bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13128: Development and Initial Utilization of a Multi-institutional Distributed Data Network Designed to Evaluate Real-world Clinical Outcomes in Patients Presenting for Percutaneous Coronary Intervention (PCI): Results From the
Building the Unique Device Identifier (UDI) Into Longitudinal Data for Medical Device Evaluation
(BUILD) Network
Authors: Muhlestein Joseph B , Graham Jove , Tcheng James , McKinnon Andrew , Knight Stacey , May Heidi T , Bair Tami L , Drozda Joseph P
Published: May 2021

Introduction:
Generating real-world evidence for regulatory and research purposes is a fundamental transformation of healthcare. To develop and demonstrate the operational components, we created the BUILD network, a framework for the longitudinal follow-up of all patients undergoing PCI at three large health systems, Mercy, Geisinger, and Intermountain. It leverages consistent data through a standardized common data model using distributed analyses without site-specific programming or external transfer of clinical data. To demonstrate BUILD’s potential, we evaluated clinical outcomes between two commonly used drug-eluting coronary stents.

Methods:
We included all patients receiving zotarolimus, or everolimus stents from 2012-19. Data were compiled from registries and electronic health/billing records systems without explicit chart abstraction, and retained at each site in the BUILD analysis database. A common query examined 32 baseline covariates, created propensity-matched cohorts, assessed for balance, and compared 1-year major adverse cardiac event (MACE) rates between groups, with weighted data combined to create event-free survival plots.

Results:
We identified 11,030 patients (Mercy=4,906, Geisinger=4,109, Intermountain=127; mean age 65±12, 69% males, 23% zotarolimus). Figure 1 shows hazard ratios and survival curves for the composite endpoints in matched cohorts. Differences in subsequent PCI, mortality, and composite MACE were not significantly different between stent types.

Conclusions:
This large real-world, multicenter demonstration project showed no statistical differences in 1-year clinical outcomes of patients receiving zotarolimus versus everolimus stents—results similar to other studies. More importantly, it demonstrated that multi-institutional data networks can be successfully developed to provide clinically relevant evidence while maintaining the source data locally on-premise at each institution.
Abstract 13133: Impact of Circadian Rhythm Disorders on Reparative Angiogenesis
Authors: Tsuzuki Kazuhito , Shimizu Yuuki , Pu Zhongyue , Suzuki Junya , Yamaguchi Shukuro , Shibata Rei , Murohara Toyoaki
Published: May 2021

Introduction:
Circadian rhythm disorder seen in shift-worker or jet-lag is major social health concerns in advanced industrialized countries. The aim of this study was to examine if circadian rhythm disorders would influence on angiogenesis and blood perfusion recovery in a mouse model of hind limb ischemia (HLI).

Methods and Results:
First, we established a jet-lag model in C57BL/6J (wild type; WT) mice (8-10 weeks old, N=10 for each) using a light controlled isolation box. Mice were exposed to advanced 8-hr light phase once every 4 days in a jet-lag group as previously described. Conversely, control mice were kept a regular condition of LD 12:12 (12-hr light and 12-hr dark). Then, we surgically induced HLI in each group. The results showed that the condition jet-lag deteriorated capillary formation detected by CD31-immunohistochemistry at post-operative day (POD) 28 and tissue blood perfusion recovery demonstrated by laser Doppler perfusion imaging (LDPI) in HLI. The expression of clock genes (i.e.
Clock, Bmal1, Per2, Cry1 and 2
) in ischemic muscles were regulated by jet-lag condition at POD7.Next, we examined whether inhibition of clock gene had any effects on angiogenesis. For this study, we focused on
Cryptochrome
(
Cry
), which is well known as one of the core-loop forming clock genes producing circadian rhythm in mammals. Our loss-of-function study revealed that the abilities of proliferation, migration and tube formation were significantly inhibited by
CRY1
and
CRY2
double knockdown in HUVECs. Interestingly, although the knockdown of
CRY1
and
CRY2
changed the mRNA expression of
PERIOD2
, it did not affect those of
BMAL1
and
CLOCK
in HUVECs. Finally, we tested if
Cry1
and
Cry2
double knockout (
Cry1/2
-DKO) mice of HLI models displayed worse blood perfusion recoveries with deterioration of angiogenesis.
Cry1/2
-DKO mice were reported to display circadian rhythm disorder in previous reports. As results, compared with control WT mice,
Cry1/2
-DKO mice revealed suppressed capillary density and tissue blood perfusion recovery in HLI model.

Conclusion:
Our data suggest that a maintenance of circadian rhythm plays an important role in reparative angiogenesis of the tissue ischemia model.
Abstract 13152: Do Survivors of Acute Coronary Syndrome Due to Unprotected Left Main Coronary Artery Occlusion Treated With Extracorporeal Membrane Oxygenation Have Higher Mortality in Chronic Phase?
Authors: Shiota Haruko , Kagawa Eisuke , Kato Masaya , Oda Noboru , Kunita Eiji , NAGAI Michiaki , Dote Keigo
Published: May 2021

Introduction:
Mortality in patients with acute coronary syndrome (ACS) due to unprotected left main coronary artery (LMA) occlusion is high. Extracorporeal membrane oxygenation (ECMO) could rapidly provide circulatory support.

Hypothesis:
This study aimed to verify the hypotheses that the patient who required circulatory support with ECMO in acute phase of LMA-ACS had greater cardiac function deterioration and had higher mortality in the chronic phase than those who did not require ECMO.

Methods:
Patients with LMA-ACS who underwent percutaneous coronary revascularization between 2000 and 2020 were enrolled in this study. The patients were divided into two groups based on whether or not they received ECMO. Thirty-day (acute phase) and 30-day to 6-year (chronic phase) survival curves were constructed by Kaplan-Meier method. The cause of death in acute and chronic phase were examined.

Results:
Among the 85 study patients, 23 (27%) were in the ECMO-group. Median age was younger in the ECMO-group (65 y [57 - 72] vs. 73 y [69 - 83], p < 0.01), and male sex (67% vs. 63%) were similar in ECMO group and non-ECMO groups respectively. The prevalence of ST elevation myocardial infarction (STEMI), non-STEMI, unstable angina were 52%, 48%, and 0% vs. 15%, 42%, and 44% in the ECMO group and non-ECMO group, respectively. The 30-day mortality was significantly higher in ECMO group (61% vs. 15%, p < 0.01); however, the 30-day to 6-year mortality was similar between the two groups (41% vs. 33%, p = 0.59) (Figure). The cause of death in the acute phase were cardiac failure (79% and 67%) and those in chronic phase were cardiac failure (50% and 25%), malignancy (0% and 13%), and infection (50% and 36%).

Conclusions:
The mortality in chronic phase in LMA-ACS patients who survived up to 30 days were similar in ECMO group and non-ECMO group. Moreover the patients whose cardiac function deteriorated severely and required ECMO in acute phase had similar prognosis to those that did not require ECMO.
Abstract 13164: Tm6sf2 is a Regulator of Liver Fat Metabolism in Smooth Er Influencing Vldl Lipidation
Authors: Luo Fei , Hobbs Helen H , Cohen Jonathan C
Published: May 2021

Backgrounds:
A variant in Transmembrane 6 Superfamily Member 2 [
TM6SF2
(E167K)] that is associated with a loss of function is strongly associated with both alcoholic and nonalcoholic fatty liver disease. TM6SF2 is a polytopic protein that is expressed predominantly in the liver and small intestines. Immunolocalization studies are consistent with the protein being present in the endoplasmic reticulum (ER) and the Golgi complex.

Tm6sf2
-/-

mice replicate the phenotype of individuals with
TM6SF2
-167K variant: hepatic steatosis accompanied by hypocholesterolemia, and transaminitis. These mice have a reduced rate of secretion of VLDL-TG without any change in the rate of secretion of ApoB. Thus, TM6SF2 is required for normal lipidation of VLDL. To determine where in the secretory pathway TM6SF2 promotes lipid addition to nascent VLDL, we have generated
Tm6sf2
-/-
rats.

Methods:
Two lines of

Tm6sf2
-/-

rats with different frameshift mutations in exon 1 were generated using CRISPR/Cas9 technology. Rats were fasted 4 hours and tissues were collected and frozen at -80°C. Cell fractionation studies were performed to isolate the smooth and rough ER along with
trans
- and
cis
-Golgi membranes.

Result:
Both lines of rats were confirmed by immunoblotting to produce no TM6SF2 in the liver or intestines. The phenotype of the

Tm6sf2
-/-

rats resembles that of mice and humans. Cell fractionation studies revealed that TM6SF2 mainly localized to the smooth ER. Unlike what was observed previously by immunocytochemistry, no TM6SF2 was found in the Golgi fraction. Analysis of the lipid profile of the Golgi apparatus in the KO rat revealed that the majority triglyceride (TG) and fatty acids (FA) subclasses were decreased by one to two folds compared to WT in terms of TG or FA to ApoB48 ratios.

Conclusions:
TM6SF2 is localized predominantly in the smooth ER and regulates the lipidation of VLDL.
Abstract 13173: Unusual Fatigue and Failure to Utilize Emergency Medical Services Are Associated With Prolonged Prehospital Delay for Suspected Acute Coronary Syndrome
Authors: Devon Holli A , Daya Mohamud R , Knight Elizabeth , Brecht Mary-Lynn , Su Erica , Zegre-hemsey Jessica K , Mirzaei Sahereh , Frisch Stephanie O , Mooney Mary , Rosenfeld Anne G
Published: May 2021

Introduction:
Rapid reperfusion reduces infarct size and mortality for acute coronary syndrome (ACS) but efficacy is time dependent. Time to presentation in the Emergency Department (ED) remains excessive and patient-controlled prehospital delay may be a modifiable variable for intervention. The aim of the study was to determine if transportation factors and clinical presentation predicted prehospital delay for suspected ACS stratified by final diagnosis (ACS vs. no ACS).

Hypothesis:
Symptoms other than chest pain would contribute to longer prehospital delay that would vary by final diagnosis.

Methods:
Secondary analysis of data collected from a multi-center prospective study. A heterogeneous sample of ED patients with symptoms suggestive of ACS were enrolled at five sites in the US. Accelerated failure time (AFT) models were used to specify a direct relationship between delay time and variables to predict prehospital delay by final diagnosis.

Results:
The sample of 975 adults included 609 (62.5%) men and 366 (37.5%) women who were predominantly Caucasian (69.1%), had a mean age of 60.32 (±14.07) years, and had lower income levels (66.4% ≤$50,000 annually). Median delay time was 6.68 (1.91, 24.94) hours and only 26.2% had a prehospital delay of 2 hours or less. Patients with and without ACS presenting with unusual fatigue (TR=1.71, p=0.002; TR=1.54,
p=0.003
, respectively) or self-transporting to the ED experienced significantly longer prehospital delay (TR 1.93, p<0.001; TR 1.71,
p<0.001
, respectively). Predictors of shorter delay in patients with ACS were shoulder pain and lightheadedness (TR=0.65,
p
=0.013 and TR=0.67,
p
=0.022, respectively). Predictors of shorter delay for patients ruled-out for ACS were the presence of chest pain, sweating (TR=0.071,
p
=0.025 and TR=0.073,
p
=0.032, respectively).

Conclusion:
Patients self-transporting to the ED had prolonged prehospital delays. Encouraging the use of EMS is an important modifiable factor for patients with symptoms concerning for ACS. Calling 911 can be positively framed to at risk patients and the community as having advanced care come to them since EMS diagnostic capabilities include 12-lead ECG acquisition and possibly high sensitivity troponin assays.
Abstract 13196: The Utility of Silent Myocardial Infarction on Electrocardiogram as an ASCVD Risk Enhancer for Primary Prevention: The Multi-Ethnic Study of Atherosclerosis
Authors: Singleton Matthew J , German Charles , Soliman Elsayed Z , Burke Gregory , Yeboah Joseph
Published: May 2021

Introduction:
The 2018 AHA/ACC cholesterol guidelines introduced a new list of markers called “risk enhancers” that, if present, confer an increased risk of atherosclerotic cardiovascular disease (ASCVD). Notably absent is silent myocardial infarction (SMI) on electrocardiogram (ECG), even though SMI has been shown to be associated with future ASCVD.

Hypothesis:
Adding SMI to the pooled cohort equation (PCE) will improve risk discrimination and classification in those with intermediate ASCVD risk (5 - 20% 10-year risk).

Methods:
SMI was defined as a major Q-wave abnormality or minor Q/QS waves in the setting of major ST-T abnormalities in the absence of history of clinical cardiovascular disease. Incident ASCVD events included myocardial infarction, coronary heart disease death, and fatal and non-fatal stroke.

Results:
Among 2,278 intermediate-risk MESA participants, 48 (2.1%) had SMI at baseline. Over 32,150 person-years (median 15.8), incident ASCVD events occurred in 297/2,230 (13%) of those without SMI and 13/48 (27%) of those with SMI. In a Cox proportional hazards model that was adjusted for calculated 10-year ASCVD risk based on the PCE, SMI was associated with increased risk of ASCVD (HR 2.22, 95% CI 1.27 - 3.87, p = 0.005). Adding SMI to the PCE did not improve discrimination, with areas under the receiver operating characteristic curves for models without and with SMI of 0.5812 and 0.5874, respectively (p-value for difference 0.22; Figure 1a). The net reclassification improvement for adding SMI as a risk enhancer to reclassify participants from intermediate-risk to high-risk was 0.0242 (95% CI 0.0011 - 0.0472, p = 0.04; Figure 1b).

Conclusions:
Our findings suggest that the prevalence of SMI is 2.1% among those without known clinical cardiovascular disease considered intermediate-risk by the pooled cohort equation. In our analysis, SMI only modestly improved classification of risk, suggesting that it may not be very useful as an ASCVD risk enhancer.
Abstract 13303: Cardio-ankle Vascular Index Predicts New Onset Stroke in Patients With Heart Failure
Authors: Hotsuki Yu , YOSHIHISA Akiomi , Sato Yu , Ichijo Yasuhiro , Watanabe Koichiro , Kimishima Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Takeishi Yasuchika
Published: May 2021

Aim:
We aimed to evaluate the implication of cardio-ankle vascular index (CAVI) to predict new onset stroke in patients with heart failure (HF).

Methods and Results:
This was a prospective observational study, which recruited clinical data of a total of 898 patients hospitalized for HF. According to the survival classification and regression tree analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.6. We divided patients into two groups: the high CAVI group (CAVI > 9.6, n = 230, 25.6%) and the low CAVI group (CAVI ≤ 9.6, n = 668, 74.4%). We compared the patients’ characteristics and occurrence of new onset stroke. The high CAVI group was older (73.5 vs. 66.0 years old, P < 0.001) and had a higher prevalence of male sex (74.3% vs. 62.0%, P = 0.001) and prior stroke (23.5% vs. 17.5%, P = 0.047). The high CAVI group showed higher levels of B-type natriuretic peptide (246.0 vs. 165.1 pg/mL, P < 0.001) and lower levels of estimated glomerular filtration rate (51.6 vs. 61.8 mL/kg/1.73 m2, P < 0.001). In contrast, left ventricular ejection fraction, and prevalence of other co-morbidities such as hypertension, diabetes mellitus, dyslipidemia, chronic obstructive pulmonary disease was comparable between the two groups. The Kaplan-Meier analysis demonstrated that rate of new onset stroke was higher in the high CAVI group than in the low CAVI group (
Figure
, log-rank P = 0.001). After adjusting for potential confounding factors, high CAVI was an independent predictor of new onset stroke (hazard ratio 2.359, 95% confidence interval 1.223-4.513, P=0.010).

Conclusions:
CAVI independently predicts new onset stroke in patients with HF.
Abstract 13317: Acute Pulmonary Embolism in Covid-19 Patients: Presenting Characteristics, Outcomes and Risk Stratification Strategies
Authors: Xu Hai , Martin Angel , SINGH Avneet , Narasimhan Mangala , Lau Joe , Weinberg Mitchell , jauhar rajiv , Rao Gaurav
Published: May 2021

Introduction:
Pulmonary Embolism in coronavirus disease 2019 (COVID-19) patients have been increasingly reported in observational studies. However, limited knowledge describing their diagnostic features and clinical outcomes exist to date. Our study aims to systemically analyze their clinical characteristics and to investigate strategies for risk stratification.

Methods:
We retrospectively studied 101 patients with concurrent diagnoses of acute pulmonary embolism and COVID-19 infection, admitted at two tertiary hospitals within the Northwell Health System in New York City area. Clinical features including laboratory and imaging findings, therapeutic interventions, intensive care unit (ICU) admission, mortality and length of stay were recorded. D-dimer values were respectively documented at COVID-19 and PE diagnoses for comparison. Pulmonary Severity Index (PESI) scores were used for risk stratification of clinical outcomes.

Results:
The most common comorbidities were hypertension (50%), obesity (27%) and hyperlipidemia (32%) among our study cohort. Baseline D-dimer abnormalities (4647.0 ± 8281.8) were noted on admission with a 3-fold increase at the time of PE diagnosis (13288.4 ± 14917.9; p<0.05). 5 (5%) patients required systemic thrombolysis and 12 (12%) patients experienced moderate to severe bleeding. 31 (31%) patients developed acute kidney injury (AKI) and 1 (1%) patient required renal replacement therapy. Throughout hospitalization, 23 (23%) patients were admitted to intensive care units, of which 20 (20%) patients received invasive mechanical ventilation. The overall mortality rate was 20%. Majority of patients (65%) had Intermediate to high risk PESI scores (>85), which portended a worse prognosis with higher mortality rate and length of stay.

Conclusions:
This study provides characteristics and early outcomes for hospitalized patients with COVID-19 and acute pulmonary embolism. D-dimer levels and PESI scores may be utilized to risk stratify and guide management in this patient population. Our results should serve to alert the medical community to heighted vigilance of this VTE complication associated with COVID-19 infection, despite the preliminary and retrospective nature inherent to this study.
Abstract 13321: Pattern of Recovery of the Impaired Left Ventricle Varies by Valve Lesion
Authors: Ibrahim Michael , Spelde Audrey , Szeto Wilson Y , Acker Michael A , Atluri Pavan , Vallabhajosyula Prashanth , Bavaria Joseph E , Desai Nimesh D , Williams Matthew
Published: May 2021

Introduction:
Aortic stenosis (AS) causes pressure overload of the left ventricle, while regurgitation (AR) causes volume overload. These pathologic insults result in biologically different forms of ventricular impairment. Whether this is clinically meaningful is unknown. We hypothesized that long term clinical and echocardiographic recovery of the impaired ventricle from pressure (AS) and volume (AR) overload would be different.

Methods:
We compared the results of surgical aortic valve replacement (AVR) in patients with a pre-operative ejection fraction (EF) of 0.35 or less (excluding endocarditis) due to AS, AR or mixed disease. We reviewed long term echocardiographic and clinical follow-up. We constructed a mixed-effects model of EF and left ventricular end diastolic diameter (LVEDD) to understand ventricular recovery over the short (in-hospital), intermediate (3-6 month) and longer (>24 months) terms. We sought to identify factors associated with clinical and echocardiographic recovery using multivariable analysis.

Results:
Between July 2011 and 2017, 136 patients with pre-operative EF of 0.35 or less and severe AS (83), severe AR (18) or mixed AS and AR (35) underwent AVR. There were two deaths within 30 days in the AS group (1.5% total 30d mortality). Survival at 1, 2 and 5 years did not differ significantly between AS, AR and mixed groups. Baseline EF did not differ between the groups. Ejection fraction increased significantly, but followed a different pattern in AS, AR and mixed groups over time. LVEDD was significantly higher in the AR group, and regressed in all patient cohorts, again following a different pattern for AS and AR. Baseline EF and LVEDD predicted long term fate of the LV but did not determine survival. Factors associated with poor long term survival were age, baseline albumin, length of stay prior to surgery and previous cardiac interventions.

Conclusions:
While the impaired ventricle appears to recover in AS, AR and mixed disease, the pattern of this recovery appears to be early in AS and delayed in AR. Baseline clinical factors, rather than echocardiographic status of the LV appear to determine late survival.
Abstract 13337: Increased Serum Immunoglobulin G4 Level is a Novel Predictor of Cardiovascular Events Independent of Established Risk Factors: Results From the Real-cad Study
Authors: Sakamoto Aiko , Aizawa Kenichi , Uemura Kohei , Komuro Issei , Matsuyama Yutaka , Nagai Ryozo
Published: May 2021

Background:
Inflammation is a mediator of atherosclerosis progression. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may play a specific role in cardiovascular disease.

Methods:
We used a case-cohort design to analyze the association of serum IgG4 levels with future cardiovascular events. The sample included 561 cases of the primary end point, defined as cardiovascular death, myocardial infarction, ischemic stroke, or unstable angina, and a random subcohort of 1688 (1409 males; mean age, 68.1 ± 8.4 years), of whom 73 were also cases, selected from 12413 eligible participants with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study.

Results:
This case-cohort study had a median follow-up of 3.9 years (interquartile range [IR] 2.9-4.6). Serum IgG4 levels at baseline were 45.3 mg/dL (IR 37.9-58.9), and 845 (50%) took high-dose statins in the subcohort sample. In Cox regression using age, gender, statin dose, high-sensitivity C-reactive protein (hsCRP), body mass index, estimated glomerular filtration rate (eGFR), hypertension, diabetes, and serum lipid profiles, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, as covariates, the highest IgG4 quartile was predictive of the primary end point at 4 years (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.03-2.00, P=0.031), compared with the lowest quartile. Similar results were observed for the secondary end point, a composite of the primary end point plus coronary revascularization (HR 1.60, 95% CI 1.16-2.20, P=0.004).

Conclusions:
Elevated serum IgG4 level at baseline predicted long-term cardiovascular outcomes independent of established risk factors and high-dose statin therapy in patients with stable CAD. Serum IgG4 may reflect residual cardiovascular risk.
Abstract 13350: Primary Payer Status Influences Management and Outcomes in Non-ST Elevation Myocardial Infarction
Authors: Desai Viral K , Singh Vikas , Vallabhajosyula Saraschandra
Published: May 2021

Introduction:
Multiple previous studies have shown that insurance status of the patient impacts the management and overall outcomes of patients presenting with acute myocardial infarction. There are limited data on the impact of primary payer status in patients with non ST segment elevation myocardial infarction (NSTEMI).

Hypothesis:
Primary payer status influences management and overall outcomes independent of the clinical and hospital-based characteristics in NSTEMI patients.

Methods and Results:
Adult (>18 years) NSTEMI admissions were identified using the National Inpatient Sample database (2000-2017). Expected primary payer was classified into Medicare, Medicaid, private, uninsured, and others. Outcomes of interest included in-hospital mortality, use of coronary angiography, early coronary angiography and percutaneous coronary intervention (PCI), resource utilization, and discharge disposition. Of the 7,290,565 NSTEMI admissions, Medicare, Medicaid, private, uninsured, and other insurances were noted in 62.9%, 6.1%, 24.1%, 4.6%, and 2.3%, respectively. Compared to others, the Medicare cohort was older (76 vs. 53-60 years), more often female (48% vs. 25-44%), of white race, and with higher comorbidity (all
p
<0.001). The Medicare cohort had higher in-hospital mortality (5.6%) compared to the other groups (1.9-3.4%),
p
<0.001. In a multivariable analysis (Medicare referent), in-hospital mortality was higher in other (adjusted odds ratio (aOR) 1.15 [95% confidence interval {CI} 1.11-1.19];
p
<0.001), and lower in Medicaid (aOR 0.95 [95% CI 0.92-0.97];
p
<0.001), private (aOR 0.77 [95% CI 0.75-0.78];
p
<0.001) and uninsured cohorts (aOR 0.97 [95% CI 0.0.94-1.00];
p
=0.06). Coronary angiography (overall 52% vs. 65-74%; early 15% vs. 22-27%) and PCI (27% vs. 35-44%) were used less frequently in the Medicare population. The Medicare population had longer lengths of hospital stay, lowest hospitalization costs and fewer discharges to home.

Conclusions:
Compared to other types of primary payers, NSTEMI admissions with Medicare insurance had lower use of coronary angiography and PCI and higher in-hospital mortality.
Abstract 13354: Effectiveness of a Complex Intervention Based on Electronic Decision Support to Improve Management of Cardiovascular Disease Risk in Primary Healthcare: A Cluster-randomised Controlled Trial
Authors: Webster Ruth , Usherwood Tim , Joshi Rohina , Saini Bandana , Armour Carol , di Tanna Gian Luca , Hespe Charlotte , Jan Stephen , Krass Ines , Laba Tracey Lea , Li Qiang , Lo Serigne , Peiris David , Reid Chris , Rodgers Anthony , Patel Anushka
Published: May 2021

Introduction:
Cardiovascular disease (CVD) risk management is suboptimal in Australian primary healthcare. Following trials demonstrating efficacy of individual components, we developed a complex intervention comprised primarily of electronic point-of-care decision support, availability of cardiovascular polypills and a pharmacy-based adherence program. We sought to determine whether this combined multifaceted intervention, compared with usual care, would improve control of CVD risk factors in the Australian primary care setting.

Methods and Results:
In a parallel-arm cluster randomized trial, 71 general practices were allocated 1:1 either to the intervention or usual care. The primary outcome was the proportion of patients at high CVD risk and not on optimal preventive treatments at baseline (“high-risk under-treated”) achieving both blood pressure (BP) and low density lipoprotein (LDL) cholesterol targets at study end (BP ≤140/90 mmHg, or ≤130/80 mmHg in people with diabetes or albuminuria; LDL <2.0 mmol/L). All outcomes were evaluated using automated extracts from the electronic medical record. After a median period of 15 months follow-up, among 4477 high-risk under-treated patients in whom follow-up data were available, there was a negligible difference between randomized groups in the proportion achieving SBP and LDL cholesterol targets (19.6% vs. 20.1%; RR 1.06 [95% CI: 0.85 to 1.32]; p=0.59). There was also no major impact of the intervention on any pre-specified secondary outcomes, mostly relating to risk factor screening, preventive medication prescription and risk factor levels. Uptake of all components of the intervention was poor, with greatest use observed for the electronic decision support component (used at least once in 10.7% of high-risk under-treated patients) and minimal use of the other two interventions.

Conclusions:
Despite the proven efficacy of individual components, this complex multifaceted intervention was poorly adopted and did not lead to relevant improvements in cardiovascular risk factor outcomes.
Abstract 13381: hiPSC of CIITA and B2M KO Derived Cardiac Cells Engineered 3D Spheroid Transplantation Induce Tachycardia in Myocardial Infarction in Swine
Authors: Mattapally Saidulu , Zhang Jianyi
Published: May 2021

Introduction:
Human induced pluripotent stem cells (hiPSCs) are among one the most significant discoveries in life sciences. As a promising —biological drug for cell therapy, multiple lineages of iPSC-derived cardiac cells have been administered in human clinical trials in multiple important organ systems. The potential immunogenicity of hiPSC-derived cardiac cells continues to be one of the concerns in large animal models.

Methods:
In the present study, WT hiPSCs were generated by transfecting male human cardiac fibroblasts with Sendai viruses coding for OCT4, SOX2, KLF4, and C-MYC.Then hiPSCs carrying knockout mutations for both HLA Class I and Class II (HLAI/II-KOhiPSC) were generated via CRISPR/Cas9 gene-editing technology (Mattapally et al, 2018). hiPSCs were differentiated into cardiomyocytes (CM) endothelial cells (ECs) and spheroid cultured was performed as previously described (Mattapally et al, 2018). We evaluated spheroid transplantation and its potency for myocardial repair in the Swine. Programmed stimulation was used to determine the arrhythmogenic outcome.

Results:
To determine the engraftment efficacy of HLAI/II KO compared to WT Spheroid, a swine study was performed. After LAD ligation in swine, 800μm spheroid was injected into the border zone of the left ventricle. After transplantation, cell engraftment was monitored by Q-PCR. At week 4, there was a significant difference between the 2 groups. Animal groups included: MI hearts treated with 500 WT Spheroid injection (MI+WT Spheroid, n=5), MI hearts treated with 500 KO Spheroid injection (n=6), MI only hearts (n=6); the fourth group of animals underwent sham surgery (Sham, n=6). Arrhythmia was studied by programmed electrical stimulations (PES) and conduction velocities measured with electrode mapping, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Engraftment of iPSC-CMs was found in both treatment groups; however, a significantly higher engraftment rate was found in KO Spheroid. The spheroid treatment is associated with significant changes in arrhythmogenicity.

Conclusion:
Our study established the improved graft but associated with arrhythmogenicity.
Abstract 13391: Cardiomyocyte Cell Cycling, Maturation, and Growth by Multinucleation in Postnatal Swine
Authors: Velayutham Nivedhitha , Alfieri Christina M , Agnew Emma J , Riggs Kyle W , Baker Richard S , Ponny Sithara Raju , Zafar Farhan , Yutzey Katherine E
Published: May 2021

Background:
Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative capacity as rodents. Here, we provide a comprehensive analysis of postnatal cardiac maturation in swine, including CM cell cycling, multinucleation and hypertrophic growth, as well as non-CM cardiac factors such as extracellular matrix (ECM), immune cells, capillaries, and neurons. Our study reveals discordance in postnatal pig heart maturational events compared to rodents.

Methods and Results:
Left-ventricular myocardium from White Yorkshire-Landrace pigs at postnatal day (P)0 to 6 months (6mo) was analyzed. Mature cardiac sarcomeric characteristics, such as fetal
TNNI1
repression and CX43 co-localization to cell junctions, were not evident until P30 in pigs. In CMs, appreciable binucleation is observed by P7, with extensive multinucleation (4-16 nuclei per CM) beyond P15. Individual CM nuclei remain predominantly diploid at all ages. CM mononucleation at ~50% incidence is observed at P7-P15, and CM mitotic activity is measurable up to 2mo. CM cross-sectional area does not increase until 2mo-6mo in pigs, though longitudinal CM growth proportional to multinucleation occurs after P15. RNAseq analysis of neonatal pig left ventricles showed increased expression of ECM maturation, immune signaling, neuronal remodeling, and reactive oxygen species response genes, highlighting significance of the non-CM milieu in postnatal mammalian heart maturation.

Conclusions:
CM maturational events such as decline of mononucleation and cell cycle arrest occur over a 2-month postnatal period in pigs, despite reported loss of heart regenerative potential by P3. Moreover, CMs grow primarily by multinucleation and longitudinal hypertrophy in older pigs, distinct from mice and humans. These differences are important to consider for preclinical testing of cardiovascular therapies using swine, and may offer opportunities to study aspects of heart regeneration unavailable in other models.
Abstract 13399: Variable Exposure to Echocardiography Pathology and Core Competencies Among Cardiology Fellows-in-training
Authors: Bierowski Matthew , Qureshi Umer , Ramedani Shayann , Grewal Simran , Shah Ravi , Park Robert , Peterson Brandon R
Published: May 2021

Introduction:
Current guidelines recommend interpretation of at least 300 echocardiograms to achieve competency in echocardiography for independent practice (level II COCATS). Recommended core competencies in echocardiography include proficiency in evaluating native and prosthetic valve diseases, pulmonary hypertension and right heart dysfunction, and suspected cardiac masses or endocarditis, among others. Whether the recommended number of cases allows for adequate exposure to the various core competencies, however, is unclear.

Hypothesis:
We investigated whether certain core competencies are less commonly encountered when using the recommended case numbers by current guidelines.

Methods:
We reviewed echocardiograms interpreted by 10 of our cardiology fellows (2 per year) who began training from July 2015 through July 2019. We recorded core competency measures encountered in the first 300 echocardiograms interpreted by each fellow, including measures of left and right ventricular dysfunction, valvular diseases, cardiac masses, aortic disease, and pericardial disease. Paired T-test was used to compare the mean occurrence between different core competencies.

Results:
Among the 3000 echocardiograms reviewed, abnormal wall motion was the most common pathology encountered, whereas each other core competency was relatively less common (p<0.05 for all comparisons, see plots below). Deficiencies in core competencies included: 9/10 fellows had no cases of aortic dissection, 3/10 had no cases of valvular mass, 2/10 had no cases of cardiac chamber mass, 2/10 had no cases of cardiac tamponade, and 1/10 had no cases of prosthetic valve dysfunction.

Conclusions:
The recommend number of echocardiograms in current guidelines does not ensure adequate exposure to all areas of echocardiography core competency. Educators should consider strategies to supplement learning in these areas to ensure experience in all areas of echocardiography core competency.
Abstract 13401: Prothymosin Alpha (Protα) Associates With Pathogenesis and Sex Predisposition in Rheumatic Heart Valve Disease
Authors: Passos Livia , Blaser Mark C , Romero Dayanna , Becker Greene Dakota , Lupieri Adrien , Sukhova Galina K , Dal-bianco Jacob P , Libby Peter , Singh Sasha A , Aikawa Masanori , Levine Robert A , Nunes Maria Do Carmo P , Aikawa Elena
Published: May 2021

Introduction:
Acute rheumatic fever (ARF) results from autoimmune responses to group A streptococcus. ARF can cause chronic rheumatic heart valve disease (RHVD), a major public health burden in low- and middle-income countries. Although ARF affects both sexes equally, females have a higher prevalence of RHVD. We identified a target protein, ProTα, that may contribute to pathophysiology of and gender predisposition in RHVD. Estradiol regulates ProTα, which influences transcriptional activity of the estrogen receptor (ER).

Methods:
Human heart valves (n=120) obtained from heart transplantation and valve replacement surgeries, including non-diseased mitral and aortic valves (NDMV and NDAV, n=17/group), rheumatic mitral and aortic valves (RMVD, n=45; RAVD, n=8) and calcifying valves from patients with calcific aortic valve disease (CAVD, n=33) underwent proteomic and network analyses, and immunohistochemical assessment of CD68, CD4, CD8 and ProTα. ProTα levels were measured in plasma and peripheral mononuclear cells (PBMCs) from RHVD patients and healthy donors (n=14/group) by ELISA and flow cytometry.

Results:
A comparison of proteomes from NDMV and NDAV established the baseline differences between valve types. 12 proteins were enriched (q<0.05) in NDMV that may indicate the mitral valve predisposition to RVHD. Proteome analysis of non-diseased and diseased valves (NDMV vs RMVD, NDAV vs RAVD) identified a total of 213 proteins enriched in RHVD (q<0.05). The expression of the 12 NDMV-enriched proteins were evaluated across the 213 proteins enriched in diseased valves, resulting in the identification of ProTα common to both the RMVD and RAVD proteomes, but absent in CAVD. Additional KEGG pathway enrichment analyses linked 6 among 213 proteins with the estrogen signaling pathway (p<0.05). Immunoreactive ProTα colocalized with T CD8 cells in RHVD. ProTα and ERα also correlated strongly in circulating T CD8 cells in RHVD (p<0.05). ProTα plasma levels were higher in RHVD patients than healthy individuals (2 fold, p<0.05).

Conclusion:
We propose that ProTα is a novel contributor to the immunopathogenesis of RHVD and may regulate sex predisposition in this disease.
Abstract 13403: Relationship Between Body Mass Index and In-hospital Outcomes After Percutaneous Coronary Intervention Among Patients With Acute Myocardial Infarction: A National In-Patient Analysis
Authors: Sanni Habeeb O , Eromosele Oseiwe B , Aibangbee Keziah E , Ogunsua Adedotun , Chukwuma Vivian N , Diala Chiamaka S , Lukan Abdulkareem O , Fasanmi Oluwafisayo S , Olagoke Olakanmi , Abu Hawa O , Igbinomwanhia Efehi
Published: May 2021

Background:
Body mass index (BMI), has been shown to be related to major adverse cardiovascular events, and overall mortality after percutaneous coronary intervention (PCI). However, the relationship between BMI, and important cardiovascular outcomes, as well as healthcare utilization have not been extensively explored in a national sample.

Objectives:
Examine the relationship between BMI and in-hospital mortality, cardiogenic shock, cardiac arrest, length of hospital stay (LOS), and cost of hospitalization.

Methods:
Adults who had a primary diagnosis of Acute Myocardial Infarction (AMI) who underwent a PCI were identified from the 2016 and 2017 National Inpatient Sample using ICD10 codes. BMI was classified BMI into: <20 kg/m
2
, 20-29.9 kg/m
2
(reference), 30-34.9 kg/m
2
(Obesity class I), 35-39.9 kg/m
2
(Obesity class II) and ≥40 kg/m
2
(Obesity class III). Weighted multivariable logistic and linear regression models were used as appropriate.

Results:
Among 22,953 patients who had AMI and PCI done with reported BMI, 67.9% were male, and 76.2% were Non-Hispanic White. Compared to the reference group, obesity class I, II and III, showed an incremental higher odd of mortality, while patients with BMI <20 kg/m
2
had non-significant lower odds of mortality (Table). Obesity class I and II had lower odds of cardiogenic shock compared to the reference group, while those in the extremes i.e. <20 kg/m
2
and ≥40 kg/m
2
showed no significant difference (Table).The odds of cardiac arrest were not significantly different across the various BMI categories (Table). Obesity class III patients had significantly higher mean LOS and cost of hospitalization compared to the reference group (Table).

Conclusion:
Our study highlights the relationship between BMI and important clinical outcomes after PCI. These findings buttress the need for healthcare providers to identify high risk patients for worse outcomes after PCI and institute targeted interventions for improved clinical outcomes.
Abstract 13412: Electronic Consultation for the Management of Atrial Fibrillation is Associated With Higher Healthcare Costs
Authors: Manning Evan S , Whittington Melanie D , Kirsh Susan R , Kenney Rachael , ToddStenberg Jeffrey , Au David H , Ho Michael , Simonetti Joseph
Published: May 2021

Introduction:
A study of 42,000 cardiology consults within the Veterans Health Administration (VHA) in 2016 found that patients who received electronic consultation (e-consults) had similar healthcare costs at 6 months compared to those who received face-to-face (F2F) consults. However, results may have been confounded if patients with less costly conditions received e-consults. Our aim was to compare costs between those receiving F2F vs. e-consults for a similar indication.

Hypothesis:
Electronic rather than F2F consultation for atrial fibrillation (AF) management will be associated with lower total healthcare costs.

Methods:
We conducted a retrospective cohort study of a national sample of VHA patients who received cardiology consultation in 2016. We used a natural language processing script to identify consults for AF management. Primary outcomes were total healthcare costs at 3 and 6 months. Secondary outcomes included inpatient and outpatient costs. We compared costs between groups using a generalized linear model with a gamma distribution and log link. We adjusted for community wage and Charlson comorbidity indices, distance to nearest facility, age, and gender. Standard errors were clustered at the facility level.

Results:
We sampled 176 F2F and 136 e-consults from 43 facilities. Mean total 6-month costs were $12,928 (95% confidence interval [CI]: 1,377; 40,644) and $8,286 (95% CI: 959; 31,320) among e-consult and F2F groups, respectively. The e-consult group had 12.3% higher 3-month (p<0.001) and 41.5% higher 6-month total healthcare costs (p<0.001) in comparison to the F2F group. At 3 months, the e-consult group had 25.1% lower inpatient costs (p<0.001) and 32.5% higher outpatient costs (p<0.001). At 6 months, the e-consult group had 6.3% higher inpatient costs (p<0.001) and 48.4% higher outpatient costs (p<0.001).

Conclusions:
Use of e-consults for AF management is associated with reduced inpatient costs at 3 months, but higher total costs, which were largely driven by outpatient costs. Improving our understanding of healthcare utilization after initial consultation, or in differences in reasons for consultation within AF management may help explain these differences.
Abstract 13426: The Dual GIP/GLP-1 Receptor Agonist Tirzepatide Improves Cardiovascular Risk Protein Biomarkers in Patients With Type 2 Diabetes
Authors: Wilson Jonathan M , Lin Yanzhu , Considine Gary , Cox Amy L , Bowsman Lenden M , Robins Deborah A , Riesmeyer Jeffrey S , Haupt Axel , Duffin Kevin , Ruotolo Giacomo
Published: May 2021

Introduction:
The dual GIP/GLP-1 receptor agonist tirzepatide dose-dependently reduced HbA1c and body weight in patients with obesity and type 2 diabetes (T2D) in a Phase 2 trial.

Hypothesis:
In this post hoc analysis, additional biomarkers of inflammation, endothelial dysfunction, and cellular stress were measured to better understand possible additional effects of tirzepatide treatment on cardiovascular risk factors.

Methods:
Patients with T2D were randomly assigned to receive either once-weekly subcutaneous injection of tirzepatide (1, 5, 10, or 15 mg), GLP-1 receptor agonist dulaglutide (1.5 mg), or placebo for 26 weeks. Soluble ICAM-1 and VCAM-1, IL-6, NT-proBNP, hsCRP and GDF-15 were assessed by immunoassay at baseline and 26 weeks in stored serum or EDTA plasma samples. Results were analyzed in a modified intent-to-treat population using a mixed effect model for repeated measures.

Results:
At 26 weeks, tirzepatide dose-dependently decreased ICAM-1 levels compared to baseline (Table). ICAM-1 levels were also significantly lower with tirzepatide 15 mg than placebo or dulaglutide. Moreover, tirzepatide 15 mg significantly decreased hsCRP levels from baseline compared with placebo. GDF-15 levels were decreased from baseline with all tirzepatide doses and with dulaglutide; however, changes in GDF-15 levels with tirzepatide were not significantly different from those with placebo or dulaglutide. Levels of IL-6, VCAM-1 or NT-proBNP were unchanged in all groups.

Conclusions:
In a 26-week study in patients with obesity and T2D, treatment with tirzepatide dose-dependently decreased circulating levels of specific biomarkers of inflammation and endothelial dysfunction previously associated with cardiovascular events, thus suggesting a net improvement in the cardiovascular risk profile of these patients. Clinical relevance of these changes will be assessed in the planned cardiovascular outcome study SURPASS-CVOT (NCT04255433).
Abstract 13428: Cardiac Troponin T Level is Associated With Myocardial Recovery in Fulminant Myocarditis
Authors: Kondo Toru , Shibata Naoki , kazama shingo , Kimura Yuki , Oishi Hideo , Kuwayama Tasuku , Hiraiwa Hiroaki , Morimoto Ryota , OKUMURA TAKAHIRO , Murohara Toyoaki
Published: May 2021

Background:
Fulminant myocarditis (FM) is a fatal disease that causes rapid-onset severe heart failure requiring inotropes or mechanical circulatory support (MCS). Because insufficient myocardial recovery requires durable left ventricular assist device or heart transplantation, the course of myocardial recovery should be predicted.

Hypothesis:
Cardiac troponins, which elevates due to myocardial damage, may associate with myocardial recovery in FM.

Purpose:
We aimed to investigate the relationship between cardiac troponin T (TnT) levels and myocardial recovery course in patients with FM.

Method:
We performed a retrospective medical record review of 19 patients with FM requiring MCS from May 2012 to January 2020. The serial changes of one-week left ventricular ejection fraction (LVEF) after MCS implantation according to TnT levels were evaluated.

Results:
Median age was 50 years and 10 patients were male. As for initial MCS, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pumping (IABP) were used in 13 patients, IABP in 4 patients, VA-ECMO in one patient, and impella 2.5 in one patient. Median peak TnT level within one week after MCS implantation were 4.43 (2.47 - 34.6) ng/mL. The patients were divided into High-TnT group and Low-TnT group according to median peak TnT level. All patients in both groups were alive until 7 days after MCS implantation, and LVEF on day 7 was significantly lower in the High-TnT group (Fig). TnT level was highest on day 1 and gradually decreased in the High-TnT group (Fig). Six patients died during hospitalization in the High-TnT group, in contrast, only one patient died in the Low-TnT group (p=0.020). Peak TnT level in patients with LVEF ≥30% (n=8) on day 7 was significantly lower than in patients with LVEF <30% (2.40 vs 13.5 ng/mL, p=0.012), however, other laboratory parameters showed no significant differences.

Conclusion:
Higher TnT level showed impaired myocardial recovery in patients with FM.