bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8808: Early Repolarization Syndrome: Valsalva Maneuver in Familial Screening
Authors: Gourraud Jean Baptiste , Le Scouarnec Solena , Sacher Frederic , Chatel Stephanie , Chavernac Pascal , Mabo Philippe , Redon Richard , Schott Jean Jacques , Lemarec Herve , Haissaguerre Michel , Probst Vincent
Published: April 2024

Introduction:
Early repolarization (ER) has been recently linked with idiopathic ventricular fibrillation. In spite of a frequent familial past history of SCD, ER identification in relatives is limited by variability of the ER over the time and with the variation of autonomic tone and heart rate. The aim of the study was to test the ability of valsalva maneuver (VM) to identify larges families affected by early repolarization syndrome (ERS).

Methods:
We have screened relatives of 2 families in which SCD occurred with ERS. Patients were considered to be affected in the presence of a positive deflection on the S wave in two consecutive leads and at least a 1 mm amplitude above baseline. A VM was performed in relatives to increase or reveal ER. Comparison between heart rate and J wave amplitude before and after VM was performed with a paired Student's t-test.

Results:
In the first family, 4 SCD occured whose one with an ER pattern. We identified 25 other ER out of 82 available ECG (prevalence 34%). In the second family, 4 SCD occurred whose one with an ER pattern. We identified 17 other ER out of 29 available ECG (prevalence 58%). In those families, ER is transmitted with an autosomal dominant trait through respectively 5 and 4 generations. VM was performed for 80 relatives. It increased ER amplitude in 17/20 (85%) affected patients and revealed ER in 17/60 (28%) patients unaffected at rest. VM succeeded in unmasking pattern for 5/11 (45%) expected carrier of ER previously considered as unaffected. Heart rate at rest was 75 ± 13 bpm and decreased of 3,9 ± 7,9 bpm (p<0,001) during the test without any differences between groups.

Conclusion:
Malignant forms of ER can be transmitted as an autosomal dominant trait in large families. VM could be helpful to unmask ER for familial screening of relatives. Further investigations are required to assess prognosis of VM.
Abstract 8812: Direct Renin Inhibitor Ameliorates Insulin Resistance by Improving Insulin Signaling in the Skeletal Muscle in Experimental Post-Infarct Heart Failure
Authors: Fukushima Arata , Kinugawa Shintaro , Yokota Takashi , Mochamad Sobrin A , Takahashi Masashige , Homma Tsuneaki , Suga Tadashi , Takada Shingo , Masaki Yoshihiro , Kadoguchi Tomoyasu , Okita Kouichi , Tsutsui Hiroyuki
Published: April 2024

Background
Insulin resistance has been shown to occur as a consequence of heart failure (HF). The activation of renin-angiotensin system may play an important role in this phenomenon. We thus investigated the effects of direct renin inhibitor, aliskiren, on the insulin resistance and the insulin signaling in the skeletal muscle from experimental HF after myocardial infarction (MI).

Methods
MI was created in male C57BL/6J mice by ligating the left coronary artery, and sham operation was also performed. Mice were divided into 4 groups; sham-operated (sham, n=10), sham treated with aliskiren (10mg/kg/day, n=10), MI (n=10), and MI treated with aliskiren (MI+Ali, n=10). After 4 weeks, echocardiographic and hemodynamic measurements were performed. Plasma glucose levels after intraperitoneal glucose or insulin load were measured. Proteins regulating insulin signaling were measured in the lower extremity skeletal muscle tissues by Western blot analysis. The lucigenin chemiluminescence elicited by •O
2
-
and NAD(P)H oxidase activities were also measured in the skeletal muscle.

Results
Heart rate and aortic blood pressure were not affected by aliskiren in either group. MI mice showed left ventricular (LV) dilatation, dysfunction and an increase in LV end-diastolic pressure, which were not affected by aliskiren. Infarct size was comparable between MI and MI+Ali. Plasma glucose levels at baseline and after glucose load did not differ among groups. However, the decrease in plasma glucose after insulin load was smaller in MI than sham (14±5 vs. 36±2 %, p<0.05), and was significantly ameliorated in MI+Ali (34±5 %, p<0.05). Insulin-stimulated serine-phosphorylation of Akt and the translocation of glucose transporter-4 from cytosol to membrane were decreased in MI by 57 and 69 % of sham, respectively, Aliskiren significantly ameliorated them by 86 and 93 % of sham, respectively. Moreover, •O
2
-
production and NAD(P)H oxidase activities were increased in MI and this increase was also inhibited in MI+Ali. Such effects of aliskiren were not observed in sham mice.

Conclusions
Aliskiren ameliorated insulin resistance associated with HF by improving insulin signaling, at least in part, via the inhibition of NAD(P)H oxidase-induced •O
2
-
production in the skeletal muscle.
Abstract 8824: Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients
Authors: Chen Fabian , Maccubbin Darbie , Weimer Anderson Jennifer , McCrary Sisk Christine , Kher Uma , Olsson Anders , Bays Harold E
Published: April 2024

Extended-release niacin (ERN) produces improvements across the lipid profile in patients with dyslipidemia, but is underutilized due to flushing, a process primarily mediated by prostaglandin D
2
(PGD
2
). The PGD
2
receptor antagonist, laropiprant (LRPT), reduces ERN-induced flushing in patients with dyslipidemia. This study tested the hypothesis that, after 20 weeks of the fixed-dose combination ERN/LRPT, patients who continued on ERN/LRPT would have less flushing than patients who had LRPT withdrawn, but continued on ERN alone. After a 2-week placebo run-in, 1152 patients with dyslipidemia were randomized 2:2:1 to one of three daily treatment groups: (1) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg for the remainder of the study; (2) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg from 5 to 20 weeks, then ERN 2g without laropiprant from 21 to 32 weeks; or (3) placebo for the duration of the study. The key endpoints were based on the Global Flushing Severity Score (GFSS) from the previously validated Flushing Symptom Questionnaire: the number of days/week with moderate or greater GFSS ≥4 (primary) and the percentage of patients with maximum GFSS ≥4 (secondary) during the post-withdrawal period of the study (weeks 21 to 32). ERN/LRPT produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p<0.001; see fig) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%). There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups. In summary, following 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less flushing than patients who had LRPT withdrawn, and continued with ERN alone. This study supports the long-term efficacy (> 24 weeks) of ERN/LRPT in reducing flushing symptoms.
Abstract 8891: Serum 25-Hydroxyvitamin D3 Level is Correlated with Cardiometabolic Risk But Not Increased Carotid Artery Intima-Media Thickness in High-Risk Children
Authors: Cheraghi Nikoo , Dai Hongying , Raghuveer Geetha
Published: April 2024

Background:
Some literature supports a link between cardiometabolic risk and vitamin D deficiency among adolescents. Currently, there are no studies examining the effects of vitamin D deficiency on the vasculature in high-risk children.

Purpose:
To determine whether there is a correlation between vitamin D levels, cardiometabolic risk, and carotid artery intima-media thickness (CIMT), a marker of subclinical atherosclerosis, among high-risk children.

Methods:
Serum 25-hydroxyvitamin D3 levels were compared to CIMT in 74 high-risk children with multiple modifiable atherosclerosis-promoting risk factors. Vitamin D was categorized into three levels (Insufficient < 20 ngm/mL, Borderline 20 to 30 ngm/mL, and Sufficient > 30 ngm/mL). Modifiable atherosclerosis-promoting risk factors that were included were BMI Z score, Systolic blood pressure (SBP), Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL C), Insulin, & Tobacco smoke exposure history.

Results:
Age was 13.7 ± 3.1 years (6-22 years); 45 % Male; 62% White. Vitamin D was 23.1 ± 9.4 ngm/mL (range 6-63 ngm/ml). Vitamin D levels were Insufficient in 20%, Borderline in 57% and Sufficient in 23%. BMI Z score 1.4 ± 1.1, SBP 117 ± 10 mmHg, TC 215 ± 45 mg/dL, TG 195 ± 302 mg/dL, HDL C 46 ± 60, Insulin 17 ± 22 uIU/mL, Tobacco smoke exposure history 30%. Mean modifiable atherosclerosis promoting risk factor score was 3.3 ± 1.6. CIMT mean was 0.48 ± 0.04 mm; CIMT maximum was 0.54 ± 0.06 mm. There was an inverse correlation between vitamin D levels and risk factor score
(Figure)
. Multivariative analysis adjusting for risk factor score did not confirm any association between vitamin D and mean (p= 0.23) or maximum (p= 0.40) CIMT.

Conclusion:
Among high-risk children, vitamin D levels are inversely correlated to cardiometabolic risk but there was no association with CIMT.
Abstract 8898: Gender Difference in Right Ventricular Diastolic Function in Normal Subjects
Authors: Otsuka Takenori , Suzuki Makoto , Yoshikawa Hisao , Hashimoto Gou , Ishikawa Youko , Ishida Takako , Osaki Tsukasa , Itou Naoshi , Ono Tsuyoshi , Yamamoto Masato , Nakamura Masato , Sugi Kaoru
Published: April 2024

Background:
Normative Doppler values and determinants for gender difference of right ventricular diastolic function in healthy subjects have not been fully elucidated. The purpose of this study is to verify the difference of right ventricular diastolic function between men and women at each age.

Method:
One hundred sixty nine male and 221 female in healthy subject, aged 20 to 90, were examined by both tricuspid inflow velocity and tricuspid annulus velocity by tissue Doppler imaging. All subjects were divided into 7 groups as 20s, 30s, 40s, 50s, 60s,70s, 80s depend on their age.

Results
:The tricuspid E velocity was significantly decreased with age(p<0.0001). But E velocitywas no differences significantly in all generation between men and women. The tricuspid A velocity was significantly increased with age(p<0.0001). But A velocity was no differences significantly in all generation between men and women (Table). Ratio of tricuspid E and A velocity (E/A) was significantly decreased with age.But no differences were observed in ratio of E/A in all generation between men and women. (20s: 2.0±0.6 vs 2.5±0.6 p=0.03,30s: 1.9±0.5 vs 2.1±0.5 p=NS, 40s: 1.6±0.4 vs 1.9±0.5 p=NS, 50s: 1.3±0.3 vs 1.5±0.4p=NS, 60s: 1.2±0.2 vs 1.2±0.3 p=NS, 70s: 1.1±0.3 vs 1.1±0.3 p=NS, 80s: 1.2±0.3vs 1.2±0.3 p=NS, total: 1.4±0.5 vs 1.5±0.6 p=NS). Early diastole velocity of tricuspid annulus (Ea) by tissue Doppler method was significantly decreased with age (p<0.0001). But Ea was no differences significantly in all generation between men and women (Table).

Conclusions:
Our results provide the normative Doppler values of right ventricular diastolic function for age decades. The assessment of right ventricular diastolic function obtained from Doppler method should be considered their age. There was no differences significantly of right ventricular diastolic function between men and women.
Abstract 89: Penn State Hershey: 4-Year Experience in Mild Therapeutic Hypothermia Program---Lessons Learned
Authors: Ettinger Steven M , Blosser Sandralee , Terndrup Thomas , Reichwein Raymond , Sarfield Erin , Bressler Sonya , Burkholder Jill , Lazar Michael , Stephenson Edward , LaCoe Christopher L , Wengert Patti A
Published: April 2024

Introduction:
Mild Therapeutic Hypothermia (MTH) improves neurological outcomes in patients (pts) following sudden cardiac arrest with return of spontaneous circulation (SCA-ROSC). The Penn State Hershey Medical Center assembled a multispecialty team and formalized a MTH program in October 2007. Indications were expanded to include pts presenting with cerebrovascular trauma (CVT) and stroke in addition to SCA-ROSC.

Methods:
A multidisciplinary team of nurses and physicians (Emergency Medicine, Interventional Cardiology and Neurology) along with EMS (Life Lion) reviewed the scientific literature and created educational programs that were provided to the critical care units in the hospital. An electronic order set was created to standardize protocol. Life Lion provided education to Emergency Medicine programs at regional hospitals.

Results:
From October 1, 2007-March 29, 2011, 149 pts were enrolled in the MTH program (97 men, mean age 61.4 yr; 52 women, mean age 58.0 yr). 100 pts were enrolled for SCA; 1 pt enrolled following ICD failure; 5 pts enrolled post-CABG (cooling with ECMO); and 43 pts were enrolled following CVT/stroke. SCA-ROSC ranged from 5-45 min. Cardiac rhythm at the time of first medical contact (FMC) was as follows: VFib/VT:58 pts; asystole/PEA:42 pts; NSR:49 pts. Time to cooling (target 33°C) ranged from 2.5 - 10 hours with 3 pts receiving pre-hospital cooling. 64 pts (43%) survived to hospital discharge. 85 pts died (57%). Pittsburgh cerebral-performance category (CPC) level I-II was observed in 54.7% (n=35); CPC Level III-V was observed in 35.9% (n=23). 21 pts were discharged to a rehab facility. Of pts with FMC rhythm VFib/VT (n=56) there were 26 deaths (survival rate 53.6%). Of pts with FMC rhythm Asystole/PEA (n=39) there were 31 deaths (survival rate 20.5%).

Conclusion:
The MTH program was successfully implemented at our institution in pts presenting with SCA-ROSC and CVT/stroke. Pts with FMC cardiac rhythm of VFib/VT demonstrated better survival and neurological outcomes with MTH as compared to pts with FMC cardiac rhythm of asystole/PEA. Elements that have contributed to the success of our program include: a multidisciplinary approach; nursing leadership with an educational focus; and standardization of medical order sets.
Abstract 8915: Utility of Transmural Myocardial Strain Profile to Predict Early Left Ventricular Dysfunction in Patients with Duchenne Muscular Dystrophy
Authors: Yamamoto Tetsushi , Tanaka Hidekazu , Imanishi Takamitsu , Hayashi Nobuhide , Takeshima Yasuhiro , Kawai Hiroya , Kawano Seiji , Hirata Ken-ichi
Published: April 2024

Background:
Myocardial damage in Duchenne muscular dystrophy (DMD) leads to lethal outcome. Therefore, early detection of myocardial changes in DMD is important because earlier treatment might help to prevent the development of myocardial fibrosis. Transmural myocardial strain distribution can be obtained as a form of transmural strain profile using myocardial tissue Doppler strain imaging. Accordingly, the aim of this study was to test the hypothesis that transmural strain profile (TMSP) analysis can predict future left ventricular (LV) dysfunction in DMD patients with preserved ejection fraction (EF).

Methods:
We studied 57 consecutive DMD patients who did not have LV wall motion abnormality; EF 60±7% (all ≥ 55%), aged 11±3 years. Echocardiography was performed at baseline and 1-year follow-up. TMSP was evaluated in the posterior wall from mid-LV short-axis view (Aplio-XG Toshiba Corp.).

Results:
Thirty-seven patients (65%) had normal TMSP pattern (Group 1), and the remaining 20 patients (35%) were classified as TMSP with a notch (Group 2). The peak strain value in the posterior wall and EF were similar between two groups. Of 20 patients in Group 2, 8 patients (40%) had wall motion abnormality in the posterior wall at 1-year follow-up. On the other hand, no patient in Group 1 had wall motion abnormality at 1-year follow-up (p<0.001 vs. Group 2).

Conclusions:
Subclinical LV dysfunction can be detected with TMSP in DMD patients who do not have wall motion abnormalities by conventional echocardiography. TMSP with notch was useful at evaluating early subtle changes in DMD patients, and may be useful for predicting future LV dysfunction.
Abstract 8920: Iron Deficiency is an Ominous Predictor of Mortality in Stable Heart Failure Patients in the Community
Authors: Ghosh Sudip , Zhang Chuan , Smith Jude , Dexter Jonathan , Carroll-Hawkins Collette , OKelly Noel I
Published: April 2024

Background:
Iron deficiency (ID) has been shown to be linked with multi-faceted clinical consequences in patients with heart failure (HF) enrolled in clinical trials. The predictive value of ID has not been evaluated in ambulatory left ventricular systolic dysfunction (LVSD) patients in the community.

METHODS AND RESULTS:
We evaluated 512 patients (10.4%) with stable LVSD under the care of a regional nurse-led community heart failure team between June 2007 - November 2009. 92% of patients were on loop diuretics; 83% on ACE Inhibitors, 92% on β-blockers and 48% on aldosterone antagonists. Mean age of the patients was 77.9 ± 4.1 years, 43% were females and mean NYHA class was 2.2 ± 0.7. Absolute Iron deficiency was defined as ferritin <100 µg/L and functional anemia as hemoglobin (Hb) between 9-12g/dl. Mean Hb levels were 14.1± 0.7; 13.9 ± 0.3; 14.0 ± 0.6 and 13.7± 0.2 g/dL at 0, 6, 12 and 24 months. Mean serum ferritin levels in the entire study population were 212 ± 14.9 µg/L at the start and 197 ± 13.8 µg/L at the end. The prevalence of ID and anemia was 21.3 ± 2 % (+95% CI) and 9.4 ± 1.3% respectively at the start of the study. These figures were 21.5±2.1% (ID) and 8.4± 1.7 % (anemia) at the end of the study. 2-year survival was 88% in the entire population; 83% in the anemic group (p=NS) and 76% in ID patients (p<0.001). Risk-adjusted hazard ratios for 24 month mortality were 1.42 (1.09-1.98) and 1.05 (0.87-1.51) for ID and anemic patients respectively.

CONCLUSIONS:
ID is common in ambulatory HF patients in the community and is associated with worse clinical outcomes. It is also a stronger independent predictor for mortality than anemia in stable LVSD patients.
Abstract 8926: Rosiglitazone Acutely Improves Flow Mediated Dilation and Favorably Alters Endothelial Microparticle and Progenitor Cell Numbers in Euglycemic, Senescent Monkeys
Authors: Sokolowski Sharon A , Huang Chunli , Schroeder Richard L , Smith Andrew H , Beebe David A , Wang Miao , Knight Delvin R
Published: April 2024

Background:
Rosiglitazone, 6 hours after dosing, rapidly increases endothelial-dependent flow mediated dilation (FMD) in subjects with healthy endothelium. Whether this acute improvement in FMD occurs in the presence of endothelial dysfunction is unknown. We test the hypothesis that rosiglitazone acutely improves FMD in senescent monkeys with endothelial dysfunction and that the improvement coincides with favorable changes in circulating biomarkers of endothelial health, endothelial progenitor cells (EPC) and endothelial microparticles (EMP). Euglycemic monkeys were used to avoid rosiglitazone’s glucose-lowering effects.

Methods and Results:
In a crossover design, 6 fasted
M. fascicularis
monkeys (5M/1F; 17 ± 1 yr) were dosed ≥2 weeks apart with vehicle or rosiglitazone at a dose (1 mg/kg, PO) that did not affect baseline hemodynamics, fasting plasma glucose (65 ± 6 mg/dL), insulin (10 ± 3 µlU/mL), total cholesterol (79 ± 7 mg/dL) or triglycerides (59 ± 6 mg/dL). EPC and EMP were sampled 6 h after dosing and measured by flow cytometry. Monkeys were then sedated (midazolam + torbugesic) and baseline femoral artery diameter (4mm segment) measured by ultrasonography. FMD was calculated as the peak %change from baseline following a 5-minute cessation of blood flow below the knee. FMD was lower in these monkeys (17.6 ± 1.3%) vs. young adults (≥25%). Rosiglitazone (vs. vehicle) increased (p<0.01) FMD to 21.3 ± 1.6% (vs.16.9 ± 1.4%) without affecting baseline diameter (1.52 ± 0.04 vs.1.51 ± 0.04 mm). Rosiglitazone (vs. vehicle) increased (p<0.01) EPC [CD45- CD31+ CD34+ VEGFR2+] to 7116 ± 1296 (vs. 4786 ± 1102) cells/ml and decreased (p<0.04) EMP [CD45- CD42a- CD54(ICAM-1)+] to 26669 ± 11112 (vs. 62245 ± 9772) EMP/ml; EMP [CD45- CD42a- CD105(endoglin)+] and EMP [CD45- CD42a- CD144(VE-cadherin)+] also trended lower. (Mean ± SEM; paired t-test).

Conclusion:
Rosiglitazone acutely improves the endothelial dysfunction in senescent monkeys. This increased FMD is independent of its metabolic effects on glucose and lipids and coincides with stimulation of EPC and with suppression of EMP linked to endothelial cell adhesion and potentially apoptosis. Whether these EPC and EMP changes directly contribute to the enhanced endothelial function warrants further study.
Abstract 8952: Results of the Pediatric Lead Extractability and Survival Evaluation (PLEASE) Study
Authors: Berul Charles I , Freedenberg Vicki , Atallah Joseph , Balaji Seshadri , Bar-Cohen Yaniv , Batra Anjan S , Cannon Bryan C , Ceresnak Scott , Chun Terrence U , Cohen Mitchell I , Collins Kathryn K , Dubin Anne M , Erickson Christopher C , Franklin Wayne H , Kertesz Naomi J , LaPage Martin J , Law Ian H , Moak Jeffrey P , Papagiannis John , Paul Thomas , Tanel Ronn E , Tisma-Dupanovic Svetlana , Wilkoff Bruce L , Zimmerman Frank , Cecchin Frank
Published: April 2024

Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease (CHD) patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. Manufacturers developed distinct strategies for this issue: thinner lead bodies or a Gore ePTFE coil coating. Both design changes were thought to improve ease of lead removal, but have not been directly compared in children or adults. The purpose of this study was to assess thin and ePTFE-coated ICD lead survival in pediatric and CHD pts.

Methods:
The Pediatric Lead Extractability and Survival Evaluation (PLEASE) Study began as a Phase IV multicenter open-label prospective study [
NCT00335036
], facilitated by the Pediatric & Congenital EP Society. Initially designed as a randomized study, it changed to a parallel assignment registry when 1 lead had an advisory due to high incidence of failure, prompting concern about continued clinical equipoise. Pediatric and CHD pts who underwent ICD lead implant from 2005-2010 were eligible. The end date was NCDR ICD Registry v2.0 release (includes pediatric & lead data). 23 centers participated; each site obtained IRB approval. De-identified data was sent to the PI center for verification and statistical analyses.

Results:
A total of 982 ICD pts (357 VVI, 558 DDD, 67 CRT-D) entered the PLEASE study, incl. 423 pts (43%) with CHD. Mean age at implant = 18.3 ± 9.9 yrs. Thin (< 7Fr) ICD leads accounted for 51%, 23% were ePTFE-coated, 26% neither thin nor coated. There were 113 ICD lead failures (11.5%) at a mean lead-age of 2.2 ± 1.7 yrs, causing shocks in 55 pts. Failure occurred in 21% of thin leads vs 3.5% of ePTFE leads (p<0.01). Extraction was performed on 142 (14.5%) leads overall; 21% of thin leads (incl. extraction of 29 functioning leads due to recall) vs. 4.4% of ePTFE leads (p<0.01). There were 7 major extraction complications (4.9%), but no procedural mortality. Among thin leads, 90/270 (33.3%) of recalled leads failed vs 15/229 (6.6%) non-recalled thin leads.

Conclusions:
This Phase IV study demonstrates that ICD leads in children and CHD pts have suboptimal performance overall. Thinner leads were much more likely to fail and/or be extracted compared with ePTFE leads, chiefly driven by one lead type.
Abstract 8961: Essential Role of Caveolin-3 in Adiponectin Signalsome Formation and Adiponectin Cardioprotection
Authors: Wang Yajing , Gao Erhe , Wang Xiaoliang , Jasmin Jean-Francois , Lau Wayne Bond , Li Rong , Yuan Yuexing , Yi Wei , Chuprun Kurt , Lisanti Michael P , Koch Walter J , Ma Xin-Liang
Published: April 2024

Adiponectin (APN) is an adipocyte-derived cardioprotective molecule, and systemic APN malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. Although several APN receptors and multiple cytosolic effector molecules have been identified, signaling mechanisms linking receptors with effectors remain largely undefined. Caveolin (Cav) interacts with multiple membrane/intracellular proteins and regulates transmembrane signaling. However, the role of Cav in APN signaling remains unknown. Our current study determined the role of Cav3 (the predominant Cav form in cardiomyocytes) in APN signaling and investigated the underlying molecular mechanisms. Compared to wild type (WT), Cav-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery, P<0.05). Most importantly, the cardioprotective effects of APN observed in WT were either markedly reduced (P<0.01) or completely lost in Cav-3KO, although key APN signaling molecules, including APN receptors (AdipoRs), APPL1, and AMPK were normal in these animals. Molecular/cellular experiments revealed that AdipoR1 co-localizes with Cav-3, forming AdipoR1/Cav-3 complex via specific Cav-3 scaffolding domain binding motifs. AdipoR1/Cav-3 interaction is required for both APN-initiated AMPK-dependent and AMPK-independent intracellular cardioprotective signaling. Moreover, APPL1 and adenylate cyclase (AC), two immediately downstream molecules respectively requisite for AMPK-dependent and AMPK-independent signaling, form a protein complex with AdipoR1 in Cav-3 dependent fashion. Finally, in contrast to APN (which failed to cardioprotect in Cav-3KO mice), AICAR (an AMPK activator) and db-cAMP (a PKA activator) co-administration significantly reduced myocardial infarct size and improved cardiac function in Cav-3KO animals. These results demonstrated for the first time that Cav-3 is an essential molecule in the formation of a membrane-situated signalsome for APN transmembrane signaling. Pathological alteration in APN signalsome formation may impair APN transmembrane signaling and contribute to systemic APN malfunction.
Abstract 8978: NADPH Oxidase Inhibition Improves Cardiac Dysfunction Through Cardiac Mast Cell Stabilization and Suppression of the Renin-Angiotensin System
Authors: Matsumoto Takehiro , Wada Atsuyuki , Ohnishi Masato , Fujii Masanori , Yamamoto Takashi , Dohke Tomohiro , Takayama Tomoyuki , Tsutamoto Takayoshi , Horie Minoru
Published: April 2024

Reactive oxygen species (ROS) participate in the pathogenesis of cardiac inflammation and the activation of the renin-angiotensin (RA) system in the progression of heart failure (HF). NADPH oxidase is one of the major sources of the ROS production. Mast cells migrated into the failing heart mainly recruited by the locally produced chemokine, stem cell factor, and are involved in the inflammatory process since they generate various substances such as not only chymase which is an ACE independent angiotensin-II formation enzyme but also tumor necrotic factor (TNF)-alpha and transforming growth factor (TGF)-beta in HF. However, It has not been well documented whether NADPH oxidase inhibition affects cardiac inflammatory changes via mast cells and the RA system in HF. Thus, we evaluated the long-term effects of a specific NADPH oxidase inhibitor; apocynin (15mg/kg/day; n=6) on changes in cardiac function and the expression of several inflammatory related genes in dogs with tachycardia induced HF. Cardiac contractile function markedly deteriorated and left ventricular (LV) end-diastolic pressure (EDP) was increased after the induction of HF. However, apocynin significantly improved the ejection fraction and decreased the elevated LVEDP. The inhibitor significantly decreased the enhanced superoxide production (vehicle 78 vs. apocynin 40RLU/min/mg, p<0.05) and NADPH oxidase activity (vehicle 3300 vs. apocynin 1400RLU/min/mg, p<0.05) in the LV assessed by lucigenin-enhanced chemiluminescence compared with the vehicle. Cardiac ACE and NADPH oxidase subunits, gp91phox and p47phox, gene expressions significantly upregurated in HF, however, apocynine attenuated those gene activation. Moreover, apocynine decreased the number of the infiltrated mast cells and suppressed the mRNA of stem cell factor, chymase, TGF-beta, TNF-alpha in the failing heart. In conclusion, specific NADPH oxidase inhibition may become an important strategy in the treatment of cardiac dysfunction via mast cell stabilization and the suppression of RA system.
Abstract 8990: Bivalvular Transcatheter Treatment of Patients with Concomitant Aortic Stenosis and Mitral Regurgitation
Authors: Baldus Stephan , Treede Hendrik , Franzen Olaf , Rudolph Volker , Schirmer Johannes , Knap Malgorzata , Schlüter Michael , Reichenspurner Hermann , Blankenberg Stefan
Published: April 2024

Transcatheter techniques to treat severe aortic stenosis (AS) or significant mitral regurgitation (MR) in patients deemed at high surgical risk have shown to be safe and efficacious in either clinical entity. For AS, transcatheter aortic valve replacement (TAVR) using the Sapien/Sapien XT prosthesis (Edwards Lifesciences) via transfemoral (TF) or transapical (TA) access or the CoreValve prosthesis (Medtronic) via TF access has become a viable therapeutic option, whereas in MR, considerable clinical experience has been gained with transvenous/transseptal implantation of the MitraClip (MC) device (Abbott Vascular). To date, little information is available on transcatheter treatment for both AS and MR in the same patient. By May 2011, 263 TAVR and 233 MC procedures had been performed at our center. Eleven patients (78 ± 6 years, 9 men [82%]) underwent both TAVR and MC implantation. In the first 8 patients treated, TAVR (5 TA, 3 TF) preceded MC by a median of 84 (range, 4 to 348) days, whereas in the last 3 patients TAVR (1 TA, 2 TF) and, subsequently, MC were performed in a single session. All TAVR procedures (7 Sapien [n=4]/Sapien XT [n=3], 4 CoreValve prostheses) were successfully completed, resulting acutely in a significant increase in effective orifice area from 0.90 ± 0.12 to 1.82 ± 0.58 cm
2
(
P
= 0.0114) and a significant decrease in mean transaortic pressure gradient from 22 ± 10 to 7 ± 2 mmHg (
P
= 0.0077). MC implantation (1 clip, n=8; 2 clips, n=2; 3 clips, n=1) succeeded in reducing MR severity to <=2+ in 10 patients (MR 1+, n=5; MR 2+, n=5); in 1 patient, MR severity remained at 3+ despite placement of 2 clips. Permanent pacemaker implantation was required in 5 patients (4 Sapien/Sapien XT, 1 CoreValve); 1 patient sustained a stroke 19 days after bivalvular treatment in a single session. Post TAVR, no patient had transvalvular aortic regurgitation (AR); minor (grade 1) paravalvular AR was present at discharge in 8 patients. Patients were followed for a median of 210 (range, 69 to 398) days. Two patients (18%; 95% CI, 2% to 52%) died of persistent cardiac decompensation at 73 and 398 days after successful bivalvular treatment. We conclude that bivalvular transcatheter treatment of concomitant AS and MR is feasible, efficacious and safe, even if performed in a single session.
Abstract 9011: Randomized Study of Endovascular versus Epicardial Lead Placement for Resynchronization Therapy (REVERT)
Authors: Steinberg Jonathan S , Garikipati Naga V , Chaudhry Farooq , Paruchuri Praveena , Adhaduk Mehul , Upadhyay Khushbu , Nutheti Mohan , Kamath Ganesh , Joshi Rajeev , Argulian Edgar , DeRose Joseph J , Balaram Sandhya , Swistel Daniel , Mittal Suneet
Published: April 2024

Introduction:
Cardiac resynchronization therapy (CRT) is used to treat heart failure (HF) with prolonged QRS, with the LV lead typically placed transvenously (TV). Because CRT benefit correlates with concordant placement of the LV lead at the site of latest contraction, we hypothesized that epicardial (EPI) lead placement using a (robotic) surgical approach would afford more consistent access to the optimal site and result in improved clinical outcomes. The REVERT trial is the first prospective randomized clinical trial comparing EPI to TV lead placement for CRT.

Methods:
Twenty six pts (67.7 ± 8.7 yrs; EF 21.8 ± 8.2 %; QRS 159.5 ± 14 ms) with NYHA class III/IV HF were randomized to an EPI (n=12) or TV (n=14) LV lead implantation guided by preoperative echo dyssynchrony studies. Pts in both groups had similar baseline characteristics.

Results:
Compared to TV pts, EPI pts were slightly more likely to have LV lead placed concordantly (91% vs 71%, p= 0.34). However, the primary endpoint of LV end systolic volume index at 12 mos improved similarly in each group (Figure). There was also no difference in 2° endpoints at 12 mos (Table).

Conclusions:
In this randomized trial of primary CRT implantation, EPI LV lead placement, despite high concordancy, did not result in improved clinical outcomes vs TV lead placement.
Abstract 9012: Comparison of Clinic and Ambulatory Blood Pressure Variability as Predictors for Cardiovascular Events in Patients with Hypertension
Authors: Eguchi Kazuo , Hoshide Satoshi , Shimada Kazuyuki , Kario Kazuomi
Published: April 2024

Background:
Clinic blood pressure variability (BPV) has been shown to be a prognostic indicator in hypertensive patients. However, it is not known if clinic BPV is superior to ambulatory blood pressure (ABP) variability in predicting cardiovascular disease (CVD).

Methods:
We performed ABP monitoring in 457 hypertensives. The clinic BP readings during follow up were picked up from the medical records, and calculated as the means or standard deviations (SDs). The mean age of the subjects was 67.0 ± 9.2 years, and they were followed for 66 ± 27 months. Stroke, myocardial infarction, and sudden cardiac death were defined as
Hard
CVD events, and these plus angina, heart failure, and other CVD were defined as
All
CVD events. Cox regression analyses were performed with adjustment for significant covariates.

Results:
As shown in the
Figures
, increased clinic BPV was associated with All CVD events, while increased sleep BPV was associated with Hard CVD events. In multivariable analyses, SD in clinic BP was an independent predictor for All CVD events (P=0.008), even when the SD in awake SBP or sleep SBP was entered in the same model. On the other hand, SD in sleep SBP (P=0.04), but not SD in awake SBP (P=0.23), was an independent predictor for Hard CVD events when they were entered with SD in clinic SBP (P=0.20) in the same model. With regard to mean BP, both ambulatory and clinic mean SBP predicted All CVD events, but the predictability of mean awake SBP (P=0.02) and mean sleep SBP (P=0.008) were better than that of mean clinic SBP (P=0.11 and 0.09, respectively).

Conclusions:
Clinic BPV was better than ambulatory BPV in predicting All cardiovascular events including angina and heart failure, but ambulatory BPV was better in the case of Hard outcomes. These findings suggest that each BPV measure can be separately used for the prediction of cardiovascular outcomes.
Abstract 9065: Dose-Dependent Rescue Effects by a Desensitizing TnI Molecule in a RCM Mouse Model
Authors: Jean-Charles Pierre-Yves , Li Yuejin , Nan Changlong , Chen Guozhen , Feng Han-Zhong , Jin Jian-Ping , Huang Xupei
Published: April 2024

We have previously demonstrated that the R193H mutation of cardiac troponin I (cTnI) caused restrictive cardiomyopathy (RCM) and early death in transgenic mice (Du et al., 2006). RCM mutants are also characterized by increased myofilament Ca
2+
sensitivity and impaired cardiac relaxation (Gomes et al., 2005; Du et al., 2008). Restrictive cleavage of the N-terminal extension of cTnI has been shown to desensitize myofilament to Ca
2+
and enhance diastolic function in transgenic mice (Yu et al., 2001; Feng et al., 2008; McConnell et al., 2009). N-terminal truncated cTnI (cTnI-ND) also had the ability to correct the diastolic dysfunction and increase the lifespan of RCM mice expressing the cTnI R193H mutant in a wild type cTnI null background (Li et al, 2010). In the present study, we produced double transgenic mice (Double-TG) expressing different levels of mutant cTnI R193H and cTnI-ND to investigate the dose-dependent rescue effect of cTnI-ND and determine the mechanisms behind its protective role in young and aged RCM mice. In 2-month-old Double-TG mice, the rescue of these animals is secondary to the desensitization of their myofilament to Ca
2+
and the fixing of their cardiac relaxation impairment by cTnI-ND. The correction of the diastolic dysfunction by cTnI-ND occurs in a dose-dependent manner as evidenced by cell-based assays, measuring cardiac cell contractility of the various Double-TG mouse lines, and by echocardiography. In addition, in 8-10-month-old Double-TG mice, the rescue of RCM mice by cTnI-ND is characterized by both the restoration of their diastolic function and the amelioration of their systolic function, since both diastolic and systolic functions deteriorate in aged RCM mice. Thus, this study allows determining the efficiency of cTnI-ND in the treatment of RCM and evaluating how the dosage of RCM mutant proteins may influence the cardiac function. Also, consistent with the beneficial effect of cTnI-ND on the function of non-myopathic aging hearts (Biesiadescki et al., 2010), these data demonstrate the ability of cTnI-ND to rescue the RCM phenotype not only by correcting diastolic dysfunction in young RCM mice, but also by improving systolic function in aged RCM mice.
Abstract 9142: Post Procedural Changes of P-wave Duration can Predict Recurrence of Atrial Fibrillation after Circumferential Pulmonary Vein Isolation
Authors: Egami Yasuyuki , Nishino Masami , Taniike Masayuki , Makino Nobuhiko , Kato Hiroyasu , Shutta Ryu , Morita Hisaki , Tanouchi Jun , Yamada Yoshio
Published: April 2024

Background:
It has been reported that the significant shortening of P-wave duration after pulmonary vein isolation was related to successful outcome. However, the impact of the clinical outcomes after circumferential pulmonary vein isolation (CPVI) on the serial changes of P-wave characteristics is not clear. We hypothesized that the recurrence of atrial fibrillation (AF) prolonged P-wave duration and the recurrence of AF after CPVI affected the P-wave parameters by P-wave signal averaged electrocardiogram (P-SAECG).

Methods:
Fifty-nine patients (65±7years, 41 male) with AF (paroxysmal AF : n=44, persistent AF : n=15) who underwent CPVI alone and received P-SAECG at 2 days, 2 weeks, and 4weeks after CPVI were enrolled in this study. By using P-SAECG, the filtered P-wave duration (FPD) and root mean square voltage for the last 20msec (RMS20) were measured and the serial changes of FPD and RMS20 were calculated. AF recurrence was defined as patient's symptom and any episode of AF lasting > 30 seconds on surface 12-leads ECG or 24-hour Holter ECG during follow-up periods except for 2 months post CPVI.

Results:
The patients were followed for 6±3 months. The recurrences of AF occurred in 18 of 59 patients (31%). The results of P-SAECG parameters were shown as table. The FPD of 2 days, 2weeks and 4weeks after CPVI in AF recurrence group was significantly longer than that in sinus rhythm (SR) maintenance group and the ΔFPD 4weeks in AF recurrence group was significantly prolonged than that in SR maintenance group. Using FPD 4weeks as cutoff value of > 130.5 msec to predict AF recurrence, the sensitivity and specificity were 65% and 61%, respectively. Using ΔFPD 4weeks as cutoff value of > 3.5 msec to predict AF recurrence, the sensitivity and specificity were 71% and 63%, respectively.

Conclusion:
The longer FPD and prolongation of FPD for one month after CPVI can predict the recurrence of AF after CPVI.
Abstract 9149: Mechanism of Thyroid-Hormone-Deficiency-Caused Cardiac Injury in a Rat Model: Effects of Left Ventricle and Myocyte Functional Performance, [Ca
2+
]
i
Transient Response and Beta-Adrenergic Modulation
Authors: Shao Qun , Cheng Heng-Jie , Callahan Michael F , Wong Steven H , Wesley Deborah J , Li Wei-Min , Cheng Che Ping
Published: April 2024

Background.
Thyroid hormone deficiency is associated in some patients with the development of congestive cardiomyopathy. However, the mechanism is unclear. Although hemodynamic abnormalities have been described, the cardiac pathophysiology is unclear. We assessed cardiac insufficiency in male SD rats with methimazole-induced hypothyroidism (Hypo). We tested the hypothesis that Hypo rats would demonstrate impaired left ventricular (LV) myocyte function and [Ca
2+
]
i
regulation with desensitization of cardiac β-adrenergic signaling.

Methods.
We compared myocyte β
1
-adrenoceptor (AR) expression and assessed LV and myocyte basal systolic and diastolic function, peak [Ca
2+
]
i
transient ([Ca
2+
]
iT
) and response to β-adrenergic simulation in 10 normal control (C) and 6 Hypo rats induced by methimazole (∼30 mg/kg/day for 8 weeks in the drinking water).

Results.
Compared to controls, total serum concentrations of T
3
and T
4
were significantly reduced in Hypo rats (T
3
: 21.5 vs 99.5 ng/dl and T
4
: 1.0 vs 4.8 μg/dl). Ejection fraction (33% vs 63%), LV contractility measured by E
ES
(0.7 vs 1.2 mmHg/μl) and M
SW
(57.2 vs 88.9 mmHg) were significantly decreased. LV time constant of relaxation (τ) (16.8 vs 10.7 ms) was increased by 57%. Importantly, these abnormalities of LV in Hypo rats were paralleled by concomitant depressions in myocyte contraction and relaxation indicated by decreased dL/dt
max
(57%, Hypo: 63.5±5.4 vs C: 147.8±5.6 μm/s) and dR/dt
max
(52%, 59.4±7.4 vs 123.8±7.5 μm/s) with reduced [Ca
2+
]
iT
(-31%, 0.18 vs 0.26) and markedly slowed the decline of [Ca
2+
]
i
. β
1
-AR expression decreased about 36% in Hypo compared with controls (0.48 vs 0.75). This was accompanied by attenuated responses to β-adrenergic stimulation. Isoproterenol (10
-8
M) produced significantly less increases in dL/dt
max
(30.7% vs 92.9%), dR/dt
max
(23.4% vs 66.9%), and [Ca
2+
]
iT
(17% vs 34%) in Hypo myocytes compared to normal.

Conclusions.
Hypothyroidism produces LV and myocyte systolic and diastolic dysfunction, [Ca
2+
]
iT
reduction and decreased myocyte β
1
-AR expression with impaired β-adrenergic regulation. The defects in cardiomyocyte force-generating capacity and relaxation process with impaired [Ca
2+
]
i
regulation may be the primary cause of hypothyroid cardiomyopathy.
Abstract 9157: Which Patients with Heart Failure Have the Poorest Health Literacy?
Authors: Moser Debra K , Pelter Michele M , Nesbitt Thomas , Robinson Susan , Biddle Martha J , Cooper Lawton , Dracup Kathleen
Published: April 2024

Background:
Emerging interest in health literacy has resulted in appreciation of poor health literacy as a major obstacle to engaging in self-care of heart failure (HF), yet little is known about health literacy in this population.

Objective:
To determine predictors of health literacy in a sample of patients with HF from among relevant sociodemographic, clinical and psychosocial variables.

Methods:
We enrolled 612 patients with HF living in rural areas of the United States in a randomized controlled trial of a self-care intervention. This report includes baseline data from the 516 (mean age 65 ± 13 years; 41.3% female; 33.8% NYHA class III/IV) on whom we have full data on health literacy. Potential predictors were age, gender, education level, income, employment status, marital status, NYHA class, comorbidity burden, body mass index, anxiety, depression and perceived control. We measured health literacy using the Short Test of Functional Health Literacy Assessment, comorbidity burden using the Charlson comorbidity index, anxiety using the anxiety scale of the Brief Symptom Inventory, depression using the Patient Health Questionnaire-9, and perceived control using the Control Attitudes Scale-revised. Multiple hierarchical linear regression was used to determine predictors of health literacy.

Results:
The model explained 26% of the variance in health literacy (p < 0.001 for model). The following variables were significant independent predictors of poor health literacy: lower income (p = 0.006), education level of less than high school (p < 0.001), male gender (p < 0.001), older age (p < 0.001), and perceptions of low control related to HF (p = 0.007). None of the clinical variables and neither anxiety nor depression were significant predictors.

Conclusion:
A well-defined group of HF patients at risk for poor health literacy can be identified by sociodemographic variables and perceptions of control. This information can provide clinicians with information about which patients with HF may have problems with health literacy. Patients with poor health literacy often are not recognized by clinicians. When a patient possesses one or more of the characteristics identified in this study, the clinician should have a high index of suspicion for poor health literacy.
Abstract 9184: Reduction in Mortality among Patients with Left Bundle Branch Block Treated with Cardiac Resynchronization Therapy: Results from the MADIT-CRT Trial
Authors: Goldstein Robert E , Krone Ronald J , Haigney Mark C , McNitt Scott A , Moss Arthur J
Published: April 2024

MADIT-CRT demonstrated a reduction in a composite endpoint, first occurrence of worsening heart failure or death, in mildly symptomatic patients with advanced left ventricular dysfunction receiving cardiac resynchronization therapy combined with an ICD (CRT-D) relative to similar patients receiving only an ICD in an average 2.4 year follow-up. Mortality in the short-term follow-up was not different between treatment groups. With additional follow-up, averaging 3.6 years since device implant, 191 deaths occurred among the 1820 enrollees. Among all study patients and among the 536 patients with baseline conduction defects other than left bundle branch block (LBBB), death rates were still not different in subjects receiving CRT-D or ICD. Among the 70% of patients with left bundle branch block (LBBB; n=1281) at baseline, extended follow-up revealed a statistically significant reduction in death (p=0.047) in patients receiving CRT-D relative to those receiving ICD alone (see Kaplan-Meier graph). The Forest plot shows the consistency of reduction in mortality with CRT-D therapy in almost all LBBB subgroups, especially in females. In conclusion, extended follow-up in MADIT-CRT showed that CRT-D reduced mortality in mildly symptomatic patients with LBBB, sinus rhythm, EF ≤30%, and QRS≥130 msec. This life-saving benefit of CRT-D was evident in almost all LBBB subgroups, but it was not seen in any of the subgroups of patients without LBBB.
Abstract 9201: Transplantation of Adipose Tissue-Derived Multi-Lineage Progenitor Cells Reduces Serum Cholesterol in Hyperlipidemic Watanabe Rabbits
Authors: Okura Hanayuki , Saga Ayami , Soeda Mayumi , Tani Jyunko , Moriyama Mariko , Moriyama Hiroyuki , Yamashita Sihizuya , Ichinose Akihiro , Tahara Shinya , Hayakawa Takao , Matsuyama Akifumi
Published: April 2024

Background
: Familial hypercholesterolemia (FH) is an autosomal co-dominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis. We examined the response to
in situ
stem cell therapy using adipose tissue-derived multi-lineage progenitor stem cells (hADMPC) in the LDL-receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH.

Methods
: WHHL rabbits received either normal control rabbit-derived, GFP-rabbit-derived or WHHL rabbit-derived ADMPC (normal-ADMPC, GFP-ADMPC and diseased-ADMPC, respectively) via the portal vein. This was followed by 12-week immunosuppressive therapy to avoid allogenic rejection.
In situ
survival and differentiation of the ADMPC into hepatocytes was examined by flow cytometry and immunohistochemical analysis, respectively. Lipid profile was examined before-, and 4-, 8- and 12 weeks after transplantation. LDL clearance was examined at the end of the study by125I-LDL turnover.

Results
:
In situ
survival of GFP-ADMPC was confirmed after transplantation. The cells integrated into the hepatic parenchyma and co-expressed GFP and hepatocyte markers such as albumin, indicating that the cells were reprogrammed into hepatocytes-like cells
in situ
. Transplantation of normal-ADMPC but not diseased-ADMPC resulted in a significant reduction of serum total- and LDL- cholesterol after transplantation. 125I-LDL turnover study showed significant improvement in the rate of LDL clearance in the WHHL rabbits with transplanted normal-ADMPC but not in those transplanted with diseased-ADMPC.

Conclusion
: Transplantation of ADMPC but not diseased ones corrected the metabolic defects in WHHL rabbits, suggesting that ADMPC transplantation is a potentially useful therapy for FH.