bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12402: Noninvasive Evaluation of the Feature of Hypertensive Heart Failure With Preserved and Reduced Ejection Fraction using Three-dimensional Speckle Tracking Echocardiography With High Volume Rate
Authors: Minatoguchi Shingo , Kawasaki Masanori , Tanaka Ryuhei , Saeki Maki , Nagaya Maki , Sato Noriaki , Kaneda Mayumi , Matsuoka Reiko , Miwa Hirotaka , Yoshizane Takashi , Iwama Makoto , Hirose Takeshi , Ono Koji , Arai Masazumi , Noda Toshiyuki , Minatoguchi Shinya
Published: April 2024

Background:
Left ventricular (LV) systolic and diastolic property in hypertension (HTN) may be deteriorated by pressure overload that causes LV hypertrophy (LVH) and fibrosis, resulting in hypertensive heart failure (HHF). HHF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) is mainly caused by systolic dysfunction or diastolic dysfunction, respectively. Some of HHF have combined dysfunction and LV torsion may play an important role to maintain systolic performance even in HHF.

Methods:
We examined 31 controls (age 65±12), 94 HTN (age 69±11), 24 HFpEF (EF≧50%) (age 79±10) and 13 HFrEF (EF<50%) (age 66±13) by one-beat real-time 3-dimensional speckle tracking echocardiography with volume rate of 70-80vps (3D-STE). LV radial strain rate at systole (SR-S) and torsion were assessed as an index that reflects LV contractility. Tau, SR at isovolumic relaxation (SR-IVR) and untorsion rate were assessed as relaxation. Pulmonary capillary wedge pressure (PCWP) was estimated as 10.8 - 12.4 x log {left atrial (LA) active emptying function / LA minimum volume} as we recently reported. Tau was calculated as IVR time / (ln 0.9 x systolic blood pressure - ln PCWP). LV stress was calculated as LV radius x pressure / thickness. LV stiffness was estimated as LV diastolic stress / strain.

Results:
LVEF in HFpEF was comparable to control and HTN, whereas LV SR-S and torsion were reduced associated with increased systolic stress. LVEF, SR-S and torsion were reduced in HFrEF compared to control. Tau and untorsion rate were deteriorated in HFrEF. LV SR-IVR was deteriorated in only HFpEF. LV stiffness in HFpEF and HFrEF were increased associated with increased diastolic stress (table).

Conclusion:
Noninvasive 3D-STE examination revealed that LVEF in HFrEF was decreased associated with decreased contractility and increased systolic stress and that LV diastolic function such as LV relaxation and stiffness in HFpEF was deteriorated associated with increased PCWP and diastolic stress.
Abstract 12496: A New Arrhythmic Threat to America. Chikungunya Myocarditis
Authors: Mendoza Ivan , Morr Igor , Mendoza Ivan , Torres Jaime , Gonzalez Karina , Meza Yolimar , Villalobos Iris , Marques Juan , Misticchio Francesca , Vasquez Rosalin , Morr Carlos , Morr Claudia
Published: April 2024

Background:
The mosquito-borne Chikungunya virus infection is one of the most important emerging virus diseases globally. Local transmission has been found in the United States. There are very few published reports concerning the cardiac complications in general and less of arrhythmias in particular. Chikungunya can be fatal: there have been sudden deaths reports .

Objective:
To investigate arrhythmic complications of Chikungunya myocarditis.

Methods:
Prospective multicenter observational study of 280 patients with a Chikunguya infection from a Venezuelan Outbreak.

Clinical evaluation, ECG, laboratory including virological evaluation and cardiac biomarkers, Echocardiogram, Holter and cardiac MRI procedures were carried out.

Results:
Of the 280 patients examined, 113 patients were male, with a mean age of 59 ± 9; 270 patients presented with fever and polyarthralgia and 85 developed palpitations.

Arrhythmias occured in 45% of cases; they included bradyarrhythmias (33%), atrial and ventricular ectopic beats and tachyarrhythmias in which atrial fibrillation was observed in 19 cases. There were also ectopic atrial tachycardia and non sustained ventricular tachycardia, conduction disturbances and 3 cases of sudden death.

Conclusion:
Physicians should know that almost half of the Chikungunya patients will develop arrhythmias and manifest or silent myocarditis. In the proper epidemiological context, the triad of fever, polyarthralgia and new arrhythmia including bradiarrhythmias suggest Chikungunya Myocarditis.
Abstract 12501: Abnormal Activation of TGFβ Signaling as a Pathogenesis of Left Ventricular Non-compaction Cardiomyopathy
Authors: Kodo Kazuki , Ong Sang-Ging , Jahanbani Fereshteh , Termglinchan Vittavat , Keiichi Hirono , InanlooRahatloo Kolsoum , Ebert Antje D , Shukla Praveen , Abilez Oscar J , Churko Jared M , Karakikes Ioannis , Jung Gwanghyun , Ichida Fukiko , Snyder Michael P , Bernstein Daniel , Wu Joseph C
Published: April 2024

Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and has a unique phenotype with characteristically extensive hypertrabeculation of the left ventricle, similar to the embryonic left ventricle, suggesting a developmental defect of the embryonic myocardium. However, in-depth investigation of this disease has been challenging due to the lack of animal models that can faithfully recapitulate the clinical phenotype of LVNC. In this study, we demonstrated that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in cardiac transcription factor TBX20 recapitulated a developmental defect consistent with the LVNC phenotype at the single-cell level. We first performed genetic tests and identified two TBX20 mutations, Y317* and T262M from multiple members in a family with LVNC history and one isolated patient. We then utilized iPSC-CMs to show that increased transforming growth factor beta (TGFβ) signaling is one of the central mechanisms underlying the pathogenesis of LVNC caused by TBX20 mutation. LVNC iPSC-CMs demonstrated decreased proliferative capacity due to abnormal activation of TGFβ signaling (Figs. A-B). TBX20 regulated the expression of TGFβ signaling modifiers including ITGAV and the Smad cofactor, PRDM16, which is a known genetic cause of LVNC. Genome editing of PRDM16 in control iPSC-CMs led to proliferation defects as seen in LVNC iPSC-CMs. Inhibition of abnormal TGFβ signaling by TGFβ receptor-1 inhibitors or ITGAV inhibitor, or genetic correction of the TBX20 mutation using TALEN reversed the proliferation defects seen in LVNC iPSC-CMs (Figs. C-D). Our results demonstrate that iPSC-CMs are a useful tool for the exploration of novel mechanisms underlying poorly understood cardiomyopathies such as LVNC. Here we provide the first evidence of activation of TGFβ signaling as playing a role in the pathogenesis of LVNC.
Abstract 12738: Improvement in Renal Function After Left Ventricular Assist Device Placement is a Prognostic Marker for Survival
Authors: Mohamedali Burhan , Yost Gardner , Bhat Geetha
Published: April 2024

Introduction:
Chronic renal dysfunction is common in end stage heart failure. Left Ventricular Assist Devices (LVADs) are increasingly being used in such patients. In this study, we evaluated patients who had poor renal function prior to LVAD placement with subsequent improvement in renal function after LVAD implantation.

Hypothesis:
Patients with poor renal function after LVAD implant have a poor prognosis.

Methods:
In this study, 229 patients with LVADs were enrolled. Patients were divided into 3 groups. Group 1 had patients with pre- and post-implant GFR of <60. Group II consisted of pre-implant Glomerular Filtration Rate (GFR) of <60, but subsequent improvement to ≥60 post-LVAD, and Group III comprised of patients with pre- and post-LVAD GFR of ≥60. Chi square testing and Kaplan-Meier (KM) survival analysis was performed.

Results:
The three groups had a mean pre-implant and post-implant GFR: Group I (N=95), 43±13 vs. 45±10, Group 2 (N=56) 48±8 vs. 75±15 and Group III (N=78) 81±18 vs. 89±22 respectively. There was a significant difference in overall survival between the three groups (42% vs 63% vs 73%, p<0.001). KM survival analysis also revealed significant differences in survival between the groups (Mean survival of 1037 days vs 1675 days vs 1745 days, p=0.015). When individual groups were analyzed, there was a significant difference between Group I vs II and Group I vs III, however; there was no difference in survival between Group II and III (Figure 1).

Conclusions:
Our findings suggest that patients with poor renal function pre-LVAD can be distinguished into two distinct phenotypes consisting of patients who improve their GFR to ≥60 after LVAD surgery and patients whose low GFR persists even after LVAD implantation. Survival of patients with improvement in GFR tended to normalize to their peers with pre-implant GFR of ≥60. Post-LVAD GFR can serve as an important prognostic marker for LVAD patients.
Abstract 12806: A Speckle-tracking Echocardiographic Multi-layer LV Global Strain Study to Evaluate Specific Compensation Mechanisms to Maintain Cardiac Function in Subjects With Hypertrophied LV Myocardium
Authors: Ozawa Koya , Funabashi Nobusada , Takaoka Hiroyuki , Kobayashi Yoshio
Published: April 2024

Introduction:
A novel transthoracic echocardiography (TTE) technique enables multi-layer measurement of left ventricular (LV) endocardial and epicardial layer myocardial strain.

Hypothesis:
There may be compensation mechanisms to maintain cardiac function in subjects with hypertrophied LV myocardium. To evaluate mechanisms in hypertrophied LV myocardium in subjects with preserved LV ejection fraction (LVEF) using multi-layer TTE analysis.

Methods:
A total of 105 subjects with preserved LVEF (41 hypertrophic cardiomyopathy subjects (31 male; 62±15 yr), 40 with severe aortic stenosis (19 male; 74±5 yr; transaortic maximum velocity 4.8±0.6m/s; aortic valve area index 0.46±0.12cm2/m2), and 24 controls (12 male; 54±18 yr)) underwent TTE (Vivid E9). Apical 4-, 2-, and 3-chamber GLS views and parasternal short axis GCS views at mitral valve level, papillary muscle, and apex were acquired. Strain measurements (absolute values) of endocarial and epicardial layers were performed.

Results:
Correlation coefficients (CC) between inter ventricular septum thickness in end diastole (IVSTd) and endocardial and epicardial GLS were -0.62, and -0.60 for apical 4 chamber, -0.60, and -0.62 for 2 chamber, and -0.58, and -0.57 for 3 chamber views, and -0.64, and -0.64 for averaged, respectively. GLS values showed significant negative correlation with degree of LV hypertrophy. CC between IVSTd and GCS values of endocardial and epicardial layer were -0.17, and -0.42 for mitral valve, -0.17, and -0.38 for papillary muscle, -0.15, and -0.37 for apex levels, respectively. GCS degree of correlation with IVSTd was < GLS, especially in endocardial layer. GCS values of endocardial layer did not significantly correlate with IVSTd for all levels.

Conclusions:
GLS and GCS decrease proportionally with increase in degree of LV hypertrophy. Degree of decrement of GCS was smaller than with GLS, especially in endocardial layer. This may be a compensation mechanism to maintain cardiac function.
Abstract 12834: Effects of Different Targeted Temperature on the Outcomes of CPR in a Rat Model of Cardiac Arrest
Authors: Tang Ziren , Yang Zhengfei , Wang Jiangang , Yin Lu , Zhao Shen , Wu Xiaobo , Kline Jena , Tang Wanchun
Published: April 2024

Introduction:
Therapeutic hypothermia improves the outcomes following resuscitation. The current hypothermia range (32-34°C) recommended by the
American Heart Association
is based mainly on two clinical studies. The benefits and the adverse effects of the temperature management at this range are still controversial. In the present study, we compared the effects of different body temperatures (33°C, 36°C, 37°C and 38°C) after resuscitation on the outcomes of CPR in a rat model of cardiac arrest.

Methods:
Ventricular fibrillation was electrically induced and untreated for 8 mins. Defibrillation was attempted after 8 mins of CPR. The animals were then randomized into 4 groups (
n
=10): hypothermia at 33°C (T33), hypothermia at 36°C (T36), normothermic (T37) and hyperthermia (T38). The variable core temperatures were maintained for 6 hours. Myocardial function and sublingual microcirculation were measured at baseline, 1, 2, 3 and 6 hours after the return of spontaneous circulation (ROSC). Survival and neurological function were evaluated at 24, 48 and 72 hours after ROSC.

Results:
The measurements were significantly better in the animals treated with hypothermia regardless of the cooling depth when compared with the normothermic group. Better sublingual microcirculation at 6 hours post-resuscitation was observed in the T36 group when compared with the T33 group. Significantly worse myocardial function and sublingual microcirculation were observed in the T38 animals when compared to the T37 group.

Conclusions:
Mild reduction of core temperature to 36°C early after ROSC improved post-resuscitation myocardial and neurological functions and survival to the same extent as 33°C but with less impairment of microcirculation.
Abstract 12910: The Utility of Automatic Cardiology Referral for Patients With Heart Failure at a Tertiary Academic Medical Center: The Automated MEdical Record driven Implantable CArdioverter-defibrillator Heart Failure Pilot Study (AMERICA-HF Study)
Authors: Barnett Adam S , Sun Albert , Koontz Jason , Eapen Zubin J , Patel Chetan B , Velazquez Eric J , Atwater Brett D
Published: April 2024

Introduction:
Patients with heart failure (HF) receive guideline-recommended therapies more frequently when treated by specialists in cardiology. However, a significant percentage of HF patients are not referred to cardiology. In addition, implantable cardioverter defibrillator (ICD) therapy remains underutilized in the general HF population.

Hypothesis:
Automatic referral of patients with HF to a general cardiologist or electrophysiologist using the electronic medical record (EMR) improves utilization of guideline-recommended therapies.

Methods:
In this pilot study, we determined the proportion of HF patients actively receiving outpatient cardiology care at our institution and assessed the utilization of guideline-recommended therapies. Patients with a prior diagnosis of HF who underwent an echocardiogram within the Duke University Health System between August 1, 2013 and July 31, 2014 were identified by retrospective EMR search. Patients with an ejection fraction >35% and those deceased at the time of EMR search were excluded. Patients were classified as “cardiology care” based on the attendance of at least one outpatient cardiology visit during the year prior to the echocardiogram or sooner; all other patients were classified as “no cardiology care”. Utilization of medical and device-based HF therapies were assessed in both groups.

Results:
A total of 1151 patients with a prior diagnosis of HF underwent an echocardiogram during the specified time period. Of these, 425 were eligible for the study. The majority of patients (n=388, 91%) were found to be receiving care from a cardiology provider. Patients receiving cardiology care were more likely to be treated with beta blockers (84% vs. 46%, p<0.0001), ACE inhibitors/ARBs (76% vs. 57%, p=0.01), aldosterone antagonists (52% vs 22%, p<0.0001), and ICDs (71% vs. 38%, p<0.001). In the cardiology care group, the underutilization rate of ICD therapy was 4.4% after accounting for contraindications.

Conclusions:
The vast majority of HF patients in this study were actively receiving cardiology care. In addition, appropriate ICD utilization was very high in patients managed by cardiology. Therefore, an automatic referral process would be unlikely to improve HF care at our institution.
Abstract 12942: Modified Glucose-Insulin-Potassium Regimen Provides Cardiac and Renal Protection With Improved Tissue Perfusion and Metabolism in Patients Undergoing Cardiopulmonary Bypass Surgery
Authors: Li Jia , Zhao Kun , Zhang Yue , Cui Qin , Zhao Rong , Yang Jian , Yu Shiqiang , Yi Dinghua , Gao Feng
Published: April 2024

Background:
Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention but clinical trials have yielded mixed results, presumably due to varying formulas and treatment timing of GIK. This study evaluated the effects of modified GIK given perioperatively in patients undergoing cardiopulmonary bypass (CPB) surgery.

Methods and Results:
In this prospective, randomized, double-blinded trial with 930 patients, 750 mL GIK (200 g/L glucose, 66.7 U/L insulin and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg/h 10 min before anesthesia. The primary outcome was the incidence of major adverse cardiac events (MACE). No significant difference in mortality was observed between the two groups. GIK therapy reduced the incidence of MACE (OR, 0.57; 95% CI, 0.43-0.75; P<0.001), enhanced cardiac function recovery with better glucose controlled without increasing perioperative blood glucose compared with placebo group. These benefits were associated with increased glucose uptake (9.5±4.6% vs. 5.6±2.6% in Placebo, P=0.005) and less lactate excretion (8.4 ± 9.2% vs. 33.4 ± 22.6% in Placebo, P<0.001) evidenced by the difference between arterial and coronary sinus, more glycogen store analyzed by transmission electron micrograph, and increased phosphorylation of IRS-1 and Akt in the hearts of GIK-treated patients. Importantly, GIK therapy significantly reduced blood lactate at 1 h, 6 h and 12 h after operation compared with placebo group (all P<0.001), indicating a enhanced tissue perfusion during CPB. Accordingly, patients treated with GIK had decreased markers of renal and hepatic injury, lower incidences of acute kidney injury and extended intensive care.

Conclusions:
Modified GIK regimen administrated perioperatively reduced the incidence of MACE and preserved cardiac and renal function in patients undergoing CPB surgery. These benefits were associated with activation of insulin signaling, improved myocardial metabolism and enhanced systemic tissue perfusion afforded by GIK.

Clinical Trial Registration_URL:
www.clinicaltrials.gov
. Unique identifier: NCT01516138.
Abstract 12972: Ultrasound of the Spleen Reduces Myocardial Ischemia-Reperfusion Injury by Stimulating a Splenic Anti-inflammatory Pathway
Authors: Tian Yikui , Gigliotti Joseph C , Wu Di , Klibanov Alexander L , Kron Irving L , Yang Zequan
Published: April 2024

Background:
Accumulating evidence now shows that a cardio-splenic axis plays critical role in post-ischemic reperfusion injury of the heart. Here, we tested a nonpharmacologic, noninvasive, ultrasound-based treatment of the spleen to reduce myocardial ischemia-reperfusion injury in mice.

Methods and Results:
C57BL6 (B6) mice and IL-10 Knockout (KO) mice underwent 40 min of LAD occlusion followed by 60 min of reperfusion. Ultrasound of the spleen (US-treated, US-T) versus ultrasound of the liver (US-control, US-C) was performed 24 hours before LAD occlusion. The TTC & Blue staining results showed that risk regions of all groups were identical. US-treated mice had significantly smaller myocardial infarct size than the US-control mice (p<0.05). In B6 mice, splenectomy (SPLX) performed 30 min before ischemia reduced infarct size. Acute adoptive transfer of splenocytes (SPAT) from US-control B6 mice performed 25 min before ischemia significantly exacerbated the infarct size in SPLX mice. However, SPAT of the US-treated splenocytes abrogated this exacerbation of the infarct size (Figure). Western blot analysis showed that ultrasound significantly increased the splenic phosphorylation Akt levels at 24 hours after US treatment. Furthermore, splenic ultrasound failed to protect the myocardial ischemia-reperfusion injury in IL-10 KO mice.

Conclusions:
These results suggested that an ultrasound-based treatment could have therapeutic potential for attenuation of post-ischemic myocardial reperfusion injury, possibly by stimulating a splenic anti-inflammatory effect via an Akt-IL-10 Pathway.
Abstract 13013: Bleeding Risk and Major adverse Events in Patients With Cancer on Oral Anticoagulation Therapy
Authors: Lee Yong-Joon , Park Jin-kyu , Uhm Jae-Sun , Kim Jong-Yun , Pak Hui-Nam , Lee Moon-Hyoung , Sung Jung-Hoon , Joung Boyoung
Published: April 2024

Introduction:
Bleeding and thromboembolism are the major concerns for oral anticoagulation therapy (OAT), especially in atrial fibrillation (AF) patients with history of cancer. The aim of this study was to evaluate the usefulness of OAT in AF patients with cancer for protecting major stroke and brain hemorrhage.

Methods:
The study included 2,168 AF patients with cancer at a tertiary hospital. We compared composite end points including major adverse cardiac events (MACE) and major bleeding between patients with OAT (OAT+, n=1,182) and without OAT (OAT-, n=936).

Results:
CHA
2
DS
2
-VASc and HAS-BELD score were higher in OAC+ than OAT- group. During the follow up period of 3.9 ± 2.8 years, 142 (12%) and 88 (9%) patients had MACE in OAT+ and OAT-, respectively (p = 0.055). Major bleeding (11% vs. 8%, p=0.023) and composite endpoints (21% vs. 16%, p = 0.002) were significantly higher in OAT+ than OAT- group. OAT+ patients had lower cumulative survival free of composite endpoints than OAT- patients (p=0.024). Among 230 MACE and 207 major bleeding events, 117 (47%) and 86 (42%) events occurred within first year after the diagnosis of cancer. During this period, optimal INR level was achieved in only 288 (24%) patients because of cancer treatment. OAT failed to prevent MACE in stomach and renal cancer patients with statistical significance (Figure 1A*). Furthermore, OAT+ patients with prostate, thyroid, pancreato-biliary, head-neck and breast cancers tended to have more MACE than OAT- group.

Conclusion:
In AF patients with cancer, composite end point including MACE and bleeding was not improved by OAT at the first year because of poor control of INR. Therefore, meticulous control of INR is needed in these patients. Moreover, OAT might fail to prevent MACE in specific cancers.
Abstract 13130: Age-associated Reductions in Junctophilin-2 and Amphiphysin-2 Associate With Disruption of T-tubules and Intracellular Calcium Regulation in Myocytes From the Mouse Left Ventricle
Authors: Cheah Lih-Tyng , Lancaster Matthew K
Published: April 2024

With progressive aging cardiac contractile performance declines. Our hypothesis was that this dysfunction is contributed to by aging-related ultra structural changes in cardiac myocytes. Single myocytes were obtained from the left ventricle of male C57Bl6 mice at the ages of 6, 12, 18 and 24 months, covering the majority of the lifespan. Di-8-Anepps labelling was used to visualize membrane structures, and whole-cell patch clamp to assess membrane capacitance. An age-correlated hypertrophy was evident. Cell width increased by a total of 41.4±0.3% (mean±SD) and cell length by 20.3±0.2% across the age range studied (n=82 cells from 7 hearts at each age, p<0.01 by ANOVA) indicating progressive concentric and eccentric hypertrophy. Accompanying this an 18.4±2.5% reduction in T-tubule density was identified between the ages of 6 and 24 months (p<0.01), despite a 36±18% rise in cell capacitance. At the microstructure level T-tubule arrangement also changed with transverse-orientated T-tubules falling 39±11%, whilst longitudinal T-tubules increased 9±4% (6 vs. 24 months, p<0.01 in each case). Accompanying this remodeling western blot analysis found amphiphysin-2, involved in T-tubule formation, and, junctophilin-2, key for associating sarcoendoplasmic reticulum with T-tubules, were both significantly reduced in left ventricular tissue at 24 months of age by 63±17% and 57±18% respectively compared with tissue from animals at 6 months (both p<0.01, n=7). Functionally time to peak of the calcium transient in field-stimulated myocytes, was prolonged by 36±12% in myocytes from animals at 24 months compared with that observed in cells from 6 month old animals (n=7 cells from 6 animals at each age p=0.01, by ANOVA). In localized regions of individual myocytes from aged animals reduced T-tubule density associated with even greater localized delays in the rise of the transient. Overall there was greater heterogeneity in the calcium rise across myocytes from aged animals compared with the essentially synchronous rise seen in those from young (6 month) animals. In conclusion aging associates with myocyte hypertrophy and T-tubule disruption, in turn associating with disruption of cellular calcium control.
Abstract 13185: Association Between Bariatric Surgery and Emergency Department Visits and Hospitalizations for Atrial Fibrillation
Authors: Shimada Yuichi J , Tsugawa Yusuke , Hasegawa Kohei
Published: April 2024

Introduction:
Atrial fibrillation (AF) carries a large societal burden. Although studies suggested reduction of AF-related symptoms after bariatric surgery, little is known about whether bariatric surgery affects harder clinical endpoints related to AF.

Hypothesis:
Bariatric surgery is associated with a reduction in the rate of ED visits and hospitalizations for AF.

Methods:
We performed a self-controlled case series study of obese patients with AF who underwent bariatric surgery, using the population-based ED and inpatient sample in 3 states (California, Florida, and Nebraska). Primary outcome was ED visit or hospitalization for AF from 2005 to 2011. We used conditional logistic regression to compare each patient's rate of the outcome event during sequential 12-month periods, using pre-surgery months 13-24 as the reference period.

Results:
We identified 1056 patients with AF who underwent bariatric surgery. During the reference period, 12.1% (95%CI, 10.1-14.0%) of patients had an ED visit or hospitalization for AF (Figure). The rate remained unchanged in the subsequent 12-month pre-surgery period (12.6%; 95%CI, 10.1-14.6%) with adjusted odds ratio [aOR] of 1.05 (95%CI, 0.81-1.36; P=0.74) compared to the reference period. In the first 12-month post-surgery period , we observed a similar rate of ED visits or hospitalizations for AF (14.2%; 95%CI, 12.1-16.3%), corresponding to aOR of 1.20 (95%CI, 0.93-1.55; P=0.16). The rate remained stable in the subsequent 13-24 months after bariatric surgery (13.4%; 95%CI, 11.3-15.4%), corresponding to aOR of 1.12 (95%CI, 0.87-1.45; P=0.40).

Conclusions:
Our findings indicate that bariatric surgery is not associated with lower rates of AF episodes requiring ED evaluation or hospitalization among obese patients with AF. Our data facilitate further investigations to fill the gap between symptom improvement and lack of reduction in healthcare utilization in the high risk population with AF.
Abstract 13332: Ideal Cardiovascular Health Metrics Are Associated With Disability Independently of Vascular Conditions
Authors: Devulapalli Saravana , Shoirah Hazem , Dhamoon Mandip S
Published: April 2024

Background:
Individuals with disability comprise the largest health care consumer group in the US. Vascular and non-vascular conditions contribute independently to disability, but it is unclear whether vascular risk factors are associated with disability independently of vascular events. We examined whether the American Heart Association’s 7 ideal cardiovascular health (CVH) metrics were independently associated with disability in a nationally representative cohort.

Methods:
Adults age>=20 years from the National Health and Nutrition Examination Survey 2005-2012 were included. Ideal CVH was calculated as a composite of 7 measures, each scored from 0-2. Primary predictors were number of ideal CVH metrics and score of CVH metrics. The outcome was a dichotomous score from 20 activities of daily living (ADL) and instrumental ADLs. Unadjusted and adjusted weighted logistic models estimated associations between ideal CVH and disability. Secondarily, interactions were tested and each disability item was tested separately.

Results:
The total cohort included 22692 participants; mean age was 46.9 years. Cardiac disease and stroke were present in 6.6% and 2.8%; 90.3% had poor physical activity and 89.9% poor diet. Among 3975 individuals with full data on all 7 CVH metrics, the mean number of ideal CVH metrics was 3.12 (95% CI 3.05-3.20) and ideal CVH score was 7.6 (7.5-7.7). In fully adjusted models, the OR for disability was 0.90 (95% CI 0.83-0.98) per point increase in ideal CVH score, and 0.84 (0.73-0.97) per additional number of ideal CVH metrics. There were significant interactions with ideal CVH measures for cardiac disease (p =0.007 for ideal CVH score and 0.01 for number of ideal CVH indicators) and stroke (p= 0.12 and 0.11 respectively). Among those with cardiac disease and stroke, there was a paradoxical trend for increased odds of disability for increasing values of CVH. For the majority of disability items, there was an inverse relationship with ideal CVH metrics.

Conclusions:
Both ideal CVH score and number of ideal CVH metrics were strongly and significantly associated with reduced odds of disability independently of vascular and non-vascular conditions. Poorer CVH may cause subclinical vascular disease resulting in disability.
Abstract 13444: Longer Telomere Length is Associated With More Distensible Carotid Arteries in a Healthy Adult Population
Authors: Vaidya Dhananjay , Yanek Lisa R , Iyer Kruthika R , Taub Margaret A , Kalyani Rita R , Kral Brian G , Becker Diane M , Becker Lewis C , Mathias Rasika A
Published: April 2024

Introduction:
Chronological age is associated with loss of arterial distensibility leading to greater cardiac afterload and inefficient systemic perfusion. It is not known if cellular aging, marked by a loss of telomeres, underlies vascular aging. We thus examined the association of leukocyte telomere length (LTL) with common carotid distensibility (CD) in a healthy adult population.

Methods:
We analyzed data from 119 adults free of clinical cardiovascular disease (ages 21-80 years, 39% African American, 60% women, from 99 families) with familial history of early onset coronary artery disease (30x coverage, Illumina HiSeq) for both 4 (LTL4) and 7 (LTL7) contiguous telomere motif repeats (TTAGGG or CCCTAA) using the approach of Ding et al (2014). Mean CD of both carotid arteries was calculated from systolic and diastolic carotid diameters measured using B-mode ultrasound and simultaneous measurement of brachial artery pulse pressure (follow-up time 0-5 years from the LTL visit). We used mixed model regression to account for non-independence of data in families.

Results:
The mean (SD) of LTL4 was 94851 (16370) and of LTL7 was 80666 (15001) repeats. Adjusting for age at LTL measurement, follow-up time to carotid measurement, sex, race, systolic and diastolic blood pressure, LDL- and HDL-cholesterol levels, current smoking and diabetes, 1 SD higher level of LTL4 was associated with 2.0 х 10
-4
(p = 0.027), and 1 SD higher level of LTL7 with 1.8 х 10
-4
mmHg
-1
(p = 0.048) higher CD, which is equivalent to CD at a chronological age that is lower by 4.4 and 4.0 years, respectively. Hypertension is not significantly associated with CD (p = 0.49) when added to this model.

Conclusions:
Greater LTL is associated with more distensible carotid arteries independent of cardiac risk factors including chronological age and blood pressure. Preserved telomere length represents healthy cellular aging in terms of fewer cell divisions, and thus greater vascular reparative reserve, which may lead to preserved arterial distensibility. This mechanism may partly explain the reported association of greater telomere length with lower risk of vascular events including coronary disease, heart failure and stroke.
Abstract 13447: An Injectable Conductive Polymer Hydrogel Improves Electrical Conduction Velocity in the Injured Heart
Authors: Cui Zhi , Ni Nathan C , Wu Jun , Yau Terrence M , Weisel Richard D , Li Ren-Ke
Published: April 2024

Introduction:
Scar formation after a myocardial infarction (MI) delays electrical impulse propagation, inducing dysynchronous cardiac activation and uncoordinated contraction. We generated an injectable biocompatible conductive polymer that not only stabilized the infarct region, but also facilitated electrical signal propagation across the scar tissue to enhance synchronous ventricular contraction.

Methods/Results:
Oxidative polymerization was employed to conjugate polypyrrole (PPY) to chitosan (CHI) and hydrogels were created by glutaraldehyde crosslinking. Biomaterials with 4 different PPY:CHI ratios (CHI, 3PPY:10CHI, 3 PPY:100 CHI, 3 PPY:1000CHI ) were generated. Electrical conductivity was measured by two-probe cyclic voltammetry. The 3PPY:10CHI ratio had significantly greater conductivity than the other concentrations (2.37х10-4±6.25х10-5S/cm, n=6, P<0.05). Improved electrical propagation was demonstrated when neonatal rat cardiomyocytes cultured on 3PPY:10CHI had significantly higher Ca2+ transient propagation velocity (by optical mapping with a fluo-4/AM indicator) than those cultured on other concentrations (17.25±2.23cm/s, n=15, P<0.05). Thus, 3PPY:10CHI was employed for in vivo studies employing a cryoinjury model (with a uniform scar size). Saline, CHI, and 3PPY:10CHI were injected into Sprague-Dawley rat hearts 1 week after injury. The sequence of cardiac electrical activation was visualized using an optical mapping system 1 month post-injection. Saline (57.7±2.5cm/s, n=4)- and CHI (47.1±3.5cm/s, n=3)-injected hearts showed disrupted propagation patterns and significantly reduced conduction velocity, while 3PPY:10CHI (74.3±4.7cm/s, n=5)-treated hearts had higher conduction velocities that were similar to healthy controls (81.3±0.59cm/s, n=3).

Conclusion:
A polypyrrole-conjugated chitosan hydrogel supported cell attachment and improved electrical conductivity in vitro. The 3PPY:10CHI biomaterial enhanced Ca2+ transient propagation in cultured cardiomyocytes and intra-myocardial injection of the material improved longitudinal electrical impulse propagation across the scar. This new biomaterial may be a new potential therapy to synchronize cardiac contraction.
Abstract 13483: Peptide Inhibition of PTEN Improves Metabolic Recovery and Outcomes in a Murine Cardiac Arrest Model
Authors: Zhu Xiangdong , Wang Huashan , Wang Youhua , Li Jing , Leff Alan R , Vanden Hoek Terry L
Published: April 2024

Introduction:
Recent work shows that PTEN inhibition protects against cardiomyocyte contractile dysfunction and death following ischemia/reperfusion. To further determine whether PTEN inhibition improves metabolic recovery and survival in a mouse model of cardiac arrest, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) based on the c-terminal PDZ binding motif of PTEN for rapid tissue delivery. We hypothesized that TAT-PTEN9c interferes with endogenous PTEN binding to cell membrane adaptors resulting in increased Akt activation, causing Akt-enhanced glucose utilization (with decreased diversion of glucose via the alternate polyol pathway to sorbitol) and improved survival.

Methods:
Mouse cardiomyocytes were isolated from 1-3 day old mouse pups. Western blot was used to identify concentrations of TAT-PTEN9c that enhanced Akt phosphorylation in mouse cardiomyocytes exposed to oxidant stress. C57BL6 mice were then subjected to an established KCL-induced 8 min cardiac arrest protocol. 30 mice after CPR were randomly assigned to receive saline or TAT-PTEN9c. MAP, ETCO2, and ECG were recorded until 4 h after successful cardiopulmonary resuscitation (CPR). TAT-PTEN9c (7.8 mg/kg) was given intravenously (IV) after CPR (n=10). As a measure of impaired glucose utilization, sorbitol content in heart and brain was determined by a fluorescence assay of NADH formation using sorbitol dehydrogenase and NAD+.

Results:
TAT-PTEN9c peptide enhanced Akt activation in neonatal mouse cardiomyoctes in a concentration-dependent manner. Survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 2 h (14/15, 93% vs. 9/15, 60%, P < 0.05) and 4 h (10/15, 67% vs. 6/15, 40%, P < 0.05) after CPR. Treated mice had increased Akt phosphorylation within 30 min after CPR in heart and brain tissues with significantly decreased sorbitol content, suggesting improved metabolic recovery and glucose utilization.

Conclusion:
TAT-PTEN9c can be used after CPR in a mouse SCA model to rapidly enhance Akt activation and decrease glucose shunting via the polyol pathway in critical organs, preventing early cardiovascular collapse and death. Further work exploring the role of tissue sorbitol in sudden cardiac arrest injury is needed.
Abstract 14128: Predictors of Long-Term Mortality for Survivors of Out-Of-Hospital Cardiac Arrest
Authors: Shuvy Mony , Morrison Laurie J , Scales Damon , Wijeysundera Harindra C , Qiu Feng , Dorian Paul , Verbeek Richard P , Buick Jason , Tu Jack V , Koh Maria , Ko Dennis T
Published: April 2024

Background:
Although outcomes of out-of-hospital cardiac arrest (OHCA) patients have improved substantially over time, little is known regarding factors that may influence their longer term prognosis. The main objective of this study was to examine independent predictors of long-term mortality for OHCA survivors.

Methods:
A population-based study was conducted using the Toronto Rescu Epistry database with linkage to administrative data in Ontario, Canada. OHCA patients who survived to hospital discharge in the Great Toronto Area from 2005 to 2010 were included. Multivariable hierarchical regression models were constructed to determine the independent association of factors predicting 1-year and 3-years mortality.

Results:
Among the 13,755 OHCA patients who were eligible for study inclusion, 704 patients were alive at discharge and were included in this analysis. Their mean age was 60 years old, 27% were women, 35% had diabetes, and 9.4% had previous myocardial infarction. Mortality rates were 11.5% at one year and 19.6% at three years. Older age, cerebrovascular disease (OR = 2.74), renal disease (OR = 4.12) were significantly associated with higher mortality at one year (Table). In contrast, patients who had shockable initial rhythm (OR = 0.31), those who received coronary revascularization (OR = 0.41), or implantable cardioverter defibrillator (OR = 0.19) were associated with substantially lower risk of mortality. Factors associated with 3-year mortality were mostly similar as compared to one year, except for cancer which was highly significant for 3-year mortality (OR = 6). These models had high discrimination ability with area under the ROC of 0.89 for 1-year model and 0.88 for 3-year model.

Conclusions:
Non-cardiac comorbidities are the main drivers of adverse mortality for long term survivors of OHCA. Invasive cardiac procedures such as coronary revascularizations and ICD implantations are associated with significantly improved outcomes.
Abstract 14205: A Role of Inositol 1,4,5-trisphosphate Receptors to Inhibit the Progression of Pulmonary Arterial Hypertension
Authors: Shibata Akimichi , Uchida Keiko , Ishizaki Reina , Tsuchihashi Takatoshi , Maeda Jun , Mikoshiba Katsuhiko , Yamagishi Hiroyuki
Published: April 2024

Backgroud:
Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel in response to extracellular stimulation. There are three subtypes of IP3R (IP3R1, 2 and 3) and IP3R2 may be predominantly expressed in the pulmonary arterial smooth muscle cells (PASMCs).

Objectives:
To elucidate the role of IP3R2 in the progression of pulmonary arterial hypertension (PAH).

Methods:
The detailed expression pattern of IP3R2 in pulmonary vasculature during development and adulthood was investigated in lung sections of transgenic mice in which a LacZ reporter gene was knocked into the IP3R2 locus. In order to elucidate whether IP3R2 play a role in progression of PAH, we utilized chronic hypoxia (10% O2 for 6 weeks) -induced PAH mouse models. The severity of PAH was evaluated by transthoracic echocardiography, the weight of right ventricle, and the thickness of tunica media of pulmonary arteries, and compared between wild type (WT) and IP3R2 knock out (KO) mice. Proliferation and apoptosis in PASMCs were also assessed in both mice by immuno-staining with anti-phospho-histone H3 (PHH3) antibody and TUNEL assay, respectively. Further, in vitro, capacitative Ca2+ entry was assessed by Ca2+ imaging in primarily cultured PASMCs from WT and IP3R2 KO lungs by loading with fluorescent Ca2+ probe (Fluo-4AM).

Results:
Strong expression of the IP3R2 was detected in pulmonary arteries, predominantly in medial wall, from embryonic periods to the adulthood. IP3R2 KO mice showed higher RV pressure than those in WT mice by echocardiography. RV hypertrophy and medial wall thickness of PASMCs were more severely progressed in KO. There was no significant increase of PHH3 positive cells, while there was significant decrease of TUNEL positive cells in KO PASMCs compared with WT, suggesting that apoptosis was inhibited in KO PASMCs. Ca2+ imaging revealed that store-operated Ca2+ entry (SOCE) was enhanced in KO compared with WT. Taken together, loss of IP3R2 function leads to the acceleration of the progression of chronic hypoxia-induced PAH, with depressed apoptosis and enhanced SOCE in PASMCs.

Conclusions:
Although IP3R2 functions in increase of cytosolic Ca2+, it may play an inhibitory role in pathophysiology of PAH by influencing to the apoptosis and SOCE in PASMCs.
Abstract 14206: The Ryanodine Receptor Calcium Leak Does Not Contribute to the Development of Heart Failure
Authors: Mohamed Belal A , Neef Stefan , Lbik Dawid , Khadjeh Sara , Sossalla Samuel , Lehnart Stephan , Hasenfuss Gerd , Toischer Karl
Published: April 2024

Rationale:
Increased sarcoplasmic reticulum (SR) Ca2+ leak via cardiac ryanodine receptor (RyR2) is thought to play a role in heart failure (HF) development. Inhibition of this leak has been suggested to be an emerging therapeutic strategy. However, some studies have raised controversy as to the importance of SR Ca2+ leak in HF development. Previously, we and others have shown that pressure overload (PO) and myocardial infarction (MI) models result in an increased SR Ca2+ leak and maladaptive cardiac remodeling.

Objective:
We sought to determine whether inhibiting SR Ca2+ leak in PO or MI could avert HF progression.

Methods and Results:
Wild-type C57BL/6J mice treated with or without RyR2 stabilizer, Rycal S36, were exposed to two model of chronic cardiac stress, transaortic constriction (TAC)-induced PO or permanent coronary artery occlusion-induced MI. Left ventricular structural and functional remodeling were determined after surgeries. SR Ca2+ leak was significantly reduced in S36-treated mice versus placebo controls after surgeries. However, both placebo- and S36-treated mice developed pathological cardiac remodeling and systolic dysfunction nearly to the same extent in both experimental models. Interestingly, there was a trend, but not significant, toward improved survival in S36-treated mice compared to that in placebo (P = 0.12 and 0.13 in TAC-S36 and MI-S36, respectively).

Conclusion:
These results strongly support the idea that SR Ca2+ leak is irrelevant to the development of cardiac dysfunction after TAC or MI. The minimal reduced mortality after TAC or MI suggests a possible antiarrhythmic effect of the Rycal S36, which needs further investigations.
Abstract 14251: Nuclear Accumulation of Muscle LIM Protein is Regulated by Myocyte Contractility and Correlates With Cardiac Function in the Transition to Heart Failure
Authors: Paudyal Anju , Dewan Sukriti , Ikie Cindy , de Tombe Pieter D , Boateng Samuel Y
Published: April 2024

Prolonged increases in hemodynamic load lead to a loss of mechanosensing and heart failure because myocytes are unable to adapt to alterations in mechanical stress. We have previously shown that a decreased ratio of cytoplasmic to nuclear Muscle LIM protein (the MLP ratio) is associated with a loss of mechanosensitivity in human heart failure. However, the type and duration of mechanical stress that leads to impaired mechanosensitivity is unknown. In this study, we tested whether passive or active stress/strain was more important in modulating the MLP ratio (a measure of mechanosensitivity) and determined whether this correlated with heart function during the transition to failure. To test this, we exposed cultured neonatal rat myocytes to 48 h of 10% cyclic mechanical stretch at 1 Hz to mimic the passive forces associated with changes in blood pressure and volume. To mimic the forces generated by crossbridge activity during systole, we electrically paced myocytes at 6.8 V (1Hz) for 48 hours. The MLP ratio decreased 50% (p<0.05, n=4 cultures) only in response to electrical pacing, suggesting impaired mechanosensitivity. We then inhibited contractility by treating myocytes with 10μM blebbistatin which resulted in a 3 fold increase in the MLP ratio (n=8 cultures, p<0.05). This indicates that myocyte contractility regulates MLP nuclear shuttling and mechanosensitivity. To examine how mechanosensitivity changes during the transition to heart failure, we examined a guinea pig model of angiotensin II infusion (400ng/kg/min). The hearts were examined at 4, 8 and 12 weeks post-operatively. Using subcellular fractionation we showed that the MLP ratio increased 88% (n=4, P=0.009) during compensated phase at 8 weeks, but decreased significantly during heart failure at 12 weeks (p=0.0003, n=4). Furthermore, the MLP ratio correlated significantly with the E/A ratio (r=0.71, p<0.01 n=12), a clinical measure of diastolic function. This data indicate that impaired cardiac mechanosensitivity resulting in a reduced MLP ratio is regulated predominantly by myofilament crossbridge activity rather than passive strain. Increased mechanical stress within the contracting myofilaments contributes to the loss of mechanosensing during the transition to heart failure.
Abstract 14335: Predictors of Hospital Readmission in Patients With Critical Limb Ischemia Treated With Endovascular Therapy
Authors: Raeisi-Giglou Pejman , Reed Grant W , Salehi Negar , Malik Umair , Kafa Rami , Maier Michael , Shishehbor Mehdi H
Published: April 2024

Introduction:
Patients with critical limb ischemia (CLI) are at high risk for hospital readmission after endovascular therapy. Identifying predictors of readmission and understanding the prognosis of patients readmitted may improve outcomes.

Methods:
In this prospective study of 252 patients with CLI after endovascular therapy, predictors of readmission were determined by Cox proportional hazards analysis. Readmission was stratified by wound status (no wound, wound present but healed by readmission, and persistent wound). The incidence of major adverse limb events (MALE; major amputation, endartectomy, or surgical bypass) was compared in patients readmitted and not readmitted via Kaplan-Meier analysis.

Results:
During a median follow-up of 381 days (interquartile range [IQR], 115-718 days), 140 (56%) patients were readmitted. Median days to readmission was 83 (IQR 33-190 days). Independent predictors of readmission are shown in the Table. When analyzed as a time-dependent covariate, wound healing was associated with less risk of readmission (Hazard Ratio 0.39; 95% Confidence Interval 0.22-0.68; p<0.001). Readmission was most frequent in patients with unhealed wounds, and those with healed wounds were less likely to be readmitted than those without wounds (Figure A). MALE was more common in patients readmitted (Figure B).

Conclusions:
Patients with CLI and unhealed wounds are at increased risk of readmission after endovascular therapy. Other independent predictors of readmission include presence of multiple wounds, age ≥ 70 years, male gender, history of heart failure, dialysis dependence, and lack of aspirin use. Readmission is associated with increased MALE.