bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18039: Cardiac Catheterization in the Early Postoperative Period Following Congenital Cardiac Surgery
Authors: Nicholson George T , Ehrlich Alex , Kim Dennis W , Vincent Robert N , Glanville Michelle , Petit Christopher J
Published: April 2024

Background:
Early postoperative cardiac catheterization (EPOCC) is regarded as high-risk, particularly when patients are unstable or when interventions upon suture lines are anticipated. There are little data available demonstrating safety of EPOCC.

Objective:
The purpose of this study was to describe the safety of catheterizations performed in ≤ 30 days after congenital heart surgery.

Methods/Results:
All EPOCC performed within 30 days after congenital heart surgery between November 2004 and May 2013 were retrospectively reviewed. One-hundred and ninety-one patients, median age 0.4 years (range 0-18.5 years), weight 5.3 kg (range 2.2-98.5 kg) underwent EPOCC on median postoperative day 6 (range 0-30 days). One-hundred and twenty-seven catheterizations were diagnostic while 64 pts underwent a total of 89 interventional procedures. At time of EPOCC, 21 patients were receiving extracorporeal cardiopulmonary (ECMO) support. Among the 89 interventions were 64 dilation procedures, 60 of which were at surgical anastomotic areas. There was one procedural mortality due to tear during angioplasty. In addition, there were 4 major complications including need for ECMO support (n=2) and need for resuscitation (n=2). There were 42 deaths (21%) prior to hospital discharge. Interventional EPOCC was not associated with increased risk of mortality (p=0.87) as compared to those who only underwent a diagnostic catheterization. Binary logistic regression demonstrated that ECMO support at time of EPOCC (p=0.001), lower weight at EPOCC (p<0.001), and younger age at EPOCC (p<0.001) were associated with mortality.

Conclusion:
EPOCC is in most cases safe, even in small, critically ill children. Interventions, including angioplasty and stenting across suture lines, can be safely performed, though caution is essential. Interventional EPOCC is not associated with increased risk of mortality.
Abstract 18041: RNAseq Identifies Differential Expression of Platelet Transcripts Between Hyper and Hypo-Aggregation to Collagen
Authors: Qayyum Rehan , Faraday Nauder , Becker Diane M , Kral Brian G , Becker Lewis C
Published: April 2024

Background:
Platelet aggregation plays an important role in the pathogenesis of myocardial infarction, and high platelet aggregability is associated with increased risk of events. We hypothesized that inter-individual variability in platelet function is associated with differences in the mRNA transcripts found in platelets from hyper-aggregators and hypo-aggregators.

Methods:
Ten individuals with family history of early onset coronary artery disease were enrolled. Individuals were divided into hyper- and hypo-aggregators based on maximal aggregation to collagen using whole blood impedance aggregometry. RNA was extracted from leukocyte-depleted platelet-rich plasma and approximately 70 million 100bp paired-end reads per sample were obtained using an Illumina HiSeq 2500. RNA-seq analysis was performed using Bowtie/TopHat/Cufflinks software pipeline. Genes with expression ≥ 0.3 fragments per kilobase of transcript per million reads (FPKM) were considered to be expressed. Genes with ≥ 2-fold change in expression on log2 scale and FDR<0.1 were considered to be significantly differentially expressed.

Results:
Study sample consisted of 2 females and 3 males in each group. Among the 12,105 expressed genes, the most highly expressed nonubiquitous genes included GPX1, PPBP, PF4, & TUBB1, confirming our methodologies. Hyper-aggregability was associated with up-regulation of 69 genes (such as MTRNR2L1 [anti-apoptotic], DEFA1 [innate immune response], and MYL4 [myosin light chain]). On the other hand, 50 genes were significantly down-regulated in hyper-aggregators (such as CCL3L1 [chemotactic for lymphocytes], CXCL5 [chemokine], and TUBB2A[beta-tubulin]). Gene ontology enrichment analysis found that genes related to innate immune response were up-regulated while genes related to B- and T-lymphocyte regulation were down-regulated in hyper-aggregators.

Conclusion:
RNA-seq and gene ontology analyses found that hyper- and hypo-aggregators have significant differences in gene expression. Increased expression of innate immune pathway genes in hyper-aggregators highlights the relationship of inflammation with increased platelet aggregation and suggests a role of platelets in innate immune response.
Abstract 18069: Evaluation of Potential Antiplatelet Effects of CSL112, a Novel Formulation of Human Apolipoprotein A-I: Results From a Phase 2a Study
Authors: Gurbel Paul A , Bliden Kevin P , D’Andrea Denise M , Henderson Karen W , Alexander John H , Tantry Udaya S , Shear Charles , Tricoci Pierluigi
Published: April 2024

Background:
CSL112, a novel formulation of apoA-I purified from human plasma and reconstituted to form HDL particles, is in development for the treatment of patients with coronary artery disease. Prior data with a similar compound (CSL111) indicated a potential short-term platelet inhibitory effect. We assessed the potential antiplatelet effects of CSL112 in a phase 2a multicenter, randomized, ascending dose study in subjects with stable atherosclerotic disease.

Methods:
Subjects (n=44) on aspirin (75-325 mg/day) and clopidogrel (75 mg/day, n=37) or prasugrel (10 mg/day, n=7) for >30 days in addition to standard of care therapy were randomized to a single dose of placebo or CSL112: 1.7, 3.4, and 6.8g. Conventional platelet aggregation in response to 2 mM arachidonic acid (AA), 5 and 10 μM adenosine diphosphate (ADP), and 4μg/mL collagen were performed at baseline and 8, 12, 24 and 48 h post-dosing. The change from baseline in maximal aggregation was determined and compared by ANOVA analysis among the treatments at any time point.

Results:
Baseline characteristics were well balanced across treatment groups. Compared to placebo, CSL112 did not show any time or dose dependent effects on maximum platelet aggregation in response to any agonist (p>0.05 for all tests) [Table].

Conclusion:
CSL112, when co-administered with dual antiplatelet therapy, does not significantly influence platelet aggregation in response to AA, ADP and collagen. Based on these data, it is anticipated that CSL112 will not affect hemostasis when administered with concomitant antiplatelet therapies.
Abstract 18108: Decreased Fmo3 Expression is Associated With Increased Atherosclerosis and Impaired Liver Function in Apolipoprotein E Null Mice
Authors: Shih Diana M , Che Nam , Meng Yonghong , Wu Judy , Wang Zeneng , Hasin Yehudit , Beaven Simon W , Brown J M , Lee Richard , Graham Mark J , Hazen Stanely L , Lusis Aldons J
Published: April 2024

Recent studies demonstrated a strong positive association between blood trimethylamine-N-oxide (TMAO) level and risk for cardiovascular disease. Dietary choline is converted to trimethylamine (TMA) by the gut bacteria, and TMA is then converted to TMAO in the liver, mainly by flavin containing monooxygenase 3 (Fmo3). To examine how FMO3 expression influences atherogenesis, we administered two different FMO3 or control antisense oligonucleotdies (ASOs) to apolipoprotein E (apoE) null mice for 15 weeks. During the last 12 weeks of the ASO treatment, the mice received a chow diet containing 1% choline to enhance TMA production. Hepatic FMO3 mRNA levels were decreased by 80% in mice that received either FMO3 ASO #1 or #2 versus those that received the control ASO. As expected, circulating TMA and TMAO levels were significantly increased and decreased, respectively, in the mice that received the two FMO3 ASOs versus the controls. Other observed changes in the FMO3 ASO-treated mice included: decreased plasma triglyceride, HDL, and glucose levels. Significantly increased VLDL/IDL/LDL cholesterol was observed only in FMO3 ASO #2-treated mice versus the controls. FMO3 ASO treatment increased circulating total bile acid levels by more than 2-fold. Compared to controls, serum markers of hepatic inflammation and necrosis (ALT, AST) were significantly increased in FMO3 ASO treated mice. Histological examination revealed obvious hepatic steatosis and increased inflammatory cell infiltration, suggesting that FMO3 abrogation may be a reasonable model for non-alcoholic steatohepatitis (NASH). We also found a significant increase in quantitative triglyceride and cholesterol content of these livers. Transcriptional profiling by microarrays showed increased hepatic expression of inflammatory genes in mice that received FMO3 ASOs versus the controls. In addition, a significant increase in spleen weight in these mice suggests increased systemic inflammation. Finally, FMO3 knockdown increased atherosclerosis by more than 50% when compared to controls (p < 0.01). This work demonstrates that blocking FMO3 activity has a major impact on liver physiology and atherosclerosis. Our study suggests a protective role for FMO3 in atherosclerosis and liver function.
Abstract 18167: MCP-1/CCR2 Desensitizes the SDF-1/CXCR4 Signaling in Bone Marrow Stem/Progenitor Cells
Authors: Xu Shiyue , Jung Hosung , Tao Jun , Miller Richard , Qin Gangjian
Published: April 2024

Background:
SDF-1/CXCR4 axis plays a pivotal role in the regulation of bone marrow (BM) stem/progenitor cell trafficking, thereby contributing to the ischemic tissue repair. CCR2 receptor is also widely expressed in the BM mononuclear cells, and the MCP-1/CCR2 axis has been shown to regulate the migration of these cells during inflammation. More recent evidence suggests that CCR2 and CXCR4 can form hetero-dimmers; however, the biological significance of the crosstalk between these two chemotactic pathways is not clear. Here, we

hypothesize

that MCP-1/CCR2 suppresses BM stem/progenitor cell trafficking through desensitization of SDF-1/CXCR4 signaling.

Methods and Results:
By using MCP1-RFP/CXCR4-eGFP double transgenic mice, we examined the endocytosis of MCP-1 in BM cells after systemic injection of lipopolysaccharide (LPS) and found that MCP-1 endocytosis occurred predominantly in CXCR4-positive stem/progenitor cells. Then we measured the MCP-1- and/or SDF-1-induced intracellular calcium transient by Fura2-based calcium imaging in the isolated BM cells. Our results showed that more than 80% of MCP-1-responsive cells also responded to SDF-1 treatment. However, in the cells pretreated with escalating doses of MCP-1 (10, 20, and 40 nM), a dose-dependent desensitization of SDF-1 activity was observed (
p
<0.05, 20 nM vs. 10 nM;
p
<0.001, 40 nM vs. 10 nM or 20 nM). Moreover, systemic administration of AMD3100 in mice significantly increased CCR2-positive stem/progenitor cells in the peripheral blood (n=4 each;
p
<0.01).

Conclusions:
Activation of MCP-1/CCR2 desensitizes SDF-1/CXCR4 signaling in BM stem/progenitor cells; targeting MCP-1/CCR2 axis may enhance the effectiveness of CXCR4-mediated stem/progenitor cell homing and tissue repair in ischemic heart disease.
Abstract 18186: The Role of Vascular Smooth Muscle Kv 1.5 Channels in Coronary Metabolic Dilation
Authors: Ohanyan Vahagn A , Luli Jordan , Yin Liya , Logan Suzanna , Enrick Molly , Stevanov Kelly , Kolz Christopher L , Kmetz John , Bratz Ian , Chilian William M
Published: April 2024

The coupling of flow to metabolism in the heart is termed coronary metabolic dilation and enables the proper supply of oxygen and nutrients to sustain cardiac function. Previously we found that mice null for Kv1.5 channels (Kv1.5
-/-
) have blunted metabolic dilation, and during high metabolic demand flow is insufficient to meet the needs of the myocardium leading to ischemia. However these mice were null for the channel in all organs, and the expression of Kv1.5 channels in cardiac myocytes, in addition to smooth muscle, is well established. For metabolic dilation, we hypothesized a scheme in which expression of Kv1.5 channels in smooth muscle is key for the process; therefore we determined if expression of the channels only in smooth muscle in the Kv1.5
-/-
background would rescue the phenotype of impaired metabolic dilation. We created a line of transgenic mice with doxycycline inducible Kv1.5 channel expression in smooth muscle (SM22 promoter). Expression was induced by 7 days of doxycycline treatment and increased approximately 8-fold over that in wild type mice (WT). Myocardial blood flow was measured using contrast echocardiography. Myocardial blood flow and hemodynamic measurements were done at baseline and during norepinephrine (NE) injection (0.5-5 μg/kg/min) to increase metabolic demand as defined by the pressure rate product (PRP: mean arterial pressure x heart rate). As shown in the figure, blood flow during increased metabolism (PRP) was significantly decreased in Kv1.5
-/-
mice compared to WT. In the transgenic mice with Kv1.5 overexpression, the coupling of flow to metabolism was increased during NE compared to WT and Kv1.5
-/-
.

Based on these data, we conclude that expression of Kv1.5 channels in vascular smooth muscle rescues the phenotype of impaired metabolic dilation in the coronary circulation of Kv1.5
-/-
.

These results suggest that Kv1.5 channels in vascular smooth muscle are critical for the coupling of flow to metabolism in the heart.
Abstract 18244: Implication of Obesity on Length of Stay and Cost in Atrial Fibrillation Patients- An Objective Evidence
Authors: Parikh Valay , Patel Nilay , Savani Ghanshyambhai T , Bhalara Vipulkumar , Patel Nileshkumar J , Chothani Ankit , Shah Neeraj , Sullivan Erinmarie , Mehta Kathan , Singh Vikas , Deshmukh Abhishek , Rathod Ankit , Badheka Apurva O , Kowalski Marcin , Mitrani Raul D , Viles-Gonzalez Juan
Published: April 2024

Background:
Obesity is considered to be an important co-morbidity in patients with atrial fibrillation (AF). However, its direct implication in terms of cost and length of stay is missing.

METHODS:
We queried the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) between 2000 and 2010 using the ICD9-CM code of 427.31 for atrial fibrillation as a primary discharge diagnosis and 278.01 for obesity as a secondary diagnosis. Participants with >18 years of age were only included. The NIS represents 20% of all hospitals in the US. All analyses were performed using the designated weighting specified to the NIS data base to represent national trends. We compared baseline characteristics, length of stay and total cost in obese and non-obese group.

RESULTS:
We studied 4092578 patients admitted with primary diagnosis of AF. Obese population was younger, had more diabetes and hypertension. Obese population had more private insurance including HMO and fewer medicares and Medicaid insurance. They were more likely to have invasive cardiac work-up including percutaneous cardiac interventions (PCI). Compare to non-obese population, obese patients had a longer length of stay (4.07 vs. 3.59, p<0.0001) mainly driven by length of stay >2 days (61.6% vs. 52%). Their adjusted total hospitalization cost was also higher as compared to non-obese population ($ 25632 vs. $ 21957, p<0.0001).

CONCLUSION:
This is one of the largest studies to evaluate the implications of obesity on health care resource utilization in patients admitted with atrial fibrillation. Length of stay and cost were higher in obese population as compared to non-obese population. Considering the fact that both obesity and atrial fibrillation are in epidemic proportion right now, financial implication can be huge.
Abstract 18332: Diagnostic Yield of Transesophageal Echocardiography for Infective Endocarditis in Patients Referred for Suspected Endocarditis
Authors: Slucca Michela , Spevack Daniel M
Published: April 2024

Background:
The expert panel that authored the 2011 Appropriate Use Criteria for Echocardiography considered the use of transesophageal echocardiography (TEE) to be appropriate when used to diagnose infective endocarditis (IE) with a moderate or high pretest probability. The panel appropriate use score was 9, the highest possible score achievable. Few published data are currently available to support this recommendation. We aimed to define the diagnostic yield of TEE in a population with moderate or high pretest probability for IE.

Methods:
Consecutive TEE reports (n=6,189) acquired between 1/1/2005 and 12/31/2012 at our institution were reviewed for the presence of possible or definite endocarditis. TEE were acquired from 5,347 individual patients. Endocarditis was considered to be present if a new vegetation was demonstrated or there was obvious abscess formation. The diagnostic yield for endocarditis was compared between exams performed for different indications.

Results:
The study group was 62 ± 15 years old and 55% male. Most TEE (78%) were performed on inpatients. TEE findings are reported in the Table. The yields for definite and possible IE were 9% and 8% respectively amongst subjects with bacteremia referred for suspected IE. Those referred for suspected IE had increased odds for finding definite IE (odds ratio (OR) 4.2, 95% CI: 2.7, 6.6, p<0.001). Amongst those referred for suspected IE, prosthetic valve (OR 2.4, 95% CI: 1.5, 3.8, p<0.001) and pacemaker/ICD (OR 16, 95% CI: 6, 44, p<0.001) were independent predictors of definite IE.

Conclusion:
The diagnostic yield for finding IE on TEE in subjects with bacteremia referred for suspected IE is reasonably high. Our findings support the current recommendations for use of TEE in this population.
Abstract 18404: Warfarin Persistence in Atrial Fibrillation: The Michigan Anticoagulation Quality Improvement Initiative Experience
Authors: Lopez Alexis , Barnes Geoff D , Gu Xiaokui , Haymart Brian , Kline-Rogers Eva , Almany Steve , Kozlowski Jay , Besley Dennis , Ahsan Syed , Krol Gregory D , Kaatz Scott , Froehlich James B
Published: April 2024

Introduction:
Warfarin reduces the risk of stroke in patients with atrial fibrillation (AF), but increases the risk of bleeding. In clinical trials, persistence with warfarin therapy ranges from 75-79% at one year, but few studies offer real-world estimates of warfarin persistence. There is limited data demonstrating the relationship between CHADS2 and HAS-BLED scores with adherence to warfarin.

Methods:
New patients treated with warfarin for stroke prevention in AF were followed at seven anticoagulation clinics involved in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) collaborative. Patients were excluded if they had additional indications for warfarin such as artificial valve, DVT, or PE. Risk factors for CHADS2 and HAS-BLED scores and reasons for warfarin discontinuation were abstracted from patient charts. Kaplan-Meier (KM) curves were constructed to characterize drug therapy discontinuation rates at one year. Cox proportional hazard regression and logistic regression analyses were performed to assess the effects on warfarin persistence by CHADS2 and HAS-BLED scores.

Results:
Of 1,973 eligible patients, 153 (7.8%) switched to non-warfarin therapy (e.g. dabigatran). In the remaining 1820 patients, one year persistence is 63% based on KM estimates. One year persistence by low, intermediate, or high CHADS2 score was 29%, 58%, and 73%, respectively. One year persistence for low, intermediate, or high HAS-BLED score was 41%, 66% and 76%, respectively. Warfarin persistence at one year was associated with an increasing CHADS2 (OR 1.244, CI 1.045-1.482) but not associated with HAS-BLED score (OR 1.016, CI 0.839-1.231) in multivariate analysis.

Conclusions:
A significant proportion of patients taking warfarin for SPAF discontinue therapy by one year. In the multivariate analysis, patients at higher risk of stroke, but not bleeding, are more likely to remain on warfarin therapy. Efforts to improve warfarin persistence need further investigation.
Abstract 18485: Transgenic Expression of a Kir6.1 Gain-of-Function Mutation in the Mouse Heart Results in Av Nodal Conduction Abnormalities
Authors: Zhang Haixia , Levin Mark , Uchida Keita , Verbsky John W , Nichols Colin G
Published: April 2024

While consensus exists that Kir6.2 gives rise to the pore forming subunit of KATP channels in mouse heart, there is growing evidence that Kir6.1 is also present in mouse cardiomyocytes. Furthermore, Kir6.1 gain-of-function mutation (GOF) is associated with Early Repolarization (ERS) and Brugada Syndromes. It is unclear, however, whether the consequences of the Kir6.1 GOF result from abnormalities in cardiomyocytes, or other cell types in the heart. To assess the consequence of Kir6.1 GOF in cardiomyocytes, we generated Kir6.1[G343D] (GOF) mice under α-myosin heavy chain promoter. Patch-clamp data shows decreased sensitivity to ATP inhibition in GOF myocytes (EC50 = 43.5 ± 6.1 μM in GOF, 8.3 ± 3.1 μM in WT; p = 0.0007), with no significant change in peak current density (WT: 128 ± 23 pA/pF; GOF: 103 ± 24 pA/pF, p = NS). In vivo electrophysiology testing using programmed electrical stimulation (PES) shows slowed sinus cycle length (SCL, ms) (WT:120 ± 8.7; GOF: 134.0 ± 19.7, p = 0.04), and prolonged atrioventricular interval (AVI, ms) for GOF (WT: 38.0 ± 4.3; GOF: 46.7 ± 4.3, p = 0.02). Kir6.1 GOF mice show prolonged atrioventricular effective refractory period (AVERP, ms) (WT: 49.2 ± 6.6; GOF: 65.7 ± 8.4, p = 0.0001) and diminished anterograde AV node conduction, as seen by right atrial (RA) pacing resulting in 1:1 capture (pacing cycle length, ms) (WT: 73.0 ± 8.4, GOF: 85.0 ± 5.0, p = 0.02), Wenckebach (WT: 68.0 ± 8.4; GOF: 79.3 ± 6.1, p = 0.049) and 2:1 capture (WT: 54 ± 4.2; GOF: 63.6 ± 6.3, p = 0.049). However, the Kir6.1 GOF mice did not show any differences in either atrial refractory period (AERP, ms) (WT: 37.5 ± 2.7, GOF: 37.1 ± 10.75, p = NS) or ventricular refractory period (VERP, ms) (WT: 45 ± 9.4, GOF: 44.2 ± 7.36, p = NS). In summary, Kir6.1 GOF mice display significant AV nodal conduction abnormalities, providing a potential model of Kir6.1-dependent ERS.
Abstract 18541: Morning Surge of Ventricular Arrhythmias in a New Arrhythmogenic Canine Model of Heart Failure is Associated With Attenuation of Heart Rate and Autonomic Adaptation but Reduced Cardiac Chaos
Authors: Zhu Yujie , Hanafy Mohamed A , Killingsworth Cheryl R , Walcott Gregory P , Young Martin E , Pogwizd Steven M
Published: April 2024

Introduction:
Ventricular arrhythmias in heart failure (HF) can be modulated by autonomic stimulation that is reflected by heart rate variability (HRV). Noninvasive measures of nonlinear dynamics (NLD) assess cardiac chaos, decrease of which can be detrimental in patients with HF. Holter monitoring of HF patients (to assess HRV & NLD) is limited by concurrent medication use. The aim of this study was to assess arrhythmia development, heart rate (HR) dynamics and nonlinear dynamics in a new arrhythmogenic canine model of HF.

Methods:
HF was induced in dogs (N=25) by aortic insufficiency & aortic constriction and assessed by echocardiography. Holter monitoring was performed to study time-of-day variation in arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including Shannon entropy (SE), detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), and correlation dimension (CD)) at baseline, 240 days (240d) and 720 days (720d) after HF induction.

Results:
LV fractional shortening decreased from 43.4±0.7 vs 27.5±0.8 % (p<0.01). Both PVCs and VT showed an early morning rise (2.1-fold & 1.9-fold increase at 6AM-noon vs midnight-6AM). An early morning rise in HR at baseline (ΔHR=13.53±1.42 bpm) was attenuated with development of HF (ΔHR=7.06±0.26 and 6.69±2.44 bpm at 240d & 720d; p<0.01, p<0.05), and was shifted to later in the day. Likewise early morning rise in the ratio of low frequency to high frequency (LF/HF, reflecting the ratio of sympathetic to parasympathetic inflow) at baseline was markedly attenuated with HF (p<0.05 at 240d & 720d), suggesting reduced early morning sympathetic adaptation. For nonlinear dynamics, SE, DFAα1, DFAα2, and CD all decreased with HF (3.04±0.02 vs 2.82±0.07, 0.67±0.03 to 0.46±0.03, 0.69±0.02 to 0.56±0.03, all p<0.01; and 1.88±0.13 vs 1.12±0.25, p<0.05 for baseline vs 720d), indicating decreased cardiac chaos in HF dogs.

Conclusions:
In this new arrhythmogenic canine model of HF, an early morning surge in ventricular arrhythmias was associated with attenuation of morning HR rise and blunting of autonomic oscillation. Measures of nonlinear dynamics reflected a consistent decrease in cardiac chaos and loss of complexity of heart rate that could be contributing to ventricular arrhythmias in this setting.
Abstract 18564: The Interaction of Age and Exercise Capacity in the Prediction of All-Cause Mortality: Data From the FIT Project
Authors: Blaha Michael J , Zhong Yichen , Whelton Seamus , Nasir Khurram , Blumenthal Roger S , Schairer John R , Keteyian Steve J , Al-Mallah Mouaz
Published: April 2024

Background:
Cardiorespiratory fitness, measured clinically as exercise capacity, is a strong predictor of survival. We investigated whether this favorable prognosis is consistent across age groups, particularly in the young and the elderly.

Methods:
This retrospective cohort study included 56,592 patients without known CAD or CHF (median age 53 years old, 51% men, 64% Caucasian) who underwent clinical treadmill stress testing at Henry Ford Hospital between 1991 and 2009. Patients were followed 11.1 ± 4.6 years for the occurrence of all-cause mortality assessed via search of the Death Master File. We first calculated median METS attained on the treadmill by age decile. Then in multivariable models within each age decile, we assessed the prognostic value of: 1) METS above/below median for age; 2) METS by category; and 3) METS as a continuous variable. Models were adjusted for age (continuous), sex, race, SBP/DBP, hypertension, hyperlipidemia, smoking, diabetes, family history of CAD, obesity, COPD and cardiovascular medication use, and indication for stress test.

Results:
Median METS decreased with age, from 13 for patients 80 (p<0.001). Older patients were less likely to achieve target heart rate (p<0.001). There were 6,105 deaths during follow-up. By any measure, increasing exercise capacity was a powerful predictor of survival across all age deciles, although there was an interaction with age (Figure). The relative reduction with increasing fitness was greatest in younger patients and decreased with age. The absolute risk reduction was greatest in older patients.

Conclusion:
Improved cardiorespiratory fitness - as assess clinically by improved exercise capacity - is a powerful predictor of survival across all age groups, although an interaction exists with age. Younger patients have a greater relative reduction in mortality with increasing fitness, while older patients have a greater absolute reduction in mortality.
Abstract 18582: Left Atrial Mechanics in Heart Failure With Preserved Ejection Fraction: Prognostic Utility of Left Atrial Strain and Tissue Doppler A’ Velocities
Authors: Freed Benjamin H , Aguilar Frank G , Maganti Kameswari , Burke Michael A , Shah Sanjiv J
Published: April 2024

Background:
Left atrial (LA) size and function are useful parameters for identifying patients with heart failure and preserved ejection fraction (HFpEF). In HFpEF patients, the prognostic utility of poor LA mechanics (reduced LA strain or reservoir function and/or tissue Doppler imaging [TDI] A’ velocities) has not been explored. We hypothesized that reduced LA strain and A’ velocities are independently associated with adverse outcomes.

Methods:
We prospectively evaluated LA mechanics in 86 patients with HFpEF. All patients underwent comprehensive echocardiography, including Doppler, TDI, and speckle-tracking analysis. The following measurements were made in all patients: TDI systolic (S’), early diastolic (E’), and late diastolic/atrial (A’) velocities as well as LV global longitudinal (LVGLS), RV free wall (RVFWS), and global longitudinal LA peak positive strain. Patients were followed every 3 months for the composite outcome of heart failure hospitalization, cardiovascular hospitalization, and death. Unadjusted and multivariable-adjusted Cox proportional hazards analyses were used to determine the prognostic utility of each parameter.

Results:
The mean age was 63±13 y, 71% female. Patients had objective evidence of HFpEF (LVEF 62±7%; PCWP 25±11 mmHg). Reduced LA peak positive strain and A’ velocities were both associated with adverse outcomes (Figure). LA peak positive strain: unadjusted HR=2.1 (95% CI 1.3-3.2; P=0.001); adjusted HR=1.8 (95% CI 1.1-3.0; P=0.015) after controlling for age, sex, LA volume index, atrial fibrillation, CAD, and GFR. A’ velocities: unadjusted HR 2.1 (95% CI 1.4-3.4; P=0.001); adjusted HR 2.3 (95% CI 1.4-4.0; P=0.002). None of the other parameters (E’, S’, LVGLS, or RVFWS) were significantly associated with adverse outcomes.

Conclusions:
LA reservoir function and TDI A’ velocities are independently associated with adverse outcomes in HFpEF patients.
Abstract 18664: Rate of Accuracy in a System of Cath Lab Activation - The RASCAL Study
Authors: Engvall Gustav , Skibniewski Mikolaj , Janzon Magnus , De Muinck Ebo , Alfredsson Joakim
Published: April 2024

Primary PCI is the recommended treatment of choice for patients with STEMI. Treatment is based on ECG and symptoms alone why concern has been raised about overuse of invasive assessment. We designed this study to evaluate the accuracy of cath lab activation in a STEMI network with prehospital evaluation of ECG.

Method:
We performed an analysis of the STEMI network in Östergötland County, Sweden, including two spoke hospitals and one hub hospital. Patients presenting with definitive or suspected MI either with direct admission to the cath lab or admitted to a CCU between December 1, 2009 and November 30, 2011 were included. Patients were identified in the Swedish National Quality Registry (SWEDEHEART), and we then reviewed medical records including ECG, cardiac enzyme levels and clinical assessment to decide if patients had a STEMI.

Results:
Of 675 patients admitted directly to the cath lab, 554 were judged as STEMI resulting in a general accuracy of 82%. We then measured the accuracy for the different ways of arrival at the cath lab, resulting in 89% (355/399) for patients admitted from the ambulance, 74% (140/190) for patients admitted from emergency wards, and 69% (59/86) for patients admitted from any other hospital ward. Of all 652 patients judged as STEMI, 584 (90%) were either directly admitted to the cath lab or referred from the ambulance directly to the CCU of the hub hospital for clinical evaluation. The remaining group of 68 patients contained 22 patients presenting with symptom onset more than 12 hours before their first medical contact, and 26 patients with comorbidity as contraindication for primary PCI.

Conclusion:
In our STEMI network we found a high rate of accuracy for cath lab activation at 82%, without reducing direct admittance of STEMI patients. High accuracy for cath lab activation with maintained high rate of direct admittance saves time, money and myocardium.
Abstract 18774: Electromechanical and Scar-Mediated Interactions in Cardiac Resynchronization Therapy Based on Cardiac Magnetic Resonance
Authors: Bilchick Kenneth C , Kuruvilla Sujith , Hamirani Yasmin , Ramachandran Raghav , Parker Katherine M , Clarke Samantha A , Darby Andrew E , Mason Pamela , Ferguson John D , Mangrum J M , Malhotra Rohit , DiMarco John P , Holmes Jeffrey , Salerno Michael , Kramer Christopher M , Epstein Frederick H
Published: April 2024

Background:
Mechanical dyssynchrony (MD), left ventricular (LV) lead electrical timing relative to QRS onset (QLV, or normalized for QRS width as LVLED), percent LV scar volume (PSV), and scar at the LV lead position (LP-SCAR) are important determinants of the response to cardiac resynchronization therapy (CRT), but their interactions are not well understood.

Objective:
We sought to determine these electrical, mechanical, and scar-mediated interactions in a clinical CRT cohort.

Methods:
Patients undergoing CRT first had cardiac magnetic resonance (CMR) with cine DENSE (displacement encoding with stimulated echoes) and late gadolinium enhancement (LGE), echocardiography, and cardiopulmonary exercise testing, followed by repeat testing at 6 months. Factors influencing CRT response (defined as a 15% reduction in LVESV) and clinical events up to 5 years after CRT were analyzed using logistic and Cox proportional hazards regression, respectively.

Results:
The 70 patients studied (66 ± 13 years old, 26% F) had an LVEF of 22.0 ± 8.2%, and 51% had positive LGE (PSV 10.0% [IQR 6.3%-16.7%]). 36 (51%) were CRT responders, 16 (23%) died during follow-up, 24 (34%) had the combined endpoint of heart failure hospitalization (HFH) or death, and 10 (14%) had sustained ventricular tachycardia (VT). Predictors of CRT nonresponse included CURE ≥ 0.70 (OR 73.2, 95% C.I. 8.8-605.8), QLV ≤ 90 ms (OR 9.0 [2.6-31.0]), and LP-SCAR (OR 2.9 [1.1-7.6]). The logistic model with these 3 covariates was highly predictive of CRT nonresponse (AUC 0.933; p < 0.001). Electromechanical factors also predicted clinical events. The best Cox model for death consisted of CURE ≥ 0.70 (HR 3.88 [1.38-10.88]) and LVLED ≤ 0.50 (HR 5.12 [1.79, 14.69]), while LVLED ≤ 0.50 also predicted the combined endpoint of HFH or death (HR 3.64 [1.57, 8.46]). Of note, LP-SCAR and CURE influenced VT events (p=0.07).

Conclusions:
The clinical course after CRT-D implantation reflects complex interactions between electrical, mechanical, and scar-mediated factors that can be understood well with CMR. A model combining CMR-derived mechanical and scar-mediated factors with electrical parameters accurately predicts both CRT nonresponse and adverse clinical events, such as heart failure hospitalization and death.
Abstract 18776: Endothelial Function is Not Affected by Fresh or Storage-Aged Autologous Blood Transfusions in Healthy Individuals
Authors: Ashraf Khuram , Smith Graham , Sher Salman , Neuman Robert , Roback John , Quyyumi Arshed
Published: April 2024

Background:
Red cells play a modulating role in nitric oxide (NO)-mediated signaling and hypoxic vasodilation that may be influenced by blood transfusions, particularly with storage-aged blood (pRBCs). We have shown that brachial artery endothelial function, measured as flow-mediated vasodilation (FMD) is adversely affected in patients receiving aged compared to fresh pRBCs. Here we investigated endothelial NO activity in healthy subjects receiving autologous pRBCs with the hypothesis that aged pRBCs will impair endothelial conductance vessel and microvascular function.

Methods:
Sixteen healthy participants (aged 31±10 years, 38% female) were transfused 1 unit of fresh (aged 3-7 days) and subsequently with storage-aged (35-42 days) autologous pRBCs. Endothelial function was measured using FMD and reactive hyperemia index (RHI), a measure of microvascular function, was measured using pulsatile arterial tonometry (Itamar Inc., n=7), before, 1 hour, and 24 hours after transfusion. Data were analyzed by repeated measures ANOVA.

Results:
Hemoglobin was similar before both transfusions (p=0.066) and increased by 1.02±1.0 g/dL (±SD) and 1.2±1.2 g/dL with fresh and storage-aged transfusions, respectively. The FMD before, 1 hr and 24 hr after transfusion of fresh pRBCs (7.8±6.9%, 8.2±4.8% and 6.9±4.3%) or stored pRBCs (7.1±5.5%, 7.4±4.7% and 8.5±4.9%) was similar,( p=0.45). The RHI before, 1 hr and 24 hr after transfusion of fresh pRBCs ( 2.45±0.23, 2.26±0.08 and 2.26±0.21) showed no significant changes, p=0.87 or stored pRBCs ( 2.25±0.67, 2.27±0.53 and 2.22±0.26, p=0.42).

Conclusions:
Vascular NO activity and microvascular dilatory capacity are not impaired by transfusion of fresh or storage-aged autologous pRBC in healthy individuals, unlike findings with allogeneic transfusions in patients. These differences suggest that the risks of aged blood transfusions are likely to be greater in patients with vascular disease who have underlying endothelial dysfunction.
Abstract 18783: Hospitalization for Atrial Fibrillation Increases in the Elderly: Recent Analysis From TuRkish Atrial Fibrillation Data Base
Authors: Evranos Banu , Aytemir Kudret , Yavuz BÜnyamin , Oto Emre , Ata Naim , Katircioglu öztÜrk Deniz , Karaagaoglu Ergun , GÜvenir Altay , özcan SelÇuk , Ertugay Emre , Koselerli Rasim , BÜrkan AbdÜlkadir , Kuruca Mustafa , Gokalp Ilhan Yadigar , Camm John A , Oto Ali M
Published: April 2024

Objective:
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhytmia and constitutes a major public health problem. Patients with AF often have a variety of co-morbidities and need frequent hospitalizations. The present retrospective cohort study used medical claims data to evaluate the rates of hospitalization in patients with AF in Turkey.

Methods:
We analyzed the records of patients over the age 18 who had the diagnosis of non-valvular atrial fibrillation (AF) according to ICD-10 code I48 from a claims and utilization management system called MEDULA which processes claims for all health insurance funds in Turkey since 2007. Covering close to 100 % of the population, MEDULA is comprised of pharmacy, inpatient, outpatient and laboratory claims and covers 23,500 pharmacies, 20,000 general practitioners, 850 government hospitals, 60 university hospitals and 500 private hospitals. In this study we have used completely anonymized data

Results:
Of an eligible study population of 402674 patients with AF (mean age 68,3 years, 44,2% men), 102334 patients (25,4%) were hospitalized, 68951 (17,1%) were rehospitalized. Seventy seven percent of females and sixty seven percent of males older than 65 years were hospitalized.

The most common admission diagnoses were congestive heart failure (47,1%), ischemic stroke or transient ischemic attack (21,1%), gastrointestinal bleeding (5%), hemorrhagic stroke (1,5%) and thromboemboli (1,4%). Twenty nine percent of coumadin users, 27,2% of aspirin users, 23,9% klopidogrel users 23,3 % of clopidogrel+aspirin users and 21,1% of none user patients were hospitalized. When we performed time-to event analysis we found that the earliest hospitalizations were for coumadin users due to bleeding (p<0.001).

Conclusions:
Elderly patients, especially females, with AF underwent frequent hospitalization both for CV and non-CV causes. Anticoagulant therapy with warfarin did not reduce hospitalization rate as a result of increased hospitalizations due to bleeding complications. Therefore, measures that lower bleedings and inpatient readmission rates may reduce the increasing cost of treating patients with AF and reduce the burden on health economics.
Abstract 18832: High-Resolution, Whole Heart T1 Mapping in a Chronic Atrial Fibrillation Model
Authors: Kholmovski Eugene G , Kim Daniel , Vijayakumar Sathya , Ranjan Ravi , Dosdall Derek , Higuchi Koji , MacLeod Rob , Marrouche Nassir F
Published: April 2024

Introduction:
Cardiac fibrosis is a marker of adverse remodeling of the heart. Cardiac T1 mapping is the only non-invasive method to assess diffuse myocardial fibrosis. However, existing T1 mapping techniques are not applicable for whole heart mapping with adequate spatial resolution to accurately evaluate the thin atrial wall. We have developed a novel, high-resolution, whole heart T1 mapping technique which can be used to characterize fibrosis in all cardiac chambers simultaneously.

Methods:
We applied the whole heart T1 mapping technique to study fibrosis progression in a canine, chronic atrial fibrillation (AF) model. Dogs (n=8) were subjected to rapid atrial pacing (RAP) and underwent baseline (n=8) and 8-month RAP MRIs (n=4) to evaluate myocardial fibrosis. Whole heart T1 mapping was performed on a 3 Tesla MRI scanner during slow contrast infusion (0.05 micromol/kg/sec of Gd-BOPTA). Spatial resolution of T1 mapping scans was 1.25x1.25x2.5 mm. T1 mapping was performed at least 30 minutes after start of slow contrast infusion to achieve steady-state for contrast distribution.

Results:
Figure 1a shows representative image of cardiac T1 maps that visualize the myocardium of all cardiac chambers clearly. Myocardium of LV and LA has similar T1 values in baseline scans (p=NS), which decreased significantly in the LV and LA 8 months after initialization of RAP (p<0.05, Fig. 1b). This change in T1 indicates increased fibrosis of left ventricle and atrium after 8 months of AF.

Conclusions:
High-resolution, whole heart T1 mapping technique can be used to non-invasively assess diffuse myocardial fibrosis in all cardiac chambers. T1 mapping indicates that 8-months RAP results in increased LV and LA fibrosis.
Abstract 18841: Outcomes of Septal Myomectomy in the United States: A 13-year perspective
Authors: Panaich Sidakpal S , Mehta Kathan , Patel Nileshkumar J , Shah Neeraj , Chothani Ankit , Grover Peeyush , Singh Vikas , Rathod Ankit , Pant Sadip , Bhalara Vipulkumar , Savani Ghanshyambhai T , Deshmukh Abhishek , Mehta Jay L , Badheka Apurva O
Published: April 2024

Background:
Septal Myomectomy (MM) is the primary modality for left ventricular outflow tract (LVOT) gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM) patients with refractory symptoms. Extended follow-up data for MM from a large multi-center registry is sparse.

METHODS:
We queried the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) between 1998 and 2010 using ICD9 procedure code 37.33 for MM. Only adult patients with HOCM (ICD-9-CM code 425.1) were included. Out of these, patients with any arrhythmia diagnosis were excluded. The NIS represents 20% of all hospitals in the US. We defined severity of co-morbidities using Deyo modification of Charlson co-morbidity index (CCI), where higher scores (0-33) represent increasing burden. Three level hierarchical mixed models were created to identify independent multivariate predictors of complications and mortality for MM. Hierarchical mixed effects linear regression models were used to evaluate cost of hospitalization and length of stay (LOS).

RESULTS:
The overall mortality was 5.9%. 5.4% of the patients had significant post-operative bleeding necessitating transfusion while 8.7% had complete heart block requiring a pacemaker. Increasing CCI was associated with a higher rate of complications and mortality (OR 2.42, 95% CI (1.17-4.98), p-value 0.02). The mean cost of hospitalization was $40,444 +/- 1,786 while the average LOS was 8.69 +/- 0.35 days. Occurrence of any post-operative complications was associated with an increased cost of hospitalization (+$33,870, p<.01) and LOS (+6.1 days, p<.01).

Conclusions:
We observed a relatively higher mortality rate for surgical MM than published literature with cardiac complications being most common specifically complete heart block. Increasing severity of co-morbidities was predictive of poorer outcomes while a higher burden of post-operative complications was associated with a higher cost of hospitalization and LOS.
Abstract 18886: A Thought-Controlled Immersive Virtual Reality Platform for Motor Learning Applied With Cortical and Basal Ganglia Stroke Survivors
Authors: Doud Alexander J , Cassady Kaitlin , Grande Andrew , He Bin
Published: April 2024

An immersive, virtual reality platform using a sensorimotor rhythm- brain-computer interface was used in a cohort of 6 hemiparetic stroke survivors. The subject’s controlled the system with accuracies of up to 81% in a binary classification task. The 3D virtual reality platform displayed photorealistic human hands moving in coordination with the patient’s thoughts, overlaying the patient’s own hands.

Background:
The National Stroke Association estimated that stroke management cost the United States 73.7 billion dollars in 2010. Evidence based management of the patient’s rehabilitation relies heavily on constraint induced movement therapy, and close work with a physical therapist. Approaches that reduce the burden of retraining the motor system from both a patient and provider standpoint could be of substantial impact.

Methods:
The system was presented to 6 subjects with histories of basal ganglia or cortical stroke leading to unilateral hemiparesis. The patient’s viewed the stimulus using 3D anaglyph glasses to produce the illusion that they were seeing their own arms through the lid of the stimulus box. EEG data were acquired at 1000Hz during all experimental trials.

Results:
Using the system described, the subject’s were able to achieve control accuracies as high as 87.4% (Cursor) or 81% (VR) in a binary classification task (reach left or right) and showed progression of skill in as little as three, two-hour experimental sessions. A comparison of this system to a standard cursor feedback control task suggests that use of the immersive virtual reality system allowed subjects to produce more sustained and homogenous motor imagery as assessed by spectral analysis of subject EEG.

Discussion:
Pairing the motor imagination task with the virtual reality photorealistic motor feedback promotes a consistent and sustained motor imagery signal as compared to a standard cursor control task. Recent controlled trials on the efficacy of brain-computer interface show statistically significant changes in Fugl-Meyer motor scores when using a sensorimotor rhythm based BCI with physical therapy. By creating a training platform that requires low caregiver overhead, the system could serve as an affordable rehabilitation option in the management of stroke.
Abstract 18906: Combining Perindopril With a Calcium Channel Blocker and a Lipid Lowering Agent Significantly Decreases Mortality: A Subgroup Analysis of Europa
Authors: Bertrand Michel , Mourad Jean-Jacques
Published: April 2024

Background:
Management of patients with stable ischemic heart disease (IHD), in addition to heart rate control and antiplatelet therapy, relies on the administration of blood pressure lowering therapies and lipid normalization. However, the ACTION trial revealed that a strategy with a calcium channel blocker (CCB) and a lipid lowering therapy (LLT) alone, on top of conventional care, was not sufficient to provide further protection regarding cardiovascular events and death. Since a medical need remains for CCB, mainly in case of angina, we investigated if, as globally recommended by current guidelines for IHD patients, the addition of an ACE inhibitor would provide additional benefit in this specific population.

Methods:
The EUROPA trial evaluated the cardioprotective effect of perindopril in a low-risk population with coronary artery disease but no signs of heart failure for a mean follow-up of 4.2 years (75% of class I, 21% with class II, 3% Class III and 1% class IV angina status). The database was reanalyzed to compare the benefit of the addition of perindopril or placebo in patients receiving a CCB/LLT strategy at baseline and all along the trial (1056 patients).

Results:
Patients receiving perindopril on top of a CCB and a LLT displayed a significant 46% relative reduction of the primary endpoint (p=0.023), a composite of cardiovascular death, myocardial infarction and cardiac arrest, compared to those only having CCB/LLT. In addition, the triple combination allowed relative risk reductions of respectively 58% (p=0.027) and 71% (p=0.028) for all-cause and cardiovascular mortality. Non-significant decreases in myocardial infarction (28%) and heart failure (41%) seemed to support at least partly the positive impact on mortality.

Conclusion:
The addition of an ACE inhibitor to a CCB/LLT strategy clearly demonstrated a reduction of mortality in this post-hoc analysis of EUROPA and confirmed results previously obtained in high-risk hypertensive patients in the ASCOT study.