bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14950:
SLCO1B1
Genotype is Associated With Atorvastatin Discontinuation
Authors: Voora Deepak , Baye Jordan , Mcdermaid Adam D , Gowda Smitha N , Eric Larson A , Russell Wilke A
Published: November 2020

Introduction:
Atorvastatin is commonly prescribed to prevent cardiovascular disease; however, long-term adherence can be eroded by statin associated musculoskeletal symptoms (SAMS). Genetic variants in
SLCO1B1
are associated with SAMS in patients using simvastatin; the association of these variants with adherence or SAMS has been less well characterized for atorvastatin.

Methods:
We tested the association between a loss of function genetic variant in
SLCO1B1
and atorvastatin discontinuation in a large multi-specialty group practice. Using the electronic medical record (EMR) at Sanford Health, we defined a retrospective cohort of 8453 patients who were tested for
SLCO1B1*5
(rs4149056, Val174Ala) through routine clinical care. Patients were included if they had received an atorvastatin prescription prior to genetic testing and had valid
SLCO1B1
results. Patients were classified as discontinued (or not) based on their active medication list at the time of genetic testing. Clinical characteristics including demographics, diagnosis codes, smoking status, concomitant medications, and laboratory values for renal function and all creatine kinase (CK) values prior to testing, were extracted from the EMR. A Kruskal-Wallis test was used to compare longitudinal CK values vs. discontinuation. Logistic regression was used to test the relationship between
SLCO1B1*5
and atorvastatin discontinuation for any reason.

Results:
There were 1752 patients available for analysis (mean age 64 years, 44% female, 2% non-Caucasian, 89% primary prevention indication). 1025 (58%) discontinued atorvastatin prior to
SLCO1B1
testing. The number of
SLCO1B1*5
alleles was associated with atorvastatin discontinuation (odds ratio per allele = 1.22, 95% confidence interval = 1.004 - 1.47, p = 0.04). Among the 495 patients with available CK levels, atorvastatin discontinuation was associated with higher mean CK levels than those who continued (Kruskal-Wallis test, p = 0.02).

Conclusions:
Atorvastatin discontinuation is common in real world patients at risk for cardiovascular disease. Carriers of
SLCO1B1*5
are at increased risk for premature atorvastatin discontinuation - an effect which may reflect an excess risk of statin myopathy.
Abstract 14977: St-elevation Myocardial Infarction in Multi Vessel Coronary Artery Disease- What to Do? Network Meta-analysis of Revascularization Strategies
Authors: Ivanov Alexander , Ravishankar Bharat , Thaker Rishi , marwaha rachit , Kutkut Issa
Published: November 2020

Background:
Primary Percutaneous Coronary Intervention (PCI) is the preferred treatment for patients presenting with ST-elevation myocardial infarction (STEMI). Despite multiple randomized clinical trials (RCT) best revascularization strategy (RS) in patients with STEMI and multivessel disease (MVD) remains unknown. We aimed to use network meta-analysis to compare currently used approaches.

Methods:
We searched for RCT comparing RSs in patients with MVD undergoing PCI for STEMI. We identified and compared RCT with arms evaluating at least two of the following approaches: culprit only revascularization (CoR), complete revascularization during initial intervention (CR) and staged procedure with culprit vessel revascularization followed by non culprit significant lesions intervention during the initial hospitalization. Our primary outcome was all-cause mortality. We combined direct and indirect data to perform a network meta-analysis.

Results:
A total of 7,779 patients from 13 RCT were included in this analysis (Fig. 1). Overall, this is an unbalanced network with only 1 arm comparing CR and SR. Complete revascularization during initial procedure was associated with a significant reduction in mortality with RR 0.47 (0.34; 0.65), p<0.01, when compared to culprit only approach. There was a higher risk of mortality associated with SR, when compared to CR, with RR 1.9 (1.29; 2.82), p<0.01. There was no mortality risk difference between CoR and SR, RR 0.89 (0.72,1.11), p>0.5 (Fig. 2). There was no evidence of a model inconsistency in an overall comparison, p>0.21. There was a design by treatment interaction in SR vs CoR comparison, p<0.01.

Conclusion:
Complete revascularization during primary PCI in patients presenting with STEMI and MVD was associated with significant mortality reduction when compared to culprit only lesion revascularization. There may be design by treatment interaction limiting comparison of staged and culprit only strategies.
Abstract 14979: Endostatin as a Predictor of Severity and Survival in Pediatric Congenital Heart Disease Associated Pulmonary Hypertension
Authors: Daly Caroline , Griffiths Megan , Yang Jun , Nies Melanie , Damico Rachel L , IVY Dunbar D , Austin Eric D , Pauciulo Michael , Nichols Bill , Everett Allen D
Published: November 2020

Introduction:
Pediatric pulmonary arterial hypertension (PAH) is a multifactorial pulmonary vascular disease with high mortality. Endostatin (ES), an angiogenic inhibitor, is associated with disease severity and mortality in adults with PAH and poor lung growth in children.

Hypothesis:
Increased ES is associated with worse disease severity and outcomes in pediatric PAH.

Methods:
Serum ES levels were measured in two cohorts of pediatric PAH (IPAH, FPAH and APAH) patients; the cross-sectional CCHMC PAH Biobank (PAHB, N=175) and a longitudinal cohort from Children’s Hospital of Colorado (CHC, N=61). Outcomes included medical therapy, functional and hemodynamic measures, and survival (death, transplant, palliative shunt). Adjusted logistic and linear regressions and Kaplan-Meier analysis were used to assess the relationship between ES and clinical outcomes.

Results:
In both cohorts, ES was significantly higher in PAH associated with congenital heart disease (APAH-CHD, PAHB n=70, p=0.002; CHC n=29, p=0.007) and was highest in those with a ventricular shunt (n=24, p=0.001). In APAH-CHD, ES was associated with a decreased 6MWD (-108m, -187- -30, p=0.01) and increased mean right atrial pressure (mRAP 1.8mmHg, 0.3-3.3, p=0.02). Longitudinally, in the APAH-CHD subgroup when adjusted for age, sex, and multiple time points, higher ES was associated with increased PVRi and mPAP (PVRi 2.5WU*m
2
, 0.7-4.3, p=0.007; mPAP 10mmHg, 4.5-15, p<0.001). Kaplan-Meier analysis (Figure 1) demonstrated that ES was associated with worse outcomes in both cohorts, with an adjusted Cox proportional hazard ratio of 4.3 (1.13-16, p=0.03) in the PAHB.

Conclusions:
ES was associated with worse functional measures, pulmonary vascular hemodynamics, and survival in pediatric APAH-CHD. These observations suggest that serum ES could act as a pulmonary vascular specific biomarker to identify those who are at increased risk of developing PAH and predict poor outcomes in APAH-CHD.
Abstract 14980: Describing Atrioventricular Conduction in Patients With Chronic Atrial Fibrillation During Hospitalization for COVID-19 - Less RR Interval Variation is Associated With Worse Outcomes
Authors: Junarta Joey , Riley Joshua M , Pavri Behzad B
Published: November 2020

Introduction:
Myriad cardiovascular manifestations have been reported with COVID-19. We previously reported that failure of PR interval shortening with increasing heart rate (HR) in COVID-19 patients (pts) is associated with adverse outcomes. Here we report on atrioventricular (AV) conduction and clinical outcomes in pts with chronic atrial fibrillation (cAF) while hospitalized for COVID-19.

Methods:
A retrospective review of all admitted (Feb 01 - Jun 01) COVID-19 pts with cAF was performed. Clinical and ECG characteristics were collected. The ventricular response in cAF was compared during pre-COVID-19 to COVID-19 admissions. Mean HR, shortest RR, and longest RR intervals were recorded. Regularization of ventricular rate was assessed by difference between the longest and shortest RR intervals (ΔRR), with a smaller ΔRR indicating greater regularization. The cohort was divided into tertiles based on ΔRR. Clinical outcomes during COVID-19 were correlated to AV conduction based on the ventricular response.

Results:
A total of 189 ECGs (106 pre-COVID-19, 83 COVID-19) from 34 patients were included. Mean age 78.6 ± 11.4 years, male 48.6%. Comparing pre-COVID-19 vs. COVID-19 ECGs of all patients showed: mean HR (95.0 ± 24.3 vs. 99.5 ± 23.5 BPM; p=0.20), shortest conducted RR interval (514.9 ± 133.3 vs. 502.5 ± 141.6 ms; p=0.53), longest conducted RR interval (932.2 ± 250.0 vs. 794.7 ± 168.0 ms;
p<0.01
), and ΔRR range (417.3 ± 165.7 vs. 292.2 ± 104.2 ms;
p<0.01
). Pts who showed a more regularized ventricular response (smaller ΔRR) during a COVID-19 admission had longer ICU length of stay and numerically greater need for intubation (Table 1).

Conclusion:
In pts with cAF, the average ventricular rates were more regularized during COVID-19 compared to prior illnesses with comparable HRs. Importantly, pts with the most regularized ventricular response were more likely to have a longer ICU stay compared to pts whose ventricular rate was more irregular.
Abstract 14984: Post-Discharge Beta-Blockers and Early Mortality and Readmission in Older Patients With Heart Failure: An Instrumental Variable Analysis
Authors: Gilstrap Lauren , Austin Andrea , Gladders Barbara , Barnato Amber , Tosteson Anna , O'Malley James , Skinner Jonathan
Published: November 2020

Introduction:
The rate of growth of the older heart failure population has outpaced that of any other age group. Importantly, these older patients were underrepresented in the early beta-blocker trials and there are several reasons, including a decreased potential for mortality benefit and an increased risk of side effects, why the risk/benefit trade-off may be different in this older population.

Hypothesis:
The association between receipt of a beta-blocker at the time of hospital discharge and early mortality and readmissions in heart failure with reduced ejection fraction (HFrEF) patients aged ≥75 is not significantly different than among HFrEF patients <75 years old.

Methods:
We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of beneficiaries with ≥1 hospitalization for HFrEF between 2008 and 2016 and determined beta-blocker use at hospital discharge. The primary outcome was 90-day, all-cause mortality; the secondary outcome was 90-day, all-cause readmission. To address both measured and unmeasured confounding, we used the two-stage least squared instrumental variable analysis method.

Results:
Among all HFrEF patients, receipt of a beta-blocker at the time of discharge was associated with a -4.34% (95% CI -6.26% to -2.42%, p<0.001) decrease in 90-day mortality and a -4.67% (95% CI -7.41% to -1.91%, p=0.001) decrease in 90-day readmission rates. Among patients >75 years old, receipt of a beta-blocker was also associated with a significant -4.74% decrease (95% CI -7.13% to -2.34%, p<0.001) in 90-day mortality and a -4.67% (95% CI -8.96% to -2.93%, p<0.00) decrease in 90-day readmissions.

Conclusions:
We find that patients aged ≥75 years who receive a beta-blocker at HFrEF discharge have significantly lower 90-day mortality and readmission rates. The magnitude of benefit from beta-blocker therapy after HFrEF discharge does not appear to wane with age.
Abstract 14985: Presence of Repolarization Gradients Reverses Post-infarct Ventricular Tachycardia Exit and Entrance Sites in Personalized Digital Hearts
Authors: Sung Eric , Prakosa Adityo , Trayanova Natalia
Published: November 2020

Introduction:
Post-infarct ventricular tachycardias (VT) arise due to structural remodeling (scarring). Physiological repolarization gradients (apicobasal and transmural) exist in the human heart, but the effects on post-infarct VT dynamics are unknown.

Hypothesis:
We hypothesized that incorporation of repolarization gradients in personalized digital hearts of post-infarct patients impacts VT exit sites without altering the location of the VTs.

Methods:
3D late-gadolinium enhanced CMR images were acquired from 7 post-infarct patients. Personalized image-based computational heart models (digital hearts) representing scar and infarct border zone distributions were constructed. Apicobasal (AB) and transmural (TM) repolarization gradients were incorporated using a validated method (Fig A). VTs were induced at baseline (no repolarization gradient) via rapid pacing in the right ventricular apex, using two pacing cycle lengths, mimicking non-invasive programmed stimulation. Pacing protocols that induced baseline VTs were repeated under AB and TM conditions.

Results:
Ten VTs were induced in baseline digital hearts. 8 AB VTs and 8 TM VTs were induced; the remaining 2 VTs for both AB and TM digital hearts could not be induced. 5/8 induced AB VTs had VT exit sites matching baseline VT exit sites; the remaining 3/8 AB VTs had reversed VT exit and entrance sites from the corresponding baseline VTs (Fig B, VT 1 & 2). 4/8 induced TM VTs had exit sites that matched those at baseline; the remaining TM VTs had exit and entrance sites reversed from those of baseline VTs (Fig B, VT 1, 2 & 3). All 8 AB VTs and 8 TM VTs had the same location as corresponding baseline VTs.

Conclusion:
AB and TM repolarization gradients can act to reverse VT entrance and exit sites without changing VT location. Thus, incorporation of physiological repolarization gradients into personalized digital hearts may not impact VT ablation targeting but may affect accurate prediction of VT exit or entrance sites.
Abstract 14993: Dysfunctional Extracellular Microvesicles in Andean Highlanders With Excessive Erythrocytosis
Authors: Brewster Madden , Bain Anthony R , Garcia Vinicius P , Fandl Hannah K , Stone Rachel , DeSouza Noah M , Greiner Jared J , Tymko Michael M , Villafuerte Francisco C , Ainslie Philip N
Published: November 2020

Background:
Chronic mountain sickness, a maladaptation to high altitude (>2,500 m) characterized by excessive erythrocytosis (EE) and often severe hypoxemia, is prevalent in Andean highlanders. EE increases the risk of cardiovascular events and contributes to vascular dysfunction. Circulating extracellular microvesicles (MVs) are key mediators of cardiovascular health and disease through their interaction with the vascular endothelium. The experimental aim of this study was to determine the effects of MVs isolated from adults with EE on endothelial cell inflammation, oxidative stress, apoptosis and nitric oxide (NO) production.

Methods:
Twenty-six male residents of Cerro de Pasco, Peru (4,340 m) were studied: 12 highlanders without EE (healthy; age: 40±4 yr; BMI: 26.4±1.7; Hb: 17.4±0.5 g/dL, SpO
2
: 86.9±1.0%) and 14 highlanders with EE (EE: 43±4 yr; 26.2±0.9; 24.4±0.4 g/dL; 79.7±1.6%). MVs were isolated from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with MVs from either healthy or EE men.

Results:
MVs from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8±2.7 vs 77.1±1.9 pg/mL) and IL-8 (62.0±2.7 vs 53.3±2.2 pg/mL) compared with MVs from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3±6.0 vs 74.9±7.8.9 AU) was not significantly affected, MVs from EE men resulted in ~25% higher (P<0.05) expression of p-NF-κB p65 (Ser536; active NF-κB) (173.6±14.3 vs 132.8±12.2 AU). Additionally, cell expression of the anti-inflammatory miR-146a and miR-181b were significantly suppressed by EE MVs. Cell oxidative stress and apoptotic susceptibility were not significantly affected by MVs from EE men. However, eNOS activation (231.3±15.5 vs 286.6±23.0 AU) and NO production (8.3±0.6 vs 10.7±0.7 μM/L) were significantly lower in cells treated with MVs from EE vs healthy men.

Conclusion:
Increased inflammation and decreased eNOS activity and NO production renders the vascular endothelium highly susceptible to atherosclerosis and thrombosis. Andean highlanders with EE exhibit dysfunctional circulating extracellular MVs that induce a proatherogenic endothelial phenotype contributing to their increased cardiovascular risk.
Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study
Authors: Watson Francesca , Ardissino Maddalena , Amin Ravi J , Arhi Chanpreet , Collins Peter , Moussa Osama , Purkayastha Sanjay
Published: November 2020

Introduction:
Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM.

Hypothesis:
Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM.

Methods:
A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually.

Results:
Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls.

Conclusions:
In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.
Abstract 15007: Association Of Dual Eligibility For Medicare And Medicaid With Heart Failure Quality And Outcomes Among Gwtg-hf Hospitals
Authors: Bahiru Ehete M , Ziaeian Boback , Moucheraud Corrina , Agarwal Anubha , Haolin Xu , Matsouak Roland A , Devore Adam D , Heidenreich Paul A , Allen Larry A , Yancy Clyde W , Fonarow Gregg C
Published: November 2020

Introduction:
The Centers for Medicare & Medicaid Services (CMS) is using a new peer group-based payment system to compare hospital performance which classifies hospitals into quintiles based on their share of dual eligible beneficiaries for Medicare and Medicaid. This study evaluated the association of percent dual eligibility for Medicare Medicaid with HF quality of care and outcomes.

Methods:
This is a retrospective analysis of patients hospitalized for HF using the Get With The Guidelines-HF (GWTG-HF) registry between July, 1 2010 - December 31, 2017. Study endpoints included HF process of care measures, in-hospital mortality, 30-day all-cause or HF readmissions, 30-day all-cause mortality. We included patients aged ≥65 years old with available data on dual eligibility status. Hospitals were divided into quintiles based on their share dual eligible patients. Quality and outcomes were analyzed using unadjusted and adjusted multivariable logistic regression models.

Results:
A total of 258,995 HF hospitalizations from 455 sites were included in the primary analysis of the study. Hospitals in the highest dual eligibility quintile (Q5) tended to care for patients who were younger, more likely female, belong to racial minority groups, or located in rural areas compared with Q1 sites. After multivariable adjustment, hospitals with the highest quintile of dual eligibility (Q5 sites) were associated with lower rates of key process measures including evidence-based beta blocker prescription (aOR: 0.70, 95% CI [0.52,0.94]), measure of left ventricular function (aOR: 0.39, 95% CI [0.21,0.72]), anticoagulation for atrial fibrillation or atrial flutter (aOR: 0.68, 95% CI [0.51,0.91]). Differences in clinical outcomes were seen with higher 30-day all-cause (aOR: 1.24, 95% CI [1.14,1.35]) and HF (aOR: 1.14, 95% CI [1.03,1.27]) readmissions in higher dual eligible Q5 sites compared to Q1 sites. Risk-adjusted in-hospital and 30-day mortality did not significantly differ in Q1 vs Q5 hospitals.

Conclusions:
Higher dual eligibility quintile sites were associated with lower rates of key HF quality of care process measures and higher 30-day all-cause or HF readmissions compared to lower dual eligibility quintile sites.
Abstract 15009: Hospital Readmission Among Anticoagulated Nonagenarians With Atrial Fibrillation: A Nationwide Cohort Sample
Authors: Barssoum Kiro , Elkaryoni Ahmed , Muhanna Adel , Shatla Islam , Abdelkarim Islam , Wimmer Alan P
Published: November 2020

Background:
The prevalence of atrial fibrillation (AF) increases with age, reaching 10% among those above the age of 80. The safety and efficacy of using anticoagulation (AC) to prevent stroke among nonagenarians are not well understood, due underrepresentation of this cohort in landmark clinical trials of oral anticoagulants. We sought to explore readmission rates for all-cause, gastrointestinal bleeding, and acute cerebrovascular events for nonagenarians on AC for AF compared to patients younger than 90.

Methods:
By using the Nationwide Readmission Database (NRD) from 2010-2015 and ICD-9-CM codes, we identified patients hospitalized with diagnoses of AF and chronic AC, and excluded patients under age 18, those who died during the index admission, and those with pulmonary embolism, deep vein thrombosis or a prosthetic valve. Patients hospitalized in December for each calendar year were excluded to allow 30-day follow-up for all patients since the database resets annually. Chi-Square test was used to compare readmission rates between the two groups and a linear test was used to analyze the trend for AC use across years.

Results:
Our criteria identified a total of 1,456,114 patients, of whom 132,476 (9.0%) were ≥ 90 years old. Use of AC for AF among nonagenarians increased over the years of the study from 12.3% in 2010 to 22.7% in 2015 (p<0.001). Thirty-day readmission rates in nonagenarians vs. those < 90 were: all-cause - 16.9% vs. 17.2% (p=0.03), gastrointestinal bleeding - 0.5% vs. 0.4% (p<0.001), and acute cerebrovascular events - 0.8% vs. 0.5% (p<0.001).

Conclusion:
Although the differences were small, nonagenarians treated with AC for AF had a lower 30-day all-cause readmission rate but higher gastrointestinal bleeding and acute cerebrovascular event re-hospitalization rates. Further investigations are warranted to explore the benefit vs. risk of using AC in this vulnerable population of patients.
Abstract 15024: Efficacy of Bretylium in Termination of Treatment Resistant Ventricular Tachycardia and Ventricular Fibrillation
Authors: Molnar Janos , Somberg John C
Published: November 2020

Bretylium is the only drug approved by the FDA specifically to terminate ventricular fibrillation (VF). It has also been approved to treat life threatening ventricular tachycardia (VT) as a second line agent. Due to shortage of drug substance, bretylium became unavailable for clinical use and has been dropped from ACLS guidelines in 2000. Recently, intravenous (IV) bretylium became available again in the U.S. This study evaluated the efficacy of bretylium IV in the termination of treatment resistant VT and VF. In 4 studies, a total of 85 patients with sustained VT and/or VF were administered IV bretylium 5 mg/kg: 23 patients had VT and 62 had VF. Resistant VT/VF was defined as VT or VF that could not be terminated by shock or other anti-arrhythmics or recurred before bretylium was administered. All patients received IV lidocaine; 71 received between 1 to 5 additional antiarrhythmics, and all patients with VF received DC shocks and failed all pharmacologic therapies prior to bretylium administration. Overall, 61 patients (72%) were successfully treated with IV bretylium and 31 survived to discharge from the hospital (36%). A meta-analysis of these studies indicates that the weighted conversion rate across the studies was 70% (see figure). The only study that compared IV bretylium and amiodarone did not find superiority of amiodarone in the suppression of hemodynamically destabilizing VT or VF. In patients with resistant VT or VF bretylium is reported to be effective in acute termination of the VT or VF that otherwise was not responsive to shock or other anti-arrhythmic drugs. These results suggest that bretylium should be employed in the pharmacotherapy of VT and VF when DC shock or other anti-arrhythmic drugs fail. The studies this report is based on are small studies and thus there is a need for a large controlled clinical trial to provide a better understanding of bretyliums effectiveness and if a higher than 30 mg/kg dose of bretylium would be more effective.
Abstract 15033: Chronic Inhibition of Mitochondrial Reactive Oxygen Species Protects Against Endothelial SK Channel Dysfunction in Diabetes
Authors: Xing Hang , Zhang Zhiqi , Song Yi , shi guangbin , Harrington Elizabeth , Feng Jun
Published: November 2020

Introduction:
Oxidative stress plays an important role in the development of pathological condition in diabetes. Persistent oxidative stress during diabetes may result in impaired endothelium-independent vasodilation, by reducing small-conductance Ca
2+
-activated K
+
(SK) channel activity. The mitochondria are main sources of reactive oxygen species (ROS) in diabetes, and mitochondria-targeted antioxidant mito-TEMPO (MT) prevents ROS generation has been found in a variety of disorders. However, few studies are available on the dysfunction of vasodilation and endothelial SK channels in diabetes after a chronic use of MT.

Purpose:
We investigated the chronic administration of MT on vasodilation in coronary arteries, and endothelial SK channel activity with or without diabetes.

Methods:
MT (1mg/kg) was applied to diabetic and health mice (n = 6/group) for 1 month.
In-vitro
relaxation response of pre-contracted arteries was examined in the presence or absence of the vasodilatory agents. Isolated endothelium was studied using whole-cell patch clamp recording SK channels currents.

Results:
Coronary arteries dilation was decreased in diabetic mice compared with that in health (
p
<0.05). After one month treatment with MT, coronary arteries dilation was significantly improved when compared with that in non-treatment diabetic mice (
p
<0.05). Interestingly, coronary arteries dilation was no significantly changed in health mice whether to treat with MT or not. Similar changes were seen in patch clamp recording, impaired currents of SK channels in endothelial cells of diabetic mice were significantly improved after chronic treatment with MT (
p
<0.05, Fig) and currents of SK channels were no changed in health mice whether to treat with MT or not.

Conclusions:
MT appears to improve coronary endothelial function/dilation by protection of SK channel activity in diabetes, and administration of MT may be a novel strategy to treat vascular complications in diabetes.
Abstract 15080: Chronic Mild Sleep Curtailment Increases Markers of Adiposity While Maintained Healthy Sleep Reduces These Measures in Women
Authors: Zuraikat Faris M , Scaccia Samantha E , RoyChoudhury Arindam , St-Onge Marie-Pierre
Published: November 2020

Introduction:
Over one-third of US adults do not achieve adequate sleep duration of 7 or more h per night. Short sleep is linked to higher odds of cardiometabolic diseases, including obesity. However, whether prolonged insufficient sleep causes increased body weight or adiposity remains unclear.

Objective:
To compare, in women, changes in body weight and composition in response to prolonged mild sleep restriction (SR) vs maintenance of healthy, habitual sleep (HS).

Methods:
Women (n=55; age: 35±13 y; BMI: 25.5±3.5 kg/m
2
) with average adequate sleep duration (total sleep time [TST]=455±23 min) took part in a randomized crossover study with two 6-wk phases: HS and SR. In HS, usual bed and wake times (determined from 2 wk wrist actigraphy and sleep logs) were maintained. In SR, TST was reduced by 1.5 h/night. Sleep was measured continuously and verified weekly for compliance. Body weight and composition were measured at 0 and 6 wk using magnetic resonance imaging (MRI). Linear-mixed models tested interactions of sleep condition with week on outcome measures.

Results:
Average TST was reduced in SR and unchanged in HS (-87±19 vs -7±26 min, P<0.01). Significant study condition by week interactions were observed for whole-body volume (WBV), waist circumference (WC), and skeletal muscle. In HS, WBV and WC decreased while these measures increased in SR (WBV: -0.47±0.22 vs 0.27±0.05 L, P=0.02; WC: -1.04 ± 0.78 vs 1.16 ± 0.54 cm, P=0.04). Results were similar for skeletal muscle (-0.19 ± 0.07 vs 0.17 ± 0.01 L, P<0.01). A trend for a reduction in weight was observed in HS relative to SR (-0.39±0.31 vs 0.34±0.09 kg, P=0.09).

Conclusions:
This is the first evidence that prolonged insufficient sleep leads to increased body size in women. Conversely, maintaining adequate sleep may improve body composition. Our data suggest that healthy sleep duration should be a key component of strategies to improve cardiovascular health in women.
Abstract 15393: Automatic Multi-structural Cardiac Segmentation of 2d Echocardiography With Convolutional Neural Networks
Authors: Zhang Xiaoyan , Stough Joshua V , Raghunath Sushravya M , Ulloa Cerna Alvaro , vanMaanen David , Fornwalt Brandon , Haggerty Christopher M
Published: November 2020

Introduction:
The use of convolutional neural networks (CNN) to automatically segment the heart from echocardiography images has garnered recent attention, but generalizable performance segmenting multiple cardiac structures has not been demonstrated. The objective of the present work was to develop a 2D CNN model to automatically and accurately segment the left ventricular (LV) endo- and epicardial and left atrial (LA) endocardial surfaces from an independent, external clinical dataset.

Methods:
A modified U-net CNN was trained using 10-fold cross-validation and augmentation within the published CAMUS echocardiography dataset to segment the LV and LA from apical 2- and 4-chamber images. For external validation, this model was applied to 3,087 echocardiograms from Geisinger for which the physician-reported LV ejection fraction (EF) was within 10% of the reported bi-plane EF, signifying confidence in quality of the underlying images. LV end-diastolic and end-systolic volumes (EDV, ESV), LA volume (LAV), and LV mass (LVM) were estimated using Simpson’s bi-plane summation. We compared performance against two published segmentation models.

Results:
Our model agreed well with clinically-reported values, based on small median absolute errors in percent of clinical measures (MAE; Table 1) and biases, and narrow limits of agreement (mean bias/coefficient of variation (%): LV EDV 10.3/10.6, ESV 6.3/13.1, EF 0.5/6.3, LVM 13.9/10.1, and LAV 3.1/9.5). Moreover, the observed MAE for each metric was within the previously reported limits of inter-observer variability for 2D echo. Compared to two previously published models, our model exhibited smaller MAE in all measures tested (Table 1).

Conclusions:
Our model exhibits accurate, generalizable performance in multi-structural echocardiography segmentation, with accuracy meeting or exceeding current leading models. Such models hold great promise for translational research and precision medicine efforts.
Abstract 15409: The Need for Lesion-specific Stent Optimization Criteria in Intravascular Ultrasound-guided Intervention for Diffuse Long Coronary Lesions: An Individual Patient-level Pooled Analysis of Four Randomized Controlled Trials
Authors: Kim Daehoon , Kim Byeong-Keuk , Lee Seung-Jun , Hong Sung-jin , Ahn Chul-min , Kim Jung-Sun , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo
Published: November 2020

Introduction:
Achieving stent optimization on intravascular ultrasound (IVUS) is associated with favorable clinical outcomes in new-generation drug-eluting stents (DESs) implantation. Little is known about the stent optimization criteria in lesion subsets assorted according to vessel size and lesion length.

Hypothesis:
We hypothesized lesion-specific IVUS criteria could provide a better prediction for the outcomes after DES implantation for diffuse coronary lesions.

Methods:
From four randomized trials comparing IVUS and angiography guidance in long coronary lesions, a total of 1,194 patients who underwent IVUS-guided intervention with DESs ≥26 mm in length were included. Primary endpoint was a major adverse cardiac event (MACE), defined as a composite of cardiovascular death, myocardial infarction, target vessel revascularization, or stent thrombosis at 1 year following intervention.

Results:
MACE occurred in 41 (3.4%) patients. Among possible combinations of absolute and relative expansion criteria, the combination best predicting MACE was minimal stent area (MSA) ≥5.4 mm
2
or 80% of mean lumen area (MLA) (Youden index=0.250) in overall patients. In 2x2 factorial subgroup analyses, the MSA cutoff was 4.9 mm
2
or 85% of MLA for shorter (<30 mm) lesions with a smaller vessel diameter (reference vessel diameter [RVD] <3.0 mm) (Index=0.616) and 5.6 mm
2
or 85% for shorter lesions with a larger vessel diameter (RVD ≥3.0 mm) (Index=0.211). In longer lesions (≥30 mm), the MSA cutoff was 5.5 mm
2
or 70% of MLA for smaller vessels (RVD <3.0 mm) (Index=0.469), and 6.2 mm
2
or 70% for larger vessels (RVD ≥3.0 mm) (Index=0.578).

Conclusions:
When IVUS is used to optimize DES implantations for long coronary stenoses, applying different criteria according to angiographic parameters might improve the outcomes. In relatively longer lesions with a larger vessel diameter, pursuing to achieve a higher absolute MSA value rather than relative expansion might be more important.
Abstract 15448: Association of Kidney Dysfunction and Damage to Incident Heart Failure With Reduced and Preserved Ejection Fraction in Older, Community-dwelling Adults: The Atherosclerosis Risk in Communities Study
Authors: Buckley Leo F , Claggett Brian , Matsushita Kunihiro , Skali Hicham , Coresh Josef , Konety Suma H , Wagenknecht Lynne E , Mosley Thomas , Shah Amil M
Published: November 2020

Introduction:
Older adults are at heightened risk for both kidney disease and heart failure, but there is limited data regarding the associations of kidney damage and dysfunction with incident heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction in late life.

Hypothesis:
Kidney dysfunction, as assessed by lower estimated glomerular filtration rate (eGFR), and kidney damage, as assessed by higher urine albumin-to-creatinine ratio (UACR), are each independently associated with incident HFrEF and HFpEF in late life.

Methods:
We studied 4,563 elderly participants in the community-based, prospective ARIC study who were free of HF at study Visit 5 (2011-2013) at which time they had UACR measured and Cystatin-C-based eGFR estimated using the CKD-EPI formula. We estimated the association of Visit 5 eGFR and UACR with post-Visit 5 incident HF overall, HFrEF, and HFpEF using multivariable Cox proportional hazards regression models adjusted for demographics, diabetes, hypertension, coronary artery disease, atrial fibrillation, body mass index, pulse pressure, and either eGFR or UACR.

Results:
The mean age at Visit 5 was 75±5 years, 57% were female, 21% were black. Mean Visit 5 eGFR was 67±18 mL/min per 1.73 m
2
and median UACR was 10.2 [6.2 to 21.4] mg-g. Lower eGFR and higher UACR each associated with older age, wider pulse pressure and higher prevalence of diabetes, hypertension, coronary disease and atrial fibrillation (all p<0.02). At a median follow-up of 5.2 years, 289 participants developed HF (127 HFpEF, 123 HFrEF, 42 with unknown LVEF). In fully adjusted models, lower Visit 5 eGFR and higher Visit 5 UACR were each associated with higher risk of incident HF overall, incident HFrEF, and incident HFpEF (
Figure
).

Conclusions:
Lower eGFR and higher UACR are independently and additively associated with both incident HFrEF and incident HFpEF in late life.
Abstract 15473: Effect of Statins on Coronary Plaque Progression Assessed by Serial Coronary Computed Tomography Angiography
Authors: Dahal Suraj , Lakshmanan Suvasini , Ahmad Khadije , Rezvanizadeh Vahid , Ghanem Ahmed K , Onuegbu Afiachukwu G , Birudaraju Divya , Kinninger April , Golub Ilana , Hamal Sajad , Dailing Christopher , Flores Fred , Roy Sion , Budoff Matthew J
Published: November 2020

Introduction:
Statins stabilize coronary plaques and reduce clinical events. However, it is unclear how statins change the total plaque burden and plaque morphology.

Hypothesis:
We aimed at investigating whether statin users have less coronary plaque progression compared to non-statins users.

Methods:
We identified 243 subjects undergoing serial computed tomography angiography, 163 taking statins and 80 who are not. Coronary plaque (total, calcified, non-calcified including fibrous, fibrous-fatty and low-attenuation plaque (LAP)) volume was measured using semi-automated plaque software (Qangio, Medis) and its change overtime between statins users and non-statins users was evaluated using Analysis of Covariance (ANCOVA) modeling adjusted for age, gender, diabetic status, presence of hypertension, past smoking use, and baseline plaque levels.

Results:
Subjects on statin therapy had higher body mass index, were more likely to be diabetic, had hyperlipidemia, and were past smokers. Median coronary artery calcium score was significantly lower in the statin group; p<0.034. Driven primarily by changes in fibrous plaque, those on statin therapy showed 25% less total plaque (P=0.013) and 31% less total non-calcified plaque (P=0.006) at follow-up than non-statin users.

Conclusions:
The current study indicates that statin use is associated with less progression of total plaque and total non-calcified plaque burden.
Abstract 15485: Hematological Changes and Coagulation Dysfunction in 633 Patients With Covid-19
Authors: Yang Mo , Deng Huixia , Li Liang , Tan Yafang , Ye Jieyu , Li Qiang
Published: November 2020

Introduction:
A previously unknown coronavirus was discovered from patients with pneumonia. The disease caused by this virus was named as coronavirus disease 2019 (COVID-19). In addition to pulmonary manifestations, hematological changes such as lymphopenia, thrombocytopenia, and coagulation dysfunction can also be found in COVID-19 patients, and the mechanism is still unclear.

Methods:
A total of 633 COVID-19 patients from Wuhan hospital of China were retrospectively analyzed. Clinical case data of all patients were collected, including gender, age, chronic underlying diseases, outcome, and blood laboratory test results. The hematological features of COVID-19 patients and the factors affecting their outcome were analyzed.

Results:
The median age was 62 years ( IQR; 51.0-70.0) and 330 (52%) were men. Lymphopenia ( lymphocyte count, 1.0 х10
9
/ L [IQR, 0.7-1.4]) occurred in 317/607 patients (52%), prolonged prothrombin time (13.8 seconds [IQR, 13.1-15.1]) in 289/486 patients (59%), increased D-Dimer level (0.7 mg/L[IQR,0.2-2.9]) in 230/411 patients (57%) and increased C-reactive protein levels (10.7 mg/L [IQR, 2.2-49.7]) in 217/426 patients (51%). Compared with the survival patients, death patients have higher white blood cell count (11.7 х 10
9
/L [IQR, 8.4 to 15.6]), neutrophil count (10.8 х 10
9
/L [IQR, 7.8 to 13.9]), neutrophil count/lymphocyte count (20.5 [IQR, 12.4-34.2]), activated partial thromboplastin time (36.8 seconds [IQR, 31.3-42.3]), prothrombin time (17.1 seconds [IQR, 14.7 to 19.7]), D-Dimer level (4.6 mg/L [IQR, 1.0 to 7.8]), C-reactive protein level (111.8 mg/L (IQR, 53.1 to 196.6), and low lymphocyte count (0.5 х 10
9
/L [IQR, 0.3 to 0.7]). The results of logistic multivariate regression analysis showed that age, neutrophil count, prothrombin time, and C-reactive protein were risk factors for patients with COVID-19.

Conclusions:
Hematological changes are common in patients with COVID-19. The early stage of the disease is mainly characterized by lymphopenia, and the late stage may be characterized by more severe lymphopenia, even neutrophils elevation, elevated C-reactive protein, and severe coagulation disorder. The pathogenesis may be mediated by a direct viral infection and/or indirect immunopathology.
Abstract 15486: Subclinical Hypothyroidism and Left Heart Strain in the General Population
Authors: Nakanishi Koki , Daimon Masao , Yoshida Yuriko , Sawada Naoko , Ishiwata Jumpei , Hirokawa Megumi , Kaneko Hidehiro , Nakao Tomoko , Mizuno Yoshiko , Morita Hiroyuki , Di Tullio Marco , Homma Shunichi , Komuro Issei
Published: November 2020

Background:
Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart dysfunction and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease.

Methods:
We examined 1,078 participants who underwent extensive cardiovascular health check-up including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit and pump strain. SCH was defined as an elevated serum thyroid stimulating hormone level with normal concentration of free thyroxine.

Results:
Mean age was 62±12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir and conduit strain (both p<0.05) compared with those with euthyroidism, whereas there was no significant difference in LV ejection fraction, LA volume index, LVGLS and LA pump strain between the 2 groups. In multivariable analyses, the presence of SCH was significantly associated with impaired LA reservoir strain, independent of age, traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters including LVGLS.

Conclusions:
In an unselected community-based cohort, individuals with SCH had significantly impaired LA function. This association may be involved in the higher incidence of HF in subjects with SCH.
Abstract 15842: Body Mass Index in Covid-19: An Independent Risk Factor for Severe Infections
Authors: du Fay de Lavallaz Jeanne , Fugar Setri , Gomez Joanne Michelle M , Swearingen Sean , Bosco Gianna , Hlepas Alexander , Simmons Alan , Clark Brian , suboc tisha , Volgman Annabelle S , Williams Kim A , Bai Charlotte
Published: November 2020

Introduction:
The coronavirus disease 2019 (COVID-19) led to a global pandemic. Comorbidities such as hypertension, diabetes mellitus, elevated cholesterol, cardiac/pulmonary diseases, and obesity were postulated as prognostic factors for a worse outcome.

Hypothesis:
Obese COVID-19 patients have a worse prognosis.

Methods:
From March to June 2020, we obtained data on all patients ≥18 y.o. who were admitted with a positive COVID-19 test at the Rush System, Chicago. Multivariable logistic regression analysis was performed between predictors and a composite outcome of intubation and in-hospital mortality.

Results:
Among the 1345 admitted patients, 69 (5%) were underweight (BMI<18.5kg/m2), 365 (27%) of normal weight (BMI 18.5-25kg/m2), 405 (30%) overweight (BMI 25-30kg/m2), 258 (19%) of obesity class I (BMI 30-35kg/m2), 119 (9%) of obesity class II (BMI 35-40kg/m2) and 129 (10%) of obesity class III (BMI >40kg/m2). In a multivariable model assessing the risk for the in-hospital death or intubation, underweight patients showed decreased risk (odds ratio (OR) 0.31) while obesity class III patients showed increased risk (OR 1.68, Figure 1) when compared to normal BMI. When accounting for obesity classes, male sex, atrial fibrillation and coronary artery disease were also independent predictors adverse outcomes.

Conclusions:
Consistent with previous research, morbidly obese patients had a higher risk for a worse outcome, even when accounting for numerous comorbidities. Underweight patients appeared to be protected. Higher body mass leads to inherent changes in lung function, increased risk of thrombosis, greater viral replication, higher release of adipokines and higher inflammation. Inversely, fewer adipocytes could possibly limit the risk for cytokine storm by reducing the amount of proinflammatory factors released.
Figure:
Odds ratios with 95% confidence intervals for the outcome of death or intubation in all COVID-19 positive admitted patients.
Abstract 15862: Abnormal Exercise-induced Aortic Stiffness in Heart Failure
Authors: Tsao Connie W , Myerson Lana , Raber Inbar , Neisius Ulf , Manning Warren J
Published: November 2020

Introduction:
Afterload conferred by aortic stiffness contributes to heart failure (HF) pathogenesis.

Hypothesis:
Patients with HF have a greater rise in aortic stiffness with physical exertion compared to individuals without HF.

Methods:
Outpatients with HF (n=21) and without HF (n=26) underwent cardiovascular magnetic resonance (1.5T CMR) at rest and following submaximal supine bicycle ergometry. Short axis cine steady-state free precession (SSFP) images were obtained to quantify left ventricular volumes and ejection fraction. Cross-sectional aortic SSFP imaging at the level of the pulmonary artery bifurcation was obtained to measure descending aorta (DA) distensibility at rest and immediately after exercise. We compared least squares (LS) means of DA distensibility between HF and control groups, adjusting for age, sex, and metabolic equivalents (METs) achieved.

Results:
Characteristics of controls and HF patients are presented in the
TABLE
. There was no difference of DA distensibility between control and HF groups either at rest or after exercise (p=0.77 and p=0.13, respectively). However, compared to controls with no significant change in aortic stiffness with exercise, individuals with HF had a reduction in DA distensibility post-exercise in analyses adjusted for age, sex, and METs achieved (
TABLE
). In subgroup analyses, patients with HF with reduced ejection fraction (n=14) had lower post-exercise DA distensibility vs. rest (adjusted-LS means 3.06 x10
-3
mm Hg
-1
, 95% CI 2.35x10
-3
—3.76x10
-3
mm Hg
-1
, vs. 4.55 x10
-3
mm Hg
-1
, 95% CI 3.84 x10
-3
—5.26 x10
-3
mm Hg
-
1, respectively, p=0.020). DA distensibility at rest vs. exercise in patients with HF with preserved ejection fraction was similar (p=0.38).

Conclusions:
Patients with HF have exercise-induced aortic stiffness not seen in individuals without HF. This may result in less favorable ventricular-vascular coupling with exertion in HF patients.

Character count: 1653 (limit=1700)