bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12745: Interleukin-4 Promotes Procollagen Type-I Alpha 1 Gene Expression via Activator Protein 1 Activation in Cardiac Fibroblasts
Authors: Peng Hongmei , Wu Min , Peterson Edward , Rhaleb Nour-Eddine
Published: April 2024

Interleukin-4 (IL-4) activates the signal transducer and activator of transcription 6 signaling pathway, resulting in the upregulation of procollagen genes and promotion of collagen production in cardiac fibroblasts (CFs). In addition, transcription factors may participate in the transcriptional activation of collagen genes. We hypothesize that IL-4 activates activator protein 1 (AP-1) via c-Jun phosphorylation, promoting transcriptional activation of the procollagen type-I alpha 1 (Col1α1) gene and collagen type-I expression in CFs. Primary mouse CFs were used. Western blot analyses revealed that IL-4 (10 ng/ml) increased phosphorylation of c-Jun, a subunit of AP-1. Additionally, our experiments utilizing electrophoretic mobility shift assay (EMSA) revealed a significant increase in DNA binding activity for AP-1 in IL-4-treated CFs compared to control cells (1.00±0.07 to 2.14±0.38 fold change versus control,
p
<0.05). Here we aimed to determine whether IL-4-activated AP-1 participates in transcriptional activation of the Col1α1 gene leading to increased collagen type-I expression in CFs. To that end, we blocked AP-1 with shRNA lentiviral particles specific for c-Jun in CFs, detected Col1α1 mRNA by qRT-PCR, and measured collagen type-I by Western blot. We found that IL-4 significantly induced Col1α1 mRNA expression after incubation with control shRNA-transduced cells for 6 hours (1.01±0.01 to 1.52±0.07 fold change versus control,
p
<0.005), and it increased collagen type-I expression after 24 hours of incubation (1.00±0.01 to 1.95±0.12 fold change versus control,
p
<0.005). In contrast, IL-4 did not increase mRNA levels of Col1α1 (1.09±0.02 to 0.98±0.03,
p
>0.05) and the collagen type-I (0.95±0.05 to 1.01±0.10,
p
>0.05) in c-Jun shRNA-transfected cells. Our data demonstrate that IL-4-activated AP-1, an ubiquitous transcription factor containing phosphorylated c-Jun, enhanced Col1α1 gene expression and collagen type-I expression in CFs. Data generated from this study provides a novel molecular basis for potential treatment of cardiac fibrosis by targeting IL-4-induced signaling in CFs.
Abstract 12752: Left Ventricular Dysfunction After Aortic Valve Replacement in Mixed Aortic Valve Disease: Are We Operating Too Late?
Authors: Egbe Alexander , Warnes Carole
Published: April 2024

Introduction:
The fate of the left ventricle (LV) after aortic valve replacement (AVR) in mixed aortic valve disease (MAVD) is unknown.

Hypothesis/objectives:
To determine prevalence and predictors of early and late left ventricular dysfunction (LVD) defined as EF <50% at 1 and 5 years post-AVR.

Methods:
Patients with moderate-severe MAVD, ejection fraction ≥50%, no documented coronary artery disease, and a minimum of 2-year follow-up after AVR were identified. Moderate-severe MAVD was defined as a combination of ≥moderate aortic stenosis and ≥moderate aortic regurgitation. EF was assessed at 1 and 5 years post-AVR.

Results:
Patients with MAVD (n=179); age 63±8 years, males 134 (75%); underwent AVR at Mayo Clinic from 1994-2010. Early LVD occurred in 38(21%). Predictors of early LVD were LV mass index/LV end-diastolic dimension (LVMI/LVEDD) >3.1 (hazard ratio [HR] 1.83, confidence interval [CI] 1.59-1.98); relative wall thickness (RWT) >0.46 (HR 2.16, CI 1.21-4.99); and older age per decade (HR 1.62, CI 1.23-3.02). Assessment of LV function was performed in 124 patients at 5 years post-AVR, and late LVD was present in 29 (23%). Predictors of late LVD were LVMI/LVEDD >3.1 (HR 1.77, CI 1.24-2.01) and RWT >0.46 (HR 1.65, CI 1.29-2.24). All-cause mortality occurred in 21 (12%), and was more common in patients with higher preoperative LV mass, P<0.05. Patients with postoperative LVD showed less regression of LV mass after AVR even after controlling for blood pressure, P<0.001.

Conclusions:
LVD can occur after AVR even in the setting of normal preoperative LV function and absence of coronary artery disease. Preoperative LV mass was predictive of LVD, and should be taken into consideration when determining the timing of AVR.

LEGENDS
Comparison of the occurrence of LVD and all-cause mortality by preoperative left ventricular mass.% of patients with early LVD (blue), late LVD (red) and death (green) between the patients with LVMI/LVEDD ratio ≤3.1 vs >3.1 (A), and ≤0.46 vs >0.46 (B)
Abstract 12771: A Novel Rotational Speed Modulation System Used With an Implantable Continuous-flow Left Ventricular Assist Device Provides Good Pulsatility on Peripheral Organ Perfusion
Authors: Naito Noritsugu , Nishimura Takashi , Iizuka Kei , Takewa Yoshiaki , Ono Minoru , Tatsumi Eisuke
Published: April 2024

Introduction:
Continuous-flow left ventricular assist devices (CFLVAD) is widely used to treat patients with end-stage heart failure. Even though the continuous flow is not physiologic, outcomes of CFLVAD have been improved. We have developed a novel rotational speed (RS) modulation system used with CFLVAD (EVAHEART), which can change RS in synchronization with the native cardiac cycle. We have reported that the system can change cardiac load and optimize coronary artery flow. We conducted the present study to investigate the influence of our system on peripheral perfusion.

Methods:
We implanted EVAHEART devices by the left ventricular apex drainage and the descending aortic perfusion via left thoracotomy in seven adult goats (56.8 ± 8.1 kg). Cardiogenic shock was induced by a beta adrenergic antagonist and coronary artery ligations. We evaluated blood flow, pulsatility index (PI), and maximum time derivative of flow rate (max dQ/dt) of carotid artery (CA), mesenteric artery (MA), renal artery (RA), respectively, using ultrasonic flow meters directly placed on the arteries. Mean tissue blood flow (TBF) of the heart and omentum and PIs of TBF were measured using the TBF meter. Venous lactate level, cerebral oxygen extraction rate (ExO2) and regional saturation of oxygen (rSO2) of brain, kidney, and leg muscle were also evaluated. Those data were collected with a bypass rate of 100% under four conditions: circuit clamp, continuous mode (constant RS), co-pulse mode (increase RS during systole), and counter-pulse mode (increase RS during diastole).

Results:
PIs of CA and RA in the copulse mode were significantly higher than those in the other modes. Max dq/dt of CA and MA were significantly higher in the copulse mode than those in the counter-pulse mode. Max dq/dt of the three arteries in the copulse mode tended to be higher than those in the other modes. PIs of TBF of the heart and the omentum in the copulse mode tended to be higher than those in the other modes. As for the metabolic changes in each mode, there were no significant differences in levels of lactate, cerebral ExO2, or rSO2.

Conclusions:
The copulse mode of our novel RS modulation system may provide better pulsatility not only in the large vessels but also in the peripheral perfusion.
Abstract 12804: The Relation between Left Atrial Function and Cardiac Output During Exercise in Left Heart Disease Patients: Insights by Combining Cardiopulmonary Exercise Testing With Stress Echo
Authors: Sugimoto Tadafumi , Bandera Francesco , Generati Greta , Alfonzetti Eleonora , Tufaro Vincenzo , Guazzi Marco
Published: April 2024

Background:
The hemodynamic response to exercise in left heart disease in relation to left atrial mechanics has never been studied. We aimed at investigating the link between left atrial function and cardiac output (CO) response during exercise in different cardiac disorders.

Methods:
73 heart failure with reduced (n=51) and preserved (n=21) ejection fraction, 53 aortic stenosis, 27 primary mitral regurgitation, 14 hypertrophic cardiomyopathy, and 42 control subjects underwent cardiopulmonary exercise testing evaluation combined with Echo-Doppler with assessment of left atrial strain (LAS) and were divided into 4 groups according to LA volume index (LAVI) and LAS at rest.

Results:
In group D (LAVI ≥34 ml/m
2
, LAS ≤23%, n=80) compared to group A (LAVI <34 ml/m
2
, LAS >23%, n=78) and group C (LAVI ≥34 ml/m
2
, LAS >23%, n=31), peak CO (6.2 ± 2.2 vs 8.5 ± 2.9 and 7.8 ± 2 L/min, P <0.05, respectively) and peak VO
2
(15.3 ± 4.1 vs 18.2 ± 6.3 and 18.1 ± 6.1 ml/kg/min, P <0.05, respectively) were significantly lower and the minute ventilation-carbon dioxide production (VE/VCO
2
) slope were significantly higher (33.2 ± 9.5 vs 27.1 ±3.7 and 27 ± 3.1, P <0.05, respectively). There were correlation between LAS both at rest and exercise vs peak VO
2
and VE/VCO
2
slope (R=0.41 and R=-0.53 at rest, R=0.44 and R=-0.45 at exercise, P <0.05, respectively, Figure A). In group B (LAVI <34 ml/m
2
, LAS ≤23%, n=19) and D, LAS both at rest and exercise significantly correlated with CO and stroke volume index (R=0.34 and R=0.38 at rest, R=0.35 and R=0.44 at exercise, P <0.05, respectively) and not in Group A and C (Figure B).

Conclusions:
In left heart disease patients, irrespective of etiology, an impaired LAS performance at rest is associated with a leftward shifted LAS vs CO response during exercise. Among this group of patients LA reservoir function is a key element of increasing CO during exercise.
Abstract 12807: Characteristics of Patients With Left Atrial Thrombi/spontaneous Echocardiographic Contrast in the Acute Phase After Cardiogenic Cerebral Infarction
Authors: Kishima Hideyuki , Mine Takanao , Takahashi Satoshi , Ashida Kenki , Ishihara Masaharu , Masuyama Tohru
Published: April 2024

Background:
Some patients have been reported to have a re-infarction in the acute phase after the onset of cardiogenic cerebral infarction (CI) due to remaining or newly formed left atrial thrombus (LAT). Those patients need strict and rapid treatment with anticoagulants. However, identification of cardiogenic CI patients at risk for re-infarction still remains unclear. We investigated the risk stratification in patients with LAT after the onset of CI.

Methods:
We retrospectively studied 97 consecutive patients (55 men, age 69±15) who had suffered acute cardiogenic CI. Neurological score (NIHSS score) and clinical factors were evaluated on admission. A standard 12-lead ECG, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and a blood sample for brain natriuretic peptide (BNP) were obtained within 24 hours after the onset of cardiogenic CI. Left atrial thrombi (LAT) and spontaneous echocardiography contrast (SEC) were assessed using TEE.

Results:
Fifteen LAT (15%) and 28 SEC (21%) were detected in 97 patients using TEE. All LAT were found in the left atrial appendage. Sixty patients showed atrial fibrillation (AF) in on admission. Patients with LAT/SEC (n = 29) had a higher prevalence of left ventricular hypertrophy (LVH, 52% vs. 13%, P <0.0001), higher NIHSS score (11.3 ± 7.7 vs. 5.9 ± 7.7, P = 0.0021), higher rate of hypertension (72% vs. 47%, P = 0.0217), higher prevalence of persistent AF (89% vs. 47%, P=0.0217), larger left atrial diameter (47 ± 9 mm vs. 39 ± 7 mm, P <0.0001), and higher hemoglobin levels (13.4 ± 2.3 g/dl vs. 12.4 ± 2.3 g/dl, P = 0.0402) compared with patients without LAT/SEC, while BNP levels were not significantly associated. On multivariate analysis, only LVH (P = 0.0241, OR 5.779, 95%CI 1.249-33.236) was independently associated with LAT/SEC.

Conclusion:
Detection of left ventricular hypertrophy in the acute phase of patients with cardiogenic cerebral infarction may provide additional risk stratification for re-infarction.
Abstract 12851: Osteoprotegerin is Associated With Major Bleeding but Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes - Insights From the PLATelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Ueland Thor , Åkerblom Axel , Ghukasyan Tatevik , Michelsen Annika E , Aukrust Pål , Becker Richard C , Bertilsson Maria , Himmelmann Anders , James Stefan K , Siegbahn Agneta , Storey Robert F , Kontny Frederic , Wallentin Lars
Published: April 2024

Introduction:
Elevated plasma levels of osteoprotegerin (OPG), a secreted cytokine receptor, might be associated with increased cardiovascular (CV) risk.

Methods:
We measured plasma OPG levels obtained on admission and at 1 month in a pre-defined subset of patients with acute coronary syndromes (ACS) randomized to 6 - 12 months treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial
(NCT00391872)
. OPG was determined by enzyme immuno-assay. Rates of CV outcomes and major bleeding were presented by baseline OPG quartile groups. The multivariable associations of OPG levels (log transformed) with the composite endpoint of CV death, non-procedural spontaneous myocardial infarction (sMI) or stroke, and with non-CABG major bleeding were assessed with Cox proportional hazards models. Five adjusted models, with co-variates and incremental addition of log transformed biomarkers, were used: 1/ randomized treatment and clinical risk factors (including: age, gender and, hypertension e.g.) 2/ CRP and white blood cell count (WBC), 3/ cystatin C, 4/ hs-Troponin T and NT-proBNP and 5/ growth differentiation factor (GDF)-15.

Results:
OPG levels were available in 5,135 (28%) patients at baseline, with a median (interquartile interval) of 2.7 (2.0 - 3.6) ng/mL. Event rates of the composite endpoint per increasing quartile group were; 5.2%, 7.5%, 9.2% and 11.9%; and for non-CABG major bleeding: 2.4%, 2.2%, 3.8% and 7.2%.

OPG levels at 1 month (n= 3,668), in patients free from any outcome event, were likewise independently associated with bleeding during follow up (n=69); with an adjusted HR of 1.43 (1.04-1.96). There was no interaction between admission OPG levels and randomized treatment.

Conclusion:
In multivariable analysis, osteoprotegerin was a strong and independent marker of major bleeding but not of ischemic CV events. Thus, OPG seems to provide important independent information on bleeding risk in patients with ACS.
Abstract 12869: Uncontrolled Blood Pressure is a Predictor of Left Atrial Remodeling and Adverse Clinical Outcome After Pulmonary Vein Isolation in Patients With Paroxysmal Atrial Fibrillation
Authors: Kamioka Masashi , Suzuki Hitoshi , Matsumoto Yoshiyuki , Nodera Minoru , Kaneshiro Takashi , Kamiyama Yoshiyuki , Takeishi Yasuchika
Published: April 2024

Aims:
Little is known about the relation of blood pressure (BP) control with left atrial (LA) remodeling and clinical outcome after atrial fibrillation (AF) ablation.

Methods:
A 101 symptomatic paroxysmal AF patients (85 males, 62.2±8.4 years) undergoing successful pulmonary vein isolation (PVI) were enrolled. Uncontrolled hypertension (HT) was defined as BP more than 140/90 mmHg calculated as mean value being recorded at least 5 different days before PVI. LA wall thickness along ablation line was measured using computed tomography before PVI. LA dimension was measured by echocardiography before and 6 months after PVI. The recurrence was determined by the documentation of AF or atrial tachycardia lasting more than 30 sec. In case of the recurrence, the second procedure was performed based on the patient’s consent. At the second procedure, if AF sustained or was induced after the pulmonary vein (PV) re-isolation or when PV was still isolated, substrate modification such as linear ablation or complex fractionated atrial electrogram ablation was performed. Patients were classified into 3 groups: group 1 (no HT, n = 48), group 2 (controlled HT, n = 34) and group 3 (uncontrolled HT, n = 19). The comparisons of the data among the groups were performed by using ANOVA and the recurrence rate of each group was analyzed by the Kaplan-Meier method.

Results:
LA wall thickness in groups 2 and 3 were greater than that of group 1. However, LA wall thickness between groups 2 and 3 did not differ. During the follow up periods of 9±4 months, LA dimension of only group 3 increased after the procedure (38.2±5.6 mm to 41.3±6.2 mm, P=0.02). Thirty-one patients showed the recurrence. The recurrence rate was significantly higher in group 3 than in groups 1 and 2 (48% vs. 26% and 22%, P<0.05, respectively). Out of 31 recurrence patients, 18 underwent the second procedure. The patients in group 3 needed substrate modification more frequently than those in group 1 (100% vs. 25%, P < 0.05).

Conclusion:
The existence of HT causes LA hypertrophy, regardless of whether HT is controlled or not. On the other hand, the uncontrolled BP induced the anatomical and electrical remodeling of LA, resulting in adverse long-term outcome after PVI.
Abstract 12908: Impact of Bystander Cardiopulmonary Resuscitation by Family Members on Return of Spontaneous Circulation and Neurological Prognosis in Patients With Out-of-Hospital Cardiac Arrests: A Nationwide, Population-Based Cohort Study
Authors: Suematsu Yasunori , Miura Shin-ichiro , Nosratola Vaziri D , Yonemoto Naohiro , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi , Saku Keijiro ,   on behalf of the Japanese Circulation Society Resuscitation Science Study (JCS-ReSS) Group
Published: April 2024

Introduction:
Out-of-hospital cardiac arrests (OHCAs) are critical events and bystander cardiopulmonary resuscitation (byCPR) affects the survival and prognosis of OHCAs. Most byCPR occur in a family setting in Japan. Although there are many reports on the effect of byCPR, there are few considerations about the person who operated byCPR in Japan.

Hypothesis:
We hypothesized that byCPR by a family member is more effective for return of spontaneous circulation (ROSC) and neurological prognosis against OHCAs of cardiac origin compared to non-family operators without emergency medical services (EMS ).

Methods:
In All-Japan Utstein Registry of the Fire and Disaster Management Agency, 1,176,363 patients who suffered from OHCAs were enrolled between 2005 and 2014. We selected 162,390 patients who were witnessed, those aged > 18 years and had OHCAs of cardiac origin. We classified the patients by age, gender, initial rhythm, verbal instruction, witness-to-CPR time by EMS, airway management, drug administration in ambulance, and secondary lifesaving treatment by doctor in ambulance.

Results:
In this study cohort, the byCPR by citizen were included family members (n=137,147), friends (n=9,132), colleagues (n=7,956), and passersby (n=8,155). The incidence of ROSC was 11.6%, 18.8%, 24.7%, and 22.2% among family members, friends, colleagues, and passersby, respectively and was significantly higher in friends (OR: 1.25, 95%CI: 1.18-1.33, p<0.000), colleagues (OR: 1.35, 95%CI: 1.28-1.44, p<0.000), or passersby (OR: 1.46, 95%CI: 1.38-1.55, p<0.000) than family members. In family members, the rates of defibrillation, first aid and chest compression were significantly lower than those in others. The time from witness to byCPR was significantly later in family members than in others. The incidence of ROSC after adjusting above-mentioned factors and the rates of defibrillation was also significantly lower in family members than in others. We also performed same investigation for neurological prognosis, and the results were similar.

Conclusions:
The incidence of ROSC and neurologically intact survival in byCPR by family members were lower than in others, regardless of the presence of defibrillation. Family members need to have education as bystanders.
Abstract 12921: Contemporary Evaluation of Female Gender and Outcomes in Heart Failure With Reduced or Preserved Left Ventricular Systolic Function
Authors: Vafaei Paniz , Leong Thomas K , Sung Sue Hee , Lee Keane K , Go Alan S
Published: April 2024

Introduction:
How gender influences prognosis in heart failure with reduced ejection fraction (HF-REF) compared to preserved ejection fraction (HF-PEF) in contemporary populations is not well described.

Hypothesis:
In a representative community-based HF population, female gender is independently associated with better outcomes in HF-REF and HF-PEF.

Methods:
Between 2005-2012, we identified adults with confirmed HF-REF or HF-PEF receiving care in Kaiser Permanente Northern California. Outcomes included death and hospitalizations for HF or any cause. We used extended Cox regression to evaluate the impact of female gender on outcomes after accounting for baseline characteristics, cardiovascular risk factors, medical history and receipt of HF and other cardiovascular therapies based on data from comprehensive electronic health records.

Results:
Among 24,257 eligible adults with HF-REF or HF-PEF, 11,227 (46%) were women and 13,030 (54%) were men. At entry, women were older and more likely to have HF-PEF, hypertension, stroke/TIA, thyroid disease, depression, and low-income status. However, women were less likely to have coronary disease, peripheral arterial disease, and dyslipidemia. Compared to men, women received more calcium blockers, diuretics and NSAIDs and less aldosterone receptor blockers, statins and antiplatelet agents. Overall rates (per 100 person-years) were high for death (14.7), HF hospitalization (16.0) and any hospitalization (74.9). After adjustment for confounders and therapies received, women were less likely than men to die, a finding that was more prominent in HF-REF (adjusted HR 0.81 [0.76-0.87]) than HF-PEF (HR 0.92 [0.88-0.97]). Additionally, though women were less likely to be admitted for HF in HF-REF (HR 0.89 [0.82-0.97]), the opposite was true in HF-PEF (HR 1.09 [1.02-1.17]). No clinically meaningful adjusted difference was seen by gender for all-cause hospitalization in HF-REF or HF-PEF.

Conclusions:
In a large, contemporary HF population, female gender was independently associated with lower mortality in both HF-REF and HF-PEF but differential associations for HF hospitalizations by HF type. Future research is needed to understand potential gender-specific mechanisms explaining variation in outcomes.
Abstract 12926: New Use of Low-dose Aspirin is Not Associated With a Significantly Increased Risk of Intracranial Bleeds: Results From a Population-based Nested Case-control Study in the United Kingdom
Authors: Garcia Rodriguez Luis , Gaist David , Soriano-Gabarró Montse , Cea Soriano Lucia
Published: April 2024

Introduction:
Low-dose aspirin protects against ischemic cardio- and cerebrovascular disease (CVD/CeVD) and colorectal cancer yet may be associated with a small increased risk of intracranial bleeds (ICB).

Aim:
To quantify the risk of ICB associated with new use of low-dose aspirin for CVD/CeVD prevention using The Health Improvement Network in the UK.

Methods:
From a source population aged 40-84 years from 2000-2012 and free of previous low-dose aspirin use, a cohort of new users of low-dose aspirin (75-300 mg; N=199,049) was identified. Each member was matched to a person free of low-dose aspirin on that day by age, sex and primary care practitioner visits in the previous year. Cohorts (mean age at entry, 59.6 years) were followed for up to 14 years (median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records and/or linkage to hospitalization data. Nested case-control analysis was conducted using cases from both cohorts. To account for changes in aspirin exposure over time, an ‘as-treated’ analysis was used. Controls (n=10,000) were frequency-matched to cases by age, sex and calendar year. Two definitions of current use were used for low-dose aspirin: use on i) 0-7 days or ii) 0-365 days before the index date (ICB date for cases, random date for controls). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression overall and stratified by CVD/CeVD status at study entry (primary or secondary prevention populations).

Results:
A total of 1635 incident cases of ICB were identified. As shown in the Table, compared with never use, current use of low-dose aspirin was not associated with a significant increase risk of ICB among the primary or secondary CVD/CeVD prevention populations, or any ICB subtype. For current use, no significant changes in ICB risk were seen between doses of 75mg, 150mg and 300mg.

Conclusions:
New use of low-dose aspirin does not significantly increase the risk of any type of ICB.
Abstract 12934: Prognostic Impact of Impaired Pulmonary Function in Acute Decompensated Heart Failure With Preserved Ejection Fraction
Authors: Kawakami Rika , Nakada Yasuki , Ueda Tomoya , Okura Hiroyuki , Saito Yoshihiko
Published: April 2024

Background:
An association between heart failure (HF) and impaired pulmonary function is clinically important. Therefore, we aimed to investigate the prognostic importance of impaired pulmonary function in acute decompensated heart failure (ADHF) patients.

Method:
This study was prospective prognostic study performed as part of NARA-HF3 study between April 2011 and December 2014. ADHF patients were tested for pulmonary function using spirometry before discharge. The following pulmonary function test (PFT) was measured; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV
1
). Patients were classified into 2 groups based on predicted FVC and FEV
1
/FVC percent predicted ratio: normal PFT groups (FVC≥80%, FEV
1
/FVC≥70%) and abnormal PFT groups (obstructive, restrictive and mixed pattern).

Result:
Among a total of 313 patients, 64.2% had abnormal spirometry
(
11.8%, 38.3% and 14.1% for
obstructive
, restrictive and mixed, respectively
).
Abnormal PFT
groups were significantly
older, had a higher prevalence of atrial fibrillation and a significantly
higher
mean
LVEF
compared to normal PFT groups. There was no significant difference in smoking history, sex, eGFR and BNP levels at discharge both groups. Abnormal PFT was found to be associated with
higher rate of
all-cause mortality or HF hospitalizations (Figure A, B). The abnormal PFT groups had worse prognosis than normal PFT groups in HF with preserved ejection fraction (HFpEF) (LVEF≥50%) but not in HF with reduced EF (HFrEF) (LVEF<50%) (Figure C, D). Cox proportional hazards regression analysis revealed that impaired pulmonary function was an independent prognostic predictor for ADHF, especially for HFpEF (HR 2.58, 95% CI 1.29 to 5.77, p=0.006).

Conclusion:
Impaired pulmonary function was associated with poor prognosis in patients with HFpEF, but not in those with HFrEF.
Abstract 12947: Clarithromycin Prevents Progression & Rupture of Aortic Aneurysm
Authors: Uchida Wataru , Yamawaki-Ogata Aika , Oshima Hideki , Usui Akihiko , Narita Yuji
Published: April 2024

Introduction:
The pathogenesis of aortic aneurysm (AA) is mainly characterized by chronic inflammation in the aortic wall with accumulation of macrophages and degradation of extracellular matrix (ECM) with increased matrix metalloproteinases (MMP), particularly MMP-2 & -9, resulting in the degradation of collagen, elastin fragmentation and smooth muscle cell apoptosis. Meanwhile, clarithromycin (CAM) is well-known potent antibiotic, otherwise, CAM has been reported to have multiple biologic effects, such as alteration of inflammatory factors including MMP-2 & -9. In this study, we investigated the effects of clarithromycin on induced AA in mice.

Methods:
Male aged apolipoprotein E deficient (ApoE-/-) mice were infused 1000 ng/kg/min Angiotensin II for 28 days to induce AA. In the CAM-treated group (CAM group: n=13), the mice were dosed with CAM (100 mg/kg/day) by the gastric tube every day. In the control group (CONT; n=13), saline was administrated. Echo-aortography was performed every week to measure aortic diameters. The aneurysm induced aorta was removed and evaluated. Elastica van-Gieson stain was performed for evaluation of ECM in the aortic wall. The elastin content of the aorta were measured. Infiltrations of inflammatory macrophages were evaluated by immunofluorescence staining against CD 206 & F4/80. Gelatin zymography was performed to evaluate MMP-2 & -9 activities in aortic tissues.

Results:
Echo-aortography showed the aortic diameters were significantly attenuated in CAM group. The incidence of AA in CONT was 100%, which was significantly decreased to 23% in CAM group. No ruptured death was observed in CAM group in contrast to 5 ruptured deaths in CONT (Log Rank test, p=0.01). CAM significantly suppressed degradation of aortic elastin (56.3% & 16.5%, p<0.001) & decreased infiltration of inflammatory macrophages (5.3% & 16.0%, p=0.005). CAM significantly attenuated MMP-2 (0.15 & 0.56, p<0.001) & MMP-9 activities (0.12 & 0.60, p<0.001) respectively.

Conclusions:
CAM prevented the development of AA & rupture through suppression of inflammatory macrophages infiltration, decreased MMP-2 & -9, & preserved elastin content.
Abstract 13004: Continuous Quality Review of ICU CPR Events: Performance, Outcomes and Effect of Systems-Level Changes
Authors: Moga Michael-Alice , Seligman Eva , Frey Genevieve , Kwon Soyang , Wald Eric
Published: April 2024

Introduction:
Outcomes of in-hospital cardiac arrest remain disappointing. Continuous quality review (CQR) has been used to improve provider, team and systems performance during CPR. Little data exists on the incidence of individual, team and systems errors during in-hospital CPR and the influence of errors and systems-level changes on outcomes are equally unexplored.

Hypothesis:
CQR will identify consistent errors in three performance domains (technical, team, systems). Environmental factors and systems changes will affect code quality and outcomes.

Methods:
Analysis of prospectively collected data describing all ICU CPR events from September 2009-December 2014 in a tertiary care children’s hospital. Monthly quality review by a multidisciplinary team focused on three quality metrics (noise, leadership and equipment failure) and was later expanded to six metrics (communication, technical or systems errors).

Results:
There were 243 arrests in 193 patients, most of whom had primary cardiac (39%) or pulmonary disease (23%). Most events occurred during the day (7am-7pm); 27% occurred on a weekend or holiday. Median compression time was 5 minutes (IQR 2-15min). Event survival was 80% (70% ROSC, 10% ECMO) and 48% of hospitalizations ended in death. Excess noise (19%), leadership confusion (11%) and equipment failure (6%) were common. Quality CPR (all 3 elements) occurred 74% of the time and was not associated with event survival. Excess noise (p<0.01) and leadership confusion (p=0.02) were more common during the day. A more recent cohort (n=34) demonstrated frequent communication, systems and technical errors (15%, 21% and 21% respectively). Only 38% of arrests had all 6 quality elements. In multivariable analysis, leadership confusion was associated with ICU survival (OR 2.2; 0.66-1). Statistical process control (SPC) only showed special cause variation in single quality metrics despite multiple systems level changes. Code incidence trended down after opening a new hospital and creation of a separate cardiac ICU service (p=0.07).

Conclusion:
Individual, team and systems errors are common during CPR in critically ill children. CQR incorporating SPC should be used to track performance and monitor the impact of QI initiatives and systems changes.
Abstract 13067: Depression and 5-Year Stroke Risk in Patients With Atrial Fibrillation
Authors: Lima Bruno B , Althouse Andrew D , Munir Muhammad B , Sharbaugh Michael S , Rollman Bruce L , Saba Samir
Published: April 2024

Introduction:
Stroke is a leading cause of death and permanent disability in patients with Atrial Fibrillation (AF). Depression is highly prevalent and previous studies have suggested that it is associated with a significantly increased risk of stroke morbidity and mortality in the general population. Here, we report the impact of depressive mood on the risk of stroke among patients with AF.

Hypothesis:
Depression increases the risk of stroke among patients with AF.

Methods:
We enrolled 5976 patients diagnosed with AF at the hospitals and clinics of the University of Pittsburgh Medical Center from January 2006 to November 2013. Depression status was determined by chart review of physicians’ diagnoses. Stroke incidence in each group is summarized with Kaplan-Meier curves; Cox proportional-hazards models were used to assess the relationship between depression and stroke risk when accounting for potential confounders.

Results:
Of the 5976 patients, 681 (11.4%) had diagnosis of depression. Patients were followed for a median of 39 months (range 1-60), during which there were 200 total strokes (35 in patients with depression). Risk of stroke was higher in patients with diagnosed depression (7.5% vs 4.7%, HR=1.70, 95% CI: 1.18-2.45, p=0.004, Figure). Even after controlling for several known stroke risk factors (age, sex, alcohol and tobacco use, congestive heart failure, previous stroke, diabetes, hypertension, vascular diseases, COPD and anticoagulant use), depressed patients had higher incidence of stroke (HR=1.45, 95% CI 0.99-2.11, p=0.054).

Conclusion:
Diagnosis of depression is associated with increased risk of ischemic stroke in patients with Atrial Fibrillation. Clinical trials remain necessary to establish whether screening AF patients for depression and then providing effective anti-depressive treatment can reduce the incidence of stroke and improve clinical outcomes.
Abstract 13254: Patient Education After CABG: Are We Teaching the Wrong Information?
Authors: Bradley Corey , Burkart Madelyn , Agarwala Ravi
Published: April 2024

This article has been retracted. Please see:

Notice of Retraction -
http://circ.ahajournals.org/content/134/Suppl_1/suppl/DC1

Introduction:
Secondary prevention after CABG improves morbidity and mortality, yet adherence remains poor. The inpatient stay for CABG is an invaluable teachable moment, and so it is imperative that the education we provide motivates adherence. There is limited data about whether patients identify their medications as preventive, or if this knowledge affects adherence behavior.

Hypothesis:
To determine if patient understanding of medication purpose and patient perception of medication importance affects adherence behavior.

Methods:
This was a prospective cohort study to evaluate medication adherence after discharge from CABG and CABG plus valve procedures at Wake Forest Baptist Hospital. A total of 49 patients met inclusion criteria and were enrolled. Participants were approached after receiving standardized nursing education before discharge and completed surveys addressing patient understanding of medication purpose and importance. Three months after discharge patients were contacted by phone and read the Morisky Medication Adherence Scale (MMAS-8), with a follow-up rate of 94%.

Results:
Only 27% of patients identified their cardiac medication regimen as lifelong and to promote future heart health. Most patients correctly identified the pharmacologic purpose of all 4 medications (aspirin, beta-blocker, ACEI, and statin). Significantly, 60% of patients with high adherence as defined by the MMAS-8 at 3 months had originally identified that daily use of their medications was important to maintaining long term health, while only 12% of those with low or medium adherence behaviors had identified the same (p = 0.000509).

Conclusions:
Patients appear to understand the mechanisms of action of cardiac medication but generally don’t appreciate their long-term preventative value. As such, patients may believe that they can discontinue the medications when objective criteria are met, such as lowered blood pressure, thus missing the potential benefit of decreased cardiac events and mortality.
Abstract 13304: Prevalence, Perfusion-Based Markers, and Exercise Manifestations of Right Ventricular Dysfunction Among 2,051 Consecutive Patients Undergoing Exercise Myocardial Perfusion Imaging
Authors: Di Franco Antonino , Weinsaft Jonathan W , Seoane Tania , Srinivasan Aparna , Kampaktsis Polydoros N , Geevarghese Alexi , Rozenstrauch Meenakshi , Khan Saadat A , Szulc Massimiliano , Ratcliffe Mark B , Levine Robert A , Morgan Ashley E , Shah Tara , Devereux Richard B , Kim Jiwon
Published: April 2024

Introduction:
Right (RV) and left ventricular (LV) performance are linked via common coronary supply: Impact of altered LV perfusion on the RV, and independent influence of RV dysfunction (RV
dys
) on effort tolerance are unknown.

Methods:
The population comprised pts undergoing myocardial perfusion imaging (MPI) and echocardiography (echo) within 1 month (5.5±7.9 days): RV
dys
was defined via standard echo criteria (TAPSE < 1.6 cm, RV S’ < 10mm/s). MPI was the reference for LV ischemia; effort tolerance was assessed via exercise treadmill testing (ETT) at time of MPI.

Results:
2051 pts (64±12 yo, 59%M) were studied; 6% had RV
dys
on echo. Pts with RV
dys
had lower LVEF (53±14 vs. 62±9%), larger LV size (55±23 vs. 48±16 ml/m
2
) and higher PA systolic pressure (34±12 vs 30±7 mmHg; all p<0.01). On MPI, summed stress score was 3 fold higher among pts with RV
dys
(6.9±8.5 v. 2.7±6.1, p<0.001). LV inferior (0.7±1.7 v. 0.2±1.0, p=0.007) and lateral ischemic defects (1.2±2.6 v. 0.2±1.1, p<0.001) were larger in pts with RV
dys
(both p<0.01); but anterior defects did not differ (p=NS): Inducible inferior and lateral perfusion defects increased likelihood for RV
dys
(both p<0.001) independent of LV function and PA pressure. Pts with RV
dys
had lesser heart rate (α 56±26 vs. 69±24 bpm) and blood pressure augmentation (α 28±31 vs. 41±27mmHg, both p<0.001) during ETT, paralleling lower effort duration (6.7±2.8 vs. 7.9±2.9 min, p<0.001): Effort duration decreased in relation to both LV and RV
dys
, as evidenced by stepwise decrements among pts with normal biventricular function, isolated LV or RV
dys
and pts with biventricular dysfunction [
Figure
]: Impaired effort tolerance was independently associated with RV
dys
(regression coefficient 0.73 [CI 0.14-1.31], p=0.02) and LV
dys
(0.71 [0.27-1.16], p=0.002), even after controlling for age and β blocker use.

Conclusions:
LV ischemia in inferior and lateral walls confers increased likelihood for RV
dys
. RV
dys
impairs exercise tolerance independent of LV
dys
.
Abstract 13421: Liver T1 Mapping MRI and Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ostovaneh Mohammad R , Fuji Tomoki , Bakhshi Hooman , Shah Ravi V , Murthy Venkatesh L , Tracy Russell P , Guallar Eliseo , Wu Colin O , Bluemke David A , Lima Joao A , Venkatesh Bharath A
Published: April 2024

Introduction:
Fatty liver disease and liver fibrosis are associated with cardiovascular disease (CVD) metabolic risk factors and events. However direct imaging of liver abnormalities using T1 mapping MRI in relation to CVD has not been investigated in large epidemiological cohorts.

Hypothesis:
Liver abnormalities (inflammation and/or fibrosis) by T1 mapping MRI are associated with CVD events.

Methods:
MESA enrolled 6814 participants free of clinical CVD at baseline, MESA1 (2000-2002). A subsample of participants underwent Modified Look-Locker T1 mapping MRI at the fifth follow-up exam, MESA5 (2010 -2012). T1 maps were analyzed avoiding vessels and biliary ducts, and pre- and post-contrast T1 times (25 minutes after injection) were calculated. Liver extracellular volume fraction (ECV) was calculated using the pre- and post-contrast T1 times of the liver and cardiac blood pool. Higher ECV and pre-contrast T1 time (PreT1) were indicative of liver abnormalities. Coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF) events were ascertained between MESA 1 and MESA 5. Multivariable linear regression analysis evaluated the cross-sectional relationship between liver ECV and T1 time with cardiac events adjusted for ASCVD/AHA risk score, liver fat content by computed tomography, alcohol use, socioeconomic status and BMI.

Results:
In 888 participants (67.83±8 years, 51% female, 60% Caucasian, 4% Chinese, 26% African-American, 10% Hispanic) there were 63 cardiac events (44 CHD, 13 CHF and 18 AF) between MESA1 and 5. Compared to controls, PreT1 and ECV were significantly higher in those with any cardiac event and AF. In multivariable analysis, PreT1 (standardized β=0.08, p=0.018) and ECV (standardized β=0.09, p=0.008) were associated with composite cardiac events.

Conclusion:
Liver abnormalities (most likely inflammation and/or fibrosis) estimated by greater liver PreT1 and ECV, are associated with cardiac events in a multi-ethnic cohort.
Abstract 13458: Survival After Out-of-hospital Cardiac Arrests and Arterial Oxygen Partial Pressure During Cardiopulmonary Resuscitation: The CRITICAL Study in Osaka, Japan
Authors: Izawa Junichi , Kitamura Tetsuhisa , Hayakawa Koichi , Yamada Tomoki , Yoshiya Kazuhisa , Abe Yoshio , Uejima Toshifumi , Ohishi Yasuo , Kiguchi Takeyuki , Kishi Masashi , Kishimoto Masafumi , Nakao Shota , Nishimura Tetsuro , Hayashi Yasuyuki , Morooka Takaya , Sokabe Taku , Matsuyama Tasuku , Shimazu Takeshi , Kawamura Takashi , Iwami Taku ,   The Osaka CRITICAL Study Investigators
Published: April 2024

Introduction:
The current resuscitation guidelines recommend the use of the highest possible inspired oxygen concentration during cardiopulmonary resuscitation (CPR). On the other hand, there are conflicting results that PaO
2
after return of spontaneous circulation might be harmful to better outcome.

Hypothesis:
The objective of this study is to investigate the association between PaO
2
during CPR and survival after out-of-hospital cardiac arrests (OHCA).

Methods:
Study design: Multicenter cohort study. In Osaka Prefecture, Japan, we registered all consecutive OHCA patients who were transported to institutions participating in our CRITICAL registry since July 1, 2012. From this registry, we included non-traumatic adult OHCA patients with arterial blood gas sampled at the hospitals during CPR. The main exposure was PaO
2
in arterial blood gas analysis during CPR. We classified PaO
2
values as three categories (hypoxemia: 0-60 mmHg; normoxemia: 60-300 mmHg; and hyperoxemia: ≥300 mmHg), referring to previous studies. The primary outcome was survival at one-month after OHCA. Multivariable logistic regression analysis was used to adjust confounders.

Results:
We analyzed 710 patients. Among them, 4.5% (N = 32) survived at one month and 1.5% (N = 11) had a neurologically favorable outcome. As PaO
2
categories during CPR became higher, one-month survival increased (3.0% [16/528] in hypoxemia, 6.6% [11/166] in normoxemia, and 31.2% [5/16] in hyperoxemia). The adjusted odds ratio (AOR) for one-month survival, controlling for first documented rhythm and bystander witness, reffered to the hypoxemia group was 1.98 (95%CI 0.83-4.69, P=0.120 ) in normoxemia and 8.03 (95%CI 2.16-29.80, P=0.002) in hyperoxemia group.

Conclusions:
Higher PaO
2
categories during CPR were associated with better survival at one-month in non-traumatic adult OHCA patients. During CPR, maintaining high PaO
2
might be useful for improving outcomes of OHCA patients.
Abstract 13480: High Resolution MRI for Characterization of Inflammation within Abdominal Aortic Aneurysm
Authors: Zhu Chengcheng , Hope Thomas A , Haraldsson Henrik , Faraji Farshid , Saloner David , Hope Michael
Published: April 2024

Background:
Abdominal aortic aneurysms (AAAs) with focal inflammation have been reported to grow 3 times faster than those without. Ultrasmall superparamagnetic iron oxide (USPIO) particles can identify inflammation (macrophages) in vivo using MRI. USPIOs induce both T1 and T2* shortening. Previous studies used 2D T2* mapping methods, which had limited slice resolution (5mm). We aim to evaluate 3D higher resolution techniques for inflammation imaging.

Hypothesis:
3D MRI can identify AAA inflammation with high resolution.

Methods:
Four MRI sequences were evaluated at 3T: traditional 2D T2* mapping (5mm slice); black blood fast-spin-echo (FSE) and ultra-short-TE (UTE) sequences with 1.3mm isotropic resolution, scan time 7 and 4 minutes; gradient echo (GRE) with 1.3x1.3x2.6mm
3
resolution in a breathhold (17s). Sequences were firstly tested in saline phantoms with USPIO concentrations 0.94mg Fe/L to 600mg Fe/L. 27 patients (all male, age 69±4.7, diameter 4.3±1.0cm) underwent MRI before and 2-3 days after USPIO injection. All patients had T2* and FSE scans. GRE and UTE were preliminary tested in 8 and 5 patients.

Results:
Phantom Study:
UTE signal continually rises with increasing USPIO concentrations, whereas T2* values drop. Both FSE and GRE show signal increase-and-drop curves, however with different peaks (7.5 versus 60mg Fe/L).
Patient study:
In 27 patients, 10 patients were inflammation positive (T2* value decrease >60%,
Figure 1
), and all showed FSE signal change: 3 drop, 3 increases, 4 both). GRE and UTE showed signal enhance (
Figure 1b
). 6 of them (60%) underwent intervention. Of the 17 negative patients, only 1 had intervention (p=0.004).

Conclusion:
3D high resolution MRI can be used to identify USPIO uptake within AAA, with good agreement with traditional 2D T2* mapping method. AAA inflammation is related to progressive disease. These methods may help risk stratify patients with AAA disease by characterizing and quantifying inflammation.
Abstract 13486: Patient and Procedural Factors Are Associated With Autonomic and Endothelial Dysfunction in Adolescent and Young Adult Fontan Survivors
Authors: Goldstein Bryan H , Marino Bradley S , Gao Zhiqian , Khoury Philip R , Amos Michelle A , Mays Wayne A , Veldtman Gruschen R , Redington Andrew N , Urbina Elaine M
Published: April 2024

Introduction:
Vascular dysfunction is associated with diminished functional capacity and quality of life in adolescent and young adult Fontan survivors. Patient and procedural factors associated with diminished endothelial and autonomic function have not been established.

Methods:
Cross-sectional single-institution study of Fontan survivors ages 8-25 years. Anthropometric characteristics were obtained. Endothelial function was assessed with brachial flow mediated dilation (FMD) and peripheral arterial tonometry reactive hyperemia index (lnRHI; EndoPAT). Autonomic function was assessed by heart rate variability (HRV; SphygmoCor). Records were reviewed for anatomic, hemodynamic and surgical characteristics, which served as predictor variables while vascular measures served as outcome variables. Bivariate predictors (p<0.1) were candidates for inclusion in multivariable models. Model development utilized linear regression techniques.

Results:
Sixty patients (52% male, 90% Caucasian) completed the protocol with a mean age of 13.9 ± 4.1 years and duration of Fontan circulation of 9.9 ± 4.2 years. Median weight was 43.5 (IQR 31.4, 58.3) kg and BMI was 18.7 (16.1, 22.6) kg/m
2
. A single left ventricle was present in 65%. Mean FMD was 10.2 ± 5.5% and lnRHI was 0.236 ± 0.398. Median HRV was 41.2 (29.4, 52.0) ms. Major determinants of FMD included height, total # of surgeries and stage I palliation length of stay (LOS) (R
2
0.29, p<0.001), whereas determinants of lnRHI included prior Norwood procedure, systolic blood pressure, resting heart rate and oxygen saturation (SaO
2
), mixed venous SaO
2
and cardiac index (CI) at pre-Fontan catheterization (cath) and total # of hospitalizations (R
2
0.27, p=0.01). Major determinants of HRV included total duration of surgical circulatory arrest, CI at pre-Fontan cath and Fontan completion LOS (R
2
0.39, p=0.006). Traditional cardiovascular risk factors including weight and BMI were not independent determinants.

Conclusions:
Multiple patient and procedural factors are associated with diminished endothelial and autonomic function in adolescent and young adult Fontan survivors. Targeted intervention of modifiable risk factors may improve long-term vascular health and functional status.