bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9001: Transcatheter Aortic Valve Implantation Reduces Neither 30-day nor Midterm Mortality Over Aortic Valve Replacement in High-risk Patients: A meta-analysis of Randomized and Adjusted Observational Studies
Authors: Goto Shin-nosuke , Takagi Hisato , Iwata Kotaro , Yamamoto Hirotaka , Umemoto Takuya
Published: April 2024

Background:
Our preliminary meta-analysis suggests that transcatheter aortic valve implantation (TAVI) may not reduce 30-day mortality rate over surgical aortic valve replacement (AVR) in high-risk patients with severe aortic stenosis (AS). We performed an updated formal meta-analysis of TAVI versus AVR for reduction of not only early but also late all-cause mortality in AS.

Methods:
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials weresearched through February 2012. Eligible studies were randomized controlled trials or adjusted observational comparative studies of TAVI versus AVR enrolling individuals with AS and reporting 30-day and/or ≥6-month all-cause mortality as an outcome. Odds ratios (ORs) and/or hazard ratios (HRs) with 95% confidence intervals (CIs) (adjusted ORs and/or adjusted HRs in case of observational studies) were abstracted from each individual study.

Results:
Only one randomized controlled trial and 11 adjusted observational comparative studies enrolling 4134 patients with severe AS were identified. Pooled analysis suggested no significant difference in both 30-day (OR, 0.85; 95% CI, 0.64 to 1.13;
P
=0.26) and midterm total mortality (HR, 0.99; 95% CI, 0.83 to 1.20; P=0.96; Figure) among patients assigned to TAVI versus AVR. Exclusion of any single study from the analysis did not substantively alter the overall result of our analysis. There was no evidence of significant publication bias.

Conclusions:
We found that, based on a meta-analysis of data on >4000 patients from 12 studies, TAVI is likely ineffective in reduction of both 30-day and midterm all-cause mortality in high-risk patients with AS.
Abstract 9050: Drug-Drug Interactions Between Aspirin and NSAIDs are Predicted by Kinetics of Cyclooxygenase-1 Inhibition
Authors: Saxena Aaruni , Gohlke Holger , Singh Supriya , Schroer Karsten , Hohlfeld Thomas
Published: April 2024

Background and aims
: Therapy with NSAIDs may interfere with antiplatelet activity of aspirin. The mechanism of this drug-drug interaction has not yet been established on the level of enzyme kinetics and quantitative structure-activity relationship (QSAR).

Methods:
Time-dependent kinetics (log K) for the onset of COX-1 inhibition was measured for 17 common NSAIDs using arachidonic acid-induced COX-1 activity (human platelet microsomes, bioluminescence). IC50 values of all NSAIDs were determined by arachidonic acid-induced platelet thromboxane (TX) formation in platelet rich plasma, as well as the in vitro interaction with aspirin. Dragon and SYSTAT softwares served to develop QSAR models in which dependent parameters were log K and IC50 and independent parameters were structural/physico-chemical parameters (MoR32m, G2v, L3S, representing the shape, size and polarizibility).

Results:
All NSAIDs could be classified into a time-dependent (slow onset) or a time-independent (fast onset) mode of inhibition. Time-dependent NSAIDs included diclofenac, flurbiprofen, indomethacin, ketoprofen and ketorolac. These NSAIDs did not decrease TX inhibition by aspirin. In contrast, all other studied NSAIDs were time-independent inhibitors and prevented inhibiton by aspirin. The inhibition kinetics (log K) and IC50 were correlated with MoR32m, G2v and L3S (equations 1 and 2). eq.1: -log IC50 = 4.54 (±0.99) MoR32m - 64.62 (±12.58) G2v + 3.41 (±0.56) L3S + 8.59; r = 0.91; r2 = 0.84; s = 0.41; F = 22.81; PRESS = 5.00. eq.2: -log K = 2.35 (±0.69) MoR32m - 16.50 (±8.68) G2v + 1.18 (±0.39) L3S + 1.61; r = 0.74; r2 = 0.55; s = 0.29; F = 5.49, PRESS= 3.01; r, correlation coefficient; s, standard deviation; F, Fisher’s test; PRESS, sum of square differences.

Conclusions:
NSAIDs decrease the antiplatelet activity of aspirin. This is highly dependent on the inhibition kinetics of platelet COX-1, whereas the inhibition kinetics and IC50 values for TX inhibition further depends on MoR32m, G2v and L3S of a particular NSAID. Time-independent NSAIDs decrease the anti-platelet activity of aspirin. Therefore, time-dependent NSAIDs should be preferred in patients on antiplatelet treatment with aspirin. The QSAR models may predict the kinetics and enzyme inhibition by NSAIDs.
Abstract 9117: Changes in Left Ventricular Diastolic and Left Atrial Function One Month After Transcatheter and Surgical Aortic Valve Replacement in Severe Aortic Valve Stenosis
Authors: Harada Kenji , Tanaka Jun , Jilaihawi Hasan , Stegic Jasminka , Doctor Niraj , Kashif Mohammad , Nakamura Mamoo , Chakravarty Tarun , Makkar Raj , Takahiro Shiota
Published: April 2024

Background:
In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, the NYHA functional class was improved at 1 year in both the transcatheter aortic valve replacement (TAVR) and the surgical bioprosthetic aortic valve replacement (SAVR). However, more patients in TAVR than in SAVR had a reduction in symptoms at 30 days. As part of a single center PARTNER trial experience, we compared left ventricular (LV) and left atrial (LA) function in patients after TAVR with those with SAVR for the treatment of severe aortic valve stenosis at one month follow-up.

Methods and Results:
A total of 83 severe aortic valve stenosis patients with preserved LV systolic function (EF > 40%) and without moderate or severe valvular regurgitation were included in the study: 52 patients underwent TAVR and 31 patients underwent SAVR. Echocardiographic parameters were similar between the two groups. In each group, LVEF and peak early diastolic mitral annular velocity (e') increased significantly at one month follow-up. The ratio of peak S-wave to D-wave from pulmonary vain flow (PVS/PVD) was higher in the TAVR group as compared with the baseline, while there is no significant difference in SAVR group. LV end-diastolic dimension (LVEDD), left atrial area (LAA), the ratio of early transmitral flow velocity (E) to e' (E/e') and LV mass index significantly decreased as compared with baseline in each group (Table 1). There were no significant differences between the two groups in LVEDD, EF, LAA, PVS/PVD, e', E/e' and LV mass index one month after the procedure. At one month follow-up, however, the changes (post minus pre) of LAA, PVS/PVD, e' and E/e' were significantly larger in the TAVR group than the SAVR group (Table2).

Conclusion:
In patients with severe aortic stenosis, both TAVR and SAVR improved LV systolic and diastolic function and LA function one month after intervention. In particular, the improvement after TAVR appeared to be greater than after SAVR.
Abstract 9141: Distance, Treatment Strategy, and Mode of Transfer for Primary PCI in Patients Presenting to a Hospital Without PCI Capability: A Report from ACTION Registry®-GWTG™ and The AHA Mission: Lifeline Program
Authors: Nicholson Benjamin D , Dhindsa Harinder S , Roe Matthew T , Chen Anita Y , Jollis James G , Kontos Michael C
Published: April 2024

Background:
Many STEMI patients (pts) present to non-PCI hospitals, requiring interhospital transfer for primary PCI. The impact of distance and mode of transport to the PCI center on the ability to meet guideline recommended reperfusion times is not clear.

Methods:
Data from the ACTION Registry®-GWTG™ were used to determine reperfusion strategy (fibrinolytics, primary PCI), total time to reperfusion (Total D2B; difference between non-PCI hospital presenting time and PCI time) and transfer mode (ground, air) for pts having interhospital transfer for primary PCI. Distance between the pt’s home zip code and the PCI hospital zip code were used to estimate travel distance.

Results:
From 7/1/08-3/3/11, 13,974 STEMI pts were transferred to 323 PCI hospitals. The median distance from the pt’s home to the primary PCI hospital was 26 miles (IQR 13,40) (ground 20 mi; air 37 mi; p<.001). Pts transported by air had a similar median age (59 yrs), but were more likely to have heart failure (8.0% vs 6.4%; p<.01) and shock (8.9% vs 6.8%; p<0.001). The Total D2B time for the 11,722 pts transferred for primary PCI was 115 min (IQR 93,147), with air time significantly longer [median 123 min vs 110 min; p <0.001]. A total of 5,577 (56%) pts had a Total D2B ≤120 min, with only 2,215 (22%) ≤90 min. Total D2B time ≤120 min was more likely in ground pts (60% vs 47%; p <.001). At distances 25 mi, air transport predominated (TABLE). Fibrinolytic therapy administration increased as distance increased.

Conclusions:
Interhospital transfer for primary PCI is associated with prolonged reperfusion times, despite increased use of air transport for longer distance transfers. These delays should prompt increased consideration of fibrinolytic therapy use prior to transfer by some hospitals. Conversely, the relatively short distance most pts live from a primary PCI hospital should prompt greater emphasis on EMS hospital bypass protocols.
Abstract 9231: The Association of Calcium Supplementation and Incident Cardiovascular Events: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Agarwal Subhashish , Nettleton Jennifer A , de Boer Ian , Ix Joachim H , Siscovick David , Eng John , Bild Diane , Burke Gregory L , Herrington David M
Published: April 2024

Introduction:
Some reports indicate that calcium supplements are associated with adverse cardiovascular (CVD) events in post-menopausal women. We investigated the association between calcium supplements and CVD events in a multi-ethnic cohort.

Methods:
We studied 6,237 participants (2472 Caucasian, 790 Chinese, 1615 African-American, and 1360 Hispanic) in the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort study of adults, ages 45-84, free of clinical CVD who had data on dietary calcium intake, calcium supplements and covariates. Cox proportional hazard models were used to study the association between daily calcium supplements (none [reference], 1-500 mg, 500-1000 mg, and >1000 mg) and 6.1 year incident CVD events after adjusting for age, race, sex, education level, household income, site, total and HDL cholesterol, dietary calcium intake, lipid medication use, systolic blood pressure, anti-hypertensive medications, diabetes status, body mass index (BMI), estimated glomerular filtration rate (eGFR), physical activity, and smoking.

Results:
Calcium supplements were taken by 2,870 MESA participants. There were 357 CVD events over 6.1 years of follow up. The cumulative 6.1 year CVD event rate for calcium supplement was 5.5% versus 6.4% for non-users. Adjusted hazard ratio (HR, 95% CI) for incident CVD for any calcium supplementation versus none was 0.92 (0.74-1.14). HR's (95%CI) were: Calcium 1-500: 0.84 (0.64-1.08); Calcium 500-1000: 0.89 (0.58-1.32); and Calcium 1000 mg: 1.21 (0.84-1.70). In a similar separate analysis of postmenopausal women (n=2,703), calcium supplement, as in above-mentioned categories, was not associated with incident CVD events. Additionally, no significant interaction was noted between calcium supplements and incident CVD events by race or chronic kidney disease (CKD=eGFR ≤ 60 ml/min/1.73 m
2
), (calcium x race, p=0.3; calcium x CKD, p=0.9).

Conclusion:
In this multi-ethnic observational cohort calcium supplementation was not associated with incident CVD events in either men or women including postmenopausal women.
Abstract 9309: Daily Respiratory Rate Trends are Significantly Elevated Prior to HF Admissions
Authors: Goetze Stephan , Lambiase Pier , Schilling Richard , Trappe Hans-Joachim , Winter Siegmund , Zhang Yi , Wold Nicholas , Manola Ljubomir , Kestens Dries , Thompson Julie , on behalf of NOTICE-HF investigators
Published: April 2024

Introduction:
Implantable devices are capable of monitoring respiration by measuring intra-thoracic impedance. Respiratory rate (RR), one of the vital signs, increases with activity, stress, worsening heart failure (HF) and other diseases. We hypothesize that RR is increased in the days leading up to a HF admission compared with those observed at a random time in HF patients.

Methods:
HF patients indicated for ICD or CRT-D were implanted with INCEPTA
TM
and followed for 9 months. The device trended daily maximum (max), median (med) and minimum (min) RR up to a year. We retrospectively compared changes in averaged daily RRs (ΔRR) between a baseline and an event window (28-32 and 1-5 days before an index time respectively). The index time was defined as the day of first HF hospital admission in patients who had a HF admission (HF group) and the day of 6-month follow-up (6MFU) in patients who completed the study without a HF admission (control group). Patients who had fewer than 3 valid data points during either of the 5-day windows were excluded. Wilcoxon rank sum test was used to detect non-zero difference in ΔRR between groups.

Results:
Of the 121 patients enrolled, 100 had sufficient data for the analysis (10 with HF admissions). The figure boxplot shows all 3 RRs were significantly elevated prior to HF admissions. ΔRR (breath/minute) was significantly larger prior to a HF admission in the HF group, than observed prior to the 6MFU in the control group (max ΔRR: 2.4± 2.9 vs. -0.05± 1.8, p = .006; med: 2.2± 2.7 vs. 0.02± 1.1 p = .004; min 1.5±1.9 vs. 0.05±1.2, p = .04).

Conclusions:
This study showed a significantly larger change in daily RR trends prior to a HF admission than was observed at a random time in patients who did not decompensate. Ambulatory daily RR trends may be a valuable addition to standard management for HF patients.
Abstract 9311: Association of Traumatic Brain Injury with Subclinical Atherosclerosis Measured by Coronary Artery Calcium
Authors: Ahmadi Naser , Hajsadeghi Fereshteh , Babaei Hormoz , Ebrahimi Ramin
Published: April 2024

Background:
Traumatic brain injury (TBI) is a devastating condition resulted in cerebral edema and ischemia. Pre-clinical studies have documented production of cytokine, growth factor and inflammatory biomarkers following TBI. This study investigates the relation of TBI with subclinical atherosclerosis measured by coronary artery calcium (CAC).

Method:
This nested case-control study consists of 543 Veterans (age 59±10 years, 100% male) with and without TBI who underwent CAC scanning. VA electronic medical records from veterans were used to evaluate medical and psychological diagnoses, procedures, and risk factors. Logistic regression analysis was employed to assess the association of TBI with CAC. CAC was defined as 0, 1-100, 101-400 and 400+.

Results:
TBI was more prevalent with the presence and severity of CAC (p0 was significantly higher in individuals with TBI as compared to those without TBI (81.2% vs. 60.1%, p=0.0001). After adjustment for age and conventional risk factors, the relative risk of CAC>0 was 176% higher in TBI as compared without TBI (RR: 2.76 (95%CI 1.5-4.9, p=0.001). Similarly, the median CAC was higher in TBI as compared to normal subjects (129A Agatston score vs. 52A Agatston score, p=0.001). After adjustment of risk factors, the relative risk of CAC 1-100, 101-400 and 400+ was 2.22(95%CI 1.03-4.78, p=0.04), 2.98(95%CI 1.49-5.97,p=0.002) and 3.26 (95%CI 1.74-6.14, p=0.001) in individuals with TBI as compared to their matched subjects without TBI, respectively.

Conclusion:
TBI is independently associated with the presence and severity of subclinical atherosclerosis measured by CAC. This highlights the importance of cardiovascular risk stratification in subjects with TBI.
Abstract 9421: The Role of B-type Natriuretic Peptide as a Prognostic Factor for Endocarditis at the Emergency Room
Authors: Gualandro Danielle M , Goldstein Priscila , Seguro Luis F , Siciliano Rinaldo , Strabelli Tania , Arias Viviane , Mansur Alfredo J , Accorsi Tarso A , Grinberg Max , Oliveira Mucio T
Published: April 2024

Background:
Some prognostic factors for infective endocarditis (IE) are well established, but the role of B-type natriuretic peptide (BNP) at admission has not been well studied. Objective: The purpose of this study was to access the admission BNP value as a prognostic factor in patients with IE.

Methods:
Between July 2009 and January 2011, consecutive patients with IE admitted to the emergency room were prospectively enrolled. Patients were included if they met possible or definite Duke’s criteria for IE. The association between elevated BNP and in-hospital death was determined.

Results:
From 104 patients analyzed, 67 were male (48%), the mean age was 52.6±19.1 years. During follow-up, 32 (30.8%) patients died. In univariate analysis, staphylococcal infection (P<0.001, HR 3.94; CI, 1.94-8.0), dyspnea at presentation (P=0.015, HR 2.41; CI, 1.20-4.86), sepsis at presentation (P=0.017, HR 2.34; CI, 1.16-4.72), left ventricular ejection fraction ≤ 55% (P<0.001, HR 3.97; CI, 1.86-8.43), C-reactive protein (CRP) > 120 mg/L, (P<0.001, HR 4.04; CI, 1.91-8.55), creatinine > 1 mg/dL (P=0.006, HR 2.92; CI, 1.26-6.76), and BNP > 200 pg/mL (P<0.001, HR 12.51; CI, 2.98-52.48) were associated with in-hospital mortality. In multivariate analysis, BNP values > 200 pg/ml (P<0.001, HR 2.41; CI, 1.20-4.86), staphylococcal infection (P=0.006, HR 2.89; CI, 1.39-6.02), dyspnea at presentation (P=0.003, HR 3.17; CI, 1.49-6.76), and CRP > 120 mg/L, (P<0.001, HR 3.86; CI, 1.76-8.46) were independent predictors of in-hospital mortality.

Conclusion:
As important as the classic prognostic factors, elevated BNP levels on admission were related to fatal outcomes in IE patients.
Abstract 9506: Clinical Correlates and Reference Intervals for Transmitral Doppler Early Filling Velocity to Tissue Doppler Early Diastolic Velocity Ratio from Infancy to Adolescence
Authors: Harada Kenji , Harada Yukiko
Published: April 2024

Background:
Transmitral Doppler early filling velocity to tissue Doppler early diastolic velocity (E/E’) ratio is an index for left ventricular (LV) filling pressure, but data on the factors affecting E/E’ ratio are limited in children. The purpose of this study is to investigate the relationships between E/E’ ratio and age, BMI z-score, LV geometry, and LV function from infancy to adolescence.

Methods:
Echocardiography with tissue Doppler imaging was performed in 1049 normal subjects aged 4 months to 20 years. LV end-diastolic volume, LV mass, mass to volume ratio, ejection fraction (EF), isovolumic relaxation time (IRT) and tissue Doppler-derived myocardial performance index (MPI) were assessed.

Results:
Median E/E’ ratio was 7.21 (5th to 95th percentile, 5.37 to 9.73). The E/E’ ratio in younger children (< 5 years) was significantly higher than that in older children (≥ 5 years) and decreased significantly with age (r = -0.43, p < 0.01) (Fig A). E/E’ ratio decreased significantly with BMI (r = -0.23, p < 0.01) (Fig B), however, no significant relationship between E/E’ ratio and BMI z-score was observed. There were weak but significant relationships between E/E’ ratio and heart rate (r =0.36, p < 0.01), systolic blood pressure (r =-0.20, p < 0.01), EF (r = 0.14, p < 0.01), IRT(r =-0.29, p < 0.01), and MPI(r =-0.21, p < 0.01). E/E’ ratio did not correlate with LV mass to volume ratio. Multiple regression analysis revealed that independent predictor of E/E’ ratio was age.

Conclusions:
We provide the first evidence of age-related decrease in E/E’ ratio from infancy to adolescence. Age-specific reference values should be considered in the interpretation of diastolic function during childhood.
Abstract 9592: Left Ventricular Hypertrophy Reduction and Clinical Events. A Meta-regression Analysis of 14 Studies in 12,809 Hypertensive Patients
Authors: Savarese Gianluigi , Costanzo Pierluigi , Rosano Giuseppe , Musella Francesca , Casaretti Laura , Vassallo Enrico , Paolillo Stefania , Marsico Fabio , Perrone-Filardi Pasquale
Published: April 2024

Objective:
Left ventricular hypertrophy (LVH) is an independent risk factor for clinical events (CE), and disappearance of LVH is associated with reduction of cardiovascular risk. However, whether a continuous relationship between reduction of LVH and risk of CE exists has not been investigated.

Methods:
Randomized clinical trials evaluating LVH at baseline and reporting quantitative LVH changes and CE (all-cause death, myocardial infarction (MI), stroke or new onset heart failure) were included. Meta-regression analysis was performed to test the relationship between changes in LVH and incidence of the composite outcome (all-cause death, MI, stroke or new onset heart failure) and between changes of LVH and occurrence of each component of the composite outcome. Analysis of potential confounder variables was also performed.

Results:
Fourteen trials including 12,809 participants and reporting 2,259 events were included. Follow-up ranged from 0.50 to 5 years, with mean 1.97±1.50 years. Mean age was 62±5 years and 52% of patients were women. The composite outcome was significantly reduced by active treatments (odds ratio [OR]: 0.851, 95% confidence intervals [CI]: 0.780 to 0.929, p<0.001), as well stroke (OR: 0.756, CI:0.638 to 0.895, p<0.001) whereas MI (OR:1.031, CI:0.846 to 1.255, p=0.763) and new onset heart failure (OR:0.994, CI:0.798 to 1.238, p=0.955) were not significantly reduced by treatments. LVH changes did not predict the reduction of the risk of the composite outcome (t=0.69, p=0.50)(Figure) or all-cause death (t=-1.27, p=0.26), stroke (t=0.15, p=0.89), MI (t=1.20, p=0.28) and new onset heart failure (t=0.69, p=0.50). No significant influence on the association of baseline patients and studies characteristics was found.

Conclusions:
A significant continuous relationship between LVH changes and CE could not be demonstrated in hypertensive patients, independently on the technique or drug used. patients.
Abstract 9637: Outcomes in Pediatric Cardiac Arrest with Pulseless Ventricular Tachycardia or Ventricular Fibrillation with use of Amiodarone versus Lidocaine
Authors: Valdes Santiago O , Donoghue Aaron J , Hoyme Derek B , Berg Marc D , Berg Robert A , Samson Ricardo A
Published: April 2024

BACKGROUND: Current PALS guidelines recommend amiodarone for cardiac arrest associated with refractory pulseless ventricular tachycardia (pVT) and ventricular fibrillation (VF), based on a single pediatric study and extrapolation from adult data. We sought to compare outcomes of refractory pVT/VF arrest treated with amiodarone or lidocaine.

METHODS: Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients < 18 years old with pVT/VF cardiac arrest treated with amiodarone, lidocaine or both were included. Patients receiving amiodarone or lidocaine prior to arrest were excluded. Univariate analysis compared Utstein outcomes (ROSC, 24 hour survival, survival to discharge) between those receiving amiodarone, lidocaine or both (chi square analysis). Multivariate analysis was done to estimate the association between amiodarone and lidocaine and survival outcomes while controlling for potential confounders among patient, event and treatment characteristics.

RESULTS: A total of 358 patients met all inclusion criteria. Utstein outcomes are summarized below. Univariate analysis demonstrated significant differences between groups in ROSC and 24 hour survival; survival to discharge did not differ significantly. Multivariate analysis showed improved 24 hour survival with lidocaine compared to amiodarone (adjusted odds ratio 1.78, 95% CI 1.12 - 2.84) while controlling for the above confounders. Neither amiodarone or lidocaine was significantly associated with ROSC or survival to discharge.

CONCLUSIONS: For children with in-hospital refractory pVT/VF, lidocaine use without amiodarone was independently associated with improved 24 hour survival. Amiodarone alone or in combination with lidocaine was not associated with superior rates of ROSC, survival at 24 hours, or survival to discharge. Lidocaine should be considered in the treatment of pediatric cardiac arrest with pVT/VF.
Abstract 9724: The Use of the Model for End-Stage Liver Disease Score Predicts 90-Day Mortality in Patients Undergoing HeartMate II Implantation
Authors: Kransdorf Evan , Moriguchi Jaime , Kittleson Michelle , Runyan Carmelita , Olay Charito , Jocson Rhodora , Czer Lawrence , Trento Alfredo , Esmailian Fardad , Kobashigawa Jon
Published: April 2024

Purpose:
Careful patient selection for left ventricular assist device (LVAD) therapy is essential to ensure optimal outcomes after device implantation. Although several risk assessment scores are available, there is no consensus on the most accurate score to use in patients undergoing HeartMate II (HMII) implantation. The Lietz-Miller Destination Therapy Risk Score (DTRS) was derived from analysis of patients undergoing HeartMate XVE implantation for destination therapy (Lietz et al.
Circulation
2007). The Model for End-Stage Liver Disease (MELD) was shown to predict outcome in patients undergoing primarily HeartMate I implantation (Matthews et al.
Circulation
2010). We evaluated the utility of these scores in predicting outcomes following HMII implantation.

Methods:
Retrospective analysis was performed on 48 patients undergoing HMII implantation at our institution between 2009 and 2011. The DTRS and MELD scores were calculated from clinical data on day of device implantation and outcomes assessed.

Results:
Device implantation was for bridge to transplant (69%) or destination therapy (31%). 14 patients (29%) underwent heart transplant and 17 patients died (35%), with a mean LVAD support time of 301 days and 85 days, respectively. At end of the study period 17 patients were alive (mean LVAD support time 389 days). The majority of deaths (71%) occurred within 90 days of device implantation. Mortality at 90 days was higher in patients with INTERMACS class 1 (class 1 29.4% vs. class 2 to 4 22.6%), high-risk DTRS values (high 33.3% vs. low-medium 22.2%), and high MELD values (MELD 20 50% vs. MELD < 20 16.6%). Only a MELD score 20 was statistically associated with outcome at 90 days with a hazard ratio of 3.5 (p=0.03) using a Cox proportional hazards model.

Conclusions:
A MELD score 20 predicts mortality at 90 days in patients undergoing HMII implantation. Further validation of the MELD score in a larger population is needed. Elaboration of the score using cardiac-specific factors may further improve its predictive ability.
Abstract 9767: Direct-renin-inhibitor Aliskiren Therapy Consistently Suppresses Enhanced Cardiac Sympathetic Activity and Improves Left Ventricular Remodeling in Patients with Systolic Heart Failure
Authors: Yoshihiro Imamura , Tsutsumi Takaki , Yamada Akira
Published: April 2024

Introduction:
Adding aliskiren to heart failure (HF) therapy was reported to reduce plasma brain natriuretic peptide (BNP) concentration. However, the effects of aliskiren on cardiac sympathetic nerve activity and on cardiac function have not yet been clarified. Hypothesis: We assessed the hypothesis that adding aliskiren to standard therapy would be effective to suppress cardiac sympathetic nerve function and improve cardiac function.

Methods:
We enrolled 38 patients with mild HF (NYHA class II). The inclusion criteria were: 1) in stable condition for at least six months; 2) receiving standard therapy including an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker and a beta-blocker; 3) have systolic dysfunction (left ventricular ejection fraction: LVEF of < 45%); 4) without diabetes; and 5) without renal dysfunction (serum creatinine of > 1.2 mg/dL). We randomly assigned 18 patients to receive additional aliskiren treatment of 150 mg/d (aliskiren group), while 20 patients continued standard therapy (control). All patients underwent neurohormonal measurements, echocardiography and 123I-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 were obtained three and 12 months later.

Results:
In the aliskiren group, plasma renin activity and BNP fell significantly. MIBG analysis showed a consistent decrease in WR and a consistent increase in H/M ratio over 12 months only in the aliskiren group (WR %: 39.6 ± 3.1 vs 32.0 ± 2.1, 32.8 ± 3.7, p = 0.013, H/M: 2.80 ± 0.16 vs 3.12 ± 0.22, 3.05 ± 0.20 p = 0.015 at each follow-up period). The LVEF improved although not significantly (p = 0.074). The LV end-diastolic volume (EDV) and end-systolic volume (ESV) improved significantly (EDV index mL/m2: 92.8±6.4 vs 79.7±5.8, 82.3±5.3, p = 0.042 and ESV index: 56.6±4.8 vs 46.4±4.5, 48.6±4.4, p = 0.021). In the control group, these data remained unchanged.

Conclusions:
In HF patients receiving standard therapy but still continuing to have cardiac dysfunction, the addition of aliskiren consistently suppresses cardiac sympathetic activity over 12 months and improves left ventricular remodeling.
Abstract 9771: Aggressive Treatment of Cardiovascular Risk Factors: Effects on Atherosclerosis and Arterial Age
Authors: Wilson Matthew D , Gibson Cheryl A , Powell Sara D , Backes James M , Eldringhoff David , Moriarty Patrick M
Published: April 2024

Background:
Atherosclerosis, the major cause of cardiovascular disease (CVD), involves the abnormal deposit of cholesterol within the intima of the arterial wall. Arteriosclerosis is the annual thickening (roughly 0.01 mm per year) of the arterial wall (media) based generally on aging. An indirect method of diagnosing atherosclerosis involves ultrasound analysis of the common carotid intima-media wall thickness (CCIMT) to evaluate a patient's arterial age. Arterial age is a term representing the combination of wall thickness based both on atherosclerosis and arteriosclerosis.

Hypothesis:
Aggressively treating CVD risk factors will reduce atherosclerosis and arterial age as measured by CCIMT analysis.

Methods:
An observational study of 220 patients (121 m, mean age 58 yrs) treated in a CVD prevention clinic and with at least 1 CVD risk factor. Two ultrasounds were performed by the same sonographer, approximately 3 years apart, with a computerized edge-detection device (MICROMAXX, Sonosite) measuring 100 markers within 1 cm area of the CCIMT wall, 1 cm proximal to the bulb, to provide the maximum thickness. Arterial age was estimated based on data of previous epidemiology studies stored within the MICROMAXX.

Results:
After a mean follow up of 3.05 years, the observed values for maximum CCIMT (see table) were significantly lower (p<0.0001) than expected. While patients' chronological age increased by 3 years, their arterial age decreased by 1.53 years (p<0.0001), translating into a 4.57 year difference compared to the expected change. Reduction of total cholesterol was the only risk factor found to be significantly associated with reduction in vascular age (p<.027).

Conclusion:
In patients with CVD risk factors, aggressive clinical treatment resulted in statistically significant reductions in the rate of maximum CCIMT progression and reversing arterial age. Longer follow-up is needed to determine if these findings also translate to fewer clinical events.
Abstract 9791: GPR119 Agonism Affects Lipoprotein Particle Remodeling in Dyslipidemic Monkeys
Authors: Shadoan Melanie K , Bergquist Mandy L , Wagner Janice D , Roller Shane G , Nunez Derek J , Young Andrew A , Brown Kathleen K , Prescott Judith S , Feldman Paul L
Published: April 2024

GSK1292263 (GSK263), a small molecule agonist of G-protein coupled receptor 119 (GPR119), significantly increases fasting HDLc, and decreases triglyceride (TG), and LDLc concentrations in both diabetic and dyslipidemic patients. The mechanism of these improvements is unclear, as no other GPR119 agonists have been reported to show similar lipid effects. Studies in non-primate preclinical models have not recapitulated the breadth of lipid effects seen in patients with GSK263. Thus, the purpose of the current study was (i) to determine if dyslipidemic non-human primates respond to GSK263 and (ii) to evaluate if the lipid improvements are a GPR119 class effect by testing another potent agonist (GSK706) as a comparator. We used a 3-period crossover design with 2 weeks active treatment followed by a 2 week washout period to evaluate the effects of Vehicle, GSK263 (25 mg/kg, comparable exposure to a clinically efficacious dose), and GSK706 (10 mg/kg, to achieve bio-equivalent GPR119 agonism to GSK263) in hypertriglyceridemic cynomolgus monkeys (N=15). Drug was administered once daily in a piece of fruit which was voluntarily consumed. For each treatment period, fasting plasma lipids and lipoproteins (by FPLC and NMR, LipoProfile®) were assessed at baseline and after 14 days of dosing. Neither GSK263 nor GSK706 had significant effects on LDLc or fasting TG, but both robustly increased HDLc by ∼20%, similar in magnitude to that seen in patients. NMR analysis shows that treatment with GSK263 and GSK706 (i) decreased number of LDL particles by ∼20%, decreased number of small, dense LDL particles by ∼36%, increased LDL size by ∼1%; (ii) increased HDL size by ∼3%, increased number of large HDL particles by ∼23%, decreased number of small HDL particles by ∼32%; (iii) decreased number of large VLDL/chylomicrons by ∼30% and tended to increase the number of small VLDL particles. Two selective GPR119 agonists have been shown to shift lipoprotein particle remodeling in the direction of potential cardiovascular benefit in monkeys. The effects of GSK263 on lipoprotein metabolism in the dyslipidemic monkey are largely concordant with the human clinical results and may suggest a receptor class effect, since both GPR119 agonists confer the same lipid improvements.
Abstract 9847: Glomerular Filtration Rate in Pediatric Heart Transplant Recipients Can be Measured During Routine Catheterization and is Best Estimated by the Full CKiD Formula
Authors: Lin Kimberly Y , Shaddy Robert E , Schwartz George , Furth Susan L , Ruebner Rebecca L
Published: April 2024

Identification of chronic kidney disease (CKD) after pediatric heart transplantation (PHT) is limited by inaccuracies in creatinine-based estimates of glomerular filtration rate (GFR); iohexol plasma clearance is a proven method of measuring GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol during routine coronary angiography in PHT recipients, and that the recently developed CKiD GFR estimating formula, utilizing serum creatinine and cystatin C, provides a better estimate of GFR than creatinine or cystatin equations alone. We performed a cross-sectional study of PHT recipients, ages 2-18 yrs, undergoing surveillance coronary angiography. GFR was measured by obtaining iohexol levels at 2, 4, and 5 hours post-iohexol infusion for angiography, then calculating area under the curve of iohexol disappearance from plasma. Agreement between measured GFR and multiple GFR estimating equations was assessed with Bland Altman plots, correlation, and % of estimates within +/- 10 and 30% of measured GFR. Of 40 enrolled subjects, 31 had complete GFR data. Median age was 15.0 yrs [IQR 7.6, 16.6], time since HT was 5.9 yrs [2.0, 10.8], height %ile was 26 (7, 48), serum creatinine was 0.7 (0.5, 0.8) mg/dL, cystatin C was 0.83 (0.72, 0.91) mg/L, and measured GFR was 89.5 (78.7-107.0) ml/min/1.73m
2
(mean 93.8, SD22.5). A comparison of measured GFR to estimated GFR is shown in Table 1; the full CKiD formula showed best agreement with measured GFR.

Conclusions:
1. We describe a novel modified iohexol plasma clearance method to measure GFR in PHT recipients undergoing coronary angiography. 2. Measured median GFR in this cohort is 89.5 ml/min/1.73m2, suggesting early CKD. 3. The full CKiD formula performs best with respect to bias, accuracy, and correlation.
Abstract 9899: Effect of Renal Sympathetic Denervation on Atrial Fibrillation
Authors: Zhao Qingyan , Dai Zixuan , Yu Shengbo , Wang Xule , Xiao Jinping , Huang Congxin
Published: April 2024

Introduction
- The fundamental mechanisms underlying atrial fibrillation (AF) have not been elucidated. Much attention has been devoted to assess the role of renin-angiotensin-aldosterone system (RAAS) in AF.

Hypothesis
- We assessed the hypothesis that renal sympathetic denervation had effect on atrial substrate remodeling and inhibited inducilibity of AF by preventing RAAS.

Methods
- Thirteen dogs were randomly divided into control group (7 dogs) and renal artery ablation (RAA) group (6 dogs). In control group, at first, AF was induced by anterior right ganglionated plexi (ARGP) stimulation. Then, rapid atrial pacing was performed for 7 hours and atrial effective refractory period (AERP) was measured. Subsequently, pacing was stopped and AF was induced again by atrial burst pacing. In RAA group, dogs were raised for 6 weeks after each renal artery ablation. After that, the procedure of pacing and electrophysiological measurement was nearly same as in the control group. Densities of autonomic nerve, Cx43 and ANP in pulmonary veins (PVs) and atrial tissues were measured and levels of TGF-β, Ang II and aldosterone in blood were studied.

Results
- There was a persistent decrease in AERP in both the two groups. The voltage in the sinus rate slowing response and the threshold for AF inducilibity increased during ARGP stimulation after renal sympathetic denervation (3.5±1.6V vs 1.6±0.3V, P=0.03; 5.1V±1.0V vs 2.1V±0.7V, P=0.03). Induced number of times and duration of AF was higher in control group than that in RAA group after rapid pacing. The plasma Ang II and aldosterone concentration increased in control group while decreased in RAA group after rapid pacing. Furthermore, levels of ANP in right atrium and densities of Cx43 in PVs were lower in RAA group than that in control group (ANP: 220.5±37.6 pg/ml vs 164.4±22.0 pg/ml, P=0.02; Cx43: 1.91 vs 0.92, P[[Unable to Display Character: ]]0.01). There was no significant difference in the densities of autonomic nerve and TGF-β between the two groups.

Conclusions
[[Unable to Display Character: ]]Renal sympathetic denervation results in atrial substrate remodeling and markedly decrease the inducilibity of AF by inhibiting activity of RAA.
Abstract 9932: Chronic Urotensin II Receptor Blockade Causes Regression of Heart Failure: Beneficial Effects on Neurohormonal Activation, Cardiomyocyte Contractile Function [Ca
2+
]i Regulation and Beta-Adrenergic Modulation
Authors: Cheng Che Ping , Zhou Peng , Cheng Heng-Jie , Shao Qun , Sane David C , Little William C
Published: April 2024

Background.
Heart failure (HF) is associated with increased levels of urotensin-II (UII) and upregulation of UII-mediated cardiac inhibitory pathway. This suggests that cardiac UII activation contributes to HF progression and may be a therapeutic target. However, the role and mechanism of chronic UII receptor antagonist (UII-ANT) in HF are unclear. We assessed the hypothesis that blocking UII improves cardiomyocyte function, [Ca
2+
]
i
regulation, and β-adrenergic receptor (AR) signaling effectiveness, thus limiting HF progression.

Methods.
We compared sympathetic nervous system (SNS) activation, LV myocyte β
1
-AR protein expression, and myocyte contractile and Ca
2+
current (I
Ca,L
) responses to isoproterenol (ISO) in 3 groups of age-matched adult mice (8/group) over 8 weeks (W): 1) HF [after onset of HF induced by ISO (170 mg/kg sq for 2 days) for 4 W and then receiving placebo], 2) HF/UII-ANT [after onset of HF and then receiving urantide, a potent UII-ANT (10
-5
M/kg/day sq via osmotic mini pump), given for 4W], and 3) C (controls).

Results.
Compared with C, ISO-treated mice had established HF with significantly increased plasma norepinephrine (NE) (3474 vs 668 pg/ml) and decreased ejection fraction (EF, 35% vs 63%). In HF, cardiomyocyte basal functional performance and I
Ca,L
were significantly depressed with 42% reductions in cell contraction (dL/dt
max
, 78 vs 134 µm/s), relaxation (dR/dt
max
, 69 vs 120 µm/s) and a 48% decreased I
Ca,L
(3.7 vs 7.2 pA/pF). Importantly, compared with normal myocytes, superfusion of ISO (10
-8
M) caused significantly less increases in dL/dt
max
(30% vs 69%), dR/dt
max
(29% vs 64%), and I
Ca,L
(12% vs 36%) in HF myocytes. These changes were associated with significantly decreased myocyte β
1
-AR (0.37 vs 0.61) protein. In HF/UII-ANT mice, plasma NE (908 pg/ml), EF (59%), and myocyte β
1
-AR (0.57) expression returned close to C levels. Basal myocyte contraction and I
Ca,L
significantly improved, and ISO-induced increase in dL/dt
max
(66%), dR/dt
max
(60%), and peak I
Ca,L
(34%) were significantly augmented.

Conclusion.
Chronic UII-ANT prevents HF-induced SNS activation and downregulation of LV myocyte β
1
-ARs and leads to the preservation of myocyte function, I
Ca,L
, and β-adrenergic responsiveness in a mouse model of progressive HF.
Abstract 18012: Insights into the Cardiorenal Syndrome Type II in the Rat
Authors: Angelini Annalisa , Castellani Chiara , Virzì Maria G , Fedrigo Marny , Thiene Gaetano , Valente Marialuisa , Ronco Claudio , Vescovo Giorgio
Published: April 2024

Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure.

We studied the development of kidney injury in a model of right CHF monocrotaline (MCT) treated rats.

Methods:
10 Sprague-Dawley rats were treated with MCT for 4 weeks until they developed HF. 11 were taken as control (C). Heart failure was confirmed on transverse heart histologic sections looking at RV hypetrophy /dilatation and BNP plasma levels. Cytokine profile was assessed by Multiplex array on sera. pNGAL, pCreatinine (ELISA), kidney tissue NGAL (RT-PCR) were performed. Kidney cell apoptosis was assessed by TUNEL.

Results:
MCT rats showed higher BNP values (MCT 4.7±1.2 vs C 1.5±0.5pg/mL p<0.004 ), marked RV Hypetrophy and dilatation (RVMass/RVVolume MCT 1.46±0.31vs C 2.4±0.8 p<0.01). TNFα (MCT 1325.37±559.95vsC84.46±64.50 pg/ml ), IL1(MCT183.71±51.61vsC78.31±26.07), IL4 (MCT 731.67±154.83 vs C 316.62±12.55pg/ml), IL6 (MCT 5314.983±1632.98 vs C1754.01±188.85), IL10 (MCT2613.10±934.04vs C847.70±152.19 pg/ml) were all increased (p<0.05) as well as Creatinine (MCT 0.95±0.4 vs C 0.57±0.4 ug/mL, p<0.05). Both plasma (MCT 0.56±0.28 vs C 0.25±0.16 ug/mL,p<0.02) and kidney tissue NGAL (MCT 70.7±8.7vs C 32.1±9.9 AU, p<0.001) were significantly increased and a higher number of kidney apoptotic cells was found (MCT 184.01±47.6 vs C 16.3±11.6 cells/mm2, p< 0.0001). In C rats apoptosis was found only on tubular or vascular cells, while in MCT also a lot of interstitial cells was found. In MCT rats apoptosis was found in medullar part of kidney with focal aspect.

Conclusion:
CHF in the rat is accompanied by deterioration of kidney function (CRSII). A rise of creatinine and NGAL, an early biomarker of kidney damage, was detected. Kidney cells apoptosis triggered by circulating pro-inflammatory cytokines represent the final insult to the kidney due to the CHF-induced perturbation of neuro-endocrine and inflammatory milieu.
Abstract 18043: P38 MAP Kinase Negatively Regulates the Slow Force Response to Myocardial Stretch by Affecting NHE1 Phosphorylation
Authors: Villa-Abrille María C , Díaz Romina G , Zavala Maite , Ennis Irene L , Pérez Néstor G , Cingolani Horacio E
Published: April 2024

Mechanical stretch is an important physiological and pathological stimulus to the heart. Stretch induces a biphasic increase in myocardial force generation: A first phase due to the Frank-Starling mechanism, followed by a slower increase in force called slow force response (SFR). The SFR is blunted by AT1 or ETA receptor blockade, by NHE1 inhibition and by reactive oxygen species scavenging. This suggests that it is the mechanical counterpart of an autocrine/paracrine mechanism involving release of angiotensin II (AngII) and endothelin (ET) leading to redox sensitive NHE1 phosphorylation with its consequent activation. Since previous evidence indicates that p38 MAP kinase (p38) negatively regulates the AngII/ET positive inotropic effect in the heart, we hypothesized that the same mechanism would modulate the magnitude of the SFR. Isolated rat papillary muscles were stretched from 92 to 98 % of Lmax. The SFR was 117 ± 2 % of the initial rapid phase (n=6, P<0.05 vs. rapid phase) and was significantly increased after p38 inhibition with 10 umol/L SB202190 (127 ± 2 %, n=6, P<0.05 vs. control SFR), indicating that p38 negatively regulates the SFR development. Since we previously demonstrated that NHE1 activation is a key factor in the chain of events leading to the SFR, we hypothesized that p38 may be modulating NHE1 activity. As an initial approach, we explored the effect of SB202190 on NHE1 activity after an acidic load (ammonium prepulse) in the absence of bicarbonate. p38 inhibition significantly increased maximal NHE1-mediated proton efflux detected at the onset of the acidic recovery [JH+ (mmol/L/min): 2.35 ± 0.25 (n=5) vs. 3.70 ± 0.39 (n=4), P<0.05]. Consistently, under p38 inhibition myocardial stretch promoted a greater increase in ERK1/2 [in % of non stretched control: 166.26 ± 16.35 (stretch, n=3) vs. 231.74 ± 13.70 (strech+SB202190, n=3), P<0.05], and NHE1 [in % of non stretched control: 119 ± 2 (stretch, n=4) vs. 148 ± 9 (strech+SB202190, n=4), P<0.05] phosphorylation. Our results suggest that under physiological conditions p38 activation after myocardial stretch limits the increase in force during the SFR thorough a mechanism that modulates NHE1 phosphorylation.
Abstract 181: Relation between Electrocardiographic Changes and Neurologic Outcomes in Patients Treated with Hypothermia after Out-of-hospital Ventricular Fibrillation Cardiac Arrest: J-PULSE-Hypo Registry
Authors: Tahara Yoshio , Kimura Kazuo , Morimura Naoto , Nagao Ken , Yonemoto Naohiro , Yokoyama Hiroyuki , Nonogi Hiroshi ,   the J-PULSE-Hypo Investigators
Published: April 2024

Background:
The 2010 American Heart Association Guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) recommend that comatose adult patients with return of spontaneous circulation (ROSC) after out-of-hospital ventricular fibrillation (VF) cardiac arrest should receive therapeutic hypothermia (Class I). However, it remains unclear whether therapeutic hypothermia is effective for cardiac arrest patients whose have VF initially, but not at hospital arrival.

Methods:
We conducted a multicenter retrospective study at 14 institutions to evaluate the effect of therapeutic hypothermia on out-of-hospital cardiac arrest between January 2005 and March 2011. The study committee entrusted each hospital with the timing of cooling, cooling methods, target temperature, duration, and rewarming rate. Patients were divided into the VF-VF group, VF-PEA (pulseless electrical activity) group, and VF-Asystole group according to the pre-hospital initial rhythm and the hospital arrival rhythm, and neurologic outcomes at 90 days after cardiac arrest were compared. A favorable outcome was defined as a Cerebral Performance Category (CPC) of 1-2.

Results:
A total of 135 patients were studied. There were no significant differences among the VF-VF group (n=83), the VF-PEA group (n=35), and the VF-Asystole group (n=17) in age, sex, frequency of witnessed cardiac arrest, the presence of bystander CPR, time to achieving target temperature, or duration of therapeutic hypothermia. The rate of favorable outcomes was higher in the VF-VF group (46%) than in the VF-PEA group (23%; p<0.01) and the VF-Asystole group (6%; p<0.01). Multivariate analysis showed that VF rhythm at hospital arrival was an independent predictor of favorable outcomes at 90 days after cardiac arrest.

Conclusions:
Our results suggest that therapeutic hypothermia after ROSC most effectively improves neurologic outcomes in patients who have VF initially as well as at hospital arrival, with no ROSC by the time of hospital arrival. Additional therapeutic strategies are needed to improve neurologic outcomes in patients who have VF initially with no ROSC and a rhythm other than VF at hospital arrival.