bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 92: Documentation Discrepancies of Time-Dependent Critical Events in Out of Hospital Cardiac Arrest
Authors: Frisch Adam , Reynolds Joshua C , Condle Joseph , Gruen Danielle , Callaway Clifton
Published: April 2024

Background:
The timing of and interval between prehospital interventions and patient-related events during out of-hospital cardiac arrest (OHCA) resuscitation are important for system design and patient outcome. Since most prehospital research relies on data abstraction from the medical record, it is imperative to assure the accuracy and precision of time-stamped events in prehospital documentation. Austere environments and/or limited human resources may impair the accuracy and precision of this documentation. OHCA is a time-sensitive disease that necessitates rapid interventions; even small errors in timing documentation may introduce unrecognized bias into analysis.

Objective:
Determine the accuracy and precision of EMS documentation of time-stamped events during OHCA.

Hypothesis:
Times of critical events (CE) in OHCA documented by EMS are inaccurate when compared to audio documentation of the same cases.

Methods:
We reviewed prehospital documentation of OHCA resuscitation from two regional EMS agencies. We abstracted the documented times of CE in the prehospital medical record, as well as synchronized, time-stamped audio recordings from the monitor/defibrillator corresponding to each case. CE included IV/IO access, first epinephrine administration, successful airway placement, and return of spontaneous circulation. We compared the difference in minutes between medical record and audio sources, rounding down to the whole minute.

Results:
A total of 411 patients suffered OOHCA during the study period. Of these, 192 patients had both documentation times and audio times for at least one CE. A total of 422 CEs were documented. A median absolute difference of 2 minutes (IQR 1-4 minutes) was found for all CE. 136 (32.8%) of the cardiac arrest cases had 2 or more CE documented. There was a median discrepancy of 4.5 minutes (Range 0-27, IQR 1-4.5) in the interval between CE in the same case. Within case error shows that the differences are random, and not simply related to synchronization of timing devices.

Conclusion:
Documentation may introduce an error of 2 minutes in the times of CE and 4.5 minutes in the estimated intervals between CE. These errors are meaningful for studies of time dependent diseases like OHCA.
Abstract 9265: Differences in Negative T Waves Between Severe Acute Pulmonary Embolism and Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Tsukhara Kengo , Maejima Nobuhiko , Iwahashi Noriaki , Tahara Yoshio , Konishi Masaaki , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
Patients with severe acute pulmonary embolism (APE) often have precordial negative T waves (NegT). However, this ECG finding is also found in acute coronary syndrome (ACS) due to the left anterior descending coronary artery (LAD) disease. Early differential diagnosis is essential to select an appropriate treatment strategy.

Methods:
We studied admission ECGs in 79 patients with APE who had right ventricular dysfunction and 202 patients with ACS who were admitted within 48 h from symptom onset and had NegT in leads V1-4. Right ventricular dysfunction was defined as right ventricular dilation, paradoxical septal wall motion, or moderare/severere tricuspid regurgitation on admission echocardiography. All patients with ACS underwent coronary angiography during hospitalization, and the most severe stenosis and/or intracoronary thrombus in the LAD was confirmed.

Results:
In patients with APE and ACS, at admission, systolic blood pressure was 109±27 and 151±26 mmHg (p<0.01); heart rate was 103±20 and 74±15 bpm (p<0.01); the rates of positive troponin T were 51% and 46% (p=0.36); and the amplitude of maximal NegT was 3.6±1.9 and 4.6±3.4 mm (p=0.02). The prevalence of NegT ≥1.0 mm is shown in Figure, using the anatomically contiguous Cabrera sequence to display limb leads, and it significantly differed in all leads except -aVR between 2 groups. NegT in both leads III and V1 were observed in 91% of patients with APE, as compared with only 3% of those with ACS (p<0.01). This ECG finding identified APE with 91% sensitivity, 97% specificity, and 95% predictive accuracy, which had the highest diagnostic accuracy.

Conclusions:
In patients with severe APE and ACS caused by LAD disease who had precordial NegT, NegT in both leads III and V1 strongly suggests severe APE.
Abstract 9314: Clinical Impact of Heterozygous Carrier of ATP-binding Cassette Sub-family G Member 5 Gene on Asymptomatic Normolipidemic Patients: Evidence From Familial Gene Analysis
Authors: Tada Hayato , Kawashiri Masa-aki , Nakanishi Chiaki , Konno Tetsuo , Sakata Kenji , Hayashi Kenshi , Yoshimuta Tsuyoshi , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Yamagishi Masakazu
Published: April 2024

Background:
Sitosterolemia is a rare recessive form of inherited disease characterized by increased levels of plant sterols such as sitosterol, the cause of which is ATP-binding cassette (ABC) sub-family G member 5 (ABCG5) or ABCG8 gene mutations. However, few data exist regarding the clinical features and significance of heterozygous sitosterolemic carrier due to the rarity of this disease. The aim of our study was to determine the clinical impact of heterozygous mutation carriers of ABCG5 or ABCG8 gene.

Methods and Results:
We performed genetic analyses of ABCG5 and ABCG8 genes for the 15 family members of patients with homozygous sitosterolemia from different 3 families, and investigated their serum sitosterol levels as well as their lipid levels. We identified 12 heterozygous carriers (male=6, mean age=40) which exhibit single mutation in ABCG5 gene among these families (c.130C>T, c.1306G>A, c.1813_1817delCTTTT) as well as 3 normal family members (male=1, mean age=48). Although there were no significant differences in TC, TG, HDL-C, and LDL-C levels between heterozygous carriers and normal family members, serum sitosterol level of heterozygous carriers was significantly higher than that of normal family members (10.8±4.3 vs 2.7±0.5 μg/ml, p<0.05). Interestingly, heterozygous carriers showed neither xanthomas nor any coronary artery diseases.

Conclusions:
These results demonstrate that heterozygous ABCG5 gene mutation carriers which are somewhat difficult to be identified by the conventional methods may exist among the common normolipidemic patients without significant clinical manifestations. We suggest that the functional analysis of ABCG5 or ABCG8 may facilitate identifying hyper sitosterolemic carriers.
Abstract 9317: Impact of Trastuzumab-Induced Cardiotoxicity and Subsequent Trastuzumab Interruption on Breast Cancer Outcome
Authors: Yu Anthony F , Yadav Nandini U , Manrique Carlos R , Thaler Howard T , Hudis Clifford A , Dang Chau T , Steingart Richard M
Published: April 2024

Background:
Trastuzumab (T) improves disease free and overall survival among pts with HER2 (+) breast cancer (BCA); however this benefit is attenuated by the risk of trastuzumab-induced cardiotoxicity (TIC). Current guidelines recommend interruption of T for CHF or a significant reduction in LVEF, but the impact of this practice on BCA outcomes is unknown.

Methods:
All patients with HER2 (+) BCA receiving adjuvant T with chemotherapy in clinical practice at a single cancer center between January 2005 and June 2010 were studied. Tumor characteristics, cardiac risk factors, LVEF, BCA chemotherapy, and BCA outcomes were obtained from the medical record. The log rank test and Cox proportional model were used to evaluate the association between these variables and time to BCA recurrence.

Results:
Overall, 546 pts with HER2 (+) BCA treated with T were studied; 448 (82%) pts were treated with anthracyclines prior to T. Mean age was 51 yrs (range 26-81); mean follow-up was 4.4 yrs (range 0.6-7.6). T was interrupted for > 1 cycle (> 6 weeks) in 83 (15%) pts. TIC was the reason for interruption in 54 (9.9%) pts; 18 (3.3%) had symptoms of CHF with a decline in LVEF, while 36 (6.6%) had an asymptomatic decline in LVEF. Other reasons for interruption included non-cardiac adverse events (n=11), BCA progression (n=7), and pt request (n=7). Cumulative dose of T was lower among pts with interruption (median 76 vs. 106 mg/kg, p < 0.0001). Early recurrence of BCA was associated with number of positive lymph nodes (p<0.0001), negative progesterone receptor status (p=0.005), interruption of T > 1 cycle for any cause (p=0.006), and interruption of T > 1 cycle due to TIC (p=0.049, Table).

Conclusions:
TIC was the most common reason for interruption of T and was significantly associated with BCA recurrence. These results suggest that coordination of care between cardiologists and oncologists to limit T interruptions while effectively treating cardiotoxicity has the potential to improve outcomes in women with BCA.
Abstract 9320: Ultrafiltration is Associated With Improved Clinical Symptoms but not Rehospitalization or Mortality When Compared to Intravenous Diuretics in Acute Decompensated Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Authors: Shah Sachil , Joseph Georges , Donath Elie M , Moss Noah , Robert Rosenstein S
Published: April 2024

Introduction:
Acute decompensated heart failure (ADHF) is a leading cause for hospitalizations in the US. Intravenous loop diuretics are the first-line therapy for ADHF but 40% of patients are discharged with unresolved congestion resulting in higher re-hospitalization and mortality rates. Ultrafiltration (UF) is a promising intervention that allows rapid removal of isotonic fluid in patients with ADHF. Studies comparing UF to diuretics have been inconsistent in their results regarding clinical outcomes. In this meta-analysis we aim to demonstrate that UF is associated with improvements in decongestion, clinical symptoms and mortality compared to diuretic use.

Methods:
A comprehensive literature search was performed to identify all RCTs from PubMed, EMBASE and Cochrane. Trials were included if they met following criteria: (1) randomization with a control group (2) comparison of UF with a loop diuretic and (3) a diagnosis of ADHF. The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by using a fixed-effects model if no heterogeneity was detected among the studies. A random effects model was applied if significant heterogeneity remained using the fixed effects analysis. A p-value of 0.05 was used to denote statistical significance.

Results:
Nine RCTs, including 605 patients (303 received diuretics, 302 received UF), were included in meta-analysis. When compared to diuretics, UF was associated with a reduced risk of clinical worsening (OR 0.57, 95% CI: 0.38-0.86, p-value 0.007), an increased likelihood for clinical decongestion (OR 2.32, 95% CI: 1.09-4.91, p-value 0.03), greater weight reduction (0.97 Kg, 95% CI: 0.52 - 1.42, p-value <0.0001) and greater volume reduction (1.11 L, 95% CI: 0.68-1.54, p-value <0.0001). The overall risk of re-hospitalization (OR 0.92, 95% CI: 0.62-1.38, p-value 0.70) and risk of return to emergency department (OR 0.69, 95% CI: 0.44-1.08, p-value 0.10) were not significantly improved by UF treatment. UF was not associated with a reduced risk of mortality (OR 0.99, 95% CI: 0.60-1.62, p-value 0.97).

Conclusions:
UF is associated with significant improvements in clinical decongestion and volume reduction but not in rates of re-hospitalization, return to emergency department or mortality.
Abstract 9419: Clinical Impact of Incidental Findings Detected on Computed Tomography in Patients Evaluated for Transcatheter Aortic Valve Replacement
Authors: Orme Nicholas M , Wright Thomas C , Harmon Gil E , Nkomo Vuyisile T , Williamson Eric E , Sorajja Paul , Foley Thomas A , Greason Kevin L , Suri Rakesh M , Rihal Charanjit S , Young Phillip M
Published: April 2024

Background:
Patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR) undergo aortoiliac computed tomographic angiography (CTA) of the chest/abdomen/pelvis. Despite the increasing number of TAVR procedures worldwide, little is known regarding the clinical significance of non-cardiovascular incidental findings (IFs) on TAVR-CTA scans.

Objective:
To determine the frequency, clinical significance and impact on survival of non-cardiovascular IFs detected on TAVR-CTA scans.

Methods:
CTA studies for 424 consecutive patients being evaluated for TAVR were reviewed for non-cardiovascular IFs (62% male, median age 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival.

Results:
An IF was present in nearly all patients (99%). The mean number of IFs per patient was 5.3 (±2.8; range 0-14). After excluding obviously benign IFs, 67% had at least one potentially pathologic IF (mean 1.1±1.0). Factors associated with higher numbers of IFs were age (p<0.0001) and use of IV contrast (p=0.03). IFs prompted clinical work-up in 39 patients (9.2%) and delayed or cancelled procedures in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of IFs was predictive of poor overall survival before (HR 1.09; 95% CI (1.02 to 1.70), p=0.02) and after adjustment for baseline clinical variables (HR 1.07; (1.0 to 1.15); p=0.04).

Conclusions:
This investigation demonstrates that IFs are present in nearly all TAVR-CTA scans, commonly require further clinical evaluation, and are associated with poorer survival. TAVR institutions should have mechanisms in place to ensure communication and follow-up of IFs.
Abstract 9450: Exercise Reduces Myocardial Doxorubicin Accumulation by Upregulating Multidrug Resistance Protein Expression
Authors: Gibson Noah M , Quinn Colin J , Pfannenstiel Keith B , Bashore Alex C , Hydock David S , Hayward Reid
Published: April 2024

Background:
The anthracycline antibiotic doxorubicin (DOX) is an effective antineoplastic agent. However, treatment with DOX is associated with a dose-dependent cardiotoxicity that can lead to dilated cardiomyopathy and congestive heart failure. While previous studies have reported that exercise preconditioning can reduce DOX accumulation within the myocardium, the mechanisms are unknown. Members of the ATP binding cassette transporter superfamily, multidrug resistance proteins 1, 2 and 7 (MRP-1. -2, -7) are known to extrude DOX from cells and their expression may factor into the degree of cardiac DOX accumulation and therefore the severity of cardiac dysfunction. We hypothesized that exercise elicits an upregulation of MRP expression, which leads to a reduction in DOX accumulation.

Methods and Results:
Male Sprague-Dawley rats were randomly assigned to undergo 10-weeks of voluntary wheel running (WR: n=15) or remain sedentary (SED: n=15). Upon completion of 10-weeks, rats were further randomized to receive a 15mg/kg body weight bolus i.p. injection of DOX (WR-DOX: n=8, SED-DOX: n=7) or equivalent volume of saline (WR-SAL: n=8, SED-SAL: n=7). Animals were sacrificed 24-hours following injection and hearts were excised, flushed of blood, and left ventricles were isolated. High performance liquid chromatography was utilized to quantify myocardial DOX accumulation and Western blotting to analyze MRP expression. A significant reduction in DOX accumulation was observed in WR animals when compared to SED (1055±189 ng/g vs. 1284±151 ng/g). When compared to SED-SAL, all groups exhibited an increase in MRP-2 and MRP-7 expression (WR-DOX: MRP-2, 83% increase; MRP-7, 337% increase. SED-DOX: MRP-2, 107% increase; MRP-7, 193% increase. WR-SAL: MRP-2, 99% increase; MRP-7, 179% increase). In addition, MRP-1 was significantly increased in DOX treated groups (WR-DOX: 136% increase. SED-DOX: 79% increase), however, no significant differences were observed with exercise (WR-SAL: 56% increase).

Conclusion:
An upregulation of myocardial MRP-2 and MRP-7 expression with exercise contributes to a decrease in myocardial DOX accumulation and may result in a subsequent cardioprotective effect. DOX exposure alone also induces an upregluation of MRPs.
Abstract 9458: Left Ventricular Deformation Analysis Using Vendor Dependent and Vendor Independent Three-Dimensional Speckle Tracking Software: A Validation Study
Authors: Shimada Eriko , Zhu Meihua , Kimura Sumito , Streiff Cole , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Accurate quantification of myocardial deformation by three dimensional speckle-tracking echocardiography (3DSTE) is useful. A high variability in 3DSTE-derived values has been observed among different ultrasound machines and analysis software. The aim of this study was to compare vendor dependent and vendor independent speckle-tracking software packages using 3D data acquired by the same machine with sonomicrometry as reference method and to elucidate the feasibility of a vendor-independent software.

Methods:
Ten harvested porcine hearts with 3 sonomicrometry crystals in the endomyocardium of the anterior walls were attached to a pulsatile pump. Hearts are pumped at 5 stroke volumes ranging 30 to 70 ml, with constant rotation and compaction to simulate normal cardiac motion. Echo images were acquired using a Siemens Acuson SC2000. After baseline imaging, glutaraldehyde was injected in the mid-anterior segment simulating myocardial infarction (MI). Images were analyzed using a Siemens analysis package and TomTec Arena program to evaluate the circumferential and longitudinal strain (CS, LS) values in the mid-anterior segment.

Results:
When comparing strain data obtained by each software systems and sonomicrometry, Pearson correlation coefficients (
R
) of CS and LS determined by the Siemens program were 0.84 and 0.89 (both p<0.05). TomTec Arena produced data with
R
value of 0.84 and 0.9 (both p<0.05). After simulated MI induction, CS and LS derived from both software systems were significantly decreased and had a good correlation with sonomicrometry with
R
values ranging from 0.73 to 0.76 (all p<0.05).

Conclusions:
Both vendor-dependent and independent software systems for 3D speckle-tracking echocardiography showed the ability to accurately detect myocardial deformation.
Abstract 9461: Prevalence and Characteristics of Spontaneous and Adenosine-Induced Acute PV Reconnection Associated With IV Corticosteroid Use During Pulmonary Vein Isolation
Authors: Macle Laurent , Andrade Jason , Vanella Agustin , Nattel Stanley , Rivard Lena , Guerra Peter G , Dubuc Marc , Thibault Bernard , Talajic Mario , Dyrda Katia , Mondesert Blandine , Nozza Anna , Roy Denis , Khairy Paul
Published: April 2024

Background:
Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is associated with PV to left atrium re-conduction. Intraprocedural corticosteroids may limit RF-induced tissue edema and prevent post-ablation inflammatory responses. We prospectively evaluated the impact of pre-ablation IV corticosteroids on the prevalence of spontaneous and adenosine-induced acute PV reconnection following PVI and on long-term success rates after ablation.

Methods:
Prior to wide circumferential PVI 45 patients received a single IV bolus of 250 mg of hydrocortisone immediately following transseptal access (steroid group), whereas another 45 consecutive patients underwent standard PVI without IV hydrocortisone (non-steroid group). Post PVI, acute PV reconnection was systematically assessed in each PV (prevalence and location) using a circular mapping catheter during a 20-min waiting period (spontaneous PV reconnection), followed by provocation with IV adenosine (dormant conduction). All patients were followed at 3, 6, and 12 months.

Results:
Spontaneous PV reconnection during the 20-min waiting period was observed in 9% of PVs (31/358), with no significant difference between the 2 groups (5.5% steroid vs 11.4% non-steroid; p=0.10). Dormant conduction was unmasked in a significantly higher proportion of PVs in the steroid group when compared to the non-steroid group (32.8% of PVs [60/183] vs. 21.1% of PVs [37/175] P=0.03). On multivariate GEE analysis, steroid use remained independently associated with dormant PV conduction (P=0.03). There was no difference in the segmental distribution of reconnection between the two groups. The one-year freedom from recurrent AF did not differ between groups (P=0.37). Radiofrequency time was significantly longer in the steroid group (58±21 vs. 48±18 minutes, P=0.006), whereas procedure duration and fluoroscopy time were comparable (p=0.55, and p=0.44).

Conclusions:
A single bolus of hydrocortisone 250 mg IV prior to PVI results in greater RF requirements for PV isolation and higher prevalence of dormant PV conduction unmasked by adenosine without affecting long-term outcomes. The utility of these approaches requires evaluation in a long-term prospective randomized study.
Abstract 9542: Do ICDs Prevent Hip Fractures or Are Physicians Selecting Appropriate Candidates for ICDs?
Authors: Setoguchi Soko , Warner Stevenson Lynne , Stewart Garrick G , Bhatt Deepak L , Epstein Andrew E , Desai Manisha , Williams Lauren , Chen Chih-Ying
Published: April 2024

Background:
In real world practice, treatments are not randomly allocated but selected based on indications and other considerations. If not taken into account, these selection factors can impact comparative effectiveness estimates in observational studies.

Objective:
To assess the potential contribution of unmeasured general health status to patient selection in assessing clinical effectiveness of ICDs for primary prevention.

Methods:
Linking CMS ICD registry, National Cardiovascular Data Registry (NCDR®) ICD Registry™, a heart failure (HF) registry, and Medicare files (2005-2009), we identified HF patients ≥66 years who were eligible for primary prevention ICDs. We compared the risk of nontraumatic hip fracture, skilled nursing facility (SNF) admissions, and 30-day mortality between hospitalized HF patients with and without ICDs. Crude and adjusted hazard ratios were estimated by Cox proportional hazards regression.

Results:
Compared with 17,853 patients without ICDs, 11,573 patients with ICDs were younger and had lower ejection fractions and more cardiac hospitalizations, but fewer noncardiac hospitalizations and comorbid conditions. Patients with ICDs had greater freedom from unrelated events: hip fracture (HR 0.39; 95% CI, 0.37-0.41, Figure), SNF admission (HR 0.53 95% CI, 0.50-0.55), and 30-day mortality (HR 0.10; 95% CI, 0.09-0.12%). After adjustment for multiple measured patient characteristics, risks in the two groups were less disparate but still substantially lower in ICD patients (HRs ranged from 0.20 to 0.84).

Conclusion:
The lower risks of these outcomes likely reflect unmeasured differences in comorbidity burden and frailty. These findings highlight potential pitfalls of observational comparative effectiveness research. The findings also support that physicians in clinical practice consider general health status in selecting patients for ICD implantation, avoiding implantation in patients who are less likely to benefit.
Abstract 9634: Reclassification of Cardiovascular Risk by Including Ultrasound Detected Plaque of the Femoral and Carotid Arteries Improves Identification of High-Risk Subjects
Authors: Postley John , Luo Yanting , Wong Nathan D , Gardin Julius M
Published: April 2024

Background:
Current Cardiovascular Disease (CVD) predictive algorithms recognize traditional risk factors in populations but have failed to identify many of those at highest risk because of detectable vascular disease. We compared an enhanced algorithm, "Lifetime Risk" (LR), with Framingham Risk Score (FRS) algorithms both 10-yr and 30-yr in their ability to identify subjects at highest risk for developing an initial CVD event by including ultrasound detected carotid or femoral artery plaque.

Methods:
We performed Ultrasound Examination (UE) of both carotid and femoral arteries in 939 adults (36% women) between the ages of 30 and 60 after excluding those with previous CVD (myocardial infarction, angina, stroke or claudication). Subjects were categorized into low-, intermediate- and high-risk groups on the basis of respective published criteria for the algorithms. Subjects in the low- and intermediate-risk groups were reclassified as high risk if UE showed any arterial plaque.

Results:
Overall, low- and intermediate-risk men allocated by LR required less reclassification(17%) than men allocated by 30-yr FRS (24%) (p<0.001) or 10-yr FRS (37%) (p<0.001) because of plaque detected by UE. Similarly, low- and intermediate-risk women allocated by LR required less reclassification (14%) than women allocated byy 30-yr FRS (24%) (p<0.001) or 10-yr FRS (31%) (p<0.001) (Table). Of men categorized as low risk by 10-yr FRS (23%) and LR (24%) were reclassified as high-risk and of women categorized as low-risk by 10-yr FRS (25%), 30-yr FRS (13%) and LR (24%) wre reclassified as high-risk because of plaque detected by UE.

Conclusions:
Our study which included UE of easily accessible arteries showed increased sensitivity of LR, compared to 10-yr and 30-yr FRS, for the identification of both males and females at high risk for CVD events based on the presence of easily detectable arterial plaque.
Abstract 9642: An Image Based Evaluation of Dynamic Heart Function Following Different Cardiopulmonary Bypass Techniques, Using New High-Resolution 4D Echocardiography
Authors: Vachhani Priyanka , Deb Rohini , Ashraf Shahryar , Mandi Kaavya , Truong Kevin , Tam Lydia , Chen Vivian , Zhang Jiahui , Streiff Cole , Zhu Meihua , Langley Stephen , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
In this study, we evaluated the impact of different cardiopulmonary bypass methods on dynamic heart function.

Methods:
We studied 12 open-chest piglets (3-5kg). Body temperature, oxygen saturation, blood gases and vital signs were continually monitored. Baseline 4D full volume image loops were acquired from the heart surface with a 4Z1c matrix transducer on a Siemens SC 2000 ultrasound system at frame rate > 30 VPS. Five piglets were subjected to cross-circulation cardiopulmonary bypass for 2 hours using an adult matched donor. Seven piglets were subjected to conventional bypass for the same duration, 3 with matched blood at body temperature (normothermic) and 4 with matched hypothermic blood. After 2 hours of bypass, normal circulation was restored, 4D images acquired after stabilization and images were analyzed offline using VMM motion analysis software from Siemens.

Results:
In piglets with cross-circulation, average peak apical and basal rotation was slightly increased (0.25-0.95°) and average peak strain (both circumferential and longitudinal) values were diminished in all segments (2.25-4.15%, p=0.039). Piglets with normothermic cardiopulmonary bypass showed similar mechanical changes in LV strain and rotation (p=0.017). Piglets with hypothermic bypass, however, showed a greater increase in LV rotation (1.25-1.75°) and greater depression of strain values (4.25-6.15%).

Conclusion:
New 4D echo is feasible to monitor dynamic heart function after cardiopulmonary bypass.
Abstract 9675: Does the Degree of Left Ventricular Dysfunction or Symptom Status Influence the Risk of Stroke or Systemic Embolism Among Patients With Atrial Fibrillation and Heart Failure?-Results From the ACTIVE Study
Authors: Sandhu Roopinder K , Connolly Stuart J , Hohnloser Stefan , Pfeffer Marc , McAlister Finlay , Healey Jeff
Published: April 2024

Background:
Heart failure (HF) is a major component of widely applied stroke risk stratification schemes in atrial fibrillation (AF). However, data regarding the relationship between left ventricular (LV) dysfunction or HF symptoms and risk of stroke/systemic embolism among HF patients remains sparse.

Methods:
A total of 3487 participants from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF at baseline were randomized to anti-platelet therapy. Patients with HF were categorized as having preserved vs reduced ejection fraction (PEF ≥ 0.50, REF < 0.50). If reduced, the degree of LV dysfunction was classified as mild, moderate or severe. HF symptoms were assessed using New York Heart Association (NYHA) class I-IV. Cox proportional-hazards models were used to estimate hazard ratios (HR, 95% CI) for stroke/systemic embolism across categories of LV dysfunction and NYHA class.

Results:
At baseline, 875 (47%) had HF-PEF, 982 (53%) had HF-REF; the degree of LV dysfunction was classified as mild in 25%, moderate in 25% and severe in 14%. During 3.6 years of follow-up, 211 patients had stroke/systemic embolism. In multivariable analysis, independent predictors of stroke were age ≥ 75 years (HR 2.83, 1.80-4.44), diabetes (HR 1.45, 1.03-2.03), diastolic blood pressure (per 1 mmHg, HR 1.02, 1.01-1.04), peripheral arterial disease(HR 1.94, 1.10-3.41), female(HR 1.48, 1.07-2.05) and prior stroke/transient ischemic attack (HR 1.77, 1.23-2.54) however EF < 0.50, LV dysfunction or NYHA class were not predictors. Compared to those with HF-REF, patients with HF-PEF exhibited similar risk of stroke/systemic embolism: 4.18% vs. 3.83% per year, HR 0.89, 95% CI 0.65-1.22 after controlling for AF risk factors. Compared to normal LV function, there was no significant trend across categories of LV systolic dysfunction (p for trend, 0.57). The risk of stroke/systemic embolism was similar in HF patients with NYHA class I (4.0% per year, referent category), II (4.0%, HR 0.87, 0.60-1.26), III (3.9%, HR 0.62, 0.38-1.02), or IV (2.8%, 0.60, 0.14-2.55).

Conclusion:
Among patients with a history of HF, the presence or absence of LV dysfunction or severity of HF symptoms did not influence the risk of stroke/systemic embolism.
Abstract 9809: Upregulation of Aldosterone by Steroidogenesis Acute Regulatory Protein (StAR) is Associated With Connective Tissue Growth Factor-Mediated Pulmonary Vascular Fibrosis in Pulmonary Arterial Hypertension In Vivo
Authors: Maron Bradley A , Annis Sofia , Chan Stephen Y , Loscalzo Joseph , Leopold Jane A
Published: April 2024

Hyperaldosteronsim is associated with increased pulmonary vascular remodeling in patients with pulmonary arterial hypertension (PAH). In cardiomyocytes, aldosterone (ALDO) promotes collagen deposition by increasing levels of connective tissue growth factor (CTGF). The role of CTGF in ALDO-mediated vascular remodeling in PAH, however, is not known. We hypothesized that upregulation of CTGF by ALDO is a novel signaling mechanism that modulates pulmonary vascular fibrosis in PAH. To test this hypothesis, cultured human pulmonary artery endothelial cells were exposed to ALDO (10
-9
-10
-7
mol/l) for 24 hr and changes in CTGF levels were assessed by immunoblotting. Compared to vehicle control, ALDO induced a dose-dependent increase in CTGF expression (3.4 ± 0.2 vs. 6.7 ± 1.9 vs. 10.4 ± 1.6 vs. 17.6 ± 1.9 units, P=0.02). We next investigated the effect of ALDO on CTGF in PAH in vivo. Compared to controls, rats exposed to SU-5416 (20 mg/kg) and hypoxia (10% O
2
) (Su/Hyp) for 21 d demonstrated increased pulmonary artery systolic pressure (PASP) (26 ± 2 vs. 81 ± 5 mmHg, P<0.05), which was associated with a 397% (P<0.02) increase in plasma ALDO levels. Next, we investigated changes in levels of steroidogenic acute regulatory protein (StAR) as a mechanism by which to account for hyperALDO in PAH. Compared to controls, immunohistochemistry revealed increased StAR in the pulmonary arterioles of Su/Hyp-PAH rats (19.2 ± 0.9 vs. 30.2 ± 0.5 units, P<0.01) and in patients with PAH (14.3 ± 1.4 vs. 19.3 ± 0.9 units, P<0.02). Immunohistochemistry revealed that compared to controls, Su/Hyp-PAH rats expressed increased levels of CTGF (88.1 ± 11.5 vs. 171.8 ± 5.9 units, P<0.01) and collagen III (61.5 ± 18.7 vs. 126.5 ± 6.3 units, P<0.01) in pulmonary arterioles. ALDO antagonism with eplerenone (0.6 mg/g chow) decreased CTGF and collagen III levels in SU/Hyp-PAH by 81% (p<0.01) and 38% (P<0.01), respectively, to decrease PASP (81 ± 5 vs. 62 ± 7 mmHg, P<0.05). These data demonstrate that upregulation of StAR is associated with hyperALDO in PAH, which promotes vascular fibrosis through a mechanism involving CTGF. Identifying StAR and/or CTGF as novel treatment target(s) to attenuate pulmonary vascular fibrosis has potential therapeutic implications for patients with PAH.
Abstract 9812: The Symptom Status Questionnaire is a Reliable and Valid Symptom Instrument for Patients With Heart Failure
Authors: Heo Seongkum , Moser Debra K , Dunbar Sandra B , Pressler Susan J , Kim Jinshil , Lennie Terry A
Published: April 2024

Background and Purpose:
Patients with heart failure (HF) experience physical symptoms, poor health-related quality of life (HRQOL), and high rates of hospitalization. Physical symptoms are associated with HRQOL and are major antecedents of hospitalization. However, reliable and valid physical symptom instruments have not been established for use in patients with HF. This study, therefore, examined the psychometric properties of the Symptom Status Questionnaire-Heart Failure (SSQ-HF) in patients with HF.

Method:
Data on symptoms were collected from 249 Patients (age 61, 67% male, 45% in New York Heart Association functional class III/IV). Internal consistency reliability was assessed using Cronbach’s alpha. Item homogeneity was assessed using item-total and inter-item correlations. Construct validity was assessed using factor analysis and testing hypotheses on known relationships. The SSQ-HF is a 7-item questionnaire asking about the presence, frequency, severity, and distress of common HF symptoms during the past 4 weeks. Data on depressive symptoms (using the Beck Depression Inventory II), HRQOL (using the Minnesota Living with Heart Failure Questionnaire), and event-free survival were collected to test known relationships. Event-free survival was defined as the time from enrollment to the first event of all-cause hospitalization, emergency department visit, or death.

Results:
Cronbach’s alpha was .80, supporting internal consistency reliability. Item-total correlation coefficients and inter-item correlation coefficients were acceptable. One factor was extracted, and all the items demonstrated moderate to strong loadings (> .40), indicating acceptable construct validity. As hypothesized, more severe symptoms were associated with more depressive symptoms, poorer HRQOL, and shorter event-free survival, providing further evidence for the construct validity of the SSQ-HF.

Conclusions:
The findings of this study support the reliability and validity of the SSQ-HF. Clinicians and researchers can use this instrument to assess physical symptoms in patients with HF.
Abstract 9955: Echocardiographic Markers of Right Ventricular Function, Body-Mass Index, and Sleep Apnea in the Wisconsin Sleep Cohort
Authors: Korcarz Claudia E , Barnet Jodi H , Hla K. M , Young Terry B , Peppard Paul E , Stein James H
Published: April 2024

Background:
Sleep-disordered breathing (SDB) is associated with increased cardiovascular disease risk and adverse cardiac remodeling due to increased sympathetic activity, oxidative stress and intermittent hypoxia. We characterized echocardiographic markers of right ventricular (RV) function in a large cohort with SDB.

Methods:
Between 2009 and 2012, transthoracic echocardiography was performed in a population-based cohort study evaluating the association of SDB and cardiovascular disease risk. Overnight polysomnography was performed ~1 month prior. SDB was characterized by the apnea-hypopnea index (AHI, events/hour). Participants on continuous positive airway pressure were excluded. RV systolic function was assessed from apical views and described by RV fractional area change (RVFAC), RV free wall strain (%) and strain rate (s
-1
), Tricuspid Annular Plane Systolic Excursion (TAPSE, mm), and qualitatively by an experienced echocardiographer. Associations between echocardiographic markers and AHI were adjusted for covariates in multivariable linear and logistic regression models.

Results:
The 352 subjects were mean (standard deviation) 64.6 (7.3) years old (49% female). They had a body-mass index (BMI) of 30.5 (6.4) kg/m
2
, systolic blood pressure (SBP) of 127 (13.6) mmHg, and ejection fraction of 61.4 (5.8) %. 52% had hypertension. Mean AHI was 5.8 (7.8) events/hour; 7.7% had moderate-severe SDB (AHI ≥15 events/hour). After adjustment for age, sex, BMI, smoking status, lung disease, SBP and use of antihypertensive medications, subjects with higher AHI had lower global RV strain rate (β=-0.12 s
-1
/events/hour, p=0.03) and TAPSE (β=-0.07 mm/events/hour, p=0.03). Increased AHI was a significant predictor of visually assessed RV systolic dysfunction, but only in models that did not include BMI (OR=1.04; 95% confidence interval 1.01 -1.08 events/hour; p=0.015). RVFAC (p=0.20) and RV free wall global strain (p=0.21) were not associated with AHI.

Conclusion:
SDB is associated with RV dysfunction independent of its associations with obesity and hypertension. Quantification of RV global strain rate and TAPSE permit more objective assessment of RV function and are less sensitive to the confounding effects of BMI.
Abstract 10209: The Severity of the Metabolic Syndrome Increases over Time within Individuals, Independent of Baseline Metabolic Syndrome Status and Medication Use: The Atherosclerosis Risk in Communities Study
Authors: Vishnu Abhishek , Gurka Matthew J , DeBoer Mark D
Published: April 2024

Background:
Clinical significance of traditional ATP-III metabolic syndrome (MetS) is a subject of debate, possibly due to its inability to track disease progression over time. We have developed a continuous MetS severity z-score such that the relative contributions of each of the MetS components to the overall severity score vary by sex- and race/ethnicity, and thus the score changes over time with MetS components. We aim to examine how MetS severity changes over time within individuals.

Methods:
Changes in MetS severity score were assessed over a 12-year period (Visits 1-4) among 9,291 participants of the Atherosclerosis Risk in Communities study, after excluding those with baseline MetS, CVD or diabetes. Age-adjusted rate of change in the MetS severity score and MetS prevalence as assessed using ATP-III MetS criteria were compared among sex- and racial/ethnic subgroups. Further, effects of age (<50, 50-60, and >60 years) and use of medications for hypertension, diabetes and dyslipidemia on MetS severity progression were examined.

Results:
MetS severity z-scores increased among 76% of participants between visits 1 and 4, with an overall increase in z-score from 0.08 (±0.77) at baseline to 0.48 (±0.96) at visit 4. The greatest progression was observed among African-American women. Baseline MetS severity z-scores predicted the time until ATP-III MetS diagnosis, with 90.2% of individuals with score of ≥1.0 (n=1,097) progressing to ATP-III MetS by visit 4. Score progression was higher among those younger (<50 years) at baseline but was independent of baseline MetS status or the use of medications to treat blood pressure, lipids and diabetes.

Conclusion:
The severity of metabolic derangements as measured using this sex- and race/ethnicity specific MetS z-score increases over time within individuals and predicts diagnosis of ATP-III MetS. These data may have implications for tracking MetS related risk over time within individuals.
Abstract 10293: Regional Right Ventricular Dysfunction in Acute Pulmonary Embolism Associated With Increased Clot Burden and Greater RV Dysfunction
Authors: Tuzovic Mirela , Adigopula Sasikanth , Amsallem Myriam , Kobayashi Yukari , Boulate David , Krishnan Gomathi , Liang David , Schnittger Ingela , McConnell Michael V , Haddad François
Published: April 2024

Introduction:
Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. We assessed the hypothesis that RRVD is associated with increased burden of PE and greater RV dysfunction.

Methods:
We identified all consecutive patients admitted at Stanford’s emergency department between 1999 and 2014 who underwent both computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) within 2 days of each other for suspected acute PE, in order to investigate the relationship between RRVD, PE clot burden, RV size/function, and biomarkers. Patients with PE were divided according to clot burden as follows: central or multilobar PE versus peripheral PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV function was assessed by fractional area change and free-wall longitudinal strain. Echocardiograms were also assessed for reproducibility.

Results:
Eighty-two patients were included (mean age 66 ±17 years, 43% male, 51 with acute PE). RRVD was present in 41% of PEs and absent in all patients without PE. Eighty-six percent (86%) of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81% vs. 30%, p<0.01) and dysfunction (86% vs. 23%, p<0.01). Troponin level was positive in 38% of patients with RRVD versus 13% in PE without RRVD (p=0.08), while the NT-proBNP level was positive in 67% versus 73% (p=0.88), respectively. RRVD showed excellent concordance between readers (87%).

Conclusion:
The “McConnell sign” of RRVD is a reproducible finding associated with an increased clot burden and greater degree of RV dysfunction in patients with acute PE.
Abstract 10806: The Role of Neuronal Nitric Oxide Synthase on the Vascular Hyporeactivity and Multiple Organ Failure Associated With Hemorrhagic Shock
Authors: Sordi Regina , Chiazza Fausto , Collino Massimo , Assreuy Jamil , Thiemermann Christoph
Published: April 2024

Introduction:
Trauma can cause severe hemorrhage leading to a state of global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Several studies have shown the participation of nNOS-derived NO in the pathogenesis of the systemic inflammatory response and sepsis. However, the role of nNOS in HS is poorly understood.

Hypothesis:
The aim of this study is to investigate the role of nNOS-derived NO in the MOF associated with HS.

Methods:
Rats were subjected to HS under sodium thiopental anesthesia (120 mg/kg; i.p.). The blood pressure was reduced to 30 ± 2 mmHg for 90 min, followed by resuscitation with the shed blood. Rats were treated with 3 different nNOS inhbitors (S-methyl-L-thiocitrulline, ARL 17477 or 7 nitroindazol) or vehicle upon resuscitation. Four hours later, organ injury and dysfunction and the signaling events involved in the observed protective effects of nNOS inhibitors were investigated.

Results:
When compared to sham rats, HS resulted in a significant decrease in creatinine clearance and rises in serum creatinine, creatine kinase, lactate, aspartate and alanine aminotransferases, indicating the development of MOF. HS also resulted in vascular hyporeactivity to norepinephrine. Treatment of HS-rats with nNOS inhibitors protected animals against the MOF and vascular dysfunction induced by HS. When compared to HS control, analysis of kidney and liver tissue from HS rats treated with nNOS inhibitors revealed decreases in phosphorylation of IκB and p65 nuclear translocation of NF-κB, reduction in iNOS expression, NOx production and protein nitrosylation. nNOS inhibitors treatment also attenuated systemic pro-inflammatory cytokines formation.

Conclusions:
Our findings show that nNOS inhibition at the onset of resuscitation protects rats against the MOF and vascular dysfunction associated with HS thorough the attenuation of NF-κB activation and consequent reduction of NF-κB-dependent proteins (such as iNOS and pro-inflammatory cytokines), and thorough the attenuation of proteins nitrosylation by NO-derived species.
Abstract 10864: Effect of Fructose vs Sucrose and Sucralose on Glucose, Insulin and Triglyceride Levels in a Solid Mixed Meal in Healthy People
Authors: Gallagher Clare , Clifton Peter , Pedersen Eva , Keogh Jennifer
Published: April 2024

Background:
Fructose, a nutritive sweetener with a low GI has been shown in previous studies to elevate TGs when compared to a glucose control. There is limited data available on the effect of fructose in a mixed meal. The aim of this study was to determine the effects of sucrose, fructose and sucralose on triglyceride, glucose and insulin response in an acute study in healthy individuals.

Methods:
This study was a randomised cross-over design. Twenty-seven participants with a median age of 40, and a BMI of 26.3kg/m2 completed the study. Fructose (52g), sucrose (65g) and Sucralose (6g of Splenda) were delivered as sweet taste-balanced muffins with a standardised fat load (66g). Blood samples were taken at baseline and every 30 minutes for 4 hours. Glucose, triglyceride and insulin concentrations over time, area under the curve (AUC) and incremental area under the curve (iAUC) were analysed.

Results:
No significant difference was found between the three sweeteners for triglyceride and glucose concentrations, AUC and iAUC. A significant difference was found for insulin treatment (p = 0.001), time*treatment (p = 0.035), AUC (p =0.000) and iAUC (p =0.000). Post hoc analysis showed that fructose had a significantly lower response than either sucrose (p = 0.006) or sucralose (p = 0.041).

Conclusion:
Fructose at a moderate dose did not significantly elevate triglycerides in comparison to sucrose or sucralose. No significant difference in the glycaemic response between the meals was found. These results indicate that these sweeteners can be safely interchanged for normal mixed meals. Fructose showed a lower insulin response which may be beneficial long-term in those at risk of type 2 diabetes.
Abstract 10881: Importance of Stroke Volume Index Assessed by Echocardiography for Stratification of Low Gradient Severe Aortic Stenosis With Normal Left Ventricular Function
Authors: Shen Hong , Stacey Brandon , Applegate Bob , Zhao David , Vasu Sujethra , Upadhya Bharathi , Gandhi Sanjay , Pu Min
Published: April 2024

Background:
The prognosis and need for aortic valve intervention in patients with low-gradient (LG) severe aortic stenosis (AS) and normal left ventricular (LV) function remain controversial. We hypothesized that echocardiography (echo) could be used for the stratification of high risk patients when accurate assessment of stroke volume (SV) is obtained.

Methods:
The study included 207 patients with LG severe AS (aortic valve area (AVA) ≤ 1.0cm2, mean gradient < 40mmHg) and normal LV function (LVEF ≥ 50%). In order to improve the accuracy of SV calculation by echo, we measured the LV outflow tract diameter (LVOT) at two locations: 5mm below the aortic annulus (recommended by the American Society of Echocardiography) and at the aortic valve annulus (common in clinical practice). Patients were divided into two groups based on SV index (SVi). Group I had SVi < 35mL/m2 (n=75) and Group II had SVi ≥ 35mL/m2 (n=97) calculated based on both locations using continuity equation. Patients with discrepancy in SVi calculation at the two LVOT locations (potential LVOT-velocity mismatch) were excluded (n=35). Mean follow-up time was 3.0±1.6 years.

Results:
There was no significant difference in age (78±11 vs. 77±11 years), LVEF (58±6 vs. 60±6%), mean aortic valve gradient (30±5 vs. 31±5 mmHg) and LV mass index (115±34 vs. 109±31 g/m2) between Group I and Group II. Group I had larger body surface area (1.97±0.25 vs. 1.84±0.25 m2), smaller AVA index (0.36±0.08 vs. 0.50±0.09 cm2/m2), higher valvuloarterial impedance (6.1±1.6 vs. 4.0±0.8 mmHg/mL/m2) and lower 3-year cumulative survival (61% vs. 75%, p=0.03) than Group II. Multivariable analysis showed SVi was a strong predictor of mortality among LG severe AS patients (HR 0.95, CI: 0.91-0.99, P=0.02). For Group I, those with medical management had a two-fold increased risks of death compared to those who underwent AS intervention (HR: 2.74, CI: 1.13-6.67, p=0.03). However, there was no survival benefit associated with AS intervention in Group II (HR: 0.73, CI: 0.29-1.80, p=0.49).

Conclusion:
LG severe AS with normal LV function consists of heterogeneous patients carrying different prognosis depending on SVi. If low SVi is accurately assessed by Doppler echo, AS intervention may be beneficial. Further clinical trials are warranted.