bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11771: Health Self-efficacy is Associated With Increased Physical Activity in Patients With Coronary Heart Disease
Authors: Bachmann Justin M , Wallston Kenneth A , Roumie Christianne L , Munoz Daniel , Patel Niral , Kripalani Sunil
Published: April 2024

Introduction:
Physical inactivity is strongly associated with morbidity and mortality, especially in patients with coronary heart disease (CHD). Low levels of health self-efficacy, or a patient’s belief in his ability to engage in behaviors to improve his health, may serve as a barrier to regular physical activity in CHD patients. We evaluated the association of health self-efficacy with physical activity in the Mid-South Coronary Heart Disease Cohort Study (MCHDCS).

Methods:
The MCHDCS is a prospective cohort of outpatients with CHD. Participants complete a set of validated demographic, psychological, social, behavioral, and functional measures. Health self-efficacy is assayed using two items from the Perceived Health Competence Scale (PHCS-2) that comprise a ten point scale with higher scores indicating better self-efficacy. Physical activity is evaluated with the International Physical Activity Questionnaire, which measures activity in metabolic equivalent (MET)-minutes/week. Less than 600 MET-minutes/week is considered to be a low physical activity level. We used negative binomial and ordinal logistic regression to evaluate the association of self-efficacy with physical activity.

Results:
A total of 1612 MCHDCS participants (31% female, 9% minority, mean age 67.5
+
10.6 years) were included in the analysis. The majority of participants had low physical activity levels, with a median of 540 (interquartile range 100 to 1600) MET-minutes/week. Each one point increase on the PHCS-2 scale was associated with an 8.7% increase (95% confidence interval 2.9%-14.9%, p=0.003) in MET-minutes/week after adjustment for socioeconomic status as well as depression, health literacy, social support and other factors (Table).

Conclusions:
Health self-efficacy is associated with physical activity in patients with CHD. Further study is needed to determine whether interventions to increase self-efficacy will raise levels of physical activity in this population.
Abstract 11820: NG2+ Cells Protect Against Cardiac Remodeling and Failure After Myocardial Infarction in Mice
Authors: Offerhaus Joost , Rainer Peter , Andersen Peter , Bedja Djahida , Lee Dong I , Shenje Lincoln , Cingolani Oscar H
Published: April 2024

Introduction:
Myocardial infarction kills cells, leading to cardiac remodeling (CR) and heart failure. Pericytes are microvascular mural cells that have been recently shown to have plasticity and cardiac regenerative potential, and also to interfere with CR, yet different niches present in cardiac tissue together with many cell markers that characterize resident pericytes have raised interrogate regarding their cell-specific differentiation capabilities. NG2 is a cell trans-membrane proteoglycan receptor and the most robust marker for pericytes. NG2 is normally present in embryonic cardiac myocytes, but in the adult heart its expression is only limited to pericytes and pericyte-like cells.

Hypothesis:
NG2+ cells are protective after myocardial infarction in the adult heart.

Methods:
Myocardial infarction (MI) was performed by coronary artery ligation in double transgenic mice (NG2cre-Z/EG) that express NG2-GFP under cre-lox technology, in mice lacking NG2 (NG2 -/-), and in wilt type littermate controls (WT). Cardiac histology was performed using Masson staining for fibrosis (Optical) and immunohistochemistry (Confocal) microscopy. Cardiac function was assessed by fractional shortening (FS) determined by echocardiography.

Results:
7 days after MI, NG2 positive cardiac myocytes were seen in the double transgenic mice (co-staining with alpha-sarcomeric actinin) more abundantly in the infarct border zone (confocal microscopy), as opposed to those subjected to sham MI, in which NG2+ cells were mainly limited to pericytes (192 ± 26 vs 1730 ± 290 NG2+ve cardiac myocytes/cm2; p <0.001). Cardiac function deteriorated more after 4 weeks in NG2-/- compared to WT (FS = 21 ± 2.1 vs. 12.5 ± 1.1 %, WT and NG2 -/- respectively; p < 0.001). Histologic examination of cardiac tissue revealed more interstitial fibrosis in the NG2-/- hearts (1.1 ± 0.2 vs 2.3 ± 0.3 %, WT and NG2-/-), seen mainly in the remote infarct zone. Quantitative analysis (qPCR) in different progenitor cell lines also revealed co-expression of NG2 with ISL-1, a robust cardiac stem cell marker.

Conclusions:
Our findings indicate that NG2+ cells play a key role in post-MI cardiac remodeling, and suggest a potential therapeutic role of resident NG2+ cells in HF.
Abstract 11833: Lipid-rich Core Quantification in Carotid Atherosclerosis Using MRI T2 Mapping - Relation to Clinical Presentation and Plaque Macrophage Activation
Authors: Chai Joshua T , Biasiolli Luca , Li Linqing , Alkhalil Mohammad , Galassi Francesca , Darby Chris , Halliday Alison , Hands Linda , Magee Timothy , Perkins Jeremy , Sideso Ed , Handa Ashok , Jezzard Peter , Robson Matthew D , Choudhury Robin P
Published: April 2024

Introduction:
Non-invasive plaque lipid quantification is appealing both for treatment selection and as predictor of future plaque events. However, current MRI methods are insensitive, require a coalesced mass of lipid and rely on multicontrast acquisition. We sought to: (1) provide tissue validation of quantitative T2 maps to measure plaque lipid; and (2) investigate whether this technique could discern differences in plaque characteristics between symptomatic and asymptomatic plaques. We also hypothesised that plaque lipid content correlates with differential plaque macrophage activation.

Methods:
40 patients scheduled for carotid endarterectomy were recruited for 3T carotid MRI. Lipid Area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. Plaque macrophages were procured using laser-capture microdissection from frozen tissue and subjected to microarray analysis.

Results:
Lipid Area (%) on T2 mapping and histology showed excellent correlation, both by individual slices (R = 0.85, P < 0.001) and plaque average (R = 0.83, P < 0.001). Lipid Area (%) on T2 maps was significantly higher in symptomatic compared to asymptomatic plaques (31.5 ± 3.7% vs. 15.8 ± 3.1%, P = 0.005) despite similar degrees of carotid stenosis. ROC curve analysis showed that T2 mapping has a fair to good ability to discriminate between symptomatic and asymptomatic plaques. Finally, using gene set enrichment analysis, plaque lipid content by T2 map positively correlated with distinct patterns of macrophage activation e.g. INF-STAT1 pathway (P < 0.01, FDR < 0.25).

Conclusions:
MRI T2 mapping accurately quantifies plaque lipid non-invasively. Greater plaque lipid content was found in symptomatic plaques; and this correlated with inflammatory pathway activation in plaque macrophages. This new technique may find a role in determining optimum treatment e.g. providing an indication for intensive lipid-lowering, or anti-inflammatory therapy.
Abstract 11920: Forecasting Short-term Atrial Fibrillation Recurrence Based on Past Atrial Fibrillation Recurrence Patterns
Authors: Charitos Efstratios I , Ziegler Paul D
Published: April 2024

Introduction:
Atrial fibrillation (AF) is considered a random phenomenon with regards to its initiation, recurrence pattern, and termination.

Hypothesis:
We sought to investigate if and how well the amount and pattern of past AF recurrence can forecast short term (30 day) future AF recurrence.

Methods:
We reconstructed the cardiac rhythm histories of 1195 patients with implantable cardiac devices (age 73 ± 10 years, follow-up: 349 ± 40 days, mean AF burden: 11%). The weekly amount (AF burden) and pattern of AF recurrence (AF density) of the 1st 150 days (1st half of the rhythm history) for each patient was used to construct a supervised machine learning algorithm (random forest regression model) with the aim to predict the amount of AF recurrence during days 151-180. Validation of the algorithm was performed on the 2nd half of the observation period of the same patients (AF pattern of days 150-300 to predict AF recurrence in days 301-330). An additional 2nd external validation of the algorithm was performed on a separate patient cohort consisting of 574 patients (age 69 ± 13 years, follow-up: 365 days, mean AF burden: 12%).

Results:
In the training cohort, the algorithm accounted for 86% of the observed variance with a mean squared error rate of 0.01. Variable importance measures revealed that the past amount (AF burden) and pattern (AF density) exhibited an important influence on future AF recurrence with decreasing importance for more remote events. AF recurrence up to 6 weeks in the past influenced short term (30 day) future AF recurrence. Validation of the algorithm on the 2nd half of the observation period and the external patient cohort revealed low median AF burden prediction errors of 0.004 [0.002-0.004] and 0.004 [0.003-0.028], respectively (Figure).

Conclusions:
The amount and temporal pattern of past AF recurrence (up to 6 weeks) is associated with short term future AF recurrence. This predictive ability attenuates progressively over time and merits further investigation.
Abstract 11955: Development of
in vivo
, Tissue-Engineered, Autologous, 3D Heart Valvular Tissue, Type SC Biovalve With Excellent Mechanical Properties, Valular Functions, and
in vivo
Performances
Authors: Nakayama Yasuhide , Takewa Yoshiaki , Moriwaki Takeshi , Sumikura Hirohito , Miyamoto Shinji , Okamoto Keitaro , Funayama Marina , Furukoshi Maya , Tatsumi Eisuke
Published: April 2024

Background:
Autologous pericardium is widely used for the reconstruction of intracardiac structures and pulmonary artery, and for aortic valve leaflets after fixation with glutaraldehyde for mechanical strengthening. We developed autologous prosthetic tissues by using in-body tissue architecture (IBTA) technology, which is a novel and practical approach of regenerative medicine based on the tissue encapsulation phenomenon of foreign materials in living bodies. In this study, IBTA-based heart valves with robust tissue wall [Biovalve (BV) Type SC] were prepared by using a novel caged mold. The mechanical properties of the valves were compared with human pericardium, and in vivo durability was evaluated in animal implantation study after in vitro evaluation using a pulsatile circulation circuit.

Methods and Results:
The BV preparation molds could be produced rapidly by using a 3D printing machine, based on the designed 3D-shape and size of native heart valves regardless of their type. Upon 1- or 2-month goat subcutaneous embedding of the molds aortic or pulmonary valve-shaped BVs (diameter 5-30 mm) were formed as type SC from completely autologous connective tissue with collagen and fibroblasts. All surfaces of the BVs that were in contact with blood were highly smooth and flat. The three leaflet tissues were seamlessly connected with the surrounding conduit tissue, and showed homogeneous wall thickness and excellent mechanical strength that was equivalent to or more than that of the human pericardium, with individual or regional differences. As an aortic valve, in vitro evaluation of the BV showed excellent valvular functions (regurgitation ratio 5.7% at 70 beats per minute). In a goat model, postoperative echocardiography after surgical replacement of the biovalves with stents showed smooth movement of the leaflets with little regurgitation under systemic circulation. In all implantation studies, the luminal surface after implantation was very smooth and fully covered with thin neointima, including endothelial cells without thrombus formation.

Conclusion:
Functional, completely autologous, robust, 3D aortic or pulmonary BVs showing the potential for clinical application were developed by in-body embedding of specially designed molds.
Abstract 12096: Interruptions of Views Are Associated With Failed Endotracheal Intubation and Shallow Laryngoscopic Blade Position is Associated With Longer Attempt Time in the Prehospital Settings
Authors: Naito Hiromichi , Guyette Francis X , Callaway Clifton W
Published: April 2024

Introduction:
Endotracheal intubation (ETI) is an essential skill for the critically ill patient. Prehospital ETI can be complicated by austere conditions and limited support, sometimes resulting in failure to intubate. Video laryngoscopy (VL) is primary a technical augmentation to facilitate ETI. VL also provides opportunity for evaluation of the technique or airway conditions during ETI.

Hypothesis:
We tested whether clinical variables were associated with failed ETI and longer attempt time performed by prehospital providers.

Methods:
A retrospective case control study was conducted with patients transported from Dec 2009 to Feb 2015 by air critical care medical service. The VL used in the study has the ability to display and digitally record the procedure which can be reviewed after the incident. An ETI attempt was defined by placing the VL into patient’s mouth. We obtained outcome variables and blade tip position during the procedure. The primary outcome measure was successful ETI attempt and the secondary outcome measure was time to accomplish a successful attempt. A multivariable logistic regression model was used for the primary outcome. Cox proportional hazards regression analysis was used for the secondary outcome.

Results:
304 intubation attempts in 268 patients were analyzed. There were 244 successful attempts and 60 failed attempts. Blade tip generally moved from shallower position to vallecular. 53.5% of the attempt was at shallow position 4 sec after the initiation of the procedure. Longer attempt time (p = 0.02; OR 0.98), higher Cormak-Lehane view (p < 0.001; OR 0.22), bodily fluids obstructing the view (p = 0.007; OR 0.26), and VL equipment error (p < 0.001; OR 0.13) were associated with failed attempts. The bodily fluids obstructing the view (p < 0.001; HR 0.51), and VL equipment error (p = 0.003; HR 0.42) were also associated with longer ETI attempt time. Shallow placement of blade tip at 4 seconds of intubation (p < 0.001; HR 0.40) was another factor associated with longer ETI attempt time.

Conclusions:
The variables interrupting the view during ETI were the major concerns associated with failed ETI attempts. The result also demonstrated high frequency of the shallow blade tip position and longer attempt time in this situation.
Abstract 12148: Impact of Multiple Plaque Ruptures and Cavity Area on Intraprocedural Stent Thrombosis: Intravascular Ultrasound Analysis
Authors: Morofuji Toru , Inaba Shinji , Hitsumoto Tatsuro , Hara Kayo , Morioka Hiroe , Higashi Haruhiko , Saito Makoto , Ohshima Kiyotaka , Ikeda Shuntaro , Hamada Mareomi , Sumimoto Takumi
Published: April 2024

Objectives:
We examined characteristics of lesions in cases of intraprocedural stent thrombosis (IPST) using intravascular ultrasound (IVUS).

Background:
IPST is a rare complication occurring during percutaneous coronary intervention (PCI) that leads to poor outcomes. However, factors that contribute to IPST remain largely unknown.

Methods:
We retrospectively analyzed 1,504 consecutive stent-implanted lesions in 1,324 patients [326 with ST-segment elevation myocardial infarction (STEMI), 403 with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and 595 with stable angina]. IVUS characteristics of plaques that led to IPST were compared with those of a matched control (non-IPST) group (n = 15) without evidence of IPST matched by age; gender; lesion location; or STEMI, NSTE-ACS, or stable angina. Positive remodeling was defined as a lesion greater than the mean reference external elastic membrane cross-sectional area. Continuous variables were displayed as median and 1st and 3rd interquartile range.

Results:
IPST occurred in 5 (0.4%; 3 with STEMI, 2 with NSTE-ACS) of 1,324 patients during PCI. Plaque burden at the minimum lumen area site was significantly greater in the IPST group than in the non-IPST group (93.0% vs. 87.9%, P = 0.0035). All 5 culprit lesions that led to IPST had ruptured plaques with positive remodeling and attenuation. The maximum cavity area was larger in the IPST group than in the non-IPST group (4.6 [4.3, 6.5] mm2 vs. 0 [0, 1.9] mm2, P = 0.0011), whereas plaque rupture was also observed in 40% of subjects in the non-IPST group. Multiple plaque ruptures in the culprit lesion were far more common in the IPST group (80.0% vs. 6.7%, P = 0.0049).

Conclusion:
Multiple plaque ruptures and a larger cavity area were associated with IPST occurrence. IVUS assessment may help predict the development of IPST during PCI.
Abstract 12234: Effects of Reducing Exposure to Air Pollution With a Filter on Exercise: A Randomized, Prospective, Double-Blind, Controlled Study of Heart Failure
Authors: Vieira Jefferson L , Guimaraes Guilherme V , de Andre Paulo A , Saldiva Paulo H , Bocchi Edimar A
Published: April 2024

Background:
The benefits of respiratory filters on patients with heart failure (HF) exposed to air pollution during daily activities have not been established.

Methods:
We tested the short-term effects of a filter intervention (FILTER) in a double-blind,randomized and 3-way crossover study with 30 HF patients and 15 control volunteers exposed, in three separate sessions, to clean air, dilute diesel exhaust (DE) or filtered DE. Pre-specified endpoints included variation in exercise tolerance (six-minute walking test [6mwt meters]; systemic blood pressure [BP mmHg], heart rate [HR bpm] and respiratory rate [RR rpm] responses) and gas-exchange variables (oxygen uptake [VO2 ml/kg/min]; oxygen saturation [Sat.O2 %]; ventilation and carbon dioxide production ratio [VE/VCO2 slope]; oxygen uptake per heart beat [O2Pulse ml/beat]; pulmonary ventilation [VE l/min]; tidal volume [Vt ml]; functional estimate of dead space [VD/Vt]) during a submaximal test.

Results:
In HF patients, DE adversely affected VO2 (11.0±3.9 vs. 8.4±2.8 ml/Kg/min; p < 0.001) (figure), 6mwt (243.3±13.0 vs. 220.8±13.7 m; p = 0.030), and O2Pulse (8.9±1.0 vs. 7.8±0.7 ml/beat; p < 0.001). When compared to DE-protocol, the FILTER reduced the particulate concentration from 325±31 to 25±6 μg/m3 (p < 0.001), and in HF patients it was associated with an increase in VO2 (10.4±3.8 ml/Kg/min; p < 0.001) (figure) and O2Pulse (9.7±1.1 ml/beat; p < 0.001). FILTER was also associated, in HF and control groups, with significantly higher pulmonary ventilation, tidal volumes, functional estimate of dead space and CO2 exchange. Other variables as VE/VCO2 slope, HR, BP and RR did not differ between exposure protocols.

Conclusion:
Air pollution adversely affects exercise tolerance in HF patients. FILTER can reduce the particulate concentration during DE-exposure, preventing pollution-effects on VO2 and O2Pulse.

ClinicalTrials.gov
Identifier: NCT01960920
Abstract 12304: Activation of the Exosome Biogenesis Pathway in Cardiomyocytes by Overexpression of Hsp20 Improves Cardiac Function and Angiogenesis in Diabetic Mice
Authors: Gu Hiatao , Wang Xiaohong , Huang Wei , Wang Yigang , Fan Guo-Chang
Published: April 2024

Background:
Exosomes derived from cardiomycytes are able to affect endothelial cell growth. Increased Hsp20 levels in myocytes have been shown to promote cardiac angiogenesis. Given that diabetic hearts exhibit severe microvascular rarefaction and impaired angiogenesis, we asked whether overexpression of Hsp20 could attenuate diabetes-triggered cardiac adverse remodeling, and if so, whether Hsp20-mediated cardioprotection is associated with the activation of exosome biogenesis/release.

Methods and Results:
2-mon old male wild-type (WT) mice and transgenic (TG) mice with heart-specific overexpression of Hsp20 (10-fold) underwent daily peritoneal injection of streptozotocin (STZ, 50μg/g) for 5 days to induce diabetic condition (>300mg/dl). Control mice were received injections of citrate buffer. 3-month later, we observed that the left ventricular ejection fraction (EF) and fractional shortening (FS) were reduced by 43% and 35%, respectively, in STZ-injected WT mice, compare to controls. However, STZ-induced cardiac dysfunction was significantly attenuated in Hsp20-TG mice, compared to WTs. The wheat germ agglutinin (WGA) staining displayed that the size of cardiomyocytes was significantly increased in STZ-WT hearts, but not in STZ-Hsp20TG samples, compared to controls. Similarly, STZ could greatly induce myocardial fibrosis and apoptosis in WT hearts, but not significant in Hsp20-TGs. In addition, the density of myocardial blood vessels, measured by Isolectin IB4 staining, was decreased to a greater degree in STZ-WTs than STZ-TGs. Mechanistically, we observed that Hsp20 interacted with Tsg101, an initiator of exosome biogenesis in cells. As a result, the levels of Tsg101, Rab11a/b and Rab35, factors known to participate in exosome biogenesis/release, were significantly increased in Hsp20TG hearts, compared to WTs. Accordingly, blockade of exosome generation with GW4869 (2.5μg/g), a specific inhibitor of exosome biogenesis, offset cardio-protective effects observed in STZ-treated Hsp20-TG mice.

Conclusions:
This study indicates that overexpression of Hsp20 protects mouse hearts against diabetes-induced cardiac adverse remodeling via activation of exosome biogenesis/release in cardiomyocytes, at least in part.
Abstract 12323: Effect of Prompt Revascularization on Outcomes in Diabetic Patients With Stable Ischemic Heart Disease Depends on Prior Myocardial Infarction Status and Mode of Revascularization
Authors: Chung Matthew J , Novak Eric , Brown David L
Published: April 2024

Introduction:
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial found no benefit from prompt revascularization in addition to optimal medical therapy (PR+OMT) compared with OMT alone in diabetics with stable ischemic heart disease (SIHD). However, diabetics with prior myocardial infarction (PMI) are a higher risk group. Thus, we examined whether PMI status altered the effect of PR+OMT versus OMT alone on outcomes in diabetics with SIHD.

Methods:
BARI 2D randomized 2368 diabetics with SIHD to either PR+OMT with PCI or CABG or OMT alone. PMI was defined by reported history of MI or abnormal Q-waves on ECG. For patients with PMI and no PMI, we used Kaplan-Meier analysis to compare the rate of death, MI, stroke, congestive heart failure (CHF) and a composite of death/MI/stroke between patients randomized to PR+OMT versus OMT alone.

Results:
Of 2280 patients with known PMI status, 936 (41%) had PMI and 1344 (59%) did not. Baseline variables including age, sex, race, BMI, history of CHF, hypertension, hyperlipidemia, tobacco use, abnormal ejection fraction, prior revascularization, CAD severity, creatinine, glycemic control and use of guideline-directed medical therapy were similar between the two treatment strategies within each group. In patients with PMI, PR+OMT had no effect on any outcome compared with OMT alone. In those without PMI, PR+OMT was associated with higher 5-year event free rates of MI (91% vs. 85%, P = 0.002) and death/MI/stroke (81% vs. 76%, P = 0.04) compared with OMT alone, although these differences were limited to patients treated with CABG.

Conclusions:
In diabetics with SIHD and PMI, PR+OMT did not improve outcomes compared with OMT alone. However, in those without PMI, PR+OMT reduced the rate of MI and a composite of death/MI/stroke when treated with CABG, but not PCI. These findings, if confirmed in a prospective study, may improve outcomes in diabetics with SIHD through appropriate selection of a revascularization strategy.
Abstract 12343: Bariatric Surgery is Associated With Reduced Rate of Emergency Department Visits and Hospitalizations for Heart Failure Exacerbation Among Obese Patients With Heart Failure
Authors: Shimada Yuichi J , Tsugawa Yusuke , Brown David F , Hasegawa Kohei
Published: April 2024

Introduction:
Heart failure (HF) is a significant societal burden. Obesity is known as a possible risk factor for HF exacerbation. However, little is known as to whether weight loss interventions, such as bariatric surgery, effectively reduce the rate of HF exacerbation.

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

Methods:
We performed a self-controlled case series study (each individual serves as his/her own control) of obese patients with HF 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 HF exacerbation 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 1664 patients with HF who underwent bariatric surgery. During the reference period, 14.4% (95% CI, 12.7-16.0%) of patients had an ED visit or hospitalization for HF exacerbation (Figure). The rate remained unchanged in the subsequent 12-month pre-surgery period (13.3 [11.7-15.0]%); adjusted odds ratio (aOR) 0.92 [0.75-1.12]; P=0.39). In the first 12-month period after bariatric surgery, we observed a significantly lower rate of ED visits or hospitalizations for HF exacerbation (8.7 [7.4-10.1]%; aOR 0.56 [0.45-0.70]; P<0.0001). The rate remained significantly lower in the subsequent 13-24 months after bariatric surgery (8.7 [7.4-10.1]%; aOR 0.56 [0.45-0.70]; P<0.0001). In contrast, we did not observe a significant reduction in the rate of HF exacerbation with non-bariatric surgery (i.e., cholecystectomy, hysterectomy).

Conclusions:
Our findings indicate that bariatric surgery is associated with lower rates of HF exacerbations requiring ED evaluation or hospitalization among obese patients with HF.
Abstract 12376: Analysis of Novel Target Molecules of Nobiletin, a Potent Therapeutic Agent Against Heart Failure
Authors: Sunagawa Yoichi , Ogawahara Shintaro , Funamoto Masafumi , Sakurai Ryoga , Hieda Kehima , Katanasaka Yasufumi , Asakawa Tomohiro , Kan Toshiyuki , Murakami Akira , Wada Hiromichi , Murakami Akira , Hasegawa Koji , Morimoto Tatsuya
Published: April 2024

Introduction:
Maladaptive hypertrophy is being recognized as a critical event during the development of heart failure. We screened some natural compounds and found that nobiletin, contained in
Citrus depressa
, prevented the development of heart failure in rats with myocardial infarction. However, the target molecule of nobiletin in cardiomyocytes is still unclear.

Hypothesis:
To solve this problem, we attempted to identify novel nobiletin-binding proteins by a proteomics approach and investigate its functional mechanism in mice.

Methods and Results:
Nobiletin-binding proteins were purified from rat heart using biotin-conjugated nobiletin or biotin alone and identified by LC-LC/MS-MS. One of them, nobiletin-binding protein 1 (NBP1) which related to cellular metabolic pathway, physically bound to biotin-conjugated nobiletin by pull-down assay. Nobiletin also activated enzyme activity of NBP1
in vitro
. In cardiomyocyte, knockdown of NBP1 failed to nobiletin-mediated anti-hypertrophic effect, and overexpression of NBP1 inhibited phenylephrine-induced ANF and ET-1 promoter activities and cardiomyocyte hypertrophy. TG mice carrying NBP1 gene under the CAG promoter and WT mice were subjected to sham or transarotic constriction (TAC). After 8 weeks, NBP1-TG mice resisted pressure-overload induced cardiac hypertrophy and systolic dysfunction compared to WT mice without affecting blood pressure. The quantitative mRNA analysis showed that TAC-induced ANF, BNP, and β-MHC gene transcriptions were reduced in left ventricle of NBP1-TG mice compared to those of WT mice.

Conclusions:
Proteomics analysis on molecular targets of nobiletin is useful to delineate nobiletin-mediated signaling pathways and anti-hypertrophic effect in cardiomyocytes. These finding suggest that nobiletin inhibits cardiomyocyte hypertrophy and the development of heart failure through the functional regulation of NBP1 activity. A natural compound, Nobiletin, might be a candidate for heart failure agent in human.
Abstract 12745: Amelioration of Mitochondrial Injury During Cardiac Resuscitation by the Combined Administration of α-Methylnorepinephrine and Zoniporide
Authors: Radhakrishnan Jeejabai , Lamoureux Lorissa , Baetiong Alvin , Gazmuri Raúl J
Published: April 2024

Introduction:
We have shown in a rat model of VF and closed-chest resuscitation that plasma levels of cytochrome c - a marker of mitochondrial injury - are inversely related to survival and both influenced by interventions that attenuate mitochondrial injury. We have also shown that administration of zoniporide (ZNP) - an NHE-1 inhibitor - combined with α-methylnorepinephrine (α-MNE) - a peripheral selective α2-adrenoreceptor agonist is highly effective for resuscitation.

Hypothesis:
We hypothesized that the ZNP/α-MNE combination exerts its beneficial effects partly by attenuating mitochondrial injury.

Methods:
VF was electrically induced in 48 male retired breeder rats and left untreated for 8 minutes. Resuscitation was attempted by 8 minutes of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest compression establishing 4 groups of 12 rats each. Successfully resuscitated rats were monitored for 240 minutes. Plasma cytochrome c levels were measured by an electrochemiluminescence (ECL) immunoassay developed by us using antibodies provided in a DuoSet IC, Rat/Mouse Total Cytochrome c kit (R&D systems). The ECL signal was measured using a QuickPlex SQ 120 multiplex imager from MesoScale Discovery (MSD).

Results:
Post-Resuscitation (PR) plasma cytochrome c levels (fold increase over baseline) were markedly attenuated in groups that received ZNP demonstrating statistical significance at PR 180 minutes (Figure). Cytochrome c levels were positively correlated with lactate levels and marginally negatively correlated with cardiac work index at PR 180 (Figure). PR lactate levels were reduced in all treatment groups with the greatest effect by the ZNP/α-MNE combination.

Conclusions:
We confirm that the ZNP/α-MNE combination exerts resuscitation benefits by ameliorating mitochondrial injury.
Abstract 12897: Long-term Risk of Atrial Fibrillation in Adults Diagnosed With Atrial Septal Defect in Childhood
Authors: Karunanithi Zarmiga , Nyboe Camilla , Hjortdal Vibeke E
Published: April 2024

Atrial fibrillation (AF) is very common in patients with atrial septal defects (ASD). The impact of closure on the prevalence and especially the correct timing is controversial. We investigated the risk of AF in patients diagnosed with ASD in childhood, both with and without closure, compared with a general population cohort.

Data on all Danish ASD patients diagnosed before the age of 18 years between 1963 and 1994 was obtained from national registries. Follow-up was continued until outcome, death, emigration or 31st of Dec 2011. Hazard ratios were calculated using Cox proportional hazards regression and cumulative incidences estimated using Fine and Gray’s competing risk regression.

A total of 1,111 patients met the inclusion criteria, and each was matched on age and gender with 10 controls. Mean age at diagnosis was 4.9 years (range 0-17.9 years). Mean follow-up since diagnosis was 26.3 years (range 1-53.3 years). A total of 642 patients had closure performed either surgically or percutaneously with 402 before the age of 10 years.

Patients with an unclosed ASD had an increased risk of AF (HR 16.4, 95% CI: 6.8; 39.8) compared with the general population cohort. For patients with closure the risk was similarly high (HR 18.1, 95% CI: 9.8; 33.5). Closure before (HR 17.9, 95% CI: 7.5; 42.7) and after (HR 18.4, 95% CI: 7.7; 43.8) the age of 10 did not affect the risk of AF later in life. Cumulative incidences after 10 years was 0.6% [0.1; 4.4] and after 50 years 9.8% [6.7; 14.12].

In conclusion, risk of AF is high despite closure in childhood. Closure being insufficient protection against development of AF in adulthood speaks for causality other than the mere presence of an ASD. Furthermore, ASD patients (regardless of closure) call for follow-up investigation past the 5th decade.
Abstract 12901: Removal of Dabigatran Using Sorbent Hemadsorption
Authors: Angheloiu George O , van Ryn Joanne , Goss Ashley M
Published: April 2024

Background:
Dabigatran is a direct thrombin inhibitor that has been demonstrated to be superior to warfarin in protecting against stokes in patients with atrial fibrillation. The risk of a major bleed is lower with dabigatran than with warfarin, however 1.5% of patients treated with the former drug experience gastro-intestinal bleeding episodes versus 1.02% per year for warfarin. While a reversal agent for Dabigatran has been developed, we designed and tested an alternative removal method that in addition to novel anticoagulants can remove antiplatelets (100% removal rate of Ticagrelor from blood; results submitted in parallel abstract) and radiocontrast agents (96% removal rate), two other classes of agents frequently used in cardiology and known to lead to unwanted events such as bleeding or acute kidney injury respectively.

Hypothesis:
Dabigatran can be adsorbed by Cytosorb sorbent beads.

Methods:
We performed first-pass bench experiments using a mix of 0.35 mg of Dabigatran in 1000 ml 4% bovine serum albumin (BSA) saline solution rendering a dilution of 350 ng/ml similar with therapeutic concentration levels of Dabigatran in patients with non-valvular atrial fibrillation. 100 ml solution was passed through 10 ml, 20 ml and 40 ml sorbent at an injection rate of 1 ml/min for 100 minutes. Dabigatran concentration was measured in the affluent and effluent solution using a liquid chromatography technique with tandem mass spectrometric detection (LC/MS/MS).

Results:
The Dabigatran removal rate was 100% using a 40 cc column of Cytosorb, and approximately 94% with the 10 ml and 20 ml columns.

Conclusion:
Sorbent adsorption demonstrates robust removal of Dabigatran from BSA solution. This creates the premises of an all-including method possibly able to remove three classes of agents frequently used in cardiology: anticoagulants, antiplatelets and radiocontrast agents.
Abstract 12904: Ticagrelor Removal From Human Blood
Authors: Angheloiu George O , Gugiu Bogdan G , Pandey Rishikesh , Ruse Cristian , Brooks Cheryl , Dasari Ramachandra , Hawranko Alyssa , Whatling Carl
Published: April 2024

Background:
In acute coronary events, ticagrelor is recommended to be loaded prior to cardiac catheterization. In the PLATO study the rate of severe bleeding on ticagrelor in patients who needed urgent bypass graft surgery was high but similar for ticagrelor and clopidogrel. The reversible binding mode of action of ticagrelor onto the P2Y12 receptor provides an opportunity for drug removal not possible for the thienopyridines (clopidogrel and prasugrel) which are all irreversibly binding to P2Y12.

Objective:
Our goal was to devise an efficient method for ticagrelor removal from blood.

Methods:
Ticagrelor removal was measured in two sets of experiments. The first set was performed in a first-pass manner and used as drug vehicle bovine serum albumin (BSA) solution (0.4% and 4%), while the second set employed in three experiments blood either bought from BioreclamationIVT (older than 24 hours) or freshly collected from a healthy volunteer and mixed with ticagrelor at a concentration of approximately 5.1 ug/mL. BSA solution as well as blood carrying ticagrelor were passed at various velocities through columns containing two types of sorbent (Cytosorb and Porapak Q). Ticagrelor concentration was measured from the affluent and effluent solution using a liquid chromatography technique with tandem mass spectrometric detection LC/MS/MS).

Results:
Ticagrelor removal peaked at 99% and 100% using 40 mL Cytsorb and Porapak Q columns, respectively, during BSA experiments. The most efficient ticagrelor drug removal from blood was obtained with 260 mL sorbent (113 g of Cytosorb), with a peak removal from whole blood of 100% and 99% from blood cells during a 10-hour recirculating experiment reaching blood and plasma levels of 15 and 2 ng/mL, respectively, much below the ticagrelor platelet aggregation inhibition IC50 levels (30 ng/mL). Cytosorb has been also shown to absorb in bench experiments 99% of dabigatran in albumin solution and up to 96% of radiocontrast, creating the premises of a possible all-inclusive method of antiplatelets, anticoagulants, and radiocontrast removal.

Conclusion:
Sorbent adsorption demonstrates robust removal of ticagrelor from BSA solution and human blood samples.
Abstract 12917: Model of End-stage Liver Disease Excluding INR (MELD-XI) Scoring System Provides the Additional Long-Term Prognostic Information to Malnutrition in Patients Admitted With Acute Decompensated Heart Failure
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Seo Masahiro , Ikeda Iyo , Fukunami Masatake
Published: April 2024

Backgrounds:
Hospitalization for acute decompensated heart failure (ADHF) is associated with a high mortality after discharge. Liver dysfunction has a prognostic impact on the outcome of patients with advanced heart failure. A model of end-stage liver disease excluding INR (MELD-XI), a robust scoring system of liver dysfunction, has been shown to provide prognostic information in heart failure patients. Malnutrition is also associated with poor outcome in ADHF pts. However, there is no information available on the long-term prognostic significance of MELD-XI score in patients admitted with acute decompensated heart failure (ADHF), relating to malnutrition.

Methods and Results:
We studied 303 consecutive ADHF patients discharged with survival. MELD-XI score was calculated by the following formula: 5.11·ln(bilirubin)+11.79·ln(creatinine)+9.44. Nutritional status was evaluated by Geriatric Nutritional Risk Index (GNRI) calculated as follows: 14.89·serumalbumin (g/dl) + 41.7·BMI/22. During a follow-up period of 5.0±4.3 yrs, 75 patients had cardiovascular death (CVD). At multivariate Cox analysis, MELD-XI score (p=0.0025) and GNRI (p=0.0025) were significantly independently associated with CVD, independently of systolic blood pressure, serum sodium level and prior heart failure hospitalization. ROC analysis revealed that MELD-XI score of 12 was a fair discriminator for CVD (AUC 0.70 [0.64-0.77]). In group with malnutrition (GNRI<96.5: median value), patients with high MELD-XI score (≥12) had a higher risk of CVD than those with low MELD score (43% vs 25%, p=0.02, HR 1.9 [1.1-3.3]). In group without hyponatremia (GNRI≥96.5), patients with high MELD-XI score also had a higher risk of CVD (38% vs 11%, p<0.0001, HR 4.4 [2.0-10.0]).

Conclusion:
A MELD-XI scoring system could provide the additional long-term prognostic information to malnutrition in ADHF patients.
Abstract 12927: Concurrent Pneumonia has no Association With 30-Day All-Cause or Heart Failure Readmissions but is Associated With Higher 30-Day Pneumonia Readmission and MayBe Associated With Higher 30-Day All-Cause Mortality in Older Medicare Beneficiaries Hospitalized for Heart Failure
Authors: Inampudi Chakradhari , Fletcher Ross D , Zhang Sijian , Morgan Charity , Deedwania Prakash , Fonarow Gregg C , Aronow Wilbert S , Wu Wen-Chih , Brown Cynthia J , Anker Stepfan D , Allman Richard M , Ahmed Ali
Published: April 2024

Background:
Pneumonia (20%) is the second leading cause for 30-day all-cause readmission after heart failure (HF; 27%). However, little is known about the impact of pneumonia during index HF hospitalization on 30-day all-cause readmission.

Methods:
Of the 8049 Medicare beneficiaries hospitalized for decompensated HF (72% with known HF) discharged alive from 106 U.S. hospitals (1998-2001), 2048 (25%) had pneumonia (1670 on admission and 378 in-hospital). Using propensity scores for pneumonia, we assembled a matched cohort of 1982 pairs of patients balanced on 33 baseline characteristics.

Results:
30-day all-cause readmissions occurred in 899 (23%) of matched patients and there was no difference between those with and without pneumonia (HR, 1.00; 95% CI, 0.88-1.15; p=0.947; Fig, left). 30-day pneumonia readmission occurred in 41 matched patients which was higher among those with pneumonia (HR, 1.96; 95% CI, 1.03-3.74; p=0.041). 30-day HF readmission occurred in 342 patients but had no association with pneumonia (HR, 1.10; 95% CI, 0.89-1.36; p=0.365). 30-day all-cause death occurred in 303 patients, which was higher among those with pneumonia (9% vs 7%; HR, 1.26; 95% CI, 1.00-1.58; p=0.046; Fig, right). These associations persisted throughout 12 months post-discharge.

Conclusions:
Among patients with HF, on-admission or in-hospital pneumonia during index hospital admission is associated with significantly higher 30-day death and pneumonia readmissions but not with 30-day all-cause or HF readmissions
Abstract 13043: Atrial Fibrillation is Associated With Cardiovascular Events in Obese Japanese With One or More Cardiovascular Risk Factors: Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Watanabe Hiroaki , Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: April 2024

Introduction:
Obesity has been shown as a risk of incidence and durability of atrial fibrillation. However, the relationship between obesity and prognosis of patients with atrial fibrillation remains unclear.

Hypothesis:
We assessed the hypothesis that obesity was associated with cardiovascular events in atrial fibrillation patients with cardiovascular risk factors.

Methods:
We enrolled 3,585 patients in the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We conducted 12-lead electrocardiography, and atrial fibrillation was identified based on electrocardiography. Obesity was defined as body mass index over than 25 kg/m2. The primary endpoints were fatal/nonfatal cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection).

Results:
The number of patients whose electrocardiograms revealed atrial fibrillation was eighty-four. In obese patients, atrial fibrillation patients (N=35) suffered more cardiovascular events (log rank 7.17, p=0.007) than sinus rhythm patients (N=1282), but in nonobese patients, cardiovascular events were similar (log rank 0.10, p=0.76) in atrial fibrillation (N=48) and sinus rhythm patients (N=2220). After adjusting for age, gender, hypertension, smoking, and diabetes, atrial fibrillation was an independent predictor of cardiovascular events in the obese group (hazard ratio 3.02, 95% confidence interval 1.18-7.78).

Conclusions:
There was a significant difference in the association between atrial fibrillation and subsequent cardiovascular events in the presence or absence of obesity. Weight reduction might improve the prognosis of atrial fibrillation patients.
Abstract 13074: Convergent Ablation for Long-Standing Persistent Atrial Fibrillation: Single Center Experience From a Large Regional Medical Center
Authors: Piedad Bryan , Luu Theresa , Blatt Jacob , Riley Michael , Egoavil Cesar , Dercola John , Martinelli Karen , Kanuru Narendra
Published: April 2024

Introduction:
The treatment of long-standing, persistent AF is challenging. Conventional transvenous radiofrequency (RF) ablation strategies have provided only modest success, often requiring multiple procedures to maintain normal sinus rhythm. The convergent ablation procedure is a hybrid approach, involving a minimally invasive epicardial ablation combined with a traditional transvenous endocardial ablation. This comprehensive approach may offer a more effective treatment for long-standing persistent AF.

Methods:
From 12/2013 through 05/2015, we performed 50 convergent ablations (40 male; 10 female) for symptomatic, long-standing persistent AF. Mean age was 64.1±9.2 years with a mean CHADS-VASC score of 2.5±1.5. Mean LA volume was 161.5±44.5 cc. Mean weight was 103.3 kg ± 23.1 kg, and mean LVEF was 51.7%±21.7%. All patients had failed at least one anti-arrhythmic medication. Epicardial ablation was performed via a sub-xyphoid, endoscopic approach followed by transvenous endocardial ablation (32 RF and 18 cryoablation). Transvenous cavo-tricuspid isthmus (CTI) ablation was performed in all patients using RF energy.

Results:
Mean procedural time was 2.4±0.6 hours (epicardial) and 2.9±0.75 hours (endocardial). Acute procedural success was 100%, defined as complete pulmonary vein isolation, comprehensive ablation of the posterior LA, and CTI block. Mean hospital stay was 3.4±1.7 days. At mean follow-up of 206±150 days, 47 remain in NSR (94%). Of those patients who underwent transvenous radiofrequency (RF) ablation, 29 of 32 were in sinus rhythm (91%), while 18 of 18 of those who underwent cryo-ablation were in sinus rhythm (100%). At last follow-up, anti-arrhythmic therapy was discontinued in 22 patients (44%). Major complications occurred in 2 patients (4%): rectus hematoma and pericardial tamponade.

Conclusions:
Convergent ablation is an effective treatment for long-standing persistent AF, demonstrating high success rates with low complication rates. Longer follow-up and prospective, randomized trials are needed.
Abstract 13077: Maternal and Fetal Outcomes Among Pregnant Women With Frequent Premature Ventricular Complexes
Authors: Tong Calvin Ka Wing , Deyell Marc W , Wheeler Miriam , Kiess Marla , Rychel Valerie , Grewal Jasmine
Published: April 2024

Introduction:
Premature ventricular complexes (PVCs) in pregnancy are being increasingly recognized and many women have associated symptoms. Although thought to be benign, there is limited data on maternal and fetal outcomes in pregnancies with frequent PVCs. The objectives of this study were to describe the PVC burden and patterns, and to assess maternal and fetal outcomes in pregnancies with frequent PVCs.

Methods:
In this prospective observational cohort study, 40 consecutive pregnancies referred to our institution between January 2010 and March 2015 with PVC burden of greater than 0.1% on Holter studies were included. We reviewed electrocardiograms to identify PVC morphologies and Holter studies to determine PVC burden. PVC burden were stratified into low (n = 20) and high (n = 20) severity based on the median PVC burden of 6.8%. Student’s t-tests and Fisher’s exact test were used to evaluate difference in maternal and fetal outcomes by severity of PVC burden and beta-blocker (BB) use. Paired t-test was used to compare changes in PVC burden from antepartum to postpartum. Pearson analysis was performed to evaluate correlation between PVC burden and cardiac function.

Results:
Antepartum palpitations, pre-syncope, congestive heart failure, syncope, and deterioration in NYHA class were present in 70%, 25%, 5%, 2.5%, and 10% respectively. Fifty-five percent continued to have palpitation postpartum. Ninety-two percent of PVCs originated from right ventricular outflow tract. PVC burden decreased from 9.3 ± 9 % antepartum to 3.9 ± 5.4 % postpartum (
p
= 0.118). There was no correlation between PVC burden and left ventricular end diastolic and end systolic dimensions, and left ventricular ejection fraction (r = 0.08,
p
= 0.74; r = 0.03,
p
= 0.92; r = -0.16,
p
= 0.50). Gestation at delivery was 39 ± 2 weeks with newborn weight of 3251 ± 576 grams. APGAR scores at 1 and 5 minutes were 8 ± 2 and 9 ± 1 respectively. One newborn had intrauterine growth restriction and 3 had meconium liquor. There was no difference in the above outcomes in subgroup analyses based on severity of PVC burden and BB use.

Conclusions:
Maternal and fetal outcomes in pregnancies with frequent PVCs were favorable. Severity of PVC burden and BB use did not have significant impact on maternal and fetal outcomes.