (48.1%) did not receive any AC treatment during post-index. Of those treated with an AC, 30,802 (84.2%) were treated with warfarin and 5,799 (15.8%) were treated with a NOAC. TTR was calculated for 7,034 (22.8%) of those receiving warfarin, of which 3,215 (45.7%) had a TTR≥60%. PDC≥80% was observed for 13,758 (57.9%) of the remaining warfarin users and 3,353 (58.7%) of NOAC users. A total of 64,191 (90.8%) patients had a HASBLED score ≥3.

CONCLUSIONS:
A large proportion of NVAF patients at high risk for stroke are untreated or potentially undertreated_as evidenced by the low TTR values and low adherence estimates observed here. These patients’ high risk levels for stroke and major bleeding necessitate optimal prophylactic treatment with AC and careful management. Further research with providers may identify potential causes for non-treatment and undertreatment with AC in high risk NVAF patients.
Abstract 19143: Role of Cardiac Biomarkers in Diagnosing Takotsubo Cardiomyopathy from Left Anterior Descending Artery ST Elevation Myocardial Infarction
Authors: Akbar Ghulam , Badri Marwan , Prince Catherine , Saeed Wajeeha , Mirrani Ghazi , Ameen Muhammad , Soomro Armaghan Y , Shapiro Timothy , Sardar Muhammad R
Published: July 2021

Introduction:
Takostubo cardiomyopathy (TK) and STEMI in the proximal to mid LAD territory (LAD-S) may have similar clinical, ECG and echocardiographic presentation. The two can only be differentiated using coronary angiography.

Hypothesis:
We hypothesized that the ratio of serum BNP to troponin-I(TnI) will help in distinguishing TK from LAD-S. Previously it has been studied in TK and STEMI from any coronary artery lesion. This is the first study to tease out LAD-S and TK by using BNP/TnI ratio .

Methods:
We retrospectively compared patients who presented with LAD-S and patients with TK (confirmed with non-obstructive coronary angiography, classic echocardiographic appearance and subsequent improvement of LV function). Patients who did not have BNP and TnI available were excluded.

Results:
Out of 313 patients with LAD-S and 464 with possible TK, 39 and 62 patients were included respectively. Mean BNP and TnI levels were 788, 57.6ng/dl and 923, 3.4ng/dl in LAD-S and TK respectively. A BNP/TnI ratio of ≤6.4 was 100% sensitive and 41% specific to diagnose LAD-S, and therefore has 100% negative predictive value. A BNP/TnI ratio of ≥2388 was 80% sensitive and 93% specific for diagnosing TK.

Conclusion:
BNP/TnI ratio <6.4 is reliable to rule out TK and lead to the diagnosis of LAD-S in patients with typical echocardiographic findings. Further, larger observational studies are needed to validate the use of biomarkers for this purpose.
Abstract 19160: Insulin Resistance over a 10-Year Period is Associated with Coronary Atherosclerosis in HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study
Authors: Brener Michael , Post Wendy S , Reynolds Sandra , Palella Frank J , Jacobson Lisa P , Dobs Adrian , George Richard T , Witt Mallory , Budoff Matthew , Kingsley Lawrence , Brown Todd T
Published: July 2021

Aims:
HIV infection and its treatments are associated with insulin resistance and diabetes, which may influence the risk of coronary artery disease (CAD). We investigated the degree of insulin resistance in HIV-infected and uninfected men and its association with coronary atherosclerosis.

Methods:
We conducted a multicenter, cross-sectional study which included 448 HIV-infected and 306 uninfected men, ages 40 to 70 years old, without a history of prior coronary revascularization from the Multicenter AIDS Cohort Study (MACS). Coronary computed tomography angiography (CTA) was performed to identify the presence of coronary artery plaque, to characterize plaque composition (calcified, non-calcified, and mixed), and to identify coronary artery stenoses > 50%. Insulin resistance was evaluated by the homeostatic model assessment (HOMA-IR) measured at each semi-annual visit between 2003 and 2014. The mean HOMA-IR was calculated from all visits before participants underwent CTA. Associations between HOMA-IR and the prevalence of plaque or of stenosis > 50% were assessed with logistic regression by adjusting for age, race, HIV serostatus, and CAD risk factors.

Results:
Mean HOMA-IR compiled over a median of 8.4 years was higher in HIV-infected than uninfected men (3.2 vs. 2.7, p = 0.002), but the prevalence of stenosis > 50% was similar (17% vs. 15%, p = 0.41). In fully adjusted models comparing men in the highest and lowest tertiles of mean HOMA-IR, mean HOMA-IR was associated with the presence of stenosis > 50% (OR = 2.81 [95% CI, 1.51-5.22]), but not with any particular plaque type. There was no significant interaction between HIV serostatus and associations between mean HOMA-IR and coronary stenosis. Among HIV-infected men, further adjustment for HIV disease control and severity (suppressed HIV-1 RNA, CD4 T-cell count) did not alter the association between mean HOMA-IR and the presence of stenosis > 50% (OR = 2.67 [95% CI, 1.26-5.89]).

Conclusions:
Insulin resistance over a 10 year period was greater among HIV-infected than uninfected men and was associated with coronary artery stenosis, but not with any specific plaque type. Our findings suggest that insulin resistance is a potential mechanism mediating the increased risk of CAD among HIV-infected men.
Abstract 19163: Implication of DNA Damage Signaling and Epigenetic Readers in Metabolic Disorder Observed in Vascular Wall of Ischemic Patients
Authors: Meloche Jolyane , Henry Sarah , Le Guen Marie , Charbonneau Eric , Provencher Steeve , Bonnet Sebastien
Published: July 2021

Background:
Coronary artery stenosis is characterized by coronary artery smooth muscle cell (CoASMC) proliferation and survival in detrimental conditions (increased inflammation, oxidized lipids, shear stress) known to cause DNA damage. In cancer, increased cell proliferation was attributed to DNA damage signaling activation secondary to mitochondrial/metabolic dysfunction. This leads to the upregulation of Poly(ADP)ribose-polymerase 1 (PARP-1), a critical enzyme acting as a DNA damage sensor, and the epigenetic reader Bromodomain-containing protein 4 (BRD4), both known to contribute to cell survival and proliferation. In light of these observations, we hypothesized that impaired mitochondria/metabolism triggers DNA damage signaling in coronary artery stenosis leading to CoASMC proliferation and thus vessel narrowing.

Method/Results:
Primary cultured human CoASMC from patients with stenosis (n=3) exhibit signs of mitochondrial dysfunction including hyperpolarization (TMRM; n=3, p<0.05), downregulation metabolic sensors Sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1 (PGC1-α) expression (western blot (WB); n=3, p<0.05). These cells also exhibit enhanced glycolysis compared to control hCoASMC (Seahorse Bioscience XF24e; n=3, p<0.05). These mitochondrial/metabolic abnormalities enhance DNA damage signaling in human coronary arteries with stenosis (53BP1; n=8, p<0.05), as well as PARP-1 and BRD4 expression (WB; n=4, p<0.05) compared to control arteries. This pathogenic phenotype is also present in isolated hCoASMC issued from stenosis, as they have more DNA damage sites (γH2AX; n=5, p<0.05) and exhibit increased PARP-1 and BRD4 expression (WB; n=4, p<0.05) compared to control hCoASMC. PARP-1 and BRD4 activation in pathologic hCoASMC promote proliferation (Ki67; n=5, p<0.05) by downregulating cell cycle inhibitors p300 and p21 (WB; n=3, p<0.05), leading to cell survival (MTT assay; n=3, p<0.05). This pathological phenotype was reversed upon treatment with a PARP-1 (Veliparib, 10μM) or a BRD4 (JQ1, 1μM) inhibitor.

Conclusion:
Our study suggests an important role for BRD4 signaling and metabolic disorder in coronary diseases and opens the door to new avenues of investigation and treatment.
Abstract 19185: Upregulation of DJ-1 Protein after Prolonged Ischemia in a Murine Model for Myocardial Ischemia and Reperfusion
Authors: Seres Tamas , Klawitter Jelena , Christians Uwe , Eckle Tobias
Published: July 2021

Introduction:
Upregulation of cardiac DJ-1 protein might be a cardio-protective mechanism under conditions of ischemia or ischemia and reperfusion by regulating mitogen activated protein (MAP) kinases or inducing enzymes for detoxification and glutathione metabolism. We recently observed that significantly elevated DJ-1 protein expression was associated with decreased expression of phosphatase and tensin homolog (PTEN) and increased phosphorylation of the cell protective kinase AKT (protein kinase B) in human heart tissue samples from patients with chronic ischemic cardiomyopathy.

Hypothesis:
The expression of DJ-1 protein and its interaction with PTEN and AKT during ischemia or ischemia and reperfusion in a murine heart model might play a cardio-protective role.

Methods:
The level of DJ-1 was analyzed from the area at risk after 30 or 60-minute ischemia or 30-minute ischemia with 30 or 60 minutes of reperfusion using C57BL/6J mice (n=3). The changes in DJ-1 expression were correlated with the expression of PTEN and AKT and phosphorylation of ERK1/2 (extracellular signal regulated kinase) and P38. The protein levels and their phosphorylation were evaluated by Western blot analysis.

Results:
Expression of DJ-1 increased significantly after 60 minutes of ischemia while PTEN decreased after 30 minutes of ischemia followed by 30 or 60 minutes of reperfusion both were associated with increased phosphorylation of AKT. The phosphorylation of ERK1/2 was increased at all time points of ischemia or ischemia and reperfusion while phosphorylation of P38 was increased only during ischemia and reperfusion.

Conclusions:
The increased expression of DJ-1 protein is a potential marker for prolonged ischemia. Although, PTEN expression were not decreased with increased DJ-1 levels, a direct inhibiting effect of DJ-1 on PTEN might increase the phosphorylation of the cell protective AKT during 60-minute ischemia. A DJ-1 independent decrease of PTEN expression might contribute to the increased AKT phosphorylation during ischemia reperfusion. Phosphorylation of ERK1/2 was a sensitive marker of early or late ischemia and ischemia and reperfusion. The role of the DJ-1-AKT interaction in preventing P38 phosphorylation during ischemia needs further investigation.
Abstract 19192: Utility of Cardiac Computed Tomography in Detecting Malposition of Left Ventricular Assist Devices Associated With Pump Thrombosis
Authors: Kassi Mahwash , Choi Su-Yeon , Cordero-Reyes Andrea M , Bhimaraj Arvind , Trachtenberg Barry H , Ashrith Guha , Loebe Matthias , Estep Jerry D , Chang Su Min
Published: July 2021

Introduction:
Pump thrombosis is a potentially life-threatening event that currently presents a diagnostic challenge. We therefore sought to explore the diagnostic utility and the association of measured cardiac computed tomography (CT) parameters in patients with LVAD malfunction due to pump thrombosis.

Methods:
From 2009 to 2013, 150 patients underwent placement of Heart Mate II continuous flow pump at our institution. Of these 52 patients, underwent cardiac CT with contrast either as part of a prospective protocol or for suspected malfunction. 14 patients had pump thrombosis per the INTERMACS criteria and the remaining were used as controls. Rigorous linear and area measurements for the inflow and outflow tracts of LVADs were performed.

Results:
The mean age of the population was 55 ± 11, 36 were male, and 28 had ischemic cardiomyopathy. Results are shown in table 1. For inflow cannula, measurement of axial area shown in figure 1, was significantly higher in the pump thrombosis group compared to the control group 31±16 cm2 vs 20 ± 12 cm2 (p=.02). Although, the difference in the acute angle for the inflow cannula relative to the perpendicular axis between the midpoint of the mitral annulus and tip of inflow cannulas was not significantly different between the two groups, there was a trend towards greater angulation in the pump thrombosis group (60 ± 6 vs 53 ± 15) and there was a positive correlation between both measurements r=0.513, p-value= 0.003.

Conclusions:
Area in the axial view of the ventricle at the site of the inflow cannula tip may be a surrogate for off axis placement of the cannula. This area may be helpful in predicting pump thrombosis in patients.
Abstract 19212: The Zinc-finger Protein 148(zfp148) Attenuates Aortic Aneurysm Formation and is a Novel Smooth Muscle Cell Regulator
Authors: Salmon Morgan , Pope Nicolas H , Johnston William F , Davis John P , Owens Gary K , Merchant Juanita L , Upchurch Gilbert R , Ailawadi Gorav
Published: July 2021

Objective:
Previously, we found that the zinc-finger protein 148(ZFP148) binds to smooth muscle(SMC) genes following ligation injury; however, it has no known role in aortic aneurysm formation. The study objective was to determine whether ZFP148 is important in AA formation.

Methods:
ZFP148 was examined via qPCR in human aortic aneurysms(n=12/group). 8-12 week male C57/B6 mice (n=6/group) underwent elastase perfusion and were harvested at 3, 7, and 14 days for qPCR for ZFP148. Separately, 8-12 week male (n=10/group) ZFP flx/flx Myh11 Cre+(SMC tamoxifen ZFP148 KO), Myh11 ZFP148 flx/wt Cre+ and Myh11 ZFP wt/wt Cre+ underwent elastase perfusion. At 14 days, maximal aortic dilation was measured with video micrometry. ZFP148 flx/flx ERT Cre+ (n=10/group) and ZFP148 flx/flx ERT Cre-(WT) mice also underwent elastase perfusion. A separate set of mice were bred to an ApoE-/- background and administered Angiotensin II via osmotic pump. Aortic samples were evaluated with histology for α-actin, macrophages, neutrophils, T lymphocytes, caspase3, Ki67, and elastin. In vitro ZFP148 was knocked down using siRNA in smooth muscle cells and stimulated with elastase, or IL-1β.

Results:
ZFP148 expression was elevated in human and murine AA. Maximal aortic dilation was significantly reduced in SMC ZFP148 KO mice compared with controls (55.7 ± 6.32% versus 106.4 ± 8.43%, p<0.05). Maximal aortic dilation of ERT Cre+ ZFP148 mice was significantly decreased versus WT controls (50.4± 8.65% versus 101.3± 9.43%, p<0.05). Knock-out of ZFP148 in both elastase models demonstrated reduced macrophage, T-cell, Ki-67, Caspase3 and neutrophil staining. Kaplan-Meier curves demonstrated increased survival in SM-MHC ZFP148 flx/flx (Chi2=4.357, p=0.0421) and flx/wt mice (Chi2=4.169, p=0.0476) compared to their WT controls following Angiotensin II infusion. Knock-down of ZFP148 followed by treatment with elastase or IL-1β in SMCs attenuated the down-regulation of SM22α, SM-MHC, and SMαA. ZFP148 bound via ChIP analysis to SMC marker genes in vitro and in vivo and was found to bind within the proximal promoter region of SmαA and SM22α.

Conclusions:
ZFP148 KO attenuates AA formation and binds to smooth muscle marker genes. ZFP148 could represent a novel regulator of vascular disease.
Abstract 19220: Potential of Human Cardiac Progenitor Cells from Young versus Old Donor Hearts in Cardiac Protection against Ischemic Left Ventricular Dysfunction and Late Remodeling
Authors: Walravens Ann Sophie , Caluwé Ellen , Trenson Sander , Gillijns Hilde , Vanden Driessche Nina , Beerens Manu , Wu Ming , Luttun Aernout , Janssens Stefan
Published: July 2021

Introduction:
Recent discovery of c-Kit
+
resident cardiac progenitor cells (CPC) has demonstrated cardiac regenerative capacity, which is lost upon increasing age in mice. Accordingly, we hypothesized that c-KIT
+
-selected CPC from young human hearts (yCPC) have a greater myocardial repair potential after myocardial infarction (MI) than CPC from old patients (oCPC).

Methods:
After Ethics Committee approval, cardiac biopsies from young (1-15y old) and old (58-80y old) patients, undergoing corrective or valve surgery were obtained. After collagenase-based digestion, cells were culture-expanded for 2 passages prior to c-KIT
+
selection using magnetic beads. Purity was confirmed using qRT-PCR for
c-KIT, GATA4, CD90, CD105, DDR2, CD31
and
MYH11
expression levels. To trace transplanted cells, CPC were lentivirally tagged with GFP. After permanent LAD coronary artery ligation in immunodeficient mice, 250,000 CPCs were injected in the infarct border zone (4x 62,500 cells/2.5 μl; yCPC,
n
=8; oCPC,
n
=6; or PBS,
n
=6). Cardiac ultrasound (VisualSonics, 3D 30 MHz probe) was performed at baseline, 1 and 35 days after MI. At 35 days post-MI, infarct remodeling and cell survival was evaluated using Sirius red and CPC engraftment by anti-GFP staining.

Results:
In contrast to low
MYH11
and
CD31
expression levels,
c-KIT
and
GATA4
were markedly and equally expressed in yCPC and oCPC, whereas transcript levels of
DDR2, CD105
and
CD90
were 89, 109 and 56% higher in oCPC compared to yCPC. Systolic function was better preserved in yCPC than in oCPC and PBS-treated mice 24h after MI (LVEF from baseline - D1: 53±1 - 38±3
vs.
52±3 - 30±5
vs.
50±3 - 27±4%; ESVi from baseline - D1: 3.7±0.2 - 5.1±0.4
vs.
3.8±0.5 - 6.2±0.7
vs.
3.9±0.5 - 6.5±0.6ml/mm
2
). Moreover, after 35 days, the dilatory response was reduced in yCPC compared to oCPC and PBS-treated mice (EDVi from D1 - D35: 8.3±0.5 - 13.5±1.3
vs.
8.8±0.5 - 16.7±1.8
vs.
8.5±0.5 - 16.6±1.3ml/mm
2
). Improved remodeling was consistent with a markedly greater rim of surviving myocardium while anti-GFP staining showed only rarely retained CPC.

Conclusions:
In summary, these findings suggest enhanced protection by c-KIT
+
CPC isolated from young donor hearts against acute systolic left ventricular dysfunction and late remodeling after MI.
Abstract 19269: Relations and Predictive Value of Post-load and Fasting Glucose for Incident Cardiovascular Disease and Mortality in Older Adults: the Cardiovascular Health Study
Authors: Brutsaert Erika , Shitole Sanyog , Biggs Mary Lou , Mukamal Kenneth , De Boer Ian , Thacker Evan , Barzilay Joshua , Djousse Luc , Ix Joachim H , Smith Nicholas , Kaplan Robert , Siscovick David , Psaty Bruce , Kizer Jorge
Published: July 2021

Introduction:
Elders have a high prevalence of post-load hyperglycemia, which may go undetected with standard screening. Post-load glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in advanced old age are sparse. Whether post-load glucose improves risk prediction for CVD and death after accounting for fasting glucose has not been examined.

Methods:
Fasting and 2-hour post-load glucose were measured at baseline (1989) and follow-up (1996) visits in a prospective study of community-dwelling adults initially ≥65 years old (Cardiovascular Health Study). To evaluate if previously reported associations of fasting and post-load glucose with incident CVD from the baseline visit persist later in life, and apply to mortality, we focused on the 1996 visit (n=2394). To determine the incremental value of post-load glucose for risk prediction, we examined whether it could significantly reclassify baseline (1989) participants (≤75 years) into cholesterol treatment categories based on recent guidelines (n=2542).

Results:
Among participants in the 1996 visit (mean age 77), there were 543 incident CVD events and 1698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with CVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and mortality (HR per SD, 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with either outcome were abolished, but those for post-load glucose remained unchanged. Among subjects ≤75 years old in 1989, there were 416 CVD events and 740 deaths at 10-year follow-up. Post-load glucose did not enhance reclassification using the 7.5% 10-year risk threshold, nor did it improve the C-statistic.

Conclusion:
In adults surviving to advanced old age, post-load glucose was associated with CVD and mortality independently of fasting glucose, but not vice versa, although there was no associated improvement in risk prediction. These findings affirm the robust association of post-load glucose with CVD and death late in life, but do not support the value of routine oral glucose tolerance testing for prediction of these outcomes in older adults.