bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16708: Socioeconomic Status and the Incidence of Atrial Fibrillation in Whites and African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Misialek Jeffrey R , Rose Kathryn M , Everson-Rose Susan A , Soliman Elsayed Z , Clark Cari J , Lopez Faye L , Alonso Alvaro
Published: April 2024

Background:
Lower socioeconomic status (SES) has been associated with a higher risk of cardiovascular disease (CVD) overall. However, the association of SES and atrial fibrillation (AF) has not been investigated to date.

Methods:
We studied 14,352 men and women (75% white, 55% women, mean age 54) free of AF participating in the Atherosclerosis Risk in Communities (ARIC) study. SES was assessed at baseline (1987-89) through educational level and family income. Incident AF cases through 2008 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals of AF for education and family income separately. Models were initially adjusted for age, sex, and race. Additional models further adjusted for study site, diabetes, systolic blood pressure, use of antihypertensive medications, smoking status, alcohol consumption, body mass index, and a history of other CVD (heart failure, myocardial infarction, or stroke). Interactions were tested between the measures of SES and race and sex.

Results:
Over a median follow-up time of 19.6 years, 1,648 AF cases were identified. Low income was associated with higher AF risk in the entire cohort (table), with no evidence of significant interactions between family income and sex or race. A significant multiplicative interaction was present between sex and education (p<0.0001). Low education was associated with higher AF risk in women but not in men (table). No interaction was found between education and race. Adjustment for cardiovascular risk factors and other CVD strongly attenuated all associations (table, model 2).

Conclusion:
Lower SES was associated with a higher AF risk. This association was not different between whites and African Americans; however, the impact of education on risk of AF may be more prominent for women. Cardiovascular risk factors and other CVD likely mediate this association.
Abstract 16795: Detection of Brown Adipose Tissue Activation and Mass Using Contrast Ultrasound
Authors: Clerte Maeva , Baron David M , Flynn Aidan , Raher Michael J , Bloch Kenneth D , Picard Michael H , Buys Emmanuel S , Brouckaert Peter , Scherrer-Crosbie Marielle
Published: April 2024

Obesity is an increasingly frequent condition and a risk factor for cardiovascular diseases. Brown adipose tissue (BAT), located mostly in the paravertebral and supraclavicular space in humans and between the scapulae in rodents, consumes lipids and glucose to produce heat when it is activated by norepinephrine (NE) or cold. Increasing metabolic activity and/or mass of BAT could open new therapeutic avenues to treat obesity. Currently,18F-fluorodeoxyglucose Positron Emission Tomography is the only imaging technique detecting BAT and its activation in humans. Since increased BAT blood flow is associated with BAT activation, we hypothesized that BAT contrast ultrasound (CU) could estimate the degree of BAT activation and BAT mass, both in mice and humans. To validate the ability of CU to estimate BAT perfusion, the BAT and kidney of C57BL6 wild type mice were imaged with a 14 MHz linear transducer during continuous infusion of DefinityTM microbubble contrast. The time intensity curves of the contrast were quantified and blood flow was estimated by the product of the curve plateau A and slope ß. The BAT/kidney blood flow ratio obtained with CU was compared to that measured with fluorescent microspheres. In another experiment, to validate the ability of CU to estimate BAT mass, the maximal area of perfusion of BAT was compared to the BAT weight, in mice. Finally, the BAT vascular response to activation was assessed in 6 mice before and after infusing 1µg/kg/min NE and in 7 young and lean human volunteers before and after cold exposure (16°C for 2 hours).The BAT/kidney blood flow ratio obtained by CU in mice correlated with microsphere measurements (R2=0.85, p<0.05). The maximal area of BAT measured by CU correlated with BAT weight (R2=0.58, p<0.002). Mice demonstrated a 10-fold increase in BAT perfusion after infusion of NE (Aß 0.6±0.1 vs. 5.5±0.9 dB/s, p<0.05) while kidney perfusion decreased. Similarly, BAT perfusion increased in humans after cold exposure (Aß 0.1±0.0 vs. 1.0±0.4 dB/s,p<0.05). In conclusion, contrast ultrasound imaging can be used to estimate BAT activation and its mass. This noninvasive technique free of ionizing radiation offers a method for serial evaluation and monitoring of therapies designed to activate BAT or augment its mass.
Abstract 16797: Red Cell Distribution Width and Risk of Coronary Heart Disease Among Low Risk Healthy Representative US Adults
Authors: Zalawadiya Sandip K , Panaich Sidakpal S , Veeranna Vikas , Neeraj Ashutosh , Kommuri Naga V , Afonso Luis
Published: April 2024

Objective:
Evaluate the risk reclassification properties of red cell distribution width (RDW) in low risk healthy population free of prior cardiovascular disease (CVD) and diabetes.

Background:
Red cell distribution width (RDW) is an independent predictor of future CVD events. No prior study has evaluated whether addition of RDW to traditional cardiovascular risk factors (CVRF) (age, male sex, hypertension, dyslipidemia and smoking) improves risk reclassification, especially for those at intermediate risk of CVD events.

Study Type:
Prospective observational

Methods:
15,460 participants aged ≥20 years of National Health and Nutrition Examination Survey (1988 to 1994) were evaluated. Adjusted Cox-proportional hazard analyses were performed to evaluate independent association between RDW and cardiovascular deaths (CVD and coronary heart disease (CHD)) beyond traditional CVRF, C-reactive protein, estimated glomerular filtration rate, hemoglobin, mean corpuscular volume and deficiency of nutritional factors like iron, folate and vitamin B
12
. Various calibrative and discriminatory methods were used to evaluate model with RDW and CVRF compared to model with CVRF alone. Newer reclassification index, category-less net reclassification improvement (NRI), was computed to analyze reclassification properties of RDW over traditional CVRF.

Results:
RDW independently predicted CVD (adjusted hazard ratio (aHR): 2.18, 95% Confidence interval (CI) - 1.70 to 2.82, p<0.001) and CHD (aHR 2.15, 95% CI - 1.61 to 2.88, p<0.001) mortality after adjustments. Statistically favored model including RDW and traditional CVRF reclassified 74% of overall population (95% CI - 65% to 85%, p<0.001) based on category-less NRI. Nearly 35% of those classified to have intermediate risk by traditional CVRF were reclassified into higher or lower risk categories by addition of RDW.

Conclusion:
In this nationally representative adult US population, RDW significantly improves risk reclassification beyond traditional CVRF.
Abstract 16820: Impaired KCNQ1/KCNE1 Channel Activation by Alpha-Adrenergic Receptor is Associated with Emotion/Arousal Triggered Events in Long QT Syndrome Type 1
Authors: O-Uchi Jin , Rice John J , Goldenberg Ilan , Moss Arthur J , Lopes Coeli M
Published: April 2024

Background:
Stimulation of the cardiac K
+
channel IKs (KCNQ1/KCNE1) is crucial in mediating the QT shortening at high adrenergic stimulation states, with mutations in the KCNQ1 subunit being linked to a high risk of cardiac events triggered by adrenergic stimulation. IKs is strongly regulated by β-adrenergic receptor (AR) stimulation, but little is known about the role of α
1
-AR-mediated regulation and relation to the LQT1 phenotype.

Methods:
We co-expressed wild-type and mutant KCNQ1/KCNE1 subunits together in HEK293T cells. A single cardiomyocyte model adapted from the Flaim-Giles-McCulloch model was used to simulate the effect of α
1
-AR and β-AR activation in action potential duration (APD). Mutation specific adrenergic-effects on APD were correlated to the cumulative rate for exercise and stress-triggered cardiac events (syncope, sudden death and aborted cardiac arrest) by age 40 for patients carrying the mutation.

Results:
Acute α
1
-AR activation strongly facilitated voltage dependence of IKs activation independently of β-AR stimulation (V
1/2
shift @ - 20 mV) via activation of cPKC. We measured the effect of β-AR-PKA and α
1
-AR-cPKC activation for 8 LQT1 associated mutations. For each mutant we introduced the current activation measured in a single cardiomyocyte model to simulate the overall effect of (α
1
+ β1) AR stimulation. Mutant specific α
1
- and β- AR-mediated APD showed stronger correlation to the cumulative rate of emotion/arousal triggered cardiac events than β-AR alone (α+β: R
2
=0.94, β: R
2
=0.58), while β-AR activation alone showed a better correlation with exercised triggered event rate (α+β: R
2
=0.34, β: R
2
=0.74) for patients carrying these mutations.

Conclusion:
Our study suggests that acute α
1
-AR regulation of the voltage activation of IKs may be important for QT shortening in response to strong adrenergic stimulation in the flight and fight response. In addition, impaired α
1
-AR regulation may be linked to increased risk of sudden emotion/arousal triggered cardiac events in LQT1patients.
Abstract 16841: Cardiac Deletion of Aryl Hydrocarbon Nuclear Translocator (Hypoxia Inducible Factor 1-beta) in the Adult Heart Leads to Cardiomyopathy Due to Lipid Accumulation via Peroxisome Proliferator Activated Receptor Activation
Authors: Wu Rongxue , Chawla Kusum , Ghanefar Mohsen , Ardehali Hossein
Published: April 2024

Background:
Aryl hydrocarbon receptor nuclear translocator (ARNT), also known as hypoxia-inducible factor 1-beta (HIF1-beta), serves as a binding partner for numerous basic helix-loop-helix Per/ARNT/Sim proteins, including HIF1alpha. Although HIF1alpha is known to be required for normal cardiac development, the role of ARNT in basal cardiac function in the adult is not known. We hypothesized that ARNT is required for normal cardiac physiology, and that ARNT deletion in the adult heart results in cardiomyopathy.

Methods and Results:
Cardiac-specific ARNT deletion was achieved by crossing ARNT
flox/flox
with αMHC-MCM (tamoxifen-inducible heart specific Cre) transgenic mice, followed by oral administration of tamoxifen. MCM/ARNT
+/+
(WT) littermates were used as a control. Echocardiography of the ARNT knockout (KO) mice showed enlarged left ventricle with a reduction in ejection fraction (KO vs. WT: 35.8 ± 3.6% vs. 61.2 ± 2.8%, n=12, p<0.01). Closed-chest catheterization indicated that +dP/dt (KO vs. WT: 4355 ± 538 vs. 9426 ± 180 mmHg, p<0.01) was reduced in KO mice but not in WT mice. Electron microscopy revealed lipid droplets in ARNT KO heart tissues that were confirmed by oil-red staining. Furthermore, genes involved in fatty acid oxidation were up-regulated in KO hearts, as shown by microarray analysis and qRT-PCR. We further confirmed these results
in vitro
with siRNA-mediated knock down of ARNT in H9c2 cardiac myoblasts. Compared to control siRNA transfection, ARNT knockdown led to increases in PPAR-alpha (1.7-fold, p<0.001),

fatty acid translocase

(1.4-fold, P<0.01), and acyl-coenzyme A dehydrogenase (1.6-fold, p<0.0001) mRNA levels and to enhanced triglyceride accumulation (p<0.05). Moreover, insulin resistance was noted in ARNT knockdown cells, as demonstrated by significantly reduced glucose uptake in response to insulin stimulation. These results suggest that impaired fatty acid oxidation leads to lipid accumulation in response to a reduction in ARNT levels.

Conclusion:
ARNT is essential for normal cardiac function, and a reduction in ARNT levels leads to cardiomyopathy by increasing triglyceride accumulation through a PPAR-alpha pathway.
Abstract 16890: WW45 is Required for Mst1-Dependent Inactivation of YAP and Promotion of Myocardial Damage During Ischemia-Reperfusion
Authors: Sciarretta Sebastiano , Zhai Peiyong , Sadoshima Junichi
Published: April 2024

The mammalian homolog of
Drosophila
Hippo, Mst1, is a kinase which negatively regulates cardiomyocyte (CM) growth and survival. Mst1 promotes CM apoptosis in response to oxidative stress and mediates myocardial ischemia-reperfusion (I/R) injury. In
Drosophila
, the adaptor protein Salvador is required for activation and function of Hippo. We investigated the role of the mammalian homolog of Salvador, WW45, in the regulation of Mst1 activity in the heart. To address this issue, we studied the cardiac phenotype of cardiac-specific WW45 knock-out (W-cKO) mice. At baseline, W-cKO mice were characterized by a mild increase in LV weight/body weight compared to controls (3.44 ± 0.13 vs. 2.92 ± 0.10 mg/g; p<0.05) and normal cardiac function, suggesting that endogenous WW45 negatively regulates baseline growth of the heart. After I/R (30 minutes/24 hours), W-cKO mice exhibited a significantly smaller infarct size/area at risk than controls (20.4 ± 6.0 vs. 38.2 ± 4.5%; p<0.05). Interestingly, Mst1 activation, as evaluated by its phosphorylation status (Thr183), was significantly reduced in W-cKO mice both at baseline (0.5 ± 0.01 fold, p<0.05) and during reperfusion (0.37 ± 0.04 fold, p<0.05), indicating that WW45 is required for Mst1 activation. Co-immunoprecipitation analysis showed that WW45 physically interacts with Mst1 in CMs. We further evaluated whether downregulation of WW45 affects the phosphorylation status (Ser127) and the accumulation of Yes-associated protein (YAP), a transcription factor co-factor which promotes cellular growth and survival. YAP is phosphorylated by the Hippo pathway, and, upon its phosphorylation, YAP is exported from the nucleus and degraded. The level of YAP was increased in the hearts of W-cKO mice at baseline (2.6 ± 0.03 fold, p<0.05) and during reperfusion (4.2± 0.16 fold, p<0.05), and its relative phosphorylation status was decreased (-64% and -75%, p<0.05), indicating that WW45 positively regulates phosphorylation of YAP. There was a significant increase in nuclear localization of YAP during I/R in W-cKO CMs compared to in control CMs (2.2 ± 0.26 fold, p<0.05). In conclusion, our data suggest that endogenous WW45 is required for Mst1-dependent inactivation of YAP and promotion of myocardial damage during I/R.
Abstract 16905: Parental Vigilance in Caring for Their Children with Hypoplastic Left Heart Syndrome
Authors: Meakins Leanne , Ray Lynne , Hegadoran Kathleen , Rempel Gwen
Published: April 2024

Hypoplastic left heart syndrome (HLHS) is a complex heart malformation that requires life-saving treatment within the first days of life if the child is to survive. Parents experience numerous challenges as they learn to parent a child with complex care requirements and to deal with the consequences of such intensive parenting on themselves as parents. The research question guiding this study was: Is the parenting process among parents of a child with HLHS characterized by exaggerated vigilant parental action and if so, how does this influence parental response? This research was undertaken within a program of qualitative research in which 2 studies involved parents of children with HLHS, one cohort having undergone the classic Norwood approach and the other cohort the Sano approach. Interview data from both studies underwent a secondary thematic content analysis based on the sensitizing concepts of uncertainty, protectiveness, support, and mastery of complex care. Transcribed data from 55 interviews with parents (24 mothers and 17 fathers) of young children (2 months to 5 years of age) with HLHS were analyzed for relevant and recurring themes. In mastering skills required to care for their child with HLHS, parents focused on what was
in their hands
, in contrast to what was
out of their hands.
Vigilant parental actions were evident as parents became skilled at providing complex care and protecting their child. Parents recounted when they were excessive in their vigilant actions and acknowledged that these actions were situation appropriate at times and other times exaggerated. Knowledge of vigilant and exaggerated vigilant parental actions in response to their child's complex care has implications for health care providers who provide education and support for the parents of these children. Long term follow-up, both clinically and through research is needed to assess the long term consequences of exaggerated vigilant parental action on the child, parent and family and to determine and evaluate appropriate and timely intervention.
Abstract 16944: Ablation of the LV Endocardial Surface Reveals Origin of Ventricular Arrhythmias in a Murine CPVT Model
Authors: Faggioni Michela , Venkataraman Raghav , Baudenbacher Franz , Knollmann Bjorn C
Published: April 2024

Background:
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder caused by spontaneous Ca releases from the sarcoplasmic reticulum. Cellular studies suggest that both purkinje cells and ventricular myocytes from CPVT mouse models can trigger spontaneous beats, but the precise origin of CPVT within the heart is still unknown.

Methods:
ECG and optical maps from isolated Casq2KO hearts were recorded at baseline and after LV endocardial ablation using Lugol's solution. The ablation was considered successful when the left ventricle breakthrough activation disappeared and the ECG showed a QRS morphology consistent with a complete left bundle branch block. The extent of the LV endocardial ablation was evaluated with TTC staining. Ventricular tachyarrhythmias were triggered with a bolus of isoproterenol after reducing the intrinsic sinus rate with carbachol. The origin of ventricular beats (VBs) was classified into 6 anatomical regions: right ventricular outflow track (RVOT), mid/lateral RV (RVM), RV apex (RVA), left ventricular base (LVB), mid/lateral LV (LVM), LV apex (LVA).

Results:
A total of 4334 VBs were analyzed from 16 hearts. In control conditions, 66% of VBs arose from the RV (19% RVOT, 33% RVM, 14% RVA) and 34% from the LV (11% LVB, 11% LVM, 12% LVA). LV endocardial ablation almost completely abolished VBs originating from the LV, but did not significantly change the number of RV beats (Figure). TTC staining demonstrated that ablation was restricted to <20% of LV wall thickness.

Conclusions:
The endocardial surface plays a central role in the initiation of arrhythmias in CPVT, suggesting that Purkinje fibers are the most likely culprit for the ectopic events and they should be considered as a target for both pharmacological and gene therapy.
Abstract 17048: Fifteen Year Follow-Up After Aortic Root Replacement with Stentless Biological Valve Conduits: Homograft versus Freestyle
Authors: Sponga Sandro , Dagenais Francois , Perron Jean , Voisine Pierre , Tchana-sato Vincent , Doyle Daniel , Mohammadi Siamak
Published: April 2024

Objectives:
The choice of biologic aortic valve substitute for aortic root replacement is multifaceted. Herein, we report the compared long-term outcome of two type of stentless biologic valve conduits namely homograft and Fresstyle bioprosthesis used to replace the aortic root and followed prospectively up to 15 years.

Methods:
Between 1993 and 2011, 188 patients underwent elective primary aortic root replacement with a stentless bioprosthetic aortic valve with (n=38) or without (n=150) CABG. Among these patients, 98 Freestyle and 90 homografts were implanted. All clinical and echocardioraphic data were collected prospectively. Mean overall follow-up was 8.5±3.9 years (range: 0.1-15). It was 8.4±3.8 years for Freestyle, and 8.5±4.0 years for homografts, and complete in all patients.

Results:
Patient characteristics were comparable between groups except for age and number of pre-operative diagnosis of endocarditis (
p
<0.0001) and moderate/severe aortic insufficiency (
p
<0.008). The mean age was significantly higher in the Freesstyle (65.4±8.5years) compared to homograft (48.1±13.0 years) group (
p
< 0.0001). Hospital mortality was comparable between the Freestyle and the homograft group (5.1% versus 7.8%,
p
=0.6). Ten and 15-years survival was 66.7% and 53.0% in the Freestyle versus 89.9% and 69.1% in the homograft group, respectively (
p
<0.001). Freedom from reoperation due to structural valve deterioration (SVD) at 10 and 15 years was 98.8% and.92.7% for the Freestyle compared to 87.4% and 68.6% in the homografts group, respectively (
p
=0.009). Independent risk factors for reoperation for SVD were age (OR:1.1, CI: 1.02-1.1,
p
=0.002), and use of homograft (OR:7.7, CI: 1.7-35.5,
p
=0.008). Independent risk factors for poorer long-term survival were age (OR 1.2, CI: 1.1-1.3,
p
=0.001), and lenght of hospital stay (OR 2.9, CI: 1.5-3.8,
p
=0.0003). Mean pressure gradient at the end of follow-up was 8.5±6.2 mm Hg for the Freestyle and 9.9±9.1 mm Hg for the homograft patients.

Conclusion:
The choice of stentless biologic valve for aortic root reconstruction have no influence on early and long-term survival. The use of biologic root reconstruction with Freestyle bioprostheses provides a better freedom from reoperation due to SVD compared to homografts.
Abstract 17054: N-Type Ca2+ Channel Blocker is Effective to Prevent Sudden Cardiac Death in Mice with Heart Failure
Authors: Yamada Yuko , Kuwahara Koichiro , Kinoshita Hideyuki , Kuwabara Yoshihiro , Nakagawa Yasuaki , Shibata Junko , Yamada Chinatsu , Minami Takeya , Yasuno Shinji , Usami Satoshi , Nakao Kazuyasu , Nishikimi Toshio , Ueshima Kenji , Mori Yasuo , Nakao Kazuwa
Published: April 2024

Background
- Increased sympathetic nerve activity is involved in the increased arrhythmogenicity seen in patients with chronic heart failure. N-type Ca
2+
channel (NCC) modulates sympathetic nerve activity by regulating calcium entry at sympathetic nerve terminal, which triggers the release of the neurotransmitter noradrenalin. The ability of NCC blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however.

Methods and Results
- We compared effects of cilnidipine (Cil), dual N-and L-type Ca
2+
channel blocker, with those of nitrendipine (Nit), a selective L-type Ca
2+
channel blocker, in a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor transgenic mice (dnNRSF-Tg), a mouse model of dilated cardiomyopathy leading to sudden arrhythmic death. Hemodynamic and echocardiographic analyses showed no significant difference among the control, Cil, and Nit groups. In contrast, Cil dramatically improved the survival rate (p<0.001) and reduced ventricular arrhythmia (p<0.05) among dnNRSF-Tg mice, compared with control vehicle or Nit. Cil improved the imbalance in autonomic nerve activity assessed by heart rate valiability, and also reduced the increased urinary excretion of noradrenalin seen in dnNRSF-Tg, whereas Nit did not. In addition to the pharmacological blockade, we also assessed the effect of genetic titration of NCC by crossing dnNRSF-Tg mice with the mice lacking CACNA1B encoding α1B subunit of NCC. In dnNRSF-Tg;CACNA1B
+/-
mice, survival rate was significantly improved compared with that in dnNRSF-Tg;CACNA1B
+/+
mice (p=0.001).

Conclusions
- NCC blockade ameliorated disturbed autonomic nerve function and improved survival in a mouse model of dilated cardiomyopathy and sudden death. Our findings suggest NCC blockade is a potentially useful approach to preventing sudden cardiac death in patients with heart failure.
Abstract 171: Cardiac Arrest Outcomes Data Evaluation---CODE Registry: Brazilian Registry of In-Hospital Cardiopulmonary Resuscitation
Authors: Guimarães Helio P , Avezum Álvaro , Carballo Mariana T , Laranjeira Ligia N , Mendes José R , Reis Helder J , Manetta José A , Gazoni Fernanda , Berwanger Otavio , Cavalcanti Alexandre B , Lopes Renato D ,   CODE Investigators
Published: April 2024

INTRODUCTION:
In spite of the advances and worldwide standardization for cardiopulmonary resuscitation (CPR), knowledge on the effectiveness of in-hospital CPR is not yet sufficient in Brazil.

Methods:
This cross-sectional study included, prospectively, 763 patients who presented in-hospital cardiac arrest (CA) from 2007 to 2010, in 17 hospitals. CPR was performed in 575 patients.

RESULTS:
Asystole was the CA modality most frequently found (40.7%), followed by pulseless electrical activity (39,3%). Immediate survival (recovery of spontaneous circulation - ROSC up to 24 h) was 48,8%, survival until hospital discharge was 13%, 4.3% in 6 m and 3.8% in 12 months. Independent predictors associated with higher immediate survival were: ventricular fibrillation (VF) or ventricular tachycardia (VT) without pulse as the initial rhythm of CA (RR 1.31; IC 95% 1.10 to 1.55; p = 0.002); presence of victim consciousness signs when the emergency staff arrived (RR 1.37; IC95% 1.16 to 1.61; p < 0.001); use of epinephrine (RR 1.61; IC 95% 1.32 to 1.98; p < 0.001); hypoglycemia as cause of CA (RR 1.68; IC 95% 1.11 to 2.55; p = 0.014). Independent predictors associated with lower immediate survival were: hypotension as cause of CA (RR 0.74; IC 95% 0.61 to 0.90; p = 0.003); sedentary lifestyle (RR 0.76; IC 95% 0.66 to 0.88; p < 0.001) and duration of the CPR. Independent predictors associated with hospital discharge survival were: the emergency team trained in ACLS and/or BLS (HR 3.07; IC 95% 1.39 to 6.78; p = 0.006), sinus rhythm after ROSC (HR 1.44; IC 95% 1.26 to 1.75; p = 0.002). Independent predictors of higher 6-month survival rate were: use of epinephrine, sinus rhythm after ROSC and previous MI. Independent predictors of 12-month survival were not identified.

CONCLUSION:
As independent predictors for immediate survival we identified: VF or VT without pulse as the initial rhythm, presence of signs of awareness of the victim, use of epinephrine, hypoglycemia as cause of PCR. As independent predictors associated survival until discharged: training in ACLS/BLS and the sinus rhythm after ROSC. These findings suggest a national resuscitation profile, providing relevant information, potentially representative of the in-hospital CPR in Brazil.
Abstract 17113: Dietary Supplementation of Hyodeoxycholic Acid and D-Limonene Decreased Atherosclerotic Lesion Formation in LDLR Knockout Mouse
Authors: Shih Diana M , Shaposhnik Zory , Rosales Melenie , Wang Xuping , Meng Yonghong , Wu Judy , Ratiner Boris , Zadini Filiberto , Zadini Georgio , Lusis Aldons J
Published: April 2024

In this study, we examined the effects of dietary supplementation of two natural emulsifiers, hyodeoxycholic acid (HDCA) and D-limonene (D-Lim), on atherosclerotic lesion formation in LDLRKO mouse. Female LDLRKO mice were maintained on a western diet for 8 weeks, then divided into 3 groups that received the following diets for 15 weeks before euthanization, chow diet, chow diet + 1.25% HDCA, or chow diet + 5% D-Lim. We found that 1.25% HDCA was able to significantly suppress the development of plaque area throughout the aorta (beyond the root of the aorta) by 47% (p<0.01) over 15 weeks of treatment. 5% D-lim treated mice showed a 25% (p<0.05) reduction in plaque formation. Atherosclerotic lesion size at the innominate artery was decreased by 94% (p<0.0001) and 53% (p<0.05) in the HDCA and D-Lim groups, respectively, as compared to the chow diet group. Plasma VLDL/IDL/LDL cholesterol levels were significantly decreased by 61% (p<0.0001) and 23% (p=0.01) in the HDCA and D-Lim groups, respectively, as compared to the chow diet group. We found that HDCA supplementation decreased cholesterol absorption from gut by 76% (p<0.0001), whereas D-Lim had no effect on cholesterol absorption. Interestingly, hepatic mRNA level of Cyp7a1, a key enzyme in bile acid synthesis, was significantly increased by more than 100% (p<0.05) in D-Lim group, suggesting D-Lim may act as a bile sequestrant in the gut. In addition, HDL isolated from the HDCA and D-Lim groups exhibited significantly increased ability (49% and 45% increase, respectively) to mediate cholesterol efflux from cholesterol loaded RAW 264.7 cells as compared to those of the chow diet group. In summary, our data demonstrated that HDCA supplementation decreased plasma VLDL/IDL/LDL cholesterol levels mainly through its ability to block intestinal cholesterol absorption. D-Lim decreased plasma VLDL/IDL/LDL cholesterol levels probably through decreased bile acid re-absorption in the intestine and increased conversion of cholesterol into bile acid in the liver. HDCA and D-Lim improve the cholesterol efflux ability of HDL as well. These anti-atherogenic effects resulted in significantly decreased atherosclerosis in LDLRKO mice receiving HDCA or D-Lim. HDCA and D-Lim may be new candidates for anti-atherosclerotic drugs.
Abstract 17137: Renal Dysfunction is a Potent Predictor of Stroke and Systemic Embolism Among Individuals with Atrial Fibrillation: Results from the ROCKET AF Trial
Authors: Piccini Jonathan P , Stevens Susanna R , Patel Manesh R , Mahaffey Kenneth W , Paolini John F , Nessel Christopher C , Becker Richard C , Halperin Jonathan L , Hacke Werner , Singer Daniel E , Hankey Graeme J , Breithardt Gunter , Fox Keith A , Califf Robert M
Published: April 2024

Background:
Stroke is a disabling and frequently lethal complication of atrial fibrillation (AF). Risk stratification is an essential first step in effective stroke prevention. We investigated what factors are associated with the occurrence of stroke and systemic embolism in a large, international AF trial.

Methods:
In ROCKET AF, 14,264 patients with nonvalvular AF and creatinine clearance (CrCl) ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. The primary endpoint was stroke or systemic embolism analyzed according to intention to treat. Cox proportional hazards modeling was used to identify the factors at randomization independently associated with the occurrence of stroke or systemic embolism.

Results:
At randomization, the median age was 73 yrs, median CHADS2 score was 3.0, median CHA
2
DS
2
VASc score was 5, and 52% had a history of prior stroke or TIA. Over a median follow-up of 1.94 years, 575 (4.0%) patients had a primary endpoint event. Among these patients, the median age was 74, median CHADS
2
score was 4, median CHA
2
DS
2
VASc score was 5, and 64% had prior stroke or TIA. Reduced CrCl was a strong independent predictor of stroke and systemic embolism, second only to prior stroke or TIA (Table). Additional factors associated with stroke and systemic embolism included increased diastolic BP and heart rate, and vascular disease of the heart and limbs; (C-index 0.635). This model demonstrated improved discrimination compared with the CHA
2
DS
2
VASc model (0.578), and the CHADS
2
model (0.575). The inclusion of eGFR <60 and prior stroke or TIA in a model without any other covariates led to a C-index of 0.591.

Conclusions:
In a population of patients with non-valvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic emboli. Risk stratification for stroke prevention in AF should incorporate renal function into risk estimates and potentially, subsequent therapeutic decisions.
Abstract 17146: Human Cardiosphere-Derived Cells From Advanced Heart Failure Patients Exhibit Augmented Functional Potency in a Mouse Model of Myocardial Infarction
Authors: Cheng Ke , Malliaras Konstantinos , Smith Rachel R , Blusztajn Agnieszka , De Robertis Mick , Sun Baiming , Marbán Linda , Czer Lawrence , Trento Alfredo , Marbán Eduardo
Published: April 2024

Background:
Preclinical studies and an on-going clinical study (CADUCEUS) support the notion that cardiosphere-derived cells (CDCs) from normal and recently-infarcted hearts are capable of reducing scar size and boosting cardiac function. It is unknown whether CDCs from advanced heart failure patients retain the same functional benefit.

Methods and Results:
In a mouse model of acute MI, we compared the regenerative potential of CDCs derived from 3 groups (N=6 patients in each group): 1) Normal: healthy donor hearts post-transplantation; 2) Recent MI: patients who had an MI 17-27 days before biopsy; 3) HF: hearts with dilated cardiomyopathy explanted at cardiac transplantation. A control (PBS) injection group was included. MI was induced in SCID mice by LAD ligation and 10
5
CDCs were injected intramyocardially in the MI border zone. Echocardiographic images were analyzed independently in a blinded manner. The LVEFs two hours post-MI were comparable, indicating similar initial injury among groups. Over the 3 week time course, LVEF deteriorated in the Control group while all CDC-treated groups exhibited preservation of cardiac function. 3 weeks after treatment, the highest LVEF was seen in the mice that had received HF CDCs (HF: 37.1±10.1%; Recent MI: 27.6±9.8%; Normal: 27.0±9.2%; N=6 [patients]; n=19-24[mice]; p<0.05 via One-way ANOVA with LSD post test). Flow cytometry revealed a somewhat larger fraction of c-kit+ cells in the HF CDCs (HF: 6.3±2.7%; Recent MI: 3.6±1.4%; Normal: 3.9±3.4%). Secretion of VEGF, HGF, IGF, and SDF-1 from cultured CDCs was measured by ELISA. Gene expressions of GATA-4, MEF2C, ZFRM1, FDR, HDAC2, ITA2a and LAMB1 were assessed by RT-PCR. Tube formation assay was performed as an indicator of angiogenesis. None of these
in vitro
CDC parameters differed significantly among groups nor did any strongly correlate with cardiac function
in vivo
. Interestingly, we detected a moderate positive correlation between patient age and cardiac function (R=0.4, p=0.07).

Conclusions:
Our data contradict the routine assumption that stem cells from younger donors without heart failure are superior for therapeutics. Indeed, CDCs from advanced heart failure patients exhibit augmented functional potency in a mouse model of myocardial infarction.
Abstract 17200: Cystatin C Adds Prognostic Value Over Conventional Predictors of Cardiovascular Disease Outcomes: Results from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Trial
Authors: West Malcolm , Sullivan David R , Patterson Jillian , Keech Anthony C , Nestel Paul , Glasziou Paul P , Kirby Adrienne , Zeller Tanja , Colquhoun David , Blankenberg Stefan , Simes John , Tonkin Andrew ,   LIPID study investigators
Published: April 2024

Background
Blood levels of the polypeptide, cystatin C, have been reported to be associated with increased cardiovascular mortality. However, cystatin C levels reflect renal dysfunction, and whether there is an association with cardiovascular outcomes independent of serum creatinine or eGFR is uncertain. This was examined in the LIPID study, a double-blind, randomised, placebo-controlled trial of pravastatin in patients with prior CHD. Of 9014 patients, 7863 had a baseline blood sample of sufficient volume for measurement of biomarker levels.

Methods and Results
Cystatin C levels were typically higher with higher levels of other risk factors. There was no difference in the median cystatin C level between pravastatin (median (IQR) 0.8 (0.7-0.9)) and placebo (0.8 (0.7-0.9)) groups (
P
=0.38) at baseline. The risk of different CVD events was considered in multivariate time-to-event models adjusting for pravastatin treatment,
conventional
risk factors and other novel biomarkers. Baseline cystatin C was an independent predictor of a range of CVD events. The risk of a CHD event was 66% higher in the highest than the lowest quartile of cystatin C (Q4: >0.93 mg/dL) than the lowest (Q1: ≤0.72) (HR 1.66, 95% CI 1.37-2.00). The risk of a nonhemorrhagic stroke was 85% higher in Q4. The relative effects of pravastatin were similar across all quartiles of cystatin C with higher absolute reduction in Q4. While eGFR was a significant predictor (all
P
<0.008) of all outcomes except for stroke (
P
=0.08) in a model with conventional risk factors, it was not a significant risk factor for any outcome when cystatin C was included in the model.

Conclusion
Cystatin C is an important predictor of future cardiovascular outcomes in patients with previous CHD events independent of eGFR.
Abstract 17252: Texas Adolescent Athlete Heart Screening Registry (TAAHSR): a Statewide Screening Study
Authors: Lawrence Silvana M , Fenrich Arnold , Kohl Harold W , Austin Patrick W , Hutchings Jennifer Y , Garcia Michelle , Guerrero Michael , Rodgers George
Published: April 2024

Background:
Sudden cardiac death (SCD) in athletes, though a rare event, continues to claim lives every year. Optimal athlete screening strategies have proved to be elusive.

Hypothesis:
Statewide screening of high school student athletes (SA) for hypertrophic cardiomyopathy (HCM) and other conditions associated with SCD is feasible and establishing a registry may lead to reduction in SCD and improved quality of life. Objective: Identify high school SA at risk for SCD due to presence of HCM and/or other conditions associated with SCD through screening events in the state of Texas, and establish a statewide data bank (registry).

Methods:
The target population in this observational screening study included high school age SA who voluntarily presented at screening venues in Texas from March 2010-April 2011. Demographic and cardiac history data, 12-lead ECG and limited two-dimensional echocardiogram (L-ECHO) were obtained on all SA. Studies were read either on site or remotely subsequent to data acquisition. Athletes with positive screenings (SCD-related or other abnormal findings) were referred for complete cardiology evaluation. Follow up data were compared to screening results.

Results:
Of 1002 SA screened, 840 agreed to participate in TAAHSR (71% male). Most SA were in grades 9 and 10 (63%), mostly White (55%) or Hispanic (34%). Fifty one percent reported positive at least once in the history. A total of 94 SA (11.2%) had positive screening on ECG (9.6%) and/or L-ECHO (2.1%) and referral was made. Of the 94 SA referred, follow up data were obtained in 91 (98%): Data were still pending at the time in 44 (48%) and complete in 47 (52%). Of the 94, 22 were referred for SCD-related findings: 19 ECG (15 HCM, 3 WPW and 1 Brugada) and 3 L-ECHO (1 HCM, 2 aortic root dilation). Of the 47 SA, screening findings were confirmed in 12 (25%), 3 with WPW (2 underwent ablation) and 1 with LVH considered ‘benign’ but not HCM.

Conclusion:
Establishing a registry with statewide screenings in SA for SCD-related conditions is feasible and longitudinal data to assess effectiveness is highly needed at the present time. To date, 3 SA (0.36%) were identified with SCD-related condition (WPW). Future work on cost-effectiveness analysis is imperative to determine value of widespread SA screening for SCD.
Abstract 17260: Percutaneous Recanalization of Totally Occluded Pulmonary Veins After Pulmonary Vein Isolation
Authors: Hill James , Qureshi Athar M , Latson Larry A , Prieto Lourdes
Published: April 2024

Background:
Pulmonary vein total occlusion (PVO) is an uncommon complication of pulmonary vein isolation (PVI). We have previously published our early experience with diagnosis and treatment of PVO, and now describe mid-term follow-up of attempted recanalization.

Methods:
Patients with angiographic PVO were identified from our catheterization database. Medical records and catheterization reports were reviewed for: symptoms, flow to affected lung quadrant, time from PVI to diagnosis of PVO, anatomic characteristics of occluded veins, and procedural details. Patients with severely hypoplastic veins had staged intervention with initial balloon angioplasty followed by stenting 2-4 months later to allow for vessel growth. Symptoms, quadrant flow, and status of the vein at last follow-up were ascertained.

Results:
Between 6/2005 and 6/2011, 14 patients with PVO underwent attempted recanalization. Median age was 56.9 (0.2-67.3) years, weight 88 (5.0-111.4) kg. Symptoms included dyspnea in 11, cough in 4, hemoptysis in 5 with a mean NYHA class of 2.1 ± 0.8. Flow to affected lung quadrant was severely diminished at 5.9 ± 3.7%. Median time from PVI to recanalization attempt was 16.5 (2.0-62.7) months. Reference vessel diameter was 5.3 ± 2.0 mm and length of occluded segment 8.3 ± 6.0 mm. Recanalization results are summarized in Table 1. At median follow-up of 13.3 (0-41.3) months, 10 veins remain patent with minimal diameter of 6.1 ± 2.7 mm, reference diameter of 7.8 ± 3.1 mm, and flow to affected lung quadrant 12.3 ± 7.2%, all significantly greater than pre-intervention (p<0.03). Of 10 patients completing staged intervention, 5 have no symptoms and mean NYHA class decreased to 1.5 ± 0.7.

Conclusions:
PVO recanalization can be accomplished with reasonable acute and mid-term vessel patency and significant improvement in symptoms and flow to affected lung quadrant. However, recurrent stenosis is common and repeated interventions are often necessary to maintain vessel patency.
Abstract 17290: What Factors are Associated with the Change in Endothelial Function in Patients Who Have Undergone Percutaneous Coronary Intervention?
Authors: Teragawa Hiroki , Fujii Yuichi , Takemoto Hiroaki , Nomura Shuichi , Nishioka Kenji , Higashi Yukihito , Kihara Yasuki
Published: April 2024

Background:
Endothelial function is one of markers predicting future cardiovascular events, even in patients with coronary artery disease (CAD). Thus, much interest is focused on the change in endothelial function in CAD patients who have undergone percutaneous coronary intervention (PCI). However, factors associated with the change in endothelial function in these patients remain unclear. Therefore, we investigated changes in the endothelial function of the brachial artery in patients who underwent PCI and clarified the factors affecting these changes.

Methods:
A total of 233 CAD patients (mean age: 66 years; 185 males) who underwent successful PCI for stenotic lesions were enrolled. PCI techniques included plain old balloon angioplasty in 47 patients, stenting with a bare-metal stent in 85 patients and stenting with a drug-eluting stent (DES) in 101 patients. In each patient, the diameter of the brachial artery in response to hyperemic flow (flow-mediated dilatation: FMD) and nitroglycerin spray (nitroglycerin-induced dilation: NID) was measured using high resolution ultrasonography just before and 6-8 months after PCI. The changes in FMD and NID were defined as the differences between follow-up and baseline values. Angiographic restenosis was defined as a >50% diameter reduction at the follow-up coronary angiography. The lesion morphology before PCI was determined according to the American College of Cardiology/American Heart Association classification.

Results:
In univariate analyses, body mass index (BMI, p = 0.0002), difference in NID (p = 0.0008), use of DES (p = 0.005), lesion morphology (p = 0.0314) were associated with the change in FMD. Multivariate regression analysis demonstrated that use of DES (p<0.0005) was negatively associated whereas BMI (p<0.0001) was positively associated, with the change in FMD.

Conclusions:
These results suggest that use of DES has a negative impact on the change in endothelial function; however, obesity has a positive impact on the change in endothelial function in CAD patients who underwent PCI. The former may suggest the need for a careful follow-up of patients who underwent PCI with DES and the latter finding may suggest one mechanism of obesity paradox phenomenon in CAD patients who underwent PCI.
Abstract 17304: Dense Genotyping of Candidate Gene Loci Identifies Variants Associated with Soluble E-Selectin Levels
Authors: Karakas Mahir , Baumert Jens , Thorand Barbara , Rottbauer Wolfgang , Meisinger Christa , Illig Thomas , Koenig Wolfgang
Published: April 2024

Background:
Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in a population-based sample.

Methods:
We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes (50K IBC Chip) selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. 1,508 men and women from a randomly drawn subsample of the baseline examination of the MONICA/KORA Augsburg Cohort Study, conducted between 1984 and 1995, with measurements of sE-selectin and genotyping by the 50K IBC Chip comprised the study population. Linear regression analysis with adjustment for age, sex and survey was applied to assess associations between gene variants and sE-selectin levels. The significance level was defined as 5.0e-6 accounting for multiple testing.

Results:
Twelve SNPs, all from the ABO blood group candidate gene (ABO) were significantly associated with levels of E-selectin. The strongest association was observed for
rs651007
with a change of E-selectin level per one copy of the minor allele of -18.59 ng/ml (p=5.79*10-56). All twelve SNPs had minor allele frequencies above 20% showing a substantial gene variation.

Conclusions:
Our findings indicate that the genetic variants at the ABO locus affect sE-selectin levels. These findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.
Abstract 17313: Bedside Ultrasound for Serial Assessment of Central Venous Pressure in Patients with Volume Overload
Authors: Leeman Jonathan E , Simon Marc A , Singh Madhurmeet , Johnston James R , Pacella John J
Published: April 2024

Background:
Using bedside ultrasound, we have previously shown that a greater than 17% increase in internal jugular vein (IJ) cross sectional area (CSA) during Valsalva rules out elevated right atrial pressure (RAP > 12mmHg, NPV 94%). This occurs because venous compliance increases nonlinearly with increasing pressure. Here, we sought to validate this US test in the first longitudinal study of patients undergoing acute volume removal during hemodialysis (HD) as well as patients undergoing diuresis for acute decompensated heart failure (ADHF).

Methods:
Images of the right IJ were captured using portable bedside US before and during the strain phase of a standardized Valsalva maneuver (Fig 1) on hospitalized patients who were either admitted for ADHF or undergoing HD. For HD patients (n=11), percent change in IJ CSA with Valsalva (ΔCSA) was assessed both before and after HD treatment. For ADHF patients (n=37), ΔCSA was measured both at admission and discharge.

Results:
For HD patients, analysis of US images detected elevated filling pressures (ΔCSA <17%) in 11 of the patients studied. In these subjects, a mean fluid volume of 1.8L was removed and 10 subjects demonstrated an increased ΔCSA after HD (ΔCSA increase of 45 ± 40%, p17% indicating restoration of normal filling pressures. Of the 37 ADHF patients studied with elevated filling pressures at admission (ΔCSA <17%), 27 demonstrated euvolemia after diuresis (ΔCSA increase of 57 ± 157%, p<0.01) and an average length of stay of 7.8 days.

Conclusion:
US of the IJ can be used to examine intravascular volume status in response to fluid changes that occur over the course of hours (HD) or days (ADHF). This simple bedside technique could be utilized for monitoring volume changes, both acutely and longer term, to guide volume management and overcome some of the difficulties associated with traditional visual assessment of jugular venous pulsations.