bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18572: Do Obese Children Consume More Energy at Mealtime Compared to Lean Children?
Authors: Ippisch Holly M , Summer Suzanne S , Kimball Thomas R
Published: April 2024

Overweight in childhood is known to lead to cardiac structural, functional, and vascular abnormalities making childhood obesity a major public health concern. It is often assumed that overeating at mealtime contributes to the excess weight gain, but there is limited data in pediatric populations.

HYPOTHESIS:
We assessed the hypothesis that obese children would consume greater kilocalories than their lean counterparts when exposed to identical food choices during a single meal, under semi-controlled conditions.

METHODS:
Children were provided a standardized low fat meal and allowed to eat ad lib. The meal provided significantly higher calories than what most children could comfortably eat, in order to discourage seeking additional unapproved food. The meal preparation was supervised by a dietitian and sent home with the family. The family returned the leftover food so that calorie consumption could be calculated.

RESULTS:
40 young people (23 obese, 17 lean) ages 8-19 years old (average 13.5 +/- 3.6 yrs) were recruited. The average calories consumed by the obese children were significantly lower than the amount consumed by the lean children when provided similar meals (p <0.01) (Figure). The obese children also consumed significantly less protein, carbohydrates, and fat (p < 0.05). The study was repeated on a subsequent day with similar results.

CONCLUSIONS:
When provided with a low fat meal, obese children repeatedly consumed fewer calories compared to lean children. These findings may be due to a variety of factors, such as taste and research participation, but may have important implications for calorie consumption and intervention in obese children.
Abstract 18593: Impact of National Screening Intervention on AHA's ‰Life's Simple Seven Cardiovascular Metrics
Authors: Johnson Caitlin , Rodriguez Fatima , Wang Yun , Foody JoAnne
Published: April 2024

Background:
Recent AHA recommendations promote 7 CV health metrics: not smoking; being physically active; having normal blood pressure, blood glucose and total cholesterol levels, and weight; and eating a healthy diet to reduce CV morbidity and mortality. As few studies have explored interventions to promote these "Simple 7", we examined the impact of a national screening program on CV health metrics in women.

Methods:
In 2009, Sister to Sister provided free CV screenings in 12 cities nationwide to 9,443 women, all of which were offered enrollment into a 6-month follow-up survey study. Using data collected from baseline and 6-month surveys on CVD risk, we measured changes in “Simple 7” health metrics (excluding diet) following screening intervention.

Results:
A total of 1,869 women enrolled into the study, 400 of which completed baseline and 6-month surveys. Among those completing both surveys, we observed significant overall improvement in risk scores between screening intervention and 6-month follow-up (3.8 vs. 4.2, p<0.001). We observed improvements 4 of the 6 health metrics measured (Table 1), although only blood pressure improvements were statistically significant.

Conclusion:
Screening intervention was effective in improving overall health of women at 6-months, based on optimal CV health metrics. Screenings were particularly effective in improving blood pressure control. Although larger studies are needed to further assess the impact of CV screenings on health metrics, our study suggests that screenings may serve as an effective model to promote CV health metrics, especially among women.
Abstract 18596: Conjugated Linoleic Acid Targets β2 Integrin Expression to Suppress Monocyte Adhesion
Authors: de Gaetano Monica , Dempsey Eugene , Marcone Simone , Fitzgerald Desmond J , Belton Orina
Published: April 2024

Recruitment of monocytes to the damaged endothelium characterizes the early stages of atherosclerosis. Conjugated linoleic acids (CLA) are a group of naturally occurring fatty acids which inhibit the progression and induce regression of pre-established atherosclerosis. We have previously shown that CLA inhibits human peripheral blood monocyte (HPBMC) migration. Here we demonstrate that CLA suppresses adhesion of monocytes to endothelial cells, via inhibition of β2 integrins. We further show that CLA suppresses the CXCR4 signalling pathway thus inhibiting crawling of monocytes towards CXCL12 chemokine. HPBMCs were treated with 10uM of CLA isomers (c9,t11-CLA and t10,c12-CLA), a CLA blend (80:20, c9t,11:t10,c12), control lipids and 5uM of PPARγ agonist (troglitazone) prior to adhesion to HAECs. c9,t11-CLA and CLA blend treatment inhibited monocyte adhesion to HAECs (63±3%, p<0.01 and 68±3%, p<0.01, respectively). Furthermore, c9,t11-CLA and CLA blend inhibited CD18, the β chain of β2 integrin, mRNA (48±14%, p<0.05 and 35±3%, p<0.001) and protein expression (44±13%, p<0.05, and 35±3%, p<0.001) via a PPARγ[[Unable to Display Character: ]]dependent mechanism. Flow cytometry analysis showed that c9,t11-CLA and CLA blend decreased external surface expression of both β chain (10±4%, p<0.05 and 20±5%, p<0.01), and α subunits (CD11a, 13±6%, p<0.05 and 30±5%, p<0.01; CD11b, 8±3%, p<0.05 and 27±7%, p<0.01), suggesting that CLA’s effect on CD18 transcription results in dysfunctional αβ complex formation, altering expression of LFA-1 and Mac-1 integrins. Furthermore, c9,t11-CLA and CLA blend almost completely abolished (by 82% and 89%, p<0.001) adhesion of monocytes to ICAM-1. Immunocytochemistry of adherent cells further confirmed the inhibition of cell spreading. Importantly, CLA suppresses monocyte response to chemoattraction, preventing crawling of cells through a reduction, of CXCR4 expression (c9,t11-CLA, 47±10%, p<0.05; CLA blend, 33±5%, p<0.01). Our findings suggest that CLA inhibits monocyte recruitment by suppressing their sensitivity to chemokines and by inhibiting their ability to firmly attach to ICAM-1.
Abstract 18610: Mitochondrial Transfer Restores Endothelial Dependent Vasodilation
Authors: Ohanyan Vahagn A , Kolz Christopher L , Logan Suzanna , Yin Liya , Guarini Giacinta , Chen Yeong-Renn , Chen Chwen Lih , Pung Yuh Fen , Hardwick James P , Chilian William
Published: April 2024

Although endothelial dysfunction is a hallmark of vascular disease, the mechanisms underlying this impairment are unknown. Recently, impaired mitochondrial function was observed in vascular pathologies with endothelial dysfunction; yet a causal link between mitochondrial and endothelial function is not established. We sought to establish this link by demonstrating that restoration of mitochondrial function rescues endothelium-dependent dilation in a model of endothelial dysfunction (metabolic syndrome). Initially, we evaluated activities of mitochondrial complexes I-IV in aortas), and endothelial-dependent dilation (isolated, perfused mesenteric small arteries [MA’s], 289±32 µm, id) in Zucker Obese Fatty (ZOF) and Zucker Lean (LN) rats. Activity of complex I, II, III, or IV (per mg/mitochondrial protein) was lower (56%, 65%, 72% or 59% reduction, respectively) in ZOF than LN (P<0.05). Dilation to the endothelium-independent agonist, nitroprusside (NP) was equivalent in LN and ZOF rats suggesting normal smooth muscle function. Dilation to vasoactive intestinal peptide (VIP, endothelium-dependent agonist) in LN was completely blocked by L-NAME (10
-4
M) (Figure 1). Dilation to VIP was markedly compromised in ZOF (Figure 1). To acutely restore mitochondrial function, mitochondria from livers of lean rats were isolated, labeled with Mitotracker, administered into the perfusion circuit, and “transferred” into the endothelium of MA’s of ZOF via electroporation (confirmed by Mitotracker fluorescence). Thirty minutes after electroporation, dilation of mitochondria-treated vessels (ZOF+Mito) was restored to near normal levels (Figure 1, ZOF+Mito vs LN) and significantly greater than untreated ZOF. Dilation to NP was unaffected by transfer (not shown). These results suggest that mitochondria play a key role in endothelial function, and that treatment regimens for vascular disease should consider mitochondrial directed therapies.
Abstract 18630: Cost-effectiveness of Revascularization Strategies: A Preliminary Study from ASCERT
Authors: Zhang Zugui , Edwards Fred , Kolm Paul , Grau-Sepulveda Maria , O'Brien Sean , Shahian David , Ponirakis Angelo , Klein Lloyd W , Grover Frederick L , Garratt Kirk , Mckay Charles , Weintraub William S
Published: April 2024

Background:
Using data from the Society of Thoracic Surgeons (STS) Database and the American College of Cardiology Foundation (ACCF) National Cardiovascular Data Registry (NCDR) in ASCERT, we examined the cost-effectiveness of coronary-artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI).

Methods:
The STS Database and ACCF NCDR were linked to the Centers for Medicare and Medicaid Services (CMS) claims data from years 2004 to 2008. Costs were assessed at index, 1 year and 4 years by Diagnosis Related Group for hospitalizations. Effectiveness was measured via mortality rate and converted to life year gained (LYG) from Framingham survival data. Costs and effectiveness were adjusted using propensity scores and inverse probability weighting to reduce treatment selection bias. The incremental cost-effectiveness ratio (ICER) was expressed as cost per LYG.

Results:
Among patients (86,244 in CABG group and 103,549 in PCI group) at least 65 years old with two or three vessel coronary artery disease, costs were higher for CABG by $10,951 (95% CI: $10,899 to $11,003) during the index hospitalization and by $9,906 (95% CI: $9,824 to $9,988) at 1 year, compared to PCI. At 4 years, average total costs were $32,428 for CABG versus $24,623 for PCI, a difference of $7,825 (95% CI: $7,693 to $7,927). For life time, average total costs were $88,125 for CABG versus $82,020 for PCI, a difference of $6,105 (95% CI: $5,990 to $6,327); patients undergoing CABG gained an average of 0.1268 life-years relative to PCI; the ICER of CABG, compared to PCI, was $48,135 per LYG, with 15.3%, 40.5%, 78.2%, and 85.7% of bootstrap-derived estimates <$25,000/LYG , <$50,000/LYG , <$75,000/LYG , and <$100,000/LYG, respectively.

Conclusions:
In the period of less than 1 year, CABG was more costly and less effective than PCI. However, in the long run, CABG offers lower mortality at higher cost than PCI. Using a common threshold, CABG will often be a cost-effective strategy.
Abstract 18654: Impaired Coronary Microvascular Function is Independently Associated with Fatal Cardiac Events at Long-term Follow-Up in Patients with Stable Coronary Artery Disease
Authors: van de Hoef Tim P , Bax Matthijs , Damman Peter , Delewi Ronak , Hassell Mariëlla E , Chamuleau Steven A , Voskuil Michiel , Tijssen Jan G , Piek Jan J , Meuwissen Martijn
Published: April 2024

Background:
Coronary microvascular dysfunction is increasingly recognized as an elementary component in the spectrum of coronary artery disease. Coronary flow velocity reserve (CFVR) is importantly determined by microvascular function, and may be considered a direct measure of microvascular function when measured in a reference coronary artery. We sought to determine the prognostic value of microvascular function, as assessed by measuring reference vessel CFVR (refCFVR), for long-term cardiac mortality.

Methods:
We studied consecutive patients with stable coronary artery disease in whom refCFVR was measured between April 1997 and September 2006 as part of ongoing study protocols. Patients underwent PCI of all ischemia causing lesions, as assessed by myocardial perfusion scintigraphy. Long term follow up was performed to document the occurrence of cardiac death.

Results:
RefCFVR was determined in 178 patients. During a median follow up of 11.6 years, 38 patients (15%) died of a cardiac cause. Kaplan Meier estimates of long term cardiac mortality showed a difference in mortality for high (≥3.0) and low (<3.0) refCFVR values (Figure). RefCFVR was additionally shown to be independently associated with cardiac mortality at long term follow up after multivariable adjustment (HR 0.432; 95% CI 0.213 - 0.876. P=0.02). Abnormal refCFVR was found to result from significantly lower baseline microvascular resistance, and a consequent increase in baseline flow velocity in patients with an abnormal refCFVR (6.96±2.54 mmHg/cm/s when refCFVR ≥3.0, versus 5.46±1.82 mmHg/cm/s when refCFVR <3.0; P<0.001). In contrast, hyperemic resistances, as well as flow velocities, were comparable between groups (P=NS for both).

Conclusion:
Impaired coronary microvascular is independently associated with long-term cardiac mortality in patients with stable coronary artery disease.
Abstract 18677: The ACEF Risk Score Exhibits Superior Predictive Ability for Adverse Clinical Outcomes in Women Undergoing PCI
Authors: Kovacic Jason C , Limaye Atul M , Gukathasan Nilusha , Sartori Samantha , Trost Biana , Narechania Birju , Thapi Roja , Kim Michael C , Moreno Pedro , Baber Usman , Dangas George , Mehran Roxana , Sharma Samin K , Kini Annapoorna
Published: April 2024

Objectives:
Women are known to experience worse clinical outcomes than men following percutaneous coronary intervention (PCI). Rather than a gender-specific effect, this is believed to be due to a greater burden of baseline cardiovascular risk factors. We therefore sought to identify which of the commonly used risk scores identify female patients at particular risk for adverse clinical events following PCI.

Methods:
Patients with triple vessel and/or LM disease with 12 month follow-up were studied from our single center PCI registry (n=584; mean age 69.8±12.3). Exclusion criteria included STEMI presentation, prior revascularization, and shock. Clinical events at 12 months were compared to baseline risk scores, based on area under the receiver operating characteristic curves (AUC; all comparisons females vs. males, respectively). The following scores were evaluated and compared: SYNTAX risk score (SRS), ACEF, modified ACEF (ACEFmod), NCDR, Clinical SYNTAX score (CSS), and NY State Risk Score (NYSRS).

Results:
Women (n=179, 30.7%), were older (75.8±10.6 vs. 67.2±12.2; p≤0.0001) and more often presented with CCS class III/IV angina. The SRS was the only risk score for which women and men had similar scoresvalues; for all other scores women had significantly higher scores values than men. For mortality, the ACEF score was the only score to show significantly better predictive ability in females (AUC 0.85 vs. 0.70; p<0.05) (Figure). For myocardial infarction, both the ACEF (0.79 vs. 0.49; p<0.005) and NYSRS (0.75 vs. 0.48; p<0.05) showed superior predictive ability in females. No score demonstrated gender specificity for TLR. For overall MACE (mortality+MI+TLR), the ACEF score was the only score with greater predictive ability in females versus males (0.69 vs. 0.56; p<0.05) (Figure).

Conclusions:
The ACEF score is simple to calculate (using only Age, Creatinine and Ejection Fraction) and offers superior clinical outcome prediction in females undergoing PCI.
Abstract 18681: Molecular Imaging of Angiogenesis in Atherosclerosis Using a Caspase 3 Targeted PET Tracer
18
F-CP18
Authors: Tamarappoo Balaji K , Su Helen , Gorodny Natalia , Arteaga Janna , Gomez Luis Felipe , Gangadarmath Umesh , Mu Fanrong , Walsh Joseph , Szardenings Katrin A , Kolb Hartmuth
Published: April 2024

Background:
Rupture of unstable coronary artery plaque results in luminal thrombosis and myocardial infarction. Smooth muscle migration, neovascularization and apoptosis are believed to constitute key steps that precede plaque rupture. Identification of plaque with enhanced apoptosis may therefore allow differentation of stable from high-risk plaque. We have developed [
18
F]CP18, a PET tracer that is cleaved by caspase 3, a terminal enzyme in the apoptosis cascade. We sought to test the ability of this tracer to detect plaque apoptosis in an ApoE double knockout mouse model of atherosclerosis.

Methods:
ApoE knockout mice (n=6) were fed a high fat western diet for 30 weeks at the end of which 250µCi of
18
F-CP18 was injected intravenously. Mice were sacrificed 60 min post-injection and the aorta was excised. Ex-vivo autoradiography was performed using either whole aorta or 10 µm-thick transverse sections of the aorta mounted on glass slides. Apoptotic activity and plaque inflammation in tissue sections from similar locations in the aorta were visually assessed using TUNEL staining and CD68 antibody staining respectively. Lipid deposition was visualized by oil red O staining with an H&E counterstain.

Results:
In the ApoE KO mice fed a high fat diet, atherosclerotic plaque visualized by Oil Red O was present in the aortic root and aortic arch. Qualitative analysis of ex-vivo autoradiography of the aorta showed preferential uptake of
18
F-CP18 by aortic plaque at these same locations. Tunel staining and CD68 staining co-localized with plaques that exhibited increased
18
F-CP18 uptake. In contrast, in ApoE mice fed a regular diet and in wild-type mice fed the high-fat diet, there were fewer plaques in the aorta, with minimal tracer uptake and negligible histochemical evidence of macrophage influx and apoptotic activity.

Conclusion:
We were able to label a caspase 3 substrate CP18 with
18
F by click chemistry. Preliminary studies demonstrate that uptake of this tracer in aortic plaque strongly correlates with high levels of apoptotic activity by TUNEL staining and macrophage entry detected by CD68 staining.
18
F-CP18 may be a valuable imaging agent to detect plaque apoptosis and may allow early detection of hig-risk plaque.
Abstract 18709: Association of Reactive Oxygen Metabolites and High-sensitivity CRP with severity of angiographic Coronary Artery Disease
Authors: Hirata Yoshihiro , Yamamoto Eiichiro , Kusaka Hiroaki , Sugiyama Seigo , Ogawa Hisao
Published: April 2024

Background:
Reactive oxygen species (ROS) and inflammation play the role in the pathogenesis and the development of coronary artery disease (CAD), and high-sensitivity C-reactive protein (hs-CRP), a marker for low-grade inflammation, is one of the most studied biomarkers for the evaluation of CAD risk. In contrast, there is little biomarker of ROS, which is easy to assay and is widely accepted as marker of CAD. Hence, in this study, we compared associations of hs-CRP and derivatives of reactive oxygen metabolites (d-ROM), a newly and easier-to-assay marker of ROS, with the severity of CAD.

Methods:
We examined the presence of CAD by coronary angiography (coronary stenosis ≥ 50% luminal diameter narrowing) and CAD patients were divided to single-vessel disease (SVD) or multiple-vessel disease (MVD) according to the number of vessels. In consecutive CAD patients, we assessed d-ROM by simpler method for detecting hydroperoxide as a marker of ROS, and compared association between hs-CRP and severity of CAD.

Results:
In preliminary study, d-ROM values were significantly increased in CAD patients compared to control patients. In consecutive 261 CAD patients, d-ROM values were significantly higher in CAD patients with MVD (n=172) than CAD patients with SVD (n=89) (d-ROM: CAD+SVD; 332.2 ± 70.9 U.CARR versus CAD+MVD; 353.2 ± 70.5 U.CARR, p<0.05). In receiver-operating characteristic analysis, d-ROM values was a significant determinant for the severity of CAD (area under the curve; 0.60, 95% confidence interval; 0.52-0.67, p<0.01). In contrast, hs-CRP of CAD patients with MVD were not changed compared to those of CAD patients with SVD (ln[hs-CRP]: CAD+SVD; -2.79 ± 1.12 mg/dL versus CAD+MVD; -2.65 ± 1.09 mg/dL, p=0.32). By multivariate backward logistic regression analysis among various risk factors, d-ROM values, but not hs-CRP independently associated with the severity of CAD (p<0.05).

Conclusion:
d-ROM values reflecting ROS levels significantly increased in CAD patients and significantly correlated with the severity of CAD. d-ROM assay might be a more important biomarker than hs-CRP to evaluate the severity of CAD and screen for CAD in high-risk patients. Identifying the high-risk CAD patients by d-ROM may provide clinical benefits for risk stratification.
Abstract 18727: Right Ventricular Pressure Overload is More Important than Volume Overload in Producing Contralateral Ventricular Dysfunction: A Congenital Heart Disease Model
Authors: Agrawal Arpit , Cedars Ari
Published: April 2024

Intro:
It is known that right ventricular (RV) contractile failure predisposes the left ventricle (LV) to failure. Animal models in an acute setting indicate this phenomenon is due predominantly to RV volume overload causing both changes in LV geometry and suboptimal LV filling. We investigated the relative importance of chronic RV pressure versus volume overload in producing LV dysfunction using d-transposition of the great vessels with an atrial switch (TGA, RV pressure overload) and repaired tetralogy of Fallot with severe pulmonary valve insufficiency (ToF, RV volume overload) as model systems.

Methods:
We performed a single center retrospective analysis of cardiac magnetic resonance imaging (MRI) data. All adult patients with TGA and ToF who had useful MRI data were screened. Included ToF patients had pulmonary insufficiency without residual pulmonary or infundibular stenosis. Included TGA patients had mild or less aortic or tricuspid regurgitation. We assessed MRI derived LV and RV volume measurements. Correlations were assessed using Pearson’s correlation coefficient. Differences between correlation coefficients were assessed using a Fischer r to z transformation.

Results:
32 TGA and 46 ToF patients met enrollment criteria with 35 and 72 MRIs respectively having data adequate for analysis. The groups were similar in terms of sex (58 versus 51% male) and age (29.6 +/- 6.0 versus 31.0 +/- 9.7) respectively. Patients with TGA demonstrated a strong correlation between RV and LV systolic function based on ejection fraction (EF) r=0.75. They also demonstrated a strong correlation between RV end-diastolic volume indexed to body surface area (EDVi) and LV EF (r=-0.56). Although there was a trend toward increased RV EDVi in patients with ToF (119ml/m2 versus 101ml/m2 for TGA p=0.11), ToF patients had a weaker correlation between RV and LV EF (r=0.46; p=0.02 compared to TGA) and a very weak correlation between RV EDVi and LV EF (r=-0.21).

Conclusions:
The present data indicate that in the chronic setting, RV pressure rather than volume overload is of greater importance in producing LV dysfunction, implicating shared muscle fibers, neurohumoral milieu, or relative unloading of the LV as playing a greater role in this process.
Abstract 18729: Serum Heat Shock Protein-70 is Associated With Decreased Frequency and Severity of Cellular Rejection in Cardiac Transplant Patients
Authors: Al Kassem Hatem , Eapen Danny J , Manocha Pankaj , Gupta Divya , Kay Jenna , Obideen Malik , Halista Michael M , Kabani Sarah S , Niaz Adil , Kumar Saket , Book Wendy , Sikora Sergey , Sperling Laurence , Quyyumi Arshed
Published: April 2024

Background:
Heat Shock Protein-70 (HSP70) is a highly conserved intracellular protein that is up-regulated in cells undergoing stressful stimuli. A recent study demonstrated an inverse relationship between HSP70 expression and cellular rejection grade in endomyocardial biopsies (EBx)from cardiac transplant patients. Peripheral blood based HSP70 levels have not been studied in such individuals. We hypothesized that serum HSP70 levels will be associated with severity of cellular rejection in cardiac transplant patients.

Methods:
177 cardiac transplant patients (56 ± 13 years; 8.5 ± 5 years mean time from transplant) were recruited from the Emory Cardiovascular Biobank from 2004-2012. Cellular rejection was defined based on revised International Society of Heart and Lung Transplant (ISHLT) grade of 1R or higher seen on EBx. Frequency of rejection was collected from time of transplant to enrollment date. Serum HSP70 was measured using ELISA and analyzed as detectable vs non-detectable. Nonparametric correlations and ANOVA were used to study univariate relationships while linear and ordinal logistic regression (adjusted for age, gender, race, length of time since transplant, and immunosuppressant medications) were performed to analyze the relationship between HSP70 levels and frequency and severity of cellular rejection respectively.

Results:
HSP70 was detectable in 35% of patients with grade 0R ISHLT class, 33% for grade 1R, 16% for Grade 2R, 0% for Grade 3R (p for group=0.005). There was an inverse correlation between HSP70 and frequency of rejection (r= -0.2, p= 0.03) with 34% of those with detectable HSP70 in the lowest quintile based on frequency of rejection whereas 9% was detected in the highest quintile (p=0.019). In adjusted regression models, HSP70 remained a significant independent predictor of a) ISHLT class with an OR of 0.43 (p=0.02) and b) frequency of rejection (β=-1.5, p=0.05).

Conclusion:
Detectable serum HSP70 is associated with decreased frequency and severity of cellular rejection in post cardiac transplant patients. The utility of HSP70 as a marker of graft function needs further study.
Abstract 18769: Is Conservative Treatment Justified in Marfan Syndrome Patients with Non-Complicated Acute Type B Aortic Dissection? Insights from the International Registry of Acute Aortic Dissection
Authors: Gilon Dan , Pyeritz Reed E , Evangelista Arturo , O'Gara Patrick , Harris Kevin M , Braverman Alan C , Peterson Mark D , Voehringer Matthias , Suzuki Toru , Conklin Lori D , Montgomery Daniel G , Isselbacher Eric M , Nienaber Christoph A , Eagle Kim A , Korach Amit
Published: April 2024

Introduction: Conservative treatment is the treatment of choice in patients (pts) with non- complicated acute type B aortic dissection (TBAAD). This strategy has not been validated in patients with Marfan Syndrome (MFS) presenting with non-complicated TBAAD.

Methods: Our study evaluated 586 medically managed patients with non-complicated TBAAD enrolled in IRAD between 1996 and 2011. The patients were divided into groups based on the presence (N=15, 2.6%) or absence (N=571, 97.4%) of MFS. Categorical variables were analyzed using chi-square test and Fischer’s exact test where applicable. Continuous variables were analyzed using student’s t-test for normally distributed data, and test of medians for non-normally distributed data.

Results: The mean age was significantly lower for MFS patients (41.3±9.4 years vs 65±13.5 years [p<0.001]). Significantly more patients without MFS had history of hypertension (61.5% vs 40% [p<0.001]). Additionally, those with MFS had significantly higher incidence of prior aortic dissection (64.3% vs 5.8% [p<0.001]), and family history of aortic disease (75% vs 9.5% [p<0.001]). Significantly more non-MFS patients presented with hypertension (70% vs 33.3% [p<0.008]). Abdominal vessels involvement was more frequent in patients with MFS (53.3% vs 22.8% [p=0.011]). During the hospitalization, more patients with MFS had extension of their dissection (20% vs 4% [p=0.024]). None of the patients with MFS died during the index hospitalization, nor did they have new neurological or visceral ischemia. Kaplan-Meyer survival curve showed no significant difference in survival between the two groups from admission to five years follow-up.

Conclusion: The presence of dissection extension in patients with MFS warrants special in-hospital attention. However, our results indicate that, similar to patients without MFS, conservative treatment may be safe in Marfan Syndrome patients presenting with non-complicated acute type B aortic dissection. Given the limited study population, more research is needed to definitively analyze whether non-complicated TBAAD MFS patients would benefit from conservative versus more aggressive dissection management.
Abstract 18852: Adenylate Kinase Phosphotransfer and AMP Signaling Regulate Cardiomyocyte Cell Cycle and Heart Regenerative Capacity
Authors: Zhang Song , Nemutlu Emirhan , Terzic Andre , Dzeja Petras
Published: April 2024

The mammalian heart loses its regenerative potential within a week after birth. Although under certain circumstances adult cardiomyocytes can re-enter the cell cycle, initiate DNA synthesis and progress towards mitosis, however, they do not complete a conventional mitosis cycle and proceed towards endomitosis resulting in polyploidy. This suggests that high-energy dependent steps in cell cycle and myofibrillar disassembly are malfunctioning in adult cardiomyocytes. It is known that nucleotide-based energetic signaling and metabolic environment are critical for initiation of tissue regeneration after injury. The regulatory mechanisms and energetic-metabolic signaling circuits that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. Using mouse neonatal (2 and 10 days) hearts, with high and low regenerative capacity, respectively, we have determined metabolomic profiles and dynamics of phosphotransfer circuits and AMP-signaling using 18O-phosphoryl labeling mass-spectrometric and 18O-assisted 31P NMR techniques. The results demonstrate that loss of heart regenerative capacity 10 days after birth is associated with marked changes in heart metabolome and adenylate kinase (AK)-catalyzed phosphotransfer flux. Among most altered metabolites were putrescine and myo-inositol, involved in tissue regeneration, Krebs cycle and amino acid metabolites, creatinine, glucose-6-phosphate and lactate indicating rearrangements in energy and substrate metabolic systems. AK flux was the only phosphotransfer flux significantly upregulated in hearts at 10 days of age along with increased in mitochondrial and glycolytic capacities and mitochondrial AK2 expression. Increased AK2 expression was associated with augmented AMP phosphorylation, measured by generation of β-ATP[18O], and reduction of AMPK activity. Thus, increased channeling of AMP into mitochondria and reduction of AK-AMP-AMPK signaling axis could contribute to the withdrawal from completion of cell cycle in terminally differentiated adult cardiomyocytes. The uncovered metabolic signaling mechanism opens new avenues for targeted regulation of heart regenerative potential critical for repair of injured hearts.
Abstract 18888: Long-Term (10 Years) Experience of Implantable Cardioverter-Defibrillator Implantation in Patients with Hypertrophic Cardiomyopathy
Authors: Kolibash Christopher P , Jan M. F , Mori Naoyo , Niazi Imran , Mortada M. E , Tajik A. J , Sra Jasbir
Published: April 2024

Introduction:
Sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is unpredictable and the most frequent cause of premature death. Implantable cardioverter-defibrillator (ICD) therapy is an effective strategy for both primary and secondary SCD prevention in select HCM populations. However, limited data exist on the long-term follow-up of HCM patients with ICD for prevention of SCD.

Methods:
We examined consecutive patients with HCM who underwent ICD implantation at our tertiary care institution. Patients were grouped into two cohorts (A and B) based on established clinical risk markers for SCD in HCM. Patients in group A had 2 or more major risk factors (≥2RF); patients in group B had 1 or fewer risk factors (≤1RF) for SCD. The number of appropriate and inappropriate ICD shocks, all-cause mortality and early and late ICD-related complications were compared between the two groups.

Results:
Over a 10-year period, we identified 60 consecutive HCM patients (median age 52 years [interquartile range = 45-62]; 47% female) who underwent ICD implantation. Of these, 26 patients had ≥2RF (group A); 34 patients had ≤1 RF (group B). Median follow-up was 62 months for both groups. In group A, 30.8% of HCM patients (8 of 26) received an appropriate ICD shock compared to 2.9% of patients in group B (1 of 34) (p= 0.004). Also, only 2 patients (7.7%) in group A received an inappropriate ICD shock compared with 6 patients (17.6%) in group B (p=0.446). The predominant risk predictors for ICD shocks in both groups were nonsustained ventricular tachycardia on Holter monitor and history of syncope. There were no differences between groups for early and late ICD-related complications of pneumothorax, pocket hematoma, infection, lead revisions, symptomatic upper-extremity deep venous thrombosis, new atrial arrhythmias and generator changes. All-cause mortality was not statistically significant between the groups (15.4% in group A compared to 12.1% in group B (p=0.717).

Conclusion:
Hypertrophic cardiomyopathy patients with 2 or more risk factors for SCD are more likely to receive an appropriate ICD shock compared to patients with 1 or fewer risk factors. This study validates that HCM patients with at least two risk factors for SCD benefit most with ICD implantation.
Abstract 18933: Partners Together in Health (PaTH) Intervention to Reduce Cardiovascular Risk
Authors: Yates Bernice , Meza Jane L , Norman Joe , Stanek Krogstrand Kaye , Schumacher Karen
Published: April 2024

Despite proven efficacy of cardiac rehabilitation (CR) in initiating lifestyle changes, less than 50% of coronary artery bypass graft (CABG) patients maintain changes 6 month later. The objective of this feasibility study was to test the Partners Together in Health (PaTH) Intervention versus usual care in improving physical activity and healthy eating behaviors in CABG patients and spouses. We used an experimental, two-group (n=17 couples/group), repeated measures design. CABG patients in both groups participated in CR. Spouses in the PaTH group attended CR with the patient and made the same healthy eating and physical activity changes as patients. Spouses in the control group attended educational classes with the patient which is the standard of care in CR. It was hypothesized that “two persons would be better than one" at making changes and sticking with them long-term. Eating behavior was measured using 3-day food records. Physical activity was measured using the Actiheart accelerometer. Data were collected at baseline (entrance in CR), 3-months (post-CR), and 6-months. Although healthy eating was similar between patient groups at the end of CR, by 6 months, there was a trend (p<.10) for patients in the PaTH group to report better eating behavior than the control group on 3 dietary components: % fat calories (26.4% vs. 32.4%), % saturated fat calories (8.1% vs. 11.1%), and cholesterol (209.8 mg vs. 233.8 mg), respectively. Similar findings were obtained for PaTH vs. control spouses at 6-months: % fat calories (30.6% vs. 36.7%), % saturated fat calories (9.4% vs. 11.3%), and cholesterol (204.7 mg vs. 260.8 mg), respectively. No differences were found between patient groups at 3 or 6-months in the # of minutes/week of physical activity. Although patients were above the national guidelines for PA recommendations (>150 min/week at >3 METs) at 3- and 6-months, they were only participating in 162 min/week (PaTH group) vs. 182 min/week (control group) at 6-months. In contrast, spouses were engaged in approximately twice as much weekly physical activity as patients: 300 min/week (PaTH group) vs. 257.6 min/week (control group) at 6 months. Long-term maintenance of lifestyle changes is essential to positively influence health outcomes for both patients and spouses.
Abstract 18934: Inhibition of Wnt6 by Sfrp2 Regulates CPC Differentiation by Differential Modulation of Canonical and Non Canonical Wnt Pathways
Authors: Verma Amanda K , Schmeckpeper Jeffrey , Yin Lucy , Zhang Lunan , Beigi Farideh , Payne Alan , Zhang Zhiping , Pratt Richard , Dzau Victor J , Mirotsou Maria
Published: April 2024

Introduction:
We have previously shown that in vivo administration of Sfrp2, an inhibitor of canonical Wnt signaling, into injured myocardium enhanced cardiac regeneration. In vitro, Sfrp2 selectively bound to Wnt6 expressed in cardiac progenitor cells (CPCs) and induced cell cycle arrest and cardiac differentiation. Here, we explore the role of Wnt6 inhibition by Sfrp2 in modulating Wnt pathways and regulation of CPC proliferation and differentiation. We also employ lineage tracing to investigate the contribution of CPCs to the in vivo effects of Sfrp2.

Methods:
Sca1+ CPCs were established and treated with recombinant Sfrp2 or Wnt6. Wnt pathway activation was measured by Western blotting. Proliferation was assessed by BrdU. Differentiation was documented by Nkx2.5 and Gata4 staining. Recombinant Sfrp2 protein was injected in Sca1-eGFP mice after ischemia/reperfusion injury. Co-staining of GFP with cardiac markers was assessed by confocal microscopy. Cardiac function was evaluated by echocardiography.

Results:
Treatment with Wnt6 increased canonical Wnt signaling and induced a 3.9 ± 0.9 fold increase in CPC proliferation. Simultaneous addition of Sfrp2 abolished the effects of Wnt6. Sfrp2 treatment alone inhibited canonical and activated non canonical Wnt signaling through β-catenin and JNK, respectively. JNK inhibitor SP600125 repressed Sfrp2 induced differentiation. To further explore the dual role of Sfrp2 in regulating Wnt signaling, CPCs modified to express constitutive active β-catenin (CA-CPCs) were treated with Sfrp2 and found to be resistant to both cell cycle arrest and differentiation. Interestingly, Sfrp2 treatment of CA-CPCs did not result in JNK activation suggesting Sfrp2 regulates JNK indirectly. Preliminary in vivo data indicate that exogenous Sfrp2 increased CPC differentiation and restored fractional shortening and contractility 2 months post infarction.

Conclusion:
Inhibition of Wnt6 by Sfrp2 differentially regulates canonical and non canonical Wnt pathways in CPCs, permitting further lineage commitment towards cardiomyocytes. Along with its cytoprotective and antifibrotic effects, Sfrp2 enhances cardiac regeneration in vivo thus highlighting its value as a potential therapeutic agent for cardiac disease.
Abstract 19025: A Signaling Complex of HCN2/HCN4/Cav3 Resides in Caveolae of Cardiac Cells
Authors: Shi Nian-Qing , Ou Jessie , Yang Jessie , Yu Xi-Yong , Ye Bin
Published: April 2024

Macromolecular signaling complexes including ion channels present in the caveolar micro-domains can provide highly specific and localized regulation of cell function. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are key constituents of the cardiac pacemaker, regulating the rate of diastolic depolarization and cardiac rhythm. HCN4 and HCN2 are the major HCN isoforms found in cardiac tissues. HCN4 is physically associated with Caveolin-3 (Cav3), the “coat protein” for caveolae in cardiac cells. In this report, we dissected the regulation of Cav3 on HCN2. Cardiac HCN2 (60-kDa, HCN2s) or HCN4 was co-localized with Cav3 in mouse LV membrane fractions. A dominant-negative P104L-Cav3 mutation was used to “probe” the association of HCN2/Cav3. HCN2s itself does not encode currents but HCN2s/HCN4 channels generated currents resembled to those recorded from native cells. HEK293 cells expressing full-length-HCN2 (HCN2f)/WTCav3 showed comparable HCN2 density and channel activity to those cells expressing HCN2f/P104L or HCN2 alone. Bioluminescence Resonance Energy Transfer (BRET) assays in conjunction with stable HCN cell lines and lipid raft inhibitors were used to quantify the intra-molecular interactions of each HCN form and Cav3. WTCav3 or P104L was fused to a
Renilla
Luciferase (Rluc) as the “donor” while each HCN form was fused to YFP as the “acceptor”. All HCN/Cav3 pairs displayed positive BRET ratios, suggesting that HCN and Cav3 were within a 10-100 Å distance to permit energy transfer from RLuc (470-nm) to YFP (530-nm) in the presence of coelenterazine-h. We did not record positive BRET ratios from samples containing no assay substrate. Average BRET ratio data (n=6, p<0.05) suggested that the association for HCN2s/Cav3 is the strongest. The P104L study showed that aa104 is involved in the interactions of HCN2s/Cav3 or HCN4/Cav3 but not HCN2f/Cav3. Our results indicate that Cav3 interacts with HCN4 via HCN2s to form a HCN2s/HCN4/Cav3/caveolae complex, and it may play an important role in cardiac signaling.
Abstract 19032: Performance of Euroscore I, Euroscore II and STS Score for Risk Stratification of Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: D'Onofrio Augusto , Gasparetto Valeria , Rizzoli Giulio , Napodano Massimo , Tarantini Giuseppe , Bianco Roberto , Tessari Chiara , Isabella Giambattista , Gerosa Gino
Published: April 2024

Purpose: Objective of this single center study was to assess and compare the performance of logistic Euroscore I (ES I), logistic Euroscore II (ES II) and the Society of Thoracic Surgeons (STS) mortality score for risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR).

Methods: We analyzed data of 235 consecutive patients who underwent TAVR from June 2007 through January 2011. We calculated STS, ES1 and ES2 of each patient. Performance of the risk scores was evaluated by means of ROC curves. A logistic multivariable analysis was performed including confounding factors (age, sex) and access: percutaneous (trans-femoral and trans-subclavian) vs. surgical (trans-apical and trans-aortic) TAVI.

Results: Surgical and percutaneous TAVI were performed in 78 (33.2%) and 157 (66.8%) patients, respectively. Mean age was 80.5 ± 6.6 years. Median ES1, ES2 and STS scores were: 17.6%, 5.4% and 6.8% respectively. Thirty-day mortality was 4.3%, the incidence of combined safety events, according to VARC definitions, was 17%. The area under the ROC curve (AUC) for thirty-day mortality was 0.68, 0.66 and 0.60 for ES1, ES2 and STS, respectively (p=0.79). The AUC for combined safety events was 0.57, 0.60 and 0.57 for ES1, ES2 and STS, respectively (p=0.71). After correction for age, sex and approach the AUC for thirty-day mortality was 0.84, 0.75 and 0.74 for ES I, ES II and STS scores, respectively while the AUC for combined safety events was 0.68, 0.66 and 0.65 for ES I, ES II and STS scores, respectively. ES2 and STS performed better in predicting thirty-day mortality in surgical cases (0.75 and 0.74) while ES1 performed better in percutaneous cases (0.76).

Conclusion: According to our analysis, in patients undergoing TAVR, ES1, ES2 and STS scores for thirty-day mortality and for combined safety events provide similar but poor performance (less than 0.75). After correction for confounding factors and approach, ES1 was the only that showed AUC greater than 0.75.
Abstract 19050: Does Type of Culprit Lesion Matter in Patients with Acute Coronary Syndrome and Prior Coronary Artery Bypass Graft Surgery Undergoing Percutaneous Coronary Intervention?
Authors: Harskamp Ralf E , Beijk Marcel A , Damman Peter E , Tijssen Jan G , Krucoff Mitchell W , Lopes Renato D , de Winter Robbert J
Published: April 2024

Background: Acute coronary syndrome (ACS) in patients with prior coronary artery bypass graft (CABG) surgery may be due to graft failure or progression of native coronary artery disease. We studied whether the culprit lesion (graft vs. native) is associated with differences in hospital and long-term outcomes.

Methods: We included ACS patients with prior CABG who underwent percutaneous coronary intervention (PCI) of >=1 lesion at the Academic Medical Center - University of Amsterdam between 1998 and 2008. The primary outcome was 5-year mortality and the secondary outcome was a composite of in-hospital death, myocardial infarction, need-for-revascularization and stroke. Kaplan-Meier estimates were used to compare 5-year mortality between patients with graft vs. native culprit lesions. Predictors for 5-year mortality were identified using multivariable Cox proportional hazards modeling with backwards variable selection. Logistic regression was used to assess predictors for in-hospital outcomes.

Results: Overall, 270 patients were included, of which 146 (54.1%) had a graft culprit lesion. Mean age was 70 (SD=9.5yrs), 21.9% were women. Multi-vessel PCI was performed in 50 (18.5%) patients. 5-year mortality was similar following graft versus native culprit lesion PCI (41.3% vs. 36.4%, HR:1.16, 95%-CI:0.73-1.84, p=0.52). In-hospital death, MI, need-for-revascularization and/or stroke was also comparable (16.4% vs. 13.7%, HR:1.24 (95%-CI:0.63-2.43), p=0.53). Similar results were seen after adjusting for important covariates. Older age, lack of prior aspirin use, and cardiogenic shock were independently associated with worse clinical outcomes.

Conclusion: Type of culprit lesion (either native or graft) in patients presenting with ACS and prior CABG surgery was not associated with in-hospital or long-term clinical outcomes. Larger studies to validate our findings are warranted.
Abstract 19078: Cardiac Troponin T Measured by a Highly Sensitive Assay is Associated with Diabetes Incidence
Authors: Whelton Seamus , Lazo Mariana , Park Eun Jung , Coresh Josef , Young J. H , Brancati Frederick , Hoogeveen Ron , Ballantyne Christie , Selvin Elizabeth
Published: April 2024

Introduction:
An adverse cardiovascular disease (CVD) risk factor profile is typically present well before the clinical diagnosis of diabetes. Diabetes and hyperglycemia are risk factors for myocardial damage and subclinical atherosclerosis, but it is unclear if subclinical cardiac damage is present before the clinical diagnosis of diabetes. Hypothesis: Subclinical myocardial damage_as indicated by elevated cardiac troponin measured by a novel highly sensitive assay (hs-cTnT) will be associated with risk of diabetes.

Methods:
We conducted a prospective cohort analysis of hs-cTnT and incidence of self-reported diabetes among ARIC study participants with no known history of diabetes or CVD at baseline (1996-98). Adjusted Cox proportional hazard models included hs-cTnT as a categorical variable or as a spline.

Results:
During a median of 12 years of follow-up of 7,898 participants, there were 1,809 self-reported cases of newly diagnosed diabetes. Compared to those with undetectable hs-cTnT (<0.003ug/L), participants with hs-cTnT 0.009-0.0013 or ≥0.014ug/L had a significantly increased risk for diabetes after adjustment for diabetes risk factors: HRs of 1.18, 95% CI 1.0-1.40 and 1.32, 95% CI 1.04 - 1.69, respectively. After further adjustment for glucose, the relationship was attenuated (p-values for linear trend 0.01 before and 0.19 after adjustment) but was significant when modeled non-linearly (p-value=0.003 for spline with knot at the mean hs-cTnT of 0.005 ug/L) (Figure).

Conclusions:
Elevated levels of hs-cTnT are associated with an increased risk of developing diabetes even in the absence of a history of CVD and after adjusting for diabetes risk factors but the association is non-linear after adjustment for fasting glucose. This suggests that diabetes and heart disease may develop in parallel with myocyte necrosis preceding as well as following diabetes.