bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19455: Risk Factor Changes Had a Minor Net Contribution to the Decline in Cardiovascular Mortality in the US, 1988-2004
Authors: Tellez-Plaza Maria , Pastor-Barriuso Roberto , Redon Josep , Navas-Acien Ana , Guallar Eliseo
Published: March 2022

Introduction:
The role of primary prevention and changes in risk factors in explaining cardiovascular disease (CVD) mortality trends is controversial. Previous studies did not consider simultaneous changes in multiple cardiovascular risk factors over time.

Objectives:
To evaluate the impact of changes in smoking, obesity, physical inactivity, hypertension, diabetes, chronic kidney disease and dyslipidemia to explain the decreasing trend in CVD mortality that occurred in the US from 1988-1994 to 1999-2004.

Methods:
Cohort study of 25,297 adult men and women ≥20 years old participating in the National Health and Nutrition Examination Survey (NHANES) III and 1999-2004 Mortality Follow-up. We used causal mediation analyses with additive hazard models to estimate the absolute and relative reductions in CVD mortality rates over time explained through risk factor changes.

Results:
CVD mortality rates in the US decreased from 1988-1994 to 1999-2004 by 52.7% in men and by 45.5% women. Net changes in CVD risk factors explained 12.6 and 10.9% of this decline in men and women, respectively. The reductions in smoking and in leisure time physical inactivity rates were the main factors explaining this decline. The increased in chronic kidney disease, however, independently attenuated the decline in CVD mortality in both men and women. Adjustment for changes in self-reported use of risk factor treatments did not materially change the findings.

Conclusions:
The net impact of changes in CVD risk factors on mortality changes in the US was small. While prevention strategies have intensified, increases in the prevalence of certain risk factors, such as chronic kidney disease, seem to attenuate the impact of primary prevention interventions. The mortality decline may have been driven by clinical interventions in patients with events, by secondary prevention, or by changes in non-traditional risk factors. Our findings also suggest that primordial prevention strategies are needed to control the increase recent trends in chronic kidney disease and to maximize the benefit of preventive interventions.
Abstract 19508: Mid-term Results of the Ross Procedure in Children: A Reappraisal of the Subannular Implantation Technique
Authors: Torii Ryo , Cornejo Patricia , Tran Phan-Kiet , Tran-Lundmark Karin , Hsia Tain-Yen , Kostolny Martin , Hughes Marina , Tsang Victor
Published: March 2022

Dilatation of the pulmonary autograft is an ongoing concern in the paediatric population. Unlike those of the aortic valve leaflets, those of the pulmonary valve are directly attached to the right ventricular muscular outflow tract, and therefore at the time of the Ross procedure the pulmonary root needs to be placed within the left ventricular outflow (LVOT) tract for support.

Between 1998 and 2012, 74 children were operated with the subannular technique with interrupted sutures, at the median age of 10.2 years (range 5 months to 18 years). Mean follow up time was 5.2 years (range 3 days to 13.2 years). There were no deaths, but 3 reinterventions on the autograft for regurgitation and 2 resections of LVOT obstruction. Mean freedom from autograft and LVOT reintervention time was 12.1 years (95% CI 11.0 - 13.2). There were no significant autograft stenosis, and freedom from moderate to severe autograft regurgitation was 95% and 87.5% at 5 and 10 years, respectively. Z-scores at latest follow-up were at the annulus 0.23 (range -2.9 to +3.2), sinus of Valsalva 2.6 (range -3.1 to +5.4), and the sinotubular junction 2.9 (range -1.2 to +6.0). As expected, the correlation between time after surgery and the increase in Z-score of the root structures were positive at the level of the sinus of Valsalva (r=+0.39, p=0.003) and at the sinotubular junction (r=+0.27, p=0.049), but was negative at the annulus (r=-0.26, p=0.054). Average rate of change in Z-score was significantly lower at the annulus compared to the sinus of Valsalva (0.19 vs 0.46 Z-score/year, p < 0.001).

Our data confirms the importance of subannular support of the pulmonary autograft in the LVOT with limited annular dilatation and autograft regurgitation, and delayed need for autograft reintervention.
Abstract 19510: Cytochrome C Levels in Post-cardiac Arrest Patients
Authors: Cocchi Michael N , Andersen Lars W , Rittenberger Jon , Abella Benjamin , Gaieski David , Peberdy Mary Anne , Ornato Jospeh , Callaway Clifton , Gazmuri Raul , Donnino Michael , Liu Xiaowen
Published: March 2022

Introduction:
Cytochrome C is an essential component of the electron transport chain loosely bound to the inner mitochondrial membrane. Plasma Cytochrome C levels have shown to be elevated and associated with mortality in an animal model of cardiac arrest.

Hypothesis:
We hypothesized that cytochrome C levels would be elevated in post-cardiac arrest patients and higher in non-survivors as compared to survivors.

Methods:
We enrolled adult, out-of-hospital cardiac arrest patients with return of spontaneous circulation as part of the four-center COMICA study. Blood draws were performed after return of spontaneous circulation. We also performed blood draws in controls without acute illness. We measured plasma cytochrome C levels by applying the human cytochrome C Platinum ELISA (eBioceience, CA) kit to a MSD platform (Meso Scale Discovery, MD) to achieve greater dynamic range and sensitivity. We compared groups using the Wilcoxon Rank-Sum test. We used Spearman’s correlation coefficient (rs) to assess the correlation between Cytochrome C levels and initial lactate levels.

Results:
A total of 103 post-cardiac arrest patients and 40 controls had Cytochrome C levels measured. Cytochrome C levels were higher in post-cardiac arrest patients as compared to control subjects (2.18 nmol/L [quartiles: 0.74, 7.74] vs 0.20 nmol/L [0.03, 1.12], p < 0.001, Figure 1). Fifty-five (53%) patients in the cardiac arrest group died. Patients who died had higher Cytochrome C levels as compared to survivors (3.66 nmol/L [1.40, 14.8] vs. 1.27 nmol/L [0.16, 2.37], p = 0.001, Figure 2). There was also a significant difference in Cytochrome C levels between patients with a good vs. a poor neurological outcome (1.3 nmol/L [0.3, 3.5] vs. 2.8 nmol/L [0.9, 9.9], p = 0.04). Cytochrome C levels were correlated with initial lactate levels (rs = 0.36, p = 0.001).

Conclusion:
Cytochrome C levels are elevated in post-cardiac arrest patients and non-survivors has higher levels.
Abstract 19520: Trends in Renal Complication Rates Among Medicare Beneficiaries Undergoing PCI: Fiscal Years 2009 Through 2013
Authors: Kugelmass Aaron , Cohen David J , Reynolds Matthew R , Brown Phillip P , Simon April W , Culler Steven D
Published: March 2022

Background:
Enhanced attention has focused on contrast induced nephropathy among patients undergoing PCI. This study reports five-year trends in the rate of renal complications among Medicare Beneficiaries (MB) undergoing PCI.

Methods:
A retrospective analysis was conducted using annual MedPar data files for fiscal years (FY) 2009 through 2013. The study sample consists of 1,552,960 Medicare Beneficiaries (MB) undergoing a PCI without CABG or valve surgery. Up to 25 ICD-9-CM procedure and diagnosis codes were use to identify the outcomes of interest. POA flags were used to identify patients who experienced complications from those patients admitted with the comorbidity. The analysis is descriptive.

Results:
This analysis identifies that both new acute renal failure (ARF) and new hemodialysis (HD) increased dramatically during this period. The incidence of new HD essentially doubled in MB’s undergoing PCI during an admission. MB undergoing elective PCIs were less likely than MBs undergoing non-elective PCI to experience ARF (both present on admission and as a complication). However, MB undergoing elective PCIs were more likely than MBs undergoing non-elective PCI to have had a prior HD and experience new HD than MBs undergoing non-elective PCI.

Conclusion:
These findings suggest, that despite a longstanding focus on preventing CIN, the complication is increasing steadily and that new efforts to reduce PCI related CIN are warranted.
Abstract 19525: Heart Failure Readmission Rates: Clinical Experience With the C-Pulse® Extra-Aortic Counterpulsation System
Authors: Aggarwal Sanjeev , Kao Andrew , Prabhu Sumanth D , Slaughter Mark S
Published: March 2022

Introduction:
Heart failure-related readmission rates remain high. In the EFFECT phase I study, 61.3% of patients had repeat hospitalization within one year of initial discharge, with the majority occurring shortly postdischarge or near end of life. Analysis of Medicare beneficiaries from 2007-2009 of 1,330,157 heart failure (HF) hospitalizations found 35% of patients readmitted for the same condition within 30 days. Readmission (RA) reflects increased morbidity, impaired quality of life, and a growing economic burden on health care resources.

Hypothesis:
The US feasibility investigational study gathered data to evaluate readmission in class III/ambulatory IV HF patients receiving an extra-aortic counterpulsation system (C-Pulse®, Sunshine Heart, Inc.) designed to increase coronary blood flow, reduce the workload of the left ventricle, and improve cardiac function.

Methods:
Between April 2009 and June 2011, twenty HF patients were enrolled in a prospective US feasibility study undergoing C-Pulse device implantation procedures at 7 centers. RA data was collected at 30 days, 6 and 12 months post implant.

Results:
The study included 12 males, 18 NYHA class III and 2 ambulatory NYHA class IV patients, 7 ischemic and 13 non-ischemic. Mean age was 56±7 years. Baseline ejection fraction (EF) was 28% ± 6.1. Over 12 months, 3 of the 20 implanted C-Pulse feasibility study patients (15%) had 5 HF hospitalizations after device implantation (Clinical Events Committee adjudicated, occurring at 208 days, 205 and 245 days, 33 and 52 days). Two of the three patients had low device usage compliance prior to HF events (<30% use).

Conclusion:
Recently published data has demonstrated preliminary indications of safety and efficacy of counterpulsation therapy with the C-pulse system for the management of chronic HF. Lifetime analysis work from the EFFECT study has shown an overall RA rate of 61.3% at 12 months in patients suffering from HF. In comparison, RA rates for patients undergoing C-pulse implantation appear to be greatly reduced at 30 days and at one year. In addition, RA rates for patients undergoing C-pulse implantation are lower than RA rates reported for other forms of durable mechanical circulatory support at 30 days and 1 year.
Abstract 19546: Silencing miR-144 Enhances Regression and Reduces Progression of Atheroscleoris
Authors: Tarling Elizabeth , Cheng Joan , Wu XiaoHui , Tontonoz Peter , Sallam Tamer , Vallim Thomas
Published: March 2022

Enhancing cholesterol removal from macrophages in atherosclerotic plaques remains a major unmet pharmacological need. MicroRNA therapeutics are one approach that is currently being evaluated. MicroRNAs fine tune gene expression, and those that target ABCA1, the major cholesterol efflux transporter, are candidates for therapeutic approaches. Silencing microRNAs that target ABCA1 result in increased ABCA1 levels and activity and therefore enhance lipid removal from lesion macrophages. We previously showed that miR-144 targets ABCA1 by binding to at least 2 binding sites in the 3’ UTR region. We have now tested whether silencing miR-144, which increases ABCA1, affects atherosclerosis in two models. First, LDLR-/- mice were fed a western-type diet for 16 weeks, before being switched to regular rodent chow to promote lesion regression. One group of mice were sacrificed after 16 weeks of western diet (baseline), and the remaining animals were randomly assigned to one of 3 groups; vehicle (PBS), control anti-miR, or anti-miR-144 for 4 weeks. Silencing miR-144 significantly decreased atherosclerosis by en face analysis by 20% compared to either control. Further, silencing miR-144 modestly increased plasma HDL levels by 14%, in line with previous studies. To determine whether silencing miR-144 enhanced macrophage cholesterol efflux in mice, we used the same experimental approach. However, 2 days prior to the sacrifice, mice were injected with macrophages that had been loaded with radiolabelled cholesterol. Silencing miR-144 in vivo enhanced macrophage cholesterol efflux to plasma, liver and feces, suggesting the mechanism for the reduced atherosclerosis is due to increased cholesterol removal from plaques. Finally, we also determined whether silencing miR-144 decreased progression of atherosclerosis. LDLR-/- mice were fed a western-style diet for 16 weeks, and, at the same time, mice were treated mice with either anti miR-144, control anti miR or vehicle (PBS). Silencing miR-144 decreased atherosclerosis progression by 33% relative to controls, while HDL levels were also modestly increased (19%). Our results indicate that silencing miR-144 is a potential therapeutic strategy to reduce atherosclerosis, in both regression and progression models.
Abstract 19582: Placement of the Left Side AED Pad is Poor: Training on the Left Compared to the Right Side of a Manikin Does Not Improve Pad Placement
Authors: Stærk Mathilde , Bødtker Henrik , Rahbek Søren , Vammen Lauge , Løfgren Bo
Published: March 2022

Introduction:
Placement of automated external defibrillators (AED) pads is poor, especially placement of the left apical pad is rarely achieved. Sitting on the right side of a victim in cardiac arrest may interfere with correct left side pad placement because the rescuer has to bend over the victim to reach the left mid-axillary line. In addition, the left arm of the victim may hamper access to the left lateral side of the thorax.

Hypothesis:
Training automated external defibrillation sitting on the left side of a manikin improves AED pad placement compared to sitting to the right.

Methods:
Laypeople participating in a first aid course were randomized to learn automated external defibrillation sitting on the left or right side of a manikin during AED training. After course completion participants operated a training AED (Lifepak® CR-T AED Trainer, PhysioControl) and placed AED pads according to instructions from the AED. Pads were placed on an anatomically realistic male resuscitation torso with arms (AMBU® Man, AMBU). Participants were instructed to sit on the same side of the manikin as trained. The distance from the center of AED pads to the recommended pad position was measured.

Results:
In total, 30 volunteers were included and randomized to AED training on the left (n=14, 43% male, age: 47.9 years) and right (n=16, 25% male, age: 46.7 years) side of a manikin. There was no difference in left pad placement when trained on the left or right side (distance to recommended left apical pad position (mean±sd): 5.8±2.1 cm vs 7.0±2.4, p=0.15). The left apical electrode was in all cases placed too medial. Only a minor part of participants (left trained (36%); right trained (31%)) moved the left arm of the manikin to place the left apical pad. No difference was observed with respect to right pad placement when trained on the left or right side respectively (distance to recommended right sternal pad position (mean±sd): 2.7±1.7 cm vs 1.8±0.8 cm, p=0.10).

Conclusion:
Training automated external defibrillation on the left side of a manikin does not improve pad placement compared to training on the right side. Placement of the left apical pad is poor and future training should emphasize correct left lateral pad placement.
Abstract 19593: Sirtuin-3 is Essential for Glucagon-like Peptide-1-mediated Restoration of Diabetic Cardiomyopathy
Authors: Monji Akio , Bando Yasuko K , Kawase Haruya , Nishimura Hiroyuki , Aoyama Morihiko , Mitsui Toko , Murohara Toyoaki
Published: March 2022

Introduction:
Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase and its expression is increased by fasting and exercise in skeletal muscle; however, the impact of anti-diabetic intervention on diabetic myocardium remained uncertain.

Hypothesis:
We hypothesized that the anti-diabetic remedy glucagon-like peptide-1 agonist (exendin-4; Ex4) may ameliorate mitochondrial remodeling observed in diabetic cardiomyopathy.

Methods:
Type 2 diabetic mice [T2DM; KKAy and dietary diabetes induced by high fat and high sucrose diet (HF/HS), male 14-16 w/o] and age- and gender-matched SIRT3 knockout mice with dietary diabetes (sirHF/HS) diet were allocated into Ex4 (24 nmole/kg/day for 40 days) and vehicle (CON) groups.

Results:
T2DM-CON and sirHF/HS-CON exhibited myocardial hypertrophy, increased fibrosis, decreased cardiac capillary density, and defragmented mitochondria, which were reversed by Ex4. Consistently with the changes in mitochondrial morphology, the mitochondrial regulatory proteins mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) ratio was reduced in T2DM-CON and sirHF/HS-CON, which were ameliorated by Ex4 treatment exclusively to T2DM-CON. T2DM-CON exhibited decrease in cardiac SIRT3 level compared to nondiabetic counterpart, which was ameliorated by Ex4. Interestingly, cardiac remodeling of sirHF/HS-CON remained unchanged by Ex4 treatment, exclusively to cardiac capillary density. T2DM-CON and sirHF/HS-CON exhibited decrease in cardiac cyclic AMP level, which were attenuated by Ex4. The GLP-1 inactive analog (Ex9-39) failed to increase cardiac cyclic AMP concentration in mouse heart. In vitro analysis using cultured cardiomyocytes revealed that increase in intracellular cAMP levels by isoprotelenol (10microM) or 8-bromo-cyclic AMP (10 microM) enhanced SIRT3 mRNA, which was reversed by protein kinase A (PKA) inhibition.

Conclusions:
Our results indicate that Ex4 reversed abnormal suppression of SIRT3 in mitochondria of diabetic heart via restoration of cardiac cAMP.
Abstract 19603: Bone Morphogenetic Protein 6 and Oxidized Low-density Lipoprotein Synergistically Recruit Osteogenic Differentiation in Endothelial Cells
Authors: Yung Lai-Ming , Sánchez-Duffhues Gonzalo , ten Dijke Peter , Yu Paul B
Published: March 2022

Introduction:
Vascular calcification contributes to mortality and morbidity in atherosclerosis, chronic kidney disease, and diabetes. Vascular calcific lesions contain osteoblast-like and chondroblast-like cells, suggesting a process of endochondral or membranous ossification thought to result from the phenotypic plasticity of vascular cells. Bone morphogenetic protein (BMP) signaling potentiates atherosclerotic calcification, whereas BMP inhibition attenuates vascular inflammation and calcification in atherogenic mice.

Hypothesis:
We hypothesized endothelial cells may undergo osteogenic differentiation in response to BMP signaling and pro-atherogenic stimuli.

Methods and Results:
Among various BMP ligands tested, BMP6 and BMP9 elicited the most potent signaling in bovine aortic endothelial cells, however, only BMP6 induced osteogenic differentiation. BMP6 and oxLDL independently and synergistically induced osteogenic differentiation and mineralization, in a manner consistent with endothelial-to-mesenchymal transition. Treatment of endothelial cells with BMP6 or oxidized low-density lipoprotein (oxLDL) individually induced osteogenic and chondrogenic transcription factors Runx2 and Msx2, whereas treatment with BMP6 and oxLDL synergistically up-regulated Osterix and Osteopontin. Production of H2O2 was necessary for oxLDL-induced regulation of Runx2, Msx2, and Osterix in BAEC, and H2O2 was sufficient by itself to up-regulate these genes. Mineralization of endothelial cells in response to BMP6 or oxLDL was abrogated by scavenging reactive oxygen species or inhibiting BMP type I receptor kinases. Similar synergistic effects of BMP and oxLDL upon osteogenic and chondrogenic transcription and phenotypic plasticity in human aortic endothelial cells were observed.

Conclusion:
These findings provide a potential mechanism for the observed interactions of BMP signaling, oxidative stress, and inflammation in recruiting vascular calcification associated with atherosclerosis.
Abstract 19606: PZ-128: First in Human Pepducin Inhibitor of PAR-1 Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability
Authors: Gurbel Paul A , Bliden Kevin P , Tantry Udaya S , Turner Susan E , Gesheff Martin , Covic Lidija , Kuliopulos Athan
Published: March 2022

Background:
PZ-128 is a first-in-class cell penetrating lipopeptide pepducin that inhibits PAR-1-G protein signaling by forming a structure highly similar to the corresponding off-state juxtamembrane region of the GPCR. PZ-128 inhibited PAR-1 and thrombosis in non-human primates. Its effects in humans are unknown.

Methods and Results:
PZ-128 was administered by continuous intravenous infusion (0.01 mg/kg to 2 mg/kg) to patients with multiple cardiovascular risk factors (n=31). Safety, tolerability, and pharmacokinetic (PK) effects were assessed. Platelet receptor function was assessed by conventional aggregation at baseline and 0.5, 1, 2, 6, 24 h and 8-11 d post-dosing. There were no effects on ECG, hematologic or clinical chemistry parameters. At 0.5 mg/kg given over 2 h there was 40 % and 50 % inhibition (8 μM SFLLRN) at 0.5 and 2 h, respectively. At 1-2 mg/kg, there was 25% and 75% inhibition at 0.5 h and 95-100% inhibition at 1-2 h (p<0.05 for 1 mg dose). Maximal platelet aggregation (8 μM SFLLRN) was 66-100% recovered by 24 h at 0.5-2 mg/kg. There was no significant inhibition of PAR-4, ADP, or collagen receptors at any time point. PZ-128 plasma levels were linear with dose (R=0.99) and reached Cmax levels of 2 μM, 2.5 μM, 5 μM, and 12 μM at 0.3, 0.5, 1 and 2 mg/kg doses, respectively. The terminal elimination plasma half-life was 49 ± 6 min.

Conclusion:
PZ-128 is a promising parenteral antiplatelet agent that provided rapid, specific, dose-dependent, and reversible inhibition of platelet PAR-1 through a novel mechanism.
Abstract 19648: Post-exercise Blood Pressure Following Different Resistance Training Methods in Treated Older Hypertensive Women
Authors: Correia Ana Luiza M , Gauche Rafael , Gadelha André B , Paiva Flávio M , Neri Sílvia G , Lima Ricardo M
Published: March 2022

Introduction:
The purpose of this study was to examine post-exercise blood pressure following different resistance training methods in treated older hypertensive women.

Methods:
The sample consisted of 14 female volunteers with controlled hypertension (age 69.86 ± 5.67 years, weight 59.31 ± 9.77 kg, height 1.52 ± 0.06 m, BMI 25.76 ± 4.44 kg/m2) who attended six Laboratory visits. The first four visits aimed at collecting anthropometric data, familiarization and determining the training load. In the fifth and sixth visits, volunteers performed a traditional resistance exercise method (TRE) and a circuit resistance exercise method (CRE), in a randomized order. The sessions were separated by at least 48 hours, involved the following exercises: leg press, seated row, knee extension, bench press, knee flexion, lateral raise with dumbbells and seated calf raises. In TRE, the exercises were performed in three sets of 12 repetitions with an interval of 60 seconds between sets and exercises. In the CRE, the exercises were performed in circuit, with 3 rounds of 12 repetitions with 30 seconds rest between exercises and 60 seconds between rounds. The intensity was adjusted corresponding to the level 4 of the scale of perceived exertion to resistance exercise. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at rest, 15, 30, 45 and 60 minutes after the exercise sessions. Mean blood pressure (MBP) was calculated. Data normality was verified with the Shapiro-Wilk test. ANOVA for repeated measures (time X method) was used for data analysis. Significance was set at p <0.05.

Results:
Although mean SBP values were reduced following exercise, no significant effects of time, methods or time X method interaction were noted in SBP, DBP and MBP.

Conclusions:
Both resistance training methods, on intensity corresponding to the level 4 of perceived exertion scale, were not able to significantly alter the blood pressure of treated older hypertensive women
Abstract 19675: Management of Pump Thrombosis in Heartware Hvad Patients
Authors: Krabatsch Thomas , Kaufmann Friedrich , Hörmandinger Christoph , Müller Markus , Kretzschmar Alexandra , Pergantis Panagiotis , Falk Volkmar , Potapov Evgenij V
Published: March 2022

Introduction:
Implantable continuous-flow left ventricular assist device (LVAD) HeartWare HVAD has found broad acceptance, but a significant number of patients present with pump thrombosis (PT). We report our diagnostic and therapeutic strategy.

Methods:
We retrospectively analyzed pump thrombosis in 540 patients supported with the HeartWare HVAD in 8/2009-5/2015. Our anticoagulation protocol consisted of bridging with heparin until sufficient oral anticoagulation. Patients with clear evidence of pre- or post-device thrombus (n=5 and n=3) were excluded.

Suspected PT was defined as marked increase of LVAD power consumption, significant increase of hemolysis (according to Intermacs definitions) and/or positive signals in acoustic analysis. Confirmed PT was defined as either demonstration of thrombotic material in the explanted LVAD or complete disappearance of hemolysis and normalization of device parameters after thrombolytic therapy.

Results:
As median support in this group was 248 (range 0-2106) days the cohort represents 617 patient-years. Eighty-three episodes of PT were detected in 66 patients with 10 of these episodes successfully treated by thrombolysis (15%). PT occurred within 2-1521 days after primary implantation, median 349 days. Cumulative rate of all types of PT per patient-year (EPPY) was 0.13, with 0.11 for proven and 0.02 for suspected PT.

The decision to exchange the pump was triggered by marked hemolysis and/or high power consumption or failed thrombolysis, if initiated.

Fifty-five operative pump exchanges, including 5 after unsuccessful thrombolysis were necessary in 48 patients 5 patients experienced two and 1 patient three exchanges. Fifty pump exchanges were performed via lateral mini-thoracotomy and five through a median re-sternotomy.

Eight patients died before pump exchange. The hospital discharge rate was 62% after the first and 100% after the second and third pump exchange.

Conclusions:
Minority of pump thrombosis after HeartWare implantation could be cured medically. As most thrombosed devices can be exchanged through a lateral mini-thoracotomy with low postoperative mortality, the pump exchange should not be delayed and then even repeated thrombotic events can be handled successfully.
Abstract 19685: Liver Dysfunction as Reflected by MELD (the Model For End Stage Liver Disease) Score Could Better Predict Postoperative Outcome in Patients Undergoing Cardiac Surgery than Child-Turcotte-Pugh Classification
Authors: Murata Mai , Kato Tomoko S , Kuwaki Kenji , Kajimoto Kan , Yamamoto Taira , Amano Atsushi
Published: March 2022

Background:
Liver dysfunction increases postoperative morbidity and mortality following cardiac surgery. Child-Turcotte-Pugh (CTP) classification had been used in the evaluation of liver function. More recently, the composite model for end stage liver disease (MELD) score has become recognized as a more robust and objective scoring system than CTP classification. However, the predictive power of CTP and MELD scores for postoperative outcome in patients undergoing cardiac surgery has not yet been fully elucidated.

Methods and Results:
Postoperative outcome and preoperative liver function estimated by the CTP classification or the MELD scores were investigated in 1856 consecutive patients (69.3% male, age 66. 8±12.2 years) undergoing cardiac surgery between 2010 and 2013 at our institution. The proportions of patients in CTP class A, B and C were 91.8% (n=1704), 8.1% (n=151) and 0.05% (n=1); and mean MELD scores in patients in each CTP class were 9.4, 15.5 and 36.7, respectively. A MELD cutoff value of 12 can predict postoperative mortality with a sensitivity and specificity of 78.7 and 63.9%, respectively, with an area under the curve (AUC) from the ROC analysis of 0.75248 (p<0.0001). Child class B/C predicts morality with a sensitivity and specificity of 23.7 and 92.2%. High MELD score (>12) was associated with longer intubation time (33.6±5.1 vs. 12.2±2.7 hours, p<0.0001), longer ICU (4.8±0.3 vs. 2.2±0.2 days, p<0.0001) and total-hospital stay (34.5±1.0 vs. 22.8±0.6 days, p<0.0001) and more incidence of renal replacement therapy requirement (46.0 vs. 4.4%, p<0.0001) than those with low MELD scores (<12). The predictive strength of the MELD, MELD component variables and CTP class (B/C vs. A) were quantitatively compared based on AUC by using the DeLong test, which revealed that MELD score was the strongest predictor for morality (pairwise comparison, all p<0.05).

Conclusions:
Assessment of liver dysfunction using the MELD scoring system is useful for predicting postoperative morality and morbidity following cardiac surgery. MELD scoring system was a stronger predictor for morality than CTP classification.
Abstract 19705: Real-time Home-to-hospital Ischemic Time Dashboard in Patients With ST segment Elevation Myocardial Infarction Results in Significant Improvement of the Logistic Chain and Lower Short-term Mortality
Authors: Hermans Maaike , Velders Matthijs , Smeekes Martin , Drexhage Olivier , Ytsma Timon , Schalij Martin , Umans Victor
Published: March 2022

Introduction:
Timely reperfusion with primary percutaneous coronary intervention (PCI) in ST segment elevation myocardial infarction (STEMI) patients is associated with superior clinical outcomes. Aiming to reduce ischemic time, an innovative system for H2H time monitoring was implemented. The objective of this study was to assess the results of a real time home-to-hospital (H2H) dashboard for monitoring and evaluation of ischemic time in STEMI patients.

Methods:
Ischemic time in STEMI patients transported by Emergency Medical Services (EMS) and treated with primary PCI in the Medical Center Alkmaar before (n=843) and after the implementation of the H2H dashboard (n=441) was compared. Time points in the H2H dashboard were semi-automatically registered, enabling evaluation by the EMS and Cardiology departments. Before implementation of the H2H dashboard, time points were recorded on paper and retrospectively collected.

Results:
Median treatment delay, first medical contact (FMC) to balloon time and door-to-balloon time were significantly shorter in the H2H group (treatment delay 142 minutes [IQR 103;221 minutes] vs. 181 minutes [IQR 134;286 minutes] P value <0.001, FMC-to-balloon time 62 minutes [IQR 52;75 minutes] vs. 86 minutes [IQR 71;111 minutes] P value <0.001 and door-to-balloon time 32 minutes [IQR 25;43 minutes] vs. 52 minutes [IQR 34;76 minutes] P value <0.001). Adjusted for baseline characteristics, the H2H time monitoring dashboard was independently associated with shorter time delays. 90-Days survival rates were significantly higher in the H2H group, this was due to lower incidence of cardiogenic shock.

Conclusions:
After implementation of the H2H dashboard, significantly shorter ischemic time was observed. The use of the H2H dashboard was independently associated with shorter time delays. Short-term mortality was significantly lower in the H2H group due to lower incidence of cardiogenic shock.
Abstract 19723: Troponin Elevations in Ischemic Stroke are Associated With Stroke Severity and Advanced Age
Authors: Miller Benjamin R , M.Alkhachroum Ayham , Chami Tarek , Sila Cathy
Published: March 2022

Introduction:
Troponin elevations are common in patients with hemorrhagic stroke where they have been attributed to sympathomimetic states and stroke severity. Troponin elevations are less common in patients with ischemic stroke and have been associated with insular cortex location but there are no studies evaluating the impact of stroke severity. The diagnosis of type II MI/ myocardial strain is a co-morbidity that increases case-mix index and impacts DRG assignment.

Hypothesis:
Troponin elevations in ischemic stroke is related to stroke severity and older age, independent of severity.

Methods:
All patients with ischemic stroke at University Hospitals Case Medical Center from January 2014 to April 2015 were retrospectively reviewed. Data was collected on demographics, stroke severity by National Institutes of Health Stroke Score (NIHSS), and serial troponin values.

Results:
Of 629 patients with ischemic stroke, 478 met inclusion criteria including initial and follow up troponin levels. Elevated troponin levels were found in 28.2% of patients- 16.3% in high and 11.9% in critical ranges. Troponin elevations were associated with stroke severity. Although initial troponin values were not significantly different for the more severe ischemic strokes (NIHSS ≥ 10) vs less severe (NIHSS <10) for the initial troponin value, they were significantly higher on follow up values (p<0.001). This was more apparent when stratified by age; initial and peak troponin values increased in both age groups, more for those ≥65 (p=0.0003), but was observed for younger patients as well (<65, p=0.03).

Conclusions:
Elevated troponin levels occur in 28.2% of patients with ischemic stroke, 11.9% in the critical range, and are associated with higher stroke severity and advanced age. Patients with more severe stroke and advanced age are more likely to have troponin elevations on follow up testing thus a baseline value alone may not be sufficient to assess risk or establish the cardiac diagnosis.
Abstract 19740: Intramuscular Lipid Accumulation is Reversed by a p62-lysosomal-independent Lipophagy Pathway
Authors: Lam Truong N , Harmancey Romain , Vasquez Hernan , Gilbert Blaine , Patel Nina
Published: March 2022

Background and Hypothesis:
In the mammalian heart, autophagy is an adaptive mechanism promoting the removal of protein aggregates or damaged cell organelles. A common feature of non-ischemic heart failure is lipid accumulation. We examined whether autophagy is impaired in the muscle in chronic lipid overload and investigated whether activation of autophagy protects myocytes from lipotoxicity.

Methods:
Rat L6 myocytes were incubated over a period of 6 days with or without long chain fatty acids (equimolar mixture of oleate and palmitate, 1.0mM). At day 6, an autophagic inhibitor (bafilomycin A1, 200 nM), or an autophagic activator (rapamycin, 1 μM), or both, were added for 48 hours. Intracellular triglyceride (TG) accumulation was assessed by Oil Red O staining and immunofluorescence and was quantified colorimetrically. Protein markers of autophagic flux (LC3 and p62) and cell death (Caspase 3 cleavage) were measured by immunoblotting.

Results:
Inhibition of autophagy using bafilomycin increased TG accumulation and also increased fatty acid-mediated cell death. Conversely, activation of autophagy using rapamycin reduced both intracellular lipid accumulation and cell death. Unexpectedly, treatment with both rapamycin and bafilomycin resulted in a decrease in lipid accumulation. Immunoblotting indicated p62 degradation (autophagic flux), while immunofluorescence revealed the colocalization of p62 with lipid droplets in these cells. These findings indicate the potential association of p62 with lipid droplet turnover, which is a novel pathway for the breakdown of lipid droplets in muscle cells. TG in the extracellular medium was also assessed. The same cells treated with rapamycin and bafilomycin had higher levels of extracellular TG compared to extracellular TG of cells with other treatments. The results suggest that the p62-mediated pathway for lipid degradation ultimately exports TG’s from the cell by exocytotic mechanisms.

Conclusions:
Autophagy promotes the clearance of lipids from myocytes and switches to an alternative, p62-mediated pathway of lipophagy and exocytosis in the context of chronic lipid overload. Moreover, lipophagy promotes metabolic adaptation and myocyte survival.
Abstract 19752: Nox4 Expression Regulates Inflammation in Tgfβ-treated Vascular Smooth Muscle Cells
Authors: Lozhkin Andrey , Vendrov Aleksandr E , Pan Hua , Wickline Samuel A , Madamanchi Nageswara R , Runge Marschall S
Published: March 2022

NADPH oxidases (NOX) are a major source of reactive oxygen species in the cardiovascular system, contributing to the pathogenesis of disease. We recently reported that increased NOX4 expression in aging results in enhanced cellular and mitochondrial oxidative stress, vascular inflammation, dysfunction, and atherosclerosis. However, the role of NOX4 in the activation of inflammatory molecular pathways in vascular smooth muscle cells (VSMC) under pathophysiological conditions has not been elucidated. In this study, we investigated whether inhibition of NOX4 expression modulates proinflammatory gene expression in mouse VSMC by suppressing its expression with a novel peptide-mediated siRNA transfection approach. Using melittin derived peptide p5RHH, we achieved significantly higher transfection efficiency (92% vs 85% with Lipofectamine) and decreased toxicity (p<0.01 vs Lipofectamine in MTT assay). TGFβ, a proinflammatory cytokine, known to induce NOX4 expression significantly upregulated NOX4 mRNA (p<0.01) and protein expression (p<0.01) in VSMC. p5RHH mediated NOX4 siRNA transfection attenuated TGFβ induced upregulation of NOX4 mRNA (p<0.01) and protein (p<0.01) levels. Analysis of inflammatory marker genes, CCL2, CCL5, IL6, and VCAM-1, showed that NOX4 knockdown significantly attenuated the expression of these genes in TGFβ-treated VSMC, with the highest inhibition seen in the expression of IL6. Congruent with this, inflammatory marker gene expression, which increases with aging, was significantly lower in VSMC isolated from aged (16 months old) NOX4 knockout mice compared with the aged wild-type. TGFβ-activated kinase 1 (TAK1, also known as MAP3K7) is an upstream regulator of inflammatory signaling in cells treated with cytokines. p5RHH mediated TAK1 siRNA transfection downregulated AP1 and NFκB activation and inhibited NOX4 expression in wild-type VSMC, indicating that TAK1 regulates NOX4 expression via regulation of AP1 and NFκB. Because plasma TGFβ levels increase with aging, it may be of one of the factors contributing to increased NOX4 expression with aging. Our data indicate that NOX4 is a potential therapeutic target for modulation of inflammation in aging and aging-associated cardiovascular disease.
Abstract 19765: Barriers to Implementation of a Health Promotion Program in Harlem, New York: The FAMILIA Study, an AHA Strategically Focused Research Network Study
Authors: Bansilal Sameer , Vedanthan Rajesh , Jaslow Risa , Hadley Martha , Siskind Amy , Marcial Carmina , Soto Ana V , Kofler Claire , Fayad Zahi A , Fuster Valentin
Published: March 2022

Objective:
The Harlem area of New York City has among the highest obesity and diabetes prevalence rates in the city. Nearly half of the children in the Head Start program and about 94% of adults are overweight or obese. We sought to identify factors that may impact the implementation of an integrated family-based health promotion program for children aged 3-5 years and their caregivers in Harlem.

Methods:
We conducted a qualitative study consisting of 5 focus group discussions (FGD) at two Head Start preschool centers in Harlem, NY. The FGDs included the following participants: parents, teachers, directors, educational directors, nutritionists, cooks, health, mental health and social service professionals. Content analysis of the transcript and notes was performed to identify salient themes. Relationships between and among themes were formulated.

Findings:
Twenty-five individuals participated in the FGDs. Seven themes emerged as potential barriers to program implementation. Program implications and specific strategies to address them were generated (Table).

Conclusions:
Formative work prior to program implementation has revealed important, actionable issues that will be addressed during the intervention period. This type of approach may be useful for other health promotion programs in similar settings.
Abstract 19787: Cardiovascular Risk Assessment in the South Texas HIV+ Cohort: Is Risk Estimation or Risk Categorization More Appropriate for Patient Counseling?
Authors: Liang Yuanyuan , Ketchum Norma S , Turner Barbara J , Flores John M , Bullock Delia , Villarreal Roberto , Noel Polly H , Yin Michael T , Taylor Barbara S
Published: March 2022

Introduction:
Existing cardiovascular disease (CVD) risk calculators underestimate the risk of CVD among people with human immunodeficiency virus (HIV+). This is the first study to compare CVD risk estimations and categories in an HIV+ cohort using AHA, Framingham (FRC), and D:A:D (Data collection on Adverse Effects of Anti-HIV Drugs Study) calculators.

Methods:
Of patients seen in a public HIV clinic in South Texas ≥2 times in 2013, 668 HIV+ adults >40 years old without prevalent CVD had sufficient data for CVD risk calculations. Patients’ continuous 10 year CVD risks were estimated by three calculators and compared pairwisely using Wilcoxon signed-rank test. Patients were classified into risk categories per guidelines for each risk calculation, which differ: AHA: 10y risk<7.5% Low, ≥7.5% High; FRC: 10y risk <10% Low, 10-20% Moderate, >20% High; D:A:D: 5y risk <1% Low, 1-5% Moderate, ≥5% High. The proportion of patients at high risk was compared with McNemar’s test.

Results:
Mean patient age was 49.8y (SD=6.2), 79.9% were men, 63.3% Hispanic, 19.6% white non-Hispanic, 14.7% African American, mean BMI was 27.9 kg/m
2
(SD=5.6), 41.6% were treated for hypertension, and 17.2% had diabetes. HIV disease was relatively controlled, with 85.2% on antiretroviral therapy and 69% virologically suppressed. Median estimated 10y CVD risk was highest with FRC (all p<0.001, Table). The percentage of patients classified at high risk ranged from 20.4% to 44.2%, with D:A:D placing the highest proportion of patients into a high risk group (all p<0.001).

Conclusions:
Risk calculators behaved differently based on whether continuous risk estimates or categorical risk classifications were used. Median 10-year risk was highest with FRC, yet D:A:D classified the highest proportion of patients at elevated risk. Since CVD risk calculators underestimate risk for HIV+ adults, clinicians may find the risk categorization with AHA or D:A:D calculators more appropriate for patient counseling.
Abstract 19801: Obesity, Insulin Resistance and Loss of Dipping are Associated With Pulse Wave Velocity in Prepubertal Children
Authors: Costa Ana Luísa , Correia-Costa Liane , Caldas Afonso Alberto , Schaefer Franz , Guerra António , Moura Cláudia , Mota Cláudia , Barros Henrique , Areias José Carlos , Azevedo Ana
Published: March 2022

Introduction:
Arterial stiffness is a dynamic property of the vessels which reflects changes in their structure and function and pulse wave velocity (PWV) is a noninvasive and high-resolution technique to indirectly evaluate it. Childhood obesity is known to be associated with the development of several cardiovascular comorbidities and to the progression of atherosclerosis.

Hypothesis:
We aimed to compare carotid-femoral PWV between normal weight and overweight/obese prepubertal children and to evaluate its association with other cardiovascular risk factors.

Methods:
We conducted a cross-sectional study of 315 children aged 8-9 years that have been followed in the population-based birth cohort Generation XXI (Portugal). Anthropometrics, 24-hour ambulatory blood pressure (BP) and PWV were measured. Classification of obesity was according to World Health Organization body mass index (BMI)-for-age reference values.

Results:
Compared to normal weight children, overweight and obese children presented significantly higher levels of PWV (4.95 (P25-P75: 4.61-5.23), 5.00 (4.71-5.33), 5.10 (4.82-5.50) m/sec, respectively; p for trend<0.001). Significant positive correlations were found between PWV and total cholesterol, LDL cholesterol, triglycerides, fasting insulin and insulin resistance levels (estimated by homeostasis model assessment of insulin resistance - HOMA-IR) and with high-sensitivity C-reactive protein. In a multivariate linear regression model adjusted for sex, age, height and 24-hour systolic BP z-score, the independent determinants of PWV were BMI, HOMA-IR and the absence of dipping pattern.

Conclusions:
The association between PWV and the loss of dipping and insulin resistance levels, independently of the BMI, reinforces the contribution of these comorbidities to vascular injury in early life. Longitudinal studies are needed to strengthen the role of PWV as a valid tool for risk stratification in children.
Abstract 19802: Implantable Hemodynamic Monitoring Reduces Heart Failure Hospitalizations Due to Congestion Regardless of Perfusion Status
Authors: Miller Alan B , Gilbert Edward M , Chung Eugene S , Levy Wayne C , Teerlink John R , Carson Peter , Adamson Philip B , Abraham William T
Published: March 2022

Introduction:
Heart failure (HF) management guided by implantable hemodynamic monitoring systems reduces overall hospitalizations in NYHA Class III patients with a previous HF hospitalization.

Hypothesis:
Hemodynamic monitoring may reduce hospitalizations with accompanying low output status, as well as those resulting primarily from congestion.

Methods:
The CHAMPION Trial enrolled 550 NYHA Class III patients and randomly assigned them to a treatment group who were managed by hemodynamic monitoring using a permanently implanted pulmonary artery (PA) MEMS-based sensor or to a control group who were managed by standard clinical assessments (MEMS-sensors were implanted, but the uploaded pressures were not available to investigators). The primary endpoints were the comparison of HF hospitalization rates between the treatment and control groups assessed after 6 and 17 months of randomized follow-up. The blinded Clinical Events Committee prospectively adjudicated each HF hospitalization based on documented clinical hemodynamic characteristics: (1) well perfused/congested, (2) poorly perfused/congested or (3) poorly perfused without congestion. Group 3 events were rare and not different between groups.

Results:
Patients in the treatment group had fewer hospitalizations overall (182 hospitalizations, rate 0.46/patient/year treatment vs. 279 hospitalizations, rate 0.68/patient/year control; (HR 0.67 CI (0.55-0.80), p<0.001). The majority of hospitalizations fit the perfused/congested profile, and were decreased in the treatment group compared with control (138 vs. 224 hospitalizations, HR 0.62, CI 0.50-0.77, p<0.001). Poorly perfused/congested events were similarly reduced in the treatment group compared with control (29 vs. 44 hospitalizations, HR 0.63, CI 0.39-1.01, p=0.05).

Conclusions:
Compared to standard clinical assessments, HF managed with implantable hemodynamic monitoring results in significant reductions in heart failure hospitalization regardless of perfusion status.