bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15256: Predicting Out-of-office Blood Pressure in United States Adults
Authors: Bellows Brandon K , Xu Jingyu , Sheppard James P , Schwartz Joseph E , Shimbo Daichi , Muntner Paul , McManus Richard , Moran Andrew E , Bryant Kelsey B , Cohen Laura P , Bress Adam P , King Jordan B , Shikany James M , Green Beverly , Yano Yuichiro , Clark Donald , Zhang Yiyi
Published: May 2021

Introduction:
The Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP) algorithm accurately estimates out-of-office BP to guide ambulatory BP monitoring (ABPM) among adults in the UK and Canada with suspected high BP. We tested the validity of PROOF-BP in a diverse US population and developed a US-specific algorithm.

Methods:
We pooled data from four US studies (CARDIA, JHS, Masked Hypertension Study, and Improving Detection of Hypertension Study) that assessed both office BP and 24-hour ABPM. We included participants with >=2 office and >=10 daytime ambulatory BP readings. PROOF-BP estimates the difference between office systolic BP (SBP) and diastolic BP (DBP) and daytime ambulatory SBP and DBP using clinic BP measurements and patient characteristics. We examined the performance of PROOF-BP in US data and then used multivariable linear regression to develop a new algorithm optimized for the US population. We tested the ability of PROOF-BP to discriminate high awake ambulatory SBP and DBP (SBP/DBP >=130/80 mm Hg) using the area under the receiver-operator curve (AUROC). Models were developed in a 70% randomly selected derivation set and tested in a 30% validation set. The optimal predicted ambulatory BP thresholds were defined as those that resulted in the smallest proportion of individuals recommended for ABPM with an overall classification error <20% among those not screened.

Results:
We analyzed 3,080 individuals with a mean (SD) age of 52.0 (11.9) years, 38% were male, and 54% were black. Mean (SD) office SBP/DBP was 121.8 (16.6)/75.3 (9.8) mm Hg, mean (SD) awake ambulatory SBP/DBP was 127.3 (13.5)/78.6 (8.8) mm Hg, and 51% had awake ABPM >=130/80 mm Hg. The discrimination for high awake ABPM was similar between the existing (AUROC SBP = 0.77, DBP = 0.73) and US-specific models (AUROC SBP = 0.77, DBP = 0.72). Optimal predicted ambulatory BP thresholds with the US-specific algorithm were 125-134/75-84 mm Hg, resulting in 55% of the pooled cohort recommended for ABPM; compared to 66% recommended by the 2017 ACC/AHA guidelines.

Conclusions:
Both the original and US-specific PROOF-BP algorithms predicted high out-of-office BP among US adults. PROOF-BP may be used to guide clinical decisions and resource allocation among individuals considered for ABPM.
Abstract 15260: Higher Levels of Osteoblast-lineage Cells Are Associated With Cardiac Allograft Vasculopathy Progression
Authors: Ozcan Ilke , Toya Takumi , Corban Michel , Ahmad Ali , Loeffler Darrell , Ostlie Hunter , Kushwaha Sudhir , Lerman Lilach O , LERMAN Amir
Published: May 2021

Introduction:
Cardiac allograft vasculopathy (CAV) is a major determinant of long term graft survival. Endothelial progenitor cells (EPC) expressing osteocalcin (OC) have been linked to atherosclerosis. However, little is known regarding bone-forming osteoblast-lineage (OL) cells, and their role in atherosclerosis and CAV.

Methods:
Heart transplant patients undergoing serial Intravascular Ultrasound (IVUS) and progenitor cell studies were included in the study. OL cells, defined as cells positive for alkaline phosphatase (AP) and OC, were counted using flow cytometry on the day of baseline IVUS. A follow up IVUS was done 3 years later. Gray-scale and virtual-histology IVUS were used to evaluate vessel size, plaque burden, and plaque composition (fibrous, fibrofatty, necrotic core, calcified). Patients were divided into two groups by the median change (Δ) in necrotic core volume and plaque volume over 3 years.

Results:
A total of 55 patients (mean age 52±15 years, 65% males) were included. At baseline, median time after transplant was 4.2 years. Average vessel area at baseline and three years were 15.8 ±4.6 and 15.3 ±5.4 mm2, respectively (p=0.32). However, 24/55 patients (44%) had positive remodeling. The number of OL cells was positively correlated with Δvessel (r=0.36, p=0.01) and Δlumen areas. (r=0.30, p=0.02). Patients with greater Δplaque volume and Δnecrotic core volume had higher OL cell levels compared to those with below medians (Δplaque volume: 95 [30,348] vs. 30 [10, 90] OL per 100,000 counts, p=0.01; Δnecrotic core volume: 95 [22.5, 320] vs. 30 [10, 90] OL per 100,000 counts, p=0.03) (Fig. 1A and 1B).

Conclusions:
The number of OL cells in heart transplant patients correlates with positive vascular remodeling, accompanied by increased lumen area over 3 months. Furthermore, patients with unstable plaque features had higher OL cells, suggesting a possible role in pathologic plaque progression.
Abstract 15263: Co-existing Systemic Lupus Erythematosus Does Not Negatively Impact Outcomes of Patients Admitted for Acute Coronary Syndrome: Analysis of the National Inpatient Sample
Authors: Edigin Ehizogie , Eseaton precious O , Asemota Iriagbonse R , Akuna Emmanuel , Shaka Hafeez , Ojemolon Pius E , manadan augustine
Published: May 2021

Introduction:
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease with effects on multiple organ systems and a wide range of clinical manifestations. Cardiovascular diseases from accelerated atherosclerosis are one of the major causes of mortality in SLE patients. This study aims to compare the outcomes of patients primarily admitted for Acute Coronary Syndrome (ACS) with and without a secondary diagnosis of SLE.

Methods:
Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. This database is the largest collection of inpatient hospitalization data in the United States (U.S). The NIS was searched for hospitalizations for adult patients with ACS as principal diagnosis with and without SLE as secondary diagnosis using ICD 10 codes. The primary outcome was inpatient mortality. Secondary outcomes of interest are showed in Table 1. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used to analyze the data.

Results:
There were over 71 million discharges included in the combined 2016 and 2017 NIS database. Out of 1.3 million patients with ACS, 5,485 (0.42%) had SLE. The adjusted odds ratio (AOR) for inpatient mortality for ACS with co-existing SLE compared to those without SLE was 1.16 (95% CI 0.86-1.56, P=0.333). Hospitalizations for ACS with co-existing SLE had a decrease in adjusted mean total hospital charge of $5,164 compared to those without SLE (95% CI - {10,202-126}, P=0.045).

Conclusions:
Patients admitted primarily for ACS with a secondary diagnosis of SLE had less total hospital charges, but similar inpatient mortality, LOS, revascularization strategies, rates of IABP and PEAD placement compared to those without SLE. Though SLE is known to increase the risk of cardiovascular diseases, SLE does not negatively impact outcomes in patients primarily admitted for ACS based on U.S. national hospital billing data.
Abstract 15277: Monitoring Progression of Aneurysms of the Ascending Aorta: Timing, Cost and Radiation Exposure
Authors: Callow Alexander E , Long Jordan , Rehman Sahar , Khaliq Isna H , Boland Sebastian , Mikolich J. Ronald
Published: May 2021

Introduction:
Current guidelines of the American Heart Association (AHA) recommend annual serial imaging for patients with aneurysm of the ascending aorta (AscAoA). However, recent data (Park K-H et al. Eur J CT Surg 2017;51:959-64) have suggested that this imaging frequency may not be necessary. This study was designed to compare the progression in growth rates of AscAoA using cardiac MRI (CMR) in 2 large cohorts of patients reassessed every 1 year and every 2 years.

Methods:
An institutional cardiac imaging database was queried for all patients with AscAoA, defined as a maximum ascending aorta diameter > 3.5 cm measured perpendicular to flow using CMR. The study cohort was divided into two groups; patients who had a follow up CMR every 1 (Group A), and those who had a CMR every 2 years (Group B). AscAoA growth rates were computed for each group and statistically compared using a two-sample t-test. For analysis of cost to the healthcare system, Medicare reimbursement rates for 2019 were utilized. Published mean radiation dose for cardiac CT (CCT) was utilized to assess radiation exposure.

Results:
Of 6,210 patients in the cardiac imaging database, 1,849 had a diagnosis of AscAoA, of which 941 had serial CMR studies. Of these 941 patients, 342 had a follow up CMR every 1 year, while 206 had a follow up CMR every 2-years. The mean progression of AscAoA was 0.0247 ± 0.475 cm for Group A and 0.0598 ± 0.209 cm for Group B. The growth rate of AscAoA was not significantly different between groups (p=0.236). The Medicare reimbursement for CMR was $23,056 per 100 patients (CPT 75557) without radiation exposure. If CCT had been used for these patients, Medicare reimbursement would have been $20,174 per 100 patients (CPT 75572) with exposure to 10.5 mSv of radiation per study.

Conclusions:
There was no significant difference in progression of AscAoA diameter between Groups A and B. These data suggest that serial imaging of AscAoA every 2 years may be appropriate, with reduced cost to the healthcare system and cumulative radiation exposure. Although CMR is slightly more costly than CCT, it eliminates cumulative breast radiation exposure, a feature of particular importance for female patients.
Abstract 15281: Triglyceride Levels and Cardiovascular Outcomes After Acute Coronary Syndrome: Insights From the Odyssey Outcomes Trial
Authors: Zahger Doron , Szarek Michael , Bhatt Deepak L , Bittner Vera A , Budaj Andrzej , Diaz Rafael , Goodman Shaun G , Jukema J Wouter W , Kiss Robert G , McGinniss Jennifer , Harrington Robert A , Moriarty Patrick M , Pordy Robert , Reiner Zelijko , Loy Megan , Viigimaa Margus , White Harvey D , Zeiher Andreas M , Schwartz Gregory G , Steg Philippe G
Published: May 2021

Introduction:
It is controversial whether triglyceride (TG) levels are independently associated with post-acute coronary syndrome (ACS) major adverse cardiovascular events (MACE) in patients treated with statins. PCSK9 inhibitors such as alirocumab (ALI) produce substantial reductions in LDL-C, modest reductions in lipoprotein(a) and TG-rich lipoproteins, and reduce MACE.

Objective:
Using data from the ODYSSEY OUTCOMES trial that compared ALI with placebo in 18,924 patients with recent ACS on optimized statin treatment, we performed a prespecified analysis to determine if MACE (death from coronary heart disease, myocardial infarction, ischemic stroke, or unstable angina) was associated with baseline TG levels in patients treated with placebo, and if MACE reduction with ALI was influenced by baseline TG or the change in TG under treatment.

Methods and Results:
Proportional hazards models relating continuous baseline TG or the change in TG from baseline to Month 4 with MACE were adjusted for baseline variables: age, region, LDL-C, lipoprotein(a), diabetes, hypertension, BMI, heart failure, peripheral artery disease and cerebrovascular disease. At baseline, median TG level was 130 mg/dL. Median absolute change from baseline to month 4 in the ALI group was -17 (-49, 12) mg/dL. Within the placebo group, baseline TG was associated with MACE (HR per 10 mg/dL increment 1.007, 95% CI 1.001–1.014, p=0.03), although spline analysis suggested non-linearity (
Figure
; spline effect p=0.01) with higher risk above approximately 190 mg/dL. MACE reduction by ALI (HR 0.85, 95% CI 0.78–0.93) did not depend on baseline TG (interaction p=0.99). In the ALI group, change in TG from baseline to Month 4 did not predict MACE after Month 4 (p=0.47).

Conclusions:
Among patients with recent ACS on optimized statin treatment, baseline TG levels are an independent predictor of MACE. The beneficial effect of ALI on MACE did not depend on either baseline or on treatment TG levels .
Abstract 15288: Mitochondrial Injury in Cardiomyopathy of Neurogenic Hypertension: Role of MiR-18a-5p/HIF-1a Axis
Authors: Nandi Shyam S , Katsurada Kenichi , Sharma Neeru M , Mahata Sushil K , Patel Kaushik P
Published: May 2021

Hypertension increases the risk of heart disease, and key hallmark features of hypertensive heart disease is sympatho-excitation and mitochondrial injury. However, the molecular intermediary link between enhanced sympatho-excitation and cardiac mitochondrial injury remains unclear. Sprague-Dawley rats (250-300g) were subjected to a central infusion of Ang II (20ng/min for 14days, 0.5μl/h, i.c.v.; neurogenic hypertension (NG-HTN)) or isotonic saline (0.9% saline, i.c.v; Control (Con)) through osmotic mini-pumps. Mitochondrial injury and cardiac remodeling were assessed using Western blot, histology, immunocytochemistry and electron microscopy. Sympatho-excitatory effect on mitochondrial injury was examined in
in vitro
by administration of norepinephrine (NE) on H9c2 rat cardiomyocytes. Our NG-HTN rat model exhibited increased sympatho-excitaton and hypertension. Concomitantly, there was reduced miRNA-18a-5p (NG-HTN: 0.65±0.05 vs. Con: 1.06±0.04 vs.), but increased HIF-1α levels in the heart (NG-HTN: 1.82±0.4 vs. Con: 0.88±0.13). Increased mitochondrial untranslated protein response (UPR
mt
) marker HSP60 (NG-HTN: 1.22±0.08 vs. Con: 0.81±0.07) indicated mitochondrial proteinopathy and proteotoxic stress associated with increased mito-ROS and altered mitochondrial oxidative phosphorylation. Further, there was reduced mitochondrial biogenesis and fusion, but increased mitochondrial fission, coupled with impaired mitochondrial TIM-TOM translocase performance in NG-HTN hearts. Electron microscopy revealed mitochondrial injury in NG-HTN hearts, linked with hypertrophic cardiomyopathy and fibrosis remodeling. Our In-silico data showed increased NE decreased miR-18a-5p to target HIF-1α, and corroborated mitochondrial injury and cardiomyocyte hypertrophy in, in vitro studies. In conclusion, these results demonstrate that enhanced sympatho-excitation contributes to reduced miR-18a-5p causing increased HIF-1α in the heart leading to mitochondrial proteotoxic stress and metabolic shift, which underlies mitochondrial injury. This study identifies the key molecular intermediary links that can potentially be manipulated for therapeutic benefits for pathological cardiac remodeling in clinical HTN.
Abstract 15301: Peripheral CD56
bright
Natural Killer Cells Associate With Increased Atheroburden and Unstable Plaque Features in Humans
Authors: Kothari Hema , Drago Fabrizio , McSkimming Chantel , McNamara Coleen A
Published: May 2021

Background:
Atherosclerotic plaques in mice and humans contain natural killer (NK) cells. Data on the role of NK cells in atherosclerosis using different transgenic mice models is inconsistent. Some studies showed that NK cells augment atherosclerosis through their cytotoxic potential, while others reported no effect. Evidence in humans indicates that NK cells are atherogenic. Frequency of NK cells and expression of the activating NK cell receptors are associated with severe disease and symptomatic carotid atherosclerotic plaques in humans.

Hypothesis:
We tested if coronary artery disease (CAD) subjects with necrotic plaques have a higher frequency of the circulating NK cells.

Methods:
We performed mass cytometry on peripheral blood mononuclear cells from matched CAD subjects with low and high (n=9 each) necrotic plaque content as determined by intravascular ultrasound-virtual histology.

Results:
CAD subjects with high necrotic plaques have significantly higher atheroburden, stenosis, calcium, fatty plaque content, and lower plaque fibrosis. Interestingly, CAD subjects with high necrotic plaques exhibited a significantly higher frequency of the CD56
bright
NK cells as compared to those with low necrotic plaques (4.618 ± 0.625 vs 2.481 ± 0.37; p=0.011). Moreover, frequency of CD25
+
NK cells also trended to be higher in subjects with high necrotic plaques. The frequency of the cytotoxic CD56
dim
NK cells did not differ between the two groups. Correlation analyses demonstrated a significant positive association of CD56
bright
NK cells with atheroburden (r=0.43; p=0.04), stenosis (r=0.58; p=0.005), plaque necrotic (r=0.71; p=0.002), calcium contents (r=0.73; p=0.0001), and a negative association with the plaque fibrous content (r=0.71; p= 0.0003). CD25
+
NK cells also showed similar trending associations with burden, stenosis and plaque features.

Conclusions:
Our data provides yet another evidence of the atherogenic role of NK cells in humans and indicates that the CD56
bright
NK cells may contribute to the development of a vulnerable plaque. CD56
bright
NK cells produce proinflammatory cytokines including IFN-γ and TNF-α and cytotoxic enzymes that may contribute to increased inflammation, cell activation, and apoptosis within the plaque.
Abstract 15315: SGLT2 Inhibitor Ertugliflozin Decreases Elevated Intracellular Sodium, Improves Myocardial Energetics and Enhances Function in Metabolic Heart Disease
Authors: Croteau Dominique , Baka Tomas , Young Sara , He Huamei , Pimentel David R , Panagia Marcello , Balschi James , Colucci Wilson S , Luptak Ivan
Published: May 2021

Background:
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic drugs of great interest in cardiology due to their improvement of heart failure outcomes independent of diabetes. As SGLT2 is not expressed in cardiomyocytes, the mechanism of such benefit remains unclear. Elevated myocardial intracellular sodium [Na
+
]
i
has been found in heart failure and SGLT2 inhibition lowers [Na
+
]
i
in isolated cardiomyocytes. Elevated [Na
+
]
i
was shown to decrease mitochondrial calcium via mitochondrial Na/Ca exchanger (NCx
MITO
), resulting in decreased mitochondrial ATP synthesis. We have previously shown that mice fed a diet high in fat and sugar (HFHS) develop metabolic heart disease (MHD) characterized by decreased mitochondrial ATP synthesis with decreased phosphocreatine (PCr), worsened diastolic function and contractile reserve. We hypothesize that the SGLT2 inhibitor ertugliflozin (ERTU) decreases the elevated [Na
+
]
i
to improve energetics and contractile function in MHD.

Methods and Results:
Isolated hearts from mice after 6 months of HFHS vs. control diet (CD), +/- ERTU in the last month, were studied using
31
P and
23
Na NMR spectroscopy to measure PCr/ATP ratio and [Na
+
]
i
, respectively. As expected, HFHS hearts showed lower PCr/ATP, diastolic dysfunction (↑LVEDP) and lack of contractile reserve (↓RPP) during high work protocol compared to CD hearts. Myocardial [Na
+
]
i
was elevated more than 2-fold in HFHS compared to CD. One month of ERTU treatment decreased [Na
+
]
i
and improved energetics and contractile function in HFHS to levels similar to or better than CD. Perfusion with CGP 37157, which inhibits NCx
MITO
, improved PCr/ATP in HFHS hearts.

Conclusion:
Lowering of myocardial [Na
+
]
i
by ertugliflozin contributes to improved energetics and function in MHD. These results suggest targeting [Na
+
]
i
as an effective strategy to improve cardiac dysfunction in MHD and other forms of heart disease associated with elevated myocardial [Na
+
]
i.
Abstract 15316: Paradoxical Reduction in Myocardial Performance When Combining Two Independently Cardioprotective Agents: Mitochondrial-targeted Antioxidant MitoSNO and Adenosine Triphosphate-sensitive Potassium Channel Opener Diazoxide
Authors: Wang Jie , Suarez-Pierre Alex , Gaughan Natalie , Thomas Rosmi , Sebestyen Krisztian , Canner Joseph , Mike Murphy , Lawton Jennifer S
Published: May 2021

Introduction:
Adenosine triphosphate-sensitive potassium (K
ATP
) channel opener diazoxide (DZX) and Antioxidant MitoSNO are both independently cardioprotective in animal models. The cardioprotective mechanism of diazoxide is unknown, and involves a non-sarcolemmal location, requires the inhibition of succinate dehydrogenase, and the K
ATP
channel subunit SUR1. Mitochondrial - targeted Antioxidant MitoSNO is a S-nitrosylating agent that stalls complex 1, reduces ROS production and succinate accumulation. In an isolated myocyte model of stress due to hyperkalemic cardioplegia (CPG), that the combination of DZX and MitoSNO negated the beneficial effects of each alone.

Hypothesis:
We hypothesized that the combination of DZX and MitoSNO would negate the beneficial effects of each alone in an isolated heart model of global ischemia.

Methods:
Isolated mouse hearts underwent assessment of end diastolic pressure (EDP) and left ventricular developed pressure (LVDP) utilizing an LV balloon in a Langendorff model before and after 90 min of global ischemia. Hearts received test solution (CPG (9°C) or CPG±DZX (100μM) at onset of ischemia +/- MitoSNO (1μM/L) at end of ischemia), followed by 30 min reperfusion. LVDP and EDP were compared between groups utilizing a linear mixed model to assess the impact of treatment on the outcome, adjusting for baseline and balloon volume.

Results:
Similar to previous results, DZX improved LVDP and reduced EDP after ischemia compared to CPG (Figure). Similarly, MitoSNO improved LVDP and reduced EDP compared to CPG (Figure). The addition of MitoSNO with DZX was associated with the loss of cardioprotection observed with MitoSNO or DZX alone.

Conclusions:
Similar to data in a myocyte model, both MitoSNO and DZX provide cardioprotection that is lost with the combination of both, suggesting mutually exclusive mechanisms of action and that DZX’s mechanism requires a functional complex 1, ROS production, or succinate accumulation.
Abstract 15326: Inactivation of Mitochondrial Deacetylase Sirt3 Induces Oxidative Stress, Promotes Vascular Hypertrophy, Increases Aortic Dissections, Exacerbates Hypertension and Mortality
Authors: Dikalova Anna , Gutor Sergey , Polosukhin Vasiliy , Dikalov Sergey
Published: May 2021

Introduction:
Vascular dysfunction plays a key role in hypertension and cardiovascular disease, which causes one-third of deaths worldwide. Mitochondrial dysfunction contributes to these conditions; however, specific mechanisms are not clear. We showed inactivation of mitochondrial deacetylase Sirt3 in arterioles from patients with essential hypertension associated with superoxide dismutase inactivation, vascular inflammation and oxidative stress.

Hypothesis:
We hypothesized that the loss of vascular Sirt3 induces oxidative stress, promotes vascular dysfunction and hypertension.

Methods:
To test this hypothesis, we developed tamoxifen-inducible smooth muscle specific Sirt3 knockout mice (SmcSirt3KO) by crossing the Sirt3flox/flox mice with mice carrying a gene for inducible Cre in the vascular smooth muscle cells.

Results and Discussion:
Hypertension was modestly increased but considerably increased mortality in angiotensin II-infused SmcSirt3KO mice (35% vs 5% in WT) which was associated with higher rate of aortic dissections (50% vs 10% in WT). The basal superoxide and nitric oxide levels were not affected in SmcSirt3KO mice, however, angiotensin II infusion significantly increased superoxide and nitric oxide inactivation in SmcSirt3KO mice compared with wild-type mice supporting the pathological role of smooth muscle Sirt3 impairment. Post-mortem analysis showed high frequency of abdominal aortic aneurysms in angiotensin II-infused SmcSirt3KO mice suggesting that adverse vascular remodeling contributed to high mortality in these mice. To gain further insight into vascular pathology we performed histological examination using Verhoeff-van Gieson staining. Angiotensin II-infused SmcSirt3KO mice had 5-time higher abdominal aortic dissections rate, increased vascular hypertrophy, and disrupted elastic lamellae.

Conclusion:
Aortic dissection is a catastrophic disease with high mortality and morbidity characterized by fragmentation of elastin and smooth muscle cell dysfunction. Our data suggest that Sirt3 impairment can contribute to vascular hypertrophy, aortic dissection, end-organ-damage and mortality. It is conceivable that targeting Sirt3 may have therapeutic potential in cardiovascular disease.
Abstract 15336: Real-world Diagnostic Performance of Single-lead Handheld Electrocardiograms for Atrial Fibrillation Screening: The Vital-af Trial
Authors: Khurshid Shaan , Chang Yuchiao , Guan Wyliena , Lipsanopoulos Ana , Borowsky Leila H , Ellinor Patrick T , McManus David D , Atlas Steven , Singer Daniel , Ashburner Jeffrey M , Lubitz Steven
Published: May 2021

Introduction:
AF screening can detect undiagnosed AF, but concerns exist regarding false positives and downstream consequences. AF screening using single-lead handheld electrocardiograms (1L ECGs) is feasible, but diagnostic performance in a pragmatic screening setting is not well-understood.

Methods:
VITAL-AF is a cluster-randomized trial (NCT035115057) of population-based AF screening with 30-second 1L ECGs. Individuals aged ≥65 years receiving primary care in a study practice were eligible, with practices randomized to screening (n=8) or usual care (n=8). Screening was performed with the AliveCor Kardia 1L ECG (AliveCor US) administered by medical assistants. In addition to the AliveCor interpretation, all 1L ECGs were overread by cardiologists. We assessed the distribution of automated interpretations and predictive values using cardiologist 1L ECG overread as the gold standard.

Results:
Screening generated 38,190 tracings representing 16,496 individuals read by 13 cardiologists (median time to read: 10h, quartile 1: 5, quartile 3: 19). We removed 1,554 tracings overread as uninterpretable, resulting in 36,636 tracings in the analysis. A total of 27,251 (74.4%) tracings had an AliveCor interpretation of normal, 6,223 (17.0%) unclassified, 2,420 (6.6%) possible AF, and 742 (2.0%) no interpretation. The positive predictive value (PPV) of possible AF by AliveCor was 76.2% (95% CI 74.5-77.9,
Figure
). The negative predictive values (NPVs) were 99.7% (95% CI 99.6-99.8) for normal, 92.3% (95% CI 91.6-92.9) for unclassified, and 87.1% (95% CI 84.4-89.4) for no interpretation. Of 2,502 tracings overread as AF, 482 (19.3%) were unclassified by AliveCor.

Conclusions:
In an elderly primary care population, the PPV of possible AF by AliveCor algorithm was modest, whereas the NPV of a normal interpretation was very high. Unclassified tracings were common and enriched for AF. Abnormal findings, including unclassified 1L ECG tracings, merit follow-up testing.
Abstract 15338: Comparison of Treatment Strategies for Neonates With Tetralogy of Fallot and Pulmonary Atresia: A Report From the Congenital Catheterization Research Collaborative
Authors: Bauser Heaton Holly , Goldstein Bryan H , Petit Christopher , Qureshi Athar M , McCracken Courtney , Kelleman Michael , Nicholson George , Law Mark A , Zampi Jeffrey , Shahanavaz Shabana , Mascio Christopher , Chai Paul , Romano Jennifer , Batlivala Sarosh P , Maskatia Shiraz A , Asztalos Ivor , Smith Justin , Eilers Lindsay , Kamsheh Alicia , Healan Steven J , Pettus Joelle , Ligon Allen , dailey-schwartz andrew , Raulston James E , Pajk Amy , Glatz Andrew C , Meadows Jeffery J
Published: May 2021

Introduction:
Neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) with pulmonary blood flow supplied by the ductus arteriosus require early intervention. This may be accomplished by: initial palliation (IP) followed by complete repair (CR) or initial primary repair (PR). The optimal approach for patients with TOF/PA has not been established.

Methods:
Neonates with TOF/PA who underwent IP or PR from 2005-17 were retrospectively reviewed from the Congenital Catheterization Research Collaborative. The primary outcome was mortality. Outcomes were compared as IP vs PR and IP+CR vs PR. Secondary outcomes included hospital and procedural complications and are listed in table 1. Propensity scoring was used to adjust for baseline differences between strategies.

Results:
Of 282 neonates with TOF/PA, 106 underwent PR and 176 underwent IP (144 surgical, 32 transcatheter). Prior to initial intervention, IP patients had higher rates of mechanical ventilation (83.9% vs 72.2%, p=0.023) and DiGeorge syndrome (14.77% vs 4.72%, p=0.009). Mortality was greater in the IP cohort (HR 2.7, 95% CI 1.02 - 7.1, p = 0.046), with no mortality in the PR cohort after 6 months post-repair. After adjustment, differences in survival were no longer significant (HR 1.4, 95% CI 0.7 - 3.1, p=0.39). Both cohorts had similar mechanical ventilation duration and inotrope use as well as procedural and hospital complications. Intensive care and hospital length of stay, cardiac bypass (CPB) and anesthesia time favored PR when compared to IP+CR (p=<0.001). Early reintervention was more common in patients undergoing IP (rate ratio 1.42, p 0.003), but post-complete repair rates were similar (p=0.837).

Conclusions:
In neonates with TOF/PA, the IP approach is more often utilized in higher-risk patients. Accounting for this difference, IP and PR strategies have similar adjusted survival rates. Perioperative morbidities and lower risk for reintervention generally favor PR.
Abstract 15353: Apixaban Failure in Prevention of Ischemic Cerebrovascular Accidents in Non-valvular Atrial Fibrillation Patients
Authors: Zmaili Mohammad , Alzubi Jafar , Gad Mohamed , Abu-Haniyeh Ahmed , Saliba Walid I , Wazni Oussama M , Hussein Ayman
Published: May 2021

Introduction:
Apixaban has been increasingly used over the past decade for the prevention of ischemic strokes in atrial fibrillation (AF) patients. Nonetheless, some patients may experience ischemic strokes despite apixaban therapy. There is scarce information about factors underlying apixaban failure in AF patients.

Methods:
A system wide search was employed at the Cleveland Clinic Health System using electronic records. All patients 18 years of age or older, who were diagnosed with AF, and developed an ischemic stroke while being treated with apixaban (January 2013 through May 2019) were included. A matched controls series (no stroke on apixaban) was included accounting for antiplatelet and statin therapy, and carotid artery disease. Multivariable analyses were performed to assess for associations between clinical characteristics and stroke on apixaban.

Results:
A total of 137 patients with stroke while on apixaban were identified and matched to 137 controls. Cases and controls were comparable in a large number of clinical characteristics. There was an association between apixaban dosing and risk of stroke. About 40% of the lower (2.5 mg BID) dose of apixaban was prescribed for patients who would have qualified for full dose. Being on inappropriately low dose of apixaban was associated with a higher risk of ischemic strokes compared to appropriately prescribed doses with an adjusted OR 3.37 [1.37-8.32]. Among appropriately prescribed doses, the 5 mg BID dose showed a statistically nonsignificant lower risk of ischemic stroke compared to the 2.5 mg BID dose, adjusted OR 0.55 [0.21-1.41]. Compared to the inappropriate use of the 2.5 mg dose, the appropriate prescription of the 2.5 mg dose was associated with a lower risk of stroke adjusted OR 0.34 [0.07-1.64].

Conclusion:
In this series, there was a statistically significant association between being on an inappropriately low dose of apixaban and the odds of stroke while on apixaban therapy.
Abstract 15364: Radiation Exposure of the Base of the Heart Accelerates Coronary Atherosclerosis
Authors: Nepali Prerna Ramesh , Gabriels Karen , Mathieu Mickael , Russell James , te Poele Johannes A , Kitz Sarah , Monette Sebastien , Heeneman Sylvia , Stewart Fiona A , JAIMES Edgar A , Haimovitz-Friedman Adriana
Published: May 2021

Introduction:
Radiation therapy (RT) is used in the treatment of approximately 50% of cancer patients. Thoracic RT is commonly used in breast cancer, Hodgkin’s lymphoma, head and neck and lung cancers among others. Unfortunately, the benefits of RT are often out-weighed by the by-stander cardiovascular risks and associated non-relapse mortality in cancer survivors. Hence, the development of cardiovascular disease (CVD) in patients receiving RT remains an important clinical problem. The base of the heart has been shown to be dose-sensitive wherein basal irradiation is associated with lower patient survival in lung-cancer patients treated with curative-intent RT. Although the mechanisms for RT-induced CVD are poorly understood, direct injury to the coronary arteries endothelium has been implicated.

Hypothesis and Results:
We hypothesized that
irradiation harms heart tissue differentially depending upon the specific region that receives radiation.
In order to test this hypothesis, we irradiated different regions of the heart and measured the development of atherosclerotic plaques as compared to control unirradiated mice. Apolipoprotein E knockout (ApoE
-/-
) mice were irradiated with 16Gy to the base, apex or to the whole heart. Our results demonstrate that the base of the heart has significantly greater sensitivity to irradiation as compared to the apex, and develops atherosclerotic lesions that are equivalent to those produced by whole heart irradiation at 20 weeks post-RT. In addition, a greater number of plaques are present in the base of the heart after whole heart and basal irradiation compared to unirradiated controls at 40 weeks post-RT. Atherosclerotic plaques with subendothelial macrophage foam cell accumulation and fibrin deposits were also observed at 20 and 40 weeks post basal or whole heart RT. Ongoing studies are testing the effect of high-fat diet on the development of differential RT-induced atherosclerotic plaques in ApoE
-/-
mice and their correlation with heart function.

Conclusion:
Our studies strengthen the argument for advanced RT techniques to shield the base of the heart from radiation exposure to minimize RT-induced CVD and improve the quality of life and survival of cancer patients receiving RT.
Abstract 15389: Effect of Icosapent Ethyl on Changes in Coronary Plaque Characteristics at 9 Months in Patients With Elevated Triglycerides on Statin Therapy: Insights From EVAPORATE
Authors: Lakshmanan Suvasini , Buckler Andrew , Bhatt Deepak L , Kinninger April , Golub Ilana , Muhlestein Joseph B , Le Viet T , May Heidi T , Shaikh Kashif , Shekar Chandana , Roy Sion K , Tayek John , Nelson John R , Budoff Matthew J
Published: May 2021

Background:
Residual cardiovascular (CV) risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total CV events by 30%, but the mechanisms of benefit are not fully understood. The EVAPORATE trial evaluated the effects of IPE as adjunct to statins on adverse atherosclerotic plaque characteristics by CCTA. Here we use a novel software validated using histology to evaluate the effect of IPE on vulnerable plaque features.

Methods:
The EVAPORATE trial randomized statin-treated patients, with high TG (135-499 mg/dL), and known atherosclerosis to IPE 4 g/d or placebo. Plaque characteristics including lipid rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH) were assessed using vascuCAP
®
(Elucid Bioimaging Inc., Boston, MA). Per-patient multivariable models robust with respect to physiological variation were used to evaluate plaque progression.

Results:
A total of 60 patients had interpretable images. Relative to placebo, patients on IPE demonstrated decreased wall volume (-7.2 vs. +28.4 mm
3
), LRNC (-1.4 vs. +9.7 mm
3
), and IPH (-0.02 vs. +0.3 mm
3
), as well as increased cap thickness (+100 vs. -290 microns), indicating a migration to more stable phenotypes (p>0.05).Statistical significance was achieved when incorporated into an optimized neural network model of lipid-rich phenotype (p = 0.04), AUROC=0.7[0.63,0.77], sensitivity=0.66[0.59,0.74], specificity=0.64 [0.56,0.72], and Cohen’s kappa=0.3 [0.19,0.41]. Operating points when used as a per-patient measure of response are presented in Figure 1.

Conclusions:
This study demonstrated that IPE, when added to statin therapy, is associated with reduction in vulnerable plaque, moving patients to a more stable plaque phenotype.
Abstract 15516: Predicting Heart Failure Hospitalization in Type 2 Diabetes Mellitus: Validation of the TRS-HFDM Score in the ACCORD Trial
Authors: Elharram Malik , Huynh Thao , Ni Jiayi , Ferreira João P , Sharma Abhinav
Published: May 2021

Background:
Patients with type 2 diabetes mellitus (T2DM) are at an increased risk for developing heart failure (HF), and clinical models are needed to identify patients with a greater risk for HF hospitalization (HHF). The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM) was recently developed and validated to predict HHF in patients with T2DM in two large clinical trials (SAVOR-TIMI 53 and DECLARE-TIMI 58). We aimed to validate the TRS-HFDM in another cohort of patients with T2DM.

Methods:
We validated the TRS-HFDM score in 5,123 patients with T2DM for fatal or non-fatal HHF in the placebo arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes Study Group). The TRS-HFDM included: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. We evaluated discrimination with the Harrell C index, and calibration by comparing observed event rates for HHF with predicted risk, and the Nam-D’Agostino statistic.

Results:
During a mean follow up of 4.8 years, 212 patients (4.14%) experienced at least one HHF. The mean age was 63 ±6.7 years, and 38% were female. The baseline hemoglobin A1C was 8.3%, and 36% were on insulin. The ACCORD patients had less comorbidities with a lower proportion of patients with renal dysfunction (8% vs. 16% vs. 17%), established cardiovascular disease (35% vs.79% vs. 41%) and pre-existing HF (5% vs. 13% vs. 10%) compared to patients enrolled in the SAVOR-TIMI 53 and DECLARE TIMI-58 trials respectively. In our cohort, the TRS-HFDM score predicted well HHF events with a Harrel C index of 0.78. The integer-based score was well calibrated, with the observed Kaplan-Meier HHF rates closely predicting the Kaplan-Meier event rates at the end follow up (Nam D`Agostino test: 65.39 (p<0.0001).

Discussion:
Our findings confirm the applicability of the TRS-HFDM in a large cohort of patients with T2DM with less high-risk features than the SAVOR-TIMI 53 and DECLARE-TIMI 58 populations. Future validation of this risk score in observational cohort studies is needed to evaluate its external validity in a general clinical setting.
Abstract 15522: Multiple Brachial ‘Tornado’ Loops Encountered During Transradial Access - A Case Report With Review of Literature
Authors: Vaishnav Aditi S , Vaishnav Avani , Iyer Shankar , Vaishnav Sudhir
Published: May 2021

Introduction:
Although transradial access (TRA) is widely accepted for cardiac catheterization, technical difficulties may occur due to variations in the radial-brachial-subclavian artery anatomy.

Clinical Vignette:
A 70-year old man presented with typical angina, positive stress test and normal LV function. Elective coronary angiography via TRA was planned since there were no contraindications. A guidewire was inserted and advanced via right radial puncture. Due to resistance above the elbow, the wire was withdrawn and check shoots were taken. These revealed a brachial loop, which was crossed and straightened with a Teflon coated angioplasty wire (0.014BMW wire). On advancing further, resistance was encountered again. Check-shoots at this point revealed multiple tortuous tornado-like brachial loops. Attempts to cross these using a BMW wire and 4F-RCA guiding catheter were unsuccessful as the artery went into spasm, preventing further manipulation. Ipsilateral TRA was abandoned due to risk of arterial perforation and severe pain; contralateral TRA was not attempted due to patient’s refusal. The procedure was completed via femoral access.

Discussion:
To the best of our knowledge, this is the first report of multiple brachial loops, which highlights certain unique challenges-

1. Complex anatomic variations can occur exclusive of signs used to assess TRA amenability

2. No guidelines on procedural techniques

3. No data to guide the alternative access site as it is unknown whether brachial loops tend to occur bilaterally, unlike radial loops

4. Unlike radial and subclavian arteries, there are no data on association of demographic factors with brachial artery variations.

Conclusion:
Anatomic variations of upper limb arteries, although rare, can cause technical difficulties and TRA failure. If resistance is encountered, an angiogram should be performed through the sheath to assess anatomy, to prevent severe spasm and perforation from forceful catheter advancement.
Abstract 15524: The Methyltransferase Setd7 Drives Myocardial Ischemic Injury by Modulating the Hippo Pathway: A Study in Mice and Humans
Authors: Ambrosini Samuele , Montecucco Fabrizio , Pedicino Daniela , Akhmedov Alexander , Mohammed Shafeeq Ahmed , Liuzzo Giovanna , Beltrami Antonio Paolo P , Crea Filippo , Luescher Thomas F , Costantino Sarah , Paneni Francesco
Published: May 2021

Introduction:
Ischemic heart disease is a leading cause of death worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a significant number of MI patients develop heart failure. Protein methylation is emerging as a key biological signal implicated in the pathophysiology of cardiovascular (CV) disease. In this regard, the methyltransferase SETD7 was recently shown to methylate proteins relevant to CV homeostasis.

Hypothesis:
To investigate SETD7 role in myocardial ischemia-reperfusion (I/R) injury.

Methods:
Experiments were performed in neonatal rat ventricular myocytes (NRVM), SETD7 knockout mice (SETD7
-/-
) undergoing myocardial I/R injury, myocardial samples from patients with and without ischemic heart failure as well as peripheral blood mononuclear cells from patients with ST elevation MI (STEMI, n=25) and age-matched healthy controls (n=20).

Results:
Glucose deprivation (GD) in NRVM led to upregulation of SETD7 and direct mono-methylation of the Hippo signaling effector YAP. SETD7-dependent methylation of YAP led to its cytosolic retention thus impeding YAP binding to the promoter of pro-survival genes. Selective pharmacological inhibition of SETD7 by (R)-PFI-2 blunted YAP mono-methylation thereby restoring its nuclear retention. We show that YAP binds the promoter of antioxidant genes catalase and superoxide dismutase, thus preventing GD-induced mitochondrial oxidative stress, organelle swelling and apoptosis. Consistently, infarct size, myocardial oxidative stress and left ventricular dysfunction were reduced in SETD7
-/-
mice undergoing I/R as compared to wild-type littermates. Of clinical relevance, we found that SETD7/YAP signaling was deregulated in myocardial samples from patients with ischemic heart failure as well as in peripheral blood mononuclear cells from STEMI patients.

Conclusions:
We demonstrate that SETD7-dependent methylation of YAP is an important mechanism underpinning myocardial oxidative stress, mitochondrial damage and apoptosis during ischemia. Pharmacological modulation of SETD7 by (R)-PFI-2 may represent a potential therapeutic approach to prevent myocardial ischemic damage through modulation of the Hippo pathway.
Abstract 15530: Single-cell Analysis in Aortic Aneurysmal Tissue From Patients With Marfan Syndrome Reveals Increased Tgf-beta Production but Downregulation of Downstream Canonical Tgf-beta Signaling Pathways
Authors: Dawson Ashley , Li Yanming , Ren Pingping , Vasquez Hernan , Zhang Chen , Appel Richard , Ageedi Waleed , Luo Wei , Zhang Lin , Li Yang , Sheppard Mary B , Lu Hong S , Cassis Lisa A , Coselli Joseph S , Daugherty Alan , Shen Ying H , Lemaire Scott A
Published: May 2021

Background:
Marfan syndrome (MFS) is caused by mutations in the gene for fibrillin-1 (
FBN1
); however, the mechanisms by which these mutations cause aortic aneurysms are poorly understood. Although it was hypothesized previously that dysregulation of the complex TGF-β signaling pathway leads to aortic aneurysm formation,
FBN1
mutations appear to have a paradoxical effect on TGF-β signaling in MFS. In this study, we evaluated cell-specific TGF-β expression in non-immune cells in MFS aortic tissue.

Methods:
We performed single-cell RNA sequencing of ascending aortic aneurysm tissues from MFS patients (n=3) undergoing aneurysm repair and age-matched, non-aneurysmal control tissue from cardiac transplant donors and recipients (n=4). Non-immune cells were separated out from the data and analyzed using the Seurat package in R. Differentially expressed genes were identified using edgeR.

Results:
Conserved gene expression was used to identify populations of smooth muscle cells (SMCs; n=6), fibroblasts (n=3), and endothelial cells (ECs; n=3). We found that
TGFB1
was significantly upregulated in quiescent fibroblasts (identified by increased expression of
DCN
,
LUM
, and complement factors) with log2FC of 1.30 and FDR 8.25x10
-8
, as well as in activated fibroblasts (identified by increased expression of genes involved in blood vessel repair and healing including
ACTA2
,
NOTCH3
,
THBS2
, and
PDGFRB
) with log2FC of 1.25 and FDR 6.15x10
-22
. Despite this increase in
TGFB1
, expression of TGF-β receptor genes (predominately
TGFBR2
) as well as downstream SMAD genes was downregulated significantly in the SMC, fibroblast, and endothelial cell clusters. Finally, genes involved in the non-canonical TGF-β pathway, including
ERK
,
JNK,
and p38, were not differentially expressed in non-immune cells in MFS compared with control tissues.

Conclusion:
Increased expression of
TGFB1
in non-immune cells in MFS was driven by two clusters of fibroblasts. Despite this, our data do not support associated upregulation of other genes in the canonical or non-canonical TGF-β pathways and in fact support downregulation of canonical TGF-β signaling in non-immune cells of aneurysmal tissues from MFS patients with advanced aortic disease.
Abstract 15533: Long-term Prognostic Utility of Low-density Lipoprotein (ldl) Triglyceride in Real-world Patients With Coronary Artery Disease and Diabetes or Prediabetes
Authors: Jin Jinglu , Guo Yuanlin , Zhang Huiwen , Cao Yexuan , Liu Huihui , Zhang Yan , Wu Naqiong , Zhu Chenggang , Gao Ying , Xu Ruixia , Cui Chuanjue , Liu Geng , Sun Jing , Dong Qian , Li Jianjun
Published: May 2021

Introduction:
Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available.

Hypothesis:
LDL-TG had impact on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status.

Methods:
A total of 4381 patients with CAD were consecutively enrolled and categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. Plasma LDL-TG level was measured by an automated homogeneous assay. All subjects were followed up for the occurrence of MACEs.

Results:
During a median 5.1 (interquartile range 3.9 to 5.9) year follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride[hazard ratios (95% confidence intervals): 1.843(1.149-2.955), 1.828(1.165-2.867), 2.212(1.396-3.507), all p<0.05]. Moreover, adding LDL-TG in the original model increased the C-statistic from 0.687 to 0.704 (ΔC-statistic=0.016, p=0.028) and from 0.734 to 0.749 (ΔC-statistic =0.014, p=0.002) in Pre-DM and DM respectively.

Conclusions:
In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.