bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14714: Association of Plasma Renin and Aldosterone Levels With Future Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ambale Venkatesh Bharath , Yoneyama Kihei , Ostovaneh Mohammed , Donekal Sirisha , Murthy Venkatesh L , Shah Ravi V , Ouyang Pamela , Wu Colin O , Allison Matthew , Tracy Russell , Bluemke David A , Lima Joao A C
Published: April 2024

Introduction:
The renin-angiotensin-aldosterone-system (RAAS) has been implicated in left ventricular (LV) hypertrophy and dysfunction. We explore the association of circulating levels of plasma renin activity (PRA) and aldosterone to subclinical measures of LV structure and function from MRI.

Methods:
The MESA study enrolled 6814 participants free of cardiovascular disease at baseline (2000-2002). We included MESA participants who had blood assayed for measurement of PRA and aldosterone levels at the second/third follow-up exams (2003-2005) and underwent MRI at the fifth follow-up exam (2010 -2012). We excluded participants on hypertension medication (N=509). Harmonic phase analysis was used to compute circumferential strain and torsion from tagged MRI; LV function and structure measures were obtained from cine images. Linear regression evaluated the relationship between PRA, aldosterone and aldosterone to renin ratio (ARR) with LV structure and function. The models included adjustments for cardiovascular risk factors and demographics at the time of assays (model 1) and at the time of imaging (model 2) separately.

Results:
At the time of assays, the participants (N=384) were 59±8 years, 53% male, 43% Caucasian, 13% African-American, 17% Chinese, 28% Hispanic, 4% diabetic, with median levels of PRA 0.56 ng/ml (IQR:0.30-0.97), aldosterone 126 pg/ml (IQR:90-176) and ARR 120 ng/ml to pg/ml (IQR:53-234). Higher PRA was associated with lower LV end-diastolic volume index. Higher PRA was associated with higher mass-volume ratio and torsion. Higher ARR was associated with higher LV volume and lower torsion.

Conclusions:
In individuals not on hypertension medications, higher PRA was associated with concentric remodeling and higher torsion 7 years later but not to LV function. Also, higher ARR was associated with eccentric LV chamber remodeling and lower torsion. In conclusion, RAAS activity may be implicated in future concentric/eccentric LV remodeling.
Abstract 14732: Vortex Formation Time in Patients With Hypertrophic Cardiomyopathy
Authors: Maragiannis Dimitrios , Schutt Robert C , Alvarez Paulino A , Chin Karen , Buergler John M , Little Stephen H , Shah Dipan J , Nagueh Sherif F
Published: April 2024

Introduction:
Vortex formation time (VFT) is an index reflecting optimal vortex formation and efficiency in blood volume transport. The objective of this study was to investigate the association of VFT index with LV diastolic function and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM) and examine its changes after septal reduction therapy.

Methods:
We studied 116 HCM patients (median age 57.5 [49-65], 39.7% female) who underwent exercise stress testing with measurement of peak O2 consumption within 2 months of imaging. VFT index was calculated and the cohort was divided into 2 groups (cutoff based on prior work and our own normal controls [n=12]): VFT<3.3 (n= 70) and VFT 3.3-5.5 (n=46). Comparisons were made in the subgroup of HCM patients before and after septal reduction therapy (n=31).

Results:
Patients with VFT < 3.3 had evidence of more advanced diastolic dysfunction grade (p<0.01) and a more advanced NYHA class in comparison with patients with a VFT in the 3.3 to 5.5 range (p=0.048). In addition, patients with VFT 3.3-5.5 achieved a higher workload (7.5 vs 5.7 METs, p=0.016) and maximal oxygen consumption (21.7 vs. 17.7, p=0.003). Following septal reduction therapy VFT increased significantly from 2.8 to 3.7 (p < 0.001). LVEDV (100.9 to 112.9 mL, p=0.003) and LA volume index (50.6 to 40.0 mL/m2, p < 0.001) remodeling were observed as well as reduced septal thickness (1.9 to 1.5 cm, p<0.001) along with improvement in NYHA class (p<0.001). The change in peak O2 consumption related well to the change in VFT (r =0.9, P<0.001).

Conclusions:
Patients with HCM and VFT 3.3-5.5 are less symptomatic and have better exercise tolerance. VTF increases after septal reduction therapy in keeping with the NYHA class improvement and the change in peak O2 consumption. VFT appears to be a useful parameter to evaluate cardiac function, its relation to exercise tolerance as well as the response to treatment in HCM patients.
Abstract 14764: Left Atrial Appendage Function and Risk of Stroke After Left Atrial Appendage Electrical Isolation in Patients With Long-Standing Persistent AF: Results From the BELIEF Randomized Trial
Authors: Di Biase Luigi , Burkhardt J. David , Mohanty Prasant , Mohanty Sanghamitra , Sanchez Javier , Trivedi Chintan , Gunes Mahmut , Gökoglan Yalçin , Gianni Carola , Horton Rodney , Gallinghouse G. Joseph , Bailey Shane , Zagrodzky Jason , Hao Steven , Hongo Richard , Beheiry Salwa , Santangeli Pasquale , Casella Michela , Dello Russo Antonio , Al-Ahmad Amin , Hranitzky Patrick , Lakkireddy Dhanujaya , Tondo Claudio , Natale Andrea
Published: April 2024

Introduction:
The Belief Randomized trial sought to assess whether the empirical isolation of the left atrial appendage (LAA) in addition to an extensive ablation could improve success at follow up in patients with long standing persistent (LSP) atrial fibrillation (AF). The aim of this sub-analysis of the trial aimed to evaluate the LAA contraction at the 6 month repeat Trans-esophageal echocardiogram (TEE).

Methods:
Patients with LSP AF undergoing ablation were enrolled and randomly assigned to undergo empirical LAA isolation along with an extensive ablation or extensive ablation alone.

All patients undergoing LAA isolation received a TEE at the 6 months follow up, irrespective of their underlying rhythm. We evaluated TEE parameters and compared thromboembolic complication between groups.

Results:
We enrolled 173 pts with average age of 63.8 ± 8.5 years and 85.5% male pts.

LAA isolation was performed in 101 pts. LAA was not isolated in 72 pts. Follow-up TEE was performed in all pts with LAA isolation. The peak flow velocity in the appendage was low (<0.4 m/s) in 56.4% (57/101) patients. The doppler across the mitral valve demonstrated E-wave to A-wave ratio (E/A) of 2.64 ± 1.4. All patients had E/A >1, out of which 55.4 %( 56/101) had E/A > 2 (p=0.16). One (1.2%) LAA thrombus [Oral anticoagulant warfarin INR subtherapeutic] and 1 (1.2%) LAA smoke [Oral anticoagulant warfarin, INR : 2.24] were detected in the LAA isolation group as an incidental finding at TEE before redo ablation procedure.

One patient (0.99%) had stroke in the LAA isolation group after warfarin discontinuation due to a surgical procedure, while 3 (4.2%) stoke/TIA occurred (p=0.31) in the no LAA isolation group (2 pts on warfarin, 1 pt on aspirin).

Conclusion:
The results of this study show that LAA isolation does not increase the risk of tia/stroke at follow up. This risk appears to be related to the compliance to oral anticoagulation.
Abstract 14806: Comparison of Afterload Dependency Between Left Ventricular Myocardial Strain and Strain Rate in Healthy Subjects
Authors: Murai Daisuke , Yamada Satoshi , Iwano Hiroyuki , Hayashi Taichi , Okada Kazunori , Nishino Hisao , Nakabachi Masahiro , Abe Ayumu , Ichikawa Ayako , Yokoyama Shinobu , Kaga Sanae , Mikami Taisei , Tsutsui Hiroyuki
Published: April 2024

Background:
Left ventricular (LV) myocardial strain and strain rate (SR) both depend upon afterload. However, the difference in the afterload dependency between these 2 indices has not been investigated.

Methods:
Echocardiography was performed in 41 healthy volunteers before and during handgrip exercise. The handgrip exercise was performed at 50% of the maximum grasping power for 4 minutes. Meridional wall stress (MWS) was calculated from end-systolic LV dimension and wall thickness as well as systolic blood pressure. By using speckle tracking echocardiography, longitudinal peak strain (LS) and systolic peak SR (LSR) were measured and averaged in 3 apical views. These parameters were indicated in the absolute values.

Results:
During handgrip exercise, systolic blood pressure increased from 98±11 to 116±15 mmHg and MWS increased from 660±130 to 975±174 dyn•mm
-2
(%change: 49±18%). In response to this increase in MWS, LS decreased by 8.4±4.8% (from 17.2±1.7 to 15.7±1.4%). In comparison, LSR decreased by 6.4±5.5% (from 0.80±0.09 to 0.75±0.08 s
-1
), which was significantly smaller than the decrease in LS (p<0.05). There were significant linear correlations between MWS and LS (r=-0.53, p<0.01) or LSR (r=-0.28, p<0.05) among all points before and during handgrip exercise and the absolute value of correlation coefficient for LS (0.53) tended to be greater than that for LSR (0.28). The dispersions of LS and LSR, expressed as the root mean square error in the standardized regression analysis, were similar (0.86 SD and 0.98 SD, respectively). Therefore, the difference in the correlation coefficients was considered to be a reflection of the difference in the afterload dependency between LS and LSR, but not the dispersion of the measurements.

Conclusions:
Myocardial strain more strongly depends on afterload than myocardial strain rate in healthy subjects.
Abstract 14844: Regional Variations on Cardiovascular Outcomes in Stable Chronic Heart Failure Outpatients at Risk of or With Atherothrombosis - Insights From REACH Registry
Authors: Toda Kato Eri , Steg Philippe Gabriel , Goto Shinya , Guo Jiangping , Im KyungAh , Gaxiola Efrain , Ohman E. Magnus , Eagle Kim , Bhatt Deepak L
Published: April 2024

Background:
There is a growing recognition of geographic variation for clinical trial outcomes in patients with chronic HF. This study sought to investigate regional variation among patients with a history of HF in a registry population with or at risk for atherothrombosis.

Methods:
4 year CV outcomes of chronic HF patients (n=8,962) in Reduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of stable outpatients with established ischemic events (CAD, CVD, and/or PAD) or multiple risk factors for atherothrombosis, were analyzed by geographic regions (North America (NA), Western Europe (WE), Eastern Europe (EE), Latin America (LA), Middle East (ME), and Asia Pacific (AP)).

Results:
Among 68,236 patients enrolled, 18.1% (n=1,311) of EE patients, 15.0% (n=4,158) of NA patients, 13.9% (n=118) of ME patients, 13.1% (n=2,161) of WE patients, 7.8% (n=150) of LA patients, and 7.6% (n=1,064) of AP patients had a history of HF at baseline. The prevalence of traditional cardiovascular risk factors and the use of medical therapies varied significantly among regions. At 4 year, the rate of CV death, MI, stroke, or hospitalization for HF ranged from 27.1% in AP to 53.4% in ME (p<0.001). Similarly, a significant regional disparity was observed in recurrent HF hospitalization and CV death, however, with a different pattern for CV death (p<0.001 for both, fig.). These differences among regions persisted after adjustment for regional differences in key prognostic variables.

Conclusions:
This large long term international database demonstrated regional heterogeneity in CV event rates, including hospitalization for heart failure, in patients with or at risk for atherothrombosis and a reported history of heart failure. These findings may have implications for estimating event rates and planning clinical trials of patients with heart failure.
Abstract 14852: Clinical Performance of The HeartBuds, an Electronic Smartphone Listening Device, Compared to FDA Approved Class I and Class II Stethoscopes
Authors: Patel Ritesh S , Schwarz Julio , Danesh Valerie , Einhorn Arnold M , Bello David
Published: April 2024

Background:
Auscultation with stethoscopes is essential to the physical exam. However, the stethoscope has not appreciably changed since Leared and Cammann developed the first binaural stethoscopes in the mid 1800s. Technological advances make it possible to use smartphone technology to auscultate patients. The HeartBuds, a listening device that integrates with an iPhone app, achieves this purpose.

The purpose of this study was to compare HeartBuds’ acoustic superiority over the FDA approved class I blue disposable stethoscopes, which are commonly used in practice to reduce hospital infection rates, and demonstrate equivalence to the gold standard FDA class I analog stethoscope, the Littmann Cardiology III, and the FDA class II digital stethoscope, the Littmann Electronic 3200.

Methods:
50 adult patients were auscultated with each of the above-mentioned stethoscopes by two independent examiners. They rated their acoustic quality and completed surveys documenting body sounds heard.

Results:
The disposable stethoscope was significantly worse at identifying cardiac murmurs (p<0.002), and performed poorly when auscultating for carotid bruits (p<0.058). The HeartBuds stethoscope was equivalent to its more commonly used counterparts, the Littmann Cardiology III and the Littmann Electronic 3200. Examiners also found it to be of comparable acoustic quality to these models.

Conclusion:
HeartBuds is a smartphone compatible listening device that was superior in examining cardiovascular sounds to approved FDA Class I disposable stethoscopes, and equivalent to FDA approved class I and class II Littmann stethoscopes.
Abstract 14864: Impact of Chronic Atrial Fibrillation on 1-year Clinical Outcomes Following Percutaneous Transluminal Angioplasty in Patients With Symptomatic Peripheral Arterial Disease
Authors: Park Sang-Ho , Rha Seung Woon , Jun Ung , Choi Byoung Geol , Choi Se Yeon , Byun Jae Kyeong , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: April 2024

Background:
To date, there is no study regarding the impact of chronic atrial fibrillation (AF) on clinical outcomes following percutaneous transluminal angioplasty (PTA) in patients (pts) with symptomatic peripheral arterial disease (PAD).

Methods:
We investigated the 512 consecutive symptomatic PAD pts underwent PTA from September 2004 to December 2013. Individual and composite cumulative clinical outcomes of PAD pts with AF (n=465) at 1 year were compared with those of PAD pts with normal sinus rhythm (NSR, n=47).

Results:
In baseline characteristics, there were no significant differences in baseline clinical characteristics including gender, smoking, hypertension, diabetes, dyslipidemia, cerebrovascular accident (CVA), chronic renal insufficiency, dialysis, coronary artery disease, myocardial infarction, symptoms of PAD such as claudication, resting pain, wound, and gangrene between the two groups except age; The AF group tended to be elder than non-AF group (67.15±10.56 years vs. 70.21±8.93 years, respectively, p=0.051). At 1 year, there was no significant differences in major clinical outcomes such as the incidence of repeat PTA, target lesion revascularization (TLR), target extremity revascularization (TER), target extremity surgery (TES), above-the-knee amputation, above-the-ankle amputation, below-the-ankle amputation, acute myocardial infarction (AMI), percutaneous coronary intervention (PCI), and major adverse cerebrocardiovascular events (MACCEs) between the two groups. However, after adjustment of baseline confounders, the incidence of total death, cardiac death, and CVA were higher in the AF group as compared with non-AF group (Table).

Conclusions:
In our study, symptomatic PAD pts underwent PTA combined with AF was associated with higher incidence of mortality and stroke up to 1-year as compared with PAD pts with NSR.
Abstract 14909: Hydrogen Peroxide-Responsive Nanoparticles Reduce Myocardial Ischemia/Reperfusion Injury
Authors: Bae Soochan , Kang Changsun , Park Minhyung , Samad Mohammed A , Kang Taehi , Ke Qingen , Lee Dongwon , Kang Peter M
Published: April 2024

During myocardial ischemia/reperfusion (I/R), a large amount of reactive oxygen species (ROS) is produced which causes oxidative stress and leads to severe cellular and tissue damage. In particular, overproduction of hydrogen peroxide (H2O2) is considered as a main cause of I/R-mediated tissue damage by inducing inflammation and apoptosis. Therefore, rapid elimination of H2O2 and suppression of oxidative stress are thought to be reasonable strategies to treat myocardial I/R injury. Recently, we generated novel H2O2-responsive antioxidant polymer nanoparticles (PVAX and HPOX) that are able to target the site of ROS overproduction and impede the progression of oxidative stress-associated diseases. In this study, PVAX nanoparticles were selected as therapeutic agents for myocardial I/R injury based on the results of direct comparison studies in vitro and in vivo. To explore therapeutic effect of PVAX on cardiac I/R injury, cardiac function 2 weeks after reperfusion was evaluated. A single dose of PVAX (3mg/kg) showed a significant improvement in both cardiac output (8.1± 0.7 vs. 3.4±0.3) and fraction shortening (43.8± 0.9 vs. 31.2±3.8) compared with poly (lactic-co-glycolic acid) (PLGA) particle, a lacking H2O2 responsible nanoparticle. Consistent with cardiac function evaluation, PVAX significantly reduced the myocardial infarction /area at risk compared with PLGA (48.7±4.2 vs.14.5±2.1). In addition, PVAX effectively reduced caspase-3 activation (2.6±0.1 vs.1.4±0.1) and TUNEL-positive cells (8.2±1.8 vs. 2.7±0.6) compared with PLGA. Furthermore, PVAX significantly decreased TNF-α (5.5±0.4 vs. 3.0±0.3) and MCP-1 (2.3±0.1 vs. 1.4±0.1) mRNA levels. To explore the antioxidant effect of PVAX by scavenging ROS, dihydroethidium (DHE) staining was used as an indicator of ROS generation. PVAX effectively suppressed the generation of ROS caused by I/R while a number of DHE-positive cells were observed in a group of PLGA I/R. In addition, PVAX significantly reduced the level of NADPH oxidase (NOX) 2 and 4 expression, which favors the reduction in ROS generation after I/R. Taken together, these results suggest that H2O2-responsive antioxidant PVAX has tremendous potential as a therapeutic agent for myocardial I/R injury.
Abstract 15235: Characterization of Hypoxia-induced Long Non-coding RNAs in Endothelial Cells
Authors: Neumann Philipp , Jaé Nicolas , John David , Uchida Shizuka , Krüger Marcus , Dimmeler Stefanie
Published: April 2024

RNA deep sequencing revealed that the majority of the genome is transcribed, however, only 2% of all transcripts encode for proteins. The remaining transcripts are referred to as non-coding RNAs and can be divided into small non-coding RNAs (<200nt) and long non-coding RNAs (lncRNAs; >200nt). Recent studies suggest that lncRNAs can regulate gene expression at various stages, e.g. by acting as scaffolds, by modulating splicing, or by chromatin modification. Regarding endothelial cells (EC), the response to hypoxia and the regulation of angiogenic activity are key events in the context of several diseases, however, the involvement of regulatory lncRNAs and their molecular function is still elusive.

To systematically determine the regulation of lncRNAs by hypoxia, we performed RNA-seq in HUVEC after exposure to hypoxia (24h; 0.2% O
2
) and identified 71 lncRNAs to be significantly up- (p≤0.01) and 78 lncRNAs to be down-regulated in comparison to normoxic conditions. qRT-PCR was used to validate the hypoxia-dependent regulation of 5 selected lncRNAs (Hyp_up_1 to Hyp_up_5). Since hypoxia controls the angiogenic function of EC, we next investigated whether our candidate lncRNAs affect endothelial cell sprouting as an in vitro measurement for angiogenic response. Silencing was achieved by GapmeRs (Hyp_up_1, 3) or siRNAs (Hyp_up_2, 5). Strikingly, only silencing of Hyp_up_1 significantly reduced sprouting under basal conditions and VEGF stimulation. Therefore, we selected Hyp_up_1 for further functional characterization: First, nuclear cytoplasmic fractionation revealed its predominant nuclear localization. Second, RNA immunoprecipitation (RIP) showed that Hyp_up_1 is mainly associated with repressive chromatin marks (3meH3K27) indicating that it may be involved in epigenetic gene regulation. Third, GO term analysis based on exon array data revealed a reduced expression of angiogenesis related genes upon Hyp_up_1 silencing. Finally, using antisense affinity purification and mass spectrometry, we identified several Hyp_up_1 binding proteins and confirmed their interaction by RIP. Hyp_up_1 bound proteins included PTBP1/U2AF65, two splicing regulators, as well as LOXL2, a transcription factor known to mediate angiogenic functions in EC.
Abstract 15265: Clopidogrel Response Variability is Associated With Endothelial Dysfunction in Coronary Artery Disease Patients Receiving Dual Antiplatelet Therapy
Authors: Oikonomou Evangelos , Siasos Gerasimos , Zaromitidou Marina , Maniatis Konstantinos , Mourouzis Konstantinos , Kokkou Eleni , Antonopoulos Alexis , Zografos Theodoros , Tsalamandris Sotiris , Dimitropoulos Stathis , Zisimos Konstantinos , Kioufis Stamatis , Papavasiliou Athanasios G , Tousoulis Dimitris
Published: April 2024

Introduction:
Dual antiplatelet therapy with aspirin and a platelet P2Y12 ADP receptor antagonist is the cornerstone of treatment following percutaneous coronary intervention (PCI). Several clinical and genetic factors can cause suboptimal clopidogrel response.

Hypothesis:
Endothelial dysfunction affects clopidogrel response variability in subjects with stable coronary artery disease (CAD) after PCI.

Methods:
We consecutively enrolled 198 patients with stable CAD one month after successful PCI. All patients were receiving dual antiplatelet therapy (clopidogrel 75mg and aspirin 100mg/day). Platelet reactivity was measured by VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230. Endothelial function was evaluated by flow mediated dilation (FMD).

Results:
Patients with high on treatment platelet reactivity (32% of the study population), compared to subjects with low on treatment platelet reactivity, presented decreased FMD (4.35±2.22% vs. 5.74±3.29%, p=0.01). Moreover, an inverse association between endothelial function measurement and platelet reactivity (r=-0.24, p=0.001) was founded. Importantly, multivariate analysis after adjustment for age, gender and confounders revealed by the univariate analysis (left ventricle ejection fraction, body mass index, coronary lesion number) revealed that for every decrease in FMD by 1% there is an anticipated increased in P2Y12 reactive units by 10 units [b=-9.9, 95%CI(-19.0, -0.7), p=0.04].

Conclusions:
Endothelial dysfunction is associated with clopidogrel response variability in patients after PCI receiving dual antiplatelet therapy. These findings shed some light on the mechanisms affecting individual platelet response to antiplatelet therapy and may explain the non-straight forward association between clopidogrel dose, platelet inhibition and cardiovascular outcome.
Abstract 15300: Vigorous Physical Activity in the Women’s Health Initiative Cohort: Good or Maybe Not So Good?
Authors: Eaglehouse Yvonne L , Talbott Evelyn O , Chang Yuefang , Kuller Lewis H
Published: April 2024

Introduction:
Studies primarily of athletes have suggested that high levels of vigorous physical activity (PA) may increase the risk of amyotrophic lateral sclerosis (ALS). Case-control studies provide equivocal support for this hypothesis.

Hypothesis:
There have been no prior large cohort studies that have evaluated the relationship between vigorous PA, other risk factors, and subsequent ALS mortality among women.

Methods:
The Women’s Health Initiative (WHI), mean age of 63.6, assessed strenuous or hard PA, defined as PA that resulted in a sweat or fast heartbeat, at baseline by a self-administered questionnaire. Frequency of strenuous activity per week and duration in 20-minute intervals was collected. Metabolic equivalent (MET) intensity scores were then used to calculate the MET equivalence per week, similar to what had been used in previous WHI studies of PA. There were 165 women who were identified with ALS as the cause of death over an average 9.5 years follow-up. We excluded 4 deaths within 2 years of baseline evaluation.

Results:
Women who died from ALS were older and were predominantly white, n=145 (90%). Total hours of recreational PA was positively related to death due to ALS (p=.03) as was energy expenditure from strenuous activity (p=.045) and minutes of strenuous activity per week. In multivariate Cox models, duration of very hard or strenuous activity >40 minutes per week increased the hazards ratio of ALS, 1.67 (1.10-2.55, p=0.09 for trend), over time. Interestingly, the risk from performing no strenuous PA compared to some is similar in magnitude for total mortality [1.19 (1.12-1.27) based on 21,529 deaths], for CHD incidence [1.23 (1.10-1.37) based on 7,767 CHD events], and for breast cancer incidence [1.13 (1.03-1.25) based on 8,722 breast cancer deaths] in the WHI.

Conclusions:
This is the first cohort study that reported relationship of vigorous PA to risk of ALS even in sedentary participants. The protective effect of strenuous PA for total mortality, CHD, and breast cancer compared to the very small effect of strenuous PA on ALS risk does not compromise the overall benefit of vigorous exercise, but may provide an important clue as to the etiology of ALS.
Abstract 15325: Chromogranin B Levels are Increased in Myocardial Tissue in the Dyssynchronous Left Ventricle and Relate to Abnormalities in Regional Myocardial Deformation
Authors: Røsjø Helge , Lars van Middendorp B , Dahl Mai Britt , Ottesen Anett H , Stridsberg Mats , Christensen Geir , Prinzen Frits W , Smiseth Otto A , Remme Espen
Published: April 2024

Introduction:
Left bundle branch block (LBBB) induces abnormal activation and deformation of the LV wall. Chromogranin B (CgB) levels are increased in myocardium and plasma of heart failure patients and are linked to cardiomyocyte Ca
2+
handling.

Hypothesis:
That CgB expression is increased in distinct LV regions during LBBB and may be related to regional deformation abnormalities.

Methods:
CgB and pro-B-type natriuretic peptide (proBNP) protein levels were measured in biopsies from septum and LV lateral wall in 6 dogs with chronic LBBB (16 weeks), 8 control animals, and in 8 dogs with LBBB that received cardiac resynchronization therapy (CRT) between 8 and 16 weeks after creation of LBBB. Regional myocardial strain was assessed by speckle tracking echocardiography, LV volumes by MRI, and hemodynamics were assessed by invasive pressure measurements (LV dP/dt max and min,
tau
, LVP max and min, and LV end-diastolic pressure).

Results:
LBBB animals had increased end-diastolic volumes (55±1 vs.45±4 mL, p=0.038) but normal LV ejection fraction (50±3 vs. 55±4 %, p=0.42) compared to control animals. CgB levels were increased in both septum (p<0.001) and LV lateral wall (p=0.01) in LBBB compared to controls, despite no changes in LV proBNP levels, and with the most prominent increment found in the septum (Figure). In LBBB+CRT animals, CgB levels were 36±18% (septum) and 50±11% (LV later wall) lower compared to LBBB animals, but this difference was not statistically significant. Septal CgB levels correlated with septal early systolic rebound stretch (r=0.76, p=0.017) and lateral wall CgB levels with lateral wall pre-ejection stretch (r=0.76, p=0.018), while no correlations were found with LV dimensions or indices of global hemodynamic function.

Conclusion:
Myocardial CgB expression was increased in the absence of elevated proBNP levels in LBBB animals with preserved systolic function. Local CgB levels appear to relate to abnormal local early-systolic mechanical loading.
Abstract 15361: Self-reported Overwhelmingness is Independently Associated With Worst Performance on Advanced Cardiac Life Support Training Course Practical Examination
Authors: Oliveira Raphael A , Soares Eliane , Zampieri Fernando , Azevedo Daniel , Miotto Heberth , Braga Maria Aparecida
Published: April 2024

Background:
It remains controversial whether acute mental stress negatively influences provider performance during Advanced Cardiac Life Support (ACLS) courses. The aim of this study was to evaluate the influence of self-reported acute stress measurements and socio-demographic features on provider performance on ACLS practical exams.

Methods:
At total of 326 consecutive attendees of ACLS courses were included in a prospective observational study performed by Sociedade Mineira de Terapia Intensiva (SOMITI) training centre, Brazil. Self-reported measures (stress related to the instructor and evaluation, felling overwhelmed and a combination of evaluation-related stress and felling overwhelmed known as the stress/overload index) were provided after attendees completed their practical examinations. We performed multivariate and automated conditional inference tree analyses to appraise the factors that influence provider performance. Poor performance was defined as not passing the practical exam.

Results:
Thirty-six providers showed poor performance on the practical evaluation. Failing the practical examination was associated with both felling overwhelmed (OR: 1.63 [95% CI: 1.37-1.93], p<0.001) and the stress/overload index (OR: 1.77 [95% CI: 1.37-2.29], p<0.001). Both variables were the most prominent factors associated with poor performance according to conditional inference tree analysis. However, stress related to the evaluation was not independently associated with non-approval. Multivariate analysis revealed that increased age, a lower percentage of ACLS materials studied before the course, stress related to the instructor and occupation as a nurse were also independently associated with poor performance.

Conclusion:
Self-reported felling overwhelmed was robustly associated with poor performance on the ACLS course practical examinations.
Abstract 15506: Inhibition of the NLRP3 Inflammasome Limits the Inflammatory Injury Following Myocardial Ischemia-reperfusion in the Mouse
Authors: Toldo Stefano , Marchetti Carlo , Mauro Adolfo G , Mezzaroma Eleonora , Carbone Salvatore , Zhang Shijun , Salloum Fadi , Van Tassell Benjamin W , Abbate Antonio
Published: April 2024

Introduction:
Acute myocardial infarction (AMI) initiates as a result of severe ischemia, and while reperfusion relieves ischemic injury, limiting the overall infarct size (IS), it also triggers a secondary ischemia-independent myocardial injury occurs contributing to the final IS.

Hypothesis:
We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits the progression of IS following myocardial ischemia/reperfusion (I/R).

Methods:
Adult CD1 male mice were subjected to transient ligation the left coronary artery for 30 minutes followed by reperfusion (N=3-6 per each group). IS was measured by triphenyl tetrazolium chloride (TTC) staining method at 1, 3 and 24 hours, and with serum cardiac troponin I (cTnI) levels 24 hours after surgery. Myocardial NLPR3 expression was quantified at 3, 6 and 24 hours of reperfusion. A novel pharmacologic NLRP3 inhibitor (NLRP3inh) or vehicle were administrated intraperitoneally at time of reperfusion, or with a delay of 1 or 3 hours.

Results:
IS measured at TTC was significantly larger at 24 hours (43±4% of the area at risk) vs 3 hours (30±5%) and 1 hour (11±2%, P<0.001 for trend). NLRP3 myocardial expression was also significantly increased at 24 hours (1,097±382% of sham, P<0.001) and 6 hours (928±380%, P<0.001) vs 3 hours (111±15%). When compared with vehicle, the NLRP3inh given at reperfusion did not significantly reduce IS at 3 hours, while it significantly reduced IS at 24 hours (Figure). Administration of the NLRP3inh 1 hour after reperfusion significantly reduced IS at 24 hours, while it did not when given with a delay of 3 hours (Figure).

Conclusions:
Inhibition of the NLRP3 inflammasome within 1 hour of reperfusion limits the secondary inflammatory injury following myocardial ischemia-reperfusion.
Abstract 15575: Can Rhythm Control by Catheter Ablation Improve Exercise Capacity in Asymptomatic Patients With Chronic Atrial Fibrillation?
Authors: Nam Jong-Ho , Lee Chan-Hee , Park Kyu-Hwan , Son Jang-Won , Kim Ung , Park Jong-Seon , Shin Dong-Gu , Kim Young-Jo
Published: April 2024

Introduction:
Radiofrequency catheter ablation (RFCA) for asymptomatic atrial fibrillation (AF) is not indicated due to limited data on it’s clinical efficacy. This study evaluated the change in oxygen kinetics and cardiopulmonary performance parameters after RFCA for asymptomatic (Canadian Cardiovascular Society-Severity of AF scores = 0) Chronic AF patients.

Methods:
A total of 57 patients with asymptomatic chronic AF (age 60 ± 9 year-old, 89.5% male, AF duration 51 ± 49 months) divided into 2 groups according to sinus rhythm conversion via RFCA: Group 1 (Rate control, n=32); Group 2 (Rhythm control, n=25). The patients who achieved sinus rhythm by antiarrhythmics (n=20) and cardioversion (n=4) were excluded. All underwent two times of treadmill cardiopulmonary exercise tests (modified Bruce protocol, Quark CPET®, COSMED, Italy) before and after each treatment (follow-up periods, 250 ± 181 days). Peak oxygen uptake (Peak VO2, ml/min/Kg) as aerobic capacity, O2-pulse at peak (ml/beat) for cardiovascular response, and the slope of the increase in ventilation to the increase in CO2 output (VE-VCO2 slope) for gas exchange were compared.

Results:
The Group 1 patients were older (62 ± 7 vs. 57 ± 10 year-old) and had longer duration of AF (63 ± 52 vs. 36 ± 39 months) than the Group 2 patients. The O2-pulse at peak were much increased in Group 2 during follow-up periods (Group 1, from 10.0 ± 3.1 to 10.6 ± 3.1, P=0.137; Group 2, 12.1 ± 3.8 to 15.4 ± 3.8, P=0.003). During exercise, maximal exercise heart rate was significantly lower in Group 2 after treatment (Group 1, 162±25 vs. Group 2, 128±29 bpm, P<0.001). However, the value of Peak VO2 and VE-VCO2 slope were not different between before and after treatment, and between 2 groups.

Conclusion:
The results from the present study indicate that improvement of maximal aerobic capacity and exercise tolerance are negligible in asymptomatic patients with chronic AF following successful catheter ablation.
Abstract 15588: Folic Acid Attenuates Acute Doxorubicin-Induced Cardiomyopathy by Modulating Endothelial Nitric Oxide Synthase and Mitochondrial Integrity
Authors: Octavia Yanti , Kararigas Georgios , de Boer Martine , Kietadisorn Rinrada , Swinnen Melissa , Duimel Hans , Verheyen Fons K , Janssens Stefan , Duncker Dirk J , Moens An L
Published: April 2024

Aims:
In the pathogenesis of doxorubicin (DOXO)-induced cardiomyopathy, endothelial nitric oxide synthase (eNOS) has a pivotal role. Here we tested the hypothesis that folic acid (FA), as an eNOS modulator, attenuates DOXO-induced cardiomyopathy and mortality.

Methods:
Male C57BL/6 mice (n=265) received DOXO (1x 20 mg/kg, ip) or saline (sham). FA (10 mg/d po) or placebo was administered from 7d before DOXO administration until the end of the experiment (10d). Left ventricular (LV) function was measured by echocardiography; atrophy, fibrosis and apoptosis by hematoxylin-eosin, Picro-sirius Red and TUNEL staining, respectively; eNOS uncoupling, activity and S-glutathionylation by co-immunoprecipitation and immunoblotting; superoxide (O2-) production by lucigenin-enhanced chemiluminescence, with or without L-NAME (NOS inhibitor); cardiac NO by Griess reaction; mitochondrial function and morphology by mitochondrial oxygen consumption measurements and electron microscopy, respectively.

Results:
DOXO produced 70% mortality (P<0.01 vs sham), while mice receiving DOXO and FA (DOXOFA) had significantly lower mortality (45%; P<0.01). FA ameliorated DOXO-induced LV dysfunction, atrophy, fibrosis, and apoptosis (Table 1). Uncoupling, activity and S-glutathionylation levels of eNOS were restored in DOXOFA, and subsequently lead to a reduction in O2- production, which mainly NOS-dependent, and an increase in cardiac NO. Furthermore, FA attenuated mitochondrial dysfunction and morphological changes.

Conclusion:
FA as eNOS modulator might be a new and immediate therapeutic approach to reduce DOXO-induced cardiomyopathy.
Abstract 15607: Mitochondrial and Biochemical Effects of Repetitive Cycles of Remote Ischemic Conditioning (RIC) in Human Upper and Lower Extremities
Authors: Taft Maia Y , Kenny Elizabeth , Krehel Nicholas , Airgood Hannah , Holquist Kate , Gerstel Stacey , Corey Catherine , Rittenberger Jon , Guyette Frank X , Shiva Sruti , Dezfulian Cameron
Published: April 2024

Introduction:
RIC is protective against heart and brain ischemia. The mechanisms are still debated as are dose effects of repetitive cycles using the upper or lower extremity. Increases in reactive hyperemia (RH), plasma nitrite and reactive oxygen species (ROS) may underlie protective signaling.

Hypothesis:
Repetitive cycles of RIC will be more effective in thigh than forearm increasing plasma nitrite and inhibiting mitochondrial function with small increases in ROS.

Methods:
Ten healthy individuals were subjected to 4 cycles of 5 min of limb ischemia, delivered by blood pressure cuff occlusion, and 5 min reperfusion (RIC). Subjects were randomized to right forearm or right thigh RIC first, then crossed over to the other extremity 2 weeks later. Blood flow and perfusion were monitored using laser speckle contrast imaging and by tissue oximetry on the ipsilateral and contralateral foot or hand. Blood was obtained at baseline and after each cycle and 24 h later for determination of platelet nitrite levels (chemiluminescence), mitochondrial function (Seahorse) and superoxide (ROS) generation (mitoSOX flow cytometry) and plasma nitrite.

Results:
RH, nitrite levels, mitochondrial oximetry and ROS were similar in arm (presented below) and thigh(p>0.2). RH (178% increased blood flow, 17% increased oximetry; p<0.0001) occurred after each RIC cycle with no difference between cycles 1-4. Plasma nitrite significantly increased (23%; p=0.033) after four cycles RIC and returned to baseline 24h later. The platelet rich plasma (PRP) nitrite was highest after cycle 1 (76% increase; p=0.002) with steady reduction after each cycle (15% over baseline by cycle 4; p=0.001). With each cycle platelet mitochondrial respiration declined (24% max by cycle 4) whereas superoxide generation increased (27% max by cycle 4; p<0.05).

Conclusions:
RIC using arm or leg produce similar physiologic and biochemical effects. RH of similar degree occurs with each cycle whereas nitrite production peaks after the first cycle and is consumed with subsequent cycles coincident with gradual mitochondrial inhibition and superoxide generation. These biochemical responses have been suggested in pre-clinical work to underlie protective signaling and differ little based on extremity used.
Abstract 15753: Center Based Care Improves Survival in Patients Suffering From Peripheral Arterial Disease
Authors: Hoebaus Clemens , Tscharre Maximilian , Howanietz Marie-Therese , Winkler Alexander , Koppensteiner Renate , Schernthaner Gerit
Published: April 2024

Introduction:
Advances in cardiovascular management have ameliorated mortality rates. However, management of peripheral arterial disease (PAD) remains challenging due to the comorbidities in those mostly elderly patients.

Hypothesis:
Possible reduction of mortality in PAD patients by center-based care.

Methods:
All patients were examined at baseline at the vascular medicine center (VMC) of the Medical University Vienna. The cohort was longitudinally followed-up for five years in two groups managed by their general practitioner (GP, N=332) or VMC (N=370). VMC patients had visits every six month including physical examination of the feet, non-invasive imaging of arterial perfusion, and blood draws (glucose tolerance test, HbA1c, LDL-cholesterol). Furthermore, reassessment of the current medication schedule and, if indicated, non-invasive tests of cardiac and pulmonary function were performed.

Results:
Survival was 66% for GP managed patients and 90.8% for patients managed at VMC within five years. In a multivariate model including the known risk factors for PAD (gender, age, diabetes, smoking, hypertension, hyperlipidemia, c-reactive protein (CRP) and nephropathy) at baseline only nephropathy (HR 2.7 (95% CI: 1.38-5.45)), CRP (HR per 1STD: 1.36 (95% CI: 1.10-1.73) and age (HR per 1 STD 1.46 (95% CI: 1.03-1.86)) were connected to mortality during 5 years of follow up in VMC patients. In the GP group no single predictive risk factor could be identified. Patients in both groups were equally affected by coronary (p=0.076) or carotid artery disease (p=0.555) at baseline. Center based patients showed significantly higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), and nephropathy (p=0.001). Both groups were comparable for the risk factor smoking (p=0.988) and diabetes (p=0.074).

Conclusions:
Center based care of patients with PAD including physical examination of the feet and repetitive vascular assessment by non-invasive imaging technics improves mortality. Furthermore, constant screening for diabetes, hyperlipidemia and cardiovascular and pulmonary complications in these high-risk patients can accelerate further medical decision including medication changes.
Abstract 15797: Peri-procedural Use of Novel Anticoagulation Agents During Cardiac Device Implantation
Authors: Pillarisetti Jayasree , Maybrook Ryan , Atoui Moustapha , Annapureddy Tulasi , Vodapally Mamatha , Di Biase Luigi , Gianni Carola , Natale Andrea , Lakkireddy Dhanunjaya
Published: April 2024

Introduction:
The timing of discontinuation and re-initiation of novel anticoagulant agents (NOACs) such as dabigatran, apixaban and rivaroxaban in the peri-procedural setting is important to minimize the risk of stroke and procedure-related bleeding.

Methods:
Consecutive patients who were on treatment with either dabigatran, rivaroxaban or apixaban and underwent a cardiac device generator change, upgrade or new implantation procedure at two high volume centers were noted (Group A). Age and gender matched patients on warfarin who underwent similar procedures were collected for controls (Group B). Patients were followed for three months for hematoma and other complications.

Results:
A total of 185 patients in group A underwent above procedures with new device implant in 50%, device upgrade in 23% and generator change in 25% of patients. There were 61 patients on dabigatran, 90 on rivaroxaban, 34 on apixaban in group A and 185 patients on coumadin in group B. Mean age of the total population was 68±12 years with 71% males and 84% Whites with no differences between groups. There were more patients on dual antiplatelet therapy in group A (10%) compared to group B (1%). Mean INR in Group B was 2.1 pre and post procedure. In 3 patients, NOACs were held for 24 to 48 hours prior to the procedure, while they were continued un-interrupted in the rest of the patients. NOACs were resumed after the procedure within 24 hours in all patients except in one patient. There was no difference noted in the incidence of minor or major hematoma in each of these groups (see table). None of the patients in Group A required evacuation. Two patients in Group B developed infection of the hematoma that prompted extraction of the device. No stroke or bleeding related complications were noted in both groups

Conclusion:
Uninterrupted use of the NOACs is safe in the peri-procedural setting during implantation of cardiac devices. Our study is the first to compare the three NOACs with warfarin.
Abstract 15800: Identification of a Novel Transcript and Regulatory Mechanism for Microsomal Triglyceride Transfer Protein
Authors: Suzuki Takashi , Brown Judy J , Swift Larry L
Published: April 2024

Microsomal triglyceride transfer protein (MTP) is heterodimeric protein complex consisting of a unique 97 kDa protein with lipid transfer activity and the ubiquitous 58 kDa protein disulfide isomerase. The complex is essential for assembly of triglyceride-rich apolipoprotein (apo) B-containing lipoproteins. In tissues that do not synthesize apoB nor assemble lipoproteins, it is presumed to serve specialized needs in lipid trafficking, such as in the lipidation of CD1d in antigen presenting cells, including adipocytes.

Previous studies in our laboratory identified a novel isoform of MTP in mice that we named MTP-B. MTP-B has an alternative first exon (Ex1B) located 2.7 kbp upstream of the first exon (Ex1A) of MTP-A, the canonical isoform of MTP. The two mature isoforms, though nearly identical in sequence and function, have different tissue expression patterns.

In this study, we have identified another splice variant, MTP-C, that contains both exons Ex1B and Ex1A. PCR analysis revealed that MTP-C mRNA is expressed in a number of tissues including liver, ovary, heart, kidney, brain and testis. In CHO and HEK 293 cells transfected with MTP-C, protein expression was less than 15% of that found when the cells were transfected with MTP-A or MTP-B. In silico analysis of the 5’ untranslated region (UTR) of MTP-C revealed six ATGs (uATGs) upstream of the translation initiation site for MTP-A, which is the only viable start site in frame with the main open reading frame (ORF), and three potential upstream ORFs (uORFs). Since uATGs and uORFs are generally associated with repressed translational efficiency, we inserted the 5’ UTR of MTP-C into a pGL3 vector between the SV40 promoter and luciferase reporter gene and transfected it into CHO cells. Luciferase activity was significantly reduced (45.5 ± 6.4%) compared to pGL3-Control vector transfected cells. This suggests the reduced protein expression observed in MTP-C transfected cells resulted in part from decreased translation efficiency.

We conclude that uORFs in the 5’ UTR of MTP-C repress translation, providing a mechanism to fine tune MTP levels to meet the needs of the cell. uORFs in human MTP-C could represent novel therapeutic targets for regulation of MTP expression and plasma lipid levels.