bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 76: A Survey of Airway Skills and Equipment Available During In-Hospital Cardiac Arrest in the United Kingdom
Authors: Nolan Jerry , Bell Chambers Emma L , Bradley Tom , Astin Jeremy R , King Emma
Published: April 2024

Objectives
The Resuscitation Council (RC (UK)) recommends that cardiac arrest teams include members skilled in tracheal intubation and provides a list of the equipment that should be available at cardiac arrests. We surveyed intensive care unit (ICU) residents in all general adult ICUs in the UK to determine compliance with these guidelines. The Royal College of Anaesthetists “Initial Assessment of Competency”, normally taken after 3 months of anaesthetic training, was used to define competency in tracheal intubation.

Method
Using a standardised questionnaire, a resident in each of the 254 general adult ICUs in the UK was surveyed by telephone.

Results
Responses were obtained from a resident in 192 (76%) of ICUs. ICU residents attended cardiac arrests in 129 (67%) of hospitals; 34% of these residents were not competent in tracheal intubation. Only 124 (65%) of the arrest teams always included a member with at least 6 months anaesthetics experience. Operating department practitioners (anaesthetic assistants) were sole airway operators in 2% of teams. Cardiac arrest airway equipment data was obtained from 181 hospitals (table). Of the 25 cardiac arrest teams not using LMAs, 12 used alternative supraglottic airway devices (SADs). Capnography was routinely available to 22% of arrest teams.

Conclusions
One third of ICU residents in cardiac arrest teams are not competent in tracheal intubation. Capnography is available to only one fifth of teams. The need for intubation skills at cardiac arrests has been questioned, and may be unnecessary if members of the arrest team are competent in the use of SADs. Capnography is now recommended for confirming intubation at cardiac arrests; it also provides feedback on CPR quality and an early indication of return of spontaneous circulation. All cardiac arrest teams in the UK should have capnography available and implement its use urgently.
Abstract 8105: The Nucleotide-Binding Oligomerization Domain-Containing Protein 1 Underlies Cardiac Apoptosis in Type 2 Diabetic Mice
Authors: Fernandez-Velasco Maria , Prieto Patricia , Terron Veronica , Delgado Carmen , Martín-Sanz Paloma , Bosca Lisardo
Published: April 2024

Introduction.
The pathogenesis of diabetic cardiomyopathy is complex, and involves deregulated lipid metabolism, insulin resistance, mitochondrial dysfunction together with a chronic inflammatory state and cardiac apoptosis sensitization. It has been proposed that the innate immune response contributes to the onset of diabetes. Indeed, both Toll-like (TLRs) and Nucleotide-binding oligomerization domain-like (NLRs) receptors have been implicated in the pathogenesis of insulin resistance and diabetes. However, less is known regarding the contribution of these receptors to diabetic cardiac disease. Although increased cardiomyocyte (Cm) apoptosis has been described in the heart of diabetic (db) mice, the mechanisms for increased cell death remain unknown. NLR proteins have functions beyond those in the innate immune response, including the regulation of the apoptotic process. In this regard, a relationship between a subfamily of NLR, nucleotide-binding oligomerization domain-containing protein-1 (NOD1) and the caspase activation has been established. In this report we analyze the involvement of NOD1 in cardiac apoptosis related to type 2 diabetes.

Methods and Results.
We used a genetic mouse model of type 2 diabetes that mimics several symptoms found in type 2 diabetic patients, including obesity, hyperglycemia, hyperinsulinemia and depressed cardiac function. Our results demonstrate the expression of NOD1 in cardiac tissue, providing the first evidence of an up-regulation of NOD1-pathway in hearts of db mice. We also detect the activation of RIP2, a kinase involved in NOD1 signaling. Concomitant to these observations, chronic activation of NF-κB and apoptotic-pathways (caspase 3 and Bax over-expression and X-IAP down-regulation) were observed in hearts of db mice. At the cellular level, native Cms showed higher protein levels of NOD1 compared to wild type. As a proof of concept, both selective activation (iEDAP) and down-regulation of NOD1 (siRNA) modulate NF-κB and apoptotic-pathways in cardiac cells.

In conclusion
, our results indicate that cardiac NOD1 induction may participate in the process of Cms apoptosis related to diabetic cardiomyopathy and open a new paradigm linking NLRs to the cardiac damage related to type 2 diabetes.
Abstract 8124: Effect of Strong Lipophilic Statin Therapy on Left Atrial Structure and Function Assessed by Speckle Tracking Echocardiography in Elderly Hypertensive Patients
Authors: Fujii Tomoko , Tanaka Ryuhei , Ono Koji , Watanabe Takatomo , Goto Yoshiaki , Nagaya Maki , Onishi Noriyuki , Abe Shintaro , Matsuoka Reiko , Kato Takashi , Warita Syunichiro , Kojima Tai , Iwama Makoto , Hirose Takeshi , Tanihata Shintaro , Noda Toshiyuki , Iida Mami , Watanabe Sachiro , Kawasaki Masanori , Minatoguchi Shinya
Published: April 2024

Background:
Prevention of the processes of left atrial (LA) remodeling associated with atrial fibrillation and heart failure especially in elderly hypertensive patients (HT) may have a major public health impact. Statins may attenuate cardiac hypertrophy by inhibition of intracellular signaling molecules such as Rac 1 and may be associated with lower mortality in patients with heart failure. We assessed the hypothesis that strong lipophilic statin (pitavastatin) has a beneficial effect on LA structure and function in elderly hypertensive patients by preventing left ventricular (LV) hypertrophy through pleiotropic effect.

Methods:
LA phasic volume by Simpson's rule and LA total, passive and active emptying function (EF), and LA strain rate (SR) at systole, early diastole and atrial contraction were measured in apical 4-chamber view by speckle tracking method that can provide time-LA volume curve automatically and promptly among three groups; HT with statin group was consisted of hypertensive patients with hyperlipidemia treated with statin for more than two years (n=68, age 74±4, 32 men), HT without statin group was age-matched HT but without hyperlipidemia and statin (n=68, age 74±4, 40 men) and control group was age-matched normal subjects (n=66, age 74±6, 29 men). LV mass, LV ejection fraction and E/e’ as a diastolic function were measured.

Results:
LA volume and function in HT with statin were more preserved than HT without statin despite no difference in LDL cholesterol, blood pressure and antihypertensive drug use. SR at systole and atrial contraction in HT with statin was significantly increased associated with dilation of LA. LA volume and function in HT with statin were comparable to control (Table).

Conclusion:
Pitavastatin had a beneficial effect on LA structure and function associated with preserved diastolic function through pleiotropic effects in elderly hypertensive patients.
Abstract 8160: Risk Factors For Hospital Mortality And Morbidity Following The Norwood Procedure: Results From The Multicenter Single Ventricle Reconstruction Trial
Authors: Tabbutt Sarah , Ghanayem Nancy , Cooper David S , Frank Deborah U , Lu Minmin , Frommelt Peter , Lai Wyman W , Goldberg Caren S , Graham Eric M , Dent Krawczeski Catherine , Mahony Lynn , Ravishankar Chitra , Sleeper Lynn A , Kirsh Joel A , Lewis Alan , Lodge Andrew , Ohye Rick , Pizarro Christian , Simsic Janet , Spurrier Ellen , Stylianou Mario , Laussen Peter ,   for the Pediatric Heart Network Investigators
Published: April 2024

BACKGROUND
We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in a large prospective cohort of newborns with hypoplastic left heart syndrome and variants enrolled in the Single Ventricle Reconstruction trial.

METHODS
Potential predictors for outcome included patient and procedure related variables and center/surgeon volumes. Outcome variables occurring during the Norwood procedure and prior to hospital discharge or stage 2 surgery included: mortality, end-organ complications, length of ventilation and hospital length of stay (LOS). Variables with univariate p ≤ .2 were used as candidate predictors for multivariable regression modeling (p < .05, significant). A reliability estimate of greater than 50% obtained by bootstrapping was required for terms to remain in the mortality model.

RESULTS
Analysis included 549 patients from 15 centers. Hospital mortality was 16% at a median of 16 (1 - 149) days after the Norwood procedure. Shunt type at the end of the Norwood procedure was not a significant risk factor for mortality during the Norwood hospitalization. Independent risk factors for mortality (n=88), renal failure (n=46), sepsis (n=93), length of ventilation among survivors (7 days, range 1 - 270) and hospital LOS among survivors (24 days, range 6 - 270) are shown in the Table.

CONCLUSION
Innate patient factors, pre-operative condition and lower center volume impact post-operative mortality and morbidity during the Norwood hospitalization.
Abstract 8236: Effect of Telmisartan on Paroxymal Atrial Fibrillation in Hypertensive Patients with Different Left Atrial Size
Authors: Fogari Roberto , Mugellini Amedeo , Derosa Giuseppe , Preti Paola
Published: April 2024

Aim of this study was to evaluate the effect of telmisartan (T) and amlodipine (A) on atrial fibrillation (AF) recurrence in hypertensive patients with paroxymal AF and normal or increased left atrial (LA) size. We studied 288 mild hypertensive outpatients in sinus rhythm but will at least 2 ECG-documented episodes of AF in the previous 6 months; half of them had an inferior-superior LA dimension <45 mm, and the other half >45 mm. The patients were randomized to T 80-160 mg/od (n=72 with LA <45 mm, n= 72 with LA >45 mm) or to A 5-10 mg/od (n=72 with LA <45 mm, n= 72 with LA >45 mm) for one year. Blood pressure and a 24 h ECG were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. SBP and DBP were significantly and similarly reduced by the 2 treatments (p<0.001 vs baseline) in the 4 groups of patients. Among those with LA dimension >45 mm a total of 35 (48.6%) patients treated with A had a recurrence of AF as did 18 (25%) patients treated with T (p<0.05 vs A) Among the patients with LA dimension <45 mm a total of 23 (31.9%) patients treated with A had a recurrence of AF as did 8 (11.1%) patients treated with T (p<0.01 vs A). Despite a similar BP lowering T was more effective than A in preventing new episodes of AF and it was particularly evident in patients with normal LA size. It suggest that in this type of patients ARB treatment is to prefer to Ca blocker treatment and that earlier it is begun greater is the prevention of AF recurrences.
Abstract 8266: Double Jeopardy: The Influence of Excessive Daytime Sleepiness and Impaired Cognition on Quality of Life in Adults with Heart Failure
Authors: Riegel Barbara , Sayers Steven , Weintraub William , Ratcliffe Sarah J
Published: April 2024

Poor health-related quality of life (HRQL) is pervasive in adults with heart failure (HF). Others have shown that cognitive impairment (CI) is associated with poor HRQL, but the contribution of EDS to HRQL has not been described in HF.

Methods:
Adults with a confirmed diagnosis of stage C chronic HF were enrolled into a prospective cohort comparison study. Those with dementia, recent drug or alcohol abuse, and night shift workers were excluded. Data were obtained from 280 subjects enrolled from 3 sites in the northeastern US, 242 of whom completed the 6-month follow-up. At baseline we identified a cohort with EDS and a control group without EDS using the Epworth Sleepiness Scale (score ≥6 = EDS). Each EDS group was further subdivided into those with and without CI using a battery of 5 neuropsychological tests (score > 1.5 SD on ≥2 tests). Two disease-specific measures, Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL; higher scores indicate better HRQL. General linear modeling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL summary scores after adjusting for enrollment site, age, gender, race, income, NYHA functional class, depressive symptoms, and perceived health.

Results:
At 6-months the remaining sample was 62.5 (SD 12) years old, mostly male (63%), white (65%), and functionally compromised (72% NYHA class III/IV). Cognitive impairment and EDS were unique constructs (r=0.05, p=0.44). The cohort with EDS+ and CI+ had the lowest overall KCCQ score (KCCQ: 62.1±22.3) compared to the cohort without EDS or CI (79.1±18.3, p=<.001). A similar effect was seen on the FOSQ (FOSQ: 16.7±2.7) compared to the cohort without EDS or CI (18.7±1.8, p=<.001). The cohort with CI but without EDS was not significantly different in HRQL from the cohort without EDS or CI (KCCQ: p=0.39, FOSQ: p=0.20).

Conclusion:
Daytime sleepiness combined with CI is a significant predictor of HRQL in adults with HF. Cognitive impairment is challenging to influence but interventions designed to influence EDS may improve HRQL in this population.
Abstract 8279: Avoiding Cerebral Embolism during Ablation of Atrial Fibrillation by the Use of Radiofrequency Hot Balloon Catheter
Authors: Yamaguchi Yoshio , Sohara Hiroshi , Takeda Hiroshi , Ueno Hideki , Satake Syutaro
Published: April 2024

Background
Cerebral Embolism (CE) is a serious complication associated with conventional radiofrequency (RF) catheter ablation of atrial fibrillation (AF). It is partly because of non-uniform heating of the tissue due to direct resistive heating by RF current under regional cooling by changeable blood flow or irrigation, resulting in thrombus formation. To avoid non-uniform heating, we have developed a RF hot balloon catheter system.

Methods and Results
In this RF hot balloon catheter system, the balloon could be uniformly heated at the target temperature between 60 and 65°C, as the inner fluid of the balloon was heated by RF current (1.8 MHz), and agitated by a specially designed vibration generator (Fig). The tissue in contact with the hot balloon was ablated by heat conduction, where the lesion depth was determined by the temperature of the balloon and the delivery time of RF energy. We experimentally performed pulmonary vein (PV) isolation in 10 pigs and histological examination of serial sections of the atrial lesions and the brain after ablation. There was no thrombus formation at ablated lesion and no cerebral infarction in all 10 pigs. We treated 445 patients with AF (Paroxysmal AF (PAF), n=270; Persistent AF (Per-AF), n=77; Long persistent AF (Long-AF), n=98) by PV antral isolation or box isolation ( isolation of PV and left posterior atrium) using this system and randomly performed magnetic resonance imaging (MRI) of brains in 120 patients after ablation. Within 12 months after ablation, we have no new symptom of cerebral infarction in all patients, and no CE lesion detected by Brain MRI in 120 patients. During 12 months follow up, no AF episodes were detected without anti-arrhythmic drugs in 346 patients (PAF, n=238 (88%); Per-AF, n=53 (69%); Long-AF, n=55 (56%)).

Conclusion
PV antral isolation or box isolation using a RF hot balloon catheter system could be performed without complication of CE and successfully treat most of the patients with AF.
Abstract 8398: Trends in Clinical and Demographic Features of Patients with Acute Myocardial Infarction in the First Decade of the 21st Century. A Report from the American Heart Association Get-With-The-Guidelines Coronary Artery Disease Program
Authors: Boyer Nathan M , Laskey Warren K , Cox Margueritte , Bhatt Deepak L , Hernandez Adrian F , Peterson Eric D , Cannon Christopher P , Fonarow Gregg C
Published: April 2024

Introduction
Decreases in incidence of acute myocardial infarction (AMI) in the U.S. have been observed over the last 40 years, in part due to beneficial changes in risk factors. The composition of the U.S. population from 2000-2010 has changed and it remains unknown whether the clinical (CLIN) and demographic (DEMO) features of patients with AMI may also have changed.

Methods
We reviewed data collected from 136,238 patients with AMI admitted from 2003-2008 to hospitals participating in the American Heart Association - Get With The Guidelines Coronary Artery Disease program. The dataset was analyzed in total and stratified by type of AMI (STEMI or NSTEMI). CLIN and DEMO characteristics were assessed for each year and the odds of change in prevalence of each characteristic with time (per 1 year increase) was analyzed with univariable and multivariable logistic regression.

Results
Overall, the prevalence of obesity (30.4%) and the proportion of patients with HDL < 40 mg/dl (39.8%) increased while the prevalence of hypertension remained stable but high (68%). The proportion of patients with LDL > 100 mg/dL (32.8%) decreased over time. There was a significant increase over time in the proportion of patients with NSTEMI. Racial distribution of patients also varied significantly over time. Differences in DEMO and CLIN factors within and between AMI strata varied from the observations in the combined patient sample.

Conclusions
We observed, overall, a decreasing prevalence of younger individuals and an increasing prevalence of obesity and low HDL, findings which represent continuation of a pattern observed at the end of the 20th century. Stratum-specific differences in the prevalence of key risk factors warrant caution considering AMI a uniform entity. In light of changes in the DEMO composition of the US population from 2000-2010, these trends have important implications for projections of disease burden and targeting prevention efforts.
Abstract 8399: Circulating Mononuclear Cells with Class A Macrophage Scavenger Receptor Were Specifically Increased in Patients with Acute Coronary Syndrome
Authors: Nakayama Masafumi , Ogawa Hisao , Kaikita Koichi
Published: April 2024

Objective:
We previously remarked that class A macrophage scavenger receptor (SR-A), in peripheral blood mononuclear cells (PBMCs), was a candidate as a predictive marker for acute coronary syndrome (ACS) utilizing a gene chip microarray system. Herein, we examined SR-A levels in atherosclerotic lesions and in circulating monomuclear cells.

Methods and Results:
We obtained atherosclerotic lesion samples utilizing directional coronary atherectomies: 11 consecutive patients with unstable angina (UA); and, 13 consecutive patients with stable exertional angina (SEA). Immunohistochemical analyses revealed that SR-A was abundantly expressed in the macrophages of UA patients. SR-A mRNA levels of the atherosclerotic lesions in the UA patients and in the SEA patients were 3.8±1.5 and 1.0±0.6, respectively. SR-A mRNA levels of the coronary atherosclerotic lesions were significantly higher in the UA patients than in the SEA patients (p<0.03). Utilizing flow cytometric analysis, PBMCs were collected from 255 subjects: 67 consecutive ACS patients; 87 consecutive SEA patients; and, 101 controls. The frequencies of CD14-positive PBMCs (monocytes), that stained for SR-A, were 1.9±1.6% , 0.7±0.5% , and 0.7±0.5%, respectively. The frequency of SR-A positive monocytes was significantly higher in the ACS Group than in either the SEA or Control Groups (p<0.001); however, there were no significant differences between the Control and SEA Groups. There were no significant differences in the frequencies of SR-A positive monocytes between the patients with UA and the patients with acute myocardial infarction. In the ACS Group, the frequencies of SR-A positive monocytes at onset, at 1 day and at 7 days after onset, were 1.7±1.1%, 1.1±0.8%, and 1.1±0.5%, respectively. The frequency of SR-A positive monocytes in the ACS Group was significantly decreased within 24 hours of onset receiving orthodox medical treatment (p<0.01).

Conclusion:
The SR-A level increases in unstable atherosclerotic plaque, as well as in the PBMCs in ACS patients. SR-A is a well known macrophage marker. The detection of SR-A positive monocytes in the peripheral circulating blood provides crucial clinically and pathophysiologicaly significant information about unstable plaque in ACS patients.
Abstract 8406: The Addition of Direct Renin Inhibitor Aliskiren to Standard Therapy Suppresses Enhanced Cardiac Sympathetic Activity in Patients with Systolic Heart Failure
Authors: Yoshihiro Imamura , Takaki Tsutumi , Akira Yamada
Published: April 2024

Introduction:
Aliskiren, direct rennin inhibitor, decreases plasma brain natriuretic peptide (BNP) concentrations in patients with heart failure (HF). However, the effect of aliskiren on cardiac sympathetic nerve function is unclear.

Hypothesis and Objectives:
We examined the effects of aliskiren on neurohormonal function when added to standard therapy in patients with systolic HF, under the hypothesis that aliskiren therapy would affect sympathetic nerve function.

Methods:
We enrolled 34 patients with HF due to systolic dysfunction (LVEF of <45%), receiving standard therapy including an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker and a beta-blocker. We randomly assigned 17 patients to receive additional aliskiren treatment 150 mg/d (aliskiren group), while 17 patients continued standard therapy (control group). All patients underwent neurohormonal measurements and planar
123
I-metaiodobenzylguanidine (MIBG) imaging. In the MIBG images, the heart/mediastinum (H/M) ratio and cardiac washout rate (WR) were determined for evaluating cardiac sympathetic activity. The follow-up data was obtained three months later.

Results:
There were no significant changes in the hemodynamics in either group. In the aliskiren group, plasma renin activity fell and concomitantly, the WR decreased and H/M ratio increased during the follow-up period (WR: 39.4 ± 13.3 % to 32.9 ± 9.2 %, p = 0.009, H/M: 2.84 ± 0.68 to 3.13 ± 0.77, p = 0.016). In addition, BNP fell from 150.7 ± 102.3 pg/mL to 99.9 ± 70.5 pg/mL (p=0.001). We found a significant negative correlation between the change in WR and the baseline PRA in the aliskiren group (r = - 0.64, p = 0.004). This correlation suggests that inhibition of the circulating renin activity might be possible mechanism for sympatho-inhibitory effects by aliskiren. In the control group, MIBG imaging findings and plasma BNP concentration remained unchanged.

Conclusions:
The addition of aliskiren to standard therapy led to renin-angiotensin-aldosterone system inhibition, which subsequently led to the suppression of enhanced cardiac sympathetic activity and a decrease in plasma BNP concentrations in patients with systolic HF.
Abstract 8440: Guideline Recommended Evaluation in Patients with a First Episode of Atrial Fibrillation
Authors: Sinner Moritz , Greiner Melissa A , Mi Xioajuan , Hernandez Adrian F , Jensen Paul N , Piccini Jonathan P , Setoguchi Soko , Walkey Allan J , Heckbert Susan R , Benjamin Emelia J , Curtis Lesley H
Published: April 2024

Background:
In patients with a first episode of atrial fibrillation (AF), current guidelines specifically recommend assessment of cardiac function, valvular and ischemic heart disease, and thyroid, kidney, and liver function. We assessed the completion of guideline recommended evaluations among 244,921 patients with a new diagnosis of AF.

Methods and Results:
We studied commercially insured patients from MarketScan, aged 18-64 years (n=40,245), and a 5% nationally representative cohort of Medicare beneficiaries ≥65 years (n=204,676). All patients were first diagnosed with AF between 2000-2008. We used claims data to assess completion of guideline recommended physician visits and examinations, electrocardiograms, echocardiograms, and laboratory tests for thyroid, renal and liver function. From 2004-2007, evaluation rates increased. By 2007, all guideline recommended evaluations were completed in 17.4% of the MarketScan sample and 18.5% of the Medicare cohort (Figure). Almost all patients received electrocardiograms, and two-thirds of patients received an echocardiogram. In 2007, laboratory testing for thyroid function was performed in 31.7% of patients in the MarketScan and 34.2% in Medicare. Stratification by sex (Figure), race, or geographic region revealed only minor differences in the completeness of evaluation. Evaluation rates were stable across age groups as well (Figure), except for nonagenarians, where the rate of completed evaluation averaged across the observation period was 9.5%.

Conclusion:
In this large nationally representative study covering a wide age-range, the completion rate of guideline-recommended evaluation following a new diagnosis of AF was low. Except for nonagenarians, the evaluation completion rate varied only marginally with age, sex, race and geographic region.

Figure:
Increase of completed evaluation over time. Left: MarketScan; right: Medicare. Above: stratified by sex; Below: stratified by age groups.
Abstract 8443: Circulating MicroRNAs Expression in Human Plasma is Dysregulated by Heart Failure
Authors: D alessandra Yuri , Beltrami Antonio P , Carena Maria Cristina , Devanna Paolo , Fortini Cinzia , Cecaro Fabrizio , Ferrari Roberto , Cesselli Daniela , Toffoletto Barbara , Bergamin Natascha , Pompilio Giulio , Capogrossi Maurizio C
Published: April 2024

Purpose:
Circulating microRNAs (miRNAs) have recently been identified and proposed as novel biomarkers of several diseases. Here we examined miRNAs expression profile of heart failure (HF) patients, NYHA class I-IV, in comparison to matched controls.

Methods:
We analyzed the expression of 365 miRNAs in plasma samples from healthy donors (n= 5) and NYHA class I-IV HF patients (n= 5/group). MiRNAs expression was evaluated using TaqMan microRNA Arrays followed by a validation step.

Results
were normalized using miR-532-5p as an internal experimentally validated calibrator with low dispersion of expression levels and null association with HF. Validated miRNAs were examined in the plasma of healthy subjects (n=10) and NYHA class I-IV HF patients (n=10-14/ group).

RESULTS:
Of ∼190 miRNAs expressed in plasma of healthy subjects and HF patients we were able to identify 17 miRNAs dysregulated by HF (14 up- and 3 down-regulated), with 7 showing no expression in control samples (miR-154,-299, -376a, -379, -409-5p, -548a and -654). Expression analysis of 9 of these 17 miRNAs throughout the 4 NYHA classes showed that miR-154, -221, -376a, -409-5p and -379 are strongly overexpressed (20 to 170 folds vs controls) in all HF subjects while miR-124a, -375 and -451 exhibit a significant downregulation in class I (40%), IV (50%) and III and IV (70 and 90%) respectively. In agreement with a prior study, miR- 423-5p exhibited an increase in all HF subjects, statistically significant in NYHA classes II and IV (3 to 4 folds). Interestingly miR-379 showed marked differences between NYHA classes I and II and II and III. Further, 8 miRNAs (miR-1, -21, 146a, -548a, -299-5p, -331-5p, -654-5p and -376c) differentiated controls from NYHA class IV patients (n=14) exhibiting an up-regulation of 6 to 40 folds.

Conclusions:
A novel miRNA signature consisting of enhanced expression of 14 and decrease of 3 plasma miRNAs was found in HF patients (NYHA classes I to IV). These findings pave the way for the identification of HF dysregulated miRNAs which can be viewed as promising biomarkers of heart failure.
Abstract 8446: Human Fetal Cardiac Ejection Fraction in Normal and Diabetic Pregnancy Assessed by Matrix 3D/4D Echocardiography
Authors: Zhang Minjuan , Schaal Michael , Li Xiaokui , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Diabetic pregnancy carries higher risk of fetal development abnormality compared to normal pregnancy. Therefore, fetal growth should be monitored during diabetic pregnancy. We used a 4D matrix method to evaluate whether maternal diabetes could affect fetal heart function.

Methods:
24 women 18.0-33.1 weeks gestational age (mean 23.6 ± 4.5 weeks) were included: 12 insulin-dependent diabetic pregnant patients and 12 healthy pregnant women with the same gestational ages. A Philips iE33 ultrasound system with an X7-2 matrix array transducer was used. 4D volumes were acquired from the fetuses with an external heart rate simulator. 4D data was analyzed by QLab 6.2 software (Philips). End-systolic and end-diastolic volumes of left and right ventricles (LV, RV) and ejection fraction (EF) derived for each individual were calculated semi-automatically, and maternal blood HbA1C were recorded.

Results:
Blood HbA1C levels of the diabetic group were 6.99±1.10%, which was higher than the normal level (5.0%). LV EF of the fetuses with diabetic mothers ranged from 52.4% to 85.9% (mean 70.2 ± 11.2%), and 52.3% to 83.3% (mean 71.5 ± 10.5%) for the control group. No significant difference was shown between LV EFs (P = 0.4029). However, RV EF was 55.3% to 85.1% (mean 66.8 ± 9.9%) in the diabetic group, compared to 64.9% to 87.1%(mean 77.2 ± 7.3%) for the control group (P = 0.0108).

Conclusions:
LV EF of human fetuses of diabetic mothers was normal, but RV EF of the diabetic pregnancy group was lower.
Abstract 8520: Total beta-Adrenoceptor Knockout Slows Conduction and Reduces Inducible Arrhythmias in the Mouse Heart
Authors: Stöckigt Florian , Brixius Klara , Nickenig Georg , Lickfett Lars , Schrickel Jan W
Published: April 2024

Introduction:
Beta-Adrenocepors (ß-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (ß1, ß2 and ß3) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. We assessed the hypothesis that TKO leads to considerable changes in electrophysiological parameters.

Methods:
We performed in vivo electrophysiological studies using right heart catheterisation in 10 TKO mice at the age of 14 weeks. As controles served 10 wild type mice (WT) with identical genetic background (129SV). We analyzed standard ECG- and electrophysiological parameters and arrhythmia inducibility.

Results:
The surface ECG of TKO mice revealed a reduced heart rate (359.2 ± 20.9bpm vs. 461.1 ± 33.3bpm; p <0.001) as well as prolonged P wave (17.5 ± 3.0ms vs. 15.1 ± 1.2ms; p=0.019) and PQ time (40.8 ± 2.4ms vs. 37.3 ± 3.0ms; p=0.013) compared to WT. Intracardiac ECG revealed a significantly prolonged infrahisian conductivity (12.9 ± 1.4ms vs. 6.8 ± 1.0ms; p <0.001). Functional testing showed extended atrial and ventricular refractory periods in TKO (40.5 ± 15.5ms vs. 21.3 ± 5.8ms; p = 0.004; and 41.0 ± 9.7ms vs. 28.3 ± 6.6; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p < 0.001) and the probability of induction of ventricular tachycardias (0% vs. 26%; p < 0.001) were reduced.

Conclusion:
TKO results in significant prolongation in cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. This finding confirms the importance of ß-AR in arrhythmogenesis and their role as therapeutic target.
Abstract 8563: Chronic Administration of Oral Vasopressin Type 2 Receptor Blocker, Tolvaptan Exerts Both Myocardial And Renal Protective Effects in Rats with Hypertensive Heart Failure
Authors: Morooka Hanako , Iwanaga Yoshitaka , Takase Toru , Akahoshi Yasumitsu , Tamaki Yodo , Nakano Yoshimasa , Fujiki Hiroyuki , Miyazaki Shunichi
Published: April 2024

Background:
During the diuretic therapy in heart failure (HF), the greatest concerns include additional activation of the neurohormonal cascade and renal injury. Although the recent clinical trials have shown the efficacy of the oral vasopressin (AVP) type 2 receptors (V2R) blocker, tolvaptan, the long-term effects on the myocardium and kidney in HF patients are not clear. Therefore, we tested chronic tolvaptan administration in rat hypertensive HF model and examined the chronic effects both on myocardium and kidney.

Methods and Results:
Dahl salt-sensitive hypertensive rats were given 8% high salt diet from 6 weeks of age. Not only circulating AVP level, but also myocardial AVP and V1a receptor (V1aR) expressions, and renal V1aR, V2R and aquaporin 2 (AQP2) expressions were significantly activated during the transition to HF (18-21 weeks of age). They were chronically treated with tolvaptan (30mg/kg/day) (Tolv group: n=21) or vehicle (n=22) from the LV hypertrophic stage (11 weeks of age) until 21 weeks. Chronic tolvaptan treatment persistently increased urine volume (94% increase) and decreased urine osmolality (43% decrease). Although there was no difference in blood pressure between the two groups, the survival rate in Tolv group was improved at 21 weeks of age from 45.5% to 81.0% (log rank test: p<0.01). At HF stage, LV fractional shortening was preserved (40.2% vs. 27.5%; p<0.05) and lung congestion was suppressed in Tolv group. Serum AVP level and plasma renin activity were not changed and mRNA levels of ANP, endothelin-1 (ET-1), AVP and V1aR in LV were significantly decreased in Tolv group. In contrast, renal histopathologic damage (glomerulosclerosis and tubulointerstitial fibrosis) was ameliorated, and renal function (creatinine clearance and sodium excretion) was improved in Tolv group at HF stage. Concomitantly, not only activation of AQP2, but also those of V2R, V1aR and ET-1 in kidney were significantly suppressed (p <0.05 in all).

Conclusions:
These results indicate chronic tolvaptan treatment has beneficial effects by preventing the progressions of both LV dysfunction and renal injury in hypertensive rats with HF. The underlying mechanism may be related to the prevention of local (myocardial and renal) neurohumoral activation.
Abstract 8609: Long-Term Outcomes of Surgical Treatment for Atrial Fibrillation in a Complex Population
Authors: Cesario David A , Cunningham Mark , Baker Craig , Cohen Robbin , Lopez Becky , Starnes Vaughn
Published: April 2024

Objective:
Surgical procedures are increasingly used to treat patients with long-standing persistent atrial fibrillation (AF). We sought to evaluate the safety and efficacy of various surgical approaches to AF at a high-volume tertiary surgical referral center.

Methods:
In this retrospective, single center study, we analyze our experience with the surgical treatment of AF. We evaluated 272 consecutive patients operated on, over a 9 year period. The surgical procedure for AF performed on each patient varied and was left up to the discretion of the surgeon with 29.8%(n=80) of patients receiving a complete right and left-sided Maze procedure including pulmonary vein isolation, 20.5%(n=55) of patients receiving a left-sided Maze procedure including pulmonary vein isolation, 4.9%(n=13) of patients receiving a right-sided Maze procedure including pulmonary vein isolation and 44.8%(n=120) of patients receiving pulmonary vein isolation alone. The vast majority of patients underwent at least one concomitant surgical procedure (93.7% AF surgery + concomitant surgical procedure, 6.3% stand-alone Maze). Patients were followed for a mean period of 42.3 months (+/-27 months). Cardiac rhythm was analyzed at discharge, 1-year follow-up visit and then re-analyzed on an annual basis.

Results:
In total 265 patients were analyzed, 4 patients were lost to follow-up and 3 expired prior to one year follow-up. Survival rates at 1-year were 96.5%. 50.2% of our patients were discharged in sinus rhythm. Additionally, 12.7% of patients received a new permanent pacemaker prior to their initial hospital discharge. At the 1-year follow-up visit 77% of patients were found to be in sinus rhythm or atrial paced rhythm and 23 % of patients were in AF/flutter. Our most recent analysis revealed 71.8 % of patients remain in sinus rhythm or atrial paced rhythm at up to 9 years post-surgical intervention.

Conclusions:
Surgical procedures for AF resulted in 1-year maintenance of sinus rhythm rates of 77%. These success rates appear largely maintained over a follow-up period of up to 9 years. Our patients were taken from a complex surgical population at a busy academic surgical center. We believe these numbers reflect real-world success rates in this patient population.
Abstract 8611: The Early Calcification in Neointima of in Stent Restenosis
Authors: Kawase Yoshiaki , Honye Junko , Okubo Munenori , Miyake Taiji , Kamikawa Sigeshi , Ota Hideaki , Kondo Hiroki , Tsuchiya Kunihiko , Matsuo Hitoshi , Jang Ik-Kyung , Ueno Katsumi
Published: April 2024

Background:
It has been proven that homogeneous neointima in the early phase after stent implantation transforms into atherosclerotic tissue in their late phase and develops calcification, but there are several cases that demonstrate calcification in the neointima of in stent restenosis (CISR) in their early phase (<=365days).

Purpose:
To elucidate the timing, prevalence, and extent of CISR.

Method:
The images of intravascular ultrasound (IVUS) taken between 6/30/2009 to 2/28/2011 were analyzed. The patients were divided into two groups depending on the follow up period: (less than 365 days or greater than 365 days)

Result:
A total of 169 IVUS images were analyzed. In general, patient with CISR had higher serum creatinine levels (3.3±3.4 mg/dl vs 1.4±1.6 mg/dl; p<0.001) with a higher percentage of hemodialysis patients (36% vs 6%; p<0.0001) and longer follow up time (2136±173 days vs 796±1129 days; p<0.001) than patients without CISR. The patients who developed CISR during the early follow up period (<=365 days) were almost exclusively those on hemodialysis (88%) and accounted for 8.2% of the patients with early follow up period.

Conclusion:
The development of CISR within the early follow up period (<=365days) was observed in 8.2% of patients, most of whom required hemodialysis.
Abstract 8626: Multi Detector CT Accurately Defines Infarct Size, but not Microvascular Obstruction Post Myocardial Infarction, and Sodium Nitrite Increases Microvascular Obstruction Region Blood Flow Without Affecting CT Hypoenchancement Area
Authors: O'Sullivan John F , Leblond Anne-Laure , O'Dea John , Hristova Ivalina , Kumar Sujith , Caplice Noel M
Published: April 2024

(a) Purpose
To determine what areas of hyperenchancement and hypoenhancement on multi-detector CT (MDCT) represent in terms of infarct size and myocardial regional blood flow (RBF), and the effect of nitrite on RBF and MDCT contrast patterns.

(b) Materials and Methods
MDCT contrast-defined I, MVO, and non-infarct remote (R) areas
in vivo
were compared to matched areas defined
ex vivo
by triphenyltetrazolium chloride (TTC) staining (infarct area) and Thioflavin S exclusion (TSE) (area of MVO), and their RBF by fluorescent microspheres and flow cytometry, in 16 female Landrace pigs who underwent mid-LAD myocardial infarction (MI) (90 minutes ischemia, 120 minutes reperfusion), and treated with saline (n=8) or nitrite (n=8). All analyses were performed by at least two blinded observers.

(c) Results
There was a correlation between infarct area on CT and that defined by TTC (r
2
=0.75). There was a poor correlation between MVO on CT and MVO by TSE (r
2
=0.46). TTC and TSE identified distinct differences in flow within R (1.2 ± 0.19 ml/min/g), I (0.62 ± 0.11 ml/min/g), and MVO (0.3 ± 0.04 ml/min/g) areas, respectively. Despite increased RBF in remote (+45%) and MVO (+80 %) regions in nitrite group compared to saline, there was no corresponding change in MDCT contrast patterns. Two animals died in each group.

(d) Conclusion
MDCT is a reliable predictor of infarct size but not microvascular obstruction at 24 hours post infarction. Sodium nitrite increased RBF to MVO regions, but this was not detected by MDCT.
Abstract 8654: Low In-Treatment HDL Cholesterol Levels Strongly Predict New Heart Failure in Hypertensive Patients: The LIFE Study
Authors: Okin Peter , Hille Darcy A , Wachtell Kristian , Kjeldsen Sverre E , Lindholm Lars H , Dahlöf Björn , Devereux Richard B
Published: April 2024

Background:
Although low HDL levels predict incident heart failure (HF) in a population-based study, whether low HDL is associated with increased risk of new HF in hypertensive patients is unclear.

Methods:
Incident HF was examined in relation to in-treatment HDL levels in 8445 hypertensive patients with no history of HF with baseline HDL levels randomly assigned to losartan- or atenolol-based treatment. In-treatment HDL at each year of testing was categorized into the lowest quartile vs upper 3 quartiles according to baseline HDL levels or examined as a continuous variable with hazard ratios calculated for each SD of the baseline mean lower HDL (0.44 mmol/l).

Results:
During 4.7±1.1 years follow-up, there were 264 new HF hospitalizations (3.1%). In univariate Cox analyses, compared with HDL ≥1.21 mmol/l, in-treatment HDL <1.21 was associated with a 117% greater risk of new HF. In parallel analyses which used in-treatment HDL as a continuos variable, each 1 SD lower HDL was associated with a 45% higher HF risk. In multivariate Cox analyses adjusting for randomized treatment, age, sex, body mass index, prevalent and history of atrial fibrillation and diabetes, history of MI, ischemic heart disease, stroke, peripheral vascular disease, smoking status, baseline serum creatinine, glucose, urine albumin/creatinine ratio as standard risk factors and for incident MI, in-treatment diastolic and systolic pressure, heart rate, QRS duration, Cornell product and Sokolow-Lyon voltage criteria for left ventricular hypertrophy and non-HDL cholesterol levels as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a 102% greater risk and, in alternative analyses, each 1 SD lower HDL treated as a continuous variable with a 38% higher risk of incident HF.

Conclusions:
Lower in-treatment HDL is an independent predictor of new HF in hypertensive patients, even after adjusting for other potential risk factors and treatment effects.
Abstract 8702: Assessment of Coronary Artery Disease by Contraction Front Mapping Analysis with Real Time Three-dimensional Stress Echocardiography with Adenosine: A Comparison with Thallium Scintigraphy
Authors: Matsuoka Reiko , Kawasaki Masanori , Tanaka Ryuhei , Ono Koji , Watanabe Takatomo , Fujii Tomoko , Tokoro Fumitaka , Nagaya Maki , Onishi Noriyuki , Kawai Yoshifumi , Abe Shintaro , Goto Yoshiaki , Yoshizane Takashi , Kato Takashi , Warita Syunichiro , Kojima Tai , Iwama Makoto , Hirose Takeshi , Tanihata Shintaro , Noda Toshiyuki , Iida Mami , Watanabe Sachiro , Minatoguchi Shinya
Published: April 2024

Background:
Stress echo with adenosine is not routinely used for the assessment of coronary artery disease (CAD) because of insufficient accuracy. Visual estimation of dyssynchrony with 2-D echo is often difficult because delays <70 ms cannot be detected with human eye. Contraction front mapping (CFM) constructed by real time 3-D echocardiography (RT3DE, ACUSON SC2000) with frame rate of 40 fps provides time-volume analysis for left ventricular (LV) volume, and enables us to assess LV dyssynchrony in only one heart beat. Thus, we evaluated usefulness of stress RT3DE for the detection of CAD.

Methods
: We performed scintigraphy and CFM at rest and stress with adenosine before angiography in 35 patients with suspected CAD. CFM can automatically divide LV into 16 segments, detect dyssynchrony and provide systolic dyssynchrony index (SDI) from the dispersion of time to minimum (min) regional volume for all 16 segments (average SDI) and maximum (max) dispersion of time to min regional volume (max SDI). Coronary angiography was served as a gold standard.

Results
: Images suitable for analysis were 34 (Figure). Heart rate and LV ejection fraction were increased at stress by 12% and 11% respectively. The prevalence of CAD was 76%. Diagnostic accuracy (88% for echo vs. 87% for scintigraphy), sensitivity (88% vs. 88%) and specificity (88% vs.85%) for the detection of CAD were similar between stress RT3DE and sintigraphy. There was no significant difference in the ability to detect single- or multi-vessel disease between RT3DE and scintigraphy. Although average SDI was similar at rest and at stress (6.6±4.0% vs.7.2±4.0%) max SDI was significantly increased at stress (22±10% vs. 18±8%, p<0.05).

Conclusion:
CFM constructed by stress RT3DE as a promising technique to quantify LV dyssynchrony in only one heart beat confers similar diagnostic accuracy in detection of CAD to scintigraphy and may be useful in the clinical setting for the evaluation of patients with suspected CAD.
Abstract 8711: Double Serine Phosphorylation of P47
Phox
At 303-304 is Critical for Acute Tnfα-Induced Ros Production but Not for Mapk Activation in Endothelial Cells
Authors: Teng Lei , Li Jian-Mei
Published: April 2024

p47
phox
is a major regulatory subunit of Nox2 enzyme, which by generating superoxide plays important role in TNFα-induced endothelial dysfunction. The p47
phox
has several serines clustered within the carboxyl terminus
,
and their phosphorylation has been reported to be critical in Nox2 activation and endothelial reactive oxygen species (ROS) production in response to stimulation. To understand the mechanisms of p47
phox
phosphorylation in mediating acute TNFα redox-signaling, we replaced serines (303-4, 310, 315, 320, 328, 345, 348, 359, 370 and 379) to alanines and transfected mouse microvascular endothelial cells (SVEC4-10) with these constructs. Compared to vector controls, S303-4A (double mutation), S310A, S315A, S328A, S345A, S370A and S379A reduced significantly the TNFα (100 U/mL for 30 min)-induced ROS production (P<0.05), whereas only S328A, S345A, S370A and S379A (but not S303-4A, S310A and S315A) inhibited TNFα-induced ERK1/2 phosphorylation. The different effects of S303-304A on TNFα-induced ROS production and TNFα signaling were further investigated using coronary microvascular endothelial cells isolated from p47
phox
knockout mice. Compared to the cells transfected with a wild-type p47
phox
cDNA, S303-4A mutation significantly inhibited (~51+2%) TNFα-induced ROS production, but showed no significant effect on TNFα-induced MAPK activation, p47
phox
association with TRAF4, p47
phox
binding to p22
phox
and p47
phox
membrane translocation. Knockdown of TRAF4 with siRNA abolished TNFα-induced ERK1/2 phosphorylation in S303-4A transfected p47
phox
knockout cells. In conclusion, phosphorylation of p47
phox
at different serines plays distinct roles in endothelial cell response to acute TNFα stimulation. Double serine phosphorylation (S303 and S304) of p47
phox
is crucial in acute TNFα-induced ROS production, but not involved in TNFα-signaling through TRAF4 and MAPK in endothelial cells.