bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18661: Regulation of Lymphatic Physiology by Connexin47
Authors: Meens Merlijn J , Kutkut Issa , Sabine Amélie , Petrova Tatiana V , Kwak Brenda R
Published: July 2021

Introduction:
Mutations in GJC2, which encodes connexin47 (Cx47), are associated with lymphedema. Moreover, Cx47 mRNA was recently found in human lymphatic endothelial cells (LECs).

Hypothesis:
Lymphatic endothelial Cx47 has a role in lymphatic physiology and pathology.

Methods:
Confocal microscopy and qPCRs were used to assess expression of Cx47. Lymphatic drainage was studied by subcutaneous Evans Blue injections in the footpad of 12 week-old ApoE
-/-
or Cx47
eGFP/eGFP
ApoE
-/-
mice. Atherosclerosis was studied in 15 months-old ApoE
-/-
or Cx47
eGFP/eGFP
ApoE
-/-
mice.

Results:
Cx47 was expressed in lymphangions of mesenteric collecting vessels in Cx47
eGFP/eGFP
Prox1-mOrange2 mice as assessed by microscopy and its expression was confirmed by qPCR on mesentery, gut and skin mRNA of ApoE
-/-
but not Cx47
eGFP/eGFP
ApoE
-/-
mice. Interestingly, lymphatic drainage was enhanced in Cx47-deficient mice (n=10/11, p<0.05). To address whether Cx47 affects chronic immuno-inflammatory pathology atherosclerotic plaque formation was studied in 15-month old male ApoE
-/-
and Cx47
eGFP/eGFP
ApoE
-/-
mice on regular chow. These studies showed that Cx47-deficiency does not affect the size or composition (e.g. lipid, collagen or macrophage content) of aortic plaques in the aortic root. However, plaque development in the thoracic-abdominal aorta of 15 months-old mice tended to be larger in Cx47
eGFP/eGFP
ApoE
-/-
mice (21±5 vs 30±4 % lipid area, n=10, p=0.08). Unexpectedly, total cholesterol (TC) and LDL, but not HDL, triglycerides or free fatty acids, were increased in serum of Cx47
eGFP/eGFP
ApoE
-/-
mice as compared to ApoE
-/-
serum (TC: 472±24 vs 647±18 mg/dL, n=10, p<0.01; and LDL: 272±20 vs 443±17 mg/dL, n=10, p<0.001, respectively). Increased lymphatic drainage from plaques in Cx47
eGFP/eGFP
ApoE
-/-
mice may, partially, compensate for increased serum TC and LDL thereby preventing exuberant atherosclerotic plaque formation despite increased serum lipid levels.

Conclusions:
In conclusion, Cx47 is expressed in LECs of the lymphangion and seems implicated in multiple aspects of lymphatic (patho)physiology.
Abstract 18724: Coronary Angiography After Out-of-hospital Cardiac Arrest is Associated With Improved Neurologically Intact Survival
Authors: Hanuschak Tasha , Brooks Steven , Morrison Laurie , Peng Paul , Zhan Cathy
Published: July 2021

Introduction:
Evidence for the effectiveness of coronary angiography after out-of-hospital cardiac arrest (OHCA) is conflicting. Our objective was to evaluate the association between receiving coronary angiography within 72 hours of hospital arrival and survival with favorable neurologic outcome.

Methods:
This was a population-based retrospective cohort study of consecutive cases of adult OHCA transported to and treated at 28 hospitals in Southern Ontario between March 1, 2010 and December 31, 2014. We included patients with atraumatic OHCA, who achieved return of spontaneous circulation, and were alive 6 hours after hospital arrival. Multi-level logistic regression was used to measure the association between early coronary angiography and neurologically intact survival (Modified Rankin Score 0-2), while controlling for potential confounders and clustered data. We controlled for age, sex, initial cardiac rhythm, witness status, bystander resuscitation, EMS response time, prehospital return of spontaneous circulation, location of arrest, daytime presentation, neurologic status at hospital arrival, STEMI status, cardiac history, initiation of therapeutic hypothermia, hospital size and type, and hospital annual cardiac arrest volume.

Results:
During the period of study, 2678 consecutive OHCA patients met the inclusion criteria. The mean age was 66(±16), 31.7% were female, 54.1% had a bystander witnessed arrest, 35.2% received bystander CPR, 45.9% had a shockable initial rhythm, 30.1% had ST elevation on the first post arrest ECG, and 32.4% received coronary angiography. Receiving coronary angiography was strongly associated with neurologically intact survival (OR 2.30, CI95 1.69-3.15) and survival (OR 2.08, CI95 1.53-2.82). A similar association was observed in the subgroup of patients without STEMI (OR 3.24, CI95 2.16-4.87 and OR 2.66, CI95 1.78-3.99, respectively).

Conclusions:
Neurologically intact survival among post cardiac arrest patients may be improved with coronary angiography, particularly for patients without STEMI. This observation should be confirmed with future randomized controlled studies.
Abstract 18874: Prognostic Importance of Pulmonary Hypertension Etiology by Invasive Hemodynamics in Patients With Severe Aortic Stenosis
Authors: Cavalcante Joao L , Althouse Andrew , Campbell-Massa Ryan , Maddula Mitika , Gleason Thomas G , Katz William , Crock Frederick , Harinstein Matthew , Navid Forozan , Kliner Dustin , Schindler John T , Lee Joon S
Published: July 2021

Introduction:
Pulmonary hypertension (PH) may arise from both pre-capillary and post-capillary etiologies which can be evaluated and quantified by invasive hemodynamics (CATH). The impact of PH etiology on all-cause mortality of patients with severe aortic stenosis (AS) is unknown.

Hypothesis:
CATH classification of PH etiology allows for identification of severe AS patients with combined pre and post-capillary PH that would have the highest mortality risk.

Methods:
Retrospective data collection of patients with severe AS (AV area index ≤ 0.6 cm2/m2) and CATH with invasive hemodynamics was performed. Patients were classified as having: a) no PH (PAmean<25mmHg), b) pre-capillary PH (PAH, PAmean≥25mmHg and pulmonary capillary wedge pressure, PCWP15mmHg). Multivariate Cox-proportional hazard model was used for risk-adjustment comparisons.

Results:
A total of 187 patients were identified with mean age of 77 ± 10 years, 62% male and 38% diabetic. After a median follow-up of 18 months (IQR: 5-27 months), there were 66 deaths (35%). According to the etiology, 54 patients (29%) had no PH, 18 (10%) had PAH, 78 (42%) had passive PH, and 37 (20%) had combined PH. After adjustments for AVR (HR=0.14, 95% CI 0.05-0.35,p<0.01), age, gender, BMI, diabetes, and NYHA class, presence of combined PH by CATH was independently associated with increased risk (HR vs. no PH=2.49, 95% CI 1.09- 5.73, P=0.03). (Figure 1)

Conclusion:
Post-capillary PH is very common in severe AS (62%). Ascertainment of PH etiology by CATH is important as combined pre-post capillary PH is associated with increased short-term mortality despite adjustments for AVR and other comorbidities. Whether this risk can be decreased by further interventions needs to be investigated in future studies.
Abstract 18891: Racial Differences in End-of-life Care Associated With Heart Failure Hospitalizations in the United States: A Population-based Analysis From 2011-2012
Authors: Kumar Nilay , Khera Rohan , Garg Neetika
Published: July 2021

Background and objectives:
Racial disparities in healthcare delivery constitute a major public health problem in the US. There are few studies evaluating the effect of race on utilization of end-of-life (EOL) procedures in HF hospitalizations in the US.

Hypothesis:
Utilization of EOL procedures differs significantly between racial-ethnic groups independent of socioeconomic status (SES) or probability of in-hospital death.

Methods:
We used the 2011-2012 Nationwide/National Inpatient Sample to identify primary HF hospitalizations. EOL procedures of interest were intubation, tracheostomy and prolonged mechanical ventilation, hemodialysis, cardiopulmonary resuscitation, gastrostomy, enteral or parenteral nutrition. Relevant ICD-9 codes were used. We used residential ZIP code as a proxy for SES. Multivariate logistic models were used to evaluate racial differences in EOL care while adjusting for SES and probability of in-hospital mortality.

Results:
375,740 hospitalizations representing 1.8 million hospitalizations nationwide were included in the study. Mean age was 72.6 (SD 14.6) years and 50.1% were women. Overall 7.81% were intubated, 0.69% underwent tracheostomy, and 6.55% underwent hemodialysis, 0.55% underwent CPR, 0.22% had a gastrostomy and 0.45% received enteral or parenteral nutrition. Blacks, Hispanics, Asians or Pacific Islanders and Other races were more likely to receive EOL procedures compared to Whites after adjusting for SES and probability of in-hospital death. (Fig) Use of any EOL procedure was associated with higher age and sex adjusted odds of in-hospital mortality (OR 6.54, 6.09 - 7.04; p<0.001) and average charges ($76,917 vs. 35,841, p<0.001).

Conclusions:
Racial-ethnic minorities hospitalized for HF are significantly more likely to receive aggressive EOL care compared to Whites. The reasons for racial differences in utilization of EOL care in HF should be investigated in future studies.
Abstract 18894: The Myocardial Contraction Fraction Predicts Survival in Patients With AL Cardiac Amyloidosis. A Report From iCCAT, The International Consortium for Cardiac Amyloid Transplantation
Authors: Selby Van N , Verkouw Karla , Estep Jerry D , Witteles Ronald M , Feltrin Giuseppe , Zucker Mark , Baran David , Seldin David C , Patel Jignesh , Hanna Mazen , De Marco Teresa , Semigran Marc J , Maurer Mathew S
Published: July 2021

Background:
Cardiac amyloidosis is characterized by progressive ventricular thickening and diastolic heart failure. The left ventricular ejection fraction (EF) often remains normal even in advanced disease. The myocardial contraction fraction (MCF, the ratio of left ventricular stroke volume to myocardial volume) is a novel measure of myocardial shortening and may be superior to EF for predicting survival in cardiac amyloidosis.

Methods:
We measured MCF and EF from two-dimensional echocardiograms obtained in 86 subjects undergoing heart transplant evaluation for AL cardiac amyloidosis. Cox proportional hazards models and Kaplan-Meier survival analysis were used to compare MCF and EF as predictors of all-cause mortality. Subjects were censored at the time of heart transplant.

Results:
The mean age was 54.6 ± 7.9 years. The mean EF was 49.3 ± 12.7% and the mean MCF was 13.0 ± 5.5%. Over a median follow-up of 59 days (IQR 29-110 days), 38 subjects (44.2%) died and 48 (55.8%) underwent heart transplant. In unadjusted analyses, both MCF (HR 0.89, 95% CI 0.82-0.96, p = 0.002) and EF (HR 0.96, 95% CI 0.94-0.99, p = 0.015) predicted overall survival. In multivariate analyses adjusted for serum free light chain difference, the hazard ratio associated with each 5% absolute decrease in MCF was 2.11 (95% CI 1.32-3.38, p= 0.002). The hazard ratio associated with each 5% absolute decrease in EF was not statistically significant (HR 1.16, 95% CI 0.97-1.39, p=0.09).

Conclusions:
Myocardial contraction fraction is superior to EF for predicting survival in patients undergoing heart transplant evaluation for AL cardiac amyloidosis.
Abstract 18913: Spontaneous Coronary Artery Dissection in Women and Association With Hormonal Stressors
Authors: Eng Lim , Starovoytov Andrew , Heydari Milad , Saw Jacqueline
Published: July 2021

Background:
Spontaneous coronary artery dissection (SCAD) is an infrequent but important cause of myocardial infarction (MI) in women. Chronic exposure to hormonal therapy, fluctuation in hormonal levels, and a history of multiple pregnancies had been postulated to predispose to SCAD. However, these were not well described in the literature.

Methods:
Women with SCAD who have consented and are prospectively followed in our Vancouver General Hospital SCAD registries are included in this study. Their background hormonal exposure, pregnancy, and gynaecological histories were extracted from questionnaires, clinical histories, and medical records. These were correlated to in-hospital and long-term outcomes.

Results:
We included 187 women with SCAD, with mean age 52.6 ± 8.7 years. The majority were Caucasian (83.4%) and 74.0% had fibromuscular dysplasia. All patients presented with MI. Mean number of pregnancy in this cohort was 2.5, with 45 (24.1%) and 25 (13.4%) having ≥4 and ≥5 pregnancies, respectively. Mean number of live births (parity) was 1.8, with 52 (27.8%) having ≥3 births, and 16 (8.6%) having ≥4 births. There were 3 post-partum SCAD (<1 year) and they were still breastfeeding. In terms of hormonal therapy, 28 (15.0%) were actively on hormonal therapy; 5 (2.7%) had prior fertility treatment, 51 (27.3%) had hormone replacement therapy (HRT), 76 (40.6%) had oral contraception, and 36 (19.3%) had gynaecological procedures. There were 107 (57.2%) post-menopausal women, and 23 (12.3%) were peri-menopausal at presentation. There was no death during acute SCAD admission, but 3 died at follow-up (mean 4.1 ± 3.9yrs), and 36 (19.3%) had recurrent SCAD. Patients actively on hormones had higher rate of recurrent SCAD (32.1% vs. 15.8%, p=0.039). There was a higher recurrent MI rate in premenopausal women during index admission (8.9% vs. 1.9%, p=0.037). There was no significant difference in in-hospital and follow-up events in women with past hormonal therapy, post-partum women, or those with parity ≥4 or gravida ≥5.

Conclusion:
Significant proportion of women with SCAD had exposure to hormonal therapy or had multiple pregnancies/births. Patients actively on hormonal therapy appeared to have higher recurrent SCAD events at follow-up.
Abstract 18987: Wavefront Progression of Necrosis During Myocardial Infarction Revisited: The Wave Expands From Endo to Epi as Well as From Center to Lateral Borders
Authors: Lorca Rebeca , Jimenez-Blanco Marta , García-Ruiz Jose Manuel , Pizarro Gonzalo , Fernández-Jiménez Rodrigo , García-Álvarez Ana , Fernández-Friera Leticia , Fuster Valentin , Ibanez Borja
Published: July 2021

Background and purpose:
The widely accepted wavefront theory of myocardial necrosis during acute coronary occlusion describes its progression as a wavefront from endo towards epicardium. The lateral affection of the myocardium would be predetermined by the location of the coronary occlusion. At the time this phenomenon was firstly described, advanced imaging technology was not available. Current cardiac magnetic resonance (CMR) is able to accurately characterize the necrosis progression in vivo.

Methods:
A total of 220 patients with reperfused anterior STEMI (METOCARD-CNIC trial population) were studied. All the patients underwent cine, T2-weighted and late gadolinium enhancement CMR at day 5-7 after STEMI. Endo- and epicardial contours of each LV short axis slice was traced, and each one was divided by 100 cords for analysis. Infarct size was characterized in its 2 dimensions: lateral (defined as the percentage of cords with enhancement in every slice) and transmural extension (percentage of enhancement within each cord, nested in the lateral extension). All slices were weighed according to their relative mass. We compared these parameters between the cardioprotected metoprolol group and the control group.

Results:
A strong lineal correlation between transmural and lateral infarct extension was observed (r: 0.88, p<0.001). We found that despite the edema lateral extension was larger than the IS lateral extension, this difference decreased as the transmurality affection increased. Finally, the infarct reduction exerted by metoprolol was derived from both the transmural and lateral extensions of IS.

Conclusions:
The transmural and lateral extension of necrosis after myocardial infarction are directly correlated. A proven cardioprotective therapy prevented the necrosis progression in both dimensions. These findings cannot be explained by the classical wavefront theory, suggesting that the necrotic wavefront progresses also in the lateral direction.
Abstract 19031: Prediction and Incidence of Non-PV Trigger Foci of Atrial Fibrillation With Regard to Clinical Profile
Authors: Mukai Yasushi , Inoue Shujiro , Takase Susumu , Kawai Shunsuke , Chishaki Akiko , Sunagawa Kenji
Published: July 2021

Introduction:
Non-PV triggers play significant roles in initiating atrial fibrillation (Af). We hypothesized that location of non-PV Af triggers is predictable to some extent from clinical background and may have influence on clinical outcome after ablation.

Methods:
We analyzed consecutive 109 patients (76 men) with Af who underwent catheter ablation and investigation of Af triggers. Af was induced under recordings of intra-cardiac electrograms before ablation procedure in the following ways (1) watching spontaneous firing, (2) induction with intravenous infusion of isoproterenol and adenosine, (3) burst atrial pacing and/or intentional defibrillation to watch immediate recurrence of Af. Af triggers were analyzed and compared to clinical profiles and therapeutic outcome.

Results:
Eighty-four were paroxysmal Af and 25 were persistent. Any ectopic trigger of Af was identified in 73 patients (66%) with 99 foci. Seventy-eight foci were PVs (79%) whereas 21 (21%) were non-PV triggers. In general, non-PV foci were notably identified in female (P<0.01) whereas age, LA diameter or Af type was not significantly relevant to the presence of non-PV foci. Among non-PV foci, superior vena cava (SVC, n=5), crista terminals (CT, n=5) and left atrium (LA, n=5) were prevalent sites. CT was prevalently noted in younger females (P<0.01), whereas SVC was regardless of age. Non-PV foci in the LA were preferably noted in patients with persistent Af (P<0.05). Importantly, multiple or non-PV foci were not significantly correlated to Af recurrence after ablation, whereas LA diameter was weakly correlated.

Conclusion:
Presence and sites of non-PV foci are rather predictable by simple clinical profiles such as gender, age and type of Af. Multiple or non-PV foci may not be associated with worse clinical outcome as long as they can be successfully targeted and ablated.
Abstract 19126: Endothelial-specific Deletion of Prolyl Hydroxylase Domain Protein 2 (PHD2) Results in Severe Pulmonary Hypertension in Mice by Enhancing the HIF2alpha Signaling Pathway
Authors: Tang Haiyang , Gu Yali , Aryon Ramon , Song Shanshan , Fernandez Ruby A , Garcia Joe G , Makino Ayako , Yuan Jason X
Published: July 2021

Rationale:
Sustained pulmonary vasoconstriction and excessive vascular remodeling are major causes of elevated pulmonary vascular resistance which leads to increased pulmonary arterial pressure in patients with pulmonary hypertension. Hypoxic-inducible factor (HIF) and its upstream regulators have been linked to the hypoxia response in vascular remodeling and the development of pulmonary hypertension. In this study, we aimed at defining whether increased HIF1α and/or HIF2α, due to endothelial cell specific deletion of prolyl hydroxylase domain protein 2 (PHD2) under normoxic condition are involved in or required for the initiation and progression of pulmonary hypertension.

Methods:
PHD2, HIF1α and HIF2α conditional knockout mice were created. Right ventricle systolic pressures (RVSP), right ventricular hypertrophy by RV/(LV+S) ratios, and small pulmonary artery smooth muscle layer thickness were measured. Pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs) were isolated from wild type (WT) or knockout (KO) mice, followed with cell-based assays.

Results:
We report here that mice with targeted deletion of PHD2 developed severe pulmonary hypertension under normoxic condition. Conditional and inducible deletion of HIF2α in endothelial cells, but not smooth muscle cells, dramatically protected mice from hypoxia-induced pulmonary hypertension. HIF2α KO mice had significantly lower RVSP, RV/(LV+S) ratios, and displayed less pulmonary vascular remodeling when exposed to hypoxia compared to their WT mice.

Conclusion:
This work shows that the endothelium is responsible for the development of pulmonary hypertension and it demonstrates a crucial role of PHD2/HIF signaling for hypoxic response in pulmonary hypertension. These findings unveil temporally and spatially distinct functions for HIFs in the development of pulmonary hypertension.
Abstract 19136: Association of Smoking With Myocardial Injury and Clinical Outcome in Patients Undergoing Mechanical Reperfusion for ST-Elevation Myocardial Infarction: Insights From Cardiovascular Magnetic Resonance Imaging
Authors: Eitel Ingo , Reinstadler Sebastian , Eitel Charlotte , Fuernau Georg , de Waha Suazanne , Desch Steffen , Thiele Holger
Published: July 2021

Introduction:
There is evidence suggesting a positive effect of cigarette smoking on myocardial tissue reperfusion and clinical outcomes in patients with myocardial infarction (“smoker’s paradox”).

Hypothesis/Aim:
We aimed to evaluate the relationship of smoking status with cardiac magnetic resonance (CMR)-determined myocardial salvage and damage as well as clinical outcome in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI).

Methods:
This multicenter study included 727 consecutive STEMI patients reperfused within 12 hours after symptom onset. CMR imaging parameters (area-at-risk [AAR], infarct size [IS], myocardial salvage index [MSI], and microvascular obstruction [MVO]) were compared according to admission smoking status. Major adverse cardiac events (MACE) rates at 12 months after infarction were compared between groups.

Results:
In our study cohort 339 (46.6%) patients were current smokers. There was no difference in the extent of AAR (35[24-47] vs. 37[27-49] %LV, p=0.10), IS (16[8-25] vs. 17[10-26] %LV, p=0.21), MSI (53[29-70] vs. 52[34-71], p=0.47) or MVO (0[0-1.7] vs. 0[0-1.6] %LV, p=0.91) between smokers and non-smokers. Smokers had lower MACE (3.8% vs. 8.2%, p=0.01) and mortality (0.9% vs. 3.9%, p=0.01) rates. However, after adjustment for differences in baseline risk factors, smoking was no longer associated with MACE (HR=0.72, 95% CI 0.37 to 1.41, p=0.34) or mortality (HR=0.49, 95% CI 0.14 to 1.76, p=0.27).

Conclusion:
Smoking is not associated with PPCI efficacy (myocardial salvage) or irreversible myocardial damage in patients with acute STEMI. The lower MACE and mortality rates of smokers were entirely explained by differences in baseline risk characteristics, thus challenging the existence of a “smoker’s paradox”.
Abstract 19153: Morphine Delays and Attenuates Ticagrelor Exposure and Action in Patients With Myocardial Infarction: The Randomized, Double-blind, Placebo-controlled Impression Trial
Authors: Kubica Jacek , Adamski Piotr , Ostrowska Malgorzata , Sikora Joanna , Kubica Julia M , Sroka Wiktor , Stankowska Katarzyna , Buszko Katarzyna , Navarese Eliano P , Jilma Bernd , Siller-Matula Jolanta M , Rosc Danuta , Marszall Michal , Kozinski Marek
Published: July 2021

Introduction:
The currently available data from observational studies and a randomized trial on clopidogrel conducted in healthy volunteers suggest existence of drug-drug interactions between morphine and oral P2Y12 inhibitors, when administered together.

Hypothesis:
We aimed to test the hypothesis that morfine administered intravenously excerts the negative impact on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with myocardial infarction.

Methods:
In a single center, randomized, double-blind trial, participants were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry, while ticagrelor antiplatelet effect was measured with up to 3 different platelet function tests: vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry and VerifyNow P2Y12.

Results:
The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine administration lowered the total exposure to ticagrelor and its active metabolite by 35.6% (AUC(0-12): 6307 vs. 9791 ng·h/mL; p=0.003) and 37.1% (AUC(0-12): 1503 vs. 2388 ng·h/mL; p=0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; p=0.002) and AR-C124910XX (6 vs. 4 h; p=0.03) in morphine-treated patients. Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were associated with morphine administration (p=0.003) and the presence of ST-segment elevation myocardial infarction (p=0.010). All three methods of platelet reactivity assessment consistently showed a stronger antiplatelet effect of ticagrelor in the placebo group as reflected by a higher prevalence of high platelet reactivity in patients receiving morphine.

Conclusions:
Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction.
Abstract 19220: Hepatic Steatosis is Independently Associated With an Increased Vascular Stiffness in Overweight Subjects
Authors: Munckhof Inge v , Brand Tessa , Graaf Marinette v , Joosten Leo , Netea Mihai , Graaf Jacqueline d , Rutten Joost
Published: July 2021

Introduction:
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Subjects with NAFLD have an increased risk of cardiovascular diseases. We investigated whether an increase in hepatic steatosis is independently associated with an increase in vascular stiffness.

Methods:
We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 112 subjects, BMI > 27 kg/m2, aged 55-81 years. The amount of liver fat was quantified by MR spectroscopy. Arterial stiffness was assessed by measurement of the carotid-femoral pulse wave velocity (PWV). The association between the hepatic steatosis and vascular stiffness was investigated by linear regression analysis with and without adjustment for the conventional cardiovascular risk factors.

Results:
In univariate analysis, hepatic steasosis was found to be correlated with PWV (r = 0.267; p = 0.005). After adjustment for age, sex, heart rate, alcohol use, and BMI still a significant positive association was present with a standardized beta of 0,298 (p=0.004). Even after adjustment for conventional cardiovascular risk factors including mean arterial pressure, blood pressure lowering and anti-diabetic drugs, hepatic steatosis remained independently associated with PWV ( standardized beta 0.269, p = 0.019).

Conclusions:
In a group of overweight subjects hepatic steatosis is associated with arterial stiffness. This association is independent of blood pressure, use of antihypertensives and the other traditional cardiovascular risk factors.
Abstract 19266: Derivation of Risk Score in Predicting Deterioration in Left Ventricular Ejection Fraction in Patients With Low-flow Significant Aortic Stenosis and Initially Preserved Ejection Fraction
Authors: Tan Benjamin Y , Ngiam Nicholas J , Lee Glenn , Chan Yiong-Huak , Poh Kian-Keong
Published: July 2021

Introduction:
Low-flow significant aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF>50%) is associated with worse clinical outcomes. In classical severe AS, guidelines have indicated that deterioration of LVEF to <50% is a Class I indication for aortic valve replacement. However, predictors of LVEF deterioration in patients with low-flow AS have not been studied. We developed a model, based on clinical and echocardiographic parameters to predict LVEF deterioration to <50%.

Methods:
Consecutive subjects (n=162) with low-flow (stroke volume index <35mg/ml) significant AS and paired echocardiographic studies (>180 days apart) were studied. Significant predictors of LVEF deterioration on univariate analyses were fit into a multivariable logistic regression. A risk score was then developed by converting the B-coefficients into weights, and its performance in predicting the LVEF deterioration to <50% was evaluated.

Results:
There were 50 patients (30.9%) with significant deterioration of LVEF to <50% from baseline. A risk score was developed based on five clinical and echocardiographic predictors (History of hypertension (p=0.008) – 1 point, initial LVEF <65% (p=0.012) – 2 points, Tissue Doppler S’ velocity <7.3cm/s (p=0.049) – 1 point, End-systolic wall stress >70g/cm2 (p=0.001) – 2 points, and left ventricular mass index >100g/m2 (p=0.010) – 1 point). The risk score performed well under receiver operating characteristic curve (AUC=0.78, 95%CI 0.72-0.85, p<0.001). A score of 4 points or more was the optimal cut-off, predicting most cases (98%, 48 out of 50).

Conclusions:
Despite preserved LVEF, subclinical myocardial dysfunction may represent an important comorbidity in patients with low-flow AS, which may accelerate inappropriate left ventricular remodelling. The risk score may be used to identify patients at risk of significant LVEF deterioration, thereby allowing for closer monitoring and earlier surgical intervention.
Abstract 19275: Gender Differences in Cardiovascular- and Cancer Mortality During Long-term Follow-up After Acute Myocardial Infarction
Authors: Kvakkestad Kristin M , Fagerland Morten W , Eritsland Jan , Halvorsen Sigrun
Published: July 2021

Background:
The existence of gender differences in cause-specific mortality after acute myocardial infarction (AMI) is unknown. Aim: To study gender differences in all-cause and cause-specific mortality in women and men with AMI.

Methods:
Consecutive AMI patients were enrolled in a prospective cohort study during 2005-2011. Cardiovascular (CV) risk factors, treatment and in-hospital complications were registered. Date and cause of death were obtained from the Norwegian cause of death registry, with censoring date set to Dec 31, 2012. Patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were analysed separately. We used Kaplan Meier- and cumulative incidence function-plots to assess gender differences in CV, cancer and all-cause mortality. Cox- and Fine-Gray regression models, adjusted for age, estimated the effect of female gender.

Results:
We included 5159 NSTEMI (34% women) and 4899 STEMI (25% women) patients. Women were older and had more complications compared to men. After a median follow-up time of 1043 and 1262 days for NSTEMI and STEMI, respectively, 1461 NSTEMI (28%) and 886 STEMI (18%) patients had died. After adjustment for age, NSTEMI women had lower (HR 0.89 [95% CI: 0.80-0.99]) and STEMI women similar (HR 1.05 [95% CI: 0.91-1.22]) risk of all-cause mortality compared to men. There were no gender differences in CV mortality. We observed a non-significant trend toward lower cancer mortality in women than men with NSTEMI (adjusted subhazard ratio 0.76 [95% CI:0.56-1.03]). In both genders, CV death was more prevalent (Figure) and occurred earlier than cancer death.

Conclusion:
After adjustment for age, there were no excess risks of all-cause or CV mortality in women versus men with AMI during long-term follow-up. Possible gender differences in risk of cancer mortality needs further investigation.
Abstract 19300: Real-life Evidence of Stroke Prevention in Patients With Atrial Fibrillation: The RELIEF Study
Authors: Coleman Craig , Evers Thomas , Ehlken Birgit
Published: July 2021

Introduction:
Limited data is available on real-world outcomes in rivaroxaban compared to vitamin K antagonist (VKA) users with non-valvular atrial fibrillation (NVAF).

Hypothesis:
To assess the effectiveness of newly initiated rivaroxaban or VKA therapy among NVAF patients.

Methods:
The ‘REal-LIfe Evidence on stroke prevention in patients with atrial Fibrillation’ (RELIEF) study was a retrospective analysis performed in the outpatient setting in Germany using data from the Primary Care Physician panel of a longitudinal electronic medical record database ( IMS Disease Analyzer). Patients had to be ≥18 years of age, newly initiated on rivaroxaban or a VKA (mostly phenprocoumon in Germany) between January 2012 and October 2013, have a diagnosis of NVAF on the day of the first qualifying anticoagulant prescription (index date) or anytime during the 365 days prior, and have follow-up ≥360 days after the index date. Patients were 1:1 propensity score matched. The primary endpoint was the composite of ischemic stroke (International Classification of Disease, Tenth Revision [ICD-10] code I63), transient ischemic attack (TIA) (ICD-10 code G45, except G45.3), intracerebral hemorrhage (ICD-10 code I61), other non-traumatic intracranial hemorrhage (ICD-10 code I62), systemic embolism (ICD-10 code I74) and myocardial infarction (ICD-10 codes I21, I22). Kaplan-Meier survival analysis on the primary endpoint in the matched cohorts was performed, and the time-to-event was reported as a hazard ratio (HR) and 95% confidence interval (CI).

Results:
A total of 1,039 VKA and 1,039 rivaroxaban users were included and 57 events (20 in rivaroxaban, 37 in VKA) were identified during a one-year follow-up. The incidence of the composite endpoint was significantly lower in rivaroxaban compared to VKA users (1.97 vs. 3.68 events/100 person-years) corresponding to a hazard ratio of 0.536 (95%CI: 0.311-0.923; p=0.0245). Ischemic stroke (0.69 vs. 1.58 events/100 person-years) and TIA (0.59 vs. 1.08 events/100 person-years) were less frequent in the rivaroxaban cohort .

Conclusions:
The findings indicate that rivaroxaban may be associated with superior effectiveness compared to a VKA when utilized in a real-world setting.
Abstract 19405: Association of Deep and Superficial Abdominal Subcutaneous Tissue With Hepatic Fat Content
Authors: Munckhof Inge v , Brand Tessa , Graaf Marinette v , Graaf Jacqueline d , Rutten Joost
Published: July 2021

Introduction:
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Visceral adipose tissue (VAT) is regarded to be an important factor in the pathogenesis of NAFLD. Subcutaneous adipose tissue (SAT) is separated by the fascia superficialis into the deep SAT (dSAT) and superficial SAT (sSAT). It has been suggested that dSAT is related to an increased risk for obesity related complications, whereas sSAT has a more favorable profile. The aim of this study was to investigate the association of superficial and deep subcutaneous adipose tissue with hepatic steatosis.

Methods:
We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 133 subjects, BMI > 27 kg/m
2
, aged 55-81 years. Abdominal magnetic resonance imaging was performed at level L4-L5 to measure VAT, dSAT and sSAT volumes. The amount of liver fat was quantified by MR spectroscopy.

Results:
Men had significantly higher volumes of VAT and lower volumes of sSAT compared with women. No differences in volumes of dSAT were observed. In univariate analysis, the VAT volume was found to be correlated with hepatic steasosis (r = 0.339; p <0.001), while no significant correlation was found between total SAT, sSAT or dSAT with hepatic steatosis. After adjustment for age, alcohol use and sex, VAT was still positively correlated with hepatic steatosis with a standardized β of 0,276 (p=0.007), and sSAT, but not total SAT or dSAT, was negatively correlated with hepatic steatosis with a standardized β of -0,363 (p=0.033).

Conclusions:
VAT as measured by MRI is positively correlated with hepatic steatosis, in contrast to sSAT which is negatively correlated after adjustment for age, alcohol use and sex. We found no significant correlation between total SAT or dSAT and hepatic steatosis.
Abstract 19433: Should Bilateral Internal Thoracic Artery Grafting be Used in Patients After Recent MI?
Authors: Loberman Dan , Mohr Rephael , Medleg Mohamad , Nesher Nachum , Aizer Zahi , Paz Yoseph , Pevni Dmitri , Ben Gal Yanai
Published: July 2021

Introduction:
Bilateral internal thoracic artery(ITA) grafting is associated with improved survival. However, many surgeons are reluctant to use this revascularization technique in patients after myocardial infarction (MI) due to the risk of sternal infection and the excellent survival benefit obtained with single ITA (SITA).

Hypothesis:
Long-term outcome of bilateral ITA (BITA) grafting, might be superior to single ITA and other conduits such as saphenous veins (SVG) and radial artery (RA) in patients with multi-vessels disease after recent MI.

Methods:
871 patients who underwent BITA grafting after recent MI (<3 months prior to surgery), between 1996 and 2010, Were compared with 527 who underwent CABG with SITA and SVG or RA.

Results:
Patients undergoing SITA were older, more often female, more likely to have COPD, EF<30%, preoperative critical state, Diabetes, chronic renal failure (CRF), peripheral vascular disease (PVD) and emergency operation. In contrast, patients undergoing BITA grafting were more likely to have triple vessel disease and more often underwent CABG with three or more grafts and sequential grafts.

Operative mortality of BITA patients was lower (3.0 % vs. 5.7%, in the SITA group p=0.01), Occurrences of sternal wound infection (3% vs 2%) and strokes (2.6% vs. 3%) were similar. Mean follow-up was 11.8 (95%CI 10.95-12.56) years. Kaplan Meier survival of BITA patients was better (70.3% vs.52.6% p<0.001). Propensity score matching was used to account for differences between groups in preoperative characteristics. The 293 matched pairs thus created had similar preoperative characteristics.

Kaplan Meier 10 year survival (67.3% versus 59%, p=0.325 log-rank test), and the Cox adjusted survival of the matched groups did not reach statistical significance (HR 1.57, p=0.091). However, survival of non- emergent BITA patients was better (HR 1.256 p=0.038). Age, COPD, CHF, CRF, PVD and left main were independent predictors of decreased survival. Off-pump operations were associated with improved survival (Cox model)

Conclusions:
This study suggests that long-term outcome of arterial revascularization with BITA can be better than that of SITA in non-emergency cases after recent MI with proper patient selection
Abstract 19493: Sirt7 Contributes to Myocardial Tissue Repair by Maintaining TGF-β Signaling Pathway
Authors: Araki Satoshi , Izumiya Yasuhiro , Kimura Yuichi , Hanatani Shinsuke , Onoue Yoshiro , Yamamura Satoru , Braun Thomas , Bober Eva , Ogawa Hisao
Published: July 2021

Background:
Sirt7, one of the seven members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.

Methods and Results:
In wild type (WT) mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction (MI) and hindlimb ischemia, particularly at the active wound healing site. Homozygous Sirt7 deficient (Sirt7-/-) mice showed susceptibility to cardiac rupture after MI, delayed blood flow recovery following hindlimb ischemia and impaired wound healing after skin injury, compared to WT mice. Histological analysis showed reduced fibrosis, fibroblast differentiation and inflammatory cell infiltration in the border zone of infarction in Sirt7-/- mice. In vitro, Sirt7-/- mice-derived or Sirt7 siRNA-treated cardiac fibroblasts showed reduced TGF-β signal activation and low expression levels of fibrosis-related genes compared with WT mice-derived or control siRNA-treated cells. These changes were accompanied by reduction in TGF-β receptor I (TβRI) protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. TβRI downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase C, alpha (PICK1) was involved in this process.

Conclusions:
Sirt7 maintains TβRI by modulating autophagy and contributes to tissue repair processes.
Abstract 19523: Liver Injury in Alcohol Drinkers and Incidence of Heart Failure - The Atherosclerosis Risk in Communities Study
Authors: Silvestre Odilson M , Gonçalves Alexandra , Roca Gabriela Q , Claggett Brian , Ndumele Chiadi E , Lazo Mariana , Solomon Scott D
Published: July 2021

Introduction:
Alcohol liver toxicity occurs earlier than heart toxicity, but it is unknown if markers of liver damage predict incident heart failure (HF).

Methods:
We studied 10,263 participants from the Atherosclerosis Risk in Communities (ARIC) study, mean age 62.2±5.5 years, free of HF, who had liver enzymes measured in 2010 from stored Visit 4 (1996-99) samples. Liver enzymes were considered elevated when alanine aminotransferase (ALT) >24 UI/L(men) and >21 UI/L(women); aspartate aminotransferase (AST) > 32 UI/L(men) and >28 UI/L(women); gama-glutamyl transpeptidase (GGT)>56 UI/L(men) and >50 UI/L(women); AST:ALT ratio ≥2. Participants were classified into 3 categories based on self-reported drinking: never (21%), former (29%), and current drinkers (50%). Multivariable Cox proportional hazards models were used to evaluate the relationship between liver enzymes and incident HF (hospitalization or death) occurring after Visit 4 through 12/31/2012.

Results:
During 13.2 years of follow-up, HF occurred in 1399 (13%) participants. Higher AST, GGT, and AST:ALT ratio were associated with higher alcohol intake and incident HF among current drinkers (Figure). Compared to current drinkers with normal liver enzymes, current drinkers with increased level of AST or GGT had a higher risk of HF (1.38 HR 95%CI 1.09-1.73, p=0.005 and 1.34 HR 95% CI 1.04-1.74, p=0.02, respectively). AST:ALT ratio≥2 was associated with a 35% increased risk of HF (1.35 HR 95% CI 1.01-1.82, p=0.04) in the current drinkers group, adjusting for age, sex, race, center, hypertension, BMI, LDL, smoking, diabetes, statin use, coronary disease, quantity of alcohol, and kidney function. Elevated liver enzymes were not associated with higher incidence of HF among never and former drinkers participants.

Conclusion:
Liver damage, as marked by elevation of AST, GGT or an AST: ALT ratio≥2, was related to a higher risk of incident HF among alcohol drinkers, independently of the quantity of alcohol intake.
Abstract 19540: US Center Variability in the Incidence of Stroke for the Berlin Heart EXCOR Pediatric Ventricular Assist Device
Authors: Almond Christopher S , Lorts Angela , Rossano Joseph W , Jordan Lori C , VanderPluym Christina , Price Jack F , Daly Kevin P , Maeda Katsuhide , Shin Andrew Y , Rosenthal David N
Published: July 2021

Background:
Ventricular assist device (VAD)-related stroke is an important performance benchmark for adult VAD programs. No benchmarks are available for pediatric VAD programs where the stroke rate is higher. We sought to describe center variability in the stroke rate for the Berlin Heart EXCOR® Pediatric VAD, the most commonly used durable VAD in US children, to support pediatric VAD quality improvement efforts.

Methods:
All children age <18 years supported with a Berlin Heart EXCOR Pediatric VAD at a site participating in the EXCOR IDE or FDA Post-Approval Study were identified using the Sponsor’s database. The incidence of neurological dysfunction, defined by INTERMACS criteria, was estimated for patients at centers with at least 300 support days.

Results:
Between 2007 and March 2014, a total of 320 children underwent implantation of a Berlin Heart EXCOR Pediatric VAD at 42 centers, of which 271 patients at 25 centers met the study inclusion criteria. The baseline characteristics of the cohort have been reported previously. Overall, there were a total of 64 neurological dysfunction episodes in 53 unique patients over 20,875 days of support, yielding an overall stroke incidence of 0.31 events per 100 days of support and a prevalence of 19%. Centers varied considerably (ten-fold) in their incidence rate of stroke ranging from 0 events to 1.7 events per 100 days of support (Figure). Among 13 centers with at least 10 total implants (totaling 205 patients over 14,405 support days), the overall stroke prevalence was 20% (range 6 to 46%) (Incidence rate 0.33 events per 100 days of support). Centers with ≥10 implants did not have fewer strokes than lower volume centers (P=0.30).

Conclusion:
The incidence of stroke among pediatric VAD centers using the Berlin Heart EXCOR Pediatric VAD was 0.31 events per day of support and varied considerably across pediatric centers. These data may be useful for developing performance benchmarks for neurological dysfunction in pediatric VAD support.
Abstract 19597: Impact of Hyperglycemia on the Exercise Pressor Reflex in Nondiabetic Patients With Heart Failure
Authors: Rodriguez Milian Karel , Barecka Katarzyna , May Ross W , Krauze Tomasz , Wykretowicz Andrzej , Nowak Aneta , Palasz Anna , Guzik Przemyslaw , Sanchez-Gonzalez Marcos A
Published: July 2021

Introduction:
The HR and BP responses to exercise (exercise pressor reflex, EPR) predict adverse clinical events in patients with Heart Failure (HF). Although studies have shown that hyperglycemia may induce cardiovascular autonomic dysregulation, the association between glycemic status and EPR in HF patients is poorly understood.

Hypothesis:
Hyperglycemia would be accompanied by altered EPR after the 6-minute walk test (6MWT) in nondiabetic HF patients.

Methods:
The HR and BP (SBP and DBP) responses to 6MWT were evaluated in 215 HF ambulatory patients aged 62.4 ± 9.4 (M ± SD) years old before (BASE), immediately after (P0), 1 minute after (P1) and 3 minutes after exercise (P3). Patients were assigned to one of two groups based on their 2-hours post meal (breakfast) glycemia into normoglycemic (<140mg/dl; NG; n = 173) and hyperglycemic (HG; n =42).

Results:
To compare the HR and BP responses to the 6MWT between the groups a 4 X 2 ([BASE X P0 X P1 X P3] X [NG x HG]) repeated measures analysis of covariance using least significant difference as alpha adjustment that controlled for weight and gender were conducted. Significant (P<0.05) time-by-group interactions occurred for HR, SBP, and DBP such that HR at P0, SBP at BASE, P1 and P3 and DBP at P1 and P3 were higher in the HG group compared to the NG. In addition, we found that SBP response to exercise was blunted where as DBP remained elevated at P1 and P3 in HG group only (see Figure 1).

Conclusions:
These results demonstrate that post-meal hyperglycemia evokes an abnormal EPR in patients with HF. Such effects might be caused by a hyperglycemia-induced impaired autonomic dysregulation. Future attention should be given at the patient’s glycemic status prior to using an exercise test as it significantly contributes to the EPR.