bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8438: Sugar-Sweetened Beverage Consumption and Incident Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Shay Christina M , Nettleton Jennifer A , Lutsey Pamela L , Polonsky Tamar S , Carnethon Mercedes R , Chan Cheeling , Van Horn Linda , Burke Gregory L
Published: April 2024

Introduction:
Sugar-sweetened beverage (SSB) consumption has been associated with obesity, dyslipidemia, hypertension and type 2 diabetes (T2D). Data reporting associations between SSB intake and incident cardiovascular (CV) risk factors in large, ethnically diverse prospective cohorts are sparse. OBJECTIVE: To quantify associations between SSB consumption and risk of incident CV risk factors in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods:
SSB consumption was assessed by food frequency questionnaire at baseline (2000-2002) in 4,166 African American, Caucasian, Chinese, and Hispanic adults (45-84 years) without baseline clinical CV disease. Incident CV risk factors were identified at three follow-up exams (2002-2003, 2004-2005, and 2005-2007) and included weight gain (>3% higher than baseline); increased waist circumference (WC) (>3% higher than baseline); low HDL (HDL <40mg/dL [men] <50mg/dL [women), LDL <160mg/dL, and triglycerides (TG) 40mg/dL [men], >50mg/dL [women], LDL 150mg/dL; impaired fasting glucose (IFG) (FG 101-126 mg/dL) and T2D (FG>126 mg/dL or diabetes medication use). Except in T2D analyses, participants with diabetes were excluded and participants on lipid lowering medications were excluded from lipid analyses. Hazard ratios (95% CI) were estimated and adjusted for demographics, intentional exercise, dietary confounders (including energy intake) and baseline traditional CV risk factors. RESULTS: Compared to SSB consumption of <1 serving/day, intake of 2+ servings/day was significantly associated with greater risk for incident increased WC, hypertriglyceridemia and IFG among women; associations which were not observed in men (Figure 1).

Conclusions:
The metabolic influence of SSBs is complex and is not homogenous between men and women. Women exhibit lower energy requirements compared to men and therefore experience higher CV risk when a greater proportion of calories is consumed in the form of SSBs.
Abstract 8457: Early Neurodevelopmental Outcome in Hypoplastic Left Heart Syndrome and Related Anomalies: The Single Ventricle Reconstruction Trial
Authors: Newburger Jane W , Sleeper Lynn A , Bellinger David C , Goldberg Caren S , Tabbutt Sarah , Lu Minmin , Mussatto Kathleen A , Williams Ismee A , Gustafson Kathryn E , Mital Seema , Pike Nancy , Sood Erica , Mahle William T , Cooper David S , Dunbar-Masterson Carolyn , Dent Krawczeski Catherine , Lewis Allan , Menon Shaji , Pemberton Victoria L , Ravishankar Chitra , Atz Theresa W , Ohye Richard G , Gaynor J. W
Published: April 2024

Background:
Children with HLHS and related anomalies who survive the Norwood procedure are at risk for neurodevelopmental (ND) impairment. We evaluated the relationship of ND outcome with type of Norwood shunt, patient factors, management practices, and medical course.

Methods:
In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt vs. right-ventricle-to-pulmonary-artery shunt, 14-month ND outcome was assessed using the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development®-II. We used stepwise multivariable regression to identify risk factors for adverse ND outcome.

Results:
Among 373 transplant-free survivors, 321 (86%) returned for ND testing at age 14.3±1.1 (mean±SD) months. Mean PDI (74±19) and MDI (89±18) scores were lower than normative means (P<.001). Independent predictors of lower PDI score (R
2
= 26%) were center (P=.003), birth weight<2.5 kg (P=.023), longer Norwood hospitalization (P<.001), and more complications between Norwood procedure discharge and age 12 months (P<.001). Independent risk factors for lower MDI score (R
2
= 34%) included center (P<.001), birth weight<2.5 kg (P=.04), genetic syndrome/anomalies (P=.036), lower maternal education (P=.045), longer mechanical ventilation after the Norwood operation (P<.001), and greater number of complications after Norwood discharge to age 12 months (P<.001). We found no significant relationship of PDI or MDI score to type of Norwood shunt, perfusion type (i.e., deep hypothermic circulatory arrest, regional cerebral perfusion), other aspects of vital organ support (e.g., hematocrit, pH strategy); or cardiac anatomy including ascending aorta diameter. The relationship of predictors to ND outcome was similar in pre-specified subgroups of birth weight, preterm status, pre-Norwood head circumference, or genetic syndrome/other anomalies.

Conclusion:
ND impairment in Norwood survivors is more highly associated with innate patient factors and overall morbidity in the first year than with intraoperative management strategies. Improvement in ND outcome in this vulnerable population is thus likely to require interventions that occur outside the operating room.
Abstract 85: Influence of Age Differences for Collapse-to--Defibrillator Time on Survival in Out-of Hospital Cardiac Arrest from All-Japan Utstein Registry Data
Authors: Yonemoto Naohiro , Yokoyama Hiroyuki , Nagao Ken , Kimura Takeshi , Nonogi Hiroshi ,   JCS-ReSS group
Published: April 2024

[Background]
The study investigated influence of age differences for collapse-defibrillator time on survival in out-of hospital cardiac arrest. Several studies had the effects of age on survival from out-of hospital cardiac arrest, however those were for medium sample size.

[Method]
We used All-Japan Utstein Registry of the Fire and Disaster Management Agency with a prospective, population based, involving consecutive patients with an out-of cardiac arrest with witness with layperson, from 16 to 89 years (young adult: 16-39 age, middle: 40-64 age, older: 65-89 age) and from April 1, 2006 to December 31 2009. The primary outcome measure was survival and good neurological outcome CPC 1 or 2. We evaluated the effect of collapse-defibrillator time for the outcome in logistic regression by age group.

[Results]
1329 were young adults, 7400 were middles and 10315 were at older in the analysis. Odds ratio of the average effect of the time per five minutes by defibrillator was 1.53 and 95% confidence intervals (CI) 1.36 to 1.73, p<.0001 at young adult, 1.61 and 95%CI: 1.53 to 1.71, p<.0001 at middle, 1.77 and 95%CI: 1.67 to 1.87, p<.0001 at older (figure).

[Conclusion]
Our results suggest that the effect of the times by defibrillator has age differences. Elderly person need more to improve the delay of defibrillator.
Abstract 8633: Right Ventricular Origin of Arrhythmias in
Scn5a+/-
Mice Modeling Brugada Syndrome is Due to Reduced Na
+
and Higher K
+
Channel Expression and Function in the Right Ventricle
Authors: Martin Claire A , Siedlecka Urszula , Kemmerich Kristin , Lawrence Jason , Cartledge James , Guzadhur Laila , Brice Nicola , Grace Andrew A , Schwiening Christof , Terracciano Cesare M , Huang Christopher L
Published: April 2024

Brugada syndrome is associated with ventricular tachycardia originating in the right ventricle (RV); this has been attributed to either depolarization abnormalities or increased repolarization heterogeneities. We use a heterozygotic
Scn5a+/-
murine model to test these hypotheses. Na
v
1.5 mRNA and protein expression were lower in
Scn5a+/-
than wild-type (WT) hearts, with a further reduction in the RV (panel A, n = 4, significant differences: * = WT vs
Scn5a+/-
; # = LV vs RV). There were higher expression levels of K
v
4.2, K
v
4.3 and KChIP2 in RV than LV in both groups. Action potential (AP) upstroke velocity was decreased in
Scn5a+/-
(RV: 59.43 +/- 2.70 V/s to 30.26 +/- 4.03 V/s, p < 0.0001, n = 20), and furthermore was smaller in RV than LV. AP durations were smallest in the RV of
Scn5a+/-
myocytes. Transient outward current density (
I
to
) was greater in the RV of both WT and
Scn5a+/-
(panel B, n = 17), with similar voltage dependence of activation. Time constants of inactivation were larger in RV than LV, and voltage dependence of inactivation was shifted to more negative values in RV compared to LV, but to more positive values in
Scn5a+/-
compared to WT. Maximum Na
+
current density (
I
Na
) was decreased in
Scn5a+/-
, with a further reduction in the RV (panels C, D, n = 17). Voltage dependence of activation was unchanged, but inactivation was shifted to more negative values in
Scn5a+/-
. Maximum persistent Na
+
current density (
I
pNa
) was decreased in a similar pattern to
I
Na
(RV: -0.30 +/- 0.03 pA/pF, n = 15 vs -0.17+/- 0.02 pA/pF, n = 22, p =0.0009). Our findings show preferential upregulation of the single Scn5a gene in the LV of the
Scn5a+/-
mice compared to RV. The reduced expression of Na
+
channels in RV leads to smaller
I
Na
, resulting in slowed conduction, and smaller
I
pNa
, which in combination with increased
I
to
, results in shorter AP durations and greater heterogeneity of repolarization, thus suggesting arrhythmogenesis may be initiated by both mechanisms in the RV of
Scn5a+/-
hearts.
Abstract 8912: Pinch Proteins Are Essential for Cardiac Protein Kinase B Signaling
Authors: Frese Karen S , Meder Benjamin , Sedaghat-Hamedani Farbod , Huttner Inken G , Katus Hugo A , Rottbauer Wolfgang
Published: April 2024

Integrin-linked kinase (ILK) is essential for cell maturation, migration and proper adhesion of the cardiac intercalated disks and costameres. It furthermore is as an essential component of the cardiac mechanical stretch sensor. Until now, the precise molecular function of ILK and its associated interaction partners are still unknown. To assess the cardiac function of ILK interacting PINCH proteins, we used a reverse genetics approach in zebrafish to identify and deplete the orthologs PINCH1 and PINCH2 by injection of morpholino antisense oligonucleotides. Depletion of either PINCH isoforms independently leads to instability of the ILK-PINCH-Parvin complex, loss of stretch-responsive gene expression and progressive heart failure. The impaired cardiac function in PINCH-deficient embryos can be explained by loss of Protein kinase B activity, since Akt/PKB phosphorylation at Serine 473 is significantly reduced in PINCH-morphants and overexpression of constitutively active PKB reconstitutes their cardiac function to almost normal values. Our data demonstrate an important role of PINCH proteins in maintaining cardiac contractility by stabilizing the IPP complex and thereby regulating Akt/PKB activity in the vertebrate heart.
Abstract 9: Role of Hyperkalemia in the Transmural Activation Rate Gradient and Asystole During Long-Duration Ventricular Fibrillation (LDVF) in Isolated Canine Heart
Authors: Taylor Tyson G , Venable Paul W , Shibayama Junko , Booth Alijca E , Rhodes Nathaniel L , Warren Mark , Zaitsev Alexey V
Published: April 2024

During LDVF in globally ischemic hearts, a transmurally heterogeneous decrease in VF rate (VFR) occurs culminating in asystole. While hyperkalemia is considered to be a major modulator of excitability during ischemia, the magnitude of extracellular potassium ([K
+
]
o
) accumulation during LDVF and its role in the transmural VFR gradient and asystole remain unknown. Twelve isolated, blood perfused canine hearts underwent 20 min of global ischemia and VF; and an additional 4 hearts were subjected to VF during normoxic perfusion with varying [K
+
]
o
(2 - 15 mM). Plunge needle electrodes with electrical and K
+
sensors were used for left ventricular endocardial (ENDO) and epicardial (EPI) measurements of VFR and [K
+
]
o
. Cluster analysis revealed a dichotomy in the timing of asystole (Figure A, Inset): 6/12 hearts experienced asystole at 7.2 ± 1.0 min of ischemia (EARLY ASYS), while the remaining 6/12 hearts were still in VF at 20 min of ischemia (LATE ASYS). EARLY ASYS showed significantly faster K
+
accumulation in ENDO and EPI than LATE ASYS; neither group developed a gradient in [K
+
]
o
(Figure A). Nevertheless, a prominent ENDO-EPI VFR gradient developed during LDVF in both groups (not shown). Compared to normoxic VF, LDVF exhibited a marked decrease in VFR as a function of [K
+
]
o
. In addition, there was a significant difference in K
+
sensitivity of VFR between ENDO and EPI which was not observed during normoxic VF (Figure B). We conclude that during LDVF enhanced K
+
leak predicts early asystole, but the level of [K
+
]
o
per se cannot explain VFR decline either in EPI or ENDO. Thus, hyperkalemia is not the main determinant of electrical depression and asystole during LDVF.
Abstract 9071: P-Selectin Glycoprotein Ligand-1 Deficiency is Protective Against Perivascular Macrophage Infiltration and Obesity-Induced Endothelial Dysfunction
Authors: Wang Hui , Luo Wei , Guo Chiao , Bodary Peter F , Eitzman Daniel T
Published: April 2024

Introduction:
P-selectin glycoprotein ligand-1 (Psgl-1) is a leukocyte ligand which binds to selectins and mediates leukocyte trafficking in several disease states. The goal of the current study was to assess the effects of Psgl-1 deficiency on perivascular adipose tissue (PVAT) macrophage accumulation and endothelial dysfunction in the setting of obesity.

Methods:
Psgl-1 deficient (

Psgl-1
-/-

) and control (

Psgl-1
+/+

) mice were fed either normal or DIO chow for 10 weeks (n=5-7 mice per group). Mesenteric arterioles were then mounted on a pressure myograph to evaluate vascular function. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (Ach)-induced (with and without N-nitro-L-arginine methyl ester (L-NAME)) and sodium nitroprusside (SNP)-induced vasorelaxation were evaluated. Mesenteric PVAT macrophage content was assessed with Mac-3 immunohistochemistry.

Results:
The body weight of DIO mice was greater than standard chow-fed mice (46.5±1.4 vs 21.2±1.6g, p<0.01). NE-induced vasoconstrictions were similar between

Psgl-1
+/+

and

Psgl-1
-/-

mice on DIO or standard chow, however, relaxation responses to Ach were significantly impaired in DIO

Psgl-1
+/+

mice compared with standard chow-fed

Psgl-1
+/+

mice (maximal relaxation, 36.0±7.8% vs 73.4±5.3%, p<0.01). In contrast

Psgl-1
-/-

DIO mice were protected from endothelial dysfunction and were similar to

Psgl-1
-/-

mice on standard chow (maximal relaxation, 75.1±4.8% and 83.8±3.7%). Ach-induced vasorelaxation was completely inhibited in all groups in the presence of L-NAME. Endothelium-independent relaxation responses to SNP were similar in all groups. Mac-3 staining showed reduced macrophage content in mesenteric PVAT of DIO

Psgl-1
-/-

mice compared to DIO

Psgl-1
+/+

mice (18.2±1.5% vs 30.0±2.6% , p<0.01). Treatment of DIO

Psgl-1
+/+

mice with a Psgl-1 antibody for 4 weeks resulted in Ach-induced relaxation of 71.6±10.9%, which was similar to

Psgl-1
-/-

DIO mice.

Conclusions:
Endothelial function and vascular NO bioavailability are impaired in a DIO mouse model. Psgl-1 deficiency is protective against PVAT inflammation and endothelial dysfunction induced by obesity. Psgl-1 inhibition may be useful for treatment of obesity-related vascular diseases.
Abstract 9122: Heparin Mobilizes Multipotent Human Mesoangioblasts
Authors: Fujitaka Keisuke , Iwasaki Masayoshi , Sato Daisuke , Enoki Chiharu , Park Haengnam , Koyanagi Masamichi , Minato Naoki , Otani Hajime , Nishikawa Mitsushige , Adachi Yasushi , Ikehara Susumu , Zeiher Andreas M , Dimmeler Stefanie , Iwasaka Toshiji
Published: April 2024

The identification of clinically applicable drugs which mobilize endogenous mesenchymal progenitor cells may offer novel therapeutic application in cardiovascular diseases. We recently showed that hepatocyte growth factor (HGF) induces the mobilization of multipotent circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs). Since HGF only has a short half life, we investigated whether heparin might be useful to endogenously increase HGF levels thereby inducing the mobilization of cMABs. Heparin was infused in patients with coronary artery disease at a concentration of 200 U/kg (n=11 patients) and 300 U/kg (n=11 patients) and serum HGF levels were determined by ELISA. Consistent with published studies, heparin dose-dependently increased HGF levels to 34.4+1.9 in patients receiving 200U/kg heparin and 42.8+0.9 ng/ml in the patients treated with 300 U/kg. Moreover, heparin dose-dependently increased the number of circulating mesenchymal cell colonies. Patients receiving 200U/kg showed 0.30+0.12 colonies / mononuclear cells (x10
6
). Further increasing the heparin dosage to 300U/kg increased the number of colonies to 0.63+0.17 colonies / mononuclear cells (x10
6
). In contrast, we were never able to obtain colonies in patients receiving heparin concentrations below 100 U/kg. The mesenchymal origin of the colonies was characterised by the lack of hematopoietic progenitor cell markers CD45 and CD34. Consistent with the original characterisation of the mesoangioblasts, the colonies expressed the mesenchymal marker CD73, the HGF-receptor c-Met as well as the endothelial marker KDR. In conclusion, we demonstrate that heparin can dose-dependently mobilize mesenchymal progenitor cells in humans. These findings might open up an avenue to non-invasively obtain multipotent mesenchymal cells for therapeutic application in patients with cardiovascular disease.
Abstract 9145: Tyrosine
705
Phosphorylation of STAT3 is Causally Involved in Cardioprotection by Ischemic Postconditioning in Pigs
Authors: Skyschally Andreas , Musiolik Judith , Gedik Nilgün , Heusch Gerd
Published: April 2024

In mice, the signal transducer and activator of transcription (STAT) 3 is causally involved in protection by ischemic postconditioning (PoCo) against myocardial infarction. However, signal transduction in rodents differs from that in larger mammals. We have now determined the impact of PoCo on STAT3 activation/phosphorylation in pig hearts, which more closely resemble human hearts in size, coronary anatomy, heart rate, and infarct development. Anesthetized pigs were subjected to 90 min low flow ischemia and 120 min reperfusion, initiated with either PoCo (six cycles of 20 s reperfusion/re-occlusion, n=8) or immediate full reperfusion (IFR, n=8). Eight additional pigs were treated with the JAK/STAT inhibitor AG490 (9 µg/kg/min i.c.; 10 min before ischemia until the end of reperfusion; AG-PoCo n=4, AG-IFR n=4). Myocardial biopsies were taken at baseline, 85 min ischemia and 10, 30, and 120 min reperfusion. STAT3 phosphorylation and total STAT3 protein were quantified by Western blot analysis. Area at risk (AAR) and regional myocardial blood flow (microspheres) during ischemia were not different between groups. PoCo reduced infarct size (TTC staining) from 38±2 to 26±3 % of the AAR (p<0.05). AG490 abolished this infarct size reduction (AG-IFR: 36±4 vs. AG-PoCo: 36±1 % of AAR). STAT3 tyr
705
phosphorylation normalized to total STAT3 protein (Table 1) increased during ischemia/reperfusion; in pigs subjected to PoCo the STAT3 tyr
705
phosphorylation was even greater than with IFR (p<0.05, ANOVA). STAT3 ser
727
phosphorylation was increased with PoCo and IFR to a similar extent. AG490 attenuated the increases in STAT3 phosphorylation in both groups to values below those with IFR and PoCo.

Conclusion:
In pigs, PoCo further increases STAT3 tyr
705
phosphorylation and protects the myocardium from infarction. AG490 attenuates the STAT3 tyr
705
activation at reperfusion and abolishes PoCo's protection. Thus, in pigs STAT3 is causally involved in cardioprotection by PoCo.
Abstract 9147: Undiagnosed Diabetes Mellitus, Pre-Diabetes, and Outcomes in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes
Authors: Giraldez Roberto R , Clare Robert , Lopes Renato D , Dalby Anthony J , Prabhakaran Dorairaj , Brogan Gerald X , Giugliano Robert P , Tricoci Pierluigi , James Stefan K , Tanguay Jean-François , Pollack Charles V , Harrington Robert A , Braunwald Eugene , Newby L. K
Published: April 2024

Background:
Diabetes mellitus (DM) is associated with in-hospital and post-discharge morbidity and mortality in ACS patients. Little is known about the prevalence and outcomes of DM first diagnosed during hospitalization (undiagnosed DM) and pre-diabetes (preDM) among non-ST-segment elevation (NSTE) ACS patients.

Methods:
We used the EARLY ACS trial database to explore the prevalence and outcomes of previously undiagnosed DM and preDM among high-risk NSTE ACS patients. Known DM was a baseline characteristic on the case report form. Undiagnosed DM was defined as fasting glucose >=126 mg/dL or HbA1c >=6.5% in patients without a history of DM, and preDM as fasting glucose >=110 to <126 mg/dL. Associations between undiagnosed DM, preDM, and known DM and 30-day death or MI and 1-year death were assessed by logistic regression and Cox proportional hazards modeling, respectively, with adjustment for baseline characteristics previously associated with these events in EARLY ACS models.

Results:
Of 9406 patients, 1069 (11.4%) had undiagnosed DM, 947 (10.1%) had preDM, and 2860 (30.4%) had known DM. In general, patients with undiagnosed DM and preDM were similar in age and had similar prevalence of comorbidities as patients without DM; each of these groups was younger, had higher eCrCl, and fewer comorbidities than patients with known DM. Compared with patients without DM, the risk of 30-day death or MI was higher among patients with undiagnosed DM, but neither preDM nor known DM patients had elevated adjusted 30-day risk (Table). After adjustment, 1-year death was similar for patients with preDM and undiagnosed DM to those without DM. However, known DM patients had 32% higher 1-year mortality.

Conclusions:
Undiagnosed DM and preDM are common in high-risk NSTE ACS patients. Although patients with previously undiagnosed DM and preDM had 1-year survival similar to non-diabetic patients, the presence of previously undiagnosed DM identified patients at elevated 30-day risk.
Abstract 9161: NOX2 Inhibition Restores Contractility, Intracellular Calcium Handling and Reduces Arrhythmogenicity in Dystrophic Cardiomyopathy
Authors: Gonzalez Daniel R , Treuer Adriana V , Dulce Raul A , Lamirault Guillaume , Hare Joshua M
Published: April 2024

Background.
Dystrophic cardiomyopathy is the cardiac manifestation of three closely related diseases that include Duchenne and Becker muscular dystrophies, and X-linked dilated cardiomyopathy. Oxidative stress is characteristic of cardiomyopathies. Intracellular calcium ([Ca
2+
]
i
) handling is abnormal in the heart of the mdx mouse, a model of Duchenne muscular dystrophy. We tested the hypothesis that oxidative stress may be responsible of disturbances in Ca
2+
handling and contractility in this model.

Methods and results.
We used mdx mice with established cardiomyopathy: ejection fraction of 56.7 ± 0.5 % in mdx vs. 70.8 ± 2.4% in wild type. We found increased expression (fivefold) of the NADPH oxidase NOX2 in the mdx hearts compared to wild type, along with increased superoxide production, measured as intensity of dihydroethidium staining (p<0.05 vs. wild type). Treatment with apocyinin (30 min, 100 µmol/L), a NOX2 inhibitor, decreased superoxide in mdx (p<0.05 vs. untreated). Next, we studied the impact of NOX2 inhibition on contractility and calcium handling in isolated cardiomyocytes. Contractility, assessed as sarcomere shortening, was decreased in mdx myocytes compared to wild type (p<0.05). Pre-treatment with apocynin restored this response to normal levels. In addition, the amplitude of evoked [Ca
2+
]
i
transients (measured as fura-2 fluorescence) that was diminished in mdx myocytes (p<0.05), was also restored upon NOX2 inhibition. Total sarcoplasmic reticulum (SR) Ca
2+
content (evaluated as caffeine-induced Ca
2+
release) was reduced in mdx hearts (p<0.05). This content was normalized by apocynin treatment. At the same time, NOX2 inhibition decreased dramatically the production of spontaneous diastolic calcium release events in mdx myocytes (p<0.05, ANOVA).

Conclusions.
These results indicate that in mdx hearts, NOX2 inhibition reduces oxidative stress, improving the SR [Ca
2+
] handling and contractility. Additionally, NOX2 inhibition reduced the sensitivity of the ryanodine receptor, reducing the incidence of diastolic Ca
2+
waves. Targeting of NOX2 in may be therapeutically helpful to increase cardiac performance and avoid the incidence of ventricular arrhythmias in Duchenne and other dystrophic cardiomyopathies..
Abstract 9200: Targeted Delivery of Slow-Releasing Form of A Prostacyclin Analogue, ONO-1301®, Enhances Recruitment of Bone Marrow Derived Cell and Yields Functional Benefits in Acute Myocardial Infarction in Mice
Authors: Imanishi Yukiko , Miyagawa Shigeru , Fukushima Satsuki , Ishimaru Kazuhiko , Saito Atsuhiro , Sakai Yoshiki , Sawa Yoshiki
Published: April 2024

Background:
Prostacyclin is an endogenous factor having a variety of protective effects against ischemic pathologies. We have generated ONO-1301®, which is a synthetic prostacyclin analog characterized by chemically stable structure and enhances stromal cell derived factor-1 (SDF-1), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) secretion. Here, we hypothesized that sustained delivery of ONO-1301® may induce therapeutic effects mediated by the recruited bone marrow derived cells into the injured myocardium in acute MI mouse.

Methods and Results:
ONO-1301® was conjugated with poly-DL-lactic-co-glycolic acid microsphere to generate a biodegradable controlled-release form. Either the atelocollagen-sheet with ONO-1301® microsphere eluted (ONO group; n=28) or ONO-1301® free microsphere eluted (control group; n=40) was implanted on the left ventricular anterior wall at 15 minutes following permanent LCA occlusion in C57BL6/N mice (male, 8-weeks old). ONO-1301® was still present in the plasma at 1 month (134±26 pg/ml; n=5). Expression levels of SDF-1, HGF, and VEGF in the infarct-border area were significantly elevated for 1 month in the ONO group. Recruitment of bone marrow cell induced by ONO-1301® was investigated using the acute-MI model in GFP-expressing bone marrow-transplanted chimera mice. Two months after LCA ligation followed by ONO-1301® treatment, there was a greater retention of the GFP+ cells in the infarct area. Some of the GFP+ cells were differentiated into the capillary components. In the ONO-1301® treated hearts, LV anterior wall thickness was significantly greater and infarct size was lower at 1 month. Cardiac performance was significantly greater in the ONO group (fractional area change: 24±1%; n=18) than the control group (20±1%; n=22; P=0.011), associated with greater 1 month survival in the ONO group (61±9 vs. 36±8%; P=0.052).

Conclusions:
Targeted delivery of the slow-releasing form of ONO-1301® possibly up-regulates protective factors, and recruits bone marrow cells into the infarct area, leading to the functional and survival benefits, indicating promising strategy to be translated into the clinical arena.
Abstract 9205: CT Angiography-Based Coronary Risk Stratification in Subjects Presenting with No or Atypical Symptoms
Authors: Fujimoto Shinichiro , Kondo Takeshi , Kodama Takahide , Orihara Tadaaki , Sugiyama Junichi , Kondo Makoto , Endo Akira , Fukazawa Hiroshi , Nagaoka Hideki , Oida Akitsugu , Takase Shinichi , Narula Jagat
Published: April 2024

Backgrounds:
Coronary CT angiographic (CTA) findings of positive vessel remodeling (PR, index>1.1) and low-attenuation plaque (LAP, <30HU) referred to as 2-feature-positive plaques (2FPP) have been reported to be associated with development of subsequent acute coronary syndromes. Such angiographic observations coupled with recent technological advances in CT technology to reduce the dose of contrast medium and radiation exposure, may allow extension of indications for CTA for risk stratification in patients with asymptomatic and atypical chest symptom.

Methods:
1139 subjects (M:F=602:537, ages 30-74, 61.5±9.3 yrs) either asymptomatic or presenting with atypical chest symptom underwent coronary 64 or 320-slice MDCT angiography and coronary artery calcium scoring (CACS). Age, gender, coronary risk factors, including hypertension (HT), diabetes (DM), hyperlipidemia (HL), smoking, and and CACS were investigated as predictors for 2FPP by multivariable analysis using logistic regression analysis.

Results:
2FPP were observed in 72 patients (6.3%). Based on the Framingham Risk Score (FRS) assignments, 2FPP were observed in 0/94 (0.0%) in low, 35/806 (4.3%) in intermediate, and 3/239 (15.5%) in high risk group subjects. Logistic regression analysis revealed significant predictor for 2FPP to be a male (OR: 2.6, 95%CI 1.4-34.9, p=0.004), DM (2.4, 1.4-4.0, p=0.001), smoking (2, 1.1-3. 4, p=0.02), CACS 1-500 (2.3, 1.3-4.2, p=0.007) in intermediate and high risk group subjects. 2FPP were observed in CACS categories as follows:Risk Group CACS 0 CACS 1-500 CACS>500Intermediate 14/430 (3.3%) 19/345 (5.5%) 2/31 (6.5%)High 4/57 (7.0%) 29/150 (19.3%) 4/32 (12.5%)

Conclusions:
In asymptomatic subjects and those presenting with atypical chest pain in intermediate-risk group, CTCA is contributory to FRS. In patients with high FRS risk, 2FPP prevalence in CACS>500 was lower. Male gender, DM, smoking and CACS 1-500 were independent predictors of the presence of vulnerable plaques in more than intermediate-risk group.
Abstract 9256: Overexpression of C-Terminal Domain of Talin-1 Enhances Survival, Migration, and Differentiation of Human Cardiac Stem Cells
Authors: Sharma Umesh , He Jia-Qiang , Vu Duc M , Tang Xian-Liang , Rokosh Gregg , Bolli Roberto
Published: April 2024

Background:
Cardiac stem cells (CSCs) have emerged as a promising therapy for cardiac repair after acute MI. Talin-1 is a key downstream signaling mediator of integrins. The C-terminal part of the talin rod, talin C, contains binding sites and regulatory elements that convey essential aspects of talin function in cells. In this study, we aimed to investigate the role of talin C in the survival and migration of CSCs and their differentiation into adult cardiomyocytes.

Methods:
Utilizing a baculovirus-mediated protein expression system in mammals (BacMam), we overexpressed talin C in c-kit-positive CSCs isolated from human right atrial appendages. In a TNF-α -treated cell culture system, we examined the survival of talin C-expressing CSCs by measuring LDH release. Adhesion of CSCs to fibronectin was measured by colorimetric Azur dye assay. Cell migration at baseline and with high glucose (HG) was studied by in vitro scratch assay. Differentiation of CSCs to adult cardiomyocytes was measured by flow cytometry using troponin I as cardiac lineage marker.

Results:
Overexpressed talin C was localized to intracellular adhesion complexes and actin filaments. Overexpression of talin C inhibited TNF-α-induced cytotoxicity of CSCs (optical density: TNF-α, 0.713±0.11; TNF-α+talin C, 0.33±0.02, P<0.001, N=10, each group). Talin C overexpression prevented HG-induced loss of cell adhesion (optical density: HG, 0.92±0.07; HG+talin C, 1.05±0.046; p=0.04, N=8, each group), and enhanced CSC migration (migration index: HG, 15.34±2.7; HG+talin C, 34±4.7; p=0.03, N=3-4, each group). Furthermore, talin C overexpression increased the commitment of CSCs to a cardiac lineage (% of troponin-I positivity: control, 66.13±4.07; talin C, 80.53±1.79; p=0.05).

Conclusions:
This study demonstrates a novel role for talin C in mediating i) increased CSC survival in a high pro-inflammatory environment, ii) increased CSC migration in HG cell growth environment, and 3 iii) enhanced commitment of CSCs to a cardiac lineage in vitro. These findings suggest that talin C enhancement may improve CSC survival, homing and differentiation after transplantation.
Abstract 9296: Prediction of Six Minute Walk Test Distance Using ECG Gated 320 Slice CT, Echocardiogram and Right Heart Catheter Examinations in Subjects with Pulmonary Hypertension in Multiple Regression Models
Authors: Kataoka Akihisa , Funabashi Nobusada , Uehara Masae , Sugiura Toshihiko , Tanabe Nobuhiro , Takaoka Hiroyuki , Tatsumi Koichiro , Kobayashi Yoshio
Published: April 2024

Purpose:
The six minute walk test (6MWT) as defined by the American Thoracic Society integrates responses of pulmonary and cardiovascular systems. We tried to predict 6MWT distance in subjects with pulmonary hypertension (PH) using 320 slice CT, transthoracic echocardiogram (TTE), and right heart catheter (RHC) examinations.

Materials and Methods:
16 consecutive PH subjects (11 female, mean 54 years, 7 primary PH, 9 chronic pulmonary arterial thromboembolism) underwent retrospective ECG gated 320 slice CT, RHC and 6MWT. CT images were reconstructed every 5% from 0-95% of R-R interval. We quantified right ventricular (RV) end systole volumes (RVESV) and end diastole volumes (RVEDV), and RV ejection fraction (RVEF) by CT, maximum RV area (maxRVA) and RV fractional area change (RVFAC) by TTE, and mean pulmonary artery pressure (MPAP) by RHC.

Results:
RVEDV and RVEF were 143.8±53.2ml and 46.7±10.6%. maxRVA, RVFAC on TTE, MPAP on RHC and 6MWT distance were 26.7±5.8, 29.1±8.9%, 35.8±14.2mmHg, and 404.8±85.7m. A significant positive correlation was seen between 6MWT distance and RVFAC (0.626, P=0.01), and a negative correlation was seen between 6MWT distance and, RVEDV and MPAP (r=-0.635, and -0.648, p<0.01). All predictor variables using CT and RHC were analyzed and 6MWT distance was predicted by multiple regression formula: Y=-3.0X1 -0.6X2 -2.2X3 -45.3X4 -0.7X5 +814.1 (Y=6MWT distance, X1=age (yrs), X2= RVEDV, X3=MPAP, X4=female gender, X5= RVEF) (R2=0.725, p<0.05). All predictor variables using TTE and RHC were analyzed and 6MWT distance was predicted by multiple regression formula Y=4.2X1 -2.7X2 -57.8X3 -1.5X4 +2.4X5 +461.6 (Y= 6MWT distance, X1=RVFAC, X2=age, X3=female gender, X4 MPAP, X5=maxRVA) (R2=0.719, p<0.05).

Conclusion:
6MWT distance can be predicted by 320 slice CT as well as or slightly better than by TTE and RHC. RVEDV on CT and MPAP on RHC may be negative predictors and RVFAC on TTE may be a positive predictor for estimating 6MWT distance in subjects with PH.
Abstract 93: GlideScope Video Laryngoscopic vs Macintosh Laryngoscopic Intubation During Cardiopulmonary Resuscitation: An Observational Study and Propensity Score Matching Analysis
Authors: Kim Young-Min , Oh Young-Min , Kang Hyung-Goo , Choi Hyuk-Joong , Je Sang-Mo , Chung Sung-Phil ,   Korean Emergency Airway Management Registry Investigators
Published: April 2024

Introduction:
The use of video laryngoscope during cardiopulmonary resuscitation (CPR) has not been extensively studied. A randomized controlled trial comparing the efficacy between video and direct laryngoscopy during CPR is logistically difficult. The objective of this study was to determine whether the first-attempt success rate of intubation using GlideScope video laryngoscope (GVL) is different to Macintosh laryngoscope (MAC) during CPR.

Hypothesis:
We hypothesized that the first-attempt success rate of intubation using GVL would be higher than MAC during CPR.

Methods:
This was an observational study using a multicenter airway registry data of six emergency departments (EDs) following current CPR guidelines - minimize interruptions in chest compressions. Adults of out-of-hospital cardiac arrest intubated in the EDs from March 2006 to December 2010 were enrolled. The primary outcome was success with first attempt. Secondary outcome was intubation failure. An attempt was defined as the introduction of the laryngoscope into the mouth. Failure was defined as an esophageal intubation, changing to a different device or intubator, or more than three attempts. To reduce the effect of selection bias and potential confounding, we performed rigorous adjustment for significant differences in patient and intubator factors using a propensity-score (PS) matching analysis. The adjusted odds ratio (OR) and its 95% confidence interval (CI) for the outcomes between the laryngoscopes were calculated.

Results:
A total of 1867 eligible patients were enrolled in this study. Of those patients, GVL was used for initial attempt in 180 (9.6%). Overall first-attempt success rate were 86.1% in GVL group and 80.9% in MAC group (
p
=0.090), but failure rate was significantly different between two groups (GVL vs. MAC; 7.2% vs. 14.9%,
p
=0.006) in crude analysis. Using PS matching, 177 patients were equally assigned to each group. The adjusted OR for the first-attempt success and failure rate in GVL group compared to MAC group was 1.37 (95% CI 0.76-2.45) and 0.46 (95% CI 0.23-0.93), respectively.

Conclusions:
The first-attempt success rates of intubation during CPR were not significantly different between GVL and MAC. However, intubation failure rate of GVL was lower than MAC.
Abstract 9410: A Simple and Accurate Algorithm for Localizing Accessory Pathways in Patients with Wolff-Parkinson-White Syndrome
Authors: Taguchi Noriko , Yoshida Naoki , Yamamoto Toshihiko , Miyata Sinjiro , Fujita Masaya , Yokoi Kenichiro , kyo Seifuku , Shimano Masayuki , Suzuki Tomomichi , Tsuji Yukiomi , Hirai Makoto , Inden Yasuya , Murohara Toyoaki
Published: April 2024

Introduction:
Delta wave morphology reflects the ventricular attachment site of accessory pathway (AP). Electrocardiographic R/S ratio and QRS polarity also depend on the AP location. Many algorithms for localizing APs are based on the delta wave morphology, R/S ratio, and QRS polarity. However, they are slightly complicated and it is sometimes difficult to determine the delta wave morphology accurately. In this study, we propose a new and simple algorithm for accurate localization of APs using only the R/S ratio.

Methods:
This study consisted of 101 patients with a single anterogradely conducting AP on a 12-lead ECG. R/S ratios in leads V1, V2 and aVF were analyzed. A new algorithm was developed by correlating the 12-lead ECG findings with successful ablation sites in the 40 initial consecutive patients. This algorithm was subsequently tested in the 61 residual consecutive patients. AP locations were divided into 5 regions based on fluoroscopical anatomy.

Results:
The new algorithm and the validation results were shown (figure). Among 61 patients, all 37 patients with left free wall APs showed the R/S ratio in lead V1 ≥ 0.5 (sensitivity 100%, specificity 100%). Left anterior and lateral APs were associated with the R/S ratio in lead aVF ≥ 1 (sensitivity 97%, specificity 100%). If the R/S ratio in lead V1 was < 0.5 and the R/S ratio in lead V2 was ≥ 0.5, the AP location was midseptal or posteroseptal (sensitivity 100%, specificity 94%). If the R/S ratio in both leads V1 and V2 was < 0.5, it was right free wall or right anteroseptal (sensitivity 89%, specificity 100%). Right anterior, lateral, and anteroseptal APs were associated with the R/S ratio in lead aVF ≥ 1 (sensitivity 98%, specificity 93%). Overall sensitivity of this method was 93% and specificity was 99%. The positive and negative predictive values were 96% and 98%, respectively.

Conclusions:
This novel algorithm using only the R/S ratio in leads V1, V2 and aVF provides a simple and accurate way to identify the AP localization.
Abstract 9618: Bilateral Cardiac Sympathetic Denervation for Acute Management of Refractory Ventricular Arrhythmias
Authors: Ajijola Olujimi A , Lellouche Nicholas , Bourke Tara , Tung Roderick , Mahajan Aman , Shivkumar Kalyanam
Published: April 2024

Background:
Left cardiac sympathetic denervation (LCSD) suppresses ventricular arrhythmias (VAs), and reduces the incidence of sudden cardiac death (SCD). The role of bilateral cardiac sympathetic denervation (BCSD) remains unknown. The purpose of this study was to report the effects of BCSD in a small patient cohort.

Methods:
We reviewed records of 6 patients (5 males, age 47-75 years, 66.7% non-ischemic cardiomyopathy) who underwent BCSD to treat severe VAs refractory to all other treatment modalities. Reversible causes of VAs were addressed in all patients. All patients were on beta-blocker therapy, and at least one antiarrhythmic drug. Five patients underwent catheter mapping with endocardial and/or epicardial ablation to control VAs (mean 2.2±0.5 ablations/patient). VAs persisted in 3 patients despite prior LCSD. Surgical BCSD was successfully performed in all patients (50% simultaneously, 50% right cardiac sympathetic denervation after prior unsuccessful LCSD).

Results:
After BCSD, mean ICD shocks and anti-tachycardia pacing episodes (ATPs) decreased from 13.3±5.2 shocks and 26.8±12.6 ATPs to 0 shocks or ATPs in 3 patients, and decreased by over 50% in one patient. External shocks decreased from 11 to 0 in another patient. One patient showed no response to BCSD. All patients who responded to BCSD survived to hospital discharge. No major complications occurred in all patients. In three patients were not pacemaker-dependent, no significant changes in heart rate, PR, QRS, and corrected QT interval were noted.

Conclusion:
To our knowledge, this is the first reported cohort of patients to undergo BCSD. In these patients with electrical storm refractory to standard therapies, bilateral cardiac sympathetic denervation was safe and effective in acutely suppressing VAs, and preventing SCD.
Abstract 9703: Factors of Atrial Fibrillation in Patients with History of Paroxysmal Supraventricular Tachycardia
Authors: Brembilla-Perrot Beátrice , Khachab Hadi , Aliot Etienne , Zinzius Pierre Yves , Sellal Jean Marc
Published: April 2024

Background:
Patients with history of paroxysmal supraventricular tachycardia (PSVT) have a higher risk of atrial fibrillation (AF) than patients without PSVT. The purpose of the study was to evaluate the incidence of AF in patients seen for PSVT and to look for the factors that could favour AF.

Population:
1187 patients, 458 males (39%), 729 females (61%), mean age was 50±19 years were studied between 1980 and 2010 for PSVT confirmed by electrophysiological study (EPS). Patients with anterograde conduction through an accessory pathway (AP) were excluded.

Methods:
History of spontaneous AF was noted. Clinical factors and electrophysiological factors were collected. Patients with AF (group I) and without AF (group II) were compared. PSVT ablation was performed in 648 patients. Mean follow-up was 4.48±4.9 years.

Results:
61 patients developed documented paroxysmal or permanent AF or atrial flutter (5%). They were older than patients without AF (59±13 vs 49±19 years, p< 0.0005), were more frequently men (59% vs 37%) (p<0.002), had more frequently prior AF (24.5% vs 0.5%)(< 0.00000) and associated heart disease (18% vs 5%) (p<0.004). There were no differences at EPS concerning the mechanism of re-entry: 13% of the group I patients and 18 % from the group II had a concealed AP (NS); 87 % of the group I patients and 82 % of the group II patients had typical or atypical AV nodal re-entrant tachycardia (NS). AF induction or occurrence during EPS was more frequent in group I patients (31%) than in group II patients (9%) (p<0.00000). Multivariate analysis showed age, male gender, prior AF, heart disease and atrial vulnerability during EPS were independent predictors of AF. 52.4% of the group I patients and 54.7% from the group II underwent a successful procedure of radiofrequency ablation after EPS. Univariate comparison between both groups suggests no effect of PSVT ablation on the incidence of AF.

Conclusions:
The incidence of AF was 5% in 1187 patients consecutively admitted for PSVT and electrophysiological study. The risk of AF was correlated with the classical factors of AF: male gender, age, prior AF and the presence of heart disease. AF induction was a risk factor of AF. There was no correlation between the mechanism of reentry and the risk of AF. PSVT ablation did not prevent AF.
Abstract 9748: Exercise Oscillatory Breathing and NT-pro-BNP Levels in Stable Heart Failure Provide the Strongest Prediction of Cardiac Outcome when Combining Biomarkers with Cardiopulmonary Exercise Testing
Authors: Guazzi Marco , Boracchi Patrizia , Vicenzi Marco , Arena Ross , Reina Giuseppe
Published: April 2024

Aims:
N-terminal-pro brian natiruretic peptide (NT-pro-BNP) and cardiopulmonary exercise testing (CPET)-derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine the prediction of cardiac-related events by performing a combined analysis of NT-pro-BNP with markers of ventilatory inefficiency during exercise.

Methods and Results:
260 patients with stable CHF underwent measurement of plasma NT-pro-BNP levels prior to, at peak exercise and 1 minute recovery phase during a CPET evaluation with determination of peak oxygen uptake (VO2), ventilation to CO2 production (VE/VCO2) slope and exercise periodic breathing (EPB). Blood samples were drawn for standard measurements and for hormonal determinations both at rest and at peak exercise.

Results:
After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis showed that, among the 6 variables of interest including plasma NT-pro-BNP at rest, at peak exercise and 1 minute recovery, peak VO2, VE/VCO2 slope and EPB. NT-pro-BNP was the strongest independent predictor of cardiac death with equivalent prognostic power and strong correlation among rest, peak exercise and 1 minute recovery. Thus, only NT-pro-BNP at rest was considered (Harrel C: 0.783; CI: 0.722-0.844) followed by VE/VCO2 slope (Harrel C: 0.720; CI: 0.646-0.794), EPB (Harrel C: 0.685; CI: 0.619-0.751), and peak VO2 (Harrel C: 0.618; CI: 0.533-0.704). At bivariate stepwise analysis, among various combinations, NT-pro-BNP at rest along with EPB emerged as the strongest prognostic one (Harrel C: 0.800; CI: 0.737-0.862) to estimate the two-years incidence of cardiac death.

Conclusions:
In the refinement for robust predictors of outcome in HF patients, high NT-pro-BNP levels together with EPB led to the most powerful definition. VE/VCO2 slope and peak VO2 did not provide any further prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.
Abstract 9754: Individual-Level Cardiovascular Health Behavior and Health Factor Changes (1999-2008), Projections to 2020, and Comparisons with AHA 2020 Impact Goal Targets in US Men and Women: Results from the National Health and Nutrition Examination Surveys (NHANES)
Authors: Huffman Mark D , Capewell Simon , Ning Hongyan , Ford Earl S , Lloyd-Jones Donald M
Published: April 2024

Introduction:
A higher number of ideal health behaviors and health factors is associated with a substantial reduction in CV event rates. The AHA 2020 Impact Goals target a 20% relative improvement in overall cardiovascular (CV) health using 4 health behaviors (smoking, body mass index [BMI], physical activity, diet) and 3 health factors (cholesterol, blood pressure, plasma glucose). To date, there have been no studies to estimate future trends in individual-level CV health behavior/factor levels.

Methods:
We used data on CVD-free individuals from NHANES 2-year cycles (1999-2000, 2001-2, 2003-4, 2005-6, 2007-8) to estimate the number of poor, intermediate, and ideal health behaviors/factors per individual for men and women. We created a composite, individual-level CV health score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total scale: 0-14 points) and performed age-adjusted weighted linear regression models to produce

β

coefficients and forward projections to 2020. We compared these forward projections based on current trends with a 20% relative increase (based on the AHA Goal) in the composite CV health score from 2006 to 2020.

Results:
The mean number of ideal health behaviors/factors within individual men and women has not significantly changed from 1999 to 2008 (Table 1). The mean CV health score in men increased from 7.5 (1999-2000) to 7.7 (2007-8), but the test for trend was not significant (
β
= 0.01, p=0.67); the mean CV health score was higher in women (7.9 in 1999-2000; 8.1 in 2007-8), but the test for trend was also not significant (
β
= 0.02, p=0.06). Assuming current trends continue, CV health score projections to 2020 for men (7.7 [95% CI 5.9, 9.5]) and women (8.3 [95% CI 8.0, 8.6]) would not achieve a 20% overall change in the composite score (men: 8.8; women: 9.6).

Conclusions:
These data suggest that the AHA 2020 Impact Goals to improve CV health by 20% will not be met for individuals if current health behavior/factor trends continue.