bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16364: Physician Documentation Behaviors in Electronic Health Records as a Potential Source of Noise for Early Detection of Heart Failure
Authors: Wang Yajuan , Ng Kenney , Hu Jianying , Byrd Roy J , Steinhubl Steven R , deFilippi Christopher , Stewart Walter F
Published: July 2021

Introduction:
Electronic health records (EHRs) are a potentially rich source of data for developing predictive models for early detection of heart failure (HF). But, EHR documentation can vary both because of patient health and variation in clinical practice and behavior among physicians.

Hypothesis:
The “noise” contributed by variable physician behaviors, such as differences in the frequency and detail of documentation, could potentially confound predictive models for detection of HF. In this study, we characterized the documentation behaviors of primary care physicians (PCPs) in an effort to better understand this potential source of noise.

Methods:
We used longitudinal EHR data of a stratified random sample of 5,187 patients who were: 1) ≥50 years of age, and without a history of HF. PCPs (n=144) were identified and paired with the patients that they had treated for a minimum of 6 months. We derived 28 measures to characterize PCP behaviors - documentation frequencies of assertions and denials of selected Framingham HF signs and symptoms (FHFSS) in office visit encounter notes adjusted for patient comorbidities. Hierarchical clustering analyses (HCA) were performed on PCP documentation behaviors.

Results:
Based on HCA analyses, PCPs were clustered into 3 groups with distinct documentation behaviors. Group 1 PCPs (n=63) documented 10 out of 15 assertions, and 11 out of 13 denials of FHFSS significantly more frequently than Group 3 (n=20); while Group 2 PCPs (n=61) have significantly more frequent denial documentation behaviors than the other two (see Figure 1). No significant differences were found among patients’ chronic, episodic and cardio metabolic chronic disease counts (comorbidities) in each of the groups (p<0.05).

Conclusions:
This study identified PCP groups with distinct documentation behaviors unrelated to patient complexity. This source of noise and potential confounder should be taken into account for predictive modeling.
Abstract 16545: Gender Attitudes and the Use of Angiography Among Cardiologists
Authors: Daugherty Stacie L , Blair Irene V , Havranek Edward P , Furniss Anna , Dickinson Miriam , Main Debbi S , Karimkhani Elhum , Masoudi Frederick A
Published: July 2021

Background:
Physician bias may contribute to gender disparities in the use of angiography. We performed the first study using the Implicit Association Test (IAT) to examine gender biases and their associations with angiography decisions.

Methods:
Cardiology physicians were emailed a web-based survey that included 2 gender-IATs and a two-part clinical vignette randomized by patient gender. The IATs measured attitudes about men versus women on strength and risk-taking. The vignette represented an intermediate likelihood of CAD regardless of gender; part-1 described a patient with symptoms of CAD and part-2 described an abnormal stress test. Physicians rated the likelihood of CAD and their agreement with the usefulness of angiography for that patient. We examined the association between gender attitudes and rated usefulness of angiography for the male and female patient, adjusting for the perceived likelihood of CAD.

Results:
Of the 503 cardiologists who responded, over half associated strength and willingness to take risks with males. For both parts of the case, cardiologists’ estimated the likelihood of CAD similarly by patient gender; yet, cardiologists’ more often rated the usefulness of angiography as “high” for the male versus female patient (Part-1: 19.7% vs. 9.8%; Part-2: 73.7% vs. 64.3%; p<0.05 for both). These differences varied by gender attitudes; those with higher male-risk bias or male-strength bias rated angiography as more useful for men than for women. (Figure) After adjustment, only the relationship with male-risk bias and higher angiography rating for male patients persisted (p=0.01 for interaction).

Conclusions:
Despite similar estimates of CAD likelihood, cardiology physicians rated the usefulness of angiography higher for a standardized male than female patient. This difference significantly varied by gender-risk bias suggesting the concept of riskiness influenced decisions about angiography differently in women and male patients.
Abstract 16546: microRNA(miR)-451 Regulates Cardiac Growth and Myocardial Reactive Oxidative Species (ROS) Level via Nrf2 and AMPK Pathways
Authors: Cho Young-Eun , Zhang Chongxu , Ranjan Ravi , Christman John W , Xiao Lei , Zhao Qiong
Published: July 2021

The role of miR-451 in certain cardiac diseases was recently reported including ischemia/reperfusion and hypertrophic cardiomyopathy. Oxidative stress is known to involve in the above diseases. Currently the relationship between miR-451 and cardiac oxidative stress is unknown. We thus hypothesize that miR-451 act as a key mediator for cardiac hypertrophy via regulating myocardial ROS level and antioxidant pathways. We first compared the heart/body weight (HW/BW) ratio between age- & gender-matched miR-451 knockout (KO) and wild-type (WT) mice. Increase of HW/BW was found in KO mice (6.1±0.1 vs 4.8±0.1 mg/g in WT, p<0.01). Expression of fetal genes ANF (2.9-fold↑) and β-MHC (4.0-fold↑) was also significantly increased in KO hearts, as well as the ROS level (2.3-fold↑, p<0.05) in KO hearts. Consistently, both the protein expression and activation levels of the oxidation-regulating gene Nrf2 decreased the same extent (~33%↓, p<0.05) in KO hearts. In contrast, the protein expression of the direct antioxidants HO-1 and SOD3 were found significantly increased in KO hearts, suggesting a compensatory mechanism to quench the increased cardiac ROS. Since we previously showed that phosphorylation (p) of AMPKα was inhibited in cardiac hypertrophy, thus the p-AMPKα level was tested and found significantly (76%↓, p<0.05) decreased in KO heart, consistent with the hypertrophy in KO heart. In order to further explore the relationship between Nrf2 and AMPKα, cultured adult rat ventricular myocytes (ARVM) was treated with an Nrf2 activator sulforaphane, which induced 1.4-fold increase in p-AMPKα (p<0.01); whereas the AMPK activator AICAR didn’t affect Nrf2 expression in ARVM, suggesting Nrf2 is upstream from AMPK. When miR-451 mimics were overexpressed in cultured cardiac myocytes, Nrf2 was significantly increased (2.3-fold↑, p<0.05) with overexpression of miR-451 mimics vs control, suggesting miR-451 regulates Nrf2 expression. Taken together, our data show that miR-451 activates cardiac Nrf2 and its downstream AMPK signaling pathway; whereas antioxidants HO-1 and SOD3 act as compensatory mechanism for increased cardiac ROS when miR-451 is defect. miR-451 plays a novel protective role against cardiac oxidative stress, and also mediates cardiac hypertrophy.
Abstract 16578: Sudden Death is Less Common in Young Competitive Athletes Than in Non-athletes: But We Systematically Screen Only Athletes
Authors: Maron Barry , Haas Tammy S , Duncanson Emily R , Garberich Ross F , Baker Andrew M , Mackey-Bojack Shannon
Published: July 2021

Background:
Screening competitive athlete populations for cardiovascular disease is a topic of considerable interest, due to the highly visible sudden deaths (SDs) occurring in young people predominantly with genetic and/or congenital diseases. Media attention to these events may have created the skewed impression that SDs in high school and college students occur almost exclusively in athletes. We address here the important question of whether SDs due to cardiovascular diseases in fact occur largely in competitive athletes, compared to the frequency of such events in young people who are not engaged in sports.

Methods:
Case records of the Hennepin County (Minneapolis) Medical Examiner were interrogated to identify SDs, age 14-23 years, 2000 to 2014. The number of Hennepin County high school/college students who were competitive athletes (or non-athletes) was estimated from publicly available data sources.

Results:
Twenty-seven SDs were identified, including 3 individuals who were athletes, either with hypertrophic cardiomyopathy (HCM), a structurally normal heart, or anomalous origin of the left main coronary artery from the right aortic sinus. The other 24 deaths were in young people not involved in organized sports, including: 4 each with HCM or arrhythmogenic right ventricular cardiomyopathy, and 5 with coronary artery disease. Ratio of SDs in non-athletes to athletes was 24 to 3 or 8:1. Incidence of non-athlete SDs over 946,889 person-years was 1:39,454, i.e., 3-fold greater than that for SDs in competitive athletes over 361,841 person-years, i.e., 1:120,614.

Conclusion:
Cardiovascular SDs are less frequent in competitive athletes than in non-athletes. These data underscore a major (ethical) limitation inherent in confining cardiovascular screening to trained athletes, as is the current practice in the U.S. and elsewhere.
Abstract 16580: Safety and Efficacy of Cryoballoon Ablation in Patients With Congestive Heart Failure
Authors: Tseng Roger , Al-Zubaidi Muhanad , Homer Alexander , DanCanay Kelly , Su Wilber
Published: July 2021

Background:
Irrigated radiofrequency ablation of atrial fibrillation (AF) is challenging in patient with severe systolic congestive heart failure due to large fluid load. The use of cryoballoon ablation in patients with low ejection fraction (EF) and NYHA class II-IV congestive heart failure has not been well described, and may benefit from the lack of fluid bolus and restoration of sinus rhythm.

Method:
To evaluate the efficacy and safety of cryoballoon ablation for systolic heart failure patients with atrial fibrillation (AF). Single center retrospective review of 832 patients with AF ablation using Arctic Front Advance Cryoballoon (Medtronic, Minneapolis, MN) was performed, and 188 patients has EF less than 35% (24 paroxysmal, 122 persistent, and 42 long-standing persistent, average EF 28%) was analyzed. Procedural tolerance, complications, and impact on congestive heart failure were reviewed over a 12 months follow up.

Results:
All 188 patients (Average age 68, LA size 5.8 cm) with systolic CHF and atrial fibrillation underwent successful pulmonary vein (PV) isolation and extra-pulmonary vein lesions sets applied using cryoballoon. Non-irrigated radiofrequency ablation was used in (22%) for cavo-tricuspid isthmus flutter ablation. Acute procedural success rate was 100% with length of hospitalization of 1.1 days. Average procedural time was 2.6 hours, and fluid infusion of 0.3 liters, no significant complications was noted. Atrial fibrillation burden was monitored by implantable pacemaker or defibrillator in 118 of 188 patients (63%), and others were monitoring via wearable looping recorders every 3 months. Significant AF burden (<10% atrial high rate burden) was observed in over 67% of the patients, and improvement CHF symptoms were reported in all of the patients with reduction of atrial fibrillation burden.

Conclusions:
Cryoballoon of AF in systolic CHF population is well tolerated with high procedural success rate and low complication rate. Significant clinical improvement of CHF class was observed in patient with reduction of atrial fibrillation burden. Ongoing collection of data is needed to quantify long-term benefit.
Abstract 16614: Left Ventricular Global Function Index (A Novel Marker of Cardiac Performance) Predicts Incident Cardiovascular Events: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Nwabuo Chike C , Mewton Nathan , Opdahl Anders , Moreira Henrique T , Ogunyankin Kofo , Ambale-Venkatesh Bharath , Schreiner Pamela J , Inoue Yuko , Ohyama Yoshiaki , Jacobs David , Lloyd-Jones Donald , Lewis Beth , Gidding Samuel , Lima João
Published: July 2021

Introduction:
Left ventricle (LV) function is typically evaluated independent of LV structure and vice versa. LV global function index (LVGFI) is a novel marker of cardiac performance that accounts for LV structural alterations and has been previously validated using magnetic resonance imaging.

Hypothesis:
We evaluated the prognostic utility of LVGFI assessed by echocardiography for incident cardiovascular disease (CVD) and heart failure (HF) events in comparison to LV ejection fraction (LVEF) and LV mass

Methods:
Included were 4107 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with available m-mode echocardiographic parameters in 1990-1991 (Year-5). LV volumes were obtained using the Teichholz formula. LVGFI defined as LV stroke volume/LV global volume* 100, where LV global volume was calculated as the sum of the LV mean cavity volume (LVEDV + LVESV)/2) and myocardium volume (LV mass/density). Median follow-up time was 21.9 years. Cox regression models, adjusted for risk factors, were utilized to predict the endpoints of HF, hard CVD and all CVD events.

Results:
Mean age of participants at Year-5 was 29.8 ± 3.7 years, 55% were female, 51.3% white and mean LVGFI was 34.7 ± 6.2%. A total of 174 incident CVD events were observed during the 21.9 years median follow-up. In multivariable adjusted models, 1-SD increase in LVGFI was significantly associated with lower hazard of HF, Hazard Ratio (HR) =0.55 95% confidence interval (CI) [0.40 - 0.74]; hard CVD, HR=0.74 95% CI [0.63 - 0.88] and all CVD events, HR=0.76 95% CI [0.65 -0.88]. (Table 1). LVGFI provided incremental predictive value for incident CVD compared to LV mass and LV ejection fraction alone.(Figure 1).

Conclusions:
LVGFI in early adulthood was associated with incident HF, hard CVD and all CVD events. In this longitudinal community study, LVGFI provided robust, independent and incremental predictive value for incident CVD events.
Abstract 16619: Bone Marrow Cell Therapy Improves Left Ventricular Function And Survival in Patients With Chronic Ischemic Heart Disease and Cardiomyopathy
Authors: Samanta Anweshan , Afzal Muhammad R , Ansari Briha , Jeevanantham Vinodh , Dawn Buddhadeb
Published: July 2021

Introduction:
Results from randomized controlled trials (RCTs) of bone marrow cell (BMC) therapy for cardiac repair have been discordant. The true impact of BMC therapy in patients with chronic ischemic heart disease (CIHD) and ischemic heart failure remain unclear.

Hypothesis:
We hypothesized that BMC injection would improve clinical outcomes and left ventricular (LV) parameters in patients with CIHD.

Methods:
We performed a systematic review and meta-analysis of data from RCTs of BMC therapy on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct scar size, and clinical outcomes in patients with CIHD. Database searches based on specified criteria identified 15 eligible RCTs (enrolling 648 CIHD patients). Changes in predefined parameters were analyzed with random-effects meta-analysis. Peto odds ratio (OR) was calculated for clinical outcomes.

Results:
Compared with standard therapy, BMC transplantation improved LVEF (3.84%; 95% confidence interval [CI], 2.30 to 5.38; P<0.00001), reduced scar size (-5.90%; 95% CI, -8.03 to -3.78; P<0.00001) and LVESV (-10.37 ml; 95% CI, (-18.56 to -2.18; P=0.01). Reduction in LVEDV (-1.84 ml; 95% CI, -9.13 to 5.46; P=0.62) was not significant. The improvement in LVEF in BMC-treated patients was also significant (1.78%; 95% CI: 0.63 to 2.93; P=0.002) in a separate analysis of RCTs that used MRI. Importantly, BMC therapy reduced all-cause mortality (OR: 0.35; 95% CI 0.16 to 0.73; P=0.005) and incidence of cerebrovascular accident (CVA) (OR: 0.07; 95% CI, 0.01 to 0.55; P=0.01) and tended to reduce the incidence of heart failure (OR: 0.36; 95% CI 0.11 to 1.14; P=0.08) in patients with CIHD (Table).

Conclusions:
BMC therapy improves LVEF, LVESV, and infarct scar size in patients with CIHD. The improvement in LVEF was also confirmed in meta-analysis of RCTs using MRI. Importantly, these numerically small benefits translated into improved clinical outcomes in BMC-treated CIHD patients.
Abstract 16685: Obstructive Fibrosis Related to Transverse Conduction Slowing in Chronic Atrial Fibrillation
Authors: Angel Nathan A , Li Li , MacLeod Rob S , Marrouche Nassir , Ranjan Ravi , Dosdall Derek J
Published: July 2021

Introduction:
Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium.

Hypothesis:
We hypothesize long strands of continuous fibrosis act as a substrate that slows conduction, but only after a premature contraction.

Methods:
A high density electrode plaque was placed on 13 controls and 6 chronic AF goats (an average of 6 months of rapid pacing induced AF). Conduction slowing following a premature contraction was quantified. Atrial fibrosis was quantified into two groups, non-obstructive and obstructive fibrosis. Obstructive fibrosis was considered fibrosis that was at least the length of a myocyte (100 μm), thus potentially disrupting transverse cell to cell conduction. Non-obstructive fibrosis had a length less than 100 μm.

Results:
Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40±0.03 m/s vs. 0.53±0.15 m/s, p<0.05) but not in the longitudinal direction (0.70±0.27 m/s vs. 0.76±0.18 m/s, p = N.S.) following a premature atrial contraction. The AF goats had more obstructive fibrosis than the controls (18±8 fibers/mm
2
vs. 9±3 fibers/mm
2
, p<0.05). The control group trended towards more non-obstructive, diffuse fibrosis than the AF animals (1109±309 fibers/mm
2
vs. 718±380 fibers/mm
2
, p = 0.07, N.S).

Conclusions:
Structural and electrophysiological remodeling in chronic AF leads conduction velocity slowing transverse to fiber orientation. Histology from goats with a history of chronic AF had more obstructive fibrosis, which may lead to the conduction slowing and alteration in conduction pathways to make the tissue more susceptible to AF. The amount of obstructive fibrosis may be more important to AF outcomes than the total density of fibrosis.
Abstract 16819: Sequencing of Genetic Loci Associated With Leukocyte Telomere Length Reveals New Intronic Variants in African Americans
Authors: Mathias Rasika , Iyer Kruthika , Taub Margaret , Yanek Lisa , Becker Diane , Becker Lewis , Vaidya Dhananjay
Published: July 2021

Background:
Shorter telomere length is associated with an increased risk of coronary artery disease (CAD). A prior genomewide association study (GWAS) on 37,684 European ancestry individuals identified seven loci determining leukocyte telomere length (LTL). A genetic risk score across all 7 loci showed an association with CAD. In this study we sequenced these loci to determine whether the same risk variants could be replicated in African admixed individuals.

Methods:
We used whole genome sequence data (WGS) in 127 healthy African American subjects from GeneSTAR, a family study of early-onset CAD. LTL was calculated from WGS raw bam data (>30x coverage on the Illumina HiSeq platform) for 7 contiguous repeats of the telomere motif (TTAGGG or CCCTAA, Ding et al., 2014). Tests for association for LTL adjusting for age and sex were performed for a total of 55,821 called variants from ~1Mb subset regions of WGS genotype data centered on each of the 7 European peak GWAS SNPs.

Results:
We identified a total of 17 variants with p<5x10
-4
mapping to 6 of the 7 regions examined; none of the prior European GWAS peak SNPs were significant. The peak SNP per region in the African Americans included intronic variants rs77138331 in
ACYP2
(p=0.0005, MAF = 7%), rs149577640 in
NAF1
(p=0.002, MAF=1%), rs35387865 in
TERT
(p=0.003, MAF = 1%) and rs186486116 in
OBFC1
(p=0.004, MAF=1%). Additionally, novel intronic variants not previously observed in dbSNP located at chr19: 22190184 (p=0.005, MAF=1%) and chr2:62445438 (0.005, MAF=2%), mapping to
ZNF208
and
RTEL1
, were also identified as determinants of LTL.

Discussion:
This is the first study of telomere length in African Americans using a sequencing approach. We are unable to confirm the European-based GWAS variants but identify several associations mapping to genes of importance in telomere biology. Our results provide evidence that the set of SNPs to be included in calculation of a telomeric genetic CAD risk score may be different in populations of European and African ancestry.
Abstract 16866: Depressed Biventricular Outputs in Fetuses of Diabetic Mothers When Standardized to Estimated Fetal Weight
Authors: Hickman Jennifer , Craft Mary , Li Ling , Kulkarni Aparna , Hornberger Lisa , Danford David , Kutty Shelby
Published: July 2021

Background:
Although the results of maternal diabetes on the newborn heart are well described, in-utero cardiovascular effects of maternal diabetes and obesity are not as well understood.

Hypothesis:
Echocardiographically derived measures of right and left heart flow volumes in fetuses of diabetic mothers (FDM) and fetuses of obese mothers (FOM) differ from those of normal fetuses.

Methods:
We prospectively enrolled 264 normal fetuses, 30 FDM and 49 FOM for prenatal research echocardiography. Estimated fetal weight (EFW) based norms for aortic and pulmonary valve velocity time integrals (AVVTI, PVVTI), right and left ventricular outflow tract diameters (LVOTD, RVOTD), aortic and pulmonary valve stroke volume (AVSV, PVSV), and cardiac output (LVCO, RVCO) were derived from the 264 control group fetuses using nonlinear regression to a Gompertz growth function. Z values for each parameter were determined, then analyzed using a non-paired two-tailed t-test to compare the three groups.

Results:
The mean ± SD EFW (g) for normal fetuses, FDM and FOM were 1610 ± 1201, 964 ± 694 and 1075 ± 1013; respective mean gestational ages (weeks) were 28.1±1.3, 25.3± 5, and 25 ± 6.6. The table shows mean Z value comparisons of VTI, OTD, SV and CO for the RV and LV in the three groups.

Conclusions:
FDM have significantly lower right and left heart stroke volumes and outputs than other fetuses matched for size, while FOM did not have demonstrable right or left heart stroke volume or cardiac output changes relative to normal fetuses. Similar to their relationship with gestational age, normal right and left ventricular stroke volumes and outputs follow a non-linear correlation with estimated fetal weight. Flow volumes in macrosomic fetuses may be better normalized to EFW rather than to gestational age. Reduced placental blood flow and ventricular compliance changes may be contributing to depressed biventricular cardiac output in FDM.
Abstract 16961: Time-dependent Markers of Chronic Obstructive Pulmonary Disease Severity and Change are Associated With Increased Risk of Mortality in the General Heart Failure Population: A National Study of 50,114 Patients From the United Kingdom
Authors: Rushton Claire A , Riley Lucy , Satchithananda Duwarakan K , Jones Peter W , Kadam Umesh T
Published: July 2021

Purpose:
Heart failure (HF) carries poor prognosis which changes over time. Chronic obstructive pulmonary disease (COPD) is common in HF and increases risk of mortality but how COPD severity and change influences HF prognosis is unknown. We hypothesised that in the HF general population, comorbidity stratification by increasing severity and longitudinal change would be associated with increased mortality.

Methods:
We used a case-control study nested within the UK Clinical Practice Research Datalink database (12-year time-period to 2014), of newly diagnosed HF patients aged over 40 years. Using risk set sampling, four controls were matched to cases on calendar and follow-up time. Routinely collected clinical measures of severity and change for COPD were (i) forced expiration volume in 1 second (FEV
1
) stages, defined by Global Initiatives for Chronic Obstructive Lung Disease (GOLD) guidelines and (ii) prescribed medications in two time-windows covering 1-year prior to the match date. Conditional logistic regression was used to estimate risk ratios (RR) for all-cause mortality adjusted for known confounders.

Results:
Of the 50,114 HF sample, 5,848 (11.7%) had COPD and of these 62% died during follow-up compared to 52% of patients without COPD. COPD comorbidity risk associated with mortality stratified by GOLD stages was as follows: stage 1; adjusted RR 1.73 (95% CI 1.50-1.99) to stage 4; 3.14 (2.65, 3.73). Estimates for COPD FEV
1
change compared to no COPD were: GOLD stage same or better; 2.15 (1.97, 2.34) and GOLD stage worse; 2.70 (2.30, 3.17). The mortality estimates for medications severity were: inhalers only 1.13 (1.07,1.19), oral steroids; 1.83 (1.69,1.97) and oxygen; 2.94 (2.47, 3.51). The estimates for medications change were: no new steroids or oxygen; 1.22, (1.16, 1.28), new steroids but not oxygen; 1.84, (1.67,1.28) and new on oxygen; 3.41, (2.71,4.29).

Conclusions:
COPD is an important and common comorbidity in HF. Our results show that worse COPD severity and recent change based on routinely collected clinical data was associated with increased mortality and provides key prognostic information for clinical assessment in practice.
Abstract 16967: Increased Blood Pressure Variability is Associated With Worse Outcome in Acute Ischemic Stroke
Authors: de Havenon Adam , Wang Haimei , Stoddard Greg , Chung Lee , Majersik Jennifer
Published: July 2021

Background:
Increased blood pressure variability (BPV) is detrimental in the weeks to months after ischemic stroke, but it has not been adequately studied in the acute phase. We hypothesized that increased BPV in acute ischemic stroke (AIS) patients would be associated with worse outcome.

Methods:
We retrospectively reviewed inpatients at our hospital between 2010-2014 with an ICD-9 code of AIS; 213 were confirmed to have AIS by a vascular neurologist. A modified Rankin Score (mRS) after discharge was available in 148/213, at a mean of 86 ± 60 days. In 45/213 the discharge mRS was either 0 or 6, in which case they were included in the final analysis. BPV was measured as the standard deviation (SD) of each patient’s systolic blood pressure readings during the first 24 hours and 5 days of hospitalization (9,844 total readings), or until discharge if discharged in <5 days (Figure 1). The SBP SD was further divided in quartiles. A multivariate ordinal logistic regression with the outcome of mRS, the primary predictor of quartiles of SBP SD, and baseline NIH stroke scale (NIHSS) to control for initial stroke severity.

Results:
Mean±SD age was 64.2 ± 16.3 years, NIHSS was 12.6 ± 7.9, and mRS was 2.7 ± 2.1. The mean SBP SDs for the first 24 hours and 5 days were 12.1 ± 6.2 mm Hg and 14.1 ± 4.9 mm Hg. In the ordinal logistic regression model, the quartiles of SBP SD for the first 24 hours and 5 days were positively associated with higher mRS (OR = 1.37, 95% CI 1.01 - 1.74, p = 0.009; OR = 1.30, 95% CI 1.03 - 1.63, p = 0.028). This effect became even more pronounced in patients with the highest quartile of variability (OR = 2.76, 95% CI 1.29 - 5.88, p = 0.009; OR = 2.10, 95% CI 1.01 - 4.36, p = 0.046).

Conclusion:
In our cohort of 193 patients with AIS, there was a significant association between increased systolic BPV and worse functional outcome, after controlling for initial stroke severity. This data suggests that increased BPV may have a harmful effect for AIS patients, which warrants a prospective observational study.
Abstract 16977: Estimating the Health Workforce Requirements for Hypertension Management in Rural Western Kenya
Authors: Lee Danielle J , Kamano Jemima H , Tulienge Deborah , Kiptoo Peninah , Kofler Claire , Kimaiyo Sylvester , Fuster Valentin , Balasubramanian Hari , Vedanthan Rajesh
Published: July 2021

Background:
Hypertension is a major risk factor for cardiovascular disease, and the leading risk factor for mortality in sub-Saharan Africa. Yet hypertension treatment and control rates are low. One strategy to address inadequate hypertension treatment in Kenya is task redistribution of care from physicians to nurses. However, the workforce requirements for comprehensive hypertension treatment are not well known.

Objective:
To develop a needs-based workforce estimation model in order to estimate the health workforce requirements for stable, long-term hypertension management in Kenya.

Methods:
A mixed-methods approach was used to assess a nurse-based hypertension program in western Kenya. We conducted 7 key informant interviews and 6 focus group discussions among program managers, nurses, community health workers, community leaders, and patients. Qualitative transcripts were analyzed using content analysis with deductive and inductive codes. We also conducted time-motion studies of 118 patient encounters over 7 clinical days in 7 rural health facilities. Finally, we conducted a two-round Delphi exercise, involving anonymous surveys of 8 experts in hypertension and chronic disease care. Results of the time-motion studies and Delphi exercise were summarized using descriptive statistics. The results were inputted into a needs-based health workforce estimation model using Microsoft Excel. Sensitivity analyses were performed, using alternate input values for disease complexity, follow-up interval, and nurse productivity.

Results:
For a total of 5000 patients, with 60%, 32%, and 8% requiring follow-up visits in 1, 2, and 3 months, respectively, we estimated that 3928 patient encounters are required per month. Our data yielded an estimated clinical capacity of each nurse full-time equivalent (FTE) at 81 patient encounters/month. Thus, 49 nurse FTEs would be required to treat 5000 hypertension patients.

Conclusions:
A simple needs-based workforce estimation model for hypertension management is able to provide workforce projections that are useful for program planning, human resource allocation, and policy formulation. This approach can serve as a benchmark for future studies to manage chronic diseases in low- and middle-income countries.
Abstract 17036: Uncontrolled Apparent Treatment Resistant Hypertension is Associated With Increased Hospitalization and Increased Total Hospital Reimbursements
Authors: Vemulapalli Sreekanth , Deng Luqin , Patel Manesh , Kilgore Meredith L , Curtis Lesley H , Irvin Ryan , Svetkey Laura P , Shimbo Daichi , Calhoun David A , Muntner Paul
Published: July 2021

Background:
Apparent treatment resistant hypertension (aTRH) is defined as uncontrolled BP with three or more antihypertensives or controlled BP with 4 or more antihypertensives. ATRH is associated with increased adverse cardiovascular outcomes, however, little is known about healthcare utilization and expenses in those with aTRH.

Methods:
The study included participants 65 years and older in the nationwide Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with fee for service Medicare insurance. ATRH was defined as treatment with three or more antihypertensives of different classes. Participants were categorized as hypertensive without aTRH (no aTRH), controlled aTRH (BP ≤140/90), and uncontrolled aTRH (BP ≥ 140/90). Healthcare expenses were determined using diagnoses in Medicare parts A and B claims.

Results:
At baseline, 3933 (84.5%) had no aTRH, 247 (5.3%) had controlled aTRH, and 474 (10.2%) had uncontrolled aTRH. Compared to participants with no aTRH, those with uncontrolled aTRH and controlled aTRH were more likely to be male (45.7%, 50.4%, 53.8%) and black (48.5%, 47.0%, 35.6%), respectively. Participants with uncontrolled and controlled aTRH also had a higher prevalence of atrial fibrillation, stroke, and coronary artery disease compared to those with no aTRH. Adjusted annual median outpatient total reimbursements per patient were similar between those with uncontrolled aTRH, controlled aTRH, and no aTRH ($5248 [IQR $2904, $10006], $5697 [IQR $3104, $9930], $4525 [IQR $2587, $7923]). Uncontrolled aTRH, but not controlled aTRH was associated with an increased adjusted annual rate of hospitalizations as compared to no aTRH (risk ratio=1.13; 95% CI [IQR 1.03 - 1.24]; p=0.01). Among patients with any hospitalizations, uncontrolled aTRH was associated with the highest median annual inpatient total reimbursements ($6324 [IQR 3149, 16238]; controlled aTRH = $5507 [IQR 2197, 13884]; no aTRH $4968 [IQR 2252, 10882]).

Conclusions:
Uncontrolled aTRH is associated with an increased rate of hospitalizations and higher charges per hospitalization. Efforts to improve blood pressure control among patients with uncontrolled aTRH may also result in reduced hospitalizations and hospital charges.
Abstract 17049: Computer Simulation to Study the Effect of Structural Remodeling on Atrial Fibrillation Using Clinically-obtained Cardiac MRIs
Authors: Ng Jason , Ng Justin K , Parikh Paras , Goldberger Jeffrey J , Markl Michael , Carr James , Bai Wenjia , Kanagaratnam Prapa , Lim Phang B , Malcolme-Lawes Louisa C , Qureshi Norman A , Peters Nicholas S
Published: July 2021

Introduction:
Structural remodeling of the atria in the form of fibrosis is known to be a contributing factor for the initiation and maintenance of atrial fibrillation (AF).

Hypothesis:
Using computer simulation based on clinically-obtained MRIs, we tested the hypothesis that both dense and diffuse fibrosis play significant roles in the inducibility of AF and the effectiveness of pulmonary vein (PV) ablation.

Methods:
Magnetic resonance angiograms and delayed enhancement MRIs (DEMRIs) of the left atrium from 34 AF patients were used to construct the models for the computer simulations. Using the Fenton-Karma action potential model, three conditions were tested for AF inducibility: 1) no fibrosis, 2) diffuse fibrosis, and 3) diffuse and dense fibrosis. AF induction was attempted at each of the four PVs and episodes lasting >30 s were considered sustained. Wide area PV ablation was simulated on all sustained episodes.

Results:
With no fibrosis, sustained AF was achieved in 55.9±32.0% of induction attempts. This percentage was significantly increased to 92.6±15.7% and 93.4±12.8% with diffuse fibrosis and combined dense and diffuse fibrosis, respectively (p<0.0001 for both). PV ablation terminated 75% of episodes induced with no fibrosis, 62% with diffuse fibrosis and 60% with combined dense and diffuse fibrosis. Organized reentry usually formed after ablation with dense scar providing an anchor for reentry in episodes where dense scar is present.

Conclusions:
Both diffuse and dense fibrosis significantly increases the likelihood for AF induction and maintenance in the computer model with dense fibrosis providing additional anchor points in the left atrium for reentrant circuits.
Abstract 17185: Sympathetic Reinnervation is Required for Mammalian Cardiac Regeneration
Authors: White Ian A , Gordon Julie , Balkan Wayne , Hare Joshua M
Published: July 2021

Rationale:
Established animal models of tissue and limb regeneration demonstrate a critical dependence on concurrent reinnervation by the peripheral nervous system. The abundance of autonomic nerves in the mammalian heart suggests they play a similar role in the response to cardiac injury.

Objective:
To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration.

Methods and Results:
Crossing Wnt1:cre transgenic mice with a double-tandem (td) tomato reporter strain identified all neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. Whole mount epi-fluorescence microscopy facilitated the clear resolution of subepicardial autonomic nerves in the mouse ventricles providing unprecedented detail of the subepicardial neuroanatomy of the mouse heart. We confirmed that sympathetic nerve structures envelop the entire heart, and importantly, exhibit robust re-growth into the regenerating myocardium following resection of the left ventricular apex in neonatal mice. While innervated hearts regenerate with minimal scarring to the left ventricular myocardium, we report that innate cardiac regeneration was inhibited following sympathectomy, as determined by cross-sectional percentage of viable LV myocardium (n=9, 0.87±1.4% vs. n=6, 14.05±4.4% ; p<0.01).

Conclusions:
Ablation of post-ganglionic sympathetic nerves blocks the innate regenerative capacity of neonatal mouse hearts. Therefore, the innate ability of the neonatal mouse heart to undergo regeneration in response to injury is dependent on sympathetic innervation of the ventricular myocardium. This finding has significant implications for adult regeneration following myocardial infarction where nerve growth is hindered by age related influences and scar tissue.
Abstract 17197: The Value of Routine Near-patient Haemostasis Testing for Predicting Bleeding After Cardiac Surgery
Authors: Mumford Andrew , Harris Jessica , Plummer Zoe , Verheyden Veerle , Lee Kurtis , Rogers Chris , Reeves Barney C , Murphy Gavin J
Published: July 2021

Introduction:
Near-patient haemostasis tests assist diagnosis and treatment of blood clotting abnormalities in bleeding patients after cardiac surgery.

Aim:
To quantify the predictive value of routine near-patient haemostasis tests for coagulopathic bleeding in a large clinical trial.

Methods:
We performed a prospective cohort study of the patient characteristics and the results of 23 near-patient platelet and viscoelastometry tests in adults undergoing a range of cardiac surgery procedures. The primary outcome was clinical concern about bleeding (CCB), defined as a composite of high blood loss or pro-haemostatic treatment or re-operation for bleeding. A multivariable predictive model for CCB was developed based on the pre-operative characteristics of 1833 patients at a single cardiac centre recruited between March 2010 and August 2012. This model was validated using data for 1611 patients recruited at 16 other UK cardiac surgery centres between July 2009 and February 2013. The additional predictive value of near-patient test results was estimated in the development cohort.

Results:
CCB occurred in 449 (24.5%) patients in the development cohort. Male sex, absence of diabetes, complex procedure, anti-platelet treatment, short interval since withdrawal of anti-platelet treatment, reduced BMI, reduced pre-operative haematocrit and reduced pre-operative platelet count were independently associated with increased risk of CCB (area under RoC curve (AUR)=0.72 (0.69 to 0.75)). At 75% sensitivity, the specificity of the model was 57%. In the validation cohort, the AUR of the patient characteristics model was 0.63 (0.60 to 0.66). Adding the results of the most predictive near-patient tests performed immediately after surgery improved prediction of CCB in the development cohort (AUR 0.74; 0.72 to 0.77), but at 75% sensitivity this increased the specificity by only 4%. Adding the results of near-patient platelet tests performed before surgery did not further improve prediction of CCB (AUR 0.75; 0.72 to 0.77).

Conclusions:
Routine near-patient haemostasis tests offer little improvement in the prediction of CCB after cardiac surgery compared to pre-operative patient characteristics alone.
Abstract 17235: Trends in Endocarditis Hospitalizations at US Children's Hospitals From 2003-2014: Impact of the 2007 American Heart Association Antibiotic Prophylaxis Guidelines
Authors: Bates Katherine E , Hall Matthew , Shah Samir S , Hill Kevin D , Pasquali Sara K
Published: July 2021

Introduction:
Over the past decade, national organizations in several countries have released more restrictive guidelines for infective endocarditis (IE) prophylaxis, including the American Heart Association (AHA) 2007 guidelines. Multiple initial studies demonstrated no change in IE rates over time following release of these guidelines, however a more recent analysis over a longer time period in the UK suggested an increase in IE. This prior study primarily included adults. Current IE trends in the pediatric population are unknown.

Methods:
Children (<18 years) hospitalized with IE at 29 US centers participating in the Pediatric Health Information Systems Database from 2003-2014 were eligible for inclusion. Our primary analysis focused on IE most directly related to the change in the AHA guidelines, and included community-acquired IE cases (antibiotics covering oral streptococcal species started within 7 days of admission) in those >5 years of age (most likely to be receiving dental care). Interrupted time series analysis was used to evaluate IE rates over time indexed to total hospital admissions.

Results:
A total of 841 IE cases were identified. Median age was 13 years (interquartile range 9-15 years). In the pre-guideline period, the IE rate increased slightly over time (+0.013 IE cases/1000 hospitalizations per 6-month period, see Figure). In the post-guideline period there was a similar trend in IE rates (+0.012 IE cases/1000 hospitalizations per 6-month period) with no significant difference in slope in the pre vs. post period (p=0.9). Additional analyses in those with congenital heart disease, and in those hospitalized with any type of IE (not limited to oral streptococci) at any age, revealed similar results.

Conclusions:
In contrast to a recent UK study, we found no evidence of a change in IE hospitalization rates associated with revised IE prophylaxis guidelines over an 11 year period across 29 US children’s hospitals.
Abstract 17296: Autonomic Dysfunction in Metabolic Syndrome With Normal Blood Pressure is Associated With Exacerbate Response of Blood Pressure During Maximal Exercise
Authors: Dutra-Marques Akothirene C , Cepeda Felipe X , Rodrigues Sara , Carvalho Jefferson C , Toschi-Dias Edgar , Jordão Camila , Rondon Maria U , Alves Maria J , Trombetta Ivani C
Published: July 2021

Introduction:
Hypertensive patients presented impairment in the blood pressure (BP) response during maximal exercise test. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) are involved in the progression of metabolic syndrome (MetS) in cardiovascular disease.

Hypothesis:
(1) MetS patients with normal level of clinical BP show exaggerate peak and recovery systolic BP in response to maximal exercise; (2) Muscle sympathetic nerve activity (MSNA) and BRS are associated with these impairments.

Methods:
We selected MetS (ATP III) patients with normal BP (ASH/ISH criteria; MetS= 27, 46±1 y) and a healthy control group without MetS (C= 19, 48±2 y). We evaluated MSNA(microneurography), BRS (spontaneous BP and HR fluctuations) and auscultatory BP measures at pretest, peak, 1
st
, 2
nd
, 4
th
min of recovery during cardiopulmonary exercise test.

Results:
Compared to C, MetS had higher BMI and impairment in all MetS risk factors. MetS had higher BP at pretest, peak, 1
st
, 2
nd
, 4
th
min of recovery (P<0.05). Interestingly, we found that even MetS patients with normal BP had lower spontaneous BRS for decreases (9.38
+
0.7 vs. 12.33
+
1.25 msec/mmHg, P=0.03) and higher levels of MSNA (27
+
1 vs. 18
+
1 bursts/min, P<0.001) compared to C. Further analyses showed association between BRS for decreases with peak BP (r=-.32; P=0.04). Moreover, the MSNA had association with peak BP (r=.40; P=0.03) and BP at 1
st
min of recovery (r=.48; P=0.01). Fascinatingly, a subgroup of MetS patients with normal BP but exaggerate peak BP (systolic BP >190 mmHg for women and >210 mmHg for men) showed strong association between BRS for decreases with peak BP (r=-.70; P<0.02) and BRS for decreases with BP at 1
st
min of recovery (r=-.73; P<0.04).

Conclusion:
MetS patients even with normal BP, already show sympathetic hyperactivity and decreased baroreflex sensitivity which could explain, at least in part, the exacerbated BP response during maximal exercise.
Abstract 17320: Inhibition of Ceramide Synthesis Preserves Cardiac Function and Increases Survival in Doxorubicin-induced Cardiomyopathy
Authors: Ji Ruiping , Chang Jennifer Y , Liao Xianghai , Zhang Xiaokan , Kennel Peter , Castillero Estibaliz , Brunjes Danielle , Akashi Hirokazu , Homma Shunichi , Goldberg Ira , Schulze Paul Christian
Published: July 2021

Background:
Previous studies have linked increased ceramide and dihydroceramide (DHC) synthesis to cardiotoxicity. However, the effects of ceramide synthesis inhibition on doxorubicin (DOX)-induced cardiomyopathy are unclear.

Hypothesis:
Inhibition of de novo ceramide synthesis by myriocin maintains heart function and survival rate.

Methods:
C57BL/6J mice (8 wks, n=52) were treated with DOX (3 mg/kg every other day for 2 wks) with or without myriocin (0.3 mg/kg). Cardiac function was assessed by echocardiography. AC16 cardiomyocyte-like cells were incubated with DOX in the presence or absence of myriocin (10 uM). Ceramides were analyzed by LC/MS lipidomics. Reactive oxygen species (ROS) were measured by FACS (CellROX) and mitochondrial function determined by Seahorse analyzer.

Results:
In DOX-treated mice, inhibition of ceramide synthesis by myriocin preserved cardiac fractional shortening (29.2±2.7 vs 36.9±1.4% in myriocin; p<0.05), left ventricular systolic diameter dilation (3.2±0.1 vs 2.97±0.8 mm, p<0.05), running endurance (8.5 vs 17.5 min; p<0.05) and survival rates (35 vs 90% in myriocin, p<0.001). DOX increased cardiac total ceramides (+70%; p<0.001) and DHC (+73%; p<0.05); these increases were prevented by myriocin. Cardiac apoptosis in these cells was increased 4.1 fold by DOX and reduced by 50% with myriocin (p<0.05). In cells, DOX increased cellular ceramide content (+112.4%, p<0.01), especially C14 (+69%; p<0.05), C16 (+144%; p<0.01), C18 (+53%; p<0.05), C22 (+98%; p<0.05), C24 (+83.5%; p<0.01) and C24:1(+86%; p<0.05). Interestingly, ceramide accumulation in mitochondria of DOX-treated cells (+125%; p<0.05) was associated with decreased mitochondrial respiration (-76%; p<0.05) and respiratory capacity (-88%; p<0.05). Myriocin treatment decreased very long-chain ceramides (-52%; p<0.05), reduced apoptosis (-23%; p<0.01), and prevented proteolysis of actin protein ubiquitination (-31%; p<0.05). Also, myriocin inhibited DOX-induced increase of ROS (+32%; p<0.05).

Conclusion:
Cardiomyocyte ceramide accumulation, especially in mitochondria, is associated with mitochondrial dysfunction, cardiotoxicity and reduced survival. Pharmacological inhibition of ceramide synthesis may prevent lipotoxicity.