bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15903: An Improvement of Score Models in the Prediction of Deep Vein Thrombosis of Upper and Lower Limbs in Hospitalized Patients
Authors: Cardella Antonella Maria , D'Assoro Antonio , Puccia Giuseppe
Published: March 2022

Introduction:Deep Vein Thrombosis (DVT) of both lower and upper limbs is increasingly being recognized as a clinical entity in patients with chronic diseases hospitalized for several comorbidities. The occurrence of DVT in sites other than lower limbs is an emerging clinical presentation in a setting of a Department of Medicine. The relationship between score models, based on risk factors, symptoms and clinical signs of lower limbs DVT, and circulating biomarkers is not well studied.

Hypothesis:We hypothesized to give an additional value to score models using circulating biomarkers in the prediction of DVT in patients hospitalized in Internal Medicine Department.

Methods:We prospectively recruited 178 consecutive patients who presented a D-dimer value >500 ng/ml. In each patient Wells modified score for DVT, Hamilton score, Kahn score and St. André Hospital score were applied. We measured serum levels of albumin (%) and protein S (%). Diagnosis of DVT was made by Extended Compression Ultra-Sonography (ECUS) standardized procedure. All patients underwent also an angiographic-CT-scan

Results:In 85 (48%) patients the diagnosis of DVT was confirmed. Sites of DVT were as follows: Lower limbs venous thrombosis n=71 (84%); Upper limb venous thrombosis n=8 (9%); portal vein thrombosis n=6 (7%). Patients with DVT had significantly lower albumin levels as compared with controls (mean ± SD 47.6 ± 7.9 vs 55.4 ± 4.6 %, respectively, P<0.001) and lower Protein S (60.7 ± 26.3 vs. 87.6 ± 11.9 %, P<0.001). In this setting, the use of clinical risk scores based on symptoms and clinical signs showed low accuracy (AUC 0.690). We gave an additional value to these scores by testing in combination biomarkers and two of the best items of all clinical score models used to predict DVT: we evaluated a ROC curve analysis including value of Albumin (%), Protein S (%), previous DVT and cancer obtaining a higher accuracy (AUC 0.901, Positive Likelihood Ratio (LR+) 12.97 and Negative Likelihood Ratio (LR-) 0.17).

Conclusions:This study demonstrates that biomarkers improve the prediction of clinical scores in the diagnosis of DVT of all sites in hospitalized patients.
Abstract 15905: Incidence and Characteristics of Major Bleeding Among Rivaroxaban Users With Renal Disease and Non-valvular Atrial Fibrillation
Authors: Tamayo Sally , Patel Manesh , Yuan Zhong , Sicignano Nicholas , Hopf Kathleen , Peacock Frank
Published: March 2022

Background:
Patients with renal impairment (as compared to those without) who receive anticoagulants appear to be at increased risk of bleeding based on recent clinical trials. Rivaroxaban is a direct factor Xa inhibitor used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF).

Purpose:
To quantify the rates and better understand the pattern of major bleeding (MB) among NVAF patients with and without a coded diagnosis of renal disease (RD) who take rivaroxaban.

Methods:
Nearly 10 million electronic medical records from the Department of Defense healthcare system were evaluated to identify MB related hospitalizations among rivaroxaban users with NVAF over a 2 year period as part of an ongoing post-marketing study. A validated algorithm (Cunningham 2011) was used to identify MB. Renal disease (reflective of impaired renal function) was defined via diagnostic codes within 6 months prior to the bleeding date for MB cases, or the reporting quarter for non-MB patients. Rates of MB were quantified by renal disease status. Additional data were collected on patient characteristics and comorbidities, MB management, and outcomes.

Results:
Overall, 39,052 rivaroxaban users with NVAF were identified; 6,034 patients (15.5%) had RD. Patients with RD had a higher rate of MB than those without RD, 4.65 per 100 person-years versus 2.59 per 100 person-years, respectively. Patients with RD also had a greater prevalence of comorbidities and higher CHA
2
DS
2
-VASc scores. Key findings are presented in Table 1.

Conclusion:
In a post-marketing study of 39,052 rivaroxaban users with nonvalvular atrial fibrillation, patients with renal disease experienced a higher rate of MB than those without renal disease. This higher rate of MB may be partly due to the confounding effects of comorbidities in patients with RD, as reflected by their higher CHA
2
DS
2
-VASc scores, and is worthy of further investigation.
Abstract 15935: 20,000 Person-Years Later: Long-term Mortality in a Large Drowning Registry
Authors: Michiels Erica A , Reynolds Joshua C , Reeves Mat , Ahmadabadi Mojdeh N
Published: March 2022

Objective:
Relatively little is known about the long-term outcomes of drowning. There is some evidence of long-term neurocognitive dysfunction among small cohorts, but larger epidemiological studies are lacking. We aimed to assess the long-term mortality of drowning victims from a large registry.

Hypothesis:
We hypothesized that patients with sequelae of more severe drowning injury are at higher risk of long-term mortality.

Methods:
Secondary analysis of an existing drowning registry from Seattle, WA. We included the subset of patients that survived to hospital discharge, tabulating Utstein-style drowning variables with descriptive statistics. We used the National Death Index (NDI) to assess long-term mortality beyond the index event through 2012. Wilcoxon rank-sum and chi-square tests assessed differences between long term survivors and non-survivors. We constructed KM curves, stratified by age, sex, drowning-related cardiac arrest, and mRS at hospital discharge, and compared them with the log-rank test. Cox proportional hazard modeling tested variables associated with long-term mortality.

Results:
Of 2,824 subjects in the registry (submersion 1/74 - 7/96), 776 (27%) survived to hospital discharge and were included in our analyses (median age 5 years, IQR 2-15; 68% male). Long term survivors and non-survivors differed by age (4 years, IQR 2-15 vs. 25 years, IQR 6-46; p<0.0001), recreational substance use (4% vs. 18%; p<0.001), pre-existing comorbidities (16% vs. 38%; p=0.01), drowning-related cardiac arrest (7% vs. 25%; p<0.0001), mechanical ventilation (13% vs. 37%; p<0.0001), and seizures (2% vs. 10%; p<0.0001). Only 63 (8%) subjects died during the 19,699 person-year follow-up period. Subjects with age >40 years (p<0.0001), drowning-related cardiac arrest (p<0.0001), and mRS 4-5 (p<0.0001) were at higher risk of long-term mortality. In adjusted analyses, age (HR 1.05; 95% CI 1.03, 1.07) and mRS 4-5 at hospital discharge (HR 8.2; 95% CI 1.8, 36.4) were associated with long-term mortality.

Conclusion:
Overall mortality was low during long term follow-up. Age at the index event, drowning-related cardiac arrest, and functional status at hospital discharge were associated with subsequent long term mortality.
Abstract 15955: Impact of an Automated Chest Compression Device on Team Communication During Simulated Cardiac Arrest Resuscitations - A Pilot Study
Authors: Gittinger Matthew , Brolliar Sarah , Grand James A , Nichol Graham , Fernandez Rosemarie
Published: March 2022

Background:
Communication and teamwork failures correlate with diagnostic errors and deviations from ACLS protocols during cardiac arrest (CA) resuscitation. High task workloads stress teams’ capacity and negatively impact team effectiveness. The LUCAS
®
Chest Compression System (Physio-Control, Redmond, WA) is an automated chest compression device intended to reduce workload associated with chest compression delivery.

Objective:
To assess the impact of LUCAS on team communication and adherence to ACLS algorithms during a simulated CA resuscitation.

Methods:
Resuscitation teams (n=12) were randomly assigned to manual compressions (control) or LUCAS (intervention) during a simulated CA consisting of Phase 1, pre-arrest (Baseline), and Phase 2, ventricular fibrillation phase (Arrest). Phase 1 metrics included total team communication statements and 10 patient care actions. Phase 2 communication was measured as number of statements related to (a) CPR coordination, (b) compression performance, and (c) diagnosis. Phase 2 patient care metrics included (a) adherence to ACLS algorithm and (b) quality of compressions. Statistical analyses included descriptive statistics, paired t-test, and effect size (Hedge’s g).

Results:
In Phase 1 there was no difference in either communication or patient care outcomes. In Phase 2, teams in the intervention group (n=6) made more frequent statements focused on diagnosis (Hedge’s g = 1.88, t[df 10]=3.53, p=0.01) and fewer directed toward CPR coordination (Hedge’s g = -0.98, t[df 10] = -1.85, p = 0.1) and compression performance (Hedge’s g = -1.55, t[df 10]=-2.91, p = 0.02). Teams using the LUCAS had a 22.8% decrease (95% CI [-48.80, 3.24]) in delivery of poor quality chest compressions (Hedge’s g = 1.04, t[df 10] = -1.87, p=0.08) and fewer deviations in medication administration (Hedge’s g = -1.49, t[df 10] = -1.87, p=0.02) as compared to in the control group (n=6).

Conclusions:
In this small pilot study, use of an automated compression device was associated with an increase in team communication focused on diagnosis and improved adherence to ACLS algorithms. While not all outcomes reached statistical significance, the large effect sizes demonstrate practical significance. A larger study may reach statistical significance.
Abstract 15991: Multiple Listing Increases Access to Heart, Lung, Liver, and Kidney Transplantation
Authors: Givens Raymond C , Schulze Paul C , Mancini Donna M
Published: March 2022

Introduction:
United Network for Organ Sharing (UNOS) policy allows solid organ transplant candidates to be listed at multiple centers simultaneously. As not all candidates have the resources needed for multiple-listing, this policy may advantage wealthier patients.

Methods:
Among adult first-time, single-organ candidates in the UNOS database between January 1, 2000 and December 31, 2013 who had a recorded waitlist outcome, we identified 33,928 patients waiting for heart (HT), 24,633 for lung (LuT), 103,332 for liver (LiT) and 223,644 for kidney transplantation (KT). We used propensity score matching to address imbalances among baseline covariates and conducted competing risk analyses of waitlist outcomes.

Results:
The proportion of multiple-listed patients (ML) was 2.0%, 3.4%, 6.0% and 12.0% among HT, LuT, LiT and KT candidates, respectively. Regardless of organ type, ML candidates were younger than single-listed (SL) patients (mean age 52 ± 1 vs. 54 ± 1), more likely to be insured privately (58.9% vs 51.1%) and less likely by Medicaid (5.8% vs 10.3%), and lived in ZIP codes with higher median incomes ($93,081 ± $12,772 vs $67,690 ± $9,205); all p-values <0.0001. ML patients had proportionally higher functional status in addition to organ-specific indicators of lower acuity at initial listing. Across all organs, ML patients had longer waiting times at their initial listing centers but higher eventual transplant rates (OR [95% CI] = 1.23 [1.03-1.47], 1.56 [1.31-1.86], 1.57 [1.49-1.66] and 2.01 [1.95-2.07] for HT, LuT, LiT and KT, respectively) and lower rates of death while waiting (0.66 [0.50-0.87], 0.83 [0.67-1.03], 0.63 [0.58-0.68] and 0.53 [0.51-0.55]). Differences in waitlist outcomes between ML and SL patients were maintained after propensity score matching across all organs and in some cases were greatly accentuated. There were no consistent differences in post-transplant outcomes.

Conclusions:
Multiple listing is a rational response to organ shortage and long waiting times but appears to advantage patients with means to utilize it rather than the most medically needy. The UNOS multiple listing allowance should be reconsidered.
Abstract 15995: Etiology and Outcomes Associated With Endothelial Dysfunction in Post Cardiac Arrest Patients
Authors: Gidwani Hitesh V , Coppler Patrick , Rattan Rohit , Rahman Riaz , Shashidharan Shiva , Darwin Andrew , Adams Peter , Taft Maia , Airgood Hannah , Elmer Jonathan , Dezfulian Cameron
Published: March 2022

Background:
Endothelial dysfunction (ED) may occur after cardiac arrest (CA) both due to the underlying patient comorbidities which result in CA and the global ischemia-reperfusion which results. The prevalence of ED after CA is poorly characterized as is any association with outcomes.

Hypothesis:
ED will be more common in asphyxial arrests, after prolonged CPR times and in subjects with multiple coronary artery risk factors. ED will associate with worsened outcomes.

Methods:
Prospective, observational study of 23 CA with return of spontaneous circulation (ROSC) expected to live >48 h. ED was assessed at 0-6 hours and at 36-48 hours after ROSC using measurements of plasma nitrite (n=14) or laser speckle contrast imaging (LSCI) (n=13) before and after 6 min vaso-occlusion (VO) of forearm blood flow. VO was achieved using a blood pressure cuff inflated at 200 mm Hg. LSCI quantified blood flow at baseline (pre-VO), during ischemia (trough), upon reperfusion (hyperemia peak) and 5 min later (nadir). LSCI values were all normalized to pre-VO baseline. Plasma nitrite was measured before after VO. Plasma nitrite was quantified by reductive chemiluminescence. ED is known to result in lower plasma nitrite and reduced post-VO hyperemia and nadir. Data was gathered on patient comorbidities, CA characteristics and outcomes and means compared by Mann Whitney U for dichotomous variables and Spearman correlation for continuous variables.

Results:
Lower ischemic trough and reperfusion nadir were associated with unfavorable features and outcomes (
Table
). No patient factors were associated ED. LSCI nadir at 0-6 hrs correlated with CPR duration (r = -0.7, p =0.01) and trough correlated with number of CPR epinephrine doses (r= -0.7, p = 0.01). Plasma nitrite levels were similar in all comparisons.

Conclusions:
LSCI features characteristic of ED were more often noted with prolonged and asphyxial, non-VF CA rather than patient factors and were associated with worsened outcome.
Abstract 15997: The Effect of Combined Statin/Fibrate Therapy on Cardiovascular Disease is Influenced by Sex and Dyslipidemia: ACCORDION-Lipid Long-Term Follow-up
Authors: Elam Marshall B , Lovato Laura C , Ginsberg Henry N ,   on behalf of the ACCORD/ACCORDION Study Group
Published: March 2022

Introduction:
In the long-term ACCORD-Lipid trial of 5,518 high risk patients with type 2 diabetes, combined statin+fibrate therapy failed to reduce the composite outcome of nonfatal myocardial infarction (MI), nonfatal stroke or cardiovascular (CV) death. Pre-specified subgroup analyses identified heterogeneity in treatment effect according to gender, with a benefit for men and possible harm for women, and possible benefit for patients with both high triglyceride and low HDL-C at baseline. At trial end, 4,644 ACCORD-Lipid Trial participants consented to be followed post-trial in the passive ACCORD Follow-On (ACCORDION) Study.

Hypothesis:
Does a therapeutic strategy that initially used a fibrate to raise HDL-C/lower triglyceride levels and a statin for treatment of LDL-C for a mean of almost 5 years reduce the long-term (mean 9+ years) risk of major CVD events after 4+ more years of follow-up compared to a strategy that only used a statin for treatment of LDL-C?

Results:
During about 9 years of follow-up (from ACCORD randomization to the end of ACCORDION), the hazard ratios between participants originally randomized to statin+fibrate versus statin alone were 0.93 (0.83-1.05 95%CI, p=0.25) for the primary outcome (nonfatal MI, nonfatal stroke or CV death); 0.94 (0.84 -1.06, p=0.32) for all-cause mortality, 0.93 (0.78-1.10, p=0.37) for nonfatal MI, and 0.84 (0.69-1.01, p=0.07) for cardiovascular mortality. These hazards are similar to those observed during the trial portion of follow-up. The heterogeneity of response for gender and presence of dyslipidemia observed in ACCORD-LIPID continued to be observed after the addition of post-trial events during the extended follow-up period with hazard ratios of 0.84 (0.73-0.96) for men and 1.30 (1.01-17) for women (interaction P=0.003) and 0.73 (0.56-0.95) for dyslipidemic and 0.99 (0.86-1.13) for non-dyslipidemic subgroups (interaction P=0.048).

Conclusions:
Additional post-trial follow-up of ACCORD participants for a total of about 9 years of total follow-up did not alter the original ACCORD findings that in people with type 2 diabetes and other cardiovascular risk factors, long-term treatment with a fibrate+statin (compared to a statin alone) did not reduce the rate of CV events or all-cause mortality.
Abstract 15998: Inflammatory Cytokines and Kidney Dysfunction are Associated in Individuals With Hypertensive Emergency
Authors: Vilela-Martin Jose F , Andrade Days O , Cosenso-Martin Luciana N , Gregório Michele L , Godoy Moacir F , Souza Doroteia R , Yugar-Toledo Juan C
Published: March 2022

Introduction:
Chronic hypertension and kidney dysfunction are associated. However, scarce studies have evaluated the participation of the inflammatory process in the pathogenesis of acute elevation of blood pressure (BP) (characterized by hypertensive crisis - HC) and kidney dysfunction. Thus, this study had objectives: 1- to identify clinical profile and renal function of the individuals with HC, subdivided in urgency (HU) and hypertensive emergency (HE) and 2- to evaluate relationship between kidney function and inflammatory cytokines: interleukins (IL-1β, IL-6, IL-8, IL-18), tumoral necrosis factor (TNF-α) and anti-inflammatory cytokine 10 (IL-10) in subjects with HC (HU and HE).

Methods:
We studied 274 individuals: 74 normotensive (NT), 74 controlled hypertensive (CH), 50 with HU and 78 individuals with HE. The glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease equation (MDRD). The serum levels of cytokines were made by MULTIPLEX and ELISA technique. The Kruskall Wallis and Mann Whitney tests, and Spearman correlation were used for comparison between groups, with a significance level for p-value <0.05.

Results:
The diastolic BP and heart rate were significantly higher in the HC group (120mmHg and 85bpm, respectively) compared to the CH group (75mmHg and 68 bpm, respectively). Individuals with HE were older. Potassium was significantly lower in HE group (4,2mEq/l) compared to NT, CH and HU groups (4.5, 4.4 and 4.4mEq/L, respectively; p<0.05). The GFR was significantly lower in HE group (65ml/min/m2) in comparison to HU (73), CH (82) and NT (88mL/min/m2) (p<0,001). All measured cytokines were significantly higher in patients with HE compared to NT and CH groups. It was observed negative correlation among GFR, diastolic BP, and creatinine for all the groups (p<0,0001). There was also negative correlation between GFR and cytokines in HE individuals (p<0,05). Conclusions: Individuals with HE present GFR reduction in comparison to others studied groups. It is also observed higher cytokines levels in HE group and negative correlation between GFR and inflammatory cytokines. This suggests the involvement of inflammatory cytokines in the pathogenesis of acute hypertensive event and kidney dysfunction.
Abstract 16001: Relationship Between Serum n-3 to n-6 Poly-unsaturated Fatty Acid Ratios and Coronary Plaque Components Identified by iMap-Intravascular Ultrasound in Patients With Stable Angina Pectoris
Authors: Kojima Keisuke , Kimura Shigeki , Misawa Toru , Hayasaka Kazuto , Mizusawa Masafumi , Yamakami Yosuke , Sagawa Yuichiro , Otani Hirofumi , Hishikari Keiichi , Hikita Hiroyuki , Takahashi Atsushi
Published: March 2022

Background:
Residual risk of cardiovascular disease exists even in patients achieving low-density lipoprotein cholesterol (LDL-C) goals. A low value of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio is well known to be associated with cardiovascular events. However, the association between serum EPA/AA ratio and coronary plaque components has not been fully investigated.

Purpose:
We evaluated the relationships between serum EPA/AA ratio and coronary plaque morphology on iMap-intravascular ultrasound (IVUS) which is a 40 MHz IVUS tissue characteristic system.

Methods:
We investigated 80 consecutive coronary culprit lesions with stable angina pectoris (SAP) patients, who underwent pre-intervention iMap-IVUS. All patients were divided into two groups; groups with higher values of the median EPA/AA ratio and lower values of the median EPA/AA ratio. We assessed the relationship between the two groups.

Results:
Median values of EPA, AA and EPA/AA ratio were 67.5 (44.3-100.3) μg/ml, 174.2 (145.5-202.9) μg/ml, and 0.38 (0.23-0.60). Patients in lower EPA/AA ratio group (<0.38) showed younger age (65±11 vs 70±6, p=0.02), more OMI patients (40 vs 18%, p=0.03), higher value of LDL-C (94.5±29.3 vs 80.9±26.5 mg/dl, p=0.03), lower ejection fraction (61.4±8.8 vs 65.4±7.2%, p=0.04), greater lesion plaque area (11.5±4.4 vs 9.6±4.4 mm2, p<0.05), compared with higher EPA/AA ratio group. In multivariate analysis, LDL-C value was an independent predictor of lower EPA/AA ratio (odds ratio 1.02, 95% confidence interval 1.00-1.04, p= 0.04).

In lower LDL-C group (<70 mg/dl), EPA/AA inversely correlated with %-necrotic area and volume (r=-0.56, p=0.004, and r=-0.54, p=0.01), and positively correlated with %-fibrotic area and volume (r=0.57, p=0.003, and r=0.54, p=0.01), although EPA/AA ratio did not correlate with plaque components in higher LDL-C groups. In lower LDL-C group, for prediction of the highest %-necrotic volume tertile (>42.1%), cut-off value of EPA/AA ratio was 0.20 (sensitivity 50%, specificity 94%, area under the curve 0.77, p=0.02).

Conclusion:
serum EPA/AA ratio may be related to plaque components at the culprit site in SAP patients with low LDL-C values.
Abstract 16053: Dynamic Trans Gene Expression Regulation by eQTLs in Complex Disease Traits
Authors: Yao Chen , Joehanes Roby , Huan Tianxiao , Liu Chunyu , Johnson Andrew D , Freedman Jane , Munson Peter J , Levy Daniel
Published: March 2022

Genome-wide association studies (GWAS) have been widely used to identify genetic variants associated with complex traits. However, for many of these diseases, it remains unclear how the genetic variants exert their effect on the phenotype, and especially how they affect gene expression of remote genes (trans-eQTL). In a previous study, we found that a large proportion of trans-eQTLs are also cis-eQTLs. Therefore, we hypothesized that some trans-eQTLs influence expression of distant genes through effects on expression levels of a cis-transcript. Using 42,271 SNPs associated with 1,960 complex traits available in public data sets curated in GRASP, we first explored the gene expression associations of trait-associated SNPs in 5,257 individuals from the Framingham Heart Study (FHS) and then we tested mediation effects of cis-transcripts on trans-transcripts when both were associated with the same eQTL. At FDR<0.05, we identified 2,324 trans-eQTLs; 84% of them (1,953) were found to have cis-associated transcripts. Mediation testing suggested that for 797 (41%) of these 1953 trans-eQTLs, the disease-associated SNP may alter expression of the trans-transcript via expression of genes near the eQTL (p<0.0005 for 10,000 permutations). We searched across 7 cardiometabolic traits (BMI, systolic/ diastolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, glucose) and identified several cis mediators affecting the expression of multiple downstream genes; the cis mediators include SH2B3, ALDH2, NLRC5, PCSK7 and ALAS2. The expression of each cis mediator gene was significantly associated with one or more CVD phenotype in 5,257 FHS participants. These findings highlight a novel approach to identifying promising drug targets.
Abstract 16073: Quality of Life for Patients and Caregivers After Implantation of a Ventricular Assist Device
Authors: Bidwell Julie T , Mudd James O , Gelow Jill M , Lyons Karen S , Hiatt Shirin O , Chien Christopher V , Grady Kathleen L , Lee Christopher S
Published: March 2022

Introduction:
Ventricular Assist Device (VAD) implantation is a therapeutic option for many patients with advanced heart failure (HF). Although patient quality of life (QOL) generally improves after VAD, little is known about changes in QOL among caregivers of patients undergoing VAD implantation.

Hypothesis:
We hypothesized that patient QOL would improve and caregiver QOL would worsen after VAD implantation.

Methods:
This was a prospective longitudinal study of patients receiving VAD therapy for advanced HF and their informal caregivers (n=27 dyads). QOL was measured pre- VAD implant and at 30 and 90 days post-implant. For patients, QOL was measured with the Kansas City Cardiomyopathy Questionnaire. For caregivers, QOL was measured with the SF-36. Both measures range from 0-100; higher scores indicate better QOL. Pre vs. post VAD comparisons in QOL were examined using paired t-tests.

Results:
Caregivers and patients were 54.9±10.3 and 54.3±14.6 years of age, respectively. Most patients (88.9%) were male, and most (63.0%) were receiving a VAD as a bridge to transplant. A majority of caregivers were female (85.2%) and the patients’ spouses (77.8%). Patient QOL improved significantly from baseline (28.4±20.7) to 30 days (50.0±25.3; t=-4.1, p<0.01) and 90 days post-implant (62.7±20.0; t=-2.3, p=0.03). Caregiver QOL worsened significantly from baseline (55.2±7.1) to 30 days (51.9±10.3; t=2.4, p=0.03) and remained at that level at 90 days post-implant (52.1±1.9; t=0.3, p=0.76).

Conclusions:
Although VAD therapy is associated with QOL benefit for patients, clinicians and researchers should recognize that caregivers are at risk for significant worsening of QOL post-implant. Caregivers of patients undergoing VAD implantation may benefit from greater anticipatory guidance and ongoing support.
Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes
Authors: Zhang Xiao-Dong , Chen Wei Chun , Lee Jeong-Han , Jian Zhong , Izu Leighton , Izu Ye-Chen , Chiamvimonvat Nipavan
Published: March 2022

Background.
Small conductance Ca
2+
-activated K
+
(SK) channels play significant roles in regulating the excitability of cardiomyocytes (CMs). SK channels are unique in that they are gated solely by intracellular Ca
2+
and hence, function to integrate intracellular Ca
2+
and membrane potentials on a beat-to-beat basis in the heart. Our previous studies revealed that cardiac SK2 channels coupled with L-type Ca
2+
channels (LTCCs) through a physical bridge, α-actinin2, suggesting that LTCCs may be functionally coupled with SK2 channels by providing local Ca
2+
domain to activate the SK channels. However, a recent study suggested that sarcoplasmic reticulum (SR) Ca
2+
release is necessary and sufficient for the activation of cardiac SK channels. The objective of the study is to examine the mechanisms of SK channel activation in native CMs.

Methods and Results.
By using a voltage-clamp protocol in rabbit CMs to activate LTCCs followed immediately by a test voltage to monitor the SK currents, we recorded apamin-sensitive SK currents in response to the Ca
2+
influx. By altering the duration of activation of LTCCs, the activation of SK currents as a function of the increasing Ca
2+
influx was quantified. EGTA or BAPTA were then used to test the intracellular Ca
2+
domain necessary for SK channel activation. BAPTA but not EGTA completely disengaged the coupling between LTCCs and SK channels. SK currents coupled with Ca
2+
influx
via
LTCCs continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca
2+
store, suggesting that LTCCs provide the immediate Ca
2+
microdomain for the activation of SK channels in CMs. Super-resolution imaging of SK2, Ca
v
1.2, and ryanodine receptor 2 (RyR2) using stimulated emission depletion (STED) microscopy was performed to directly quantify the distance among SK, LTCC and RyR2 in CMs.

Conclusion.
Ca
2+
influx through LTCCs provides the immediate and efficient Ca
2+
microdomain for the activation of SK channels. Furthermore, changes in SK channel activation kinetics following SR Ca
2+
depletion suggest both LTCC-mediated Ca
2+
influx and SR Ca
2+
release are necessary for the activation of cardiac SK channels.

Funded by NIH (R01 HL085727 and R01 HL085844 to NC), VA (I01 BX000576 to NC) and AHA (14BGIA18870087 to XZ).
Abstract 16237: Predicting Long-term Prognosis in Stable Peripheral Artery Disease With Baseline Functional Capacity Estimated by the Duke Activity Status Index
Authors: Senthong Vichai , Wu Yuping , Hazen Stanley , Tang Wilson
Published: March 2022

Introduction:
The ability of a simple self-assessment tool for estimated functional capacity to predict long-term prognosis in patients with established peripheral artery disease (PAD) is unknown.

Objective:
This study examined whether subjective measurement of functional capacity estimated by using of the Duke Activity Status Index (DASI) questionnaire predicts long-term prognosis in patients with established PAD.

Methods:
We examined the relationship between DASI scores and all-cause mortality over a 5-year follow-up in 771 stable patients with established PAD.

Results:
Two hundred ten patients (27%) died over 5-year follow-up . The lowest DASI scores were associated with a 3.2-fold increased risk of 5-year all-cause mortality (HR 3.23, 95%CI 2.19-4.75, p<0.001; Figure). For overall PAD patients, after adjustments for traditional risk factors, estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hsCRP), and low DASI score remained predictive of 5-year all-cause mortality (adjusted HR 2.09, 95%CI 1.36-3.23, p<0.001). Adjusting for traditional risk factors, eGFR and hsCRP, patients with the lowest DASI scores had higher 5-year all-cause mortality (HR 2.13, 95%CI 1.1-4.12, p<0.05 for carotid artery stenosis (CAS); HR 2.06, 95%CI 1.16-3.64, p<0.05 for non-CAS; HR 2.01, 95%CI 1.11-3.66, p<0.05 for lower extremity artery stenosis (LEAD); and HR 2.15, 95%CI 1.13-4.09, p<0.005 for non-LEAD, respectively).

Conclusions:
A simple self-assessment tool of functional capacity provides independent and incremental prognostic for long-term adverse clinical events in stable patients with established PAD beyond each PAD diagnostic subtype.
Abstract 16276: A Web-based Tool for Predicting Acute Kidney Injury in ST-elevation Myocardial Infarction
Authors: Zambetti Benjamin R , Ellis Robert T , Hwang Inyong , Chumpia Mason , Heckle Mark R , Smith Blake , Crouse Mary T , Efeovbokhan Nephertiti , Thomas Fridtjof , Khouzam Rami N , Ibebuogu Uzoma N , Reed Guy L
Published: March 2022

ST-elevation myocardial infarction (STEMI) requires emergent diagnostic catheterization and therapeutic percutaneous coronary intervention. These therapies may cause acute kidney injury (AKI), a serious procedural complication that contributes to morbidity and mortality in STEMI patients. Identifying patients at risk for renal complications may save lives and reduce healthcare costs, but there is no validated tool for predicting AKI in STEMI patients.

Methods:
The UT-Methodist STEMI program is a racially diverse series of 1144 consecutive patients. We derived and validated the UT-AKI score to predict the risk of AKI in patients referred for STEMI (and not currently on dialysis). AKI was categorized by the modified AKI Network and RIFLE indices. The UT-AKI score was derived from logistic regression analysis performed on a randomly selected derivation dataset using variables with significant univariate relationships to AKI and markers of renal function. Receiver operator characteristic (ROC) curves for the UT-AKI were assessed in the derivation and validation datasets. Statistical significance was measured by appropriate parametric and non-parametric tests; a p<0.05 was considered significant.

Results:
The incidence of AKI was similar in patients undergoing diagnostic catheterization with or without PCI (12% vs. 14%, p=0.34). ROC curve analysis of the validation data set showed that the UT-AKI score (AUC 0.76 (95% CI 0.70-0.82)) was significantly better at classifying patients at risk for AKI than the ACEF (AUC 0.65 (95% CI: 0.58-0.73)), AGEF (AUC 0.65 (95% CI: 0.58-0.72)), or Mehran (AUC 0.67 (95% CI: 0.59-0.75)). The classification accuracy for the UT-AKI index was comparable for milder and severe forms of AKI.

Conclusions:
In the largest analysis of STEMI patients to date, we found no significant difference in the risk of AKI from PCI vs. diagnostic catheterization. The validation study indicates that the UT-AKI index was significantly better than other scores at classifying which patients will develop AKI. Accurate prediction of AKI may help physicians to personalize therapies and develop novel strategies to reduce kidney injury in patients with STEMI.
Abstract 16277: Gender-dimorphic Effect of Optic Atrophy Protein (OPA)-1 on Platelet Activation and Thrombosis
Authors: Souvenir Rhonda A , Fidler Trevor P , Weyrich Andrew S , Abel E. Dale
Published: March 2022

Mitochondrial dysfunction is strongly associated with many disorders including metabolic and cardiovascular diseases and their complications. Preliminary studies of platelets from the Framingham offspring cohort, revealed enrichment in transcripts encoding for the mitochondrial dynamics proteins: optic atrophy-I in females, and mitofusin II in both genders that correlated with cardiovascular risk. These transcripts encode established regulators of mitochondrial fusion, electron transport complex (ETC) assembly and apoptosis, thereby suggesting that altered mitochondrial dynamics may contribute to platelet dysfunction. Thus, to determine whether the enrichment in OPA1 transcripts in females that correlates with increased CVD risk represents an adaptive or pathophysiological response, mice with platelet-specific deletion of OPA1 (pOPA-1 KO) were generated. Male pOPA-1 KO mice exhibited compromised cristae morphology and a 50% reduction in mitochondrial DNA. Additionally, mitochondrial function assessed by an extracellular flux analyzer (XF24 Seahorse biosciences) was reduced by 50%. Mitochondrial dysfunction in male pOPA-1 KO mice was associated with heightened agonist response (a hyperactive phenotype). Male pOPA-1 KO mice had a shortened time to stable occlusion of the carotid artery as assessed in vivo by rose Bengal photochemical injury, and were more prone to develop a thrombus (14/15 knockouts vs. 4/8 controls) following permanent ligation of the inferior vena cava. In contrast, cristae morphology was normal and mitochondrial DNA unchanged in females. Additionally, the females revealed no evidence of heightened agonist response or increased incidence of thrombus formation. Thus OPA1 plays an essential role in regulating platelet mitochondrial function, platelet activation and thrombosis in males but not in females. These findings suggest that whereas maintaining OPA1 expression might be a protective adaptation in males, OPA1 induction in platelets of females with diabetes might not protect against platelet hyperactivation.
Abstract 16306: Characteristics of Left Ventricular Summit Ventricular Arrhythmias Ablation - The Inaccessible Peak
Authors: Pillarisetti Jayasree , Annapureddy Tulasi , Neeurmalla Ravali , Molugu Maruthsakhi , Vodapally Mamatha , Maybrook Ryan , Atoui Mousthapha , Reddy Madhu , Lakkireddy Dhanunjaya
Published: March 2022

Introduction:
Ventricular arrhythmias (VA) arising from the left ventricular (LV summit) are often inaccessible especially in the region superior to the coronary sinus (CS) and ablation at multiple sites may be required. We sought to define the procedural characteristics and outcomes in this group of patients.

Methods:
Consecutive patients who underwent ventricular premature beat (VPB) ablation at our academic center were obtained. Patients with VPBs arising from the LV summit were noted and their charts were reviewed for clinical and procedural characteristics.

Results:
There were a total of 110 patients who underwent VPB ablation between January 2012 to March 2015. Of these there were 13 patients whose VA site of origin was determined to be from the LV summit intra-procedurally. Mean age of the patients was 53±16 years with 85% whites and 54% males. Mean QRS duration was 117±33ms. 11 patients were on a beta-blocker, 1 on a class Ia agent and 2 on no medications. Mean EF pre and post procedure was 41±14% and 47±10%. Mean PVC burden was 26%. EKG morphology showed LBBB pattern pattern in V1 with transition in V3 (in 6 patients), RBBB pattern (7 patients) with inferior axis and negative lateral leads. Mean procedure and fluoroscopic times were 266±82 and 45±20 minutes respectively. Acute success was obtained in 69% (n=9) and partial success in 15% (n=2). Acute success was obtained by ablating in the CS alone in 3 patients, epicardially alone in 3 patients and endocardially in 1 patient. In the other 2 patients, epi and endocardial ablation was performed in 1 patient and endo, epi and CS ablation in the other patient to obtain acute success. In the 2 patients with partial success, epicardial and CS ablation in 1 patient and endocardial and CS ablation in the other was performed. In one patient no ablation was performed and in another patient ablation was performed in all 3 sites without any success. Long term recurrence > 3 months occurred in 1 patient with acute success. A power of 30 to 50 watts was used in the CS, 30 to 45 watts in the epicardium and 30 to 50 watts in the endocardium.

Conclusion:
Epicardial or CS ablation alone was successful in terminating VPBS arising from the LV summit in about half of the patients with epicardial and/or endocardial and/or CS ablation required in few others.
Abstract 16347: The Association of Depressive Symptoms and the Intermountain Mortality Risk Score to All-cause Mortality
Authors: May Heidi T , Anderson Jeffrey L , Reiss-Brennan Brenda , Muhlestein Joseph B , Bair Tami L , Lappé Donald L , Brunisholz Kimberly D , Knight Stacey , Horne Benjamin D
Published: March 2022

Introduction:
The patient health questionnaire (PHQ)-9 is widely used for the diagnosis and assessment of depression severity, but further study is needed regarding whether it provides prognostic information for major events such as mortality. The sex-specific Intermountain Mortality Risk Score (IMRS©) is a widely-validated risk stratification tool that utilizes the complete blood count (CBC), basic metabolic profile (BMP), and age to predict all-cause mortality.

Hypothesis:
IMRS is associated with all-cause mortality among subgroups defined by depressive symptoms.

Methods:
Patients who completed a PHQ-9, were ≥40 years, and had a CBC and BMP tested as part of their clinical care were studied. Prior validated sex-specific IMRS weightings and risk stratifications of low, moderate, and high were used. Patients were stratified by depressive symptoms of none (PHQ-9 score <10), mild (PHQ-9 score 10-14), and moderate to severe (PHQ-9 score ≥15). Multivariable Cox hazard regression was performed among all patients and within strata defined by depressive symptoms to determine associations of IMRS and depressive symptoms with all-cause mortality.

Results:
A total of 11,583 females (age: 58.7±12.7 years) and 7,814 males (age: 59.9±12.5 years) were evaluated. Both PHQ-9 and IMRS stratifications were associated with all-cause mortality in a step-wise manner, which persisted despite multivariable adjustment (Table). In categories defined by depressive symptoms, IMRS markedly stratified risk of mortality (Table).

Conclusion:
IMRS and severity of depression were independent predictors of mortality risk among patients screened for depression. Further, IMRS was a powerful predictor of mortality within each level of depressive symptoms. This study suggests a need to evaluate IMRS as a tool for informing clinical risk stratification among patients with symptoms of depression and directing additional resources to those at highest risk of major adverse events.
Abstract 16350: Regulation of Gene Expression in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes Using Magnetic Nanoparticles
Authors: Yamoah Megan A , Sirish Padmini , Sharma Janhavi , Chen Wei Chun , Lee Jeong-Han , Chavez Karen S , Wang Wenying , Lieu Deborah K , López Javier E , Zhang Xiaodong
Published: March 2022

Background.
Delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration and has potential for clinical applications. Gene transfection into hiPSC and hiPSC-CMs, however, is more difficult than for somatic cells. Despite multiple other methods (i.e. nucleofection, lipofectamine, and viral-based transduction), efficiency, cytotoxicity, safety and cost remain unsatisfactory. Increasingly, nanoparticles (NPs) have been used in biomedical research as a powerful tool in drug delivery and personalized medicine. The objective of this study is to examine the regulation of gene expression in hiPSC and hiPSC-CMs using magnetic NPs.

Methods and Results.
HiPSCs and hiPSC-CMs were transfected using magnetic NPs. Confocal microscopy and flow cytometry confirmed and quantitated the transfection efficiency. Enhanced green fluorescence protein (eGFP) and eGFP-fused membrane proteins served as positive controls. We compared the transfection efficiency of hiPSCs with that of human embryonic kidney cells (HEK 293). We observed that the averaged efficiency in hiPSCs is 43 ± 2 % compared to that of 62 ± 4% in HEK 293. Further analysis of the transfected hiPSCs showed that the pluripotency is not altered by NPs. NPs were also used to direct cardiac differentiation using cardiomyocyte-specific transcription factors. Finally, robust transfection of hiPSC-CMs was obtained using NPs to direct the expression of small-conductance Ca
2+
-activated K
+
(SK) channels. Patch-clamp recordings demonstrated successful maturation of hiPSC-CMs with respect to the resting membrane potentials and spontaneous action potentials.

Conclusion.
The difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers an enhanced approach to direct cardiac differentiation and maturation of hiPSC-CMs without the need for viral vector generation.

Funded by AHA (14BGIA18870087 to XZ), NIH K12 (#UL1 TR000002 to JEL) and Harold Amos Medical Faculty Development Program, RWJ Foundation (to JEL), and California Institute of Regenerative Medicine (CIRM, RB4-05764 to DKL), and Fellowship Awards to PS and JS from CIRM Training Program to UC Davis.
Abstract 16395: Comparing Cardiopulmonary Exercise Measures of Men and Women With HFrEF and Their Relationship to Prognosis: The Henry Ford HospITal CardioPulmonary Exercise Testing (FIT-CPET) Project
Authors: Ehrman Jonathan K , Brawner Clinton A , Aldred Heather , Shfiq Ali , Hassan Raakesh , Lanfear David , Keteyian Steven J
Published: March 2022

Introduction:
Several cardiopulmonary exercise test (CPET) variables (e.g., peak oxygen consumption (VO2), ventilatory efficiency (VE-VCO2) slope, and % predicted peak VO2 (%pVO2)) are regularly used to estimate prognosis in patients with systolic heart failure (HFrEF). Although known sex differences in physiology (i.e., muscle mass, lung volume) result in lower peak VO2 values in healthy women vs. men, this influence on CPET variables and subsequent prognosis in patients with HFrEF is not well described.

Purpose:
Compare the peak VO2, VE-VCO2 slope and %pVO2 values in men and women that correspond to prognosis using the International Society of Heart Transplant (ISHT) reported North American 1 and 3-y cardiac transplant survival rates (i.e., 86% and 79%, respectively).

Methods:
Patients with a CPET between 1997 and 2010 were identified. HFrEF was confirmed through a manual query of the medical record. Deaths through December 2011 were identified from the National Death Index. Receiver operator characteristic (ROC) curves were developed for each CPET measure and the threshold values and area under the curve (AUC) values associated with 86% and 79% specificity for each sex were determined.

Results:
A total of 1,201 patients (33% female; 55% Black; 33% ischemic; age = 55 + 13 y; BMI = 31 +7 kg.m-2; EF = 22 + 9%) were included in this analysis. Specificity threshold values and the corresponding AUC, for each CPX variable, are shown in the Table. At 1-y there were 167 (14%) deaths with a 10% event rate for women and 16% for men. At 3-y there were 335 (31%) deaths with a 25% event rate for women and 35% for men.

Conclusions:
In this large, racially diverse population both peak VO2 and %pVO2 had clinically meaningful differences for risk stratification thresholds depending on sex. This was not true for VE-VCO2 slope. Clinical decisions regarding the need for advanced therapies such as transplant or ventricular assist devices, when based on peak VO2 or %pVO2, might consider the patient’s sex.
Abstract 16399: Use and Customization of Risk Scores for Predicting Cardiovascular Events Using Electronic Health Record Data
Authors: Wolfson Julian , Vock David M , Bandyopadhyay Sunayan , Adomavicius Gediminas , O'Connor Patrick J , Vazquez-Benitez Gabriela X
Published: March 2022

Background:
The Framingham Risk Score (FRS) and the ACC/AHA Pooled Cohort Score (PCS) are widely used in clinical practice to guide individual patient care decisions. However, these risk scores have been estimated and validated mostly using data from longitudinal cohort studies and their performance when applied to patient data extracted from electronic health records is less well-established.

Methods:
Risk factor and outcomes data were obtained from the electronic medical records and insurance claims of 84,130 adults aged 40-79 receiving care at a large health care delivery and insurance organization from 2001-2011. We assessed calibration and discrimination for four risk scores: the published versions FRS and PCS, and versions obtained by re-fitting the FRS and PCS Cox regression models using a subset of the available data. Population subgroups where the various models gave highly divergent risk predictions were identified using recursive partitioning techniques.

Results:
The original FRS was well-calibrated (Calibration statistic
K
< 5.7, p = 0.13), but the original PCS was not (
K
= 30, p < 0.001). The original PCS yielded somewhat better discrimination than the original FRS (C-statistic
C
= 0.757 vs. 0.738). The refitted FRS (
K
= 1.4, p = 0.71 and
C
= 0.754) and refitted PCS (
K
= 8, p = 0.046 and
C
= 0.756) were both well-calibrated and showed good discrimination. The original and refitted FRS disagreed substantially on the risks of individuals within a number of population subgroups, most of which encompassed individuals under the age of 60; the original and refitted PCS differed substantially in their risk predictions for African-American males; and the refitted FRS and PCS produced similar risk predictions across subgroups.

Conclusions:
Both the FRS and PCS are appropriate for use in clinical decision support systems which rely on electronic health data, though it may be advisable to refit the statistical models they are based on using available data from the target population to ensure acceptable calibration and discrimination performance.