bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17543: The Chicken or the Eggs? Examining the Causal Relationship Between the Development of Atrioventricular Valve Regurgitation and Ventricular Dysfunction in Patients With Functionally Single-Ventricle Physiology
Authors: Kotani Yasuhiro , Chetan Devin , Senthilnathan Selvi , Saedi Arezou , Caldarone Christopher A , Van Arsdell Glen S , Mertens Luc , Honjo Osami
Published: July 2021

Introduction:
Development of atrioventricular valve regurgitation (AVVR) with or without ventricular dysfunction (VD) often occurs during the first 6 months of life and has a significant impact on outcomes for single-ventricle patients. Yet, it is not well known whether AVVR causes VD or vice versa. Thus, we sought to identify the timing and causal relationship between AVVR and VD.

Methods:
Among 156 consecutive single-ventricle patients who had staged palliation (2005- 2012), 28 who had AVV repair at the time of stage II (n=24, 86%) or inter-stage (n=4, 14%) were reviewed. Diagnosis included HLHS in 17 (61%) patients, tricuspid atresia in 2 (7%), and others in 9 (32%). Ventricular morphology was left-dominant in 6 (21%) patients and right-dominant in 22 (79%). AVV morphology included mitral in 6 (21%) patients, tricuspid in 18 (64%), and common in 4 (14%). Serial echocardiograms were reviewed to identify the timing of development of AVVR and/or VD.

Results:
After stage I palliation, ventricular end-diastolic dimension (VEDD) z-score significantly increased from 4.01 to 5.69 (p<0.01) AVVR (Figure). By the time of stage II palliation, VEDD further increased and subsequent AVV annular dilation occurred, resulting in 23 patients with significant AVVR. None of the patients, however, had significant VD before stage II palliation/AVV repair, but 9 patients developed significant VD after AVV repair.

Conclusions:
Ventricular dilation occurred immediately after stage I palliation and continued until stage II palliation. Secondary annular dilation occurred inter-stage and this further triggered the development of AVVR. Tangible ventricular dysfunction was not seen before AVV repair, however, important ventricular dysfunction was unmasked after volume unloading surgery. Heart failure management and early intervention to significant AVVR may reduce the incidence of ventricular dysfunction following AVV repair.
Abstract 17571: Use of Goal Directed Transesophageal Echocardiography in the Arresting Patient
Authors: Ahsan Shoeb , Arntfield Robert
Published: July 2021

Background:
With outcomes from cardiac arrest remaining generally poor, there is an urgency to evaluate interventions that allow physicians to manage cardiac arrest more effectively. Transesophageal echocardiography (TEE) can be used at the point of care in a goal-directed manner and can rapidly provide a flurry of data on cardiac structure and function. TEE in the arrested patient is unobtrusive to resuscitation and can provide vital information regarding the potential etiology of arrest, guidance of certain procedures and prognosis. As such, some centers, including our own, have adopted increasingly routine use of TEE in this context. Given the paucity of data in this area, we sought to examine the influence of point-of-care TEE conducted by emergency physicians or intensivists at our institution for patients in or immediately after cardiac arrest.

Methods:
Goal-directed TEE in the emergency department (ED) or intensive care units (ICU) and their reports were archived in a dedicated point-of-care ultrasound imaging database. We conducted a search of all TEE examinations archived between December 2012 and April 2015 in the peri-arrest period (in or immediately after cardiac arrest). The details from reports were abstracted. TEE-directed management changes were noted when recommendation(s) regarding initiation/escalation of inotropes, fluid administration, termination of resuscitation or surgical procedure were featured in the TEE report.

Results:
A total of 57 peri-arrest TEE exams were identified (21 in ICUs and 36 in EDs). Goal-directed TEE changed management in 61.4% of cases. TEE facilitated the escalation/initiation of inotropes (35.3%), decision to terminate resuscitation (32.4%), guided fluid management (23.5%) and surgical procedures (8.8%). TEE studies altered management in 66.7% of cases in the Intensive Care Unit and in 58.3% of cases in the Emergency Department.

Conclusions:
Goal-directed TEE performed by emergency physicians or intensivists has an impact on management on patients in the peri-arrest setting the majority of the time. Given the lack of reliable diagnostic and therapeutic options in arresting patients, a larger study examining the influence of goal-directed TEE on patient outcomes in cardiac arrest should be carried out.
Abstract 17580: Angina Pectoris in Diabetic Patients: Insights From the Duke Databank for Cardiovascular Disease
Authors: Mentz Robert J , Banks Adam Z , Broderick Samuel , DeVore Adam D , Chiswell Karen , Shaw Linda K , Fiuzat Mona , Velazquez Eric J , Felker G. Michael , O'Connor Christopher M
Published: July 2021

Background:
Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The association between the presence or absence of AP in DM patients with CAD is unknown.

Methods:
We analyzed DM patients with obstructive CAD who underwent coronary angiography at Duke University Medical Center from 2002 to 2011 and compared patients without AP to those with AP. DM and AP were defined based on physician-obtained past medical history at catheterization. Patients were categorized as no AP, atypical AP or typical AP within the 6 weeks prior. We assessed the association with subsequent cardiovascular (CV) death/CV hospitalization and all-cause mortality in patients with no or atypical AP relative to typical AP using multivariable Cox proportional hazards analysis.

Results:
In the Duke Databank, 5550 patients met criteria for inclusion and 1732 (31%) had no AP, 1075 (19%) had atypical AP and 2743 (50%) had typical AP. Those without AP more often had a prior MI and lower ejection fraction, but had similar HbA1c values compared to those with atypical AP or typical AP. Over a median follow-up of 5.4 years (IQR: 2.9-8.8), the lack of recent AP was associated with increased risk for outcomes (Table). Following adjustment, the lack of recent AP was independently associated with increased mortality compared to typical AP.

Conclusions:
In DM patients with CAD, the lack of AP was associated with increased mortality, but similar risk for CV events compared to patients with typical AP. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival.
Abstract 17598: More Than One in Five Older Veterans are Hospitalized for Bleeding Following Initiation of Warfarin for Atrial Fibrillation
Authors: Dodson John A , Petrone Andrew , Gagnon David , Tinetti Mary E , Krumholz Harlan M , Gaziano J. Michael
Published: July 2021

Introduction:
Clinicians are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation (AF) due to concerns over bleeding risk.

Hypothesis:
As many data on bleeding events are from trials of rigorously selected patients, we hypothesized that major bleeding events (requiring hospitalization) would be more common than previously reported.

Methods:
We created a retrospective cohort of 31,951 Veterans with AF aged ≥75 years who were new referrals to VA anticoagulation clinics (warfarin) from 1/1/02 - 12/31/12. Patients with comorbid conditions requiring warfarin (e.g. pulmonary embolus) were excluded. Data were extracted from the VA electronic medical record and linked with Medicare claims data for subsequent hospitalizations. The primary outcome was any hospitalization for bleeding. We identified bleeding subtypes by source, and compared characteristics of patients with and without bleeding hospitalizations.

Results:
Mean population age was 81.1 years, 98.1% were male, and 8.4% were nonwhite. Over a median follow-up period of 2.62 years, 7288 patients (22.8%) were hospitalized for bleeding. There were 12,004 total bleeding events; overall, 980 (13.4%) patients experienced multiple events. The most common bleeding sources (first event) were gastrointestinal (50.8%), genitourinary (21.6%), and intracranial (9.4%) (Figure). The median time to first bleeding event was 1.59 years. Patients hospitalized for bleeding were more likely to have coronary disease (48.4% vs. 40.9%, P<0.01); COPD (28.4% vs. 24.7%, P<0.01); chronic kidney disease (17.8% vs. 16.0%, P<0.01); CHF (34.7% vs. 29.5%, P<0.01), and labile INR (63.3% vs. 53.7%, P<0.01). The rate of hospitalization for stroke over the same time period was 5.0%.

Conclusions:
After initiating warfarin, over one in five older Veterans are hospitalized for bleeding, most commonly from a gastrointestinal source. Comorbidity burden and labile INR place these patients at increased risk.
Abstract 17607: MicroRNA Expression Profiles in Endomyocardial Biopsies From Patients With Myocarditis - Association With Left Ventricular Function and Clinical Events
Authors: Besler Christian , Urban Daniel , Watzka Stefan , Klingel Karin , Kandolf Reinhard , Schuler Gerhard , Adams Volker , Lurz Philipp
Published: July 2021

Background:
Myocarditis represents an important cause of chronic dilated cardiomyopathy. Predicting the clinical course of patients with myocarditis is difficult and the prognostic value of current histological markers remains controversial. We tested whether expression of selected microRNAs (miRNAs) in endomyocardial biopsies is related to left ventricular (LV) function and clinical events in patients with myocarditis.

Methods:
Endomyocardial biopsies were obtained from patients with non-inflammatory dilated cardiomyopathy (n=22) and histologically proven myocarditis (n=81). Based on literature search, we predefined a set of 6 miRNAs implicated in inflammation (miR-155, miR-146b), heart failure (miR-21, miR-133a), endothelial cell (miR-126) and skeletal muscle function (miR-206). Expression of these miRNAs in endomyocardial biopsies was quantified by RT-PCR.

Results:
Expression of miR-133a, miR-206 and miR-155 was markedly upregulated in endomyocardial biopsies from patients with myocarditis as compared to patients with dilated cardiomyopathy, irrespective of viral or non-viral etiology. Levels of miR-133a (R=0,68, P<0,01) and miR-155 (R=0,65, P<0,01) significantly correlated with CD68 cell count in endomyocardial biopsies from patients with myocarditis. Patients with myocarditis and preserved LV function at study entry displayed higher endomyocardial expression of miR-133a than patients with reduced LV function. Higher expression levels of miR-133a were associated with improved LV function during a mean follow-up of 3,1 years. Importantly, in a Kaplan-Meier estimate, patients with myocarditis and miR-133a levels above median showed longer survival free of death and malignant arrhythmias.

Conclusion:
The present study demonstrates that in a predefined set of miRNAs, relevant to cardiovascular pathology, endomyocardial miR-133a levels correlate with macrophage infiltration, improved LV function and clinical outcome in a comparatively large cohort of patients with histologically proven myocarditis. miR-133a may serve as a potential novel biomarker and therapeutic target in human myocarditis.
Abstract 17616: Recurrent Copy Number Variants are Enriched in Bicuspid Aortic Valve and Affect Cardiac Developmental Genes
Authors: Prakash Siddharth , Hanchard Neil A , Guo Dong-Chuan ,   GenTAC Consortium,   Bicuspid Aortic Valve Consortium, McBride Kim L , Belmont John W , Body Simon C , Milewicz Dianna M
Published: July 2021

Introduction:
Bicuspid Aortic Valve (BAV) is the most common adult congenital heart defect. The spectrum of BAV ranges from chromosomal disorders such as Turner syndrome to sporadic isolated disease of unknown cause. We hypothesized that genomic copy number variants (CNVs) contribute causally to BAV.

Methods:
We conducted genome-wide SNP array analyses of BAV cases in six European American cohorts (3533 total subjects, 31% BAV, 45% female, ages 1-94 years) with sporadic or familial thoracic aortic aneurysms (37%), congenital left ventricular outflow tract obstructive defects (47%) or Turner syndrome (10%). Genotyping was performed on Illumina Omni microarrays, using PennCNV, Nexus and CNVPartition for CNV detection. Thresholds were set at a minimum of six consecutive SNPs for CNVs that were identified by at least two algorithms and intersect with known genes. A total of 1380 BAV cases were compared to 1065 cases with tricuspid aortic valves and 7013 dbGAP controls without a history of cardiovascular disease using association tests for rare CNVs as implemented in PLINK. Pathway and functional analyses of rare CNVs were performed using the ToppGene analysis suite. Genes within rare CNVs were prioritized by their connectivity to genes in the Notch pathway or established roles in human or animal cardiac phenotypes.

Results:
We identified 12 rare CNV regions that were recurrent in at least three different BAV groups and were absent or extremely rare (frequency <0.1%) in controls. Four of these regions involved genes that cause aortic valve or outflow tract defects when mutated. The largest and most prevalent of the recurrent CNVs were at Xq28 (four duplications and two deletions), at 22q11.21, telomeric to the DiGeorge syndrome critical region (four deletions, three duplications), and at 7p15.2 (four deletions). The percentage of individuals harboring rare CNVs was significantly greater in BAV cases than in tricuspid or dbGAP controls.

Conclusions:
We identified multiple loci affected by rare CNVs in BAV subjects, demonstrating the genetic heterogeneity of BAV and implicating alterations of candidate genes at these loci in the pathogenesis of BAV.
Abstract 17617: Post-cardiac Arrest Mortality Rates With Different Levels of Targeted Temperature Management within Patient Illness Severity Categories
Authors: Rittenberger Jon C , Coppler Patrick , Guyette Francis X , Callaway Clifton W , Elmer Jonathan , Doshi Ankur A , Slowey Daniel ,   The Post Cardiac Arrest Service
Published: July 2021

Introduction:
There are 380,000 out-of-hospital cardiac arrests (OHCA) in the United States each year. Controlling temperature improves outcome. It is unknown if different illness severity may require different goal temperatures.

Hypothesis:
When controlling for Pittsburgh Cardiac Arrest Category (PCAC), there is no difference in mortality between treatment at 33°C or 36°C.

Methods:
Review of existing QI database between 12/2013 and 12/2014. We abstracted location of arrest, primary rhythm, initial illness severity (PCAC), survival, presence of fever and neurologic outcome. We defined four categories of PCAC: I) awake, II) coma + mild cardiopulmonary dysfunction, III) coma + moderate-severe cardiopulmonary dysfunction, and IV) coma without brainstem reflexes. Good neurologic outcome was defined as a CPC of 1-2 or mRS of 0-2. Chi-squared analysis compared the cohorts. Logistic regression was used to determine factors associated with survival and good neurologic outcome. Candidate variables included age, primary rhythm of arrest, PCAC, development of fever in the first 48 hours and goal temperature.

Results:
Of 165 patients studied, 102 (62%) were male, with a mean age of 58 (SD = 18). The most common primary rhythm was VF/VT (53; 32%). Goal temperature of 36°C was used in 92 (56%), temperature of 33°C was used in 60 (36%), and no temperature management was used in 13 (36%). Fever was more common in patients treated with goal temperature of 36°C (28% vs. 7%; p=0.004).

Survival did not differ between temperature management strategies (PCAC II 33°C: 2 (50%), PCAC II 36°C 24 (80%); PCAC III 33°C: 3 (75%), PCAC III 36°C: 6 (43%); PCAC IV 33°C: 4 (8%), PCAC IV 36°C: 7 (18%). In the multivariate analysis, only PCAC was associated with survival (OR 0.35; 95% CI 0.23, 0.55), good CPC (OR 0.30; 95% CI 0.15, 0.61) and good mRS (OR 0.33; 95% CI 0.16, 0.67).

Conclusions:
After accounting for PCAC, survival and good neurologic do not differ between temperature management strategies of 33°C or 36°C. Fever is more common in patients treated at goal temperature of 36°C. We noted a systematic trend towards application of 33°C to higher illness severity patients. This bias needs to be robustly controlled for in future observational work to prevent confounding by indication.
Abstract 17683: LCZ696 vs. ACEI/ARB for Hypertension: A Meta-analysis of Randomized Controlled Trials
Authors: Alrifai Abdulah , Al Halabi shadi , Chait Robert
Published: July 2021

Introduction:
LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and Neprilysin. The use of LCZ696 in Heart Failure is promising compared to ACEI or ARB. The use of LCZ696 for blood pressure has been studied but controversial. We performed a meta-analysis of randomized controlled trials (RCTs) comparing LCZ696 to ACEI/ARB for lowering systolic blood pressure effect.

Objectives:
To assess the efficacy of LCZ696 on systolic blood pressure in comparison to angiotensin-converting-enzyme inhibitor (ACEI)/Angiotensin II receptor antagonist (ARB).

Methods:
We searched PubMed, Medline, Embase and Cochrane for prospective RCTs that compared LCZ696 versus ACEI or ARB in patients with established diagnosis of essential hypertension. Trials that included patients with essential hypertension with or without heart failure were randomized to either LCZ696 or ACEI or ARB, and that also reported at least one of the studied outcomes were included. Study quality was assessed using the Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mean differences were calculated using the random effect model.

Results:
Three RCTs met our inclusion criteria and included 8996 patients who had mild-moderate essential hypertension and were between18-75 years. They were randomized to LCZ696 versus ACEI or ARB. The use of LCZ696 was associated with improved systolic blood pressure control when compared to the control group (MD -3.89; 95% CI -7.75, -0.04; P=0.05).

Conclusions:
Our findings suggest that the use of LCZ696 in hypertensive patients provides better reduction of blood pressure when compared to an ACEI or an ARB.
Abstract 17689: Omega-3 Fatty Acid Supplementation Reduces Inflammation and Improves Physical Function in Patient With Coronary Artery Disease
Authors: Alfaddagh Abdulhamied , Welty Francine K
Published: July 2021

Introduction:
Poor physical function impairs fitness and is associated with worse cardiovascular outcomes and all-cause mortality. Arthritis and joint dysfunction limit physical function in coronary artery disease (CAD) patients.

Hypothesis:
Omega-3 fatty acids (FA) improve physical function in CAD patients through reducing inflammation.

Methods:
We randomized 249 subjects with stable CAD to 3.6 of omega-3 FA (1.86 g of eicosapentaenoic acid + 1.5 g of docosahexaenoic acid) per day or no omega-3 (control) for one year. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to evaluate pain, stiffness and physical function at baseline and one year follow-up. Inflammation was assessed by total white blood cell (WBC) count and its subsets as well as urine microalbumin-creatinine ratio (MCR).

Results:
Mean age was 63.0 ± 7.58 years; 17% were women. Controls had worsening stiffness (% Δ = 8.4%; p = 0.036) at 1 year follow-up while those on omega-3 FA had no change (% Δ = 0.4%, p = 0.886 - see Table)(a lower percent change indicates better functioning). Compared to controls, those on omega-3 FA had better physical function (% Δ = 8.5% vs. -2.8%, p = 0.011), and total WOMAC scores (% Δ = 7.8% vs. -2.5%, p = 0.011) and a significant decrease in WBC (% Δ = -3.5 vs. -9.4%; p=0.009) and neutrophils (% Δ = -3.5% vs. -11.6%; p=0.005) at one year follow-up. MCR significantly worsened only in the control group (% Δ = 53.3%, p = 0.037) at one year follow-up (p-value for control vs. omega-3 FAs groups = 0.026). Monocytes were decreased in the omega-3 FAs group at one year compared to baseline (% Δ = -11.1%, p < 0.001) and directly correlated with physical function and total scores (p = 0.033 and p = 0.024, respectively).

Conclusions:
Omega-3 FAs attenuate worsening of physical function over a one year period in CAD patients possibly mediated through an anti-inflammatory effect. Therefore, omega-3 FA may benefit CAD patients by improving their physical function.
Abstract 17692: Arrhythmogenic Mechanisms in Hemorrhagic Shock-induced Heart and Comparable Effect of Different Hemoglobin Concentration of Two Artificial Oxygen Carriers
Authors: Takase Bonpei , Higashimura Yuko , Tanaka Yoshihiro , Hashmoto Kenichi
Published: July 2021

Lethal ventricular arrhythmias (VT/VF) are serious complications after resuscitation of severe hemorrhagic shock (HS). To investigate mechanisms of arrhythmogenesis after HS and a role of two different concentration of oxygenated liposome-encapsulated human hemoglobin (LHb [Hgb=6g] or HbV [Hgb=10g]), optical mapping analysis (OMP) and electrophysiological study (EPS) were performed using rat HS model. HS was induced by withdrawing 30% blood from aorta (shock alone). Rats were resuscitated by transfusing saline, 5% albumin (5%ALB), LHb, HbV or oxygenated autologous washed red blood cells (wRBC: n=7, per group). After excising heart, OMP and EPS were performed in isolated Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay (VCD) with impaired action potential duration dispersion (APDd) in both ventricles in shock alone, saline, and 5%ALB whereas VCD and APDd were substantially attenuated in LHb, HbV or wRBC (a). VT/VF was easily provoked by burst pacing stimulus to LV in saline and 5%ALB while few VT/VF was induced in LHb, LbV or wRBC (b).

Conclusion:
Ventricular electrical remodeling of abnormal VCD and APDd after HS causes VT/VF. LHb, LbV and wRBC comparably prevent VT/VF possible by attenuating ischemia-reperfusion injury in HS. Especially, even low concentration of hemoglobin in LHb is comparably effective with closely normal concentration of HbV.
Abstract 17705: Overestimation by Common Cardiovascular Risk Scores Amongst Primary Prevention Patients in the Cholesterol Treatment Trialists’ Collaboration (CTTC) Database
Authors: Fulcher Jordan , O'Connell Rachel , Keech Anthony ,   Cholesterol Treatment Trialists' Collaboration
Published: July 2021

Introduction:
Cardiovascular risk calculators are increasingly used to guide treatment recommendations. We examined the accuracy of popular risk calculators amongst primary prevention, control arm patients of statin trials in the CTTC database

Methods:
Using individual patient data we compared our previously modelled and highly correlated (r=0.997) five year derived vascular risk of participants in the control arms of 22 randomised statin trials without known vascular disease at baseline with 5 year equivalent Framingham, QRisk2 and Pooled Cohort Equations (PCE) scores for each patient.

Results:
Data was available for 31050 patients with a CTTC derived median five year absolute risk of 6.2% (IQR 4.0-10.2). There was a similar paired sample correlation between CTTC derived risk and each risk score (Framingham 0.68, QRisk2 0.65, PCE 0.68, all p10%) was 85% for Framingham, 64% for QRisk2 and 55% for PCE scores. Fewer than half of all patients had an absolute difference between predicted and CTTC five year risk of less than 2.5% (Table 2).

Conclusions:
QRisk2 and Pooled Cohort Equations scores outperform Framingham scores when applied to primary prevention control arm patients in the Cholesterol Treatment Trialists’ database. However for all risk calculators accuracy is limited and risk overestimation occurs in the majority of individuals. This may have implications when predicted risk levels are used to guide recommendations and estimate cost effectiveness for cardiovascular therapies.
Abstract 17713: Data Driven Modeling of Electronic Health Record Data to Detect Pre-diagnostic Heart Failure in Primary Care
Authors: Ng Kenney , Stewart Walter F , deFilippi Christopher , Wang Yajuan , Byrd Roy J , Steinhubl Steven R , Daar Zahar , Law Heather , Hu Jianying
Published: July 2021

Introduction:
Electronic health records (EHRs) represent an opportunity for real-time early risk prediction. EHR records were used to determine the extent to which machine learning tools and a purely data driven approach to modeling (DDM) could detect heart failure subtypes, i.e., preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), 12 months before a clinical diagnosis.

Methods:
Incident HF cases were identified from Geisinger Clinic primary care patients age 50-85, diagnosed between 2001 and 2010 and further defined as HFrEF if LVEF≤40 and HFpEF if LVEF>50. Controls were chosen to match HF cases by age, gender, location and primary care physician. EHR data were extracted on demographics, ICD-9 codes, medication orders, clinical and behavioral measures. Modeling was completed to detect HF using data from a 24-month observation window 12 months before the HF diagnosis. Patient feature vectors were generated from the data and summarized by one or more aggregation functions (e.g., counts, means). For the HF endpoint, modeling was done with and without patients who had an acute coronary syndrome (ACS) event within 12 months of the diagnosis. Regularized logistic regression was applied using information gain feature selection and 10-fold cross validation. Model performance was assessed by the area under the ROC curve (AUC) and complexity by the number of selected features.

Results:
Performance for HFpEF is better than for HFrEF. The HFpEF model is more complex than the HFrEF model as indicated by more EHR information that was needed to discriminate the HFpEF cases from controls. Performance with and without ACS cases is similar though models including ACS cases are more complex than models excluding them (Table).

Conclusions:
Purely data driven approaches to modeling can be used to detect HF 12 months before clinical diagnosis. Model performance and complexity varies with the HF subtypes indicating differences in the complexity of modeling the HF subtypes.
Abstract 17718: New Oral Anticoagulants: Bleeding Rates Among Medicare Beneficiaries With Atrial Fibrillation
Authors: Roth Gregory , Smith Jeremy , Bekelis Kimon , Morden Nancy E
Published: July 2021

Introduction:
In randomized trials of patients with non-valvular atrial fibrillation (AF), new oral anticoagulants (NOACs) have been shown to confer a lower risk of major bleeding than warfarin. Outside of these select study settings, bleeding outcomes for these medications have not been examined sufficiently. We studied a national sample of patients with AF to explore bleeding risks associated with NOACs in routine clinical settings.

Methods:
Using a 40% Medicare random sample denominator file and associated inpatient, outpatient and prescription administrative data from 2009-2012, we identified patients age 65 and older with new onset, non-valvular AF. Cox regression models estimated risk of upper gastrointestinal (UGI) and nontraumatic intracranial (IC) bleeding associated with NOAC (dabigatran and rivaroxaban) compared to warfarin use, adjusting for individual characteristics, morbidities, and time-varying medication use. The analysis excluded person-months with concurrent prescriptions filled for an antiplatelet medication (e.g. clopidogrel).

Results:
We identified 157,390 incident AF patients, mean age 77.8 (standard deviation (SD) 7.8); mean follow up was 10.8 months (SD 6.9); In the first year post-index diagnosis, 41.5% of patients received some oral anticoagulant; of these, 28.2% used NOACs (75% dabigatran, 25% rivaroxaban). Overall 24,661 bleeding events were observed (11,015 UGI and 1,868 IC). Out of 1,487,675 person-months, 212,670 (14.3%) were excluded due to concurrent prescription antiplatelet exposure. Compared to warfarin, the hazard ratio for bleeding associated with NOAC was 1.33 (95% CI 1.21 to 1.47) for UGI, 0.59 (95% CI 0.42 to 0.82) for IC, and 1.09 (95% CI 1.02, 1.17) for all significant bleeding combined.

Conclusions:
Compared with warfarin, NOACs were associated with a lower risk of IC bleeding, a higher risk of UGI bleeding and a modestly higher risk of significant bleeding overall. These results should inform clinical decision-making and selection of individualized thromboembolism prophylaxis strategies among AF patients. Further studies are needed to illuminate the divergent UGI and IC bleeding risks observed and to identify patient-level factors predictive of these outcomes.
Abstract 17804: Echocardiographic and Radiologic Predictors of Atrial Fibrillation in Acute Ischemic Stroke
Authors: Mittal Shilpi , Modak Janhavi , Staff Ilene , Phipps Michael , Fortunato Gilbert , McCullough Louise D
Published: July 2021

Introduction:
Atrial fibrillation (AF) is an important risk factor for stroke. Approximately 15-25% of cryptogenic ischemic strokes (CIS) are due to AF.

Hypothesis:
Patients with echocardiographic markers including left atrial dilatation (LAD) and valvular disease and/or radiologic findings including a hyper-dense vessel sign (HDV sign), prior cortical or cerebellar stroke, and hemorrhagic transformation (HT) are more likely to have stroke due to AF.

Methods:
This is a single center, retrospective case control study of patients admitted with acute ischemic stroke (AIS) from 2008-2013. Patients with a new diagnosis of stroke and a defined stroke etiology (large vessel, cardio-embolic, small vessel and other, TOAST classification) were included. CIS patients or those without imaging/echocardiographic studies were excluded. Images were reviewed for prior stroke, HT, a HDV sign and stroke location (left or right anterior, posterior, multifocal). Echocardiograms were reviewed for LAD, ejection fraction<35%, moderate-severe mitral regurgitation (MR), moderate-severe aortic regurgitation, mitral stenosis, aortic stenosis, left ventricular segmental akinesis, diastolic dysfunction, LVH and patent foramen ovale.

Results:
Charts of 600 patients were reviewed and 383 patients were included in the analysis. 185 patients had AF as the etiology of their stroke. The remainder had no known AF. Univariate and multivariate logistic regression was performed using SPSS. LAD, moderate to severe MR, HDV sign, and HT were found to accurately predict AF in patients with AIS. LAD had an OR of 6.9 (CI 4.4-10.8, p<.0001) and HDV predicted AF with an OR of 2.2 (CI 1.2-4.2, p<.016) even after controlling for LAD, MR, and HT.

Conclusion:
Echocardiographic and radiologic markers help predict AF as a stroke etiology in AIS patients. This is the first study, to the best of our knowledge, to show that HDV sign is a positive predictor of AF. Prospective studies with larger cohorts are needed to confirm these findings in CIS patients. These markers could be added to demographic information to enhance prediction of occult AF and the need for chronic cardiac monitoring.
Abstract 17826: Long-term Survivors With Transposition of the Great Arteries After Arterial Switch Operation Show No Signs of Adverse Myocardial Remodeling
Authors: Grotenhuis Heynric B , Mertens Luc , Cifra Barbara , Riessenkampff Eugenie , Manlhiot Cedric , Grosse-Wortmann Lars
Published: July 2021

Background:
The arterial switch operation (ASO) for transposition of the great arteries (TGA) involves coronary translocation. The altered coronary geometry may lead to subclinical myocardial ischemia, which may result in myocardial scarring and diffuse myocardial fibrosis. We hypothesized that myocardial fibrosis is present late after ASO, despite excellent functional outcomes of the ASO in most patients.

Methods:
30 pediatric TGA patients after ASO were prospectively studied by cardiac magnetic resonance imaging (CMR). Late gadolinium enhancement (LGE) was used to detect discrete myocardial scarring. Native T1 relaxation times and extracellular volumes (ECVs) at the mid-ventricular short-axis level of the left ventricle (LV) were used to quantify diffuse myocardial fibrosis. The midventricular short-axis slice was divided into 6 segments. Patients were compared to 21 healthy controls.

Results:
Mean ages at ASO and at CMR were 6.3±5.2 days and 15.4±2.9 years, respectively. Mean age of controls at CMR was 14.1±2.6 years. TGA patients showed preserved LV ejection fraction (57±5% vs. 59±4% in controls, p=0.08) and similar indexed LV mass (54±10g/m2 vs. 49±9%, p=0.12). LV end-diastolic and end-systolic volumes were mildly increased (104±20ml/m2 vs. 89±11ml/m2, p=0.01 and 46±13ml/m2 vs. 36±6ml/m2, p<0.01, respectively). None of the TGA patients demonstrated evidence of localized myocardial scarring by LGE. Native T1 times and ECV values for all 6 LV segments were not significantly different to controls. There was no association between global T1 times or global ECV and LV volumes and ejection fraction. Furthermore, native T1 and ECV were not associated with bypass and cross-clamp times at the time of the ASO, or with coronary artery patterns.

Conclusions:
Adolescent TGA patients late after ASO have preserved systolic LV function. There is no evidence of myocardial scarring or fibrosis. Our results suggest excellent long-term myocardial and cardiac health after the ASO, paralleling the encouraging clinical outcomes with this procedure.
Abstract 17852: Epinephrine Does Not Impact Survival and May Worsen Neurological Outcomes in Out-of-hospital Cardiac Arrest: Meta-analysis of Randomized Control Trials
Authors: Altabaqchali Sayf , Kumar Shashi , Aziz Emad , Herzog Eyal , William Cody , Kanaan Salim , Molina Marcos , Pierce Walter , Timmerman Segio , Kumari Rina , Maniotis Christos , Chantziara Klio , Gursoy Erdal , Benjo Cezar , Benjo Alex
Published: July 2021

Background:
Advanced cardiac life support is a corner stone in the management of cardiac arrest and epinephrine is an important part of its armamentarium. Randomized controlled trials and observational studies have demonstrated inconsistent results regarding the benefits of epinephrine in out-of-hospital cardiac arrest. We conducted a meta-analysis to evaluate mortality and neurological outcomes.

Methods:
All randomized controlled trials regarding out of hospital cardiac resuscitation were sought using PubMed and Scopus databases from 1963 until June 2015. We calculated the chances of patients surviving to hospital admission and through discharge as well as having a good neurological outcome. Data was analyzed with RevMan 5.2 software.

Results:
Epinephrine was found to be associated with a higher rate of hospital arrival but not survival to discharge. Epinephrine also had numerically less favorable neurologic outcomes neurological but despite that this was seen in all trials this did not reach statistical significance (OR 0.71, CI95% 0.45-1.12, p 0.14).

Conclusion:
There is no data to support the use of epinephrine in out-of-hospital cardiac arrest patients. Increased unjustified financial and perhaps social costs seem to be present. Larger randomized controlled trials are needed.
Abstract 17861: Injectable Shear-thinning Hydrogels to Deliver Endothelial Progenitor Cells, Reduce Ventricular Strain, and Dynamic Stiffness to Stabilize Cardiac Function Following Ischemic Injury
Authors: Gaffey Ann C , Chen Minna H , Trubelja Alen , Venkataraman Chantel M , Chen Carol W , S Susan , Sehgal Chandra M , Burdick Jason A , Atluri Pavan
Published: July 2021

The ventricle undergoes adverse remodeling, post-infarction. We developed an injectable shear-thinning hyaluronic acid hydrogel(STG) and endothelial progenitor cell construct(STG-EPC) to enhance vasculogenesis(shown previously) and mechanically stabilize the infarcted myocardium. We hypothesize that this tissue-engineered therapy will minimize adverse remodeling and maintain myocardial tensile properties in a clinically translatable therapy.

EPCs(DiLDL+ VEGFR2+ CD34+) were harvested from adult Wistar Rats and suspended in STG. STG-EPC constructs were circumferentially injected at the borderzone of ischemic rat myocardium, following LAD ligation. Engraftment and retention were assessed by near infrared cellular tag. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed in 4 groups: control(PBS), EPC injection(EPC), STG injection(STG), and STG-EPC construct(STG-EPC). High-resolution ultrasound with speckle tracking (VSI Vevo 2100) allowed analysis of regional epicardial and endocardial strain. Uniaxial testing assessed tensile strength.

STG-EPC injection significantly increased engraftment, migration, and retention of the EPCs one-week post implant compared to EPC (0.7 vs 0.4 RFU, p=0.02). Using strain echocardiography a significant increase in left ventricular function was noted in the STG-EPC cohort. Strain echocardiography examination revealed a significant retention of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with STG-EPC therapy. A reduction in dynamic stiffness was noted in the STG-EPC cohort.(Table)

This novel injectable shear-thinning hyaluronic acid hydrogel seeded with EPCs demonstrates stabilization of borderzone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. There is a markedly increased retention of delivered stem cells with this tissue engineered therapy.
Abstract 17965: Bendopnea is a Marker of Elevated VE/VC02 Slope in Patients With Heart Failure
Authors: Thibodeau Jennifer T , Dominguez-Rodriguez Alberto , Abreu-Gonzalez Pedro , Jimenez-Sosa Alejandro , Aranda Jr Juan M , Drazner Mark H
Published: July 2021

Introduction:
In patients with advanced heart failure, shortness of breath while bending forwards, e.g. when putting on their shoes, is a recently described symptom termed “bendopnea”.

Hypothesis:
Whether bendopnea is associated with well validated markers of heart failure severity measured by cardiopulmonary exercise (CPX) testing, such as peak VO2 or VE/VCO2 slope, is not known.

Methods:
Bendopnea was assessed prior to a CPX in a prospective study of 95 subjects with systolic HF who were referred for functional evaluation. Standard CPX techniques were used including measurement of peak VO2 and VE/VCO2 slope. Multivariable linear regression analysis was performed to adjust the associations of bendopnea and CPX parameters for potential confounders.

Results:
The study cohort was predominantly male (72%), nonischemic cardiomyopathy (54%), NYHA class 3 or 4 (86%), with a mean age of 55 ± 14 years and LVEF 26 ± 4%. Bendopnea was present in 30 of 95 (31.5%) subjects. The association of bendopnea with key CPX parameters (Table) is shown. Peak VO2 was similar in both groups but patients with bendopnea had a higher VE/VCO2 slope (35.28 ± 2.72 vs 30.31 ± 6.41, P< 0.001) and trended towards having a lower oxygen pulse. The association of bendopnea with VE/VCO2 slope persisted in multivariable analysis.

Conclusions:
Bendopnea was independently associated with elevated VE/VCO2 slope in advanced HF patients. These data suggest that bendopnea is a marker of HF disease severity.
Abstract 17967: Systemic Hypertension in Children After Superior Cavo-pulmonary Shunt is Associated With Cerebrovascular Dysautoregulation
Authors: Cabrera Antonio G , Easley Ronald B , Dugan Rachel , Goldsworthy Michelle , Kibler Katherine K , McKenzie Emmett D , Fraser Charles D , Heinle Jeffrey S , Andropoulos Dean B , Shekerdemian Lara S , Penny Daniel J , Brady Kenneth M
Published: July 2021

Introduction:
Hypertension is frequently seen after superior cavo-pulmonary shunt. It is unknown if hypertension is necessary to maintain cerebral blood flow due to increased cerebral venous pressure. We sought to determine the range of arterial blood pressures (ABP) associated with intact and impaired autoregulation after superior cavo-pulmonary shunt.

Hypothesis:
Hypertension (mean ABP>60 mmHg) is associated with cerebrovascular dysautoregulation after superior cavo-pulmonary shunt.

Methods:
All patients < 12 months undergoing superior cavo-pulmonary shunt from 10/2014 were eligible. Subjects underwent continuous 100 Hz monitoring of ABP, pulmonary arterial pressure (PAP), and near-infrared spectroscopy measurements of cerebral oximetry (rSO
2
) and cerebral blood volume (CBV). Cerebrovascular autoregulation was measured by the hemoglobin volume index (HVx). ABP and CBV were low-pass filtered as 10 sec average values. Pearson’s correlation coefficient was performed over 300 sec windows. The associations between HVx changes relative to ABP and PAP were tested using linear regression with generalized estimation of equations. Optimal ABP and PAP defined by lowest HVx was determined using a curve-fit algorithm. The relationship between PAP and ABP was tested by piecewise regression.

Results:
Ten patients were enrolled. Median age and weight were 6.5 months and 6.2 kg. Optimal ABP and PAP were obtained in 7/10. HVx became impaired with increased ABP (top panel) and increased PAP (middle panel), indicating worse cerebrovascular dysautoregulation. PAP increased with increasing ABP (r = 0.55, p<0.0001) with an intercept of 72 mmHg above which ΔPAP/ΔABP doubled from 0.23 [0.22- 0.24] to 0.46 [0.43 - 0.49] (bottom panel). Elevations of ABP above optimal for HVx did not improve rSO2 (p>0.05).

Conclusion:
Hypertension after superior cavo-pulmonary shunt is associated with elevated PAP, no improvement in rSO
2
, and cerebrovascular dysautoregulation.
Abstract 17979: Nurse Practitioners Recognize, Address Depression-cardiovascular Disease in Older Adults
Authors: Novosel Lorraine M , Smialek Salina A
Published: July 2021

Depression is a risk factor for as well as a comorbidity of cardiovascular disease (CVD) in older adults (OA). Providers must target efforts toward the prevention, recognition, diagnosis, and treatment of depression to reduce CVD burden and morbidity and mortality among our rapidly growing aging population. While the AHA recommends routine screening for depression in all individuals with heart disease and the scientific community considers elevating depression to the status of "formal" CVD risk factor, depression remains under-diagnosed and sub-optimally treated by cardiology and primary care physicians. Nurse practitioners (NPs), utilizing a biopsychosocial model of care have a significant role in screening, health promotion, and risk reduction efforts and are positioned to play a vital role in primary care. This mixed-method study explored NPs’ knowledge, screening and risk reduction behaviors related to depression-CVD in OA. We hypothesized that NPs integrate depression screening, diagnosis and treatment into CVD risk reduction and management. Methods. A national sample of NPs (N=118) completed an anonymous survey. A subset (n=12) participated in a follow-up interview.

Results:
The NPs were aware of the high prevalence of depression among OA with CVD and identified depression as a risk for CVD. One-half were unaware of the AHA recommendation for depression screening or Medicare depression screening and cardiovascular preventive services. Yet, 70% routinely screened their OA patients, and OA patients with CVD for depression. The NPs (92.7%) were confident in their ability to address classic CVD risks and stressed the importance of a quality patient relationship to optimize depression care. A majority (64%) felt it would be at least “somewhat” easy to incorporate depression into their routine CVD risk reduction practices if depression became a “formal” CVD risk factor. Inadequate counseling skills and lack of mental health resources were cited as challenges. Conclusions. NPs are confident in their ability to promote CVD risk reduction among their OA patients and recognize and address depression in cardiovascular care. They are prepared to incorporate depression into CVD risk reduction practice but lack depression counseling resources.
Abstract 17981: Decreased Oscillatory Pattern of Sympathetic Nerve Activity is Associated With Arterial Baroreflex Dysfunction in Chronic Heart Failure Patients
Authors: Toschi-Dias Edgar , Groehs Raphaela V , Antunes-Correa Ligia M , Trevizan Patrícia F , Lobo Denise M , Oliveira Patrícia , Alves Maria Janieire N , Almeida Dirceu R , Negrao Carlos Eduardo , Rondon Maria Urbana P
Published: July 2021

Background:
Sympathetic activation and arterial baroreflex (ABR) dysfunction typify chronic heart failure (CHF). In addition, decreased oscillatory pattern of muscle sympathetic nerve activity (MSNA, LF
MSNA
/HF
MSNA
) seems to contribute to sympathetic exacerbation in patients with CHF. Unknown is whether the LF
MSNA
/HF
MSNA
is associated with ABR dysfunction in CHF patients. To answer this question, we investigated the association between gain, latency and coupling of ABR function and LF
MSNA
/HF
MSNA
in CHF patients.

Methods and Results:
Forty-three CHF patients, Functional Class II to III, NYHA, ejection fraction ≤40% were allocated into two groups according to the level of LF
MSNA
/HF
MSNA
index: 1) Higher LF
MSNA
/HF
MSNA
(n=21, 52±2 years) and 2) Lower LF
MSNA
/HF
MSNA
(n=22, 54±1 years). Blood pressure (BP, oscillometric beat-to-beat basis) and MSNA (microneurography technique) were recorded during 10 min at rest. Spectral and cross-spectral analyses of BP and MSNA variabilities were conducted to assess the LF
MSNA
/HF
MSNA
and the gain, latency and coupling between BP and MSNA of ABR function. Etiology, ejection fraction, gain and latency of ABR function were similar between groups. However, the patients with lower LF
MSNA
/HF
MSNA
had increased MSNA bursts frequency (53±2vs. 39±3 bursts/min, P<0.01) and total activity (180±15 vs. 126±17 a.u, P=0.03) compared to the patients with higher LF
MSNA
/HF
MSNA
. In contrast, the patients with lower LF
MSNA
/HF
MSNA
had reduced coupling of ABR function (69±3 vs. 80±2 %, P<0.01). Further analysis showed a significant association between the coupling of ABR function and LF
MSNA
/HF
MSNA
(R=0.36, P=0.02).

Conclusions:
There is an inverse association between the LF
MSNA
/HF
MSNA
index and sympathetic nerve activity. In addition, there is a direct association between the LF
MSNA
/HF
MSNA
index and the coupling of ABR, which suggests that the ABR dysfunction explains, at least in part, the augmented sympathetic nerve activity in CHF patients.